@article{KuecuekgoezeLeimkuehler2018, author = {K{\"u}{\c{c}}{\"u}kg{\"o}ze, G{\"o}khan and Leimk{\"u}hler, Silke}, title = {Direct comparison of the four aldehyde oxidase enzymes present in mouse gives insight into their substrate specificities}, series = {PLOS ONE}, volume = {13}, journal = {PLOS ONE}, number = {1}, publisher = {Public Library of Science}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0191819}, pages = {20}, year = {2018}, abstract = {Mammalian aldehyde oxidases (AOXs) are molybdo-flavoenzymes which are present in many tissues in various mammalian species, including humans and rodents. Different species contain a different number of AOX isoforms. In particular, the reasons why mammals other than humans express a multiplicity of tissue-specific AOX enzymes is unknown. In mouse, the isoforms mAOX1, mAOX3, mAOX4 and mAOX2 are present. We previously established a codon-optimized heterologous expression systems for the mAOX1-4 isoforms in Escherichia coli that gives yield to sufficient amounts of active protein for kinetic characterizations and sets the basis in this study for site-directed mutagenesis and structure-function studies. A direct and simultaneous comparison of the enzymatic properties and characteristics of the four enzymes on a larger number of substrates has never been performed. Here, thirty different structurally related aromatic, aliphatic and N-heterocyclic compounds were used as substrates, and the kinetic parameters of all four mAOX enzymes were directly compared. The results show that especially mAOX4 displays a higher substrate selectivity, while no major differences between mAOX1, mAOX2 and mAOX3 were identified. Generally, mAOX1 was the enzyme with the highest catalytic turnover for most substrates. To understand the factors that contribute to the substrate specificity of mAOX4, site-directed mutagenesis was applied to substitute amino acids in the substrate-binding funnel by the ones present in mAOX1, mAOX3, and mAOX2. An increase in activity was obtained by the amino acid exchange M1088V in the active site identified to be specific for mAOX4, to the amino acid identified in mAOX3.}, language = {en} } @misc{LucknerDunsingChiantiaetal.2018, author = {Luckner, Madlen and Dunsing, Valentin and Chiantia, Salvatore and Hermann, Andreas}, title = {Oligomerization and nuclear shuttling dynamics of viral proteins studied by quantitative molecular brightness analysis using fluorescence correlation spectroscopy}, series = {Biophysical journal}, volume = {114}, journal = {Biophysical journal}, number = {3}, publisher = {Cell Press}, address = {Cambridge}, issn = {0006-3495}, doi = {10.1016/j.bpj.2017.11.1951}, pages = {350A -- 350A}, year = {2018}, language = {en} } @misc{DunsingMagnusLiebschetal.2018, author = {Dunsing, Valentin and Magnus, Mayer and Liebsch, Filip and Multhaup, Gerhard and Chiantia, Salvatore}, title = {Direct Evidence of APLP1 Trans Interactions in Cell-Cell Adhesion Platforms Investigated via Fluorescence Fluctuation Spectroscopy}, series = {Biophysical journal}, volume = {114}, journal = {Biophysical journal}, number = {3}, publisher = {Cell Press}, address = {Cambridge}, issn = {0006-3495}, doi = {10.1016/j.bpj.2017.11.2067}, pages = {373A -- 373A}, year = {2018}, abstract = {The Amyloid-precursor-like protein 1 (APLP1) is a neuronal type I transmembrane protein which plays a role in synaptic adhesion and synaptogenesis. Past investigations indicated that APLP1 is involved in the formation of protein-protein complexes that bridge the junctions between neighboring cells. Nevertheless, APLP1-APLP1 trans interactions have never been directly observed in higher eukaryotic cells. Here, we investigate APLP1 interactions and dynamics directly in living human embryonic kidney (HEK) cells, using fluorescence fluctuation spectroscopy techniques, namely cross-correlation scanning fluorescence correlation spectroscopy (sFCS) and Number\&Brightness (N\&B). Our results show that APLP1 forms homotypic trans complexes at cell-cell contacts. In the presence of zinc ions, the protein forms macroscopic clusters, exhibiting an even higher degree of trans binding and strongly reduced dynamics. Further evidence from Giant Plasma Membrane Vesicles and live cell actin staining suggests that the presence of an intact cortical cytoskeleton is required for zinc-induced cis multimerization. Subsequently, large adhesion platforms bridging interacting cells are formed through APLP1-APLP1 direct trans interactions. Taken together, our results provide direct evidence that APLP1 functions as a neuronal zinc-dependent adhesion protein and provide a more detailed understanding of the molecular mechanisms driving the formation of APLP1 adhesion platforms. Further, they show that fluorescence fluctuation spectroscopy techniques are useful tools for the investigation of protein-protein interactions at cell-cell adhesion sites.}, language = {en} } @article{StoesselSchultedosSantosetal.2018, author = {Stoessel, Daniel and Schulte, Claudia and dos Santos, Marcia C. Teixeira and Scheller, Dieter and Rebollo-Mesa, Irene and Deuschle, Christian and Walther, Dirk and Schauer, Nicolas and Berg, Daniela and da Costa, Andre Nogueira and Maetzler, Walter}, title = {Promising Metabolite Profiles in the Plasma and CSF of Early Clinical}, series = {Frontiers in Aging Neuroscience}, volume = {10}, journal = {Frontiers in Aging Neuroscience}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1663-4365}, doi = {10.3389/fnagi.2018.00051}, pages = {14}, year = {2018}, abstract = {Parkinson's disease (PD) shows high heterogeneity with regard to the underlying molecular pathogenesis involving multiple pathways and mechanisms. Diagnosis is still challenging and rests entirely on clinical features. Thus, there is an urgent need for robust diagnostic biofluid markers. Untargeted metabolomics allows establishing low-molecular compound biomarkers in a wide range of complex diseases by the measurement of various molecular classes in biofluids such as blood plasma, serum, and cerebrospinal fluid (CSF). Here, we applied untargeted high-resolution mass spectrometry to determine plasma and CSF metabolite profiles. We semiquantitatively determined small-molecule levels (<= 1.5 kDa) in the plasma and CSF from early PD patients (disease duration 0-4 years; n = 80 and 40, respectively), and sex-and age-matched controls (n = 76 and 38, respectively). We performed statistical analyses utilizing partial least square and random forest analysis with a 70/30 training and testing split approach, leading to the identification of 20 promising plasma and 14 CSF metabolites. The semetabolites differentiated the test set with an AUC of 0.8 (plasma) and 0.9 (CSF). Characteristics of the metabolites indicate perturbations in the glycerophospholipid, sphingolipid, and amino acid metabolism in PD, which underscores the high power of metabolomic approaches. Further studies will enable to develop a potential metabolite-based biomarker panel specific for PD}, language = {en} } @phdthesis{Brunacci2021, author = {Brunacci, Nadia}, title = {Oligodepsipeptides as matrix for drug delivery systems and submicron particulate carriers}, school = {Universit{\"a}t Potsdam}, year = {2021}, language = {en} } @article{PalkopoulouLipsonMallicketal.2018, author = {Palkopoulou, Eleftheria and Lipson, Mark and Mallick, Swapan and Nielsen, Svend and Rohland, Nadin and Baleka, Sina Isabelle and Karpinski, Emil and Ivancevici, Atma M. and Thu-Hien To, and Kortschak, Daniel and Raison, Joy M. and Qu, Zhipeng and Chin, Tat-Jun and Alt, Kurt W. and Claesson, Stefan and Dalen, Love and MacPhee, Ross D. E. and Meller, Harald and Rocar, Alfred L. and Ryder, Oliver A. and Heiman, David and Young, Sarah and Breen, Matthew and Williams, Christina and Aken, Bronwen L. and Ruffier, Magali and Karlsson, Elinor and Johnson, Jeremy and Di Palma, Federica and Alfoldi, Jessica and Adelsoni, David L. and Mailund, Thomas and Munch, Kasper and Lindblad-Toh, Kerstin and Hofreiter, Michael and Poinar, Hendrik and Reich, David}, title = {A comprehensive genomic history of extinct and living elephants}, series = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {11}, publisher = {National Acad. of Sciences}, address = {Washington}, issn = {0027-8424}, doi = {10.1073/pnas.1720554115}, pages = {E2566 -- E2574}, year = {2018}, language = {en} } @article{WutkeSandovalCastellanosBeneckeetal.2018, author = {Wutke, Saskia and Sandoval-Castellanos, Edson and Benecke, Norbert and D{\"o}hle, Hans-J{\"u}rgen and Friederich, Susanne and Gonzalez, Javier and Hofreiter, Michael and Lougas, Lembi and Magnell, Ola and Malaspinas, Anna-Sapfo and Morales-Muniz, Arturo and Orlando, Ludovic and Reissmann, Monika and Trinks, Alexandra and Ludwig, Arne}, title = {Decline of genetic diversity in ancient domestic stallions in Europe}, series = {Science Advances}, volume = {4}, journal = {Science Advances}, number = {4}, publisher = {American Assoc. for the Advancement of Science}, address = {Washington}, issn = {2375-2548}, doi = {10.1126/sciadv.aap9691}, pages = {7}, year = {2018}, abstract = {Present-day domestic horses are immensely diverse in their maternally inherited mitochondrial DNA, yet they show very little variation on their paternally inherited Y chromosome. Although it has recently been shown that Y chromosomal diversity in domestic horses was higher at least until the Iron Age, when and why this diversity disappeared remain controversial questions. We genotyped 16 recently discovered Y chromosomal single-nucleotide polymorphisms in 96 ancient Eurasian stallions spanning the early domestication stages (Copper and Bronze Age) to the Middle Ages. Using this Y chromosomal time series, which covers nearly the entire history of horse domestication, we reveal how Y chromosomal diversity changed over time. Our results also show that the lack of multiple stallion lineages in the extant domestic population is caused by neither a founder effect nor random demographic effects but instead is the result of artificial selection-initially during the Iron Age by nomadic people from the Eurasian steppes and later during the Roman period. Moreover, the modern domestic haplotype probably derived from another, already advantageous, haplotype, most likely after the beginning of the domestication. In line with recent findings indicating that the Przewalski and domestic horse lineages remained connected by gene flow after they diverged about 45,000 years ago, we present evidence for Y chromosomal introgression of Przewalski horses into the gene pool of European domestic horses at least until medieval times.}, language = {en} } @misc{DammhahnDingemanseNiemelaeetal.2018, author = {Dammhahn, Melanie and Dingemanse, Niels J. and Niemelae, Petri T. and Reale, Denis}, title = {Pace-of-life syndromes}, series = {Behavioral ecology and sociobiology}, volume = {72}, journal = {Behavioral ecology and sociobiology}, number = {3}, publisher = {Springer}, address = {New York}, issn = {0340-5443}, doi = {10.1007/s00265-018-2473-y}, pages = {8}, year = {2018}, abstract = {This introduction to the topical collection on Pace-of-life syndromes: a framework for the adaptive integration of behaviour, physiology, and life history provides an overview of conceptual, theoretical, methodological, and empirical progress in research on pace-of-life syndromes (POLSs) over the last decade. The topical collection has two main goals. First, we briefly describe the history of POLS research and provide a refined definition of POLS that is applicable to various key levels of variation (genetic, individual, population, species). Second, we summarise the main lessons learned from current POLS research included in this topical collection. Based on an assessment of the current state of the theoretical foundations and the empirical support of the POLS hypothesis, we propose (i) conceptual refinements of theory, particularly with respect to the role of ecology in the evolution of (sexual dimorphism in) POLS, and (ii) methodological and statistical approaches to the study of POLS at all major levels of variation. This topical collection further holds (iii) key empirical examples demonstrating how POLS structures may be studied in wild populations of (non) human animals, and (iv) a modelling paper predicting POLS under various ecological conditions. Future POLS research will profit from the development of more explicit theoretical models and stringent empirical tests of model assumptions and predictions, increased focus on how ecology shapes (sex-specific) POLS structures at multiple hierarchical levels, and the usage of appropriate statistical tests and study designs. Significance statement As an introduction to the topical collection, we summarise current conceptual, theoretical, methodological and empirical progress in research on pace-of-life syndromes (POLSs), a framework for the adaptive integration of behaviour, physiology and life history at multiple hierarchical levels of variation (genetic, individual, population, species). Mixed empirical support of POLSs, particularly at the within-species level, calls for an evaluation and refinement of the hypothesis. We provide a refined definition of POLSs facilitating testable predictions. Future research on POLSs will profit from the development of more explicit theoretical models and stringent empirical tests of model assumptions and predictions, increased focus on how ecology shapes (sex-specific) POLSs structures at multiple hierarchical levels and the usage of appropriate statistical tests and study designs.}, language = {en} } @misc{DahmaniLudwigChiantia2019, author = {Dahmani, Ismail and Ludwig, Kai and Chiantia, Salvatore}, title = {Influenza A matrix protein M1 induces lipid membrane deformation via protein multimerization}, series = {Postprints der Universit{\"a}t Potsdam Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam Mathematisch-Naturwissenschaftliche Reihe}, number = {768}, issn = {1866-8372}, doi = {10.25932/publishup-43868}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-438689}, pages = {16}, year = {2019}, abstract = {The matrix protein M1 of the Influenza A virus (IAV) is supposed to mediate viral assembly and budding at the plasma membrane (PM) of infected cells. In order for a new viral particle to form, the PM lipid bilayer has to bend into a vesicle toward the extracellular side. Studies in cellular models have proposed that different viral proteins might be responsible for inducing membrane curvature in this context (including M1), but a clear consensus has not been reached. In the present study, we use a combination of fluorescence microscopy, cryogenic transmission electron microscopy (cryo-TEM), cryo-electron tomography (cryo-ET) and scanning fluorescence correlation spectroscopy (sFCS) to investigate M1-induced membrane deformation in biophysical models of the PM. Our results indicate that M1 is indeed able to cause membrane curvature in lipid bilayers containing negatively charged lipids, in the absence of other viral components. Furthermore, we prove that protein binding is not sufficient to induce membrane restructuring. Rather, it appears that stable M1-M1 interactions and multimer formation are required in order to alter the bilayer three-dimensional structure, through the formation of a protein scaffold. Finally, our results suggest that, in a physiological context,M1-induced membrane deformation might be modulated by the initial bilayer curvature and the lateral organization of membrane components (i.e. the presence of lipid domains).}, language = {en} } @article{Schmidt2017, author = {Schmidt, Marco F.}, title = {miRNA Targeting Drugs}, series = {Drug Target miRNA: Methods and Protocols}, volume = {1517}, journal = {Drug Target miRNA: Methods and Protocols}, publisher = {Springer}, address = {New York}, isbn = {978-1-4939-6563-2}, issn = {1064-3745}, doi = {10.1007/978-1-4939-6563-2_1}, pages = {3 -- 22}, year = {2017}, abstract = {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.}, language = {en} }