TY - JOUR A1 - Wiesner-Reinhold, Melanie A1 - Barknowitz, Gitte A1 - Florian, Simone A1 - Mewis, Inga A1 - Schumacher, Fabian A1 - Schreiner, Monika A1 - Glatt, Hansruedi T1 - 1-Methoxy-3-indolylmethyl DNA adducts in six tissues, and blood protein adducts, in mice under pak choi diet: time course and persistence JF - Archives of toxicology : official journal of EUROTOX N2 - We previously showed that purified 1-methoxy-3-indolylmethyl (1-MIM) glucosinolate, a secondary plant metabolite in Brassica species, is mutagenic in various in vitro systems and forms DNA and protein adducts in mouse models. In the present study, we administered 1-MIM glucosinolate in a natural matrix to mice, by feeding a diet containing pak choi powder and extract. Groups of animals were killed after 1, 2, 4 and 8 days of pak choi diet, directly or, in the case of the 8-day treatment, after 0, 8 and 16 days of recovery with pak choi-free diet. DNA adducts [N-2-(1-MIM)-dG, N-6-(1-MIM)-dA] in six tissues, as well as protein adducts [tau N-(1-MIM)-His] in serum albumin (SA) and hemoglobin (Hb) were determined using UPLC-MS/MS with isotopically labeled internal standards. None of the samples from the 12 control animals under standard diet contained any 1-MIM adducts. All groups receiving pak choi diet showed DNA adducts in all six tissues (exception: lung of mice treated for a single day) as well as SA and Hb adducts. During the feeding period, all adduct levels continuously increased until day 8 (in the jejunum until day 4). During the 14-day recovery period, N-2-(1-MIM)-dG in liver, kidney, lung, jejunum, cecum and colon decreased to 52, 41, 59, 11, 7 and 2%, respectively, of the peak level. The time course of N-6-(1-MIM)-dA was similar. Immunohistochemical analyses indicated that cell turnover is a major mechanism of DNA adduct elimination in the intestine. In the same recovery period, protein adducts decreased more rapidly in SA than in Hb, to 0.7 and 37%, respectively, of the peak level, consistent with the differential turnover of these proteins. In conclusion, the pak choi diet lead to the formation of high levels of adducts in mice. Cell and protein turnover was a major mechanism of adduct elimination, at least in gut and blood. KW - 1-Methoxy-3-indolylmethyl glucosinolate KW - Neoglucobrassicin KW - DNA adducts KW - Blood protein adducts KW - Pak choi Y1 - 2019 U6 - https://doi.org/10.1007/s00204-019-02452-3 SN - 0340-5761 SN - 1432-0738 VL - 93 IS - 6 SP - 1515 EP - 1527 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Chapman, Eric M. A1 - Lant, Benjamin A1 - Ohashi, Yota A1 - Yu, Bin A1 - Schertzberg, Michael A1 - Go, Christopher A1 - Dogra, Deepika A1 - Koskimaki, Janne A1 - Girard, Romuald A1 - Li, Yan A1 - Fraser, Andrew G. A1 - Awad, Issam A. A1 - Abdelilah-Seyfried, Salim A1 - Gingras, Anne-Claude A1 - Derry, William Brent T1 - A conserved CCM complex promotes apoptosis non-autonomously by regulating zinc homeostasis JF - Nature Communications N2 - Apoptotic death of cells damaged by genotoxic stress requires regulatory input from surrounding tissues. The C. elegans scaffold protein KRI-1, ortholog of mammalian KRIT1/CCM1, permits DNA damage-induced apoptosis of cells in the germline by an unknown cell non-autonomous mechanism. We reveal that KRI-1 exists in a complex with CCM-2 in the intestine to negatively regulate the ERK-5/MAPK pathway. This allows the KLF-3 transcription factor to facilitate expression of the SLC39 zinc transporter gene zipt-2.3, which functions to sequester zinc in the intestine. Ablation of KRI-1 results in reduced zinc sequestration in the intestine, inhibition of IR-induced MPK-1/ERK1 activation, and apoptosis in the germline. Zinc localization is also perturbed in the vasculature of krit1(-/-) zebrafish, and SLC39 zinc transporters are mis-expressed in Cerebral Cavernous Malformations (CCM) patient tissues. This study provides new insights into the regulation of apoptosis by cross-tissue communication, and suggests a link between zinc localization and CCM disease. Y1 - 2019 U6 - https://doi.org/10.1038/s41467-019-09829-z SN - 2041-1723 VL - 10 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Luetkecosmann, Steffi A1 - Faupel, Thomas A1 - Porstmann, Silvia A1 - Porstmann, Tomas A1 - Micheel, Burkhard A1 - Hanack, Katja T1 - A cross-reactive monoclonal antibody as universal detection antibody in autoantibody diagnostic assays JF - Clinica chimica acta N2 - Diagnostics of Autoimmune Diseases involve screening of patient samples for containing autoantibodies against various antigens. To ensure quality of diagnostic assays a calibrator is needed in each assay system. Different calibrators as recombinant human monoclonal antibodies as well as chimeric antibodies against the autoantigens of interest are described. A less cost-intensive and also more representative possibility covering different targets on the antigens is the utilization of polyclonal sera from other species. Nevertheless, the detection of human autoantibodies as well as the calibration reagent containing antibodies from other species in one assay constitutes a challenge in terms of assay calibration. We therefore developed a cross-reactive monoclonal antibody which binds human as well as rabbit sera with similar affinities in the nanomolar range. We tested our monoclonal antibody S38CD11B12 successfully in the commercial Serazym (R) Anti-Cardiolipin-beta 2-GPI IgG/IgM assay and could thereby prove the eligibility of S38CD11B12 as detection antibody in autoimmune diagnostic assays using rabbit derived sera as reference material. KW - Monoclonal antibody KW - Detection KW - Autoimmune diagnostics KW - Cross reactivity KW - Assay calibration Y1 - 2019 U6 - https://doi.org/10.1016/j.cca.2019.09.003 SN - 0009-8981 SN - 1873-3492 VL - 499 SP - 87 EP - 92 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Demal, Till Joscha A1 - Heise, Melina A1 - Reiz, Benedikt A1 - Dogra, Deepika A1 - Braenne, Ingrid A1 - Reichenspurner, Hermann A1 - Männer, Jörg A1 - Aherrahrou, Zouhair A1 - Schunkert, Heribert A1 - Erdmann, Jeanette A1 - Abdelilah-Seyfried, Salim T1 - A familial congenital heart disease with a possible multigenic origin involving a mutation in BMPR1A JF - Scientific reports N2 - The genetics of many congenital heart diseases (CHDs) can only unsatisfactorily be explained by known chromosomal or Mendelian syndromes. Here, we present sequencing data of a family with a potentially multigenic origin of CHD. Twelve of nineteen family members carry a familial mutation [NM_004329.2:c.1328 G > A (p.R443H)] which encodes a predicted deleterious variant of BMPR1A. This mutation co-segregates with a linkage region on chromosome 1 that associates with the emergence of severe CHDs including Ebstein’s anomaly, atrioventricular septal defect, and others. We show that the continuous overexpression of the zebrafish homologous mutation bmpr1aap.R438H within endocardium causes a reduced AV valve area, a downregulation of Wnt/ß-catenin signalling at the AV canal, and growth of additional tissue mass in adult zebrafish hearts. This finding opens the possibility of testing genetic interactions between BMPR1A and other candidate genes within linkage region 1 which may provide a first step towards unravelling more complex genetic patterns in cardiovascular disease aetiology. Y1 - 2019 U6 - https://doi.org/10.1038/s41598-019-39648-7 SN - 2045-2322 VL - 9 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Jantzen, Friederike A1 - Wozniak, Natalia Joanna A1 - Kappel, Christian A1 - Sicard, Adrien A1 - Lenhard, Michael T1 - A high‑throughput amplicon‑based method for estimating outcrossing rates JF - Plant Methods N2 - Background: The outcrossing rate is a key determinant of the population-genetic structure of species and their long-term evolutionary trajectories. However, determining the outcrossing rate using current methods based on PCRgenotyping individual offspring of focal plants for multiple polymorphic markers is laborious and time-consuming. Results: We have developed an amplicon-based, high-throughput enabled method for estimating the outcrossing rate and have applied this to an example of scented versus non-scented Capsella (Shepherd’s Purse) genotypes. Our results show that the method is able to robustly capture differences in outcrossing rates. They also highlight potential biases in the estimates resulting from differential haplotype sharing of the focal plants with the pollen-donor population at individual amplicons. Conclusions: This novel method for estimating outcrossing rates will allow determining this key population-genetic parameter with high-throughput across many genotypes in a population, enabling studies into the genetic determinants of successful pollinator attraction and outcrossing. KW - Outcrossing KW - Mixed mating KW - Outcrossing rate KW - Capsella KW - Amplicon sequencing Y1 - 2019 U6 - https://doi.org/10.1186/s13007-019-0433-9 SN - 1746-4811 VL - 15 IS - 47 PB - BioMed Central CY - London ER - TY - JOUR A1 - Schiro, Gabriele A1 - Colangeli, Pierluigi A1 - Müller, Marina E. H. T1 - A Metabarcoding Analysis of the Mycobiome of Wheat Ears Across a Topographically Heterogeneous Field JF - Frontiers in microbiology KW - Fusarium KW - microclimate KW - canopy KW - fungal community KW - Alternaria KW - spatially induced variance Y1 - 2019 U6 - https://doi.org/10.3389/fmicb.2019.02095 SN - 1664-302X VL - 10 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Kagel, Heike A1 - Bier, Frank Fabian A1 - Frohme, Marcus A1 - Glökler, Jörn F. T1 - A Novel Optical Method To Reversibly Control Enzymatic Activity Based On Photoacids JF - Scientific reports N2 - Most biochemical reactions depend on the pH value of the aqueous environment and some are strongly favoured to occur in an acidic environment. A non-invasive control of pH to tightly regulate such reactions with defined start and end points is a highly desirable feature in certain applications, but has proven difficult to achieve so far. We report a novel optical approach to reversibly control a typical biochemical reaction by changing the pH and using acid phosphatase as a model enzyme. The reversible photoacid G-acid functions as a proton donor, changing the pH rapidly and reversibly by using high power UV LEDs as an illumination source in our experimental setup. The reaction can be tightly controlled by simply switching the light on and off and should be applicable to a wide range of other enzymatic reactions, thus enabling miniaturization and parallelization through non-invasive optical means. Y1 - 2019 U6 - https://doi.org/10.1038/s41598-019-50867-w SN - 2045-2322 VL - 9 PB - Nature Publishing Group CY - London ER - TY - JOUR A1 - Kopp, Johannes Florian A1 - Müller, Sandra Marie A1 - Pohl, Gabriele A1 - Lossow, Kristina A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja T1 - A quick and simple method for the determination of six trace elements in mammalian serum samples using ICP-MS/MS JF - Journal of trace elements in medicine and biology N2 - In order to assess the individual trace element status of humans for either medical or scientific purposes, amongst others, blood serum levels are determined. Furthermore, animal models are used to study interactions of trace elements. Most published methods require larger amounts (500-1000 mu L) of serum to achieve a reliable determination of multiple trace elements. However, oftentimes, these amounts of serum cannot be dedicated to a single analysis and the amount available for TE-determination is much lower. Therefore, a published ICP-MS/MS method for trace element determination in serum was miniaturized, optimized and validated for the measurement of Mn, Fe, Cu Zn, I and Se in as little as 50 mu L of human and murine serum and is presented in this work. For validation, recoveries of multiple LOTs and levels from commercially available human reference serum samples were determined, infra- and inter-day variations were assessed and limits of detection and quantification determined. It is shown, that the method is capable of giving accurate and reproducible results for all six elements within the relevant concentration ranges for samples from humans living in central Europe as well as from laboratory mice. As a highlight, the achieved limits of detection and quantification for Mn were found to be at 0.02 mu g/L serum and 0.05 mu g/L serum, respectively, while using an alkaline diluent for the parallel determination of iodine. Y1 - 2019 U6 - https://doi.org/10.1016/j.jtemb.2019.04.015 SN - 0946-672X VL - 54 SP - 221 EP - 225 PB - Elsevier CY - München ER - TY - JOUR A1 - Sedaghatmehr, Mastoureh A1 - Thirumalaikumar, Venkatesh P. A1 - Kamranfar, Iman A1 - Marmagne, Anne A1 - Masclaux-Daubresse, Celine A1 - Balazadeh, Salma T1 - A regulatory role of autophagy for resetting the memory of heat stress in plants JF - Plant, cell & environment : cell physiology, whole-plant physiology, community physiology N2 - As sessile life forms, plants are repeatedly confronted with adverse environmental conditions, which can impair development, growth, and reproduction. During evolution, plants have established mechanisms to orchestrate the delicate balance between growth and stress tolerance, to reset cellular biochemistry once stress vanishes, or to keep a molecular memory, which enables survival of a harsher stress that may arise later. Although there are several examples of memory in diverse plants species, the molecular machinery underlying the formation, duration, and resetting of stress memories is largely unknown so far. We report here that autophagy, a central self-degradative process, assists in resetting cellular memory of heat stress (HS) in Arabidopsis thaliana. Autophagy is induced by thermopriming (moderate HS) and, intriguingly, remains high long after stress termination. We demonstrate that autophagy mediates the specific degradation of heat shock proteins at later stages of the thermorecovery phase leading to the accumulation of protein aggregates after the second HS and a compromised heat tolerance. Autophagy mutants retain heat shock proteins longer than wild type and concomitantly display improved thermomemory. Our findings reveal a novel regulatory mechanism for HS memory in plants. KW - Arabidopsis KW - heat shock proteins KW - priming KW - resetting Y1 - 2019 U6 - https://doi.org/10.1111/pce.13426 SN - 0140-7791 SN - 1365-3040 VL - 42 IS - 3 SP - 1054 EP - 1064 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Albers, Philip A1 - Üstün, Suayib A1 - Witzel, Katja A1 - Kraner, Max Erdmund A1 - Börnke, Frederik T1 - A Remorin from Nicotiana benthamiana Interacts with the Pseudomonas Type-III Effector Protein HopZ1a and is Phosphorylated by the Immune-Related Kinase PBS1 JF - Molecular Plant-Microbe Interactions N2 - The plasma membrane (PM) is at the interface of plant-pathogen interactions and, thus, many bacterial type-III effector (T3E) proteins target membrane-associated processes to interfere with immunity. The Pseudomonas syringae T3E HopZ1a is a host cell PM-localized effector protein that has several immunity-associated host targets but also activates effector-triggered immunity in resistant backgrounds. Although HopZ1a has been shown to interfere with early defense signaling at the PM, no dedicated PM-associated HopZ1a target protein has been identified until now. Here, we show that HopZ1a interacts with the PM-associated remorin protein NbREM4 from Nicotiana benthamiana in several independent assays. NbREM4 relocalizes to membrane nanodomains after treatment with the bacterial elicitor flg22 and transient overexpression of NbREM4 in N. benthamiana induces the expression of a subset of defense-related genes. We can further show that NbREM4 interacts with the immune-related receptor-like cytoplasmic kinase avrPphB-susceptible 1 (PBS1) and is phosphorylated by PBS1 on several residues in vitro. Thus, we conclude that NbREM4 is associated with early defense signaling at the PM. The possible relevance of the HopZ1a-NbREM4 interaction for HopZ1a virulence and avirulence functions is discussed. KW - bacterial pathogenesis KW - defense signaling pathways KW - effectors KW - elicitors KW - HopZ1a KW - MAMPs KW - PAMPs KW - PBS1 KW - Pseudomonas syringae KW - remorin KW - type-3 secretion Y1 - 2019 U6 - https://doi.org/10.1094/MPMI-04-19-0105-R SN - 0894-0282 SN - 1943-7706 VL - 32 IS - 9 SP - 1229 EP - 1242 PB - Amer phytopathological SOC CY - ST Paul ER - TY - JOUR A1 - Rojas-Jimenez, Keilor A1 - Rieck, Angelika A1 - Wurzbacher, Christian A1 - Jürgens, Klaus A1 - Labrenz, Matthias A1 - Grossart, Hans-Peter T1 - A Salinity Threshold Separating Fungal Communities in the Baltic Sea JF - Frontiers in Microbiology N2 - Salinity is a significant factor for structuring microbial communities, but little is known for aquatic fungi, particularly in the pelagic zone of brackish ecosystems. In this study, we explored the diversity and composition of fungal communities following a progressive salinity decline (from 34 to 3 PSU) along three transects of ca. 2000 km in the Baltic Sea, the world’s largest estuary. Based on 18S rRNA gene sequence analysis, we detected clear changes in fungal community composition along the salinity gradient and found significant differences in composition of fungal communities established above and below a critical value of 8 PSU. At salinities below this threshold, fungal communities resembled those from freshwater environments, with a greater abundance of Chytridiomycota, particularly of the orders Rhizophydiales, Lobulomycetales, and Gromochytriales. At salinities above 8 PSU, communities were more similar to those from marine environments and, depending on the season, were dominated by a strain of the LKM11 group (Cryptomycota) or by members of Ascomycota and Basidiomycota. Our results highlight salinity as an important environmental driver also for pelagic fungi, and thus should be taken into account to better understand fungal diversity and ecological function in the aquatic realm. KW - fungal diversity KW - baltic sea KW - salinity gradient KW - brackish waters KW - chytridiomycota KW - cryptomycota Y1 - 2019 U6 - https://doi.org/10.3389/fmicb.2019.00680 SN - 1664-302X VL - 10 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Gonzalez-Fortes, Gloria M. A1 - Tassi, F. A1 - Trucchi, E. A1 - Henneberger, K. A1 - Paijmans, Johanna L. A. A1 - Diez-del-Molino, D. A1 - Schroeder, H. A1 - Susca, R. R. A1 - Barroso-Ruiz, C. A1 - Bermudez, F. J. A1 - Barroso-Medina, C. A1 - Bettencourt, A. M. S. A1 - Sampaio, H. A. A1 - Salas, A. A1 - de Lombera-Hermida, A. A1 - Fabregas Valcarce, Ramón A1 - Vaquero, M. A1 - Alonso, S. A1 - Lozano, Marina A1 - Rodriguez-Alvarez, Xose Pedro A1 - Fernandez-Rodriguez, C. A1 - Manica, Andrea A1 - Hofreiter, Michael A1 - Barbujani, Guido T1 - A western route of prehistoric human migration from Africa into the Iberian Peninsula JF - Proceedings of the Royal Society of London : B, Biological sciences N2 - Being at the western fringe of Europe, Iberia had a peculiar prehistory and a complex pattern of Neolithization. A few studies, all based on modern populations, reported the presence of DNA of likely African origin in this region, generally concluding it was the result of recent gene flow, probably during the Islamic period. Here, we provide evidence of much older gene flow from Africa to Iberia by sequencing whole genomes from four human remains from northern Portugal and southern Spain dated around 4000 years BP (from the Middle Neolithic to the Bronze Age). We found one of them to carry an unequivocal sub-Saharan mitogenome of most probably West or West-Central African origin, to our knowledge never reported before in prehistoric remains outside Africa. Our analyses of ancient nuclear genomes show small but significant levels of sub-Saharan African affinity in several ancient Iberian samples, which indicates that what we detected was not an occasional individual phenomenon, but an admixture event recognizable at the population level. We interpret this result as evidence of an early migration process from Africa into the Iberian Peninsula through a western route, possibly across the Strait of Gibraltar. KW - palaeogenome KW - Africa KW - Iberia KW - mitochondrial DNA KW - gene flow KW - admixture Y1 - 2019 U6 - https://doi.org/10.1098/rspb.2018.2288 SN - 0962-8452 SN - 1471-2954 VL - 286 IS - 1895 PB - Royal Society CY - London ER - TY - JOUR A1 - Alker, Wiebke A1 - Schwerdtle, Tanja A1 - Schomburg, Lutz A1 - Haase, Hajo T1 - A Zinpyr-1-based Fluorimetric Microassay for Free Zinc in Human Serum JF - International journal of molecular sciences N2 - Zinc is an essential trace element, making it crucial to have a reliable biomarker for evaluating an individual’s zinc status. The total serum zinc concentration, which is presently the most commonly used biomarker, is not ideal for this purpose, but a superior alternative is still missing. The free zinc concentration, which describes the fraction of zinc that is only loosely bound and easily exchangeable, has been proposed for this purpose, as it reflects the highly bioavailable part of serum zinc. This report presents a fluorescence-based method for determining the free zinc concentration in human serum samples, using the fluorescent probe Zinpyr-1. The assay has been applied on 154 commercially obtained human serum samples. Measured free zinc concentrations ranged from 0.09 to 0.42 nM with a mean of 0.22 ± 0.05 nM. It did not correlate with age or the total serum concentrations of zinc, manganese, iron or selenium. A negative correlation between the concentration of free zinc and total copper has been seen for sera from females. In addition, the free zinc concentration in sera from females (0.21 ± 0.05 nM) was significantly lower than in males (0.23 ± 0.06 nM). The assay uses a sample volume of less than 10 µL, is rapid and cost-effective and allows us to address questions regarding factors influencing the free serum zinc concentration, its connection with the body’s zinc status, and its suitability as a future biomarker for an individual’s zinc status. KW - zinc KW - free zinc KW - serum KW - biomarker KW - fluorescent probe KW - Zinypr-1 Y1 - 2019 U6 - https://doi.org/10.3390/ijms20164006 SN - 1661-6596 SN - 1422-0067 VL - 20 IS - 16 PB - MDPI CY - Basel ER - TY - JOUR A1 - Zeitler, Stefanie A1 - Ye, Lian A1 - Andreyeva, Aksana A1 - Schumacher, Fabian A1 - Monti, Juliana A1 - Nürnberg, Bernd A1 - Nowak, Gabriel A1 - Kleuser, Burkhard A1 - Reichel, Martin A1 - Fejtova, Anna A1 - Kornhuber, Johannes A1 - Rhein, Cosima A1 - Friedland, Kristina T1 - Acid sphingomyelinase - a regulator of canonical transient receptor potential channel 6 (TRPC6) activity JF - Journal of neurochemistry N2 - Recent investigations propose the acid sphingomyelinase (ASM)/ceramide system as a novel target for antidepressant action. ASM catalyzes the breakdown of the abundant membrane lipid sphingomyelin to the lipid messenger ceramide. This ASM‐induced lipid modification induces a local shift in membrane properties, which influences receptor clustering and downstream signaling. Canonical transient receptor potential channels 6 (TRPC6) are non‐selective cation channels located in the cell membrane that play an important role in dendritic growth, synaptic plasticity and cognition in the brain. They can be activated by hyperforin, an ingredient of the herbal remedy St. John’s wort for treatment of depression disorders. Because of their role in the context of major depression, we investigated the crosstalk between the ASM/ceramide system and TRPC6 ion channels in a pheochromocytoma cell line 12 neuronal cell model (PC12 rat pheochromocytoma cell line). Ca2+ imaging experiments indicated that hyperforin‐induced Ca2+ influx through TRPC6 channels is modulated by ASM activity. While antidepressants, known as functional inhibitors of ASM activity, reduced TRPC6‐mediated Ca2+ influx, extracellular application of bacterial sphingomyelinase rebalanced TRPC6 activity in a concentration‐related way. This effect was confirmed in whole‐cell patch clamp electrophysiology recordings. Lipidomic analyses revealed a decrease in very long chain ceramide/sphingomyelin molar ratio after ASM inhibition, which was connected with changes in the abundance of TRPC6 channels in flotillin‐1–positive lipid rafts as visualized by western blotting. Our data provide evidence that the ASM/ceramide system regulates TRPC6 channels likely by controlling their recruitment to specific lipid subdomains and thereby fine‐tuning their physical properties. KW - acid sphingomyelinase KW - antidepressants KW - ceramide KW - hyperforin KW - lipid rafts KW - TRPC6 Y1 - 2019 U6 - https://doi.org/10.1111/jnc.14823 SN - 0022-3042 SN - 1471-4159 VL - 150 IS - 6 SP - 678 EP - 690 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Beckmann, Nadine A1 - Becker, Katrin Anne A1 - Kadow, Stephanie A1 - Schumacher, Fabian A1 - Kramer, Melanie A1 - Kuehn, Claudine A1 - Schulz-Schaeffer, Walter J. A1 - Edwards, Michael J. A1 - Kleuser, Burkhard A1 - Gulbins, Erich A1 - Carpinteiro, Alexander T1 - Acid Sphingomyelinase Deficiency Ameliorates Farber Disease JF - International journal of molecular sciences N2 - Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can’t achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients. KW - Farber disease KW - lysosomal storage disorders KW - acid ceramidase KW - acid sphingomyelinase KW - amitriptyline Y1 - 2019 U6 - https://doi.org/10.3390/ijms20246253 SN - 1422-0067 VL - 20 IS - 24 PB - MDPI CY - Basel ER - TY - JOUR A1 - Andrés-Delgado, Laura A1 - Ernst, Alexander A1 - Galardi-Castilla, María A1 - Bazaga, David A1 - Peralta, Marina A1 - Münch, Juliane A1 - Gonzalez-Rosa, Juan M. A1 - Marques, Inês A1 - Tessadori, Federico A1 - de la Pompa, José Luis A1 - Vermot, Julien A1 - Mercader, Nadia T1 - Actin dynamics and the Bmp pathway drive apical extrusion of proepicardial cells JF - Development : Company of Biologists N2 - The epicardium, the outer mesothelial layer enclosing the myocardium, plays key roles in heart development and regeneration. During embryogenesis, the epicardium arises from the proepicardium (PE), a cell cluster that appears in the dorsal pericardium (DP) close to the venous pole of the heart. Little is known about how the PE emerges from the pericardial mesothelium. Using a zebrafish model and a combination of genetic tools, pharmacological agents and quantitative in vivo imaging, we reveal that a coordinated collective movement of DP cells drives PE formation. We found that Bmp signaling and the actomyosin cytoskeleton promote constriction of the DP, which enables PE cells to extrude apically. We provide evidence that cell extrusion, which has been described in the elimination of unfit cells from epithelia and the emergence of hematopoietic stem cells, is also a mechanism for PE cells to exit an organized mesothelium and fulfil their developmental fate to form a new tissue layer, the epicardium. KW - Actomyosin KW - Bmp KW - Cell extrusion KW - Proepicardium KW - Zebrafish KW - Heart development Y1 - 2019 U6 - https://doi.org/10.1242/dev.174961 SN - 0950-1991 SN - 1477-9129 VL - 146 IS - 13 PB - The Company of Biologists Ltd CY - Cambridge ER - TY - THES A1 - Paraskevopoulou, Sofia T1 - Adaptive genetic variation and responses to thermal stress in brachionid rotifers N2 - The importance of cryptic diversity in rotifers is well understood regarding its ecological consequences, but there remains an in depth comprehension of the underlying molecular mechanisms and forces driving speciation. Temperature has been found several times to affect species spatio-temporal distribution and organisms’ performance, but we lack information on the mechanisms that provide thermal tolerance to rotifers. High cryptic diversity was found recently in the freshwater rotifer “Brachionus calyciflorus”, showing that the complex comprises at least four species: B. calyciflorus sensu stricto (s.s.), B. fernandoi, B. dorcas, and B. elevatus. The temporal succession among species which have been observed in sympatry led to the idea that temperature might play a crucial role in species differentiation. The central aim of this study was to unravel differences in thermal tolerance between species of the former B. calyciflorus species complex by comparing phenotypic and gene expression responses. More specifically, I used the critical maximum temperature as a proxy for inter-species differences in heat-tolerance; this was modeled as a bi-dimensional phenotypic trait taking into consideration the intention and the duration of heat stress. Significant differences on heat-tolerance between species were detected, with B. calyciflorus s.s. being able to tolerate higher temperatures than B. fernandoi. Based on evidence of within species neutral genetic variation, I further examined adaptive genetic variability within two different mtDNA lineages of the heat tolerant B. calyciflorus s.s. to identify SNPs and genes under selection that might reflect their adaptive history. These analyses did not reveal adaptive genetic variation related to heat, however, they show putatively adaptive genetic variation which may reflect local adaptation. Functional enrichment of putatively positively selected genes revealed signals of adaptation in genes related to “lipid metabolism”, “xenobiotics biodegradation and metabolism” and “sensory system”, comprising candidate genes which can be utilized in studies on local adaptation. An absence of genetically-based differences in thermal adaptation between the two mtDNA lineages, together with our knowledge that B. calyciflorus s.s. can withstand a broad range of temperatures, led to the idea to further investigate shared transcriptomic responses to long-term exposure to high and low temperatures regimes. With this, I identified candidate genes that are involved in the response to temperature imposed stress. Lastly, I used comparative transcriptomics to examine responses to imposed heat-stress in heat-tolerant and heat-sensitive Brachionus species. I found considerably different patterns of gene expression in the two species. Most striking are patterns of expression regarding the heat shock proteins (hsps) between the two species. In the heat-tolerant, B. calyciflorus s.s., significant up-regulation of hsps at low temperatures was indicative of a stress response at the cooler end of the temperature regimes tested here. In contrast, in the heat-sensitive B. fernandoi, hsps generally exhibited up-regulation of these genes along with rising temperatures. Overall, identification of differences in expression of genes suggests suppression of protein biosynthesis to be a mechanism to increase thermal tolerance. Observed patterns in population growth are correlated with the hsp gene expression differences, indicating that this physiological stress response is indeed related to phenotypic life history performance. N2 - Obwohl die kryptische Diversität von Rotatorien (Rädertierchen) und die daraus resultierenden ökologischen Konsequenzen inzwischen sehr gut verstanden sind, sind die zugrunde liegenden molekularen Mechanismen und die Artbildungsprozesse bisher weitgehend unbekannt. Bekannt ist, dass die Temperatur eine bedeutende Rolle in den raum-zeitlichen Verbreitungsmustern der Arten sowie der Leistungsfähigkeit der Organismen, spielt. Es fehlen jedoch konkrete Informationen über die der Thermotoleranz zugrundeliegenden Mechanismen bei Rotatorien. Vor kurzem wurde hohe kryptische Diversität in der unter anderem in Süßwasser vorkommenden Art „Brachionus calyciflorus“ gefunden, so dass diese nun in mindestens vier Arten (B. calyciflorus sensu stricto (s.s.), B. fernandoi, B. dorcas und B. elevatus) unterteilt wurde. Beobachtungen von in Sympatrie vorkommenden Arten haben gezeigt, dass eine zeitliche Suksession innerhalb dieser Arten existiert, was vermuten lässt, dass Temperatur eine entscheidende Rolle bei der Artbildung gespielt haben könnte. Ziel dieser Arbeit ist es, Thermotoleranzunterschiede zwischen Arten des früheren B. calyciflorus-Artenkomplexes durch den Vergleich von phänotypischen und molekularen (Genexpression) Reaktionen auf Temperatur festzustellen. Die in dieser Untersuchung ermittelte kritische Maximaltemperatur wurde als Schätzer für zwischenartliche Hitzetoleranz verwendet. Mit Hilfe eines zweidimensionalen Verfahrens, welches sowohl die Dauer als auch die Stärke des Hitzestresses detektiert, konnte festgestellt werden, dass B. calyciflorus s.s. im Vergleich zu B. fernandoi hitzetoleranter ist. Auf Basis der innerartlichen genetischen Variation erfolgte eine tiefergehende Untersuchung zweier unterschiedlicher maternaler (mtDNA) Evolutionslinien der hitzetoleranteren Art B. calyciflorus s.s mit dem Ziel, unter divergenter Selektion stehende SNPs und Gene zu identifizieren, welche die Anpassung an verschiedene Temperaturen widerspiegeln könnten. Mit Hilfe dieses Experimentes war es möglich, potentiell positiv selektiere Kandidatengene zu identifizieren, welche im Zusammenhang mit dem „Lipidmetabolismus“, dem „Metabolismus und Abbau von Xenobiotika“ sowie dem „Sensorischen System“ stehen. Diese Kandidatengene lassen Rückschlüsse auf lokale Anpassungen zu. Es konnten keine genetischen Unterschiede gefunden werden, die im Zusammenhang mit der Temperaturanpassung der beiden untersuchten Evolutionslinien stehen. Um molekulare Grundlagen für die Toleranz von B. calyciflorus s.s für einen großen Temperaturbereich zu identifizieren, wurde das Transkriptom untersucht. Mit Hilfe der erhobenen Daten konnten Kandidatengene identifiziert werden, die für die Temperaturtoleranz von Bedeutung sind. Der letzte Teil dieser Arbeit konzentrierte sich auf die Untersuchung der Hitzestressantwort in einer hitzetoleranten und einer hitzesensitiven Brachionus Art. Diese Untersuchung konnte erhebliche Unterschiede in den Genexpre-ssionsmustern der beiden Arten aufzeigen. Die deutlichsten Unterschiede der Genexpression wurden hierbei in der Expression von Genen detektiert, die für die sogenannten Hitze-Schock-Proteinen (Heat-shock-proteins: hsp) codieren. In der hitzetoleranten Art B. calyciflorus s.s wurde ein signifikanter Anstieg der hsp-Genexpression bei geringen Temperaturen festgestellt, während bei der hitzesensitiven Art B. fernandoi ein signifikanter Anstieg bei hohen Temperaturen detektiert wurde. Die in dieser Arbeit gefundenen Unterschiede in der Genexpression zeigen, dass Temperaturstress eine Hemmung der Proteinbiosynthese bewirken kann, was zu einer erhöhten Thermotoleranz führt. Darüber hinaus ist Populationswachstum mit der Expression von Hitze-Schock-Proteingenen korreliert. Dies deutet darauf hin, dass die hier beschriebene physiologische Temperaturstressantwort tatsächlich mit den beobachteten phänotypischen Fitnessparametern im Zusammenhang steht. KW - Brachionus KW - zooplankton KW - temperature KW - RNA-seq KW - transcriptome KW - adaptation Y1 - 2019 ER - TY - JOUR A1 - Radchuk, Viktoriia A1 - Reed, Thomas A1 - Teplitsky, Celine A1 - van de Pol, Martijn A1 - Charmantier, Anne A1 - Hassall, Christopher A1 - Adamik, Peter A1 - Adriaensen, Frank A1 - Ahola, Markus P. A1 - Arcese, Peter A1 - Miguel Aviles, Jesus A1 - Balbontin, Javier A1 - Berg, Karl S. A1 - Borras, Antoni A1 - Burthe, Sarah A1 - Clobert, Jean A1 - Dehnhard, Nina A1 - de Lope, Florentino A1 - Dhondt, Andre A. A1 - Dingemanse, Niels J. A1 - Doi, Hideyuki A1 - Eeva, Tapio A1 - Fickel, Jörns A1 - Filella, Iolanda A1 - Fossoy, Frode A1 - Goodenough, Anne E. A1 - Hall, Stephen J. G. A1 - Hansson, Bengt A1 - Harris, Michael A1 - Hasselquist, Dennis A1 - Hickler, Thomas A1 - Jasmin Radha, Jasmin A1 - Kharouba, Heather A1 - Gabriel Martinez, Juan A1 - Mihoub, Jean-Baptiste A1 - Mills, James A. A1 - Molina-Morales, Mercedes A1 - Moksnes, Arne A1 - Ozgul, Arpat A1 - Parejo, Deseada A1 - Pilard, Philippe A1 - Poisbleau, Maud A1 - Rousset, Francois A1 - Rödel, Mark-Oliver A1 - Scott, David A1 - Carlos Senar, Juan A1 - Stefanescu, Constanti A1 - Stokke, Bard G. A1 - Kusano, Tamotsu A1 - Tarka, Maja A1 - Tarwater, Corey E. A1 - Thonicke, Kirsten A1 - Thorley, Jack A1 - Wilting, Andreas A1 - Tryjanowski, Piotr A1 - Merila, Juha A1 - Sheldon, Ben C. A1 - Moller, Anders Pape A1 - Matthysen, Erik A1 - Janzen, Fredric A1 - Dobson, F. Stephen A1 - Visser, Marcel E. A1 - Beissinger, Steven R. A1 - Courtiol, Alexandre A1 - Kramer-Schadt, Stephanie T1 - Adaptive responses of animals to climate change are most likely insufficient JF - Nature Communications N2 - Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trait changes associated with climate change are adaptive in animals. A meta-analysis focussing on birds, the taxon best represented in our dataset, suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits. We demonstrate that these advances are adaptive for some species, but imperfect as evidenced by the observed consistent selection for earlier timing. Application of a theoretical model indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species. Y1 - 2019 U6 - https://doi.org/10.1038/s41467-019-10924-4 SN - 2041-1723 VL - 10 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Langhammer, Maria A1 - Thober, Jule A1 - Lange, Martin A1 - Frank, Karin A1 - Grimm, Volker T1 - Agricultural landscape generators for simulation models BT - a review of existing solutions and an outline of future directions JF - Ecological modelling : international journal on ecological modelling and engineering and systems ecolog N2 - There is an increasing need for an assessment of the impacts of land use and land use change (LUCC). In this context, simulation models are valuable tools for investigating the impacts of stakeholder actions or policy decisions. Agricultural landscape generators (ALGs), which systematically and automatically generate realistic but simplified representations of land cover in agricultural landscapes, can provide the input for LUCC models. We reviewed existing ALGs in terms of their objectives, design and scope. We found eight ALGs that met our definition. They were based either on generic mathematical algorithms (pattern-based) or on representations of ecological or land use processes (process-based). Most ALGs integrate only a few landscape metrics, which limits the design of the landscape pattern and thus the range of applications. For example, only a few specific farming systems have been implemented. We conclude that existing ALGs contain useful approaches that can be used for specific purposes, but ideally generic modular ALGs are developed that can be used for a wide range of scenarios, regions and model types. We have compiled features of such generic ALGs and propose a possible software architecture. Considerable joint efforts are required to develop such generic ALGs, but the benefits in terms of a better understanding and development of more efficient agricultural policies would be high. KW - Agricultural landscape KW - Field pattern KW - Agricultural landscape generator KW - Landscape simulator KW - Neutral landscape model KW - Process-based model Y1 - 2019 U6 - https://doi.org/10.1016/j.ecolmodel.2018.12.010 SN - 0304-3800 SN - 1872-7026 VL - 393 SP - 135 EP - 151 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Schröter, David A1 - Neugart, Susanne A1 - Schreiner, Monika A1 - Grune, Tilman A1 - Rohn, Sascha A1 - Ott, Christiane T1 - Amaranth’s 2-Caffeoylisocitric Acid—An Anti-Inflammatory Caffeic Acid Derivative That Impairs NF-κB Signaling in LPS-Challenged RAW 264.7 Macrophages JF - Nutrients N2 - For centuries, Amaranthus sp. were used as food, ornamentals, and medication. Molecular mechanisms, explaining the health beneficial properties of amaranth, are not yet understood, but have been attributed to secondary metabolites, such as phenolic compounds. One of the most abundant phenolic compounds in amaranth leaves is 2-caffeoylisocitric acid (C-IA) and regarding food occurrence, C-IA is exclusively found in various amaranth species. In the present study, the anti-inflammatory activity of C-IA, chlorogenic acid, and caffeic acid in LPS-challenged macrophages (RAW 264.7) has been investigated and cellular contents of the caffeic acid derivatives (CADs) were quantified in the cells and media. The CADs were quantified in the cell lysates in nanomolar concentrations, indicating a cellular uptake. Treatment of LPS-challenged RAW 264.7 cells with 10 µM of CADs counteracted the LPS effects and led to significantly lower mRNA and protein levels of inducible nitric oxide synthase, tumor necrosis factor alpha, and interleukin 6, by directly decreasing the translocation of the nuclear factor κB/Rel-like containing protein 65 into the nucleus. This work provides new insights into the molecular mechanisms that attribute to amaranth’s anti-inflammatory properties and highlights C-IA’s potential as a health-beneficial compound for future research. KW - inflammation KW - caffeic acid derivatives KW - RAW 264 KW - 7 macrophages KW - NF-kappa B KW - amaranth Y1 - 2019 U6 - https://doi.org/10.3390/nu11030571 SN - 2072-6643 VL - 11 IS - 3 PB - MDPI CY - Basel ER - TY - JOUR A1 - Liu, Junzhong A1 - Feng, Lili A1 - Gu, Xueting A1 - Deng, Xian A1 - Qiu, Qi A1 - Li, Qun A1 - Zhang, Yingying A1 - Wang, Muyang A1 - Deng, Yiwen A1 - Wang, Ertao A1 - He, Yuke A1 - Bäurle, Isabel A1 - Li, Jianming A1 - Cao, Xiaofeng A1 - He, Zuhua T1 - An H3K27me3 demethylase-HSFA2 regulatory loop orchestrates transgenerational thermomemory in Arabidopsis JF - Cell research N2 - Global warming has profound effects on plant growth and fitness. Plants have evolved sophisticated epigenetic machinery to respond quickly to heat, and exhibit transgenerational memory of the heat-induced release of post-transcriptional gene silencing (PTGS). However, how thermomemory is transmitted to progeny and the physiological relevance are elusive. Here we show that heat-induced HEAT SHOCK TRANSCRIPTION FACTOR A2 (HSFA2) directly activates the H3K27me3 demethylase RELATIVE OF EARLY FLOWERING 6 (REF6), which in turn derepresses HSFA2. REF6 and HSFA2 establish a heritable feedback loop, and activate an E3 ubiquitin ligase, SUPPRESSOR OF GENE SILENCING 3 (SGS3)-INTERACTING PROTEIN 1 (SGIP1). SGIP1-mediated SGS3 degradation leads to inhibited biosynthesis of trans-acting siRNA (tasiRNA). The REF6-HSFA2 loop and reduced tasiRNA converge to release HEAT-INDUCED TAS1 TARGET 5 (HTT5), which drives early flowering but attenuates immunity. Thus, heat induces transmitted phenotypes via a coordinated epigenetic network involving histone demethylases, transcription factors, and tasiRNAs, ensuring reproductive success and transgenerational stress adaptation. KW - Chromatin KW - Epigenetic memory KW - Epigenetics KW - Innate immunity KW - Plant signalling Y1 - 2019 U6 - https://doi.org/10.1038/s41422-019-0145-8 SN - 1001-0602 SN - 1748-7838 VL - 29 IS - 5 SP - 379 EP - 390 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Braune, Annett A1 - Gütschow, Michael A1 - Blaut, Michael T1 - An NADH-Dependent Reductase from Eubacterium ramulus Catalyzes the Stereospecific Heteroring Cleavage of Flavanones and Flavanonols JF - Applied and environmental microbiology N2 - The human intestinal anaerobe Eubacterium ramulus is known for its ability to degrade various dietary flavonoids. In the present study, we demonstrate the cleavage of the heterocyclic C-ring of flavanones and flavanonols by an oxygen-sensitive NADH-dependent reductase, previously described as enoate reductase, from E. ramulus. This flavanone- and flavanonol-cleaving reductase (Fcr) was purified following its heterologous expression in Escherichia coli and further characterized. Fcr cleaved the flavanones naringenin, eriodictyol, liquiritigenin, and homoeriodictyol. Moreover, the flavanonols taxifolin and dihydrokaempferol served as substrates. The catalyzed reactions were stereospecific for the (2R)-enantiomers of the flavanone substrates and for the (25,35)-configured flavanonols. The enantioenrichment of the nonconverted stereoisomers allowed for the determination of hitherto unknown flavanone racemization rates. Fcr formed the corresponding dihydrochalcones and hydroxydihydrochalcones in the course of an unusual reductive cleavage of cyclic ether bonds. Fcr did not convert members of other flavonoid subclasses, including flavones, flavonols, and chalcones, the latter indicating that the reaction does not involve a chalcone intermediate. This view is strongly supported by the observed enantiospecificity of Fcr. Cinnamic acids, which are typical substrates of bacterial enoate reductases, were also not reduced by Fcr. Based on the presence of binding motifs for dinucleotide cofactors and a 4Fe-4S cluster in the amino acid sequence of Fcr, a cofactor-mediated hydride transfer from NADH onto C-2 of the respective substrate is proposed. IMPORTANCE Gut bacteria play a crucial role in the metabolism of dietary flavonoids, thereby contributing to their activation or inactivation after ingestion by the human host. Thus, bacterial activities in the intestine may influence the beneficial health effects of these polyphenolic plant compounds. While an increasing number of flavonoid-converting gut bacterial species have been identified, knowledge of the responsible enzymes is still limited. Here, we characterized Fcr as a key enzyme involved in the conversion of flavonoids of several subclasses by Eubacterium ramulus, a prevalent human gut bacterium. Sequence similarity of this enzyme to hypothetical proteins from other flavonoid-degrading intestinal bacteria in databases suggests a more widespread occurrence of this enzyme. Functional characterization of gene products of human intestinal microbiota enables the assignment of metagenomic sequences to specific bacteria and, more importantly, to certain activities, which is a prerequisite for targeted modulation of gut microbial functionality. KW - Eubacterium ramulus KW - enantiospecificity KW - flavanone KW - flavanonol KW - flavonoid KW - intestinal bacteria KW - naringenin KW - reductase Y1 - 2019 U6 - https://doi.org/10.1128/AEM.01233-19 SN - 0099-2240 SN - 1098-5336 VL - 85 IS - 19 PB - American Society for Microbiology CY - Washington ER - TY - JOUR A1 - Neukranz, Yannika A1 - Kotter, Annika A1 - Beilschmidt, Lena A1 - Marelja, Zvonimir A1 - Helm, Mark A1 - Graf, Ralph A1 - Leimkühler, Silke T1 - Analysis of the Cellular Roles of MOCS3 Identifies a MOCS3-Independent Localization of NFS1 at the Tips of the Centrosome JF - Biochemistry N2 - The deficiency of the molybdenum cofactor (Moco) is an autosomal recessive disease, which leads to the loss of activity of all molybdoenzymes in humans with sulfite oxidase being the essential protein. Moco deficiency generally results in death in early childhood. Moco is a sulfur-containing cofactor synthesized in the cytosol with the sulfur being provided by a sulfur relay system composed of the L-cysteine desulfurase NFS1, MOCS3, and MOCS2A. Human MOCS3 is a dual-function protein that was shown to play an important role in Moco biosynthesis and in the mcm(5)s(2) U thio modifications of nucleosides in cytosolic tRNAs for Lys, Gln, and Glu. In this study, we constructed a homozygous MOCS3 knockout in HEK293T cells using the CRISPR/Cas9 system. The effects caused by the absence of MOCS3 were analyzed in detail. We show that sulfite oxidase activity was almost completely abolished, on the basis of the absence of Moco in these cells. In addition, mcm(5)s(2)U thio-modified tRNAs were not detectable. Because the L-cysteine desulfurase NFS1 was shown to act as a sulfur donor for MOCS3 in the cytosol, we additionally investigated the impact of a MOCS3 knockout on the cellular localization of NFS1. By different methods, we identified a MOCS3-independent novel localization of NFS1 at the centrosome. Y1 - 2019 U6 - https://doi.org/10.1021/acs.biochem.8b01160 SN - 0006-2960 VL - 58 IS - 13 SP - 1786 EP - 1798 PB - American Chemical Society CY - Washington ER - TY - THES A1 - Petrovic, Nevena T1 - Analysis of the role of Forgetter2 in thermotolerance responses in Arabidopsis thaliana Y1 - 2019 ER - TY - THES A1 - Kowalski, Gabriele Joanna T1 - Animal movement patterns across habitats BT - connecting biodiversity Y1 - 2019 ER - TY - GEN A1 - Ponce, Carol Barahona A1 - Scherer, Dominique A1 - Boekstegers, Felix A1 - Garate-Calderon, Valentina A1 - Jenab, Mazda A1 - Aleksandrova, Krasimira A1 - Katzke, Verena A1 - Weiderpass, Elisabete A1 - Bonet, Catalina A1 - Moradi, Tahereh A1 - Fischer, Krista A1 - Bossers, Willem A1 - Brenner, Hermann A1 - Schöttker, Ben A1 - Holleczek, Bernd A1 - Hveem, Kristian A1 - Eklund, Niina A1 - Voelker, Uwe A1 - Waldenberger, Melanie A1 - Bermejo, Justo Lorenzo T1 - Arsenic and gallbladder cancer risk BT - Mendelian randomization analysis of European prospective data T2 - International journal of cancer KW - arsenic KW - gallbladder cancer KW - Mendelian randomization Y1 - 2019 U6 - https://doi.org/10.1002/ijc.32837 SN - 0020-7136 SN - 1097-0215 VL - 146 IS - 9 SP - 2648 EP - 2650 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Awan, Asad Bashir A1 - Schiebel, Juliane A1 - Boehm, Alexander A1 - Nitschke, Joerg A1 - Sarwar, Yasra A1 - Schierack, Peter A1 - Ali, Aamir T1 - Association of biofilm formation and cytotoxic potential with multidrug resistance in clinical isolates of pseudomonas aeruginosa JF - EXCLI Journal N2 - Multidrug resistant (MDR) Pseudomonas aeruginosa having strong biofilm potential and virulence factors are a serious threat for hospitalized patients having compromised immunity In this study, 34 P. aeruginosa isolates of human origin (17 MDR and 17 non-MDR clinical isolates) were checked for biofilm formation potential in enriched and minimal media. The biofilms were detected using crystal violet method and a modified software package of the automated VideoScan screening method. Cytotoxic potential of the isolates was also investigated on HepG2, LoVo and T24 cell lines using automated VideoScan technology. Pulse field gel electrophoresis revealed 10 PFGE types in MDR and 8 in non-MDR isolates. Although all isolates showed biofilm formation potential, strong biofilm formation was found more in enriched media than in minimal media. Eight MDR isolates showed strong biofilm potential in both enriched and minimal media by both detection methods. Strong direct correlation between crystal violet and VideoScan methods was observed in identifying strong biofilm forming isolates. High cytotoxic effect was observed by 4 isolates in all cell lines used while 6 other isolates showed high cytotoxic effect on T24 cell line only. Strong association of multidrug resistance was found with biofilm formation as strong biofilms were observed significantly higher in MDR isolates (p-value < 0.05) than non-MDR isolates. No significant association of cytotoxic potential with multidrug resistance or biofilm formation was found (p-value > 0.05). The MDR isolates showing significant cytotoxic effects and strong biofilm formation impose a serious threat for hospitalized patients with weak immune system. KW - Pseudomonas aeruginosa KW - multidrug resistance KW - biofilm KW - cytotoxicity KW - VideoScan technology Y1 - 2019 U6 - https://doi.org/10.17179/excli2018-1948 SN - 1611-2156 VL - 18 SP - 79 EP - 90 PB - Leibniz Research Centre for Working Environment and Human Factors CY - Dortmund ER - TY - JOUR A1 - Eichelmann, Fabian A1 - Schulze, Matthias Bernd A1 - Wittenbecher, Clemens A1 - Menzel, Juliane A1 - Weikert, Cornelia A1 - di Giuseppe, Romina A1 - Biemann, Ronald A1 - Isermann, Berend A1 - Fritsche, Andreas A1 - Boeing, Heiner A1 - Aleksandrova, Krasimira T1 - Association of Chemerin Plasma Concentration With Risk of Colorectal Cancer JF - JAMA network open N2 - IMPORTANCE Inflammatory processes have been suggested to have an important role in colorectal cancer (CRC) etiology. Chemerin is a recently discovered inflammatory biomarker thought to exert chemotactic, adipogenic, and angiogenic functions. However, its potential link with CRC has not been sufficiently explored. OBJECTIVE To evaluate the prospective association of circulating plasma chemerin concentrations with incident CRC. DESIGN, SETTING, AND PARTICIPANTS Prospective case-cohort study based on 27 548 initially healthy participants from the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Potsdam cohort who were followed for up to 16 years. Baseline study information and samples were collected between August 23, 1994, and September 25, 1998. Recruitment was according to random registry sampling from the geographical area of Potsdam, Germany, and surrounding municipalities. The last date of study follow-up was May 10, 2010. Statistical analysis was conducted in 2018. MAIN OUTCOMES AND MEASURES Incident CRC, colon cancer, and rectal cancer. Baseline chemerin plasma concentrations were measured by enzyme-linked immunosorbent assay. CONCLUSIONS AND RELEVANCE This study found that the association between chemerin concentration and the risk of incident CRC was linear and independent of established CRC risk factors. Further studies are warranted to evaluate chemerin as a novel immune-inflammatory agent in colorectal carcinogenesis. Y1 - 2019 U6 - https://doi.org/10.1001/jamanetworkopen.2019.0896 SN - 2574-3805 VL - 2 IS - 3 PB - American Veterinary Medical Association CY - Chicago ER - TY - JOUR A1 - Wittenbecher, Clemens A1 - Kuxhaus, Olga A1 - Boeing, Heiner A1 - Stefan, Norbert A1 - Schulze, Matthias Bernd T1 - Associations of short stature and components of height with incidence of type 2 diabetes BT - mediating effects of cardiometabolic risk factors JF - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) N2 - Aims/hypothesis This study aimed to evaluate associations of height as well as components of height (sitting height and leg length) with risk of type 2 diabetes and to explore to what extent associations are explainable by liver fat and cardiometabolic risk markers. Methods A case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study comprising 26,437 participants who provided blood samples was designed. We randomly selected a subcohort of 2500 individuals (2029 diabetes-free at baseline and with anamnestic, anthropometrical and metabolic data for analysis). Of the 820 incident diabetes cases identified in the full cohort during 7 years of follow-up, 698 remained for analyses after similar exclusions. Results After adjustment for age, potential lifestyle confounders, education and waist circumference, greater height was related to lower diabetes risk (HR per 10 cm, men 0.59 [95% CI 0.47, 0.75] and women 0.67 [0.51, 0.88], respectively). Leg length was related to lower risk among men and women, but only among men if adjusted for total height. Adjustment for liver fat and triacylglycerols, adiponectin and C-reactive protein substantially attenuated associations between height and diabetes risk, particularly among women. Conclusions/interpretation We observed inverse associations between height and risk of type 2 diabetes, which was largely related to leg length among men. The inverse associations may be partly driven by lower liver fat content and a more favourable cardiometabolic profile. KW - Adult height KW - Blood pressure KW - Diabetes incidence KW - Leg length KW - Liver fat KW - Short stature KW - Trunk length Y1 - 2019 U6 - https://doi.org/10.1007/s00125-019-04978-8 SN - 0012-186X SN - 1432-0428 VL - 62 IS - 12 SP - 2211 EP - 2221 PB - Springer CY - New York ER - TY - JOUR A1 - Hornych, Ondrej A1 - Ekrt, Libor A1 - Riedel, Felix A1 - Koutecky, Petr A1 - Košnar, Jiří T1 - Asymmetric hybridization in Central European populations of the Dryopteris carthusiana group JF - America Journal of Botany N2 - Premise Hybridization is a key process in plant speciation. Despite its importance, there is no detailed study of hybridization rates in fern populations. A proper estimate of hybridization rates is needed to understand factors regulating hybridization. Methods We studied hybridization in the European Dryopteris carthusiana group, represented by one diploid and two tetraploid species and their hybrids. We sampled 100 individuals per population in 40 mixed populations of the D. carthusiana group across Europe. All plants were identified by measuring genome size (DAPI staining) using flow cytometry. To determine the maternal parentage of hybrids, we sequenced the chloroplast region trnL-trnF of all taxa involved. Results We found hybrids in 85% of populations. Triploid D. xambroseae occurred in every population that included both parent species and is most abundant when the parent species are equally abundant. By contrast, tetraploid D. xdeweveri was rare (15 individuals total) and triploid D. xsarvelae was absent. The parentage of hybrid taxa is asymmetric. Despite expectations from previous studies, tetraploid D. dilatata is the predominant male parent of its triploid hybrid. Conclusions This is a thorough investigation of hybridization rates in natural populations of ferns. Hybridization rates differ greatly even among closely related fern taxa. In contrast to angiosperms, our data suggest that hybridization rates are highest in balanced parent populations and support the notion that some ferns possess very weak barriers to hybridization. Our results from sequencing cpDNA challenge established notions about the correlation of ploidy level and mating tendencies. KW - antheridiogens KW - Dryopteridaceae KW - ferns KW - flow cytometry KW - hybridization rate KW - interspecific hybridization KW - polyploidy KW - reproductive isolation KW - speciation KW - trnL-trnF Y1 - 2019 U6 - https://doi.org/10.1002/ajb2.1369 SN - 0002-9122 SN - 1537-2197 VL - 106 IS - 11 SP - 1477 EP - 1486 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Batsios, Petros A1 - Ishikawa-Ankerhold, Hellen Christina A1 - Roth, Heike A1 - Schleicher, Michael A1 - Wong, Catherine C. L. A1 - Müller-Taubenberger, Annette T1 - Ate1-mediated posttranslational arginylation affects substrate adhesion and cell migration in Dictyostelium discoideum JF - Molecular biology of the cell : the official publication of the American Society for Cell Biology N2 - The highly conserved enzyme arginyl-tRNA-protein transferase (Ate1) mediates arginylation, a posttranslational modification that is only incompletely understood at its molecular level. To investigate whether arginylation affects actin-dependent processes in a simple model organism, Dictyostelium discoideum, we knocked out the gene encoding Ate1 and characterized the phenotype of ate1-null cells. Visualization of actin cytoskeleton dynamics by live-cell microscopy indicated significant changes in comparison to wild-type cells. Ate1-null cells were almost completely lacking focal actin adhesion sites at the substrate-attached surface and were only weakly adhesive. In two-dimensional chemotaxis assays toward folate or cAMP, the motility of ate1-null cells was increased. However, in three-dimensional chemotaxis involving more confined conditions, the motility of ate1-null cells was significantly reduced. Live-cell imaging showed that GFP-tagged Ate1 rapidly relocates to sites of newly formed actin-rich protrusions. By mass spectrometric analysis, we identified four arginylation sites in the most abundant actin isoform of Dictyostelium, in addition to arginylation sites in other actin isoforms and several actin-binding proteins. In vitro polymerization assays with actin purified from ate1-null cells revealed a diminished polymerization capacity in comparison to wild-type actin. Our data indicate that arginylation plays a crucial role in the regulation of cytoskeletal activities. Y1 - 2019 U6 - https://doi.org/10.1091/mbc.E18-02-0132 SN - 1059-1524 SN - 1939-4586 VL - 30 IS - 4 SP - 453 EP - 466 PB - American Society for Cell Biology CY - Bethesda ER - TY - JOUR A1 - Batista, Rita A. A1 - Figueiredo, Duarte Dionisio A1 - Santos-Gonzalez, Juan A1 - Köhler, Claudia T1 - Auxin regulates endosperm cellularization in Arabidopsis JF - Genes & Development N2 - The endosperm is an ephemeral tissue that nourishes the developing embryo, similar to the placenta in mammals. In most angiosperms, endosperm development starts as a syncytium, in which nuclear divisions are not followed by cytokinesis. The timing of endosperm cellularization largely varies between species, and the event triggering this transition remains unknown. Here we show that increased auxin biosynthesis in the endosperm prevents its cellularization, leading to seed arrest. Auxin-overproducing seeds phenocopy paternal-excess triploid seeds derived from hybridizations of diploid maternal plants with tetraploid fathers. Concurrently, auxin-related genes are strongly overexpressed in triploid seeds, correlating with increased auxin activity. Reducing auxin biosynthesis and signaling reestablishes endosperm cellularization in triploid seeds and restores their viability, highlighting a causal role of increased auxin in preventing endosperm cellularization. We propose that auxin determines the time of endosperm cellularization, and thereby uncovered a central role of auxin in establishing hybridization barriers in plants. KW - auxin KW - cellularization KW - endosperm KW - hybridization barrier KW - seed development KW - triploid block Y1 - 2019 U6 - https://doi.org/10.1101/gad.316554.118 SN - 0890-9369 SN - 1549-5477 VL - 33 IS - 7-8 SP - 466 EP - 476 PB - Cold Spring Harbor Laboratory Press CY - Cold Spring Harbor, NY ER - TY - JOUR A1 - Lechthaler, Silvia A1 - Colangeli, Pierluigi A1 - Gazzabin, Moira A1 - Anfodillo, Tommaso T1 - Axial anatomy of the leaf midrib provides new insights into the hydraulic architecture and cavitation patterns of Acer pseudoplatanus leaves JF - Journal of experimental botany N2 - The structure of leaf veins is typically described by a hierarchical scheme (e.g. midrib, 1(st) order, 2nd order), which is used to predict variation in conduit diameter from one order to another whilst overlooking possible variation within the same order. We examined whether xylem conduit diameter changes within the same vein order, with resulting consequences for resistance to embolism. We measured the hydraulic diameter (D-h), and number of vessels (V-N) along the midrib and petioles of leaves of Acer pseudoplatanus, and estimated the leaf area supplied (A(leaf-sup)) at different points of the midrib and how variation in anatomical traits affected embolism resistance. We found that D-h scales with distance from the midrib tip (path length, L) with a power of 0.42, and that V-N scales with A(leaf-sup) with a power of 0.66. Total conductive area scales isometrically with A(leaf-sup). Embolism events along the midrib occurred first in the basipetal part and then at the leaf tip where vessels are narrower. The distance from the midrib tip is a good predictor of the variation in vessel diameter along the 1st order veins in A. pseudoplatanus leaves and this anatomical pattern seems to have an effect on hydraulic integrity since wider vessels at the leaf base embolize first. KW - Acer pseudoplatanus KW - Leaf cavitation KW - leaf hydraulic architecture KW - leaf midrib KW - total conductive area KW - sycamore maple KW - vessel diameter KW - vessel number Y1 - 2019 U6 - https://doi.org/10.1093/jxb/erz347 SN - 0022-0957 SN - 1460-2431 VL - 70 IS - 21 SP - 6195 EP - 6201 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Haberland, Christian A1 - Hampe, Oliver A1 - Autenrieth, Marijke A1 - Voss, Manja T1 - Balaenoptera borealis Lesson, 1828 BT - rediscovery of a holotype JF - Mammalia N2 - The whereabouts of the Balaenoptera borealis holotype, the skeleton of a 1819 stranded specimen, have been unknown since the World War II (WWII). Due to nomenclatural confusion, deficient documentation, and finally WWII bombing, which destroyed predominantly cetacean material in the Museum fib Naturkunde Berlin (MfN), the type skeleton of the sei whale sank into oblivion. Construction activities enabled a recent search and study on the remaining whale material. Here, we provide evidence that the type specimen was not destroyed. On the basis of species-wide and individual characters of the type material such as the shape of cranial elements and the pattern of the maxillary foramina, we show that the skull and mandibles, the vertebral column (except the atlas), and the ribs of the holotype remain intact. Further evidence that these skeletal remains belong to the previously missing holotype is provided by the characteristics of the spine. In addition, we analyzed ancient DNA from bone samples and confirm they are B. borealis, and the occurrence of same mitochondrial haplotypes indicate that the bones belong to the same individual. Additionally, a blue inscription was discovered at the caudal epiphysis of a thoracic vertebra; historical research matched this inscription with the material belonging to the former Anatomical-Zootomical Museum, from which the holotype was once bought. KW - Baltic Sea KW - holotype KW - museum collection KW - sei whale KW - skeleton Y1 - 2019 U6 - https://doi.org/10.1515/mammalia-2017-0149 SN - 0025-1461 SN - 1864-1547 VL - 83 IS - 4 SP - 343 EP - 351 PB - De Gruyter CY - Berlin ER - TY - THES A1 - Neumann, Bettina T1 - Bioelectrocatalytic activity of surface-confined heme catalysts BT - from natural enzymes to synthetic analogs Y1 - 2019 ER - TY - JOUR A1 - Bornhorst, Dorothee A1 - Xia, Peng A1 - Nakajima, Hiroyuki A1 - Dingare, Chaitanya A1 - Herzog, Wiebke A1 - Lecaudey, Virginie A1 - Mochizuki, Naoki A1 - Heisenberg, Carl-Philipp A1 - Yelon, Deborah A1 - Abdelilah-Seyfried, Salim T1 - Biomechanical signaling within the developing zebrafish heart attunes endocardial growth to myocardial chamber dimensions JF - Nature Communications N2 - Intra-organ communication guides morphogenetic processes that are essential for an organ to carry out complex physiological functions. In the heart, the growth of the myocardium is tightly coupled to that of the endocardium, a specialized endothelial tissue that lines its interior. Several molecular pathways have been implicated in the communication between these tissues including secreted factors, components of the extracellular matrix, or proteins involved in cell-cell communication. Yet, it is unknown how the growth of the endocardium is coordinated with that of the myocardium. Here, we show that an increased expansion of the myocardial atrial chamber volume generates higher junctional forces within endocardial cells. This leads to biomechanical signaling involving VE-cadherin, triggering nuclear localization of the Hippo pathway transcriptional regulator Yap1 and endocardial proliferation. Our work suggests that the growth of the endocardium results from myocardial chamber volume expansion and ends when the tension on the tissue is relaxed. Y1 - 2019 U6 - https://doi.org/10.1038/s41467-019-12068-x SN - 2041-1723 VL - 10 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Rieck, Christoph Paul Kurt A1 - Geiger, Daniel A1 - Munkert, Jennifer A1 - Messerschmidt, Katrin A1 - Petersen, Jan A1 - Strasser, Juliane A1 - Meitinger, Nadine A1 - Kreis, Wolfgang T1 - Biosynthetic approach to combine the first steps of cardenolide formation in Saccharomyces cerevisiae JF - Microbiologyopen N2 - A yeast expression plasmid was constructed containing a cardenolide biosynthetic module, referred to as CARD II, using the AssemblX toolkit, which enables the assembly of large DNA constructs. The genes cloned into the vector were (a) a Δ5‐3β‐hydroxysteroid dehydrogenase gene from Digitalis lanata, (b) a steroid Δ5‐isomerase gene from Comamonas testosteronii, (c) a mutated steroid‐5β‐reductase gene from Arabidopsis thaliana, and (d) a steroid 21‐hydroxylase gene from Mus musculus. A second plasmid bearing an ADR/ADX fusion gene from Bos taurus was also constructed. A Saccharomyces cerevisiae strain bearing these two plasmids was generated. This strain, termed “CARD II yeast”, was capable of producing 5β‐pregnane‐3β,21‐diol‐20‐one, a central intermediate in 5β‐cardenolide biosynthesis, starting from pregnenolone which was added to the culture medium. Using this approach, five consecutive steps in cardenolide biosynthesis were realized in baker's yeast. Y1 - 2019 U6 - https://doi.org/10.1002/mbo3.925 SN - 2045-8827 VL - 8 IS - 12 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Maaß, Stefanie T1 - Blick in die Zukunft BT - wie werden sich Pflanzengemeinschaften in Brandenburg verändern? JF - Vielfalt in der Uckermark : Forschungsprojekte 2015 - 2018 Y1 - 2019 SP - 24 EP - 25 PB - oerding print GmbH CY - Braunschweig ER - TY - JOUR A1 - Rödel, Claudia Jasmin A1 - Otten, Cecile A1 - Donat, Stefan A1 - Lourenço, Marta Sofia Rocha A1 - Fischer, Dorothea A1 - Kuropka, Benno A1 - Paolini, Alessio A1 - Freund, Christian A1 - Abdelilah-Seyfried, Salim T1 - Blood Flow Suppresses Vascular Anomalies in a Zebrafish Model of Cerebral Cavernous Malformations JF - Circulation Research N2 - RATIONALE: Pathological biomechanical signaling induces vascular anomalies including cerebral cavernous malformations (CCM), which are caused by a clonal loss of CCM1/KRIT1 (Krev interaction trapped protein 1), CCM2/MGC4607, or CCM3/PDCD10. Why patients typically experience lesions only in lowly perfused venous capillaries of the cerebrovasculature is completely unknown. OBJECTIVE: In contrast, animal models with a complete loss of CCM proteins lack a functional heart and blood flow and exhibit vascular anomalies within major blood vessels as well. This finding raises the possibility that hemodynamics may play a role in the context of this vascular pathology. METHODS AND RESULTS: Here, we used a genetic approach to restore cardiac function and blood flow in a zebrafish model of CCM1. We find that blood flow prevents cardiovascular anomalies including a hyperplastic expansion within a large Ccm1-deficient vascular bed, the lateral dorsal aorta. CONCLUSIONS: This study identifies blood flow as an important physiological factor that is protective in the cause of this devastating vascular pathology. KW - animal models KW - cerebral cavernous malformations KW - endothelial cell KW - hemodynamics KW - zebrafish Y1 - 2019 U6 - https://doi.org/10.1161/CIRCRESAHA.119.315076 SN - 0009-7330 SN - 1524-4571 VL - 125 IS - 10 SP - E43 EP - E54 PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - JOUR A1 - Groth, Detlef A1 - Scheffler, Christiane A1 - Hermanussen, Michael T1 - Body height in stunted Indonesian children depends directly on parental education and not via a nutrition mediated pathway BT - Evidence from tracing association chains by St. Nicolas House Analysis JF - Journal of biological and clinical anthropology : Anthropologischer Anzeiger ; Mitteilungsorgan der Gesellschaft für Anthropologie N2 - Background: Multiple linear correlations between parameters can be shown in correlation matrices. Correlations can be ranked, but can also be visualized in network graphs. Yet, translating a correlation matrix into a network graph is not trivial. In view of a popular child game, we propose to name this method St. Nicolas House Analysis. Material and methods: We present a new method (St. Nicolas House Analysis) that helps translating correlation matrices into network graphs. The performance of this and other network reconstruction methods was tested in randomly created virtual scale-free networks, networks consisting of bands or hubs, using balanced classification rate and the F1-Score for correctly predicting existing and non-existing edges. Thereafter we analyzed anthropometric data and information on parental education, obtained from an anthropometric survey in 908 Indonesian boys and 808 Indonesian girls. Seven parameters were analyzed: child height standard deviation score (hSDS), child BMI standard deviation scores (BMI_SDS), mid-upper-arm circumference (MUAC), mean thickness of subscapular and triceps skinfold (mean SF), and elbow breadth; as well as maternal and paternal education (years of schooling). The parameters were considered as the nodes of the network; the edges represent the correlations between the nodes. Results: Performance measures, balanced classification rate and the F1-score, showed that St. Nicolas’ House Analysis was superior to methods using sophisticated correlation value thresholds and methods based on partial correlations for analyzing bands and hubs. We applied this method also in an Indonesia data set. Ranking correlations showed the direct association between parental education and child growth. Conclusion: St. Nicolas House Analysis confirmed that growth of Indonesian school children directly depends on maternal education, with no evidence that this effect is mediated by the state of nutrition. Y1 - 2019 U6 - https://doi.org/10.1127/anthranz/2019/1027 SN - 0003-5548 VL - 76 IS - 5 SP - 445 EP - 451 PB - Schweizerbart CY - Stuttgart ER - TY - JOUR A1 - Duydu, Yalcin A1 - Basaran, Nursen A1 - Yalcin, Can Özgür A1 - Ustundag, Aylin A1 - Aydin, Sevtap A1 - Anlar, Hatice Gul A1 - Bacanli, Merve A1 - Aydos, Kaan A1 - Atabekoglu, Cem Somer A1 - Golka, Klaus A1 - Ickstadt, Katja A1 - Schwerdtle, Tanja A1 - Werner, Matthias A1 - Bolt, Hermann M. T1 - Boron-exposed male workers in Turkey BT - no change in sperm Y:X chromosome ratio and in offspring's sex ratio JF - Archives of toxicology : official journal of EUROTOX N2 - Boron-associated shifts in sex ratios at birth were suggested earlier and attributed to a decrease in Y- vs. X-bearing sperm cells. As the matter is pivotal in the discussion of reproductive toxicity of boron/borates, re-investigation in a highly borate-exposed population was required. In the present study, 304 male workers in Bandirma and Bigadic (Turkey) with different degrees of occupational and environmental exposure to boron were investigated. Boron was quantified in blood, urine and semen, and the persons were allocated to exposure groups along B blood levels. In the highest ("extreme") exposure group (n = 69), calculated mean daily boron exposures, semen boron and blood boron concentrations were 44.91 +/- 18.32 mg B/day, 1643.23 +/- 965.44 ng B/g semen and 553.83 +/- 149.52 ng B/g blood, respectively. Overall, an association between boron exposure and Y:X sperm ratios in semen was not statistically significant (p > 0.05). Also, the mean Y:X sperm ratios in semen samples of workers allocated to the different exposure groups were statistically not different in pairwise comparisons (p > 0.05). Additionally, a boron-associated shift in sex ratio at birth towards female offspring was not visible. In essence, the present results do not support an association between boron exposure and decreased Y:X sperm ratio in males, even under extreme boron exposure conditions. KW - Paternal exposure KW - Boron exposure KW - Y:X chromosome ratio KW - Sex ratio at birth Y1 - 2019 U6 - https://doi.org/10.1007/s00204-019-02391-z SN - 0340-5761 SN - 1432-0738 VL - 93 IS - 3 SP - 743 EP - 751 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Klopsch, Rebecca A1 - Baldermann, Susanne A1 - Hanschen, Franziska S. A1 - Voss, Alexander A1 - Rohn, Sascha A1 - Schreiner, Monika A1 - Neugart, Susanne T1 - Brassica-enriched wheat bread: Unraveling the impact of ontogeny and breadmaking on bioactive secondary plant metabolites of pak choi and kale JF - Food chemistry N2 - Consumption of Brassica vegetables is linked to health benefits, as they contain high concentrations of the following secondary plant metabolites (SPMs): glucosinolate breakdown products, carotenoids, chlorophylls, and phenolic compounds. Especially Brassica vegetables are consumed as microgreens (developed cotyledons). It was investigated how different ontogenetic stages (microgreens or leaves) of pak choi (Brassica rapa subsp. chinensis) and kale (Brassica oleracea var. sabellica) differ in their SPM concentration. The impact of breadmaking on SPMs in microgreens (7 days) and leaves (14 days) in pak choi and kale as a supplement in mixed wheat bread was assessed. In leaves, carotenoids, chlorophylls, and phenolic compounds were higher compared to those of microgreens. Breadmaking caused a decrease of SPMs. Chlorophyll degradation was observed, leading to pheophytin and pyropheophytin formation. In kale, sinapoylgentiobiose, a hydroxycinnamic acid derivative, concentration increased. Thus, leaves of Brassica species are suitable as natural ingredients for enhancing bioactive SPM concentrations in bread. KW - Ontogeny KW - Brassica KW - Glucosinolate breakdown product KW - Flavonoid KW - Carotenoid KW - Thermal processing Y1 - 2019 U6 - https://doi.org/10.1016/j.foodchem.2019.05.113 SN - 0308-8146 SN - 1873-7072 VL - 295 SP - 412 EP - 422 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Frommhold, Martin A1 - Heim, Arend A1 - Barabanov, Mikhail A1 - Maier, Franziska A1 - Mühle, Ralf-Udo A1 - Smirenski, Sergei M. A1 - Heim, Wieland T1 - Breeding habitat and nest-site selection by an obligatory "nest-cleptoparasite", the Amur Falcon Falco amurensis JF - Ecology and evolution N2 - The selection of a nest site is crucial for successful reproduction of birds. Animals which re-use or occupy nest sites constructed by other species often have limited choice. Little is known about the criteria of nest-stealing species to choose suitable nesting sites and habitats. Here, we analyze breeding-site selection of an obligatory "nest-cleptoparasite", the Amur Falcon Falco amurensis. We collected data on nest sites at Muraviovka Park in the Russian Far East, where the species breeds exclusively in nests of the Eurasian Magpie Pica pica. We sampled 117 Eurasian Magpie nests, 38 of which were occupied by Amur Falcons. Nest-specific variables were assessed, and a recently developed habitat classification map was used to derive landscape metrics. We found that Amur Falcons chose a wide range of nesting sites, but significantly preferred nests with a domed roof. Breeding pairs of Eurasian Hobby Falco subbuteo and Eurasian Magpie were often found to breed near the nest in about the same distance as neighboring Amur Falcon pairs. Additionally, the occurrence of the species was positively associated with bare soil cover, forest cover, and shrub patches within their home range and negatively with the distance to wetlands. Areas of wetlands and fallow land might be used for foraging since Amur Falcons mostly depend on an insect diet. Additionally, we found that rarely burned habitats were preferred. Overall, the effect of landscape variables on the choice of actual nest sites appeared to be rather small. We used different classification methods to predict the probability of occurrence, of which the Random forest method showed the highest accuracy. The areas determined as suitable habitat showed a high concordance with the actual nest locations. We conclude that Amur Falcons prefer to occupy newly built (domed) nests to ensure high nest quality, as well as nests surrounded by available feeding habitats. KW - cleptoparasitism KW - fire KW - habitat use KW - machine learning KW - magpie KW - nest-site selection KW - random forest Y1 - 2019 U6 - https://doi.org/10.1002/ece3.5878 SN - 2045-7758 VL - 9 IS - 24 SP - 14430 EP - 14441 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Lozada Gobilard, Sissi Donna A1 - Weigend, M. A1 - Fischer, E. A1 - Janssens, S. B. A1 - Ackermann, M. A1 - Abrahamczyk, Stefan T1 - Breeding systems in Balsaminaceae in relation to pollen/ovule ratio, pollination syndromes, life history and climate zone JF - Plant biology N2 - Pollen/ovule (P/O) ratios are often used as proxy for breeding systems. Here, we investigate the relations between breeding systems and P/O ratios, pollination syndromes, life history and climate zone in Balsaminaceae. We conducted controlled breeding system experiments (autonomous and active self-pollination and outcrossing tests) for 65 Balsaminaceae species, analysed pollen grain and ovule numbers and evaluated the results in combination with data on pollination syndrome, life history and climate zone on a phylogenetic basis. Based on fruit set, we assigned three breeding systems: autogamy, self-compatibility and self-incompatibility. Self-pollination led to lower fruit set than outcrossing. We neither found significant P/O differences between breeding systems nor between pollination syndromes. However, the numbers of pollen grains and ovules per flower were significantly lower in autogamous species, but pollen grain and ovule numbers did not differ between most pollination syndromes. Finally, we found no relation between breeding system and climate zone, but a relation between climate zone and life history. In Balsaminaceae reproductive traits can change under resource or pollinator limitation, leading to the evolution of autogamy, but are evolutionary rather constant and not under strong selection pressure by pollinator guild and geographic range changes. Colonisation of temperate regions, however, is correlated with transitions towards annual life history. Pollen/ovule-ratios, commonly accepted as good indicators of breeding system, have a low predictive value in Balsaminaceae. In the absence of experimental data on breeding system, additional floral traits (overall pollen grain and ovule number, traits of floral morphology) may be used as proxies. KW - Annual KW - autogamy KW - cleistogamy KW - evolution KW - fly pollination KW - Impatiens KW - outcrossing KW - perennial KW - self-incompatibility KW - temperate KW - tropical Y1 - 2018 U6 - https://doi.org/10.1111/plb.12905 SN - 1435-8603 SN - 1438-8677 VL - 21 IS - 1 SP - 157 EP - 166 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Staszek, Pawel A1 - Krasuska, Urszula A1 - Otulak-Koziel, Katarzyna A1 - Fettke, Jörg A1 - Gniazdowska, Agnieszka T1 - Canavanine-Induced Decrease in Nitric Oxide Synthesis Alters Activity of Antioxidant System but Does Not Impact S-Nitrosoglutathione Catabolism in Tomato Roots JF - Frontiers in plant science N2 - Canavanine (CAN) is a nonproteinogenic amino acid synthesized in legumes. In mammalians, as arginine analogue, it is an inhibitor of nitric oxide synthase (NOS) activity. The aim of this study was to investigate the impact of CAN-induced nitric oxide level limitation on the antioxidant system and S-nitrosoglutathione (GSNO) metabolism in roots of tomato seedlings. Treatment with CAN (10 or 50 mu M) for 24-72 h led to restriction in root growth. Arginine-dependent NOS-like activity was almost completely inhibited, demonstrating direct effect of CAN action. CAN increased total antioxidant capacity and the level of sulphydryl groups. Catalase (CAT) and superoxide dismutase (SOD) activity decreased in CAN exposed roots. CAN supplementation resulted in the decrease of transcript levels of genes coding CAT (with the exception of CAT1). Genes coding SOD (except MnSOD and CuSOD) were upregulated by CAN short treatment; prolonged exposition to 50-mu M CAN resulted in downregulation of FeSOD, CuSOD, and SODP-2. Activity of glutathione reductase dropped down after short-term (10-mu M CAN) supplementation, while glutathione peroxidase activity was not affected. Transcript levels of glutathione reductase genes declined in response to CAN. Genes coding glutathione peroxidase were upregulated by 50-mu M CAN, while 10-mu M CAN downregulated GSHPx1. Inhibition of NOS-like activity by CAN resulted in lower GSNO accumulation in root tips. Activity of GSNO reductase was decreased by short-term supplementation with CAN. In contrast, GSNO reductase protein abundance was higher, while transcript levels were slightly altered in roots exposed to CAN. This is the first report on identification of differentially nitrated proteins in response to supplementation with nonproteinogenic amino acid. Among nitrated proteins differentially modified by CAN, seed storage proteins (after short-term CAN treatment) and components of the cellular redox system (after prolonged CAN supplementation) were identified. The findings demonstrate that due to inhibition of NOS-like activity, CAN leads to modification in antioxidant system. Limitation in GSNO level is due to lower nitric oxide formation, while GSNO catabolism is less affected. We demonstrated that monodehydroascorbate reductase, activity of which is inhibited in roots of CAN-treated plants, is the protein preferentially modified by tyrosine nitration. KW - canavanine KW - cellular antioxidant system KW - GSNOR-GSNO reductase KW - nitrated proteins KW - nitric oxide-NO KW - nonproteinogenic amino acid KW - NOS-like activity KW - reactive nitrogen species (RNS) Y1 - 2019 U6 - https://doi.org/10.3389/fpls.2019.01077 SN - 1664-462X VL - 10 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Schorn, Sina A1 - Salman-Carvalho, Verena A1 - Littmann, Sten A1 - Ionescu, Danny A1 - Grossart, Hans-Peter A1 - Cypionka, Heribert T1 - Cell architecture of the giant sulfur bacterium achromatium oxaliferum BT - Extra-cytoplasmic localization of calcium carbonate bodies JF - FEMS Microbiology Ecology N2 - Achromatium oxaliferum is a large sulfur bacterium easily recognized by large intracellular calcium carbonate bodies. Although these bodies often fill major parts of the cells' volume, their role and specific intracellular location are unclear. In this study, we used various microscopy and staining techniques to identify the cell compartment harboring the calcium carbonate bodies. We observed that Achromatium cells often lost their calcium carbonate bodies, either naturally or induced by treatments with diluted acids, ethanol, sodium bicarbonate and UV radiation which did not visibly affect the overall shape and motility of the cells (except for UV radiation). The water-soluble fluorescent dye fluorescein easily diffused into empty cavities remaining after calcium carbonate loss. Membranes (stained with Nile Red) formed a network stretching throughout the cell and surrounding empty or filled calcium carbonate cavities. The cytoplasm (stained with FITC and SYBR Green for nucleic acids) appeared highly condensed and showed spots of dissolved Ca2+ (stained with Fura-2). From our observations, we conclude that the calcium carbonate bodies are located in the periplasm, in extra-cytoplasmic pockets of the cytoplasmic membrane and are thus kept separate from the cell's cytoplasm. This periplasmic localization of the carbonate bodies might explain their dynamic formation and release upon environmental changes. KW - sulfur-bacteria KW - calcium carbonate inclusions KW - extra-cytoplasmic pockets KW - calcite Y1 - 2019 U6 - https://doi.org/10.1093/femsec/fiz200 SN - 1574-6941 VL - 96 IS - 2 SP - 1 EP - 8 PB - Oxford University Press CY - Oxford ER - TY - THES A1 - Taube, Robert T1 - Characterisations of Fungal Communities in Temperate Lakes BT - with focus on diversity, abundance and methodological aspects of quantifying abundance Y1 - 2019 ER - TY - JOUR A1 - Numberger, Daniela A1 - Ganzert, Lars A1 - Zoccarato, Luca A1 - Mühldorfer, Kristin A1 - Sauer, Sascha A1 - Grossart, Hans-Peter A1 - Greenwood, Alex D. T1 - Characterization of bacterial communities in wastewater with enhanced taxonomic resolution by full-length 16S rRNA sequencing JF - Scientific reports N2 - Wastewater treatment is crucial to environmental hygiene in urban environments. However, wastewater treatment plants (WWTPs) collect chemicals, organic matter, and microorganisms including pathogens and multi-resistant bacteria from various sources which may be potentially released into the environment via WWTP effluent. To better understand microbial dynamics in WWTPs, we characterized and compared the bacterial community of the inflow and effluent of a WWTP in Berlin, Germany using full-length 16S rRNA gene sequences, which allowed for species level determination in many cases and generally resolved bacterial taxa. Significantly distinct bacterial communities were identified in the wastewater inflow and effluent samples. Dominant operational taxonomic units (OTUs) varied both temporally and spatially. Disease associated bacterial groups were efficiently reduced in their relative abundance from the effluent by the WWTP treatment process, except for Legionella and Leptospira species which demonstrated an increase in relative proportion from inflow to effluent. This indicates that WWTPs, while effective against enteric bacteria, may enrich and release other potentially pathogenic bacteria into the environment. The taxonomic resolution of full-length 16S rRNA genes allows for improved characterization of potential pathogenic taxa and other harmful bacteria which is required to reliably assess health risk. Y1 - 2019 U6 - https://doi.org/10.1038/s41598-019-46015-z SN - 2045-2322 VL - 9 PB - Nature Publ. Group CY - London ER - TY - THES A1 - Riedel, Simona T1 - Characterization of Mitochondrial ABC Transporter Homologues in Rhodobacter capsulatus T1 - Charakterisierung von Homologen zu mitochondrialen ABC Transportern in Rhodobacter capsulatus N2 - ABC-Transporter (ABC abgeleitet von ATP-Binding Cassette) gehören zur Klasse der Transmembran-Proteine und kommen in allen drei Domänen des Lebens vor. Ihr struktureller Aufbau ist dabei stets ähnlich, wohingegen konservierte Proteinsequenzen selten vorkommen. Die Transporter sind aus zwei lipophilen, membran-durchspannenden Domänen, welche auch TMDs (abgeleitet von Transmembrane spanning Domains) genannt werden, und zwei hydrophilen Domänen, die auch NBDs (abgeleitet von Nucleotide Binding Domains) genannt werden, aufgebaut. Die Vielzahl der durch ABC-Transporter beförderten Moleküle erklärt dabei die enorme Anzahl diverser TMDs. In den Mitochondrien des Menschen findet man vier ABC-Transporter (ABCB6, ABCB7, ABCB8 und ABCB10) mit funktionellen Homologen in Hefen und Pflanzen. In Bakterien hingegen können, mit Ausnahme von Rickettsiae und verwandten Bakterien, keine Homologen zu mitochondrialen ABC-Transportern identifiziert werden. Die transportierten Moleküle sowie die damit verbundenen Funktionen sind im Einzelnen bislang weitgehend unbekannt. ABCB7 und die entsprechenden Homologen in Hefen (Atm1) und in Pflanzen (ATM3) konnten mit der cytosolischen Eisen-Schwefel-Cluster-Biosynthese in Zusammenhang gebracht werden. Eine schwefelhaltige Verbindung der mitochondrialen Matrix wird mit Hilfe dieses Transporters der cytosolischen Eisen-Schwefel-Cluster-Assemblierung zur Verfügung gestellt. Die 2014 publizierten Kristallstrukturen von Atm1 (Hefe) und Atm1 aus Novosphingobium aromaticivorans offenbarten dabei eine hoch konservierte Glutathion-Bindetasche innerhalb der TMDs für ABCB7 Homologe. In der Modellpflanze Arabidopsis thaliana konnte ATM3 zusätzlich mit der Biosynthese des Molybdän-Cofaktors in Verbindung gebracht werden. In der vorliegenden Arbeit wurde das α-Proteobacterium Rhodobacter capsulatus als Modellorganismus genutzt, um mitochondriale ABC-Transporter Homologe zu untersuchen. Das Bakterium enthält zwei ABC-Transporter-Gene, rcc03139 und rcc02305, die mit den humanen mitochondrialen Transportern große Sequenzübereinstimmungen aufweisen (rcc03139: 41 % respektive 38 % Identität mit ABCB8 und ABCB10, rcc02305: 47 % identisch mit ABCB7 und ABCB6). Mit Hilfe erzeugter Interposon-Mutanten (Δrcc02305I und Δrcc03139I) konnte erstmals gezeigt werden, dass bakterielle Transporter funktionell sehr ähnliche Aufgaben wie die mitochondrialen ABC-Transporter übernehmen. Beispielsweise akkumulierten beide Interposon-Mutanten reaktive Sauerstoff-Spezies (ROS) ohne gleichzeitige Akkumulation von Glutathion oder Eisen. Weiterhin konnten wir zeigen, dass, ähnlich wie bereits für ATM3 postuliert, die Biosynthese des Molybdän-Cofaktors in Δrcc02305I verändert ist. Mit Hilfe einer lebensfähigen Doppelmutante, in der beide ABC-Transporter-Gene gleichzeitig deletiert wurden, konnten wir ausschließen, dass die beiden bakteriellen ABC-Transporter grundsätzlich redundante Funktionen haben. Durch die Analyse des Proteoms von Δrcc03139I im Vergleich zu der des Wildtyps, konnte eine extreme Beeinflussung der Tetrapyrrol Biosynthese sowie entsprechender Zielproteine identifiziert werden. Dies konnte zusätzlich durch die Quantifizierung einzelner Zwischenprodukte der Biosynthese bestätigt werden. Im Gegensatz dazu konnte anhand der Analyse des Proteoms in Verbindung mit analytischen Methoden in Δrcc02305I ein Ungleichgewicht in der Schwefelverteilung identifiziert werden. Zusammen mit der Entdeckung einer Pyridoxalphosphat (PLP) Bindestelle in Rcc02305 und anderen ABCB7-artigen Transportern, welche direkt mit dem Walker-A-Motiv der NBD überlappt, ermöglichte dies eine völlig neue Theorie, wie die schwefelhaltige Verbindung transportiert werden kann. Wir gehen davon aus, dass an PLP zunächst ein Persulfid produziert wird, welches unmittelbar mit dem Glutathion der transmembranen Bindetasche zu einem gemischten Polysulfid reagiert. Im Anschluss daran wird die ATP-Bindestelle frei und die Hydrolyse des ATPs löst eine Konformationsänderung aus, welche das gemischte Polysulfid ins Periplasma bzw. in den intermembranen Raum freigibt. N2 - ATP-binding cassette (ABC) transporters are present in all kingdoms of life and enable active transport of various different molecules across biological membranes. They all share an overall architecture of two lipophilic transmembrane spanning domains (TMDs) traversing the membrane and two hydrophilic nucleotide binding domains (NBDs) usually lacking sequence identity. The multiplicity in transported molecules is accompanied by extreme diversity in TMDs. Human mitochondria harbor four ABC transporters, namely ABCB6, ABCB7, ABCB8 and ABCB10 with functional homologues in yeast and plants. Except the ones found in Rickettsiae and related bacteria mitochondrial ABC transporters are absent in bacteria. In addition to converting energy mitochondria are important platforms for biosynthesizing various cofactors as iron sulfur clusters, molybdenum cofactor (Moco) or heme. ABCB7 (Atm1 in yeast) has been shown to connect mitochondrial with cytosolic iron sulfur cluster assembly by exporting a yet unknown sulfur containing molecule. In addition, TMDs of Atm1 display a glutathione binding pocket accessible from the matrix which has been identified in all ABCB7-like transporters and also exists in a bacterial ABC transporter homologue of Atm1 in Novosphingobium aromaticivorans. In addition, ATM3, a plant mitochondrial homologous ABC transporter to human ABCB7, has been associated with biosynthesizing Moco. In this study we used the α-proteobacterium Rhodobacter capsulatus as a model organism to characterize mitochondrial ABC transporter homologues. R. capsulatus contains two homologues to mitochondrial ABC transporters with the corresponding gene loci rcc03139 and rcc02305. They share 38 to 47 % sequence identities to human mitochondrial ABC transporters ABCB8/ABCB10 and ABCB7/ABCB6, respectively. We created interposon mutants lacking either rcc03139 or rcc02305, analyzed the physiological effects on R. capsulatus and compared the findings especially to eukaryotic deletion studies. A viable bacterial double mutant strain lacking both mitochondrial ABC transporters was constructed to investigate possible overlapping functions. Both R. capsulatus single mutants showed a severe accumulation of intracellular reactive oxygen species (ROS) in comparison to ∆nifDK which revealed to be additive in the double mutant. In the proteome of ∆rcc03139I abundancies of tetrapyrrole related proteins were significantly increased in comparison to the proteome of parental strain, which was further validated by reduced amounts of tetrapyrrole intermediates in ∆rcc03139. In contrast, in ∆rcc02305I total glutathione (GSH) was elevated when endogenous GSH biosynthesis was inhibited. In conjunction with proteomic studies we uncovered misbalanced sulfur distribution in ∆rcc02305I. Furthermore, strains lacking Rcc02305 accumulated cyclic pyranopterin monophosphate (cPMP), an intermediate of Moco biosynthesis, as it was already shown for the deletion strain of the eukaryotic counterpart ATM3 in plants. In contrast single mutant strain Δrcc03139I neither accumulated cPMP nor glutathione. Bioinformatic analysis of the amino acid sequence of Rcc02305 revealed a pyridoxal 5´phosphate (PLP) binding site which overlaps with Walker A within the NBDs of Rcc02305 and other ABCB7-like transporters. The PLP cofactor is well studied in C-DES (L-cysteine/cystine lyase from Synechocystis) for persulfide production and in L-cysteine desulfurases such as IscS and NFS1 for its role in formation of protein-bound persulfides. Based on our findings we are able to propose a new modality for the transport of the sulfur containing molecule: first of all, the transporter produces a highly reactive persulfide which is then subsequently trapped by glutathione polysulfide, already bound within the binding pocket in TMDs. Walker A becomes accessible for ATP and after hydrolysis the mixed polysulfide is released. Based on our studies we are convinced that both mitochondrial ABC transporter homologues fulfil distinct roles in R. capsulatus: Rcc02305 is a representative of Atm1/ABCB7-like transporters and important for proper sulfur distribution by exporting persulfides. In contrast Rcc03139 is a representative of ABCB6/ABCB10 related transporters and involved in biosynthesizing tetrapyrroles. KW - Rhodobacter capsulatus KW - ABC Transporter KW - ABCB7 KW - Mitochondrien KW - PLP-Walker A-Überlagerung KW - Rhodobacter capsulatus KW - ABC transporter KW - ABCB7 KW - mitochondria KW - PLP-Walker A-overlap Y1 - 2019 ER - TY - JOUR A1 - Hoffmann, Stefan A. A1 - Hao, Nan A1 - Shearwin, Keith E. A1 - Arndt, Katja Maren T1 - Characterizing transcriptional interference between converging genes in bacteria JF - ACS synthetic biology N2 - Antisense transcription is common in naturally occurring genomes and is increasingly being used in synthetic genetic circuitry as a tool for gene expression control. Mutual influence on the expression of convergent genes can be mediated by antisense RNA effects and by transcriptional interference (TI). We aimed to quantitatively characterize long-range TI between convergent genes with untranslated intergenic spacers of increasing length. After controlling for antisense RNA-mediated effects, which contributed about half of the observed total expression inhibition, the TI effect was modeled. To achieve model convergence, RNA polymerase processivity and collision resistance were assumed to be modulated by ribosome trailing. The spontaneous transcription termination rate in regions of untranslated DNA was experimentally determined. Our modeling suggests that an elongating RNA polymerase with a trailing ribosome is about 13 times more likely to resume transcription than an opposing RNA polymerase without a trailing ribosome, upon head-on collision of the two. KW - gene regulation KW - antisense transcription KW - transcriptional interference KW - mathematical modeling KW - Escherichia coli Y1 - 2019 U6 - https://doi.org/10.1021/acssynbio.8b00477 SN - 2161-5063 VL - 8 IS - 3 SP - 466 EP - 473 PB - American Chemical Society CY - Washington ER - TY - THES A1 - Schwuchow, Viola T1 - Charakterisierung der periplasmatischen Aldehyd-Oxidoreduktase (PaoABC) aus Escherichia coli N2 - Im Mittelpunkt dieser Arbeit standen Analysen zur Charakterisierung der periplasmatischen Aldehyd Oxidoreduktase aus E. coli. Kinetische Untersuchungen mit Ferricyanid als Elektronenakzeptor unter anaeroben Bedingungen zeigten für dieses Enzym eine höhere Aktivität als unter aeroben Bedingungen. Die getroffene Hypothese, dass PaoABC fähig ist Elektronen an molekularen Sauerstoff weiter zu geben, konnte bestätigt werden. Für den Umsatz aromatischer Aldehyde mit molekularem Sauerstoff wurde ein Optimum von pH 6,0 ermittelt. Dies steht im Gegensatz zur Reaktion mit Ferricyanid, mit welchem ein pH-Optimum von 4,0 gezeigt wurde. Die Reaktion von PaoABC mit molekularem Sauerstoff generiert zwar Wasserstoffperoxid, die Produktion von Superoxid konnte dagegen nicht beobachtet werden. Dass aerobe Bedingungen einen Einfluss auf das Auslösen der Expression von PaoABC haben, wurde in dieser Arbeit ebenfalls ermittelt. Im Zusammenhang mit der Produktion von ROS durch PaoABC wurde die Funktion eines kürzlich in Elektronentransfer-Distanz zum FAD identifizierten [4Fe4S]-Clusters untersucht. Ein Austausch der für die Bindung des Clusters zuständigen Cysteine führte zur Instabilität der Proteinvarianten, weswegen für diese keine weiteren Untersuchungen erfolgten. Daher wird zumindest ein struktur-stabilisierender Einfluss des [4Fe4S]-Clusters angenommen. Zur weiteren Untersuchung der Funktion dieses Clusters, wurde ein zwischen FAD und [4Fe4S]-Cluster lokalisiertes Arginin gegen ein Alanin ausgetauscht. Diese Proteinvariante zeigte eine reduzierte Geschwindigkeit der Reaktion gegenüber dem Wildtyp. Die Bildung von Superoxid konnte auch hier nicht beobachtet werden. Die Vermutung, dass dieser Cluster einen elektronen-sammelnden Mechanismus unterstützt, welcher die Radikalbildung verhindert, kann trotz allem nicht ausgeschlossen werden. Da im Umkreis des Arginins weitere geladene und aromatische Aminosäuren lokalisiert sind, können diese den notwendigen Elektronentransfer übernehmen. Neben der Ermittlung eines physiologischen Elektronenakzeptors und dessen Einfluss auf die Expression von PaoABC zeigt diese Arbeit auch, dass die Chaperone PaoD und MocA während der Reifung des MCD-Kofaktor eine gemeinsame Bindung an PaoABC realisieren. Es konnte im aktiven Zentrum von PaoABC ein Arginin beschrieben werden, welches auf Grund der engen Nachbarschaft zum MCD-Kofaktor und zum Glutamat (PaoABC-EC692) am Prozess der Substratbindung beteiligt ist. Im Zusammenhang mit dem Austausch dieses Arginins gegen ein Histidin oder ein Lysin wurden die Enzymspezifität und der Einfluss physiologischer Bedingungen, wie pH und Ionenstärke, auf die Reaktion des Enzyms untersucht. Gegenüber dem Wildtyp zeigten die Varianten mit molekularem Sauerstoff eine geringere Affinität zum Substrat aber auch eine höhere Geschwindigkeit der Reaktion. Vor allem für die Histidin-Variante konnte im gesamten pH-Bereich ein instabiles Verhalten bestimmt werden. Der Grund dafür wurde durch das Lösen der Struktur der Histidin-Variante beschreiben. Durch den Austausch der Aminosäuren entfällt die stabilisierende Wirkung der delokalisierten Elektronen des Arginins und es kommt zu einer Konformationsänderung im aktiven Zentrum. Neben der Reaktion von PaoABC mit einer Vielzahl aromatischer Aldehyde konnte auch der Umsatz von Salicylaldehyd zu Salicylsäure durch PaoABC in einer Farbreaktion bestimmt werden. Durch Ausschluss von molekularem Sauerstoff als terminaler Elektronenakzeptor, in einer enzym-gekoppelten Reaktion, erfolgte ein Elektronentransport auf Ferrocencarboxylsäure. Die Kombination aus beiden Methoden ermöglichte eine Verwendung von Ferrocen-Derivaten zur Generierung einer enzym-gekoppelten Reaktion mit PaoABC. Die Untersuchungen zu PaoABC zeigen, dass die Vielfalt der durch das Enzym katalysierten Rektionen weitere Möglichkeiten der enzymatischen Bestimmung biokatalytischer Prozesse bietet. KW - Eschericha coli KW - Periplasma KW - Aldehydoxidase KW - Aldehyd KW - Oxidoreduktase KW - Molybdän Y1 - 2019 ER - TY - JOUR A1 - Codutti, Agnese A1 - Bente, Klaas A1 - Faivre, Damien A1 - Klumpp, Stefan T1 - Chemotaxis in external fields: Simulations for active magnetic biological matter JF - PLoS Computational Biology : a new community journal N2 - The movement of microswimmers is often described by active Brownian particle models. Here we introduce a variant of these models with several internal states of the swimmer to describe stochastic strategies for directional swimming such as run and tumble or run and reverse that are used by microorganisms for chemotaxis. The model includes a mechanism to generate a directional bias for chemotaxis and interactions with external fields (e.g., gravity, magnetic field, fluid flow) that impose forces or torques on the swimmer. We show how this modified model can be applied to various scenarios: First, the run and tumble motion of E. coli is used to establish a paradigm for chemotaxis and investigate how it is affected by external forces. Then, we study magneto-aerotaxis in magnetotactic bacteria, which is biased not only by an oxygen gradient towards a preferred concentration, but also by magnetic fields, which exert a torque on an intracellular chain of magnets. We study the competition of magnetic alignment with active reorientation and show that the magnetic orientation can improve chemotaxis and thereby provide an advantage to the bacteria, even at rather large inclination angles of the magnetic field relative to the oxygen gradient, a case reminiscent of what is expected for the bacteria at or close to the equator. The highest gain in chemotactic velocity is obtained for run and tumble with a magnetic field parallel to the gradient, but in general a mechanism for reverse motion is necessary to swim against the magnetic field and a run and reverse strategy is more advantageous in the presence of a magnetic torque. This finding is consistent with observations that the dominant mode of directional changes in magnetotactic bacteria is reversal rather than tumbles. Moreover, it provides guidance for the design of future magnetic biohybrid swimmers. Author summary In this paper, we propose a modified Active Brownian particle model to describe bacterial swimming behavior under the influence of external forces and torques, in particular of a magnetic torque. This type of interaction is particularly important for magnetic biohybrids (i.e. motile bacteria coupled to a synthetic magnetic component) and for magnetotactic bacteria (i.e. bacteria with a natural intracellular magnetic chain), which perform chemotaxis to swim along chemical gradients, but are also directed by an external magnetic field. The model allows us to investigate the benefits and disadvantages of such coupling between two different directionality mechanisms. In particular we show that the magnetic torque can speed chemotaxis up in some conditions, while it can hinder it in other cases. In addition to an understanding of the swimming strategies of naturally magnetotactic organisms, the results may guide the design of future biomedical devices. Y1 - 2019 U6 - https://doi.org/10.1371/journal.pcbi.1007548 SN - 1553-734X SN - 1553-7358 VL - 15 IS - 12 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Plikk, Anna A1 - Engels, Stefan A1 - Luoto, Tomi P. A1 - Nazarova, Larisa B. A1 - Salonen, J. Sakari A1 - Helmens, Karin F. T1 - Chironomid-based temperature reconstruction for the Eemian Interglacial (MIS 5e) at Sokli, northeast Finland JF - Journal of paleolimnology N2 - The Last Interglacial (Eemian, MIS 5e) can be considered a test-bed for climate dynamics under a warmer-than-present climate. In this study we present a chironomid record from the high latitude Sokli site (N Finland), where a long continuous sediment sequence from the last interglacial has been preserved from glacial erosion. The chironomid-analysis shows a diverse fauna, with dominance of warm-water indicators and shifts in assemblage composition that can be attributed to temperature, lake depth, productivity and habitat availability. Quantitative mean July paleotemperature estimates based on the chironomid data indicate overall mean July air temperatures up to 1 degrees C warmer than present. Two cooling events can be discerned, the Tunturi event, dated to about 127.5kaBP, in the lower part of the sequence, and the Varrio event, dated to about 119kaBP, associated with the beginning of a cooling trend in the upper part of the record. Warm conditions already at the onset of the interglacial contrast with a recent chironomid-based last interglacial temperature reconstruction from Denmark, which suggests a late onset of Eemian warming. The relatively small increase in inferred temperatures compared to present day temperatures at Sokli differs from other high latitude Eemian sites, and likely reflects the influence of the Atlantic Meridional Overturning Circulation in maintaining already elevated temperatures in Fennoscandia during interglacials. KW - Paleoclimate KW - Abrupt events KW - Last Interglacial KW - AMOC KW - Transfer functions KW - Validation Y1 - 2019 U6 - https://doi.org/10.1007/s10933-018-00064-y SN - 0921-2728 SN - 1573-0417 VL - 61 IS - 3 SP - 355 EP - 371 PB - Springer Science CY - Dordrecht ER - TY - JOUR A1 - Zimmermann, Heike Hildegard A1 - Harms, Lars A1 - Epp, Laura Saskia A1 - Mewes, Nick A1 - Bernhardt, Nadine A1 - Kruse, Stefan A1 - Stoof-Leichsenring, Kathleen Rosemarie A1 - Pestryakova, Luidmila Agafyevna A1 - Wieczorek, Mareike A1 - Trense, Daronja A1 - Herzschuh, Ulrike T1 - Chloroplast and mitochondrial genetic variation of larches at the Siberian tundrataiga ecotone revealed by de novo assembly JF - PLoS one N2 - Larix populations at the tundra-taiga ecotone in northern Siberia are highly under-represented in population genetic studies, possibly due to the remoteness of these regions that can only be accessed at extraordinary expense. The genetic signatures of populations in these boundary regions are therefore largely unknown. We aim to generate organelle reference genomes for the detection of single nucleotide polymorphisms (SNPs) that can be used for paleogenetic studies. We present 19 complete chloroplast genomes and mitochondrial genomic sequences of larches from the southern lowlands of the Taymyr Peninsula (northernmost range of Larix gmelinii (Rupr.) Kuzen.), the lower Omoloy River, and the lower Kolyma River (both in the range of Larix cajanderi Mayr). The genomic data reveal 84 chloroplast SNPs and 213 putatively mitochondrial SNPs. Parsimony-based chloroplast haplotype networks show no spatial structure of individuals from different geographic origins, while the mitochondrial haplotype network shows at least a slight spatial structure with haplotypes from the Omoloy and Kolyma populations being more closely related to each other than to most of the haplotypes from the Taymyr populations. Whole genome alignments with publicly available complete chloroplast genomes of different Larix species show that among official plant barcodes only the rcbL gene contains sufficient polymorphisms, but has to be sequenced completely to distinguish the different provenances. We provide 8 novel mitochondrial SNPs that are putatively diagnostic for the separation of L. gmelinii and L. cajanderi, while 4 chloroplast SNPs have the potential to distinguish the L. gmelinii/ L. cajanderi group from other Larix species. Our organelle references can be used for a targeted primer and probe design allowing the generation of short amplicons. This is particularly important with regard to future investigations of, for example, the biogeographic history of Larix by screening ancient sedimentary DNA of Larix. Y1 - 2019 U6 - https://doi.org/10.1371/journal.pone.0216966 SN - 1932-6203 VL - 14 IS - 7 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Angeleska, Angela A1 - Nikoloski, Zoran T1 - Coherent network partitions JF - Discrete applied mathematics N2 - Graph clustering is widely applied in the analysis of cellular networks reconstructed from large-scale data or obtained from experimental evidence. Here we introduce a new type of graph clustering based on the concept of coherent partition. A coherent partition of a graph G is a partition of the vertices of G that yields only disconnected subgraphs in the complement of G. The coherence number of G is then the size of the smallest edge cut inducing a coherent partition. A coherent partition of G is optimal if the size of the inducing edge cut is the coherence number of G. Given a graph G, we study coherent partitions and the coherence number in connection to (bi)clique partitions and the (bi)clique cover number. We show that the problem of finding the coherence number is NP-hard, but is of polynomial time complexity for trees. We also discuss the relation between coherent partitions and prominent graph clustering quality measures. KW - Graph partitions KW - Network clustering KW - Coherence number KW - Coherent partition Y1 - 2019 U6 - https://doi.org/10.1016/j.dam.2019.02.048 SN - 0166-218X SN - 1872-6771 VL - 266 SP - 283 EP - 290 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Bhuvanesh, Thanga A1 - Machatschek, Rainhard Gabriel A1 - Lysyakova, Liudmila A1 - Kratz, Karl A1 - Schulz, Burkhard A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Collagen type-IV Langmuir and Langmuir-Schafer layers as model biointerfaces to direct stem cell adhesion JF - Biomedical materials : materials for tissue engineering and regenerative medicine N2 - In biomaterial development, the design of material surfaces that mimic the extra-cellular matrix (ECM) in order to achieve favorable cellular instruction is rather challenging. Collagen-type IV (Col-IV), the major scaffolding component of Basement Membranes (BM), a specialized ECM with multiple biological functions, has the propensity to form networks by self-assembly and supports adhesion of cells such as endothelial cells or stem cells. The preparation of biomimetic Col-IV network-like layers to direct cell responses is difficult. We hypothesize that the morphology of the layer, and especially the density of the available adhesion sites, regulates the cellular adhesion to the layer. The Langmuir monolayer technique allows for preparation of thin layers with precisely controlled packing density at the air-water (A-W) interface. Transferring these layers onto cell culture substrates using the Langmuir-Schafer (LS) technique should therefore provide a pathway for preparation of BM mimicking layers with controlled cell adherence properties. In situ characterization using ellipsometry and polarization modulation-infrared reflection absorption spectroscopy of Col-IV layer during compression at the A-W interface reveal that there is linear increase of surface molecule concentration with negligible orientational changes up to a surface pressure of 25 mN m(-1). Smooth and homogeneous Col-IV network-like layers are successfully transferred by LS method at 15 mN m(-1) onto poly(ethylene terephthalate) (PET), which is a common substrate for cell culture. In contrast, the organization of Col-IV on PET prepared by the traditionally employed solution deposition method results in rather inhomogeneous layers with the appearance of aggregates and multilayers. Progressive increase in the number of early adherent mesenchymal stem cells (MSCs) after 24 h by controlling the areal Col-IV density by LS transfer at 10, 15 and 20 mN m(-1) on PET is shown. The LS method offers the possibility to control protein characteristics on biomaterial surfaces such as molecular density and thereby, modulate cell responses. KW - collagen-IV KW - basement membrane KW - Langmuir-Schafer films KW - stem cell adhesion KW - protein KW - ellipsometry Y1 - 2019 U6 - https://doi.org/10.1088/1748-605X/aaf464 SN - 1748-6041 SN - 1748-605X VL - 14 IS - 2 PB - Inst. of Physics Publ. CY - Bristol ER - TY - JOUR A1 - Naseri, Gita A1 - Behrend, Jessica A1 - Rieper, Lisa A1 - Müller-Röber, Bernd T1 - COMPASS for rapid combinatorial optimization of biochemical pathways based on artificial transcription factors JF - Nature Communications N2 - Balanced expression of multiple genes is central for establishing new biosynthetic pathways or multiprotein cellular complexes. Methods for efficient combinatorial assembly of regulatory sequences (promoters) and protein coding sequences are therefore highly wanted. Here, we report a high-throughput cloning method, called COMPASS for COMbinatorial Pathway ASSembly, for the balanced expression of multiple genes in Saccharomyces cerevisiae. COMPASS employs orthogonal, plant-derived artificial transcription factors (ATFs) and homologous recombination-based cloning for the generation of thousands of individual DNA constructs in parallel. The method relies on a positive selection of correctly assembled pathway variants from both, in vivo and in vitro cloning procedures. To decrease the turnaround time in genomic engineering, COMPASS is equipped with multi-locus CRISPR/Cas9-mediated modification capacity. We demonstrate the application of COMPASS by generating cell libraries producing n-carotene and co-producing p-ionone and biosensor-responsive naringenin. COMPASS will have many applications in synthetic biology projects that require gene expression balancing. Y1 - 2019 U6 - https://doi.org/10.1038/s41467-019-10224-x SN - 2041-1723 VL - 10 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Kahl, Sandra M. A1 - Lenhard, Michael A1 - Joshi, Jasmin Radha T1 - Compensatory mechanisms to climate change in the widely distributed species Silene vulgaris JF - The journal of ecology N2 - The adaptation of plants to future climatic conditions is crucial for their survival. Not surprisingly, phenotypic responses to climate change have already been observed in many plant populations. These responses may be due to evolutionary adaptive changes or phenotypic plasticity. Especially plant species with a wide geographic range are either expected to show genetic differentiation in response to differing climate conditions or to have a high phenotypic plasticity. We investigated phenotypic responses and plasticity as an estimate of the adaptive potential in the widespread species Silene vulgaris. In a greenhouse experiment, 25 European populations covering a geographic range from the Canary Islands to Sweden were exposed to three experimental precipitation and two temperature regimes mimicking a possible climate-change scenario for central Europe. We hypothesized that southern populations have a better performance under high temperature and drought conditions, as they are already adapted to a comparable environment. We found that our treatments significantly influenced the plants, but did not reveal a latitudinal difference in response to climate treatments for most plant traits. Only flower number showed a stronger plasticity in northern European populations (e.g. Swedish populations) where numbers decreased more drastically with increased temperature and decreased precipitation treatment. Synthesis. The significant treatment response in Silene vulgaris, independent of population origin - except for the number of flowers produced - suggests a high degree of universal phenotypic plasticity in this widely distributed species. This reflects the likely adaptation strategy of the species and forms the basis for a successful survival strategy during upcoming climatic changes. However, as flower number, a strongly fitness-related trait, decreased more strongly in northern populations under a climate-change scenario, there might be limits to adaptation even in this widespread, plastic species. KW - climate change KW - global change ecology KW - latitudinal gradient KW - local adaptation KW - phenotypic plasticity KW - plant performance KW - temperature increase Y1 - 2019 U6 - https://doi.org/10.1111/1365-2745.13133 SN - 0022-0477 SN - 1365-2745 VL - 107 IS - 4 SP - 1918 EP - 1930 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Küken, Anika A1 - Nikoloski, Zoran T1 - Computational Approaches to Design and Test Plant Synthetic Metabolic Pathways JF - Plant physiology : an international journal devoted to physiology, biochemistry, cellular and molecular biology, biophysics and environmental biology of plants N2 - Successfully designed and implemented plant-specific synthetic metabolic pathways hold promise to increase crop yield and nutritional value. Advances in synthetic biology have already demonstrated the capacity to design artificial biological pathways whose behavior can be predicted and controlled in microbial systems. However, the transfer of these advances to model plants and crops faces the lack of characterization of plant cellular pathways and increased complexity due to compartmentalization and multicellularity. Modern computational developments provide the means to test the feasibility of plant synthetic metabolic pathways despite gaps in the accumulated knowledge of plant metabolism. Here, we provide a succinct systematic review of optimization-based and retrobiosynthesis approaches that can be used to design and in silico test synthetic metabolic pathways in large-scale plant context-specific metabolic models. In addition, by surveying the existing case studies, we highlight the challenges that these approaches face when applied to plants. Emphasis is placed on understanding the effect that metabolic designs can have on native metabolism, particularly with respect to metabolite concentrations and thermodynamics of biochemical reactions. In addition, we discuss the computational developments that may help to transform the identified challenges into opportunities for plant synthetic biology. Y1 - 2019 U6 - https://doi.org/10.1104/pp.18.01273 SN - 0032-0889 SN - 1532-2548 VL - 179 IS - 3 SP - 894 EP - 906 PB - American Society of Plant Physiologists CY - Rockville ER - TY - JOUR A1 - Sowemimo, Oluwakemi T. A1 - Knox-Brown, Patrick A1 - Borcherds, Wade A1 - Rindfleisch, Tobias A1 - Thalhammer, Anja A1 - Daughdrill, Gary W. T1 - Conserved Glycines Control Disorder and Function in the Cold-Regulated Protein, COR15A JF - Biomolecules N2 - Cold-regulated (COR) 15A is an intrinsically disordered protein (IDP) from Arabidopsis thaliana important for freezing tolerance. During freezing-induced cellular dehydration, COR15A transitions from a disordered to mostly alpha-helical structure. We tested whether mutations that increase the helicity of COR15A also increase its protective function. Conserved glycine residues were identified and mutated to alanine. Nuclear magnetic resonance (NMR) spectroscopy was used to identify residue-specific changes in helicity for wildtype (WT) COR15A and the mutants. Circular dichroism (CD) spectroscopy was used to monitor the coil-helix transition in response to increasing concentrations of trifluoroethanol (TFE) and ethylene glycol. The impact of the COR15A mutants on the stability of model membranes during a freeze-thaw cycle was investigated by fluorescence spectroscopy. The results of these experiments showed the mutants had a higher content of alpha-helical structure and the increased alpha-helicity improved membrane stabilization during freezing. Comparison of the TFE- and ethylene glycol-induced coil-helix transitions support our conclusion that increasing the transient helicity of COR15A in aqueous solution increases its ability to stabilize membranes during freezing. Altogether, our results suggest the conserved glycine residues are important for maintaining the disordered structure of COR15A but are also compatible with the formation of alpha-helical structure during freezing induced dehydration. KW - COR15A KW - Late embryogenesis abundant KW - intrinsically disordered proteins KW - Trifluoroethanol KW - Nuclear magnetic resonance Y1 - 2019 U6 - https://doi.org/10.3390/biom9030084 SN - 2218-273X VL - 9 IS - 3 PB - MDPI CY - Basel ER - TY - THES A1 - Schirmer, Annika T1 - Consistent individual differences in movement-related behaviour as equalising and/or stabilising mechanisms for species coexistence T1 - Konstante individuelle Unterschiede in Bewegungs-relevanten Verhaltensweisen als stabilisierende und/oder angleichende Mechanismen für die Koexistenz von Arten N2 - The facilitation of species coexistence has been a central theme in ecological research for years, highlighting two key aspects: ecological niches and competition between species. According to the competitive exclusion principle, the overlap of species niches predicts the amount of shared resources and therefore competition between species, determining their ability to coexist. Only if niches of two species are sufficiently different, thus niche overlap is low, competition within species is higher than competition between species and stable coexistence is possible. Thereby, differences in species mean traits are focused on and conspecific individuals are assumed to be interchangeable. This approach might be outdated since behaviour, as a key aspect mediating niche differentiation between species, is individual based. Individuals from one species consistently differ across time and situations in their behavioural traits. Causes and consequences of consistent behavioural differences have been thoroughly investigated stimulating their recent incorporation into ecological interactions and niche theory. Spatial components have so far been largely overlooked, although animal movement is strongly connected to several aspects of ecological niches and interactions between individuals. Furthermore, numerous movement aspects haven been proven to be crucially influenced by consistent individual differences. Considering spatial parameters could therefore crucially broaden our understanding of how individual niches are formed and ecological interactions are shaped. Furthermore, extending established concepts on species interactions by an individual component could provide new insights into how species coexistence is facilitated and local biodiversity is maintained. The main aim of this thesis was to test whether consistent inter-individual differences can facilitate the coexistence of ecological similar species. Therefore, the effects of consistent inter-individual differences on the spatial behaviour of two rodent species, the bank vole (Myodes glareolus) and the striped field mouse (Apodemus agrarius), were investigated and put in the context of: (i) individual spatial niches, (ii) interactions between species, and (iii) the importance of different levels of behavioural variation within species for their interactions. Consistent differences of study animals in boldness and exploration were quantified with the same tests in all presented studies and always combined with observations of movement and space use via automated VHF radio telemetry. Consequently, results are comparable throughout the thesis and the methods provide a common denominator for all chapters. The first two chapters are based on observations of free-ranging rodents in natural populations, while chapter III represents an experimental approach under semi-natural conditions. Chapter I focusses on the effect of consistent differences in boldness and exploration on movement and space use of bank voles and their contribution to individual spatial niche separation. Results show boldness to be the dominating predictor for spatial parameters in bank voles. Irrespective of sex, bolder individuals had larger home ranges, moved longer distances, had less spatial interactions with conspecifics and occupied different microhabitats compared to shy individuals. The same boldness-dependent spatial patterns could be observed in striped field mice which is reported in chapter II. Therefore, both study species showed individual spatial niche occupation. Chapter II builds on findings from the first chapter, investigating the effect of boldness driven individual spatial niche occupation on the interactions between species. Irrespective of species and sex, bolder individuals had more interspecific spatial interactions, but less intraspecific interactions, compared to shy individuals. Due to individual niches occupation the competitive environment individuals experience is not random. Interactions are restricted to individuals of similar behavioural type with presumably similar competitive ability, which could balance differences on the species level and support coexistence. In chapter III the experimental populations were either comprised of only shy or only bold bank voles, while striped field mice varied, creating either a shy- or bold-biased competitive community. Irrespective of behavioural type, striped field mice had more intraspecific interactions in bold-biased competitive communities. Only in a shy-biased competitive community, bolder striped field mice had less interspecific interactions compared to shy individuals. Bank voles showed no difference in intra- or interspecific interactions between populations. Chapter III highlights, that not only consistent inter-individual differences per se are important for interactions within and between species, but also the amount of behavioural variation within coexisting species. Overall, this thesis highlights the importance of considering consistent inter-individual differences in a spatial context and their connection to individual spatial niche occupation, as well as the resulting effects on interactions within and between species. Individual differences are discussed in the context of similarity of individuals, individual and species niche width, and individual and species niche overlap. Thereby, this thesis makes one step further from the existing research on individual niches towards integrating consistent inter-individual differences into the larger framework of species coexistence. N2 - Ein zentrales Thema in der Ökologie ist die Koexistenz von Arten. Zwei Aspekte sind dabei von großer Bedeutung: ökologische Nischen und zwischenartliche Konkurrenz. Das Konkurrenz-Ausschlussprinzip besagt, dass der Überlappungsgrad der Nischen zweier Arten bestimmt, wie viele Ressourcen sie teilen und damit wie stark die Konkurrenz zwischen ihnen ist. Eine stabile Koexistenz zweier Arten ist nur dann möglich, wenn ihre Nischen unterschiedlich genug sind und eine geringe Überlappung vorliegt. In diesem Fall ist die innerartliche Konkurrenz größer als die zwischenartliche, und die Bedingungen für eine langfristig stabile Koexistenz sind gegeben. Traditionell werden hierbei nur mittlere Unterschiede zwischen den Fokusarten verglichen und der Einfluss von Unterschieden zwischen Individuen nicht beachtet. Ein wesentlicher Aspekt, der die Nischendifferenzierung zwischen Tierarten beeinflusst ist deren Verhalten. Dieses ist jedoch nachweislich individuell geprägt, folglich könnte der oben erwähnte Ansatz zur Koexistenz von Arten eventuell veraltet sein. Zwischen Individuen einer Art gibt es konstante Verhaltensunterschiede, die stabil bleiben über die Zeit und zwischen verschiedenen Situationen. Ursachen und Effekte dieser Unterschiede wurden bereits in zahlreichen Tierarten untersucht, wodurch ebenfalls die Integration von individuellen Verhaltensunterschieden in das Konzept der ökologischen Nische angestoßen wurde. Aspekte der Raumnutzung von Tieren fanden hierbei bislang kaum Beachtung, obwohl sie für eine Vielzahl von Parametern, die mit Nischen in Verbindung stehen, essentiell sind. Räumliches Verhalten von Tieren wird stark durch individuelle Verhaltensunterschiede beeinflusst, weswegen es eine wichtige Rolle im Zusammenhang mit individuellen Nischen spielen sollte. Hinsichtlich der Formation individueller Nischen und ökologischer Interaktionen hat die Einbeziehung von räumlichen Aspekten das Potential entscheidende Impulse zu erbringen. Die Erweiterung bestehender Theorien zu Artinteraktionen, um eine individuelle Komponente, kann neue Einblicke schaffen wie Koexistenz zwischen Arten vermittelt und örtliche Biodiversität erhalten wird. Die hier vorliegende Arbeit befasst sich mit den Einflüssen von stabilen, individuellen Verhaltensunterschieden auf die Raumnutzung von Individuen. Dies wurde exemplarisch an zwei Nagerarten untersucht, der Rötelmaus (Myodes glareolus) und der Brandmaus (Apodemus agrarius). Dabei wird der Fokus auf die folgenden Aspekte gelegt: (i) individuelle Nischen, (ii) Interaktionen zwischen Arten, und (iii) Auswirkungen verschiedener Variationsgrade stabiler Verhaltensunterschiede auf die Interaktionen innerhalb und zwischen Arten. Alle Kapitel basieren auf der gleichen Methodik in der Datenaufnahme, da individuelle Verhaltensunterschiede stets mit dem gleichen Test quantifiziert und mit räumlichen Mustern in Zusammenhang gebracht wurden, die mit Hilfe automatischer VHF Radiotelemetrie aufgezeichnet wurden. Ergebnisse sind somit auch kapitelübergreifend vergleichbar. Kapitel eins und zwei umfassen Studien an freilebenden Nagetieren aus natürlichen Populationen, während das dritte Kapitel eine experimentelle Studie unter naturnahen Bedingungen darstellt. Das erste Kapitel handelt von den Effekten stabiler Verhaltensunterschiede in der Risikobereitschaft und dem Explorationsverhalten von Rötelmäusen auf deren Bewegungsmuster. Letztere wurden nur durch die Risikobereitschaft der Individuen beeinflusst, aber nicht durch deren Explorationsverhalten. Risikofreudigere Individuen hatten größere Streifgebiete, legten längere Strecken zurück, hatten weniger innerartliche Interaktionen und bewohnten andere Mikrohabitate als risikoscheue Individuen. Gleiche Muster konnten für die Brandmäuse gefunden werden, werden jedoch erst im zweiten Kapitel dargestellt. Beide Arten besetzen somit individuelle räumliche Nischen. Kapitel zwei baut auf dem Resultat des ersten Kapitels auf und beschäftigt sich mit den Auswirkungen von individuellen räumlichen Nischen auf die Interaktionen zwischen zwei Arten. Hierbei konnte gezeigt werden, dass unabhängig von Art und Geschlecht, risikofreudigere Individuen weniger innerartliche Interaktionen haben, dafür aber mehr zwischenartliche im Vergleich zu risikoscheuen Individuen. Die Besetzung individueller Nischen hat somit zur Folge, dass das Konkurrenz-Umfeld der Individuen abhängig von ihrem Verhaltenstyp ist. Daraus folgt, dass die Interaktionen zwischen Individuen zweier Arten beschränkt sind auf solche Individuen, die sich in ihrem Verhaltenstyp, und damit ihrer Konkurrenzkraft, ähneln. Etwaige Artunterschiede in der Konkurrenzkraft könnten dadurch ausgeglichen werden und die Koexistenz der Arten vermitteln. Im letzten Kapitel wurden experimentelle Populationen aus beiden Versuchsarten zusammengestellt. Diese unterschieden sich darin, dass die Rötelmäuse entweder ausschließlich risikoscheu oder risikobereit waren, während die Brandmäuse in ihrem Verhaltenstyp variierten. Dadurch wurden Artgemeinschaften erstellt, die entweder ein vorwiegend risikoscheues oder risikobereites Konkurrenz-Umfeld hatten. Eine reduzierte Variationsbreite der individuellen Verhaltensunterschiede in einer von zwei koexistierenden Arten führt dazu, dass sich die Interaktionsmuster innerhalb und zwischen den Arten, im Vergleich zu denen aus natürlichen Populationen verändern. Brandmäuse in einem risikobereiten Konkurrenz-Umfeld hatten mehr innerartliche Interaktionen als solche in einem risikoscheuen Konkurrenz-Umfeld, unabhängig davon ob die Brandmäuse selber risikoscheu oder risikofreudig waren. Die zwischenartlichen Interaktionen dagegen wurden nur in einem risikoscheuen Konkurrenz-Umfeld von risikobereiten Brandmäusen reduziert im Gegensatz zu risikoscheuen Individuen. Währenddessen zeigen Rötelmäuse weder in den inner- noch in den zwischenartlichen Interaktionen einen Unterschied aufgrund ihres Konkurrenz-Umfeldes. Das dritte Kapitel zeigt damit deutlich, dass nicht nur stabile individuelle Unterschiede für inner- und zwischenartliche Interaktionen von Bedeutung sind, sondern dass auch die Variationsbreite der Verhaltensunterschiede innerhalb der Arten eine entscheidende Rolle spielt. Zusammenfassend verdeutlicht die vorliegende Arbeit wie wichtig die Berücksichtigung von stabilen individuellen Verhaltensunterschieden im Hinblick auf räumliche Parameter ist. Darüber hinaus zeigen die vorliegenden Ergebnisse, dass individuelle Verhaltensunterschiede für die Besetzung individueller Nischen und damit für inner- und zwischenartlichen Interaktionen von großer Bedeutung sind. Innerhalb dieser Arbeit werden individuelle Verhaltensunterschiede in Zusammenhang mit der Ähnlichkeit von Arten, der Breite von individuellen Nischen und Artnischen, sowie deren Überlappung gebracht. Diese Arbeit stellt somit eine Erweiterung des bisherigen Forschungstandes hinsichtlich der Einbeziehung von individuellen Verhaltensunterschieden in die Theorie der Koexistenz von Arten dar. KW - ecological interactions KW - inter-individual differences KW - animal personality KW - movement ecology KW - space use Y1 - 2019 ER - TY - JOUR A1 - Günthel, Marco A1 - Donis, Daphne A1 - Kirillin, Georgiy A1 - Ionescu, Danny A1 - Bizic, Mina A1 - McGinnis, Daniel F. A1 - Grossart, Hans-Peter A1 - Tang, Kam W. T1 - Contribution of oxic methane production to surface methane emission in lakes and its global importance JF - Nature Communications N2 - Recent discovery of oxic methane production in sea and lake waters, as well as wetlands, demands re-thinking of the global methane cycle and re-assessment of the contribution of oxic waters to atmospheric methane emission. Here we analysed system-wide sources and sinks of surface-water methane in a temperate lake. Using a mass balance analysis, we show that internal methane production in well-oxygenated surface water is an important source for surface-water methane during the stratified period. Combining our results and literature reports, oxic methane contribution to emission follows a predictive function of littoral sediment area and surface mixed layer volume. The contribution of oxic methane source(s) is predicted to increase with lake size, accounting for the majority (>50%) of surface methane emission for lakes with surface areas >1 km(2). Y1 - 2019 U6 - https://doi.org/10.1038/s41467-019-13320-0 SN - 2041-1723 VL - 10 PB - Nature Publishing Group UK CY - London ER - TY - THES A1 - Wozniak, Natalia Joanna T1 - Convergent evolution of the selfing syndrome in the genus Capsella BT - inferring the genetic basis and evolutionary history of selfing syndrome traits Y1 - 2019 ER - TY - GEN A1 - Lepro, Valentino A1 - Nagel, Oliver A1 - Klumpp, Stefan A1 - Lipowsky, Reinhard A1 - Beta, Carsten T1 - Cooperative Transport by Amoeboid Cells BT - a Cellular Tug-of-War T2 - Biophysical journal Y1 - 2019 U6 - https://doi.org/10.1016/j.bpj.2018.11.682 SN - 0006-3495 SN - 1542-0086 VL - 116 IS - 3 SP - 122A EP - 122A PB - Cell Press CY - Cambridge ER - TY - JOUR A1 - Tang, Kam W. A1 - Backhaus, Liv A1 - Riemann, Lasse A1 - Koski, Marja A1 - Grossart, Hans-Peter A1 - Munk, Peter A1 - Nielsen, Torkel Gissel T1 - Copepod carcasses in the subtropical convergence zone of the Sargasso Sea BT - implications for microbial community composition, system respiration and carbon flux JF - Journal of plankton research N2 - The oligotrophic subtropical gyre covers a vast area of the Atlantic Ocean. Decades of time-series monitoring have generated detailed temporal information about zooplankton species and abundances at fixed locations within the gyre, but their live/dead status is often omitted, especially in the dynamic subtropical convergence zone (STCZ) where the water column stratification pattern can change considerably across the front as warm and cold water masses converge. We conducted a detailed survey in the North Atlantic STCZ and showed that over 85% of the copepods were typically concentrated in the upper 200 m. Copepod carcasses were present in all samples and their proportional numerical abundances increased with depth, reaching up to 91% at 300-400 m. Overall, 14-19% of the copepods within the upper 200 m were carcasses. Shipboard experiments showed that during carcass decomposition, microbial respiration increased, and the bacterial community associated with the carcasses diverged from that in the ambient water. Combining field and experimental data, we estimated that decomposing copepod carcasses constitute a negligible oxygen sink in the STCZ, but sinking carcasses may represent an overlooked portion of the passive carbon sinking flux and should be incorporated in future studies of carbon flux in this area. KW - Sargasso Sea KW - subtropical convergence zone KW - zooplankton KW - carcasses KW - carbon sinking flux Y1 - 2019 U6 - https://doi.org/10.1093/plankt/fbz038 SN - 0142-7873 SN - 1464-3774 VL - 41 IS - 4 SP - 549 EP - 560 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Mazza, Valeria A1 - Dammhahn, Melanie A1 - Eccard, Jana A1 - Palme, Rupert A1 - Zaccaroni, Marco A1 - Jacob, Jens T1 - Coping with style: individual differences in responses to environmental variation JF - Behavioral ecology and sociobiology N2 - Between-individual differences in coping with stress encompass neurophysiological, cognitive and behavioural reactions. The coping style model proposes two alternative response patterns to challenges that integrate these types of reactions. The “proactive strategy” combines a general fight-or-flight response and inflexibility in learning with a relatively low HPA (hypothalamic–pituitary–adrenal) response. The “reactive strategy” includes risk aversion, flexibility in learning and an enhanced HPA response. Although numerous studies have investigated the possible covariance of cognitive, behavioural and physiological responses, findings are still mixed. In the present study, we tested the predictions of the coping style model in an unselected population of bank voles (Myodes glareolus) (N = 70). We measured the voles’ boldness, activity, speed and flexibility in learning and faecal corticosterone metabolite levels under three conditions (holding in indoor cages, in outdoor enclosures and during open field test). Individuals were moderately consistent in their HPA response across situations. Proactive voles had significantly lower corticosterone levels than reactive conspecifics in indoor and outdoor conditions. However, we could not find any co-variation between cognitive and behavioural traits and corticosterone levels in the open field test. Our results partially support the original coping style model but suggest a more complex relationship between cognitive, behavioural and endocrine responses than was initially proposed. KW - Coping styles KW - Faecal glucocorticoid metabolites KW - Learning KW - Stress KW - Personality KW - Rodent Y1 - 2019 U6 - https://doi.org/10.1007/s00265-019-2760-2 SN - 0340-5443 SN - 1432-0762 VL - 73 IS - 10 PB - Springer CY - New York ER - TY - JOUR A1 - de la Cruz, Jorge Gonzalez A1 - Machens, Fabian A1 - Messerschmidt, Katrin A1 - Bar-Even, Arren T1 - Core Catalysis of the Reductive Glycine Pathway Demonstrated in Yeast JF - ACS synthetic biology N2 - One-carbon (C1) compounds are attractive microbial feedstocks as they can be efficiently produced from widely available resources. Formate, in particular, represents a promising growth substrate, as it can be generated from electrochemical reduction of CO2 and fed to microorganisms in a soluble form. We previously identified the synthetic reductive glycine pathway as the most efficient route for aerobic growth on formate. We further demonstrated pathway activity in Escherichia coli after expression of both native and foreign genes. Here, we explore whether the reductive glycine pathway could be established in a model microorganism using only native enzymes. We used the yeast Saccharomyces cerevisiae as host and show that overexpression of only endogenous enzymes enables glycine biosynthesis from formate and CO2 in a strain that is otherwise auxotrophic for glycine. We find the pathway to be highly active in this host, where 0.125 mM formate is sufficient to support growth. Notably, the formate-dependent growth rate of the engineered S. cerevisiae strain remained roughly constant over a very wide range of formate concentrations, 1-500 mM, indicating both high affinity for formate use and high tolerance toward elevated concentration of this C1 feedstock. Our results, as well the availability of endogenous NAD-dependent formate dehydrogenase, indicate that yeast might be an especially suitable host for engineering growth on formate. KW - metabolic engineering KW - synthetic biology KW - one-carbon metabolism KW - carbon labeling KW - tetrahydrofolate KW - glycine cleavage system Y1 - 2019 U6 - https://doi.org/10.1021/acssynbio.8b00464 SN - 2161-5063 VL - 8 IS - 5 SP - 911 EP - 917 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Frombach, Janna A1 - Unbehauen, Michael A1 - Kurniasih, Indah N. A1 - Schumacher, Fabian A1 - Volz, Pierre A1 - Hadam, Sabrina A1 - Rancan, Fiorenza A1 - Blume-Peytavi, Ulrike A1 - Kleuser, Burkhard A1 - Haag, Rainer A1 - Alexiev, Ulrike A1 - Vogt, Annika T1 - Core-multishell nanocarriers enhance drug penetration and reach keratinocytes and antigen-presenting cells in intact human skin JF - Journal of controlled release N2 - In reconstructed skin and diffusion cell studies, core-multishell nanocarriers (CMS-NC) showed great potential for drug delivery across the skin barrier. Herein, we investigated penetration, release of dexamethasone (DXM), in excised full-thickness human skin with special focus on hair follicles (HF). Four hours and 16 h after topical application of clinically relevant dosages of 10 mu g DXM/cm(2) skin encapsulated in CMS-NC (12 nm diameter, 5.8% loading), presence of DXM in the tissue as assessed by fluorescence microscopy of anti-DXM-stained tissue sections as well as ELISA and HPLC-MS/MS in tissue extracts was enhanced compared to standard LAW-creme but lower compared to DXM aqueous/alcoholic solution. Such enhanced penetration compared to conventional cremes offers high potential for topical therapies, as recurrent applications of corticosteroid solutions face limitations with regard to tolerability and fast drainage. The findings encourage more detailed investigations on where and how the nanocarrier and drug dissociate within the skin and what other factors, e.g. thermodynamic activity, influence the penetration of this formulations. Microscopic studies on the spatial distribution within the skin revealed accumulation in HF and furrows accompanied by limited cellular uptake assessed by flow cytometry (up to 9% of total epidermal cells). FLIM clearly visualized the presence of CMS-NC in the viable epidermis and dermis. When exposed in situ a fraction of up to 25% CD1a(+) cells were found within the epidermal CMS-NC+ population compared to approximately 3% CD1a(+)/CMS-NC+ cells after in vitro exposure in short-term cultures of epidermal cell suspensions. The latter reflects the natural percentage of Langerhans cells (LC) in epidermis suspensions and indicated that CMS-NC were not preferentially internalized by one cell type. The increased CMS-NC+ LC proportion after exposure within the tissue is in accordance with the strategic suprabasal LC-localization. More specifically we postulate that the extensive dendrite meshwork, their position around HF orifices and their capacity to modulate tight junctions facilitated a preferential uptake of CMS-NC by LC within the skin. This newly identified aspect of CMS-NC penetration underlines the potential of CMS-NC for dermatotherapy and encourages further investigations of CMS-NC for the delivery of other molecule classes for which intracellular delivery is even more crucial. KW - Drug delivery KW - Skin penetration KW - Cellular uptake KW - Nanoparticles KW - Dendritic cells KW - High resolution microscopy Y1 - 2019 U6 - https://doi.org/10.1016/j.jconrel.2019.02.028 SN - 0168-3659 SN - 1873-4995 VL - 299 SP - 138 EP - 148 PB - Elsevier CY - Amsterdam ER - TY - GEN A1 - Horreo, J. L. A1 - Breedveld, Merel Cathelijne A1 - Lindtke, D. A1 - Heulin, B. A1 - Surget-Groba, Yann A1 - Fitze, Patrick S. T1 - Correction: Genetic introgression among differentiated clades is lower among clades exhibiting different parity modes. - (Heredity. - 123, (2019) pg 264) T2 - Heredity N2 - The original version of this Article contained an error in the spelling of the author Y. Surget-Groba, which was incorrectly given as J. Surget-Groba. This has now been corrected in both the PDF and HTML versions of the Article. Y1 - 2019 U6 - https://doi.org/10.1038/s41437-019-0223-1 SN - 0018-067X SN - 1365-2540 VL - 123 IS - 2 SP - 285 EP - 285 PB - Nature Publ. Group CY - London ER - TY - GEN A1 - Numberger, Daniela A1 - Dreier, Carola A1 - Vullioud, Colin A1 - Gabriel, Guelsah A1 - Greenwood, Alex D. A1 - Grossart, Hans-Peter T1 - Correction: Recovery of influenza A viruses from lake water and sediments by experimental inoculation (vol 14, e0216880, 2019) T2 - PLoS one Y1 - 2019 U6 - https://doi.org/10.1371/journal.pone.0218882 SN - 1932-6203 VL - 14 IS - 6 PB - PLoS CY - San Fransisco ER - TY - GEN A1 - Höfer, Chris Tina A1 - Di Lella, Santiago A1 - Dahmani, Ismail A1 - Jungnick, Nadine A1 - Bordag, Natalie A1 - Bobone, Sara A1 - Huan, Q. A1 - Keller, S. A1 - Herrmann, A. A1 - Chiantia, Salvatore T1 - Corrigendum to: Structural determinants of the interaction between influenza A virus matrix protein M1 and lipid membranes (Biochimica et Biophysica Acta (BBA) - Biomembranes. - 1861, (2019), pg 1123-1134) T2 - Biochimica et biophysica acta : Biomembranes Y1 - 2019 U6 - https://doi.org/10.1016/j.bbamem.2019.07.002 SN - 0005-2736 SN - 1879-2642 VL - 1861 IS - 10 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Raatz, Michael A1 - van Velzen, Ellen A1 - Gaedke, Ursula T1 - Co‐adaptation impacts the robustness of predator–prey dynamics against perturbations JF - Ecology and Evolution N2 - Global change threatens the maintenance of ecosystem functions that are shaped by the persistence and dynamics of populations. It has been shown that the persistence of species increases if they possess larger trait adaptability. Here, we investigate whether trait adaptability also affects the robustness of population dynamics of interacting species and thereby shapes the reliability of ecosystem functions that are driven by these dynamics. We model co‐adaptation in a predator–prey system as changes to predator offense and prey defense due to evolution or phenotypic plasticity. We investigate how trait adaptation affects the robustness of population dynamics against press perturbations to environmental parameters and against pulse perturbations targeting species abundances and their trait values. Robustness of population dynamics is characterized by resilience, elasticity, and resistance. In addition to employing established measures for resilience and elasticity against pulse perturbations (extinction probability and return time), we propose the warping distance as a new measure for resistance against press perturbations, which compares the shapes and amplitudes of pre‐ and post‐perturbation population dynamics. As expected, we find that the robustness of population dynamics depends on the speed of adaptation, but in nontrivial ways. Elasticity increases with speed of adaptation as the system returns more rapidly to the pre‐perturbation state. Resilience, in turn, is enhanced by intermediate speeds of adaptation, as here trait adaptation dampens biomass oscillations. The resistance of population dynamics strongly depends on the target of the press perturbation, preventing a simple relationship with the adaptation speed. In general, we find that low robustness often coincides with high amplitudes of population dynamics. Hence, amplitudes may indicate the robustness against perturbations also in other natural systems with similar dynamics. Our findings show that besides counteracting extinctions, trait adaptation indeed strongly affects the robustness of population dynamics against press and pulse perturbations. KW - disturbance KW - evolutionary rescue KW - population dynamics KW - stability KW - trait adaptation Y1 - 2019 U6 - https://doi.org/10.1002/ece3.5006 SN - 2045-7758 VL - 9 IS - 7 SP - 3823 EP - 3836 PB - John Wiley & Sons CY - Hoboken, NJ ER - TY - JOUR A1 - Schwarz, Maria A1 - Lossow, Kristina A1 - Kopp, Johannes Florian A1 - Schwerdtle, Tanja A1 - Kipp, Anna Patricia T1 - Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper JF - Nutrients N2 - Trace elements, like Cu, Zn, Fe, or Se, are important for the proper functioning of antioxidant enzymes. However, in excessive amounts, they can also act as pro-oxidants. Accordingly, trace elements influence redox-modulated signaling pathways, such as the Nrf2 pathway. Vice versa, Nrf2 target genes belong to the group of transport and metal binding proteins. In order to investigate whether Nrf2 directly regulates the systemic trace element status, we used mice to study the effect of a constitutive, whole-body Nrf2 knockout on the systemic status of Cu, Zn, Fe, and Se. As the loss of selenoproteins under Se-deprived conditions has been described to further enhance Nrf2 activity, we additionally analyzed the combination of Nrf2 knockout with feeding diets that provide either suboptimal, adequate, or supplemented amounts of Se. Experiments revealed that the Nrf2 knockout partially affected the trace element concentrations of Cu, Zn, Fe, or Se in the intestine, liver, and/or plasma. However, aside from Fe, the other three trace elements were only marginally modulated in an Nrf2-dependent manner. Selenium deficiency mainly resulted in increased plasma Zn levels. One putative mediator could be the metal regulatory transcription factor 1, which was up-regulated with an increasing Se supply and downregulated in Se-supplemented Nrf2 knockout mice. KW - Nrf2 KW - selenium KW - iron KW - copper KW - zinc KW - homeostasis Y1 - 2019 U6 - https://doi.org/10.3390/nu11092112 SN - 2072-6643 VL - 11 IS - 9 PB - MDPI CY - Basel ER - TY - JOUR A1 - Jaric, Ivan A1 - Heger, Tina A1 - Monzon, Federico Castro A1 - Jeschke, Jonathan M. A1 - Kowarik, Ingo A1 - McConkey, Kim R. A1 - Pysek, Petr A1 - Sagouis, Alban A1 - Essl, Franz T1 - Crypticity in Biological Invasions JF - Trends in Ecology & Evolution N2 - Ecological effects of alien species can be dramatic, but management and prevention of negative impacts are often hindered by crypticity of the species or their ecological functions. Ecological functions can change dramatically over time, or manifest after long periods of an innocuous presence. Such cryptic processes may lead to an underestimation of long-term impacts and constrain management effectiveness. Here, we present a conceptual framework of crypticity in biological invasions. We identify the underlying mechanisms, provide evidence of their importance, and illustrate this phenomenon with case studies. This framework has potential to improve the recognition of the full risks and impacts of invasive species. Y1 - 2019 U6 - https://doi.org/10.1016/j.tree.2018.12.008 SN - 0169-5347 SN - 1872-8383 VL - 34 IS - 4 SP - 291 EP - 302 PB - Elsevier CY - London ER - TY - JOUR A1 - Jose Clemente-Moreno, Maria A1 - Omranian, Nooshin A1 - Saez, Patricia A1 - Maria Figueroa, Carlos A1 - Del-Saz, Nestor A1 - Elso, Mhartyn A1 - Poblete, Leticia A1 - Orf, Isabel A1 - Cuadros-Inostroza, Alvaro A1 - Cavieres, Lohengrin A1 - Bravo, Leon A1 - Fernie, Alisdair R. A1 - Ribas-Carbo, Miquel A1 - Flexas, Jaume A1 - Nikoloski, Zoran A1 - Brotman, Yariv A1 - Gago, Jorge T1 - Cytochrome respiration pathway and sulphur metabolism sustain stress tolerance to low temperature in the Antarctic species Colobanthus quitensis JF - New phytologist : international journal of plant science N2 - Understanding the strategies employed by plant species that live in extreme environments offers the possibility to discover stress tolerance mechanisms. We studied the physiological, antioxidant and metabolic responses to three temperature conditions (4, 15, and 23 degrees C) of Colobanthus quitensis (CQ), one of the only two native vascular species in Antarctica. We also employed Dianthus chinensis (DC), to assess the effects of the treatments in a non-Antarctic species from the same family. Using fused LASSO modelling, we associated physiological and biochemical antioxidant responses with primary metabolism. This approach allowed us to highlight the metabolic pathways driving the response specific to CQ. Low temperature imposed dramatic reductions in photosynthesis (up to 88%) but not in respiration (sustaining rates of 3.0-4.2 mu mol CO2 m(-2) s(-1)) in CQ, and no change in the physiological stress parameters was found. Its notable antioxidant capacity and mitochondrial cytochrome respiratory activity (20 and two times higher than DC, respectively), which ensure ATP production even at low temperature, was significantly associated with sulphur-containing metabolites and polyamines. Our findings potentially open new biotechnological opportunities regarding the role of antioxidant compounds and respiratory mechanisms associated with sulphur metabolism in stress tolerance strategies to low temperature. KW - Antarctica KW - antioxidant capacity KW - low temperature KW - photosynthesis KW - respiration KW - stress tolerance KW - sulphur metabolism Y1 - 2019 U6 - https://doi.org/10.1111/nph.16167 SN - 0028-646X SN - 1469-8137 VL - 225 IS - 2 SP - 754 EP - 768 PB - Wiley CY - Hoboken ER - TY - THES A1 - Gupta, Saurabh T1 - Deciphering stress acclimation mechanisms in plants with extreme abiotic stress tolerence using genomics approaches Y1 - 2019 ER - TY - JOUR A1 - Kluth, Oliver A1 - Stadion, Mandy A1 - Gottmann, Pascal A1 - Aga-Barfknecht, Heja A1 - Jähnert, Markus A1 - Scherneck, Stephan A1 - Vogel, Heike A1 - Krus, Ulrika A1 - Seelig, Anett A1 - Ling, Charlotte A1 - Gerdes, Jantje A1 - Schürmann, Annette T1 - Decreased expression of cilia genes in pancreatic islets as a risk factor for type 2 diabetes in mice and humans JF - Cell reports N2 - An insufficient adaptive beta-cell compensation is a hallmark of type 2 diabetes (T2D). Primary cilia function as versatile sensory antennae regulating various cellular processes, but their role on compensatory beta-cell replication has not been examined. Here, we identify a significant enrichment of downregulated, cilia-annotated genes in pancreatic islets of diabetes-prone NZO mice as compared with diabetes-resistant B6-ob/ob mice. Among 327 differentially expressed mouse cilia genes, 81 human orthologs are also affected in islets of diabetic donors. Islets of nondiabetic mice and humans show a substantial overlap of upregulated cilia genes that are linked to cell-cycle progression. The shRNA-mediated suppression of KIF3A, essential for ciliogenesis, impairs division of MINE beta cells as well as in dispersed primary mouse and human islet cells, as shown by decreased BrdU incorporation. These findings demonstrate the substantial role of cilia-gene regulation on islet function and T2D risk. Y1 - 2019 U6 - https://doi.org/10.1016/j.celrep.2019.02.056 SN - 2211-1247 VL - 26 IS - 11 SP - 3027 EP - 3036 PB - Cell Press CY - Maryland Heights ER - TY - JOUR A1 - Deng, Zijun A1 - Zou, Jie A1 - Wang, Weiwei A1 - Nie, Yan A1 - Tung, Wing-Tai A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Dedifferentiation of mature adipocytes with periodic exposure to cold JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Lipid-containing adipocytes can dedifferentiate into fibroblast-like cells under appropriate culture conditions, which are known as dedifferentiated fat (DFAT) cells. However, the relative low dedifferentiation efficiency with the established protocols limit their widespread applications. In this study, we found that adipocyte dedifferentiation could be promoted via periodic exposure to cold (10 degrees C) in vitro. The lipid droplets in mature adipocytes were reduced by culturing the cells in periodic cooling/heating cycles (10-37 degrees C) for one week. The periodic temperature change led to the down-regulation of the adipogenic genes (FABP4, Leptin) and up-regulation of the mitochondrial uncoupling related genes (UCP1, PGC-1 alpha, and PRDM16). In addition, the enhanced expression of the cell proliferation marker Ki67 was observed in the dedifferentiated fibroblast-like cells after periodic exposure to cold, as compared to the cells cultured in 37 degrees C. Our in vitro model provides a simple and effective approach to promote lipolysis and can be used to improve the dedifferentiation efficiency of adipocytes towards multipotent DFAT cells. KW - Adipocyte KW - dedifferentiation KW - cold KW - lipid Y1 - 2019 U6 - https://doi.org/10.3233/CH-199005 SN - 1386-0291 SN - 1875-8622 VL - 71 IS - 4 SP - 415 EP - 424 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Thomas, Jessica E. A1 - Carvalho, Gary R. A1 - Haile, James A1 - Rawlence, Nicolas J. A1 - Martin, Michael D. A1 - Ho, Simon Y. W. A1 - Sigfusson, Arnor P. A1 - Josefsson, Vigfus A. A1 - Frederiksen, Morten A1 - Linnebjerg, Jannie F. A1 - Castruita, Jose A. Samaniego A1 - Niemann, Jonas A1 - Sinding, Mikkel-Holger S. A1 - Sandoval-Velasco, Marcela A1 - Soares, Andre E. R. A1 - Lacy, Robert A1 - Barilaro, Christina A1 - Best, Juila A1 - Brandis, Dirk A1 - Cavallo, Chiara A1 - Elorza, Mikelo A1 - Garrett, Kimball L. A1 - Groot, Maaike A1 - Johansson, Friederike A1 - Lifjeld, Jan T. A1 - Nilson, Goran A1 - Serjeanston, Dale A1 - Sweet, Paul A1 - Fuller, Errol A1 - Hufthammer, Anne Karin A1 - Meldgaard, Morten A1 - Fjeldsa, Jon A1 - Shapiro, Beth A1 - Hofreiter, Michael A1 - Stewart, John R. A1 - Gilbert, M. Thomas P. A1 - Knapp, Michael T1 - Demographic reconstruction from ancient DNA supports rapid extinction of the great auk JF - eLife N2 - The great auk was once abundant and distributed across the North Atlantic. It is now extinct, having been heavily exploited for its eggs, meat, and feathers. We investigated the impact of human hunting on its demise by integrating genetic data, GPS-based ocean current data, and analyses of population viability. We sequenced complete mitochondrial genomes of 41 individuals from across the species' geographic range and reconstructed population structure and population dynamics throughout the Holocene. Taken together, our data do not provide any evidence that great auks were at risk of extinction prior to the onset of intensive human hunting in the early 16th century. In addition, our population viability analyses reveal that even if the great auk had not been under threat by environmental change, human hunting alone could have been sufficient to cause its extinction. Our results emphasise the vulnerability of even abundant and widespread species to intense and localised exploitation. Y1 - 2019 U6 - https://doi.org/10.7554/eLife.47509 SN - 2050-084X VL - 8 PB - eLife Sciences Publications CY - Cambridge ER - TY - JOUR A1 - Rancan, Fiorenza A1 - Volkmann, Hildburg A1 - Giulbudagian, Michael A1 - Schumacher, Fabian A1 - Stanko, Jessica Isolde A1 - Kleuser, Burkhard A1 - Blume-Peytavi, Ulrike A1 - Calderon, Marcelo A1 - Vogt, Annika T1 - Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels JF - Pharmaceutics : Molecular Diversity Preservation International N2 - Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was investigated in ex vivo abdominal and breast skin, while different methods for skin barrier disruption were investigated to improve skin permeability or simulate inflammatory conditions with compromised skin barrier. The amount of penetrated tacrolimus was measured in skin extracts by liquid chromatography tandem-mass spectrometry (LC-MS/MS), whereas the inflammatory markers IL-6 and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). Higher amounts of tacrolimus penetrated in breast as compared to abdominal skin or in barrier-disrupted as compared to intact skin, confirming that the stratum corneum is the main barrier for tacrolimus skin penetration. The anti-proliferative effect of the penetrated drug was measured in skin tissue/Jurkat cells co-cultures. Interestingly, tNGs exhibited similar anti-proliferative effects as the 0.1% tacrolimus ointment. We conclude that polyglycerol-based nanogels represent an interesting alternative to paraffin-based formulations for the treatment of inflammatory skin conditions. KW - tacrolimus formulation KW - nanogels KW - skin penetration KW - drug delivery KW - human excised skin KW - Jurkat cells Y1 - 2019 U6 - https://doi.org/10.3390/pharmaceutics11080394 SN - 1999-4923 VL - 11 IS - 8 PB - MDPI CY - Basel ER - TY - JOUR A1 - Brechun, Katherine E. A1 - Zhen, Danlin A1 - Jaikaran, Anna A1 - Borisenko, Vitali A1 - Kumauchi, Masato A1 - Hoff, Wouter D. A1 - Arndt, Katja Maren A1 - Woolley, Andrew G T1 - Detection of Incorporation of p-Coumaric Acid into Photoactive Yellow Protein Variants in Vivo JF - Biochemistry N2 - We report the design and characterization of photoactive yellow protein (PYP)-blue fluorescent protein (mTagBFP) fusion constructs that permit the direct assay of reconstitution and function of the PYP domain. These constructs allow for in vivo testing of co-expression systems for enzymatic production of the p-coumaric acid-based PYP chromophore, via the action of tyrosine ammonia lyase and p-coumaroyl-CoA ligase (pCL or 4CL). We find that different 4CL enzymes can function to reconstitute PYP, including 4CL from Arabidopsis thaliana that can produce similar to 100% holo-PYP protein under optimal conditions. mTagBFP fusion constructs additionally enable rapid analysis of effects of mutations on PYP photocycles. We use this mTagBFP fusion strategy to demonstrate in vivo reconstitution of several PYP-based optogenetic tools in Escherichia coli via a biosynthesized chromophore, an important step for the use of these optogenetic tools in vivo in diverse hosts. Y1 - 2019 U6 - https://doi.org/10.1021/acs.biochem.9b00279 SN - 0006-2960 VL - 58 IS - 23 SP - 2682 EP - 2694 PB - American Chemical Society CY - Washington ER - TY - THES A1 - Luzarowski, Marcin T1 - Development and application of biochemical approaches for characterisation of the protein-protein-metabolite interactome in model organisms' A. thaliana and S. cerevisiae Y1 - 2019 ER - TY - JOUR A1 - Chen, Shun-Gang A1 - Li, Ji A1 - Zhang, Fan A1 - Xiao, Bo A1 - Hu, Jia-Ming A1 - Cui, Yin-Qiu A1 - Hofreiter, Michael A1 - Hou, Xin-Dong A1 - Sheng, Gui-Lian A1 - Lai, Xu-Long A1 - Yuan, Jun-Xia T1 - Different maternal lineages revealed by ancient mitochondrial genome of Camelus bactrianus from China JF - Mitochondrial DNA Part A N2 - Domestic Bactrian camel (Camelus bactrianus) used to be one of the most important livestock species in Chinese history, as well as the major transport carrier on the ancient Silk Road. However, archeological studies on Chinese C. bactrianus are still limited, and molecular biology research on this species is mainly focused on modern specimens. In this study, we retrieved the complete mitochondrial genome from a C. bactrianus specimen, which was excavated from northwestern China and dated at 1290-1180 cal. Phylogenetic analyses using 18 mitochondrial genomes indicated that the C. bactrianus clade was divided into two maternal lineages. The majority of samples originating from Iran to Japan and Mongolia belong to subclade A1, while our sample together with two Mongolian individuals formed the much smaller subclade A2. Furthermore, the divergence time of these two maternal lineages was estimated as 165 Kya (95% credibility interval 117-222 Kya), this might indicate that several different evolutionary lineages were incorporated into the domestic gene pool during the initial domestication process. Bayesian skyline plot (BSP) analysis a slow increase in female effective population size of C. bactrianus from 5000 years ago, which to the beginning of domestication of C. bactrianus. The present study also revealed that there were extensive exchanges of genetic information among C. bactrianus populations in regions along the Silk Road. KW - Camelus bactrianus KW - mitochondrial genome KW - ancient DNA KW - phylogeny KW - maternal lineages Y1 - 2019 U6 - https://doi.org/10.1080/24701394.2019.1659250 SN - 2470-1394 SN - 2470-1408 VL - 30 IS - 7 SP - 786 EP - 793 PB - Routledge, Taylor & Francis Group CY - Abingdon ER - TY - JOUR A1 - Hassan, Rabeay Y. A. A1 - Wollenberger, Ulla T1 - Direct determination of bacterial cell viability using carbon nanotubes modified screen-printed electrodes JF - Electroanalysis : an international journal devoted to fundamental and practical aspects of electroanalysis N2 - For the early detection of bacterial infection, there is a need for rapid, sensitive, and label-free assays. Thus, in this study, nanostrucured microbial electrochemical platform is designed to monitor the viability and cell growth of S. aureus. Using multi-walled carbon nanotube modified screen-printed electrodes (MWCNTs/SPE), the cyclic voltammetric measurements showed only one irreversible oxidation peak at 600 mV vs Ag/AgCl that accounts for the viable and metabolically active bacterial cells. The assay was optimized and the secreted metabolites, in the extracellular matrix, were directly detected. The peak current showed a positive correlation with viable cell numbers ranging from OD600 nm of 0.1 to 1.1, indicating that the activity of live cells can be quantified. Consequently, responses of viable and non-viable cells of S. aureus to the effects of antibiotic and respiratory chain inhibitors were determined. Thus, the proposed nanostructure-based bacterial sensor provides a reasonable and reliable way for real-time monitoring of live-dead cell functions, and antibacterial profiling. KW - Bacterial biosensor KW - cell viability assay KW - screen printed electrodes (SPEs) KW - carbon nanotubes (CNTs) Y1 - 2019 U6 - https://doi.org/10.1002/elan.201900047 SN - 1040-0397 SN - 1521-4109 VL - 31 IS - 6 SP - 1112 EP - 1117 PB - Wiley-VCH CY - Weinheim ER - TY - THES A1 - Perlaza-Jimenez, Laura T1 - Discerning functional associations and relationships between molecules in Arabidopsis thaliana using genome-wide correlated mutations Y1 - 2019 ER - TY - JOUR A1 - Kruse, Stefan A1 - Gerdes, Alexander A1 - Kath, Nadja J. A1 - Epp, Laura Saskia A1 - Stoof-Leichsenring, Kathleen Rosemarie A1 - Pestryakova, Luidmila Agafyevna A1 - Herzschuh, Ulrike T1 - Dispersal distances and migration rates at the arctic treeline in Siberia - a genetic and simulation-based study JF - Biogeosciences N2 - A strong temperature increase in the Arctic is expected to lead to latitudinal treeline shift. This tundra-taiga turnover would cause a positive vegetation-climate feedback due to albedo decrease. However, reliable estimates of tree migration rates are currently lacking due to the complex processes involved in forest establishment, which depend strongly on seed dispersal. We aim to fill this gap using LAVESI, an individual-based and spatially explicit Larix vegetation simulator. LAVESI was designed to simulate plots within homogeneous forests. Here, we improve the implementation of the seed dispersal function via field-based investigations. We inferred the effective seed dispersal distances of a typical open-forest stand on the southern Taymyr Peninsula (northern central Siberia) from genetic parentage analysis using eight nuclear microsatellite markers. The parentage analysis gives effective seed dispersal distances (median similar to 10 m) close to the seed parents. A comparison between simulated and observed effective seed dispersal distances reveals an overestimation of recruits close to the releasing tree and a shorter dispersal distance generally. We thus adapted our model and used the newly parameterised version to simulate south-to-north transects; a slow-moving treeline front was revealed. The colonisation of the tundra areas was assisted by occasional long-distance seed dispersal events beyond the treeline area. The treeline (similar to 1 tree ha(-1)) advanced by similar to 1.6 m yr(-1), whereas the forest line (similar to 100 trees ha(-1)) advanced by only similar to 0.6 m yr(-1). We conclude that the treeline in northern central Siberia currently lags behind the current strong warming and will continue to lag in the near future. Y1 - 2019 U6 - https://doi.org/10.5194/bg-16-1211-2019 SN - 1726-4170 SN - 1726-4189 VL - 16 IS - 6 SP - 1211 EP - 1224 PB - Copernicus CY - Göttingen ER - TY - THES A1 - Tong, Hao T1 - Dissection of genetic architecture of intermediate phenotypes and predictions in plants N2 - Determining the relationship between genotype and phenotype is the key to understand the plasticity and robustness of phenotypes in nature. While the directly observable plant phenotypes (e.g. agronomic, yield and stress resistance traits) have been well-investigated, there is still a lack in our knowledge about the genetic basis of intermediate phenotypes, such as metabolic phenotypes. Dissecting the links between genotype and phenotype depends on suitable statistical models. The state-of-the-art models are developed for directly observable phenotypes, regardless the characteristics of intermediate phenotypes. This thesis aims to fill the gaps in understanding genetic architecture of intermediate phenotypes, and how they tie to composite traits, namely plant growth. The metabolite levels and reaction fluxes, as two aspects of metabolic phenotypes, are shaped by the interrelated chemical reactions formed in genome-scale metabolic network. Here, I attempt to answer the question: Can the knowledge of underlying genome-scale metabolic network improve the model performance for prediction of metabolic phenotypes and associated plant growth? To this end, two projects are investigated in this thesis. Firstly, we propose an approach that couples genomic selection with genome-scale metabolic network and metabolic profiles in Arabidopsis thaliana to predict growth. This project is the first integration of genomic data with fluxes predicted based on constraint-based modeling framework and data on biomass composition. We demonstrate that our approach leads to a considerable increase of prediction accuracy in comparison to the state-of-the-art methods in both within and across environment predictions. Therefore, our work paves the way for combining knowledge on metabolic mechanisms in the statistical approach underlying genomic selection to increase the efficiency of future plant breeding approaches. Secondly, we investigate how reliable is genomic selection for metabolite levels, and which single nucleotide polymorphisms (SNPs), obtained from different neighborhoods of a given metabolic network, contribute most to the accuracy of prediction. The results show that the local structure of first and second neighborhoods are not sufficient for predicting the genetic basis of metabolite levels in Zea mays. Furthermore, we find that the enzymatic SNPs can capture most the genetic variance and the contribution of non-enzymatic SNPs is in fact small. To comprehensively understand the genetic architecture of metabolic phenotypes, I extend my study to a local Arabidopsis thaliana population and their hybrids. We analyze the genetic architecture in primary and secondary metabolism as well as in growth. In comparison to primary metabolites, compounds from secondary metabolism were more variable and show more non-additive inheritance patterns which could be attributed to epistasis. Therefore, our study demonstrates that heterozygosity in local Arabidopsis thaliana population generates metabolic variation and may impact several tasks directly linked to metabolism. The studies in this thesis improve the knowledge of genetic architecture of metabolic phenotypes in both inbreed and hybrid population. The approaches I proposed to integrate genome-scale metabolic network with genomic data provide the opportunity to obtain mechanistic insights about the determinants of agronomically important polygenic traits. Y1 - 2019 ER - TY - JOUR A1 - Tang, Alan T. A1 - Sullivan, Katie Rose A1 - Hong, Courtney C. A1 - Goddard, Lauren M. A1 - Mahadevan, Aparna A1 - Ren, Aileen A1 - Pardo, Heidy A1 - Peiper, Amy A1 - Griffin, Erin A1 - Tanes, Ceylan A1 - Mattei, Lisa M. A1 - Yang, Jisheng A1 - Li, Li A1 - Mericko-Ishizuka, Patricia A1 - Shen, Le A1 - Hobson, Nicholas A1 - Girard, Romuald A1 - Lightle, Rhonda A1 - Moore, Thomas A1 - Shenkar, Robert A1 - Polster, Sean P. A1 - Roedel, Claudia Jasmin A1 - Li, Ning A1 - Zhu, Qin A1 - Whitehead, Kevin J. A1 - Zheng, Xiangjian A1 - Akers, Amy A1 - Morrison, Leslie A1 - Kim, Helen A1 - Bittinger, Kyle A1 - Lengner, Christopher J. A1 - Schwaninger, Markus A1 - Velcich, Anna A1 - Augenlicht, Leonard A1 - Abdelilah-Seyfried, Salim A1 - Min, Wang A1 - Marchuk, Douglas A. A1 - Awad, Issam A. A1 - Kahn, Mark L. T1 - Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation JF - Science Translational Medicine N2 - Cerebral cavernous malformation (CCM) is a genetic, cerebrovascular disease. Familial CCM is caused by genetic mutations in KRIT1, CCM2, or PDCD10. Disease onset is earlier and more severe in individuals with PDCD10 mutations. Recent studies have shown that lesions arise from excess mitogen-activated protein kinase kinase kinase 3 (MEKK3) signaling downstream of Toll-like receptor 4 (TLR4) stimulation by lipopolysaccharide derived from the gut microbiome. These findings suggest a gut-brain CCM disease axis but fail to define it or explain the poor prognosis of patients with PDCD10 mutations. Here, we demonstrate that the gut barrier is a primary determinant of CCM disease course, independent of microbiome configuration, that explains the increased severity of CCM disease associated with PDCD10 deficiency. Chemical disruption of the gut barrier with dextran sulfate sodium augments CCM formation in a mouse model, as does genetic loss of Pdcd10, but not Krit1, in gut epithelial cells. Loss of gut epithelial Pdcd10 results in disruption of the colonic mucosal barrier. Accordingly, loss of Mucin-2 or exposure to dietary emulsifiers that reduce the mucus barrier increases CCM burden analogous to loss of Pdcd10 in the gut epithelium. Last, we show that treatment with dexamethasone potently inhibits CCM formation in mice because of the combined effect of action at both brain endothelial cells and gut epithelial cells. These studies define a gut-brain disease axis in an experimental model of CCM in which a single gene is required for two critical components: gut epithelial function and brain endothelial signaling. Y1 - 2019 U6 - https://doi.org/10.1126/scitranslmed.aaw3521 SN - 1946-6234 SN - 1946-6242 VL - 11 IS - 520 PB - American Assoc. for the Advancement of Science CY - Washington ER - TY - JOUR A1 - Radchuk, Viktoriia A1 - Kramer-Schadt, Stephanie A1 - Fickel, Jörns A1 - Wilting, Andreas T1 - Distributions of mammals in Southeast Asia: The role of the legacy of climate and species body mass JF - Journal of biogeography N2 - Aim Current species distributions are shaped by present and past biotic and abiotic factors. Here, we assessed whether abiotic factors (habitat availability) in combination with past connectivity and a biotic factor (body mass) can explain the unique distribution pattern of Southeast Asian mammals, which are separated by the enigmatic biogeographic transition zone, the Isthmus of Kra (IoK), for which no strong geophysical barrier exists. Location Southeast Asia. Taxon Mammals. Methods We projected habitat suitability for 125 mammal species using climate data for the present period and for two historic periods: mid-Holocene (6 ka) and last glacial maximum (LGM 21 ka). Next, we employed a phylogenetic linear model to assess how present species distributions were affected by the suitability of areas in these different periods, habitat connectivity during LGM and species body mass. Results Our results show that cooler climate during LGM provided suitable habitat south of IoK for species presently distributed north of IoK (in mainland Indochina). However, the potentially suitable habitat for these Indochinese species did not stretch very far southwards onto the exposed Sunda Shelf. Instead, we found that the emerged landmasses connecting Borneo and Sumatra provided suitable habitat for forest dependent Sundaic species. We show that for species whose current distribution ranges are mainly located in Indochina, the area of the distribution range that is located south of IoK is explained by the suitability of habitat in the past and present in combination with the species body mass. Main conclusions We demonstrate that a strong geophysical barrier may not be necessary for maintaining a biogeographic transition zone for mammals, but that instead a combination of abiotic and biotic factors may suffice. KW - habitat suitability KW - Isthmus of Kra KW - least-cost path KW - PanTHERIA KW - phylogenetic regression KW - species distribution model Y1 - 2019 U6 - https://doi.org/10.1111/jbi.13675 SN - 0305-0270 SN - 1365-2699 VL - 46 IS - 10 SP - 2350 EP - 2362 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Medini, Wided A1 - Farhat, Nejia A1 - Al-Rawi, Shadha A1 - Mahto, Harendra A1 - Qasim, Hadeel A1 - Ben-Halima, Emna A1 - Bessrour, Mouna A1 - Chibani, Farhat A1 - Abdelly, Chedly A1 - Fettke, Jörg A1 - Rabhi, Mokded T1 - Do carbohydrate metabolism and partitioning contribute to the higher salt tolerance of Hordeum marinum compared to Hordeum vulgare? JF - Acta Physiologiae Plantarum N2 - The aim of the present work was to check whether carbohydrate metabolism and partitioning contribute to the higher salt tolerance of the facultative halophyte Hordeum marinum compared to the glycophyte Hordeum vulgare. Seedlings with the same size from the two species were hydroponically grown at 0 (control), 150, and 300 mM NaCl for 3 weeks. H. marinum maintained higher relative growth rate, which was concomitant with a higher aptitude to maintain better shoot tissue hydration and membrane integrity under saline conditions compared to H. vulgare. Gas exchanges were reduced in the two species under saline conditions, but an increase in their water use efficiency was recorded. H. marinum exhibited an increase in leaf soluble sugar concentrations under saline conditions together with an enhancement in the transglucosidase DPE2 (EC 2.4.1.25) activity at 300 mM NaCl. However, H. vulgare showed a high increase in starch phosphorylase (EC 2.4.1.1) activity under saline conditions together with a decrease in leaf glucose and starch concentrations at 300 mM NaCl. In roots, both species accumulated glucose and fructose at 150 mM NaCl, but H. marinum exhibited a marked decrease in soluble sugar concentrations and an increase in starch concentration at 300 mM NaCl. Our data constitute an initiation to the involvement of carbohydrate metabolism and partitioning in salt responses of barley species and further work is necessary to elucidate how their flexibility confers higher tolerance to H. marinum compared to H. vulgare. KW - Cultivated barley KW - DPE2 KW - Flexibility KW - Pho1 KW - Pho2 KW - Sea barley Y1 - 2019 U6 - https://doi.org/10.1007/s11738-019-2983-x SN - 0137-5881 SN - 1861-1664 VL - 41 IS - 12 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Schöpke, Benito A1 - Heinze, Johannes A1 - Pätzig, Marlene A1 - Heinken, Thilo T1 - Do dispersal traits of wetland plant species explain tolerance against isolation effects in naturally fragmented habitats? JF - Plant ecology : an international journal N2 - The effects of habitat fragmentation and isolation on plant species richness have been verified for a wide range of anthropogenically fragmented habitats, but there is currently little information about their effects in naturally small and isolated habitats. We tested whether habitat area, heterogeneity, and isolation affect the richness of wetland vascular plant species in kettle holes, i.e., small glacially created wetlands, in an agricultural landscape of 1 km(2) in NE Germany. We compared fragmentation effects with those of forest fragments in the same landscape window. Since wetland and forest species might differ in their tolerance to isolation, and because isolation effects on plant species may be trait dependent, we asked which key life history traits might foster differences in isolation tolerance between wetland and forest plants. We recorded the flora and vegetation types in 83 isolated sites that contained 81 kettle holes and 25 forest fragments. Overall, the number of wetland species increased with increasing area and heterogeneity, i.e., the number of vegetation types, while area was not a surrogate for heterogeneity in these naturally fragmented systems. Isolation did not influence the number of wetland species but decreased the number of forest species. We also found that seeds of wetland species were on average lighter, more persistent and better adapted to epizoochory, e.g., by waterfowl, than seeds of forest species. Therefore, we suggest that wetland species are more tolerant to isolation than forest species due to their higher dispersal potential in space and time, which may counterbalance the negative effects of isolation. KW - Forest species KW - Habitat fragmentation KW - Isolation KW - Kettle holes KW - Life history traits KW - Wetland species Y1 - 2019 U6 - https://doi.org/10.1007/s11258-019-00955-8 SN - 1385-0237 SN - 1573-5052 VL - 220 IS - 9 SP - 801 EP - 815 PB - Springer CY - Dordrecht ER - TY - JOUR A1 - Rossberg, Axel G. A1 - Gaedke, Ursula A1 - Kratina, Pavel T1 - Dome patterns in pelagic size spectra reveal strong trophic cascades JF - Nature Communications N2 - In ecological communities, especially the pelagic zones of aquatic ecosystems, certain bodysize ranges are often over-represented compared to others. Community size spectra, the distributions of community biomass over the logarithmic body-mass axis, tend to exhibit regularly spaced local maxima, called "domes", separated by steep troughs. Contrasting established theory, we explain these dome patterns as manifestations of top-down trophic cascades along aquatic food chains. Compiling high quality size-spectrum data and comparing these with a size-spectrum model introduced in this study, we test this theory and develop a detailed picture of the mechanisms by which bottom-up and top-down effects interact to generate dome patterns. Results imply that strong top-down trophic cascades are common in freshwater communities, much more than hitherto demonstrated, and may arise in nutrient rich marine systems as well. Transferring insights from the general theory of nonlinear pattern formation to domes patterns, we provide new interpretations of past lake-manipulation experiments. Y1 - 2019 U6 - https://doi.org/10.1038/s41467-019-12289-0 SN - 2041-1723 VL - 10 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Essl, Franz A1 - Dawson, Wayne A1 - Kreft, Holger A1 - Pergl, Jan A1 - Pysek, Petr A1 - van Kleunen, Mark A1 - Weigelt, Patrick A1 - Mang, Thomas A1 - Dullinger, Stefan A1 - Lenzner, Bernd A1 - Moser, Dietmar A1 - Maurel, Noelie A1 - Seebens, Hanno A1 - Stein, Anke A1 - Weber, Ewald A1 - Chatelain, Cyrille A1 - Inderjit, A1 - Genovesi, Piero A1 - Kartesz, John A1 - Morozova, Olga A1 - Nishino, Misako A1 - Nowak, Pauline M. A1 - Pagad, Shyama A1 - Shu, Wen-sheng A1 - Winter, Marten T1 - Drivers of the relative richness of naturalized and invasive plant species on Earth JF - AoB PLANTS N2 - Biological invasions are a defining feature of the Anthropocene, but the factors that determine the spatially uneven distribution of alien plant species are still poorly understood. Here, we present the first global analysis of the effects of biogeographic factors, the physical environment and socio-economy on the richness of naturalized and invasive alien plants. We used generalized linear mixed-effects models and variation partitioning to disentangle the relative importance of individual factors, and, more broadly, of biogeography, physical environment and socio-economy. As measures of the magnitude of permanent anthropogenic additions to the regional species pool and of species with negative environmental impacts, we calculated the relative richness of naturalized (= RRN) and invasive (= RRI) alien plant species numbers adjusted for the number of native species in 838 terrestrial regions. Socio-economic factors (per-capita gross domestic product (GDP), population density, proportion of agricultural land) were more important in explaining RRI (similar to 50 % of the explained variation) than RRN (similar to 40 %). Warm-temperate and (sub)tropical regions have higher RRN than tropical or cooler regions. We found that socio-economic pressures are more relevant for invasive than for naturalized species richness. The expectation that the southern hemisphere is more invaded than the northern hemisphere was confirmed only for RRN on islands, but not for mainland regions nor for RRI. On average, islands have similar to 6-fold RRN, and >3-fold RRI compared to mainland regions. Eighty-two islands (=26 % of all islands) harbour more naturalized alien than native plants. Our findings challenge the widely held expectation that socio-economic pressures are more relevant for plant naturalization than for invasive plants. To meet international biodiversity targets and halt the detrimental consequences of plant invasions, it is essential to disrupt the connection between socio-economic development and plant invasions by improving pathway management, early detection and rapid response. KW - Alien species richness KW - biogeography KW - invasion stages KW - islands KW - pressures KW - vascular plants Y1 - 2019 U6 - https://doi.org/10.1093/aobpla/plz051 SN - 2041-2851 VL - 11 IS - 5 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Yan, Wenhao A1 - Chen, Dijun A1 - Schumacher, Julia A1 - Durantini, Diego A1 - Engelhorn, Julia A1 - Chen, Ming A1 - Carles, Cristel C. A1 - Kaufmann, Kerstin T1 - Dynamic control of enhancer activity drives stage-specific gene expression during flower morphogenesis JF - Nature Communications N2 - Enhancers are critical for developmental stage-specific gene expression, but their dynamic regulation in plants remains poorly understood. Here we compare genome-wide localization of H3K27ac, chromatin accessibility and transcriptomic changes during flower development in Arabidopsis. H3K27ac prevalently marks promoter-proximal regions, suggesting that H3K27ac is not a hallmark for enhancers in Arabidopsis. We provide computational and experimental evidence to confirm that distal DNase. hypersensitive sites are predictive of enhancers. The predicted enhancers are highly stage-specific across flower development, significantly associated with SNPs for flowering-related phenotypes, and conserved across crucifer species. Through the integration of genome-wide transcription factor (TF) binding datasets, we find that floral master regulators and stage-specific TFs are largely enriched at developmentally dynamic enhancers. Finally, we show that enhancer clusters and intronic enhancers significantly associate with stage-specific gene regulation by floral master TFs. Our study provides insights into the functional flexibility of enhancers during plant development, as well as hints to annotate plant enhancers. Y1 - 2019 U6 - https://doi.org/10.1038/s41467-019-09513-2 SN - 2041-1723 VL - 10 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Schwarzer, Christian A1 - Joshi, Jasmin Radha T1 - Ecotypic differentiation, hybridization and clonality facilitate the persistence of a cold-adapted sedge in European bogs JF - Biological journal of the Linnean Society : a journal of evolution N2 - Recent research has shown that many cold-adapted species survived the last glacial maximum (LGM) in northern refugia. Whether this evolutionary history has had consequences for their genetic diversity and adaptive potential remains unknown. We sampled 14 populations of Carex limosa, a sedge specialized to bog ecosystems, along a latitudinal gradient from its Scandinavian core to the southern lowland range-margin in Germany. Using microsatellite and experimental common-garden data, we evaluated the impacts of global climate change along this gradient and assessed the conservation status of the southern marginal populations. Microsatellite data revealed two highly distinct genetic groups and hybrid individuals. In our common-garden experiment, the two groups showed divergent responses to increased nitrogen/phosphorus (N/P) availability, suggesting ecotypic differentiation. Each group formed genetically uniform populations at both northern and southern sampling areas. Mixed populations occurred throughout our sampling area, an area that was entirely glaciated during the LGM. The fragmented distribution implies allopatric divergence at geographically separated refugia that putatively differed in N/P availability. Molecular data and an observed low hybrid fecundity indicate the importance of clonal reproduction for hybrid populations. At the southern range-margin, however, all populations showed effects of clonality, lowered fecundity and low competitiveness, suggesting abiotic and biotic constraints to population persistence. KW - biogeography KW - bog/mire plants KW - Carex limosa KW - climate change KW - glacial divergence KW - global change KW - leading/trailing edge KW - population differentiation KW - sexual/asexual reproduction Y1 - 2019 U6 - https://doi.org/10.1093/biolinnean/blz141 SN - 0024-4066 SN - 1095-8312 VL - 128 IS - 4 SP - 909 EP - 925 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Kielar, Charlotte A1 - Xin, Yang A1 - Xu, Xiaodan A1 - Zhu, Siqi A1 - Gorin, Nelli A1 - Grundmeier, Guido A1 - Möser, Christin A1 - Smith, David M. A1 - Keller, Adrian T1 - Effect of staple age on DNA origami nanostructure assembly and stability JF - Molecules N2 - DNA origami nanostructures are widely employed in various areas of fundamental and applied research. Due to the tremendous success of the DNA origami technique in the academic field, considerable efforts currently aim at the translation of this technology from a laboratory setting to real-world applications, such as nanoelectronics, drug delivery, and biosensing. While many of these real-world applications rely on an intact DNA origami shape, they often also subject the DNA origami nanostructures to rather harsh and potentially damaging environmental and processing conditions. Furthermore, in the context of DNA origami mass production, the long-term storage of DNA origami nanostructures or their pre-assembled components also becomes an issue of high relevance, especially regarding the possible negative effects on DNA origami structural integrity. Thus, we investigated the effect of staple age on the self-assembly and stability of DNA origami nanostructures using atomic force microscopy. Different harsh processing conditions were simulated by applying different sample preparation protocols. Our results show that staple solutions may be stored at -20 degrees C for several years without impeding DNA origami self-assembly. Depending on DNA origami shape and superstructure, however, staple age may have negative effects on DNA origami stability under harsh treatment conditions. Mass spectrometry analysis of the aged staple mixtures revealed no signs of staple fragmentation. We, therefore, attribute the increased DNA origami sensitivity toward environmental conditions to an accumulation of damaged nucleobases, which undergo weaker base-pairing interactions and thus lead to reduced duplex stability. KW - DNA origami KW - atomic force microscopy KW - stability KW - storage Y1 - 2019 U6 - https://doi.org/10.3390/molecules24142577 SN - 1420-3049 VL - 24 IS - 14 PB - MDPI CY - Basel ER - TY - JOUR A1 - Kolmakova, Olesya V. A1 - Gladyshev, Michail I. A1 - Fonvielle, Jeremy Andre A1 - Ganzert, Lars A1 - Hornick, Thomas A1 - Grossart, Hans-Peter T1 - Effects of zooplankton carcasses degradation on freshwater bacterial community composition and implications for carbon cycling JF - Environmental microbiology N2 - Non-predatory mortality of zooplankton provides an abundant, yet, little studied source of high quality labile organic matter (LOM) in aquatic ecosystems. Using laboratory microcosms, we followed the decomposition of organic carbon of fresh C-13-labelled Daphnia carcasses by natural bacterioplankton. The experimental setup comprised blank microcosms, that is, artificial lake water without any organic matter additions (B), and microcosms either amended with natural humic matter (H), fresh Daphnia carcasses (D) or both, that is, humic matter and Daphnia carcasses (HD). Most of the carcass carbon was consumed and respired by the bacterial community within 15 days of incubation. A shift in the bacterial community composition shaped by labile carcass carbon and by humic matter was observed. Nevertheless, we did not observe a quantitative change in humic matter degradation by heterotrophic bacteria in the presence of LOM derived from carcasses. However, carcasses were the main factor driving the bacterial community composition suggesting that the presence of large quantities of dead zooplankton might affect the carbon cycling in aquatic ecosystems. Our results imply that organic matter derived from zooplankton carcasses is efficiently remineralized by a highly specific bacterial community, but does not interfere with the bacterial turnover of more refractory humic matter. Y1 - 2018 U6 - https://doi.org/10.1111/1462-2920.14418 SN - 1462-2912 SN - 1462-2920 VL - 21 IS - 1 SP - 34 EP - 49 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Ozcelikay, Goksu A1 - Kurbanoglu, Sevinc A1 - Zhang, Xiaorong A1 - Söz, Çağla Kosak A1 - Wollenberger, Ulla A1 - Ozkan, Sibel A. A1 - Yarman, Aysu A1 - Scheller, Frieder W. T1 - Electrochemical MIP Sensor for Butyrylcholinesterase JF - Polymers N2 - Molecularly imprinted polymers (MIPs) mimic the binding sites of antibodies by substituting the amino acid-scaffold of proteins by synthetic polymers. In this work, the first MIP for the recognition of the diagnostically relevant enzyme butyrylcholinesterase (BuChE) is presented. The MIP was prepared using electropolymerization of the functional monomer o-phenylenediamine and was deposited as a thin film on a glassy carbon electrode by oxidative potentiodynamic polymerization. Rebinding and removal of the template were detected by cyclic voltammetry using ferricyanide as a redox marker. Furthermore, the enzymatic activity of BuChE rebound to the MIP was measured via the anodic oxidation of thiocholine, the reaction product of butyrylthiocholine. The response was linear between 50 pM and 2 nM concentrations of BuChE with a detection limit of 14.7 pM. In addition to the high sensitivity for BuChE, the sensor responded towards pseudo-irreversible inhibitors in the lower mM range. KW - molecularly imprinted polymers KW - biomimetic sensors KW - butyrylcholinesterase KW - o-phenylenediamine KW - rivastigmine Y1 - 2019 U6 - https://doi.org/10.3390/polym11121970 SN - 2073-4360 VL - 11 IS - 12 PB - MDPI CY - Basel ER - TY - THES A1 - Zhang, Xiaorong T1 - Electrosynthesis and characterization of molecularly imprinted polymers for peptides and proteins Y1 - 2019 ER - TY - JOUR A1 - Romero-Mujalli, Daniel A1 - Jeltsch, Florian A1 - Tiedemann, Ralph T1 - Elevated mutation rates are unlikely to evolve in sexual species, not even under rapid environmental change JF - BMC Evolutionary Biology N2 - Background Organisms are expected to respond to changing environmental conditions through local adaptation, range shift or local extinction. The process of local adaptation can occur by genetic changes or phenotypic plasticity, and becomes especially relevant when dispersal abilities or possibilities are somehow constrained. For genetic changes to occur, mutations are the ultimate source of variation and the mutation rate in terms of a mutator locus can be subject to evolutionary change. Recent findings suggest that the evolution of the mutation rate in a sexual species can advance invasion speed and promote adaptation to novel environmental conditions. Following this idea, this work uses an individual-based model approach to investigate if the mutation rate can also evolve in a sexual species experiencing different conditions of directional climate change, under different scenarios of colored stochastic environmental noise, probability of recombination and of beneficial mutations. The color of the noise mimicked investigating the evolutionary dynamics of the mutation rate in different habitats. Results The results suggest that the mutation rate in a sexual species experiencing directional climate change scenarios can evolve and reach relatively high values mainly under conditions of complete linkage of the mutator locus and the adaptation locus. In contrast, when they are unlinked, the mutation rate can slightly increase only under scenarios where at least 50% of arising mutations are beneficial and the rate of environmental change is relatively fast. This result is robust under different scenarios of stochastic environmental noise, which supports the observation of no systematic variation in the mutation rate among organisms experiencing different habitats. Conclusions Given that 50% beneficial mutations may be an unrealistic assumption, and that recombination is ubiquitous in sexual species, the evolution of an elevated mutation rate in a sexual species experiencing directional climate change might be rather unlikely. Furthermore, when the percentage of beneficial mutations and the population size are small, sexual species (especially multicellular ones) producing few offspring may be expected to react to changing environments not by adaptive genetic change, but mainly through plasticity. Without the ability for a plastic response, such species may become – at least locally – extinct. KW - Individual-based models KW - sexual species KW - Beneficial mutations KW - Recombination KW - Directional climate change KW - Mutator locus KW - Mutation rate Y1 - 2019 U6 - https://doi.org/10.1186/s12862-019-1494-0 SN - 1471-2148 VL - 19 PB - BioMed Central CY - London ER -