TY - JOUR A1 - Adem, Fozia A. A1 - Kuete, Victor A1 - Mbaveng, Armelle T. A1 - Heydenreich, Matthias A1 - Koch, Andreas A1 - Ndakala, Albert A1 - Irungu, Beatrice A1 - Yenesew, Abiy A1 - Efferth, Thomas T1 - Cytotoxic flavonoids from two Lonchocarpus species JF - Natural Product Research N2 - A new isoflavone, 4′-prenyloxyvigvexin A (1) and a new pterocarpan, (6aR,11aR)-3,8-dimethoxybitucarpin B (2) were isolated from the leaves of Lonchocarpus bussei and the stem bark of Lonchocarpus eriocalyx, respectively. The extract of L. bussei also gave four known isoflavones, maximaisoflavone H, 7,2′-dimethoxy-3′,4′-methylenedioxyisoflavone, 6,7,3′-trimethoxy-4′,5′-methylenedioxyisoflavone, durmillone; a chalcone, 4-hydroxylonchocarpin; a geranylated phenylpropanol, colenemol; and two known pterocarpans, (6aR,11aR)-maackiain and (6aR,11aR)-edunol. (6aR,11aR)-Edunol was also isolated from the stem bark of L. eriocalyx. The structures of the isolated compounds were elucidated by spectroscopy. The cytotoxicity of the compounds was tested by resazurin assay using drug-sensitive and multidrug-resistant cancer cell lines. Significant antiproliferative effects with IC50 values below 10 μM were observed for the isoflavones 6,7,3′-trimethoxy-4′,5′-methylenedioxyisoflavone and durmillone against leukemia CCRF-CEM cells; for the chalcone, 4-hydroxylonchocarpin and durmillone against its resistant counterpart CEM/ADR5000 cells; as well as for durmillone against the resistant breast adenocarcinoma MDA-MB231/BCRP cells and resistant gliobastoma U87MG.ΔEGFR cells. KW - Lonchocarpus bussei KW - Lonchocarpus eriocalyx KW - Leguminosae KW - isoflavone KW - pterocarpan KW - cytotoxicity Y1 - 2019 U6 - https://doi.org/10.1080/14786419.2018.1462179 SN - 1478-6419 SN - 1478-6427 VL - 33 IS - 18 SP - 2609 EP - 2617 PB - Routledge, Taylor & Francis Group CY - Abingdon 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 - 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 - Altintas, Zeynep A1 - Takiden, Aref A1 - Utesch, Tillmann A1 - Mroginski, Maria A. A1 - Schmid, Bianca A1 - Scheller, Frieder W. A1 - Süssmuth, Roderich D. T1 - Integrated approaches toward high-affinity artificial protein binders obtained via computationally simulated epitopes for protein recognition JF - Advanced functional materials N2 - Widely used diagnostic tools make use of antibodies recognizing targeted molecules, but additional techniques are required in order to alleviate the disadvantages of antibodies. Herein, molecular dynamic calculations are performed for the design of high affinity artificial protein binding surfaces for the recognition of neuron specific enolase (NSE), a known cancer biomarker. Computational simulations are employed to identify particularly stabile secondary structure elements. These epitopes are used for the subsequent molecular imprinting, where surface imprinting approach is applied. The molecular imprints generated with the calculated epitopes of greater stability (Cys-Ep1) show better binding properties than those of lower stability (Cys-Ep5). The average binding strength of imprints created with stabile epitopes is found to be around twofold and fourfold higher for the NSE derived peptide and NSE protein, respectively. The recognition of NSE is investigated in a wide concentration range, where high sensitivity (limit of detection (LOD) = 0.5 ng mL(-1)) and affinity (dissociation constant (K-d) = 5.3 x 10(-11)m) are achieved using Cys-Ep1 imprints reflecting the stable structure of the template molecules. This integrated approach employing stability calculations for the identification of stabile epitopes is expected to have a major impact on the future development of high affinity protein capturing binders. KW - artificial protein binders KW - cancer markers KW - computationally simulated epitopes KW - molecular imprinting KW - protein recognition Y1 - 2019 U6 - https://doi.org/10.1002/adfm.201807332 SN - 1616-301X SN - 1616-3028 VL - 29 IS - 15 PB - Wiley-VCH CY - Weinheim 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 - 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 - GEN A1 - Arnold, Patrick T1 - The origin of morphological integration and modularity in the Mammalian Neck T2 - Journal of morphology Y1 - 2019 U6 - https://doi.org/10.1002/jmor.21003 SN - 0362-2525 SN - 1097-4687 VL - 280 SP - S13 EP - S13 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 - THES A1 - Baleka, Sina Isabelle T1 - Palaeogenetic analyses of extinct Elephantidae from temperate and subtropical climates Y1 - 2019 ER - TY - JOUR A1 - Barchewitz, Tino A1 - Guljamow, Arthur A1 - Meißner, Sven A1 - Timm, Stefan A1 - Henneberg, Manja A1 - Baumann, Otto A1 - Hagemann, Martin A1 - Dittmann, Elke T1 - Non-canonical localization of RubisCO under high-light conditions in the toxic cyanobacterium Microcystis aeruginosa PCC7806 JF - Environmental microbiology N2 - The frequent production of the hepatotoxin microcystin (MC) and its impact on the lifestyle of bloom-forming cyanobacteria are poorly understood. Here, we report that MC interferes with the assembly and the subcellular localization of RubisCO, in Microcystis aeruginosa PCC7806. Immunofluorescence, electron microscopic and cellular fractionation studies revealed a pronounced heterogeneity in the subcellular localization of RubisCO. At high cell density, RubisCO particles are largely separate from carboxysomes in M. aeruginosa and relocate to the cytoplasmic membrane under high-light conditions. We hypothesize that the binding of MC to RubisCO promotes its membrane association and enables an extreme versatility of the enzyme. Steady-state levels of the RubisCO CO2 fixation product 3-phosphoglycerate are significantly higher in the MC-producing wild type. We also detected noticeable amounts of the RubisCO oxygenase reaction product secreted into the medium that may support the mutual interaction of M. aeruginosa with its heterotrophic microbial community. Y1 - 2019 U6 - https://doi.org/10.1111/1462-2920.14837 SN - 1462-2912 SN - 1462-2920 VL - 21 IS - 12 SP - 4836 EP - 4851 PB - Wiley CY - Hoboken ER -