TY - JOUR A1 - Bobone, Sara A1 - Hilsch, Malte A1 - Storm, Julian A1 - Dunsing, Valentin A1 - Herrmann, Andreas A1 - Chiantia, Salvatore T1 - Phosphatidylserine Lateral Organization Influences the Interaction of Influenza Virus Matrix Protein 1 with Lipid Membranes JF - Journal of virology N2 - Influenza A virus matrix protein 1 (M1) is an essential component involved in the structural stability of the virus and in the budding of new virions from infected cells. A deeper understanding of the molecular basis of virion formation and the budding process is required in order to devise new therapeutic approaches. We performed a detailed investigation of the interaction between M1 and phosphatidylserine (PS) (i.e., its main binding target at the plasma membrane [PM]), as well as the distribution of PS itself, both in model membranes and in living cells. To this end, we used a combination of techniques, including Forster resonance energy transfer (FRET), confocal microscopy imaging, raster image correlation spectroscopy, and number and brightness (N&B) analysis. Our results show that PS can cluster in segregated regions in the plane of the lipid bilayer, both in model bilayers constituted of PS and phosphatidylcholine and in living cells. The viral protein M1 interacts specifically with PS-enriched domains, and such interaction in turn affects its oligomerization process. Furthermore, M1 can stabilize PS domains, as observed in model membranes. For living cells, the presence of PS clusters is suggested by N&B experiments monitoring the clustering of the PS sensor lactadherin. Also, colocalization between M1 and a fluorescent PS probe suggest that, in infected cells, the matrix protein can specifically bind to the regions of PM in which PS is clustered. Taken together, our observations provide novel evidence regarding the role of PS-rich domains in tuning M1-lipid and M1-M1 interactions at the PM of infected cells. IMPORTANCE Influenza virus particles assemble at the plasma membranes (PM) of infected cells. This process is orchestrated by the matrix protein M1, which interacts with membrane lipids while binding to the other proteins and genetic material of the virus. Despite its importance, the initial step in virus assembly (i.e., M1-lipid interaction) is still not well understood. In this work, we show that phosphatidylserine can form lipid domains in physical models of the inner leaflet of the PM. Furthermore, the spatial organization of PS in the plane of the bilayer modulates M1-M1 interactions. Finally, we show that PS domains appear to be present in the PM of living cells and that M1 seems to display a high affinity for them. KW - influenza KW - assembly KW - confocal microscopy KW - fluorescence image analysis KW - lipid rafts KW - matrix protein KW - model membranes KW - phosphatidylserine KW - plasma membrane Y1 - 2017 U6 - https://doi.org/10.1128/JVI.00267-17 SN - 0022-538X SN - 1098-5514 VL - 91 PB - American Society for Microbiology CY - Washington ER - TY - JOUR A1 - Bogin, Barry A1 - Scheffler, Christiane A1 - Hermanussen, Michael T1 - Global effects of income and income inequality on adult height and sexual dimorphism in height JF - American journal of human biology : the official journal of the Human Biology Council N2 - Objectives: Average adult height of a population is considered a biomarker of the quality of the health environment and economic conditions. The causal relationships between height and income inequality are not well understood. We analyze data from 169 countries for national average heights of men and women and national-level economic factors to test two hypotheses: (1) income inequality has a greater association with average adult height than does absolute income; and (2) neither income nor income inequality has an effect on sexual dimorphism in height. Methods: Average height data come from the NCD-RisC health risk factor collaboration. Economic indicators are derived from the World Bank data archive and include gross domestic product (GDP), Gross National Income per capita adjusted for personal purchasing power (GNI_ PPP), and income equality assessed by the Gini coefficient calculated by the Wagstaff method. Results: Hypothesis 1 is supported. Greater income equality is most predictive of average height for both sexes. GNI_ PPP explains a significant, but smaller, amount of the variation. National GDP has no association with height. Hypothesis 2 is rejected. With greater average adult height there is greater sexual dimorphism. Conclusions: Findings support a growing literature on the pernicious effects of inequality on growth in height and, by extension, on health. Gradients in height reflect gradients in social disadvantage. Inequality should be considered a pollutant that disempowers people from the resources needed for their own healthy growth and development and for the health and good growth of their children. Y1 - 2017 U6 - https://doi.org/10.1002/ajhb.22980 SN - 1042-0533 SN - 1520-6300 VL - 29 IS - 2 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Bois, Juliana A1 - Koerzdoerfer, Thomas T1 - Size-Dependence of Nonempirically Tuned DFT Starting Points for G(0)W(0) Applied to pi-Conjugated Molecular Chains JF - Journal of chemical theory and computation N2 - G(0)W(0) calculations for predicting vertical ionization potentials (IPs) and electron affinities of molecules and clusters are known to show a significant dependence on the density functional theory (DFT) starting point. A number of nonempirical procedures to find an optimal starting point have been proposed, typically based on tuning the amount of HF exchange in the underlying hybrid functional specifically for the system at hand. For the case of pi-conjugated molecular chains, these approaches lead to a significantly different amount of HF exchange for different oligomer sizes. In this study, we analyze if and how strongly this size dependence affects the ability of nonempirical tuning approaches to predict accurate IPs for pi-conjugated molecular chains of increasing chain length. To this end, we employ three different nonempirical tuning procedures for the G(0)W(0) starting point to calculate the IP of polyene oligomers up to 22 repeat units and compare the results to highly accurate coupled-cluster calculations. We find that, despite its size dependence, using an IP-tuned hybrid functional as a starting point for G(0)W(0) yields excellent agreement with the reference data for all chain lengths. Y1 - 2017 U6 - https://doi.org/10.1021/acs.jctc.7b00557 SN - 1549-9618 SN - 1549-9626 VL - 13 SP - 4962 EP - 4971 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Bolius, Sarah A1 - Wiedner, Claudia A1 - Weithoff, Guntram T1 - High local trait variability in a globally invasive cyanobacterium JF - Freshwater biology N2 - 1. During the last couple of decades, invasive species have become a worldwide problem in many freshwater systems. Besides higher plants and animals, microbes, in particular the potentially toxic cyanobacterium Cylindrospermopsis raciborskii, has attracted increasing attention, due to its spread towards temperate zones of the northern and southern hemisphere. A number of advantageous functional traits and a high intraspecific plasticity have been suggested to explain its invasion success. 2. The aim of this study was to examine intraspecific functional trait variability in 12 different isolates of C.raciborskii originating from different lakes in an invaded region in Northeast Germany. We measured growth rate, C:N:P ratios, chlorophyll-a content and the abundance of heterocysts under nutrient-replete and phosphorus-limited conditions. Moreover, the isolate-specific morphology and grazing losses by an herbivorous rotifer, as a top-down force, were studied. 3. DNA fingerprinting revealed that all isolates were genetically different. C.raciborskii exhibited a large variability in all measured traits among isolates. The C:P, N:P and Chl-a:C ratios differed by a factor of two or more. The trait variability among isolates was higher under nutrient-replete conditions, except for the C:P ratio, which varied most during phosphorus limitation. The susceptibility to grazing, calculated as maximum ingestion rates of the rotifer Brachionus calyciflorus on C.raciborskii, varied most among isolates, but was not related to any of the measured physiological or morphological traits, i.e. no trade-off was found. 4. Ecological and genetic clustering did not match, indicating that the genetic relationship based on DNA fingerprinting did not cover ecological differences. 5. Our results show a high trait variability within locally occurring and partly co-occurring C.raciborskii isolates. No overall trade-offs between the measured functional traits were found. This demonstrates the ecological relevance of linking multiple traits, e.g. competitive and consumptive. Furthermore, this study emphasises the importance of analysing more than one strain of a species, as different strains show different trait values potentially relevant for their invasibility and the field of general trait-based ecology. KW - Cylindrospermopsis raciborskii KW - functional traits KW - genotypes KW - invasion KW - stoichiometry Y1 - 2017 U6 - https://doi.org/10.1111/fwb.13028 SN - 0046-5070 SN - 1365-2427 VL - 62 SP - 1879 EP - 1890 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Braig, Friederike A1 - Kriegs, Malte A1 - Voigtlaender, Minna A1 - Habel, Beate A1 - Grob, Tobias A1 - Biskup, Karina A1 - Blanchard, Veronique A1 - Sack, Markus A1 - Thalhammer, Anja A1 - Ben Batalla, Isabel A1 - Braren, Ingke A1 - Laban, Simon A1 - Danielczyk, Antje A1 - Goletz, Steffen A1 - Jakubowicz, Elzbieta A1 - Maerkl, Bruno A1 - Trepel, Martin A1 - Knecht, Rainald A1 - Riecken, Kristoffer A1 - Fehse, Boris A1 - Loges, Sonja A1 - Bokemeyer, Carsten A1 - Binder, Mascha T1 - Cetuximab Resistance in Head and Neck Cancer Is Mediated by EGFR-K-521 Polymorphism JF - Cancer research N2 - Head and neck squamous cell carcinomas (HNSCC) exhibiting resistance to the EGFR-targeting drug cetuximab poses a challenge to their effective clinical management. Here, we report a specific mechanism of resistance in this setting based upon the presence of a single nucleotide polymorphism encoding EGFR-K-521 (K-allele), which is expressed in > 40% of HNSCC cases. Patients expressing the K-allele showed significantly shorter progressionfree survival upon palliative treatment with cetuximab plus chemotherapy or radiation. In several EGFR-mediated cancer models, cetuximab failed to inhibit downstream signaling or to kill cells harboring a high K-allele frequency. Cetuximab affinity for EGFR-K-521 was reduced slightly, but ligand-mediated EGFR acti-vation was intact. We found a lack of glycan sialyation on EGFR-K-521 that associated with reduced protein stability, suggesting a structural basis for reduced cetuximab efficacy. CetuGEX, an antibody with optimized Fc glycosylation targeting the same epitope as cetuximab, restored HNSCC sensitivity in a manner associated with antibody-dependent cellular cytotoxicity rather than EGFR pathway inhibition. Overall, our results highlight EGFR-K-521 expression as a key mechanism of cetuximab resistance to evaluate prospectively as a predictive biomarker in HNSCC patients. Further, they offer a preclinical rationale for the use of ADCC-optimized antibodies to treat tumors harboring this EGFR isoform. Y1 - 2017 U6 - https://doi.org/10.1158/0008-5472.CAN-16-0754 SN - 0008-5472 SN - 1538-7445 VL - 77 IS - 5 SP - 1188 EP - 1199 PB - American Association for Cancer Research CY - Philadelphia ER - TY - JOUR A1 - Brechun, Katherine E. A1 - Arndt, Katja Maren A1 - Woolley, G. Andrew T1 - Strategies for the photo-control of endogenous protein activity JF - Current opinion in structural biology : review of all advances ; evaluation of key references ; comprehensive listing of papers Y1 - 2017 U6 - https://doi.org/10.1016/j.sbi.2016.11.014 SN - 0959-440X SN - 1879-033X VL - 45 SP - 53 EP - 58 PB - Elsevier CY - London ER - TY - JOUR A1 - Bremer, Anne A1 - Kent, Ben A1 - Hauss, Thomas A1 - Thalhammer, Anja A1 - Yepuri, Nageshwar R. A1 - Darwish, Tamim A. A1 - Garvey, Christopher J. A1 - Bryant, Gary A1 - Hincha, Dirk K. T1 - Intrinsically Disordered Stress Protein COR15A Resides at the Membrane Surface during Dehydration JF - Biophysical journal N2 - Plants from temperate climate zones are able to increase their freezing tolerance during exposure to low, above zero temperatures in a process termed cold acclimation. During this process, several cold-regulated (COR) proteins are accumulated in the cells. One of them is COR15A, a small, intrinsically disordered protein that contributes to leaf freezing tolerance by stabilizing cellular membranes. The isolated protein folds into amphipathic a-helices in response to increased crowding conditions, such as high concentrations of glycerol. Although there is evidence for direct COR15A-membrane interactions, the orientation and depth of protein insertion were unknown. In addition, although folding due to high osmolyte concentrations had been established, the folding response of the protein under conditions of gradual dehydration had not been investigated. Here we show, using Fourier transform infrared spectroscopy, that COR15A starts to fold into a-helices already under mild dehydration conditions (97% relative humidity (RH), corresponding to freezing at -3 degrees C) and that folding gradually increases with decreasing RH. Neutron diffraction experiments at 97 and 75% RH established that the presence of COR15A had no significant influence on the structure of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membranes. However, using deuterated POPC we. could clearly establish that COR15A interacts with the membranes and penetrates below the headgroup region into the upper part of the fatty acyl chain region. This localization is in agreement with our hypothesis that COR15A-membrane interaction is at least, in part, driven by a hydrophobic interaction between the lipids and the hydrophobic face of the amphipathic protein alpha-helix. Y1 - 2017 U6 - https://doi.org/10.1016/j.bpj.2017.06.027 SN - 0006-3495 SN - 1542-0086 VL - 113 SP - 572 EP - 579 PB - Cell Press CY - Cambridge ER - TY - JOUR A1 - Bremer, Anne A1 - Wolff, Martin A1 - Thalhammer, Anja A1 - Hincha, Dirk K. T1 - Folding of intrinsically disordered plant LEA proteins is driven by glycerol-induced crowding and the presence of membranes JF - The FEBS journal N2 - Late embryogenesis abundant (LEA) proteins are related to cellular dehydration tolerance. Most LEA proteins are predicted to have no stable secondary structure in solution, i.e., to be intrinsically disordered proteins (IDPs), but they may acquire alpha-helical structure upon drying. In the model plant Arabidopsis thaliana, the LEA proteins COR15A and COR15B are highly induced upon cold treatment and are necessary for the plants to attain full freezing tolerance. Freezing leads to increased intracellular crowding due to dehydration by extracellular ice crystals. In vitro, crowding by high glycerol concentrations induced partial folding of COR15 proteins. Here, we have extended these investigations to two related proteins, LEA11 and LEA25. LEA25 is much longer than LEA11 and COR15A, but shares a conserved central sequence domain with the other two proteins. We have created two truncated versions of LEA25 (2H and 4H) to elucidate the structural and functional significance of this domain. Light scattering and CD spectroscopy showed that all five proteins were largely unstructured and monomeric in dilute solution. They folded in the presence of increasing concentrations of trifluoroethanol and glycerol. Additional folding was observed in the presence of glycerol and membranes. Fourier transform infra red spectroscopy revealed an interaction of the LEA proteins with membranes in the dry state leading to a depression in the gel to liquid-crystalline phase transition temperature. Liposome stability assays revealed a cryoprotective function of the proteins. The C- and N-terminal extensions of LEA25 were important in cryoprotection, as the central domain itself (2H, 4H) only provided a low level of protection. KW - intrinsically disordered proteins KW - late embryogenesis abundant proteins KW - osmolytes KW - protein folding KW - protein-membrane interaction Y1 - 2017 U6 - https://doi.org/10.1111/febs.14023 SN - 1742-464X SN - 1742-4658 VL - 284 SP - 919 EP - 936 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Breuer, David A1 - Nowak, Jacqueline A1 - Ivakov, Alexander A1 - Somssich, Marc A1 - Persson, Staffan A1 - Nikoloski, Zoran T1 - System-wide organization of actin cytoskeleton determines organelle transport in hypocotyl plant cells JF - Proceedings of the National Academy of Sciences of the United States of America N2 - The actin cytoskeleton is an essential intracellular filamentous structure that underpins cellular transport and cytoplasmic streaming in plant cells. However, the system-level properties of actin-based cellular trafficking remain tenuous, largely due to the inability to quantify key features of the actin cytoskeleton. Here, we developed an automated image-based, network-driven framework to accurately segment and quantify actin cytoskeletal structures and Golgi transport. We show that the actin cytoskeleton in both growing and elongated hypocotyl cells has structural properties facilitating efficient transport. Our findings suggest that the erratic movement of Golgi is a stable cellular phenomenon that might optimize distribution efficiency of cell material. Moreover, we demonstrate that Golgi transport in hypocotyl cells can be accurately predicted from the actin network topology alone. Thus, our framework provides quantitative evidence for system-wide coordination of cellular transport in plant cells and can be readily applied to investigate cytoskeletal organization and transport in other organisms. KW - actin KW - cytoskeleton KW - Golgi KW - image processing KW - networks Y1 - 2017 U6 - https://doi.org/10.1073/pnas.1706711114 SN - 0027-8424 VL - 114 SP - E5741 EP - E5749 PB - National Acad. of Sciences CY - Washington ER - TY - JOUR A1 - Brietzke, Thomas Martin A1 - Dietz, Thomas A1 - Kelling, Alexandra A1 - Schilde, Uwe A1 - Bois, Juliana A1 - Kelm, Harald A1 - Reh, Manuel A1 - Schmitz, Markus A1 - Koerzdoerfer, Thomas A1 - Leimkühler, Silke A1 - Wollenberger, Ulla A1 - Krueger, Hans-Joerg A1 - Holdt, Hans-Jürgen T1 - The 1,6,7,12-Tetraazaperylene Bridging Ligand as an Electron Reservoir and Its Disulfonato Derivative as Redox Mediator in an Enzyme-Electrode Process JF - Chemistry - a European journal N2 - The homodinuclear ruthenium(II) complex [{Ru(l-N4Me2)}(2)(-tape)](PF6)(4) {[1](PF6)(4)} (l-N4Me2=N,N-dimethyl-2,11-diaza[3.3](2,6)-pyridinophane, tape=1,6,7,12-tetraazaperylene) can store one or two electrons in the energetically low-lying * orbital of the bridging ligand tape. The corresponding singly and doubly reduced complexes [{Ru(l-N4Me2)}(2)(-tape(.-))](PF6)(3) {[2](PF6)(3)} and [{Ru(l-N4Me2)}(2)(-tape(2-))](PF6)(2) {[3](PF6)(2)}, respectively, were electrochemically generated, successfully isolated and fully characterized by single-crystal X-ray crystallography, spectroscopic methods and magnetic susceptibility measurements. The singly reduced complex [2](PF6)(3) contains the -radical tape(.-) and the doubly reduced [3](PF6)(2) the diamagnetic dianion tape(2-) as bridging ligand, respectively. Nucleophilic aromatic substitution at the bridging tape in [1](4+) by two sulfite units gave the complex [{Ru(l-N4Me2)}(2){-tape-(SO3)(2)}](2+) ([4](2+)). Complex dication [4](2+) was exploited as a redox mediator between an anaerobic homogenous reaction solution of an enzyme system (sulfite/sulfite oxidase) and the electrode via participation of the low-energy *-orbital of the disulfonato-substituted bridging ligand tape-(SO3)(2)(2-) (E-red1=-0.1V versus Ag/AgCl/1m KCl in water). KW - electrochemistry KW - enzyme catalysis KW - N-ligands KW - redox-active ligands KW - ruthenium Y1 - 2017 U6 - https://doi.org/10.1002/chem.201703639 SN - 0947-6539 SN - 1521-3765 VL - 23 SP - 15583 EP - 15587 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Busch, Verena A1 - Klaus, Valentin H. A1 - Penone, Caterina A1 - Schäfer, Deborah A1 - Boch, Steffen A1 - Prati, Daniel A1 - Müller, Jörg A1 - Socher, Stephanie A. A1 - Niinemets, Ülo A1 - Penuelas, Josep A1 - Hölzel, Norbert A1 - Fischer, Markus A1 - Kleinebecker, Till T1 - Nutrient stoichiometry and land use rather than species richness determine plant functional diversity JF - Ecology and evolution N2 - Plant functional traits reflect individual and community ecological strategies. They allow the detection of directional changes in community dynamics and ecosystemic processes, being an additional tool to assess biodiversity than species richness. Analysis of functional patterns in plant communities provides mechanistic insight into biodiversity alterations due to anthropogenic activity. Although studies have consi-dered of either anthropogenic management or nutrient availability on functional traits in temperate grasslands, studies combining effects of both drivers are scarce. Here, we assessed the impacts of management intensity (fertilization, mowing, grazing), nutrient stoichiometry (C, N, P, K), and vegetation composition on community-weighted means (CWMs) and functional diversity (Rao's Q) from seven plant traits in 150 grasslands in three regions in Germany, using data of 6 years. Land use and nutrient stoichiometry accounted for larger proportions of model variance of CWM and Rao's Q than species richness and productivity. Grazing affected all analyzed trait groups; fertilization and mowing only impacted generative traits. Grazing was clearly associated with nutrient retention strategies, that is, investing in durable structures and production of fewer, less variable seed. Phenological variability was increased. Fertilization and mowing decreased seed number/mass variability, indicating competition-related effects. Impacts of nutrient stoichiometry on trait syndromes varied. Nutrient limitation (large N:P, C:N ratios) promoted species with conservative strategies, that is, investment in durable plant structures rather than fast growth, fewer seed, and delayed flowering onset. In contrast to seed mass, leaf-economics variability was reduced under P shortage. Species diversity was positively associated with the variability of generative traits. Synthesis. Here, land use, nutrient availability, species richness, and plant functional strategies have been shown to interact complexly, driving community composition, and vegetation responses to management intensity. We suggest that deeper understanding of underlying mechanisms shaping community assembly and biodiversity will require analyzing all these parameters. KW - biodiversity exploratories KW - fertilization KW - leaf economics KW - mowing KW - nutrient availability KW - nutrient ratios KW - phosphorus KW - plant functional traits KW - plant strategies KW - seed mass Y1 - 2017 U6 - https://doi.org/10.1002/ece3.3609 SN - 2045-7758 VL - 8 IS - 1 SP - 601 EP - 616 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Bühning, Martin A1 - Friemel, Martin A1 - Leimkühler, Silke T1 - Functional Complementation Studies Reveal Different Interaction Partners of Escherichia coil IscS and Human NFS1 JF - Biochemistry N2 - The trafficking and delivery of sulfur to cofactors and nucleosides is a highly regulated and conserved process among all organisms. All sulfur transfer pathways generally have an L-cysteine desulfurase as an initial sulfur mobilizing enzyme in common, which serves as a sulfur donor for the biosynthesis of sulfur-containing biomolecules like iron sulfur (Fe-S) clusters, thiamine, biotin, lipoic acid, the molybdenum cofactor (Moco), and thiolated nucleosides in tRNA. The human L-cysteine desulfurase NFS1 and the Escherichia coli homologue IscS share a level of amino acid sequence identity of similar to 60%. While E. coli IscS has a versatile role in the cell and was shown to have numerous interaction partners, NFS1 is mainly localized in mitochondria with a crucial role in the biosynthesis of Fe-S clusters. Additionally, NFS1 is also located in smaller amounts in the cytosol with a role in Moco biosynthesis and mcm(5)s(2)U34 thio modifications of nucleosides in tRNA. NFS1 and IscS were conclusively shown to have different interaction partners in their respective organisms. Here, we used functional complementation studies of an E. coli iscS deletion strain with human NFS1 to dissect their conserved roles in the transfer of sulfur to a specific target protein. Our results show that human NFS1 and E. coli IscS share conserved binding sites for proteins involved in Fe-S cluster assembly like IscU, but not with proteins for tRNA thio modifications or Moco biosynthesis. In addition, we show that human NFS1 was almost fully able to complement the role of IscS in Moco biosynthesis when its specific interaction partner protein MOCS3 from humans was also present. Y1 - 2017 U6 - https://doi.org/10.1021/acs.biochem.7b00627 SN - 0006-2960 VL - 56 SP - 4592 EP - 4605 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Bühning, Martin A1 - Valleriani, Angelo A1 - Leimkühler, Silke T1 - The role of SufS is restricted to Fe-S cluster biosynthesis in escherichia coli JF - Biochemistry N2 - In Escherichia coli, two different systems that are important for the coordinate formation of Fe–S clusters have been identified, namely, the ISC and SUF systems. The ISC system is the housekeeping Fe–S machinery, which provides Fe–S clusters for numerous cellular proteins. The IscS protein of this system was additionally revealed to be the primary sulfur donor for several sulfur-containing molecules with important biological functions, among which are the molybdenum cofactor (Moco) and thiolated nucleosides in tRNA. Here, we show that deletion of central components of the ISC system in addition to IscS leads to an overall decrease in Fe–S cluster enzyme and molybdoenzyme activity in addition to a decrease in the number of Fe–S-dependent thiomodifications of tRNA, based on the fact that some proteins involved in Moco biosynthesis and tRNA thiolation are Fe–S-dependent. Complementation of the ISC deficient strains with the suf operon restored the activity of Fe–S-containing proteins, including the MoaA protein, which is involved in the conversion of 5′GTP to cyclic pyranopterin monophosphate in the fist step of Moco biosynthesis. While both systems share a high degree of similarity, we show that the function of their respective l-cysteine desulfurase IscS or SufS is specific for each cellular pathway. It is revealed that SufS cannot play the role of IscS in sulfur transfer for the formation of 2-thiouridine, 4-thiouridine, or the dithiolene group of molybdopterin, being unable to interact with TusA or ThiI. The results demonstrate that the role of the SUF system is exclusively restricted to Fe–S cluster assembly in the cell. Y1 - 2017 U6 - https://doi.org/10.1021/acs.biochem.7b00040 SN - 0006-2960 VL - 56 SP - 1987 EP - 2000 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Cao, Xianyong A1 - Tian, Fang A1 - Telford, Richard J. A1 - Ni, Jian A1 - Xu, Qinghai A1 - Chen, Fahu A1 - Liu, Xingqi A1 - Stebich, Martina A1 - Zhao, Yan A1 - Herzschuh, Ulrike T1 - Impacts of the spatial extent of pollen-climate calibration-set on the absolute values, range and trends of reconstructed Holocene precipitation JF - Quaternary science reviews : the international multidisciplinary research and review journal N2 - Pollen-based quantitative reconstructions of past climate variables is a standard palaeoclimatic approach. Despite knowing that the spatial extent of the calibration-set affects the reconstruction result, guidance is lacking as to how to determine a suitable spatial extent of the pollen-climate calibration-set. In this study, past mean annual precipitation (P-ann) during the Holocene (since 11.5 cal ka BP) is reconstructed repeatedly for pollen records from Qinghai Lake (36.7 degrees N, 100.5 degrees E; north-east Tibetan Plateau), Gonghai Lake (38.9 degrees N, 112.2 degrees E; north China) and Sihailongwan Lake (42.3 degrees N, 126.6 degrees E; north-east China) using calibration-sets of varying spatial extents extracted from the modern pollen dataset of China and Mongolia (2559 sampling sites and 168 pollen taxa in total). Results indicate that the spatial extent of the calibration-set has a strong impact on model performance, analogue quality and reconstruction diagnostics (absolute value, range, trend, optimum). Generally, these effects are stronger with the modern analogue technique (MAT) than with weighted averaging partial least squares (WA-PLS). With respect to fossil spectra from northern China, the spatial extent of calibration-sets should be restricted to radii between ca. 1000 and 1500 km because small-scale calibration-sets (<800 km radius) will likely fail to include enough spatial variation in the modern pollen assemblages to reflect the temporal range shifts during the Holocene, while too broad a scale calibration-set (>1500 km radius) will include taxa with very different pollen-climate relationships. (C) 2017 Elsevier Ltd. All rights reserved. KW - Analogue quality KW - Statistical significance KW - Cross-validation KW - Holocene KW - Climate reconstruction KW - WA-PLS KW - MAT Y1 - 2017 U6 - https://doi.org/10.1016/j.quascirev.2017.10.030 SN - 0277-3791 VL - 178 SP - 37 EP - 53 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Casas-Marce, Mireia A1 - Marmesat, Elena A1 - Soriano, Laura A1 - Martinez-Cruz, Begona A1 - Lucena-Perez, Maria A1 - Nocete, Francisco A1 - Rodriguez-Hidalgo, Antonio A1 - Canals, Antoni A1 - Nadal, Jordi A1 - Detry, Cleia A1 - Bernaldez-Sanchez, Eloisa A1 - Fernandez-Rodriguez, Carlos A1 - Perez-Ripoll, Manuel A1 - Stiller, Mathias A1 - Hofreiter, Michael A1 - Rodriguez, Alejandro A1 - Revilla, Eloy A1 - Delibes, Miguel A1 - Godoy, Jose A. T1 - Spatiotemporal Dynamics of Genetic Variation in the Iberian Lynx along Its Path to Extinction Reconstructed with Ancient DNA JF - Molecular biology and evolution N2 - There is the tendency to assume that endangered species have been both genetically and demographically healthier in the past, so that any genetic erosion observed today was caused by their recent decline. The Iberian lynx (Lynx pardinus) suffered a dramatic and continuous decline during the 20th century, and now shows extremely low genome- and species-wide genetic diversity among other signs of genomic erosion. We analyze ancient (N = 10), historical (N = 245), and contemporary (N = 172) samples with microsatellite and mitogenome data to reconstruct the species' demography and investigate patterns of genetic variation across space and time. Iberian lynx populations transitioned from low but significantly higher genetic diversity than today and shallow geographical differentiation millennia ago, through a structured metapopulation with varying levels of diversity during the last centuries, to two extremely genetically depauperate and differentiated remnant populations by 2002. The historical subpopulations show varying extents of genetic drift in relation to their recent size and time in isolation, but these do not predict whether the populations persisted or went finally extinct. In conclusion, current genetic patterns were mainly shaped by genetic drift, supporting the current admixture of the two genetic pools and calling for a comprehensive genetic management of the ongoing conservation program. This study illustrates how a retrospective analysis of demographic and genetic patterns of endangered species can shed light onto their evolutionary history and this, in turn, can inform conservation actions. KW - Iberian lynx KW - ancient DNA KW - paleogenetics KW - genetic erosion KW - endangered species Y1 - 2017 U6 - https://doi.org/10.1093/molbev/msx222 SN - 0737-4038 SN - 1537-1719 VL - 34 SP - 2893 EP - 2907 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Chang, Dan A1 - Knapp, Michael A1 - Enk, Jacob A1 - Lippold, Sebastian A1 - Kircher, Martin A1 - Lister, Adrian M. A1 - MacPhee, Ross D. E. A1 - Widga, Christopher A1 - Czechowski, Paul A1 - Sommer, Robert A1 - Hodges, Emily A1 - Stümpel, Nikolaus A1 - Barnes, Ian A1 - Dalén, Love A1 - Derevianko, Anatoly A1 - Germonpré, Mietje A1 - Hillebrand-Voiculescu, Alexandra A1 - Constantin, Silviu A1 - Kuznetsova, Tatyana A1 - Mol, Dick A1 - Rathgeber, Thomas A1 - Rosendahl, Wilfried A1 - Tikhonov, Alexey N. A1 - Willerslev, Eske A1 - Hannon, Greg A1 - Lalueza i Fox, Carles A1 - Joger, Ulrich A1 - Poinar, Hendrik N. A1 - Hofreiter, Michael A1 - Shapiro, Beth T1 - The evolutionary and phylogeographic history of woolly mammoths BT - a comprehensive mitogenomic analysis JF - Scientific reports N2 - Near the end of the Pleistocene epoch, populations of the woolly mammoth (Mammuthus primigenius) were distributed across parts of three continents, from western Europe and northern Asia through Beringia to the Atlantic seaboard of North America. Nonetheless, questions about the connectivity and temporal continuity of mammoth populations and species remain unanswered. We use a combination of targeted enrichment and high-throughput sequencing to assemble and interpret a data set of 143 mammoth mitochondrial genomes, sampled from fossils recovered from across their Holarctic range. Our dataset includes 54 previously unpublished mitochondrial genomes and significantly increases the coverage of the Eurasian range of the species. The resulting global phylogeny confirms that the Late Pleistocene mammoth population comprised three distinct mitochondrial lineages that began to diverge ~1.0–2.0 million years ago (Ma). We also find that mammoth mitochondrial lineages were strongly geographically partitioned throughout the Pleistocene. In combination, our genetic results and the pattern of morphological variation in time and space suggest that male-mediated gene flow, rather than large-scale dispersals, was important in the Pleistocene evolutionary history of mammoths. Y1 - 2017 U6 - https://doi.org/10.1038/srep44585 SN - 2045-2322 VL - 7 PB - Nature Publishing Group CY - London ER - TY - JOUR A1 - Connor, Daniel Oliver A1 - Danckert, Lena A1 - Hoppe, Sebastian A1 - Bier, Frank Fabian A1 - von Nickisch-Rosenegk, Markus T1 - Epitope determination of immunogenic proteins of Neisseria gonorrhoeae JF - PLoS one N2 - Neisseria gonorrhoeae is the causative organism of gonorrhoea, a sexually transmitted disease that globally accounts for an estimated 80 to 100 million new infections per year. Increasing resistances to all common antibiotics used for N. gonorrhoeae treatment pose the risk of an untreatable disease. Further knowledge of ways of infection and host immune response are needed to understand the pathogen-host interaction and to discover new treatment alternatives against this disease. Therefore, detailed information about immunogenic proteins and their properties like epitope sites could advance further research in this area. In this work, we investigated immunogenic proteins of N. gonorrhoeae for linear epitopes by microarrays. Dominant linear epitopes were identified for eleven of the nineteen investigated proteins with three polyclonal rabbit antibodies from different immunisations. Identified linear epitopes were further examined for non-specific binding with antibodies to Escherichia coli and the closely related pathogen Neisseria meningitidis. On top of that, amino acids crucial for the antibody epitope binding were detected by microarray based alanine scans. Y1 - 2017 U6 - https://doi.org/10.1371/journal.pone.0180962 SN - 1932-6203 VL - 12 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Czarnocka, Weronika A1 - Van Der Kelen, Katrien A1 - Willems, Patrick A1 - Szechynska-Hebda, Magdalena A1 - Shahnejat-Bushehri, Sara A1 - Balazadeh, Salma A1 - Rusaczonek, Anna A1 - Müller-Röber, Bernd A1 - Van Breusegem, Frank A1 - Karpinski, Stanislaw T1 - The dual role of LESION SIMULATING DISEASE 1 as a condition-dependent scaffold protein and transcription regulator JF - Plant, cell & environment : cell physiology, whole-plant physiology, community physiology N2 - Since its discovery over two decades ago as an important cell death regulator in Arabidopsis thaliana, the role of LESION SIMULATING DISEASE 1 (LSD1) has been studied intensively within both biotic and abiotic stress responses as well as with respect to plant fitness regulation. However, its molecular mode of action remains enigmatic. Here, we demonstrate that nucleo-cytoplasmic LSD1 interacts with a broad range of other proteins that are engaged in various molecular pathways such as ubiquitination, methylation, cell cycle control, gametogenesis, embryo development and cell wall formation. The interaction of LSD1 with these partners is dependent on redox status, as oxidative stress significantly changes the quantity and types of LSD1-formed complexes. Furthermore, we show that LSD1 regulates the number and size of leaf mesophyll cells and affects plant vegetative growth. Importantly, we also reveal that in addition to its function as a scaffold protein, LSD1 acts as a transcriptional regulator. Taken together, our results demonstrate that LSD1 plays a dual role within the cell by acting as a condition-dependent scaffold protein and as a transcription regulator. KW - Arabidopsis KW - thaliana KW - dry weight KW - LSD1 KW - oxidative stress KW - protein interaction KW - transcription regulation Y1 - 2017 U6 - https://doi.org/10.1111/pce.12994 SN - 0140-7791 SN - 1365-3040 VL - 40 SP - 2644 EP - 2662 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Czernitzki, Anna-Franziska A1 - Pospisil, Christina A1 - Musalek, Martin A1 - Mumm, Rebekka A1 - Scheffler, Christiane T1 - Analysis of longitudinal data of height z-scores in kindergarten children BT - a pilot study JF - Journal of biological and clinical anthropology : Anthropologischer Anzeiger ; Mitteilungsorgan der Gesellschaft für Anthropologie N2 - Changes in body height throughout extended historic periods are very complex and dynamic processes. Thispilot study aimed to investigate the pattern of longitudinal height z-scores changes in children before and after entering kindergarten. In summer 2016, we measured height and weight of 32 children from 4 groups of two kindergartens aged 3–6 years. All ages were centered according to the age of entry into the kindergarten. For each child we determined mean z-scores for height before and after entering the kindergarten, and assessed the variances for each kindergarten group. Twenty-two children targeted in height z-scores towards average height of their respective kindergarten group, 10 children did not. Due to the small numbers, the convergence in height variance however, remained insignificant (chi-squared independence test, p = 0.127). Additional studies with larger sample sizes are needed to confirm this pilot study. KW - Height z-score KW - kindergarten children KW - secular trend KW - strategic growth adjustment KW - social signal Y1 - 2017 U6 - https://doi.org/10.1127/anthranz/2017/0708 SN - 0003-5548 VL - 74 IS - 2 SP - 109 EP - 112 PB - Schweizerbart science publishers CY - Stuttgart ER - TY - JOUR A1 - Dal Bianco, Andrea A1 - Wischke, Christian A1 - Zhou, Shuo A1 - Lendlein, Andreas T1 - Controlling surface properties and permeability of polyglycerol network films JF - Polymers for advanced technologies N2 - While branched polyglycerol (PG)-based molecules are well established as hydrophilic particles, the capacity of utilizing PG in bulk materials and opportunities arising by their further surface functionalization have only recently been considered. Here we investigated how the mold used in PG network synthesis may affect surface composition and how the permeability of substances through PG can be controlled by altering network structure, i.e. introducing 20mol% oligoethylene glycol (OEG) bifunctional spacer molecules. Overall, PG-based bulk network materials were shown to be tailorable, hydrophilic, low swelling and relatively stiff polyether-based materials, with low impact of salt onto material properties. Based on these features, but also on the principal capacity of free hydroxyl groups to be used for functionalization reactions, these materials may be an interesting platform for medical and technical applications, e.g. as diffusion-rate controlling membrane in aqueous environment. Copyright (c) 2016 John Wiley & Sons, Ltd. KW - polyglycerol KW - surface properties KW - diffusion KW - network structure Y1 - 2017 U6 - https://doi.org/10.1002/pat.3917 SN - 1042-7147 SN - 1099-1581 VL - 28 SP - 1263 EP - 1268 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Dammhahn, Melanie A1 - Landry-Cuerrier, Manuelle A1 - Reale, Denis A1 - Garant, Dany A1 - Humphries, Murray M. T1 - Individual variation in energy-saving heterothermy affects survival and reproductive success JF - Functional ecology : an official journal of the British Ecological Society N2 - 1. Given fundamental energetic trade-offs among growth, maintenance and reproduction, individual differences in energy saving should have consequences for survival and reproductive success. Many endotherms use periodic heterothermy to reduce energy and water requirements and individual variation in heterothermy should have fitness consequences. However, attempts to disentangle individual- and population-level variation in heterothermy are scarce. 2. Here, we quantified patterns of heterothermy of 55 free-ranging eastern chipmunks (Tamias striatus), food-hoarding hibernators. Over five hibernation periods, we obtained a total of 7108 daily individual heterothermy indices (median: 118 per individual). 3. Based on an individual reaction norm approach, we found that the use of heterothermy was repeatable and varied among individuals of the same population under similar environmental conditions. This among-individual variation had consequences for winter survival and reproductive success. Individuals using less heterothermy at the beginning of the winter had decreased survival in resource-rich but not in resource-poor years and higher reproductive success in the subsequent breeding season. 4. These results support the hypothesis that fluctuating selection maintains heterothermic diversity and suggest that individualized ecophysiology can contribute to a more thorough understanding of the evolution of energy-saving strategies in endotherms. KW - fitness consequences KW - hibernation KW - individual differences KW - individual reaction norm KW - Tamias striatus KW - torpor Y1 - 2017 U6 - https://doi.org/10.1111/1365-2435.12797 SN - 0269-8463 SN - 1365-2435 VL - 31 SP - 866 EP - 875 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Dammhahn, Melanie A1 - Randriamoria, Toky M. A1 - Goodman, Steven M. T1 - Broad and flexible stable isotope niches in invasive non-native Rattus spp. in anthropogenic and natural habitats of central eastern Madagascar JF - BMC ecology N2 - Background: Rodents of the genus Rattus are among the most pervasive and successful invasive species, causing major vicissitudes in native ecological communities. A broad and flexible generalist diet has been suggested as key to the invasion success of Rattus spp. Here, we use an indirect approach to better understand foraging niche width, plasticity, and overlap within and between introduced Rattus spp. in anthropogenic habitats and natural humid forests of Madagascar. Results: Based on stable carbon and nitrogen isotope values measured in hair samples of 589 individual rodents, we found that Rattus rattus had an extremely wide foraging niche, encompassing the isotopic space covered by a complete endemic forest-dwelling Malagasy small mammal community. Comparisons of Bayesian standard ellipses, as well as (multivariate) mixed-modeling analyses, revealed that the stable isotope niche of R. rattus tended to change seasonally and differed between natural forests and anthropogenic habitats, indicating plasticity in feeding niches. In co-occurrence, R. rattus and Rattus norvegicus partitioned feeding niches. Isotopic mismatch of signatures of individual R. rattus and the habitat in which they were captured, indicate frequent dispersal movements for this species between natural forest and anthropogenic habitats. Conclusions: Since R. rattus are known to transmit a number of zoonoses, potentially affecting communities of endemic small mammals, as well as humans, these movements presumably increase transmission potential. Our results suggest that due to their generalist diet and potential movement between natural forest and anthropogenic habitats, Rattus spp. might affect native forest-dependent Malagasy rodents as competitors, predators, and disease vectors. The combination of these effects helps explain the invasion success of Rattus spp. and the detrimental effects of this genus on the endemic Malagasy rodent fauna. KW - Bayesian standard ellipse KW - Coexistence KW - Habitat use KW - Humid forest KW - Invasion ecology KW - Invasive species KW - Rattus rattus KW - Rattus norvegicus KW - Rodents KW - Fur KW - Stable carbon isotope KW - Stable nitrogen isotope Y1 - 2017 U6 - https://doi.org/10.1186/s12898-017-0125-0 SN - 1472-6785 VL - 17 PB - BioMed Central CY - London ER - TY - JOUR A1 - Dennis, Alice B. A1 - Patel, Vilas A1 - Oliver, Kerry M. A1 - Vorburger, Christoph T1 - Parasitoid gene expression changes after adaptation to symbiont-protected hosts JF - Evolution N2 - Reciprocal selection between aphids, their protective endosymbionts, and the parasitoid wasps that prey upon them offers an opportunity to study the basis of their coevolution. We investigated adaptation to symbiont‐conferred defense by rearing the parasitoid wasp Lysiphlebus fabarum on aphids (Aphis fabae) possessing different defensive symbiont strains (Hamiltonella defensa). After ten generations of experimental evolution, wasps showed increased abilities to parasitize aphids possessing the H. defensa strain they evolved with, but not aphids possessing the other strain. We show that the two symbiont strains encode different toxins, potentially creating different targets for counter‐adaptation. Phenotypic and behavioral comparisons suggest that neither life‐history traits nor oviposition behavior differed among evolved parasitoid lineages. In contrast, comparative transcriptomics of adult female wasps identified a suite of differentially expressed genes among lineages, even when reared in a common, symbiont‐free, aphid host. In concurrence with the specificity of each parasitoid lineages’ infectivity, most differentially expressed parasitoid transcripts were also lineage‐specific. These transcripts are enriched with putative venom toxins and contain highly expressed, potentially defensive viral particles. Together, these results suggest that wild populations of L. fabarum employ a complicated offensive arsenal with sufficient genetic variation for wasps to adapt rapidly and specifically to their hosts’ microbial defenses. KW - Adaptation KW - experimental evolution KW - gene expression KW - Lysiphlebus fabarum KW - parasitoid KW - venom Y1 - 2017 U6 - https://doi.org/10.1111/evo.13333 SN - 0014-3820 SN - 1558-5646 VL - 71 SP - 2599 EP - 2617 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Denoux, Clemence A1 - Martin-Creuzburg, Dominik A1 - Koussoroplis, Apostolos-Manuel A1 - Perriere, Fanny A1 - Desvillettes, Christian A1 - Bourdier, Gilles A1 - Bec, Alexandre T1 - Phospholipid-bound eicosapentaenoic acid (EPA) supports higher fecundity than free EPA in Daphnia magna JF - Journal of plankton research N2 - Nutrition bioassays in which polyunsaturated fatty acids (PUFA)-deficient diets were supplemented with free long-chain PUFA (>= C20) consistently revealed positive effects on somatic growth and fecundity of Daphnia. However, free PUFA are hardly available in natural diets. In general, PUFA are bound to other lipids, especially to phospholipids and triglycerides. Here, we evaluate the potential of free and phospholipid-bound dietary eicosapentaenoic acid (EPA) to support somatic growth and fecundity of Daphnia magna. In a growth experiment, supplementation of a C20 PUFA-deficient diet with free or phospholipid-bound EPA improved somatic growth rates of D. magna equally. However, the increase in fecundity was significantly more pronounced when phospholipid-bound EPA was provided. Free and phospholipid-bound EPA were provided in the same concentrations in our experiment, suggesting that the allocation to reproduction-related processes is affected differently by phospholipid-bound PUFA and free PUFA. Our finding stresses the need to consider the distribution of dietary PUFA in different lipid classes to gain a better understanding of how PUFA influence life history traits of Daphnids in the field. KW - Daphnia magna KW - food quality KW - phospholipids KW - polyunsaturated fatty acids KW - reproduction KW - somatic growth KW - trophic interactions Y1 - 2017 U6 - https://doi.org/10.1093/plankt/fbx037 SN - 0142-7873 SN - 1464-3774 VL - 39 SP - 843 EP - 848 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Dolotovskaya, Sofya A1 - Bordallo, Juan Torroba A1 - Haus, Tanja A1 - Noll, Angela A1 - Hofreiter, Michael A1 - Zinner, Dietmar A1 - Roos, Christian T1 - Comparing mitogenomic timetrees for two African savannah primate genera (Chlorocebus and Papio) JF - Zoological Journal of the Linnean Society N2 - Complete mitochondrial (mtDNA) genomes have proved to be useful in reconstructing primate phylogenies with higher resolution and confidence compared to reconstructions based on partial mtDNA sequences. Here, we analyse complete mtDNA genomes of African green monkeys (genus Chlorocebus), a widely distributed primate genus in Africa representing an interesting phylogeographical model for the evolution of savannah species. Previous studies on partial mtDNA sequences revealed nine major clades, suggesting several cases of para- and polyphyly among Chlorocebus species. However, in these studies, phylogenetic relationships among several clades were not resolved, and divergence times were not estimated. We analysed complete mtDNA genomes for ten Chlorocebus samples representing major mtDNA clades to find stronger statistical support in the phylogenetic reconstruction than in the previous studies and to estimate divergence times. Our results confirmed para- and polyphyletic relationships of most Chlorocebus species, while the support for the phylogenetic relationships between the mtDNA clades increased compared to the previous studies. Our results indicate an initial west-east division in the northern part of the Chlorocebus range with subsequent divergence into north-eastern and southern clades. This phylogeographic scenario contrasts with that for another widespread African savannah primate genus, the baboons (Papio), for which a dispersal from southern Africa into East and West Africa was suggested. KW - African green monkeys KW - baboons KW - mitochondrial genomes KW - phylogeny KW - phylogeography Y1 - 2017 U6 - https://doi.org/10.1093/zoolinnean/zlx001 SN - 0024-4082 SN - 1096-3642 VL - 181 IS - 2 SP - 471 EP - 483 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Dominguez, Marisol A1 - Tiedemann, Ralph A1 - Reboreda, Juan C. A1 - Segura, Luciano A1 - Tittarelli, Fabian A1 - Mahler, Bettina T1 - Genetic structure reveals management units for the yellow cardinal (Gubernatrix cristata), endangered by habitat loss and illegal trapping JF - Conservation genetics KW - Genetic structure KW - Gubernatrix cristata KW - Management units KW - MtDNA KW - Microsatellites KW - Hybrids Y1 - 2017 U6 - https://doi.org/10.1007/s10592-017-0964-4 SN - 1566-0621 SN - 1572-9737 VL - 18 SP - 1131 EP - 1140 PB - Springer CY - Dordrecht ER - TY - JOUR A1 - Dong, Chao A1 - Yang, Jing A1 - Reschke, Stefan A1 - Leimkühler, Silke A1 - Kirk, Martin L. T1 - Vibrational Probes of Molybdenum Cofactor-Protein Interactions in Xanthine Dehydrogenase JF - Inorganic chemistry N2 - The pyranopterin dithiolene (PDT) ligand is an integral component of the molybdenum cofactor (Moco) found in all molybdoenzymes with the sole exception of nitrogenase. However, the roles of the PDT in catalysis are still unknown. The PDT is believed to be bound to the proteins by an extensive hydrogen bonding network, and it has been suggested that these interactions may function to fine-tune Moco for electron- and atom-transfer reactivity in catalysis. Here, we use resonance Raman (rR) spectroscopy to probe Moco-protein interactions using heavy-atom congeners of lumazine, molecules that bind tightly to both wild-type xanthine dehydrogenase (wt-XDH) and its Q102G and Q197A variants following enzymatic hydroxylation to the corresponding violapterin product molecules. The resulting enzyme-product complexes possess intense near-IR absorption, allowing high-quality rR spectra to be collected on wt-XDH and the Q102G and Q197A variants. Small negative frequency shifts relative to wt-XDH are observed for the low-frequency Moco vibrations. These results are interpreted in the context of weak hydrogen-bonding and/or electrostatic interactions between Q102 and the -NH2 terminus of the PDT, and between Q197 and the terminal oxo of the Mo equivalent to O group. The Q102A, Q102G, Q197A, and Q197E variants do not appreciably affect the kinetic parameters k(red) and k(red)/K-D, indicating that a primary role for these glutamine residues is to stabilize and coordinate Moco in the active site of XO family enzymes but to not directly affect the catalytic throughput. Raman frequency shifts between wt-XDH and its Q102G variant suggest that the changes in the electron density at the Mo ion that accompany Mo oxidation during electron-transfer regeneration of the catalytically competent active site are manifest in distortions at the distant PDT amino terminus. This implies a primary role for the PDT as a conduit for facilitating enzymatic electron-transfer reactivity in xanthine oxidase family enzymes. Y1 - 2017 U6 - https://doi.org/10.1021/acs.inorgchem.7b00028 SN - 0020-1669 SN - 1520-510X VL - 56 SP - 6830 EP - 6837 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Dunsing, Valentin A1 - Mayer, Magnus A1 - Liebsch, Filip A1 - Multhaup, Gerhard A1 - Chiantia, Salvatore T1 - Direct evidence of amyloid precursor-like protein 1 trans interactions in cell-cell adhesion platforms investigated via fluorescence fluctuation spectroscopy JF - Molecular biology of the cell : the official publication of the American Society for Cell Biology N2 - The amyloid precursor-like protein 1 (APLP1) is a type I transmembrane protein that plays a role in synaptic adhesion and synaptogenesis. Past investigations indicated that APLP1 is involved in the formation of protein-protein complexes that bridge the junctions between neighboring cells. Nevertheless, APLP1-APLP1 trans interactions have never been directly observed in higher eukaryotic cells. Here, we investigated APLP1 interactions and dynamics directly in living human embryonic kidney cells using fluorescence fluctuation spectroscopy techniques, namely cross-correlation scanning fluorescence correlation spectroscopy and number and brightness analysis. Our results show that APLP1 forms homotypic trans complexes at cell-cell contacts. In the presence of zinc ions, the protein forms macroscopic clusters, exhibiting an even higher degree of trans binding and strongly reduced dynamics. Further evidence from giant plasma membrane vesicles suggests that the presence of an intact cortical cytoskeleton is required for zinc-induced cis multimerization. Subsequently, large adhesion platforms bridging interacting cells are formed through APLP1-APLP1 trans interactions. Taken together, our results provide direct evidence that APLP1 functions as a neuronal zinc-dependent adhesion protein and allow a more detailed understanding of the molecular mechanisms driving the formation of APLP1 adhesion platforms. Y1 - 2017 U6 - https://doi.org/10.1091/mbc.E17-07-0459 SN - 1059-1524 SN - 1939-4586 VL - 28 SP - 3609 EP - 3620 PB - American Society for Cell Biology CY - Bethesda ER - TY - JOUR A1 - Ebrahimian-Motlagh, Saghar A1 - Ribone, Pamela A. A1 - Thirumalaikumar, Venkatesh P. A1 - Allu, Annapurna Devi A1 - Chan, Raquel L. A1 - Mueller-Roeber, Bernd A1 - Balazadeh, Salma T1 - JUNGBRUNNEN1 Confers Drought Tolerance Downstream of the HD-Zip I Transcription Factor AtHB13 JF - Frontiers in plant science N2 - Low water availability is the major environmental factor limiting growth and productivity of plants and crops and is therefore considered of high importance for agriculture affected by climate change. Identifying regulatory components controlling the response and tolerance to drought stress is thus of major importance. The NAC transcription factor (TF) JUNGBRUNNEN1 (JUB1) from Arabidopsis thaliana extends leaf longevity under non-stress growth conditions, lowers cellular hydrogen peroxide (H2O2) level, and enhances tolerance against heat stress and salinity. Here, we additionally find that JUB1 strongly increases tolerance to drought stress in Arabidopsis when expressed from both, a constitutive (CaMV 35S) and an abiotic stress-induced (RD29A) promoter. Employing a yeast one-hybrid screen we identified HD-Zip class I TF AtHB13 as an upstream regulator of JUB1. AtHB13 has previously been reported to act as a positive regulator of drought tolerance. AtHB13 and JUB1 thereby establish a joint drought stress control module. KW - Arabidopsis KW - transcription factor KW - drought KW - JUB1 KW - HB13 Y1 - 2017 U6 - https://doi.org/10.3389/fpls.2017.02118 SN - 1664-462X VL - 8 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Eccard, Jana A1 - Dammhahn, Melanie A1 - Ylonen, Hannu T1 - The Bruce effect revisited: is pregnancy termination in female rodents an adaptation to ensure breeding success after male turnover in low densities? JF - Oecologia N2 - Pregnancy termination after encountering a strange male, the Bruce effect, is regarded as a counterstrategy of female mammals towards anticipated infanticide. While confirmed in caged rodent pairs, no verification for the Bruce effect existed from experimental field populations of small rodents. We suggest that the effect may be adaptive for breeding rodent females only under specific conditions related to populations with cyclically fluctuating densities. We investigated the occurrence of delay in birth date after experimental turnover of the breeding male under different population composition in bank voles (Myodes glareolus) in large outdoor enclosures: one-male-multiple-females (n = 6 populations/18 females), multiple-males-multiplefemales (n = 15/45), and single-male-single-female (MF treatment, n = 74/74). Most delays were observed in the MF treatment after turnover. Parallel we showed in a laboratory experiment (n = 205 females) that overwintered and primiparous females, the most abundant cohort during population lows in the increase phase of cyclic rodent populations, were more likely to delay births after turnover of the male than year-born and multiparous females. Taken together, our results suggest that the Bruce effect may be an adaptive breeding strategy for rodent females in cyclic populations specifically at low densities in the increase phase, when isolated, overwintered animals associate in MF pairs. During population lows infanticide risk and inbreeding risk may then be higher than during population highs, while also the fitness value of a litter in an increasing population is higher. Therefore, the Bruce effect may be adaptive for females during annual population lows in the increase phases, even at the costs of delaying reproduction. KW - Breeding strategies KW - Dip test KW - Infanticide KW - Myodes voles KW - Sexual conflict KW - Sexual selection Y1 - 2017 U6 - https://doi.org/10.1007/s00442-017-3904-6 SN - 0029-8549 SN - 1432-1939 VL - 185 SP - 81 EP - 94 PB - Springer CY - New York ER - TY - JOUR A1 - Eckert, Ester M. A1 - Di Cesare, Andrea A1 - Kettner, Marie Therese A1 - Arias-Andres, Maria A1 - Fontaneto, Diego A1 - Grossart, Hans-Peter A1 - Corno, Gianluca T1 - Microplastics increase impact of treated wastewater on freshwater microbial community JF - Environmental pollution N2 - Plastic pollution is a major global concern with several million microplastic particles entering every day freshwater ecosystems via wastewater discharge. Microplastic particles stimulate biofilm formation (plastisphere) throughout the water column and have the potential to affect microbial community structure if they accumulate in pelagic waters, especially enhancing the proliferation of biohazardous bacteria. To test this scenario, we simulated the inflow of treated wastewater into a temperate lake using a continuous culture system with a gradient of concentration of microplastic particles. We followed the effect of microplastics on the microbial community structure and on the occurrence of integrase 1 (intl), a marker associated with mobile genetic elements known as a proxy for anthropogenic effects on the spread of antimicrobial resistance genes. The abundance of intl increased in the plastisphere with increasing microplastic particle concentration, but not in the water surrounding the microplastic particles. Likewise, the microbial community on microplastic was more similar to the original wastewater community with increasing microplastic concentrations. Our results show that microplastic particles indeed promote persistence of typical indicators of microbial anthropogenic pollution in natural waters, and substantiate that their removal from treated wastewater should be prioritised. (C) 2017 Elsevier Ltd. All rights reserved. KW - Microplastics KW - Anthropogenic pollution KW - Treated wastewater KW - Freshwater microbial communities KW - Integrase 1 KW - Biofilm Y1 - 2017 U6 - https://doi.org/10.1016/j.envpol.2017.11.070 SN - 0269-7491 SN - 1873-6424 VL - 234 SP - 495 EP - 502 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Edenius, Lars A1 - Choi, Chang-Yong A1 - Heim, Wieland A1 - Jaakkonen, Tuomo A1 - De Jong, Adriaan A1 - Ozaki, Kiyoaki A1 - Roberge, Jean-Michel T1 - The next common and widespread bunting to go? BT - global population decline in the Rustic Bunting Emberiza rustica JF - Bird conservation international N2 - Populations of several long-distance migratory songbirds in Eurasia are in peril, drastically illustrated by the recent range-wide population collapse in the Yellow-breasted Bunting Emberiza aureola. There are signals of a strong decline also in the Rustic Bunting E. rustica, but no range-wide assessment of population trends in this superabundant and widespread bunting species has yet been undertaken. The conservation status of Rustic Bunting is ‘Least Concern’ on the global IUCN Red List, but it has recently been upgraded to ‘Vulnerable’ on the European Red List. To assess the Rustic Bunting’s global conservation status we compiled, for the first time, population data across its breeding and wintering ranges. The analysis reveals a 75–87% decline in overall population size over the last 30 years and a 32–91% decline over the last 10 years. The trend estimates indicate that the long-term (30-year) range-wide population decline in the Rustic Bunting is of similar magnitude to two well-known examples of declining species within the same genus, the Yellow-breasted Bunting and the Ortolan Bunting E. hortulana. The magnitude of the range-wide population decline over the last 10 years suggests that the Rustic Bunting could be upgraded from ‘Least Concern’ to ‘Vulnerable’ or ‘Endangered’ on the IUCN global Red List. Agricultural intensification in the wintering range and intensified levels of disturbance, including logging and fire, in the breeding range could be important drivers of the range-wide population decline, and persecution could also contribute. Untangling threat factors and their interactions on Rustic Bunting is necessary for conservation, but hampered by our currently limited understanding of the relationships between population dynamics and different threats. Y1 - 2016 U6 - https://doi.org/10.1017/S0959270916000046 SN - 0959-2709 SN - 1474-0001 VL - 27 IS - 1 SP - 35 EP - 44 PB - Cambridge Univ. Press CY - New York ER - TY - JOUR A1 - Ehmann, Lisa A1 - Zoller, Michael A1 - Minichmayr, Iris K. A1 - Scharf, Christina A1 - Maier, Barbara A1 - Schmitt, Maximilian V. A1 - Hartung, Niklas A1 - Huisinga, Wilhelm A1 - Vogeser, Michael A1 - Frey, Lorenz A1 - Zander, Johannes A1 - Kloft, Charlotte T1 - Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients BT - a prospective observational study JF - Critical care N2 - Background: Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application. Methods: A prospective observational single-centre study was performed with critically ill patients with severe infections receiving standard dosing of meropenem. Serial blood samples were drawn over 4 study days to determine meropenem serum concentrations. Renal function was assessed by creatinine clearance according to the Cockcroft and Gault equation (CLCRCG). Variability in meropenem serum concentrations was quantified at the middle and end of each monitored dosing interval. The attainment of two pharmacokinetic/pharmacodynamic targets (100% T->MIC, 50% T->4xMIC) was evaluated for minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we assessed the impact of CLCRCG on meropenem concentrations and target attainment and developed a tool for risk assessment of target non-attainment. Results: Large inter-and intra-patient variability in meropenem concentrations was observed in the critically ill population (n = 48). Attainment of the target 100% T->MIC was merely 48.4% and 20.6%, given MIC values of 2 mg/L and 8 mg/L, respectively, and similar for the target 50% T->4xMIC. A hyperbolic relationship between CLCRCG (25-255 ml/minute) and meropenem serum concentrations at the end of the dosing interval (C-8h) was derived. For infections with pathogens of MIC 2 mg/L, mild renal impairment up to augmented renal function was identified as a risk factor for target non-attainment (for MIC 8 mg/L, additionally, moderate renal impairment). Conclusions: The investigated standard meropenem dosing regimen appeared to result in insufficient meropenem exposure in a considerable fraction of critically ill patients. An easy-and free-to-use tool (the MeroRisk Calculator) for assessing the risk of target non-attainment for a given renal function and MIC value was developed. KW - beta-Lactam KW - Intensive care KW - Pharmacokinetics/Pharmacodynamics KW - Target attainment KW - Renal function KW - Risk assessment tool KW - Continuous renal replacement therapy Y1 - 2017 U6 - https://doi.org/10.1186/s13054-017-1829-4 SN - 1466-609X SN - 1364-8535 VL - 21 PB - BioMed Central CY - London ER - TY - JOUR A1 - Ehrlich, Elias A1 - Becks, Lutz A1 - Gaedke, Ursula T1 - Trait-fitness relationships determine how trade-off shapes affect species coexistence JF - Ecology : a publication of the Ecological Society of America N2 - Trade-offs between functional traits are ubiquitous in nature and can promote species coexistence depending on their shape. Classic theory predicts that convex trade-offs facilitate coexistence of specialized species with extreme trait values (extreme species) while concave trade-offs promote species with intermediate trait values (intermediate species). We show here that this prediction becomes insufficient when the traits translate non-linearly into fitness which frequently occurs in nature, e.g., an increasing length of spines reduces grazing losses only up to a certain threshold resulting in a saturating or sigmoid trait-fitness function. We present a novel, general approach to evaluate the effect of different trade-off shapes on species coexistence. We compare the trade-off curve to the invasion boundary of an intermediate species invading the two extreme species. At this boundary, the invasion fitness is zero. Thus, it separates trait combinations where invasion is or is not possible. The invasion boundary is calculated based on measurable trait-fitness relationships. If at least one of these relationships is not linear, the invasion boundary becomes non-linear, implying that convex and concave trade-offs not necessarily lead to different coexistence patterns. Therefore, we suggest a new ecological classification of trade-offs into extreme-favoring and intermediate-favoring which differs from a purely mathematical description of their shape. We apply our approach to a well-established model of an empirical predator-prey system with competing prey types facing a trade-off between edibility and half-saturation constant for nutrient uptake. We show that the survival of the intermediate prey depends on the convexity of the trade-off. Overall, our approach provides a general tool to make a priori predictions on the outcome of competition among species facing a common trade-off in dependence of the shape of the trade-off and the shape of the trait-fitness relationships. KW - coexistence KW - competition KW - fitness KW - functional traits KW - invasion boundary KW - neutrality KW - predator-prey model KW - shape KW - trade-offs Y1 - 2017 U6 - https://doi.org/10.1002/ecy.2047 SN - 0012-9658 SN - 1939-9170 VL - 98 SP - 3188 EP - 3198 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Elsner, Julia A1 - Hofreiter, Michael A1 - Schibler, Joerg A1 - Schlumbaum, Angela T1 - Ancient mtDNA diversity reveals specific population development of wild horses in Switzerland after the Last Glacial Maximum JF - PLoS one Y1 - 2017 U6 - https://doi.org/10.1371/journal.pone.0177458 SN - 1932-6203 VL - 12 SP - 17246 EP - 17256 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Endesfelder, Stefanie A1 - Weichelt, Ulrike A1 - Strauß, Evelyn A1 - Schlör, Anja A1 - Sifringer, Marco A1 - Scheuer, Till A1 - Bührer, Christoph A1 - Schmitz, Thomas T1 - Neuroprotection by caffeine in hyperoxia-induced neonatal brain injury JF - International journal of molecular sciences N2 - Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term “oxygen radical disease of prematurity”. Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6) corresponds to that of a human fetal brain at 28–32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC)), promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1), down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NFκB), reduced pro-apoptotic effectors (poly (ADP-ribose) polymerase-1 (PARP-1), apoptosis inducing factor (AIF), and caspase-3), and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP) 2, and inhibitor of metalloproteinase (TIMP) 1/2). Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. KW - anti-oxidative response KW - caffeine KW - hyperoxia KW - oxidative stress KW - preterm infants KW - developing brain Y1 - 2017 U6 - https://doi.org/10.3390/ijms18010187 SN - 1422-0067 SN - 1661-6596 VL - 18 PB - Molecular Diversity Preservation International CY - Basel ER - TY - JOUR A1 - Estendorfer, Jennifer A1 - Stempfhuber, Barbara A1 - Haury, Paula A1 - Vestergaard, Gisle A1 - Rillig, Matthias C. A1 - Joshi, Jasmin Radha A1 - Schröder, Peter A1 - Schloter, Michael T1 - The Influence of Land Use Intensity on the Plant-Associated Microbiome of Dactylis glomerata L. JF - Frontiers in plant science N2 - In this study, we investigated the impact of different land use intensities (LUI) on the root-associated microbiome of Dactylis glomerata (orchardgrass). For this purpose, eight sampling sites with different land use intensity levels but comparable soil properties were selected in the southwest of Germany. Experimental plots covered land use levels from natural grassland up to intensively managed meadows. We used 16S rRNA gene based barcoding to assess the plant-associated community structure in the endosphere, rhizosphere and bulk soil of D. glomerata. Samples were taken at the reproductive stage of the plant in early summer. Our data indicated that roots harbor a distinct bacterial community, which clearly differed from the microbiome of the rhizosphere and bulk soil. Our results revealed Pseudomonadaceae, Enterobacteriaceae and Comamonadaceae as the most abundant endophytes independently of land use intensity. Rhizosphere and bulk soil were dominated also by Proteobacteria, but the most abundant families differed from those obtained from root samples. In the soil, the effect of land use intensity was more pronounced compared to root endophytes leading to a clearly distinct pattern of bacterial communities under different LUI from rhizosphere and bulk soil vs. endophytes. Overall, a change of community structure on the plant-soil interface was observed, as the number of shared OTUs between all three compartments investigated increased with decreasing land use intensity. Thus, our findings suggest a stronger interaction of the plant with its surrounding soil under low land use intensity. Furthermore, the amount and quality of available nitrogen was identified as a major driver for shifts in the microbiome structure in all compartments. KW - Dactylis glomerata KW - land use change KW - endophytes KW - rhizosphere KW - soil microbiome KW - biodiversity Y1 - 2017 U6 - https://doi.org/10.3389/fpls.2017.00930 SN - 1664-462X VL - 8 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Falk, Thomas A1 - Kirk, Michael A1 - Lohmann, Dirk A1 - Kruger, Bertus A1 - Hüttich, Christian A1 - Kamukuenjandje, Richard T1 - The profits of excludability and transferability in redistributive land reform in central Namibia JF - Development Southern Africa N2 - Policies which redistribute property rights to land can improve the well-being of rural households and can have overall growth effects. In many cases, however, land reforms are driven mainly by politically justified objectives. Under such circumstances, little emphasis is placed on whether and, if so, how property rights can increase productivity. Following 18 years of land reform implementation in Namibia, we evaluated 65 beneficiaries in Namibia. We assess to which degree land rights affects their farm income. The study focuses on Namibia’s two main commercial land reform instruments, namely the Farm Unit Resettlement Scheme and the Affirmative Action Loan Scheme. We find evidence that the majority of land reform projects are not profitable. Further, our study confirms the importance of the right to restrict land access compared with the right to transfer. The long-term leasehold contract seemingly provides sufficient incentives to make productive use of the land. KW - Redistributive land reform KW - property rights KW - farm productivity KW - pastoralism KW - Namibia Y1 - 2017 U6 - https://doi.org/10.1080/0376835X.2016.1269633 SN - 0376-835X SN - 1470-3637 VL - 34 SP - 314 EP - 329 PB - Routledge, Taylor & Francis Group CY - Abingdon ER - TY - JOUR A1 - Fer, Istem A1 - Tietjen, Britta A1 - Jeltsch, Florian A1 - Wolff, Christian Michael T1 - The influence of El Nino-Southern Oscillation regimes on eastern African vegetation and its future implications under the RCP8.5 warming scenario JF - Biogeosciences N2 - The El Nino-Southern Oscillation (ENSO) is the main driver of the interannual variability in eastern African rainfall, with a significant impact on vegetation and agriculture and dire consequences for food and social security. In this study, we identify and quantify the ENSO contribution to the eastern African rainfall variability to forecast future eastern African vegetation response to rainfall variability related to a predicted intensified ENSO. To differentiate the vegetation variability due to ENSO, we removed the ENSO signal from the climate data using empirical orthogonal teleconnection (EOT) analysis. Then, we simulated the ecosystem carbon and water fluxes under the historical climate without components related to ENSO teleconnections. We found ENSO-driven patterns in vegetation response and confirmed that EOT analysis can successfully produce coupled tropical Pacific sea surface temperature-eastern African rainfall teleconnection from observed datasets. We further simulated eastern African vegetation response under future climate change as it is projected by climate models and under future climate change combined with a predicted increased ENSO intensity. Our EOT analysis highlights that climate simulations are still not good at capturing rainfall variability due to ENSO, and as we show here the future vegetation would be different from what is simulated under these climate model outputs lacking accurate ENSO contribution. We simulated considerable differences in eastern African vegetation growth under the influence of an intensified ENSO regime which will bring further environmental stress to a region with a reduced capacity to adapt effects of global climate change and food security. Y1 - 2017 U6 - https://doi.org/10.5194/bg-14-4355-2017 SN - 1726-4170 SN - 1726-4189 VL - 14 SP - 4355 EP - 4374 PB - Copernicus CY - Göttingen ER - TY - JOUR A1 - Fer, Istem A1 - Tietjen, Britta A1 - Jeltsch, Florian A1 - Wolff, Christian Michael T1 - The influence of El Nino-Southern Oscillation regimes on eastern African vegetation and its future implications under the RCP8.5 warming scenario JF - Biogeosciences N2 - The El Nino-Southern Oscillation (ENSO) is the main driver of the interannual variability in eastern African rainfall, with a significant impact on vegetation and agriculture and dire consequences for food and social security. In this study, we identify and quantify the ENSO contribution to the eastern African rainfall variability to forecast future eastern African vegetation response to rainfall variability related to a predicted intensified ENSO. To differentiate the vegetation variability due to ENSO, we removed the ENSO signal from the climate data using empirical orthogonal teleconnection (EOT) analysis. Then, we simulated the ecosystem carbon and water fluxes under the historical climate without components related to ENSO teleconnections. We found ENSO-driven patterns in vegetation response and confirmed that EOT analysis can successfully produce coupled tropical Pacific sea surface temperature-eastern African rainfall teleconnection from observed datasets. We further simulated eastern African vegetation response under future climate change as it is projected by climate models and under future climate change combined with a predicted increased ENSO intensity. Our EOT analysis highlights that climate simulations are still not good at capturing rainfall variability due to ENSO, and as we show here the future vegetation would be different from what is simulated under these climate model outputs lacking accurate ENSO contribution. We simulated considerable differences in eastern African vegetation growth under the influence of an intensified ENSO regime which will bring further environmental stress to a region with a reduced capacity to adapt effects of global climate change and food security. Y1 - 2017 U6 - https://doi.org/10.5194/bg-14-4355-2017 SN - 1726-4170 SN - 1726-4189 VL - 14 IS - 18 SP - 4355 EP - 4374 PB - Copernicus CY - Katlenburg-Lindau ER - TY - JOUR A1 - Fernandez-Nino, Miguel A1 - Giraldo, Daniel A1 - Lucia Gomez-Porras, Judith A1 - Dreyer, Ingo A1 - Gonzalez Barrios, Andres Fernando A1 - Arevalo-Ferro, Catalina T1 - A synthetic multi-cellular network of coupled self-sustained oscillators JF - PLoS one N2 - Engineering artificial networks from modular components is a major challenge in synthetic biology. In the past years, single units, such as switches and oscillators, were successfully constructed and implemented. The effective integration of these parts into functional artificial self-regulated networks is currently on the verge of breakthrough. Here, we describe the design of a modular higher-order synthetic genetic network assembled from two independent self-sustained synthetic units: repressilators coupled via a modified quorum-sensing circuit. The isolated communication circuit and the network of coupled oscillators were analysed in mathematical modelling and experimental approaches. We monitored clustering of cells in groups of various sizes. Within each cluster of cells, cells oscillate synchronously, whereas the theoretical modelling predicts complete synchronization of the whole cellular population to be obtained approximately after 30 days. Our data suggest that self-regulated synchronization in biological systems can occur through an intermediate, long term clustering phase. The proposed artificial multicellular network provides a system framework for exploring how a given network generates a specific behaviour. Y1 - 2017 U6 - https://doi.org/10.1371/journal.pone.0180155 SN - 1932-6203 VL - 12 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Ferrera, Isabel A1 - Sarmento, Hugo A1 - Priscu, John C. A1 - Chiuchiolo, Amy A1 - Gonzalez, Jose M. A1 - Grossart, Hans-Peter T1 - Diversity and Distribution of Freshwater Aerobic Anoxygenic Phototrophic Bacteria across a Wide Latitudinal Gradient JF - Frontiers in microbiology N2 - Aerobic anoxygenic phototrophs (AAPs) have been shown to exist in numerous marine and brackish environments where they are hypothesized to play important ecological roles. Despite their potential significance, the study of freshwater AAPs is in its infancy and limited to local investigations. Here, we explore the occurrence, diversity and distribution of AAPs in lakes covering a wide latitudinal gradient: Mongolian and German lakes located in temperate regions of Eurasia, tropical Great East African lakes, and polar permanently ice-covered Antarctic lakes. Our results show a widespread distribution of AAPs in lakes with contrasting environmental conditions and confirm that this group is composed of different members of the Alpha- and Betaproteobacteria. While latitude does not seem to strongly influence AAP abundance, clear patterns of community structure and composition along geographic regions were observed as indicated by a strong macro-geographical signal in the taxonomical composition of AAPs. Overall, our results suggest that the distribution patterns of freshwater AAPs are likely driven by a combination of small-scale environmental conditions (specific of each lake and region) and large-scale geographic factors (climatic regions across a latitudinal gradient). KW - AAP bacteria KW - photoheterotrophy KW - pufM gene KW - freshwater lakes KW - latitudinal gradients KW - biogeography Y1 - 2017 U6 - https://doi.org/10.3389/fmicb.2017.00175 SN - 1664-302X VL - 8 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Fischbach, Jens A1 - Loh, Qiuting A1 - Bier, Frank Fabian A1 - Lim, Theam Soon A1 - Frohme, Marcus A1 - Glökler, Jörn T1 - Alizarin Red S for Online Pyrophosphate Detection Identified by a Rapid Screening Method JF - Scientific reports N2 - We identified Alizarin Red S and other well known fluorescent dyes useful for the online detection of pyrophosphate in enzymatic assays, including the loop mediated isothermal amplification (LAMP) and polymerase chain reaction (PCR) assays. An iterative screening was used for a selected set of compounds to first secure enzyme compatibility, evaluate inorganic pyrophosphate sensitivity in the presence of manganese as quencher and optimize conditions for an online detection. Of the selected dyes, the inexpensive alizarin red S was found to selectively detect pyrophosphate under LAMP and PCR conditions and is superior with respect to its defined red-shifted spectrum, long shelf life and low toxicity. In addition, the newly identified properties may also be useful in other enzymatic assays which do not generate nucleic acids but are based on inorganic pyrophosphate. Finally, we propose that our screening method may provide a blueprint for rapid screening of compounds for detecting inorganic pyrophosphate. Y1 - 2017 U6 - https://doi.org/10.1038/srep45085 SN - 2045-2322 VL - 7 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Flasch, Leopold A1 - von Elm, Natalie A1 - Wester, Petra T1 - Nectar-drinking Elephantulus edwardii as a potential pollinator of Massonia echinata, endemic to the Bokkeveld plateau in South Africa JF - African journal of ecology Y1 - 2017 U6 - https://doi.org/10.1111/aje.12352 SN - 0141-6707 SN - 1365-2028 VL - 55 SP - 376 EP - 379 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Foti, Alessandro A1 - Dorendorf, Frank A1 - Leimkühler, Silke T1 - A single nucleotide polymorphism causes enhanced radical oxygen species production by human aldehyde oxidase JF - PLoS one N2 - Aldehyde oxidases (AOXs) are molybdo-flavoenzymes characterized by broad substrate specificity, oxidizing aromatic/aliphatic aldehydes into the corresponding carboxylic acids and hydroxylating various heteroaromatic rings. The enzymes use oxygen as the terminal electron acceptor and produce reduced oxygen species during turnover. The physiological function of mammalian AOX isoenzymes is still unclear, however, human AOX (hAOX1) is an emerging enzyme in phase-I drug metabolism. Indeed, the number of xenobiotics acting as hAOX1 substrates is increasing. Further, numerous single-nucleotide polymorphisms (SNPs) have been identified within the hAOX1 gene. SNPs are a major source of inter-individual variability in the human population, and SNP-based amino acid exchanges in hAOX1 reportedly modulate the catalytic function of the enzyme in either a positive or negative fashion. In this report we selected ten novel SNPs resulting in amino acid exchanges in proximity to the FAD site of hAOX1 and characterized the purified enzymes after heterologous expression in Escherichia coli. The hAOX1 variants were characterized carefully by quantitative differences in their ability to produce superoxide radical. ROS represent prominent key molecules in physiological and pathological conditions in the cell. Our data reveal significant alterations in superoxide anion production among the variants. In particular the SNP-based amino acid exchange L438V in proximity to the isoalloxanzine ring of the FAD cofactor resulted in increased rate of superoxide radical production of 75%. Considering the high toxicity of the superoxide in the cell, the hAOX1-L438V SNP variant is an eventual candidate for critical or pathological roles of this natural variant within the human population. Y1 - 2017 U6 - https://doi.org/10.1371/journal.pone.0182061 SN - 1932-6203 VL - 12 SP - 18338 EP - 18347 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Friemel, Martin A1 - Marelja, Zvonimir A1 - Li, Kuanyu A1 - Leimkühler, Silke T1 - The N-Terminus of Iron-Sulfur Cluster Assembly Factor ISD11 Is Crucial for Subcellular Targeting and Interaction with L-Cysteine Desulfurase NFS1 JF - Biochemistry N2 - Assembly of iron sulfur (FeS) clusters is an important process in living cells. The initial sulfur mobilization step for FeS cluster biosynthesis is catalyzed by L-cysteine desulfurase NFS1, a reaction that is localized in mitochondria in humans. In humans, the function of NFS1 depends on the ISD11 protein, which is required to stabilize its structure. The NFS1/ISD11 complex further interacts with scaffold protein ISCU and regulator protein frataxin, thereby forming a quaternary complex for FeS cluster formation. It has been suggested that the role of ISD11 is not restricted to its role in stabilizing the structure of NFS1, because studies of single-amino acid variants of ISD11 additionally demonstrated its importance for the correct assembly of the quaternary complex. In this study, we are focusing on the N-terminal region of ISD11 to determine the role of N-terminal amino acids in the formation of the complex with NFS1 and to reveal the mitochondria) targeting sequence for subcellular localization. Our in vitro studies with the purified proteins and in vivo studies in a cellular system show that the first 10 N-terminal amino acids of ISD11 are indispensable for the activity of NFS1 and especially the conserved "LYR" motif is essential for the role of ISD11 in forming a stable and active complex with NFS1. Y1 - 2017 U6 - https://doi.org/10.1021/acs.biochem.6b01239 SN - 0006-2960 VL - 56 SP - 1797 EP - 1808 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Fuhrmann, Saskia A1 - Kloft, Charlotte A1 - Huisinga, Wilhelm T1 - Impact of altered endogenous IgG on unspecific mAb clearance JF - Journal of pharmacokinetics and pharmacodynamics N2 - Immunodeficient mice are crucial models to evaluate the efficacy of monoclonal antibodies (mAbs). When studying mAb pharmacokinetics (PK), protection from elimination by binding to the neonatal Fc receptor (FcRn) is known to be a major process influencing the unspecific clearance of endogenous and therapeutic IgG. The concentration of endogenous IgG in immunodeficient mice, however is reduced, and this effect on the FcRn protection mechanism and subsequently on unspecific mAb clearance is unknown, yet of great importance for the interpretation of mAb PK data. We used a PBPK modelling approach to elucidate the influence of altered endogenous IgG concentrations on unspecific mAb clearance. To this end, we used PK data in immunodeficient mice, i.e. nude and severe combined immunodeficiency mice. To avoid impact of target-mediated clearance processes, we focussed on mAbs without affinity to a target antigen in these mice. In addition, intravenous immunoglobulin (IVIG) data of immunocompetent mice was used to study the impact of increased total IgG concentrations on unspecific therapeutic antibody clearance. The unspecific clearance is linear, whenever therapeutic IgG concentrations, i.e. mAb and IVIG concentrations are lower than FcRn; it can be non-linear if therapeutic IgG concentrations are larger than FcRn and endogenous IgG concentrations (e.g., under IVIG therapy). Unspecific mAb clearance of immunodeficient mice is effectively linear (under mAb doses as typically used in human). Studying the impact of reduced endogenous IgG concentrations on unspecific mAb clearance is of great relevance for the extrapolation to clinical species, e.g., when predicting mAb PK in immunosuppressed cancer patients. KW - mAb disposition KW - PBPK KW - FcRn salvage mechanism KW - Immunodeficient mice models KW - Unspecific antibody clearance Y1 - 2017 U6 - https://doi.org/10.1007/s10928-017-9524-2 SN - 1567-567X SN - 1573-8744 VL - 44 SP - 351 EP - 374 PB - Springer CY - New York ER - TY - JOUR A1 - Gall, Andrea A1 - Uebel, Udo A1 - Ebensen, Uwe A1 - Hillebrand, Helmut A1 - Meier, Sandra A1 - Singer, Gabriel A1 - Wacker, Alexander A1 - Striebel, Maren T1 - Planktotrons BT - a novel indoor mesocosm facility for aquatic biodiversity and food web research JF - Limnology and oceanography-methods N2 - We established a new indoor mesocosm facility, 12 fully controlled Planktotrons, designed to conduct marine and freshwater experiments for biodiversity and food web approaches using natural or artificial, benthic or planktonic communities. The Planktotrons are a unique and custom-tailored facility allowing long-term experiments. Wall growth can be inhibited by a rotating gate paddle with silicone lips. Additionally, temperature and light intensity are individually controllable for each Planktotron and the large volume (600 L) enables high-frequency or volume-intense measurements. In a pilot freshwater experiment various trophic levels of a pelagic food web were maintained for up to 90 d. First, an artificially assembled phytoplankton community of 11 species was inoculated in all Planktotrons. After 22 d, two ciliates were added to all, and three Daphnia species were added to six Planktotrons. After 72 d, dissolved organic matter (DOM, an alkaline soil extract) was added as an external disturbance to six of the 12 Planktotrons, involving three Planktotrons stocked with Daphnia and three without, respectively. We demonstrate the suitability of the Planktotrons for food web and biodiversity research. Variation among replicated Planktotrons (n=3 minimum) did not differ from other laboratory systems and field experiments. We investigated population dynamics and interactions among the different trophic levels, and found them affected by the sequence of ciliate and Daphnia addition and the disturbance caused by addition of DOM. Y1 - 2017 U6 - https://doi.org/10.1002/lom3.10196 SN - 1541-5856 VL - 15 SP - 663 EP - 677 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - García-Camacho, Raúl A1 - Metz, Johannes A1 - Bilton, Mark C. A1 - Tielboerger, Katja T1 - Phylogenetic structure of annual plant communities along an aridity gradient BT - Interacting effects of habitat filtering and shifting plant-plant interactions JF - Israel Journal of Plant Sciences N2 - The phylogenetic structure of communities (PSC) reveals how evolutionary history affects community assembly processes. However, there are important knowledge gaps on PSC patterns for annual communities and there is a need for studies along environmental gradients in dry ecosystems where several processes shape PSC. Here, we investigated the PSC of annual plants along an aridity gradient in Israel, including eight years, two spatial scales, the effects of shrubs on understory, and the phylogenetic signal of important traits. Increasing drought stress led to overdispersed PSC at the drier end of the gradient, indicating that species were less related than expected by chance. This was supported at a smaller spatial scale, where within the drier sites, communities in open- more arid- habitats were more overdispersed than those under nurse shrubs. Interestingly, some key traits related to drought resistance were not conserved in the phylogeny. Together, our findings suggested that while habitat filtering selected for drought resistance strategies, these strategies evolved independently along multiple contrasting evolutionary lineages. Our comprehensive PSC study provides strong evidence for the interacting effects of habitat filtering and plant- plant interactions, particularly highlighting that the conservative evolution of traits should not be assumed in future interpretations of PSC patterns. KW - Annuals KW - aridity gradient KW - community assembly rules KW - community phylogenetics KW - stress-gradient hypothesis KW - trait phylogenetic conservatism Y1 - 2017 U6 - https://doi.org/10.1080/07929978.2017.1288477 SN - 0792-9978 SN - 2223-8980 VL - 64 IS - 1-2 SP - 122 EP - 134 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Gast, Klaus A1 - Schüler, Anja A1 - Wolff, Martin A1 - Thalhammer, Anja A1 - Berchtold, Harald A1 - Nagel, Norbert A1 - Lenherr, Gudrun A1 - Hauck, Gerrit A1 - Seckler, Robert T1 - Rapid-acting and human insulins BT - Hexamer Dissociation Kinetics upon Dilution of the Pharmaceutical Formulation JF - Pharmaceutical research N2 - Comparison of the dissociation kinetics of rapid-acting insulins lispro, aspart, glulisine and human insulin under physiologically relevant conditions. Dissociation kinetics after dilution were monitored directly in terms of the average molecular mass using combined static and dynamic light scattering. Changes in tertiary structure were detected by near-UV circular dichroism. Glulisine forms compact hexamers in formulation even in the absence of Zn2+. Upon severe dilution, these rapidly dissociate into monomers in less than 10 s. In contrast, in formulations of lispro and aspart, the presence of Zn2+ and phenolic compounds is essential for formation of compact R6 hexamers. These slowly dissociate in times ranging from seconds to one hour depending on the concentration of phenolic additives. The disadvantage of the long dissociation times of lispro and aspart can be diminished by a rapid depletion of the concentration of phenolic additives independent of the insulin dilution. This is especially important in conditions similar to those after subcutaneous injection, where only minor dilution of the insulins occurs. Knowledge of the diverging dissociation mechanisms of lispro and aspart compared to glulisine will be helpful for optimizing formulation conditions of rapid-acting insulins. KW - circular dichroism KW - dissociation kinetics KW - insulin analog KW - light scattering KW - rapid-acting Y1 - 2017 U6 - https://doi.org/10.1007/s11095-017-2233-0 SN - 0724-8741 SN - 1573-904X VL - 34 IS - 795 SP - 2270 EP - 2286 PB - Springer CY - New York ER -