TY - JOUR A1 - Riaño-Pachón, Diego Mauricio A1 - Kleessen, Sabrina A1 - Neigenfind, Jost A1 - Durek, Pawel A1 - Weber, Elke A1 - Engelsberger, Wolfgang R. A1 - Walther, Dirk A1 - Selbig, Joachim A1 - Schulze, Waltraud X. A1 - Kersten, Birgit T1 - Proteome-wide survey of phosphorylation patterns affected by nuclear DNA polymorphisms in Arabidopsis thaliana JF - BMC Genomics N2 - Background: Protein phosphorylation is an important post-translational modification influencing many aspects of dynamic cellular behavior. Site-specific phosphorylation of amino acid residues serine, threonine, and tyrosine can have profound effects on protein structure, activity, stability, and interaction with other biomolecules. Phosphorylation sites can be affected in diverse ways in members of any species, one such way is through single nucleotide polymorphisms (SNPs). The availability of large numbers of experimentally identified phosphorylation sites, and of natural variation datasets in Arabidopsis thaliana prompted us to analyze the effect of non-synonymous SNPs (nsSNPs) onto phosphorylation sites. Results: From the analyses of 7,178 experimentally identified phosphorylation sites we found that: (i) Proteins with multiple phosphorylation sites occur more often than expected by chance. (ii) Phosphorylation hotspots show a preference to be located outside conserved domains. (iii) nsSNPs affected experimental phosphorylation sites as much as the corresponding non-phosphorylated amino acid residues. (iv) Losses of experimental phosphorylation sites by nsSNPs were identified in 86 A. thaliana proteins, among them receptor proteins were overrepresented. These results were confirmed by similar analyses of predicted phosphorylation sites in A. thaliana. In addition, predicted threonine phosphorylation sites showed a significant enrichment of nsSNPs towards asparagines and a significant depletion of the synonymous substitution. Proteins in which predicted phosphorylation sites were affected by nsSNPs (loss and gain), were determined to be mainly receptor proteins, stress response proteins and proteins involved in nucleotide and protein binding. Proteins involved in metabolism, catalytic activity and biosynthesis were less affected. Conclusions: We analyzed more than 7,100 experimentally identified phosphorylation sites in almost 4,300 protein-coding loci in silico, thus constituting the largest phosphoproteomics dataset for A. thaliana available to date. Our findings suggest a relatively high variability in the presence or absence of phosphorylation sites between different natural accessions in receptor and other proteins involved in signal transduction. Elucidating the effect of phosphorylation sites affected by nsSNPs on adaptive responses represents an exciting research goal for the future. KW - Gene Ontology KW - Phosphorylation Site KW - phosphorylated amino acid KW - slim term KW - single nucleotide polymorphism mapping Y1 - 2010 U6 - https://doi.org/10.1186/1471-2164-11-411 SN - 1471-2164 VL - 11 PB - Biomed Central CY - London ER - TY - JOUR A1 - Badalyan, Artavazd A1 - Dierich, Marlen A1 - Stiba, Konstanze A1 - Schwuchow, Viola A1 - Leimkühler, Silke A1 - Wollenberger, Ulla T1 - Electrical wiring of the aldehyde oxidoreductase PaoABC with a polymer containing osmium redox centers BT - biosensors for benzaldehyde and GABA JF - Biosensors N2 - Biosensors for the detection of benzaldehyde and g-aminobutyric acid (GABA) are reported using aldehyde oxidoreductase PaoABC from Escherichia coli immobilized in a polymer containing bound low potential osmium redox complexes. The electrically connected enzyme already electrooxidizes benzaldehyde at potentials below −0.15 V (vs. Ag|AgCl, 1 M KCl). The pH-dependence of benzaldehyde oxidation can be strongly influenced by the ionic strength. The effect is similar with the soluble osmium redox complex and therefore indicates a clear electrostatic effect on the bioelectrocatalytic efficiency of PaoABC in the osmium containing redox polymer. At lower ionic strength, the pH-optimum is high and can be switched to low pH-values at high ionic strength. This offers biosensing at high and low pH-values. A “reagentless” biosensor has been formed with enzyme wired onto a screen-printed electrode in a flow cell device. The response time to addition of benzaldehyde is 30 s, and the measuring range is between 10–150 µM and the detection limit of 5 µM (signal to noise ratio 3:1) of benzaldehyde. The relative standard deviation in a series (n = 13) for 200 µM benzaldehyde is 1.9%. For the biosensor, a response to succinic semialdehyde was also identified. Based on this response and the ability to work at high pH a biosensor for GABA is proposed by coimmobilizing GABA-aminotransferase (GABA-T) and PaoABC in the osmium containing redox polymer. KW - redox polymer KW - aldehyde oxidoreductase KW - ionic strength KW - benzaldehyde KW - GABA KW - biosensor Y1 - 2014 U6 - https://doi.org/10.3390/bios4040403 VL - 4 IS - 4 SP - 403 EP - 421 PB - MDPI CY - Basel ER - TY - JOUR A1 - Pajoro, Alice A1 - Madrigal, Pedro A1 - Muino, Jose M. A1 - Tomas Matus, Jose A1 - Jin, Jian A1 - Mecchia, Martin A. A1 - Debernardi, Juan M. A1 - Palatnik, Javier F. A1 - Balazadeh, Salma A1 - Arif, Muhammad A1 - Wellmer, Frank A1 - Krajewski, Pawel A1 - Riechmann, Jose-Luis A1 - Angenent, Gerco C. A1 - Kaufmann, Kerstin T1 - Dynamics of chromatin accessibility and gene regulation by MADS-domain transcription factors in flower development JF - Genome biology : biology for the post-genomic era N2 - Background: Development of eukaryotic organisms is controlled by transcription factors that trigger specific and global changes in gene expression programs. In plants, MADS-domain transcription factors act as master regulators of developmental switches and organ specification. However, the mechanisms by which these factors dynamically regulate the expression of their target genes at different developmental stages are still poorly understood. Results: We characterized the relationship of chromatin accessibility, gene expression, and DNA binding of two MADS-domain proteins at different stages of Arabidopsis flower development. Dynamic changes in APETALA1 and SEPALLATA3 DNA binding correlated with changes in gene expression, and many of the target genes could be associated with the developmental stage in which they are transcriptionally controlled. We also observe dynamic changes in chromatin accessibility during flower development. Remarkably, DNA binding of APETALA1 and SEPALLATA3 is largely independent of the accessibility status of their binding regions and it can precede increases in DNA accessibility. These results suggest that APETALA1 and SEPALLATA3 may modulate chromatin accessibility, thereby facilitating access of other transcriptional regulators to their target genes. Conclusions: Our findings indicate that different homeotic factors regulate partly overlapping, yet also distinctive sets of target genes in a partly stage-specific fashion. By combining the information from DNA-binding and gene expression data, we are able to propose models of stage-specific regulatory interactions, thereby addressing dynamics of regulatory networks throughout flower development. Furthermore, MADS-domain TFs may regulate gene expression by alternative strategies, one of which is modulation of chromatin accessibility. KW - Flower Development KW - Floral Organ KW - Floral Meristem KW - Chromatin Accessibility KW - Growth Regulate Factor Y1 - 2014 U6 - https://doi.org/10.1186/gb-2014-15-3-r41 SN - 1465-6906 SN - 1474-760X VL - 15 PB - BioMed Central CY - London ER - TY - JOUR A1 - Gamba, Cristina A1 - Jones, Eppie R. A1 - Teasdale, Matthew D. A1 - McLaughlin, Russell L. A1 - González-Fortes, Gloria M. A1 - Mattiangeli, Valeria A1 - Domboroczki, Laszlo A1 - Kovari, Ivett A1 - Pap, Ildiko A1 - Anders, Alexandra A1 - Whittle, Alasdair A1 - Dani, Janos A1 - Raczky, Pal A1 - Higham, Thomas F. G. A1 - Hofreiter, Michael A1 - Bradley, Daniel G. A1 - Pinhasi, Ron T1 - Genome flux and stasis in a five millennium transect of European prehistory JF - Nature Communications N2 - The Great Hungarian Plain was a crossroads of cultural transformations that have shaped European prehistory. Here we analyse a 5,000-year transect of human genomes, sampled from petrous bones giving consistently excellent endogenous DNA yields, from 13 Hungarian Neolithic, Copper, Bronze and Iron Age burials including two to high (similar to 22x) and seven to similar to 1x coverage, to investigate the impact of these on Europe's genetic landscape. These data suggest genomic shifts with the advent of the Neolithic, Bronze and Iron Ages, with interleaved periods of genome stability. The earliest Neolithic context genome shows a European hunter-gatherer genetic signature and a restricted ancestral population size, suggesting direct contact between cultures after the arrival of the first farmers into Europe. The latest, Iron Age, sample reveals an eastern genomic influence concordant with introduced Steppe burial rites. We observe transition towards lighter pigmentation and surprisingly, no Neolithic presence of lactase persistence. Y1 - 2014 U6 - https://doi.org/10.1038/ncomms6257 SN - 2041-1723 VL - 5 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Jones, Eppie R. A1 - González-Fortes, Gloria M. A1 - Connell, Sarah A1 - Siska, Veronika A1 - Eriksson, Anders A1 - Martiniano, Rui A1 - McLaughlin, Russell L. A1 - Llorente, Marcos Gallego A1 - Cassidy, Lara M. A1 - Gamba, Cristina A1 - Meshveliani, Tengiz A1 - Bar-Yosef, Ofer A1 - Mueller, Werner A1 - Belfer-Cohen, Anna A1 - Matskevich, Zinovi A1 - Jakeli, Nino A1 - Higham, Thomas F. G. A1 - Currat, Mathias A1 - Lordkipanidze, David A1 - Hofreiter, Michael A1 - Manica, Andrea A1 - Pinhasi, Ron A1 - Bradley, Daniel G. T1 - Upper Palaeolithic genomes reveal deep roots of modern Eurasians JF - Nature Communications N2 - We extend the scope of European palaeogenomics by sequencing the genomes of Late Upper Palaeolithic (13,300 years old, 1.4-fold coverage) and Mesolithic (9,700 years old, 15.4-fold) males from western Georgia in the Caucasus and a Late Upper Palaeolithic (13,700 years old, 9.5-fold) male from Switzerland. While we detect Late Palaeolithic-Mesolithic genomic continuity in both regions, we find that Caucasus hunter-gatherers (CHG) belong to a distinct ancient clade that split from western hunter-gatherers similar to 45 kya, shortly after the expansion of anatomically modern humans into Europe and from the ancestors of Neolithic farmers similar to 25 kya, around the Last Glacial Maximum. CHG genomes significantly contributed to the Yamnaya steppe herders who migrated into Europe similar to 3,000 BC, supporting a formative Caucasus influence on this important Early Bronze age culture. CHG left their imprint on modern populations from the Caucasus and also central and south Asia possibly marking the arrival of Indo-Aryan languages. Y1 - 2015 U6 - https://doi.org/10.1038/ncomms9912 SN - 2041-1723 VL - 6 PB - Nature Publishing Group CY - London ER - TY - JOUR A1 - Hartmann, Stefanie A1 - Hasenkamp, Natascha A1 - Mayer, Jens A1 - Michaux, Johan A1 - Morand, Serge A1 - Mazzoni, Camila J. A1 - Roca, Alfred L. A1 - Greenwood, Alex D. T1 - Endogenous murine leukemia retroviral variation across wild European and inbred strains of house mouse JF - BMC genomics N2 - Background: Endogenous murine leukemia retroviruses (MLVs) are high copy number proviral elements difficult to comprehensively characterize using standard low throughput sequencing approaches. However, high throughput approaches generate data that is challenging to process, interpret and present. Results: Next generation sequencing (NGS) data was generated for MLVs from two wild caught Mus musculus domesticus (from mainland France and Corsica) and for inbred laboratory mouse strains C3H, LP/J and SJL. Sequence reads were grouped using a novel sequence clustering approach as applied to retroviral sequences. A Markov cluster algorithm was employed, and the sequence reads were queried for matches to specific xenotropic (Xmv), polytropic (Pmv) and modified polytropic (Mpmv) viral reference sequences. Conclusions: Various MLV subtypes were more widespread than expected among the mice, which may be due to the higher coverage of NGS, or to the presence of similar sequence across many different proviral loci. The results did not correlate with variation in the major MLV receptor Xpr1, which can restrict exogenous MLVs, suggesting that endogenous MLV distribution may reflect gene flow more than past resistance to infection. KW - Murine leukemia virus KW - Endogenous retrovirus KW - Xpr1 KW - XMRV KW - Genomic evolution KW - Markov cluster algorithm Y1 - 2015 U6 - https://doi.org/10.1186/s12864-015-1766-z SN - 1471-2164 VL - 16 PB - BioMed Central CY - London ER - TY - JOUR A1 - Berry, Scott A1 - Rosa, Stefanie A1 - Howard, Martin A1 - Buhler, Marc A1 - Dean, Caroline T1 - Disruption of an RNA-binding hinge region abolishes LHP1-mediated epigenetic repression JF - Genes & Development N2 - Epigenetic maintenance of gene repression is essential for development. Polycomb complexes are central to this memory, but many aspects of the underlying mechanism remain unclear. LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) binds Polycomb-deposited H3K27me3 and is required for repression of many Polycomb target genes in Arabidopsis. Here we show that LHP1 binds RNA in vitro through the intrinsically disordered hinge region. By independently perturbing the RNA-binding hinge region and H3K27me3 (trimethylation of histone H3 at Lys27) recognition, we found that both facilitate LHP1 localization and H3K27me3 maintenance. Disruption of the RNAbinding hinge region also prevented formation of subnuclear foci, structures potentially important for epigenetic repression. KW - chromatin KW - epigenetics KW - plant biology KW - Polycomb KW - RNA Y1 - 2017 U6 - https://doi.org/10.1101/gad.305227.117 SN - 0890-9369 SN - 1549-5477 VL - 31 SP - 2115 EP - 2120 PB - Cold Spring Harbor Laboratory Press CY - Cold Spring Harbor, NY 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 - Weithoff, Guntram A1 - Taube, Anne A1 - Bolius, Sarah T1 - The invasion success of the cyanobacterium Cylindrospermopsis raciborskii in experimental mesocosms BT - genetic identity, grazing loss, competition and biotic resistance JF - Aquatic Invasions N2 - The potentially toxic, invasive cyanobacterium Cylindrospermopsis raciborskii, originating from sub-tropical regions, has spread into temperate climate zones in almost all continents. Potential factors in its success are temperature, light and nutrient levels. Grazing losses through zooplankton have been measured in the laboratory but are typically not regarded as a factor in (failed) invasion success. In some potentially suitable lakes, C. raciborskii has never been found, although it is present in water bodies close by. Therefore, we tested the invasive potential of three different isolates introduced into natural plankton communities using laboratory mesocosm experiments under three grazing levels: ambient zooplankton densities, removal of large species using 100 mu m mesh and a ca. doubling of large species. Three C. raciborskii isolates originating from the same geographic region (North-East Germany) were added separately to the four replicates of each treatment and kept in semi-continuous cultures for 21 days. Two isolates disappeared from the mesocosms and were also not viable in filtered lake water indicating that the lake water itself or the switch from culture medium to lake water led to the decay of the inoculated C. raciborskii. Only one out of the three isolates persisted in the plankton communities at a rather low level and only in the treatment without larger zooplankton. This result demonstrates that under potentially suitable environmental conditions, top-down control from zooplankton might hamper the establishment of C. raciborskii. Non-metric multidimensional scaling showed distinct variation in resident phytoplankton communities between the different grazing levels, thus differential grazing impact shaped the resident community in different ways allowing C. raciborskii only to invade under competitive (= low grazing pressure) conditions. Furthermore, even after invasion failure, the temporary presence of C. raciborskii influenced the phytoplankton community. KW - alien species KW - Cyanobacteria KW - competitive resistance KW - consumptive resistance KW - herbivory KW - harmful algae KW - microbial invasion Y1 - 2017 U6 - https://doi.org/10.3391/ai.2017.12.3.07 SN - 1798-6540 SN - 1818-5487 VL - 12 SP - 333 EP - 341 PB - Regional Euro-Asian Biological Invasions centre-reabic CY - Helsinki ER - TY - JOUR A1 - Thomas, Jessica E. A1 - Carvalho, Gary R. A1 - Haile, James A1 - Martin, Michael D. A1 - Castruita, Jose A. Samaniego A1 - Niemann, Jonas A1 - Sinding, Mikkel-Holger S. A1 - Sandoval-Velasco, Marcela A1 - Rawlence, Nicolas J. A1 - Fuller, Errol A1 - Fjeldsa, Jon A1 - Hofreiter, Michael A1 - Stewart, John R. A1 - Gilbert, M. Thomas P. A1 - Knapp, Michael T1 - An ‛Aukward’ tale BT - a genetic approach to discover the whereabouts of the Last Great Auks JF - Genes N2 - One hundred and seventy-three years ago, the last two Great Auks, Pinguinus impennis, ever reliably seen were killed. Their internal organs can be found in the collections of the Natural History Museum of Denmark, but the location of their skins has remained a mystery. In 1999, Great Auk expert Errol Fuller proposed a list of five potential candidate skins in museums around the world. Here we take a palaeogenomic approach to test which—if any—of Fuller’s candidate skins likely belong to either of the two birds. Using mitochondrial genomes from the five candidate birds (housed in museums in Bremen, Brussels, Kiel, Los Angeles, and Oldenburg) and the organs of the last two known individuals, we partially solve the mystery that has been on Great Auk scholars’ minds for generations and make new suggestions as to the whereabouts of the still-missing skin from these two birds. KW - ancient DNA KW - extinct birds KW - mitochondrial genome KW - museum specimens KW - palaeogenomics Y1 - 2017 U6 - https://doi.org/10.3390/genes8060164 SN - 2073-4425 VL - 8 IS - 6 SP - 164 PB - MDPI CY - Basel ER - TY - JOUR A1 - Gisder, Sebastian A1 - Schüler, Vivian A1 - Horchler, Lennart L. A1 - Groth, Detlef A1 - Genersch, Elke T1 - Long-Term Temporal Trends of Nosema spp. Infection Prevalence in Northeast Germany BT - Continuous Spread of Nosema ceranae, an Emerging Pathogen of Honey Bees (Apis mellifera), but No General Replacement of Nosema apis JF - Frontiers in cellular and infection microbiology N2 - The Western honey bee (Apis mellifera) is widely used as commercial pollinator in worldwide agriculture and, therefore, plays an important role in global food security. Among the parasites and pathogens threatening health and survival of honey bees are two species of microsporidia, Nosema apis and Nosema ceranae. Nosema ceranae is considered an emerging pathogen of the Western honey bee. Reports on the spread of N. ceranae suggested that this presumably highly virulent species is replacing its more benign congener N. apis in the global A. mellifera population. We here present a 12 year longitudinal cohort study on the prevalence of N. apis and N. ceranae in Northeast Germany. Between 2005 and 2016, a cohort of about 230 honey bee colonies originating from 23 apiaries was sampled twice a year (spring and autumn) resulting in a total of 5,600 bee samples which were subjected to microscopic and molecular analysis for determining the presence of infections with N. apis or/and N. ceranae. Throughout the entire study period, both N. apis- and N. ceranae-infections could be diagnosed within the cohort. Logistic regression analysis of the prevalence data demonstrated a significant increase of N. ceranae-infections over the last 12 years, both in autumn (reflecting the development during the summer) and in spring (reflecting the development over winter) samples. Cell culture experiments confirmed that N. ceranae has a higher proliferative potential than N. apis at 27. and 33 degrees C potentially explaining the increase in N. ceranae prevalence during summer. In autumn, characterized by generally low infection prevalence, this increase was accompanied by a significant decrease in N. apis- infection prevalence. In contrast, in spring, the season with a higher prevalence of infection, no significant decrease of N. apis infections despite a significant increase in N. ceranae infections could be observed. Therefore, our data do not support a general advantage of N. ceranae over N. apis and an overall replacement of N. apis by N. ceranae in the studied honey bee population. KW - honey bee KW - Apis mellifera KW - Nosema spp. KW - epidemiology KW - replacement Y1 - 2017 U6 - https://doi.org/10.3389/fcimb.2017.00301 SN - 2235-2988 VL - 7 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Paragas, Erickson M. A1 - Humphreys, Sara C. A1 - Min, Joshua A1 - Joswig-Jones, Carolyn A. A1 - Leimkühler, Silke A1 - Jones, Jeffrey P. T1 - ecoAO BT - a simple system for the study of human aldehyde oxidases role in drug metabolism JF - ACS OMEGA N2 - Although aldehyde oxidase (AO) is an important hepatic drug-metabolizing enzyme, it remains understudied and is consequently often overlooked in preclinical studies, an oversight that has resulted in the failure of multiple clinical trials. AO’s preclusion to investigation stems from the following: (1) difficulties synthesizing metabolic standards due to the chemospecificity and regiospecificity of the enzyme and (2) significant inherent variability across existing in vitro systems including liver cytosol, S9 fractions, and primary hepatocytes, which lack specificity and generate discordant expression and activity profiles. Here, we describe a practical bacterial biotransformation system, ecoAO, addressing both issues simultaneously. ecoAO is a cell paste of MoCo-producing Escherichia coli strain TP1017 expressing human AO. It exhibits specific activity toward known substrates, zoniporide, 4-trans-(N,N-dimethylamino)cinnamaldehyde, O6-benzylguanine, and zaleplon; it also has utility as a biocatalyst, yielding milligram quantities of synthetically challenging metabolite standards such as 2-oxo-zoniporide. Moreover, ecoAO enables routine determination of kcat and V/K, which are essential parameters for accurate in vivo clearance predictions. Furthermore, ecoAO has potential as a preclinical in vitro screening tool for AO activity, as demonstrated by its metabolism of 3-aminoquinoline, a previously uncharacterized substrate. ecoAO promises to provide easy access to metabolites with the potential to improve pharmacokinetic clearance predictions and guide drug development. Y1 - 2017 U6 - https://doi.org/10.1021/acsomega.7b01054 SN - 2470-1343 VL - 2 SP - 4820 EP - 4827 PB - American Chemical Society CY - Washington 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 - Lämke, Jörn A1 - Bäurle, Isabel T1 - Epigenetic and chromatin-based mechanisms in environmental stress adaptation and stress memory in plants JF - Genome biology : biology for the post-genomic era N2 - Plants frequently have to weather both biotic and abiotic stressors, and have evolved sophisticated adaptation and defense mechanisms. In recent years, chromatin modifications, nucleosome positioning, and DNA methylation have been recognized as important components in these adaptations. Given their potential epigenetic nature, such modifications may provide a mechanistic basis for a stress memory, enabling plants to respond more efficiently to recurring stress or even to prepare their offspring for potential future assaults. In this review, we discuss both the involvement of chromatin in stress responses and the current evidence on somatic, intergenerational, and transgenerational stress memory. KW - remodeling atpase brahma KW - transcriptional memory KW - DNA methylation KW - transgenerational inheritance KW - acquired thermotolerance KW - Arabidopsis-thaliana KW - gene-expression KW - responses KW - protein KW - defense Y1 - 2017 U6 - https://doi.org/10.1186/s13059-017-1263-6 SN - 1474-760X VL - 18 SP - 8685 EP - 8693 PB - BioMed Central CY - London ER - TY - JOUR A1 - Hentrich, Doreen A1 - Tauer, Klaus A1 - Espanol, Montserrat A1 - Ginebra, Maria-Pau A1 - Taubert, Andreas T1 - EDTA and NTA effectively tune the mineralization of calcium phosphate from bulk aqueous solution JF - Biomimetics N2 - This study describes the effects of nitrilotriacetic acid (NTA) and ethylenediaminotetraacetic acid (EDTA) on themineralization of calciumphosphate from bulk aqueous solution. Mineralization was performed between pH 6 and 9 and with NTA or EDTA concentrations of 0, 5, 10, and 15 mM. X-ray diffraction and infrared spectroscopy show that at low pH, mainly brushite precipitates and at higher pH, mostly hydroxyapatite forms. Both additives alter the morphology of the precipitates. Without additive, brushite precipitates as large plates. With NTA, the morphology changes to an unusual rod-like shape. With EDTA, the edges of the particles are rounded and disk-like particles form. Conductivity and pH measurements suggest that the final products form through several intermediate steps. KW - biomineralization KW - biomimetic mineralization KW - calcium phosphate KW - NTA KW - EDTA KW - precipitation KW - brushite KW - hydroxyapatite Y1 - 2017 U6 - https://doi.org/10.3390/biomimetics2040024 SN - 2313-7673 VL - 2 IS - 4 PB - MDPI CY - Basel ER - TY - JOUR A1 - Zimmermann, Heike Hildegard A1 - Raschke, Elena A1 - Epp, Laura Saskia A1 - Stoof-Leichsenring, Kathleen Rosemarie A1 - Schirrmeister, Lutz A1 - Schwamborn, Georg A1 - Herzschuh, Ulrike T1 - The history of tree and shrub taxa on Bol'shoy Lyakhovsky Island (New Siberian Archipelago) since the Last Interglacial Uncovered by Sedimentary Ancient DNA and Pollen Data JF - Genes N2 - Ecosystem boundaries, such as the Arctic-Boreal treeline, are strongly coupled with climate and were spatially highly dynamic during past glacial-interglacial cycles. Only a few studies cover vegetation changes since the last interglacial, as most of the former landscapes are inundated and difficult to access. Using pollen analysis and sedimentary ancient DNA (sedaDNA) metabarcoding, we reveal vegetation changes on Bol’shoy Lyakhovsky Island since the last interglacial from permafrost sediments. Last interglacial samples depict high levels of floral diversity with the presence of trees (Larix, Picea, Populus) and shrubs (Alnus, Betula, Ribes, Cornus, Saliceae) on the currently treeless island. After the Last Glacial Maximum, Larix re-colonised the island but disappeared along with most shrub taxa. This was probably caused by Holocene sea-level rise, which led to increased oceanic conditions on the island. Additionally, we applied two newly developed larch-specific chloroplast markers to evaluate their potential for tracking past population dynamics from environmental samples. The novel markers were successfully re-sequenced and exhibited two variants of each marker in last interglacial samples. SedaDNA can track vegetation changes as well as genetic changes across geographic space through time and can improve our understanding of past processes that shape modern patterns. KW - sedaDNA KW - metabarcoding KW - trnL KW - single-nucleotide polymorphism (SNP) KW - treeline KW - MIS 5 to 1 KW - permafrost deposits KW - radiocarbon ages KW - palaeoenvironment KW - Larix Y1 - 2017 U6 - https://doi.org/10.3390/genes8100273 SN - 2073-4425 VL - 8 IS - 10 SP - 273 PB - MDPI CY - Basel ER - TY - JOUR A1 - Wurzbacher, Christian A1 - Fuchs, Andrea A1 - Attermeyer, Katrin A1 - Frindte, Katharina A1 - Grossart, Hans-Peter A1 - Hupfer, Michael A1 - Casper, Peter A1 - Monaghan, Michael T. T1 - Shifts among Eukaryota, Bacteria, and Archaea define the vertical organization of a lake sediment JF - Microbiome N2 - Background: Lake sediments harbor diverse microbial communities that cycle carbon and nutrients while being constantly colonized and potentially buried by organic matter sinking from the water column. The interaction of activity and burial remained largely unexplored in aquatic sediments. We aimed to relate taxonomic composition to sediment biogeochemical parameters, test whether community turnover with depth resulted from taxonomic replacement or from richness effects, and to provide a basic model for the vertical community structure in sediments. Methods: We analyzed four replicate sediment cores taken from 30-m depth in oligo-mesotrophic Lake Stechlin in northern Germany. Each 30-cm core spanned ca. 170 years of sediment accumulation according to Cs-137 dating and was sectioned into layers 1-4 cm thick. We examined a full suite of biogeochemical parameters and used DNA metabarcoding to examine community composition of microbial Archaea, Bacteria, and Eukaryota. Results: Community beta-diversity indicated nearly complete turnover within the uppermost 30 cm. We observed a pronounced shift from Eukaryota- and Bacteria-dominated upper layers (<5 cm) to Bacteria-dominated intermediate layers (5-14 cm) and to deep layers (>14 cm) dominated by enigmatic Archaea that typically occur in deep-sea sediments. Taxonomic replacement was the prevalent mechanism in structuring the community composition and was linked to parameters indicative of microbial activity (e.g., CO2 and CH4 concentration, bacterial protein production). Richness loss played a lesser role but was linked to conservative parameters (e.g., C, N, P) indicative of past conditions. Conclusions: By including all three domains, we were able to directly link the exponential decay of eukaryotes with the active sediment microbial community. The dominance of Archaea in deeper layers confirms earlier findings from marine systems and establishes freshwater sediments as a potential low-energy environment, similar to deep sea sediments. We propose a general model of sediment structure and function based on microbial characteristics and burial processes. An upper "replacement horizon" is dominated by rapid taxonomic turnover with depth, high microbial activity, and biotic interactions. A lower "depauperate horizon" is characterized by low taxonomic richness, more stable "low-energy" conditions, and a dominance of enigmatic Archaea. KW - Archaea KW - Eukaryota KW - Bacteria KW - Community KW - Freshwater KW - Lake KW - DNA metabarcoding KW - Beta-diversity KW - Sediment KW - Turnover Y1 - 2017 U6 - https://doi.org/10.1186/s40168-017-0255-9 SN - 2049-2618 VL - 5 PB - BioMed Central CY - London 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 - Reil, Daniela A1 - Rosenfeld, Ulrike A1 - Imholt, Christian A1 - Schmidt, Sabrina A1 - Ulrich, Rainer G. A1 - Eccard, Jana A1 - Jacob, Jens T1 - Puumala hantavirus infections in bank vole populations BT - host and virus dynamics in Central Europe JF - BMC ecology N2 - Background In Europe, bank voles (Myodes glareolus) are widely distributed and can transmit Puumala virus (PUUV) to humans, which causes a mild to moderate form of haemorrhagic fever with renal syndrome, called nephropathia epidemica. Uncovering the link between host and virus dynamics can help to prevent human PUUV infections in the future. Bank voles were live trapped three times a year in 2010–2013 in three woodland plots in each of four regions in Germany. Bank vole population density was estimated and blood samples collected to detect PUUV specific antibodies. Results We demonstrated that fluctuation of PUUV seroprevalence is dependent not only on multi-annual but also on seasonal dynamics of rodent host abundance. Moreover, PUUV infection might affect host fitness, because seropositive individuals survived better from spring to summer than uninfected bank voles. Individual space use was independent of PUUV infections. Conclusions Our study provides robust estimations of relevant patterns and processes of the dynamics of PUUV and its rodent host in Central Europe, which are highly important for the future development of predictive models for human hantavirus infection risk KW - Myodes glareolus KW - Population dynamics KW - Puumala virus seroprevalence KW - Space use KW - Survival Y1 - 2017 U6 - https://doi.org/10.1186/s12898-017-0118-z SN - 1472-6785 VL - 17 PB - BioMed Central CY - London ER - TY - JOUR A1 - Möser, Christin A1 - Lorenz, Jessica S. A1 - Sajfutdinow, Martin A1 - Smith, David M. T1 - Pinpointed Stimulation of EphA2 Receptors via DNA-Templated Oligovalence JF - International journal of molecular sciences N2 - DNA nanostructures enable the attachment of functional molecules to nearly any unique location on their underlying structure. Due to their single-base-pair structural resolution, several ligands can be spatially arranged and closely controlled according to the geometry of their desired target, resulting in optimized binding and/or signaling interactions. Here, the efficacy of SWL, an ephrin-mimicking peptide that binds specifically to EphrinA2 (EphA2) receptors, increased by presenting up to three of these peptides on small DNA nanostructures in an oligovalent manner. Ephrin signaling pathways play crucial roles in tumor development and progression. Moreover, Eph receptors are potential targets in cancer diagnosis and treatment. Here, the quantitative impact of SWL valency on binding, phosphorylation (key player for activation) and phenotype regulation in EphA2-expressing prostate cancer cells was demonstrated. EphA2 phosphorylation was significantly increased by DNA trimers carrying three SWL peptides compared to monovalent SWL. In comparison to one of EphA2’s natural ligands ephrin-A1, which is known to bind promiscuously to multiple receptors, pinpointed targeting of EphA2 by oligovalent DNA-SWL constructs showed enhanced cell retraction. Overall, we show that DNA scaffolds can increase the potency of weak signaling peptides through oligovalent presentation and serve as potential tools for examination of complex signaling pathways. KW - DNA nanostructure KW - ephrin KW - EphA2 KW - SWL KW - PC-3 cells KW - multivalence Y1 - 2018 U6 - https://doi.org/10.3390/ijms19113482 SN - 1422-0067 VL - 19 IS - 11 PB - MDPI CY - Basel ER - TY - JOUR A1 - Schwanhold, Nadine A1 - Iobbi-Nivol, Chantal A1 - Lehmann, Angelika A1 - Leimkühler, Silke T1 - Same but different BT - Comparison of two system-specific molecular chaperones for the maturation of formate dehydrogenases JF - PLoS one N2 - The maturation of bacterial molybdoenzymes is a complex process leading to the insertion of the bulky bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor into the apoenzyme. Most molybdoenzymes were shown to contain a specific chaperone for the insertion of the bis-MGD cofactor. Formate dehydrogenases (FDH) together with their molecular chaperone partner seem to display an exception to this specificity rule, since the chaperone FdhD has been proven to be involved in the maturation of all three FDH enzymes present in Escherichia colt. Multiple roles have been suggested for FdhD-like chaperones in the past, including the involvement in a sulfur transfer reaction from the L-cysteine desulfurase IscS to bis-MGD by the action of two cysteine residues present in a conserved CXXC motif of the chaperones. However, in this study we show by phylogenetic analyses that the CXXC motif is not conserved among FdhD-like chaperones. We compared in detail the FdhD-like homologues from Rhodobacter capsulatus and E. colt and show that their roles in the maturation of FDH enzymes from different subgroups can be exchanged. We reveal that bis-MGDbinding is a common characteristic of FdhD-like proteins and that the cofactor is bound with a sulfido-ligand at the molybdenum atom to the chaperone. Generally, we reveal that the cysteine residues in the motif CXXC of the chaperone are not essential for the production of active FDH enzymes. Y1 - 2018 U6 - https://doi.org/10.1371/journal.pone.0201935 SN - 1932-6203 VL - 13 IS - 11 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Kruse, Julia A1 - Kummer, Volker A1 - Shivas, Roger G. A1 - Thines, Marco T1 - The first smut fungus, Thecaphora anthemidis sp nov (Glomosporiaceae), described from Anthemis (Asteraceae) JF - MycoKeys N2 - There are 63 known species of Thecaphora (Glomosporiaceae, Ustilaginomycotina), a third of which occur on Asteraceae. These smut fungi produce yellowish-brown to reddish-brown masses of spore balls in specific, mostly regenerative, plant organs. A species of Thecaphora was collected in the flower heads of Anthemis chia (Anthemideae, Asteraceae) on Rhodes Island, Greece, in 2015 and 2017, which represents the first smut record of a smut fungus on a host plant species in this tribe. Based on its distinctive morphology, host species and genetic divergence, this species is described as Thecaphora anthemidis sp. nov. Molecular barcodes of the ITS region are provided for this and several other species of Thecaphora. A phylogenetic and morphological comparison to closely related species showed that Th. anthemidis differed from other species of Thecaphora. Thecaphora anthemidis produced loose spore balls in the flower heads and peduncles of Anthemis chia unlike other flower-infecting species. KW - Glomosporiaceae KW - host specificity KW - internal transcribed spacer KW - molecular phylogenetics KW - smut fungi Y1 - 2018 U6 - https://doi.org/10.3897/mycokeys.41.28454 SN - 1314-4057 SN - 1314-4049 IS - 41 SP - 39 EP - 50 PB - Pensoft Publ. CY - Sofia ER - TY - JOUR A1 - Otto, Nils A1 - Marelja, Zvonimir A1 - Schoofs, Andreas A1 - Kranenburg, Holger A1 - Bittern, Jonas A1 - Yildirim, Kerem A1 - Berh, Dimitri A1 - Bethke, Maria A1 - Thomas, Silke A1 - Rode, Sandra A1 - Risse, Benjamin A1 - Jiang, Xiaoyi A1 - Pankratz, Michael A1 - Leimkühler, Silke A1 - Klämbt, Christian T1 - The sulfite oxidase Shopper controls neuronal activity by regulating glutamate homeostasis in Drosophila ensheathing glia JF - Nature Communications N2 - Specialized glial subtypes provide support to developing and functioning neural networks. Astrocytes modulate information processing by neurotransmitter recycling and release of neuromodulatory substances, whereas ensheathing glial cells have not been associated with neuromodulatory functions yet. To decipher a possible role of ensheathing glia in neuronal information processing, we screened for glial genes required in the Drosophila central nervous system for normal locomotor behavior. Shopper encodes a mitochondrial sulfite oxidase that is specifically required in ensheathing glia to regulate head bending and peristalsis. shopper mutants show elevated sulfite levels affecting the glutamate homeostasis which then act on neuronal network function. Interestingly, human patients lacking the Shopper homolog SUOX develop neurological symptoms, including seizures. Given an enhanced expression of SUOX by oligodendrocytes, our findings might indicate that in both invertebrates and vertebrates more than one glial cell type may be involved in modulating neuronal activity. Y1 - 2018 U6 - https://doi.org/10.1038/s41467-018-05645-z SN - 2041-1723 VL - 9 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Biterova, Ekaterina A1 - Esmaeeli Moghaddam Tabalvandani, Mariam A1 - Alanen, Heli I. A1 - Saaranen, Mirva A1 - Ruddock, Lloyd W. T1 - Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease JF - Scientific reports N2 - Coronary artery disease is the most common cause of death globally and is linked to a number of risk factors including serum low density lipoprotein, high density lipoprotein, triglycerides and lipoprotein(a). Recently two proteins, angiopoietin-like protein 3 and 4, have emerged from genetic studies as being factors that significantly modulate plasma triglyceride levels and coronary artery disease. The exact function and mechanism of action of both proteins remains to be elucidated, however, mutations in these proteins results in up to 34% reduction in coronary artery disease and inhibition of function results in reduced plasma triglyceride levels. Here we report the crystal structures of the fibrinogen-like domains of both proteins. These structures offer new insights into the reported loss of function mutations, the mechanisms of action of the proteins and open up the possibility for the rational design of low molecular weight inhibitors for intervention in coronary artery disease. Y1 - 2018 U6 - https://doi.org/10.1038/s41598-018-25237-7 SN - 2045-2322 VL - 8 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Dunsing, Valentin A1 - Luckner, Madlen A1 - Zuehlke, Boris A1 - Petazzi, Roberto Arturo A1 - Herrmann, Andreas A1 - Chiantia, Salvatore T1 - Optimal fluorescent protein tags for quantifying protein oligomerization in living cells JF - Scientific reports N2 - Fluorescence fluctuation spectroscopy has become a popular toolbox for non-disruptive analysis of molecular interactions in living cells. The quantification of protein oligomerization in the native cellular environment is highly relevant for a detailed understanding of complex biological processes. An important parameter in this context is the molecular brightness, which serves as a direct measure of oligomerization and can be easily extracted from temporal or spatial fluorescence fluctuations. However, fluorescent proteins (FPs) typically used in such studies suffer from complex photophysical transitions and limited maturation, inducing non-fluorescent states. Here, we show how these processes strongly affect molecular brightness measurements. We perform a systematic characterization of non-fluorescent states for commonly used FPs and provide a simple guideline for accurate, unbiased oligomerization measurements in living cells. Further, we focus on novel red FPs and demonstrate that mCherry2, an mCherry variant, possesses superior properties with regards to precise quantification of oligomerization. Y1 - 2018 U6 - https://doi.org/10.1038/s41598-018-28858-0 SN - 2045-2322 VL - 8 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Zwickel, Theresa A1 - Kahl, Sandra M. A1 - Rychlik, Michael A1 - Müller, Marina E. H. T1 - Chemotaxonomy of Mycotoxigenic Small-Spored Alternaria Fungi BT - Do Multitoxin Mixtures Act as an Indicator for Species Differentiation? JF - Frontiers in microbiology N2 - Necrotrophic as well as saprophytic small-spored Altemaria (A.) species are annually responsible for major losses of agricultural products, such as cereal crops, associated with the contamination of food and feedstuff with potential health-endangering Altemaria toxins. Knowledge of the metabolic capabilities of different species-groups to form mycotoxins is of importance for a reliable risk assessment. 93 Altemaria strains belonging to the four species groups Alternaria tenuissima, A. arborescens, A. altemata, and A. infectoria were isolated from winter wheat kernels harvested from fields in Germany and Russia and incubated under equal conditions. Chemical analysis by means of an HPLC-MS/MS multi-Alternaria-toxin-method showed that 95% of all strains were able to form at least one of the targeted 17 non-host specific Altemaria toxins. Simultaneous production of up to 15 (modified) Altemaria toxins by members of the A. tenuissima, A. arborescens, A. altemata species-groups and up to seven toxins by A. infectoria strains was demonstrated. Overall tenuazonic acid was the most extensively formed mycotoxin followed by alternariol and alternariol mono methylether, whereas altertoxin I was the most frequently detected toxin. Sulfoconjugated modifications of alternariol, alternariol mono methylether, altenuisol and altenuene were frequently determined. Unknown perylene quinone derivatives were additionally detected. Strains of the species-group A. infectoria could be segregated from strains of the other three species-groups due to significantly lower toxin levels and the specific production of infectopyrone. Apart from infectopyrone, alterperylenol was also frequently produced by 95% of the A. infectoria strains. Neither by the concentration nor by the composition of the targeted Altemaria toxins a differentiation between the species-groups A. altemata, A. tenuissima and A. arborescens was possible. KW - small-spored Alternaria fungi KW - Alternaria species-groups KW - Alternaria mycotoxins KW - chemotaxonomy KW - secondary metabolite profiling KW - LC-MS/MS KW - wheat KW - perylene quinone derivatives Y1 - 2018 U6 - https://doi.org/10.3389/fmicb.2018.01368 SN - 1664-302X VL - 9 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Heger, Tina A1 - Nikles, Gabriele A1 - Jacobs, Brooke S. T1 - Differentiation in native as well as introduced ranges BT - germination reflects mean and variance in cover of surrounding vegetation JF - AoB PLANTS N2 - Germination, a crucial phase in the life cycle of a plant, can be significantly influenced by competition and facilitation. The aim of this study was to test whether differences in cover of surrounding vegetation can lead to population differentiation in germination behaviour of an annual grassland species, and if so, whether such a differentiation can be found in the native as well as in the introduced range. We used maternal progeny of Erodium cicutarium previously propagated under uniform conditions that had been collected in multiple populations in the native and two introduced ranges, in populations representing extremes in terms of mean and variability of the cover of surrounding vegetation. In the first experiment, we tested the effect of germination temperature and mean cover at the source site on germination, and found interlinked effects of these factors. In seeds from one of the introduced ranges (California), we found indication for a 2-fold dormancy, hindering germination at high temperatures even if physical dormancy was broken and water was available. This behaviour was less strong in high cover populations, indicating cross-generational facilitating effects of dense vegetation. In the second experiment, we tested whether spatial variation in cover of surrounding vegetation has an effect on the proportion of dormant seeds. Contrary to our expectations, we found that across source regions, high variance in cover was associated with higher proportions of seeds germinating directly after storage. In all three regions, germination seemed to match the local environment in terms of climate and vegetation cover. We suggest that this is due to a combined effect of introduction of preadapted genotypes and local evolutionary processes. KW - Bet-hedging KW - competition KW - eco-evolutionary experience KW - facilitation KW - genetic adaptation KW - physical and physiological dormancy KW - preadaptation Y1 - 2018 U6 - https://doi.org/10.1093/aobpla/ply009 SN - 2041-2851 VL - 10 IS - 1 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Käch, Heidi A1 - Mathe-Hubert, Hugo A1 - Dennis, Alice B. A1 - Vorburger, Christoph T1 - Rapid evolution of symbiont-mediated resistance compromises biological control of aphids by parasitoids JF - Evolutionary applications N2 - There is growing interest in biological control as a sustainable and environmentally friendly way to control pest insects. Aphids are among the most detrimental agricultural pests worldwide, and parasitoid wasps are frequently employed for their control. The use of asexual parasitoids may improve the effectiveness of biological control because only females kill hosts and because asexual populations have a higher growth rate than sexuals. However, asexuals may have a reduced capacity to track evolutionary change in their host populations. We used a factorial experiment to compare the ability of sexual and asexual populations of the parasitoid Lysiphlebus fabarum to control caged populations of black bean aphids (Aphis fabae) of high and low clonal diversity. The aphids came from a natural population, and one-third of the aphid clones harbored Hamiltonella defensa, a heritable bacterial endosymbiont that increases resistance to parasitoids. We followed aphid and parasitoid population dynamics for 3months but found no evidence that the reproductive mode of parasitoids affected their effectiveness as biocontrol agents, independent of host clonal diversity. Parasitoids failed to control aphids in most cases, because their introduction resulted in strong selection for clones protected by H.defensa. The increasingly resistant aphid populations escaped control by parasitoids, and we even observed parasitoid extinctions in many cages. The rapid evolution of symbiont-conferred resistance in turn imposed selection on parasitoids. In cages where asexual parasitoids persisted until the end of the experiment, they became dominated by a single genotype able to overcome the protection provided by H.defensa. Thus, there was evidence for parasitoid counteradaptation, but it was generally too slow for parasitoids to regain control over aphid populations. It appears that when pest aphids possess defensive symbionts, the presence of parasitoid genotypes able to overcome symbiont-conferred resistance is more important for biocontrol success than their reproductive mode. KW - aphids KW - Aphis fabae KW - biological control KW - defensive symbiosis KW - Hamiltonella defensa KW - Lysiphlebus fabarum KW - parasitoid KW - resistance Y1 - 2018 U6 - https://doi.org/10.1111/eva.12532 SN - 1752-4571 VL - 11 IS - 2 SP - 220 EP - 230 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Shi, Jun A1 - Joshi, Jasmin Radha A1 - Tielboerger, Katja A1 - Verhoeven, Koen J. F. A1 - Macel, Mirka T1 - Costs and benefits of admixture between foreign genotypes and local populations in the field JF - Ecology and evolution N2 - Admixture is the hybridization between populations within one species. It can increase plant fitness and population viability by alleviating inbreeding depression and increasing genetic diversity. However, populations are often adapted to their local environments and admixture with distant populations could break down local adaptation by diluting the locally adapted genomes. Thus, admixed genotypes might be selected against and be outcompeted by locally adapted genotypes in the local environments. To investigate the costs and benefits of admixture, we compared the performance of admixed and within-population F1 and F2 generations of the European plant Lythrum salicaria in a reciprocal transplant experiment at three European field sites over a 2-year period. Despite strong differences between site and plant populations for most of the measured traits, including herbivory, we found limited evidence for local adaptation. The effects of admixture depended on experimental site and plant population, and were positive for some traits. Plant growth and fruit production of some populations increased in admixed offspring and this was strongest with larger parental distances. These effects were only detected in two of our three sites. Our results show that, in the absence of local adaptation, admixture may boost plant performance, and that this is particularly apparent in stressful environments. We suggest that admixture between foreign and local genotypes can potentially be considered in nature conservation to restore populations and/or increase population viability, especially in small inbred or maladapted populations. KW - heterosis KW - inbreeding depression KW - local adaptation KW - Lythrum salicaria KW - outbreeding depression Y1 - 2018 U6 - https://doi.org/10.1002/ece3.3946 SN - 2045-7758 VL - 8 IS - 7 SP - 3675 EP - 3684 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Bukowski, Alexandra R. A1 - Schittko, Conrad A1 - Petermann, Jana S. T1 - The strength of negative plant-soil feedback increases from the intraspecific to the interspecific and the functional group level JF - Ecology and evolution N2 - One of the processes that may play a key role in plant species coexistence and ecosystem functioning is plant-soil feedback, the effect of plants on associated soil communities and the resulting feedback on plant performance. Plant-soil feedback at the interspecific level (comparing growth on own soil with growth on soil from different species) has been studied extensively, while plant-soil feedback at the intraspecific level (comparing growth on own soil with growth on soil from different accessions within a species) has only recently gained attention. Very few studies have investigated the direction and strength of feedback among different taxonomic levels, and initial results have been inconclusive, discussing phylogeny, and morphology as possible determinants. To test our hypotheses that the strength of negative feedback on plant performance increases with increasing taxonomic level and that this relationship is explained by morphological similarities, we conducted a greenhouse experiment using species assigned to three taxonomic levels (intraspecific, interspecific, and functional group level). We measured certain fitness-related aboveground traits and used them along literature-derived traits to determine the influence of morphological similarities on the strength and direction of the feedback. We found that the average strength of negative feedback increased from the intraspecific over the interspecific to the functional group level. However, individual accessions and species differed in the direction and strength of the feedback. None of our results could be explained by morphological dissimilarities or individual traits. Synthesis. Our results indicate that negative plant-soil feedback is stronger if the involved plants belong to more distantly related species. We conclude that the taxonomic level is an important factor in the maintenance of plant coexistence with plant-soil feedback as a potential stabilizing mechanism and should be addressed explicitly in coexistence research, while the traits considered here seem to play a minor role. KW - Arabidopsis thaliana Col-0 KW - home-away effect KW - intraspecific diversity KW - morphological similarities KW - dissimilarities of plants KW - plant-soil (belowground) interactions KW - species coexistence KW - taxonomic levels KW - trait measurements Y1 - 2018 U6 - https://doi.org/10.1002/ece3.3755 SN - 2045-7758 VL - 8 IS - 4 SP - 2280 EP - 2289 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Küçükgöze, Gökhan A1 - Leimkühler, Silke T1 - Direct comparison of the four aldehyde oxidase enzymes present in mouse gives insight into their substrate specificities JF - PLOS ONE N2 - Mammalian aldehyde oxidases (AOXs) are molybdo-flavoenzymes which are present in many tissues in various mammalian species, including humans and rodents. Different species contain a different number of AOX isoforms. In particular, the reasons why mammals other than humans express a multiplicity of tissue-specific AOX enzymes is unknown. In mouse, the isoforms mAOX1, mAOX3, mAOX4 and mAOX2 are present. We previously established a codon-optimized heterologous expression systems for the mAOX1-4 isoforms in Escherichia coli that gives yield to sufficient amounts of active protein for kinetic characterizations and sets the basis in this study for site-directed mutagenesis and structure-function studies. A direct and simultaneous comparison of the enzymatic properties and characteristics of the four enzymes on a larger number of substrates has never been performed. Here, thirty different structurally related aromatic, aliphatic and N-heterocyclic compounds were used as substrates, and the kinetic parameters of all four mAOX enzymes were directly compared. The results show that especially mAOX4 displays a higher substrate selectivity, while no major differences between mAOX1, mAOX2 and mAOX3 were identified. Generally, mAOX1 was the enzyme with the highest catalytic turnover for most substrates. To understand the factors that contribute to the substrate specificity of mAOX4, site-directed mutagenesis was applied to substitute amino acids in the substrate-binding funnel by the ones present in mAOX1, mAOX3, and mAOX2. An increase in activity was obtained by the amino acid exchange M1088V in the active site identified to be specific for mAOX4, to the amino acid identified in mAOX3. Y1 - 2018 U6 - https://doi.org/10.1371/journal.pone.0191819 SN - 1932-6203 VL - 13 IS - 1 PB - Public Library of Science CY - San Fransisco ER - TY - JOUR A1 - Senczuk, Gabriele A1 - Havenstein, Katja A1 - Milana, Valentina A1 - Ripa, Chiara A1 - De Simone, Emanuela A1 - Tiedemann, Ralph A1 - Castiglia, Riccardo T1 - Spotlight on islands BT - on the origin and diversification of an ancient lineage of the Italian wall lizard Podarcis siculus in the western Pontine Islands JF - Scientific reports N2 - Groups of proximate continental islands may conceal more tangled phylogeographic patterns than oceanic archipelagos as a consequence of repeated sea level changes, which allow populations to experience gene flow during periods of low sea level stands and isolation by vicariant mechanisms during periods of high sea level stands. Here, we describe for the first time an ancient and diverging lineage of the Italian wall lizard Podarcis siculus from the western Pontine Islands. We used nuclear and mitochondrial DNA sequences of 156 individuals with the aim of unraveling their phylogenetic position, while microsatellite loci were used to test several a priori insular biogeographic models of migration with empirical data. Our results suggest that the western Pontine populations colonized the islands early during their Pliocene volcanic formation, while populations from the eastern Pontine Islands seem to have been introduced recently. The inter-island genetic makeup indicates an important role of historical migration, probably due to glacial land bridges connecting islands followed by a recent vicariant mechanism of isolation. Moreover, the most supported migration model predicted higher gene flow among islands which are geographically arranged in parallel. Considering the threatened status of small insular endemic populations, we suggest this new evolutionarily independent unit be given priority in conservation efforts. Y1 - 2018 U6 - https://doi.org/10.1038/s41598-018-33326-w SN - 2045-2322 VL - 8 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Pitzen, Valentin A1 - Askarzada, Sophie A1 - Gräf, Ralph A1 - Meyer, Irene T1 - CDK5RAP2 Is an Essential Scaffolding Protein of the Corona of the Dictyostelium Centrosome JF - Cells N2 - Dictyostelium centrosomes consist of a nucleus-associated cylindrical, three-layered core structure surrounded by a corona consisting of microtubule-nucleation complexes embedded in a scaffold of large coiled-coil proteins. One of them is the conserved CDK5RAP2 protein. Here we focus on the role of Dictyostelium CDK5RAP2 for maintenance of centrosome integrity, its interaction partners and its dynamic behavior during interphase and mitosis. GFP-CDK5RAP2 is present at the centrosome during the entire cell cycle except from a short period during prophase, correlating with the normal dissociation of the corona at this stage. RNAi depletion of CDK5RAP2 results in complete disorganization of centrosomes and microtubules suggesting that CDK5RAP2 is required for organization of the corona and its association to the core structure. This is in line with the observation that overexpressed GFP-CDK5RAP2 elicited supernumerary cytosolic MTOCs. The phenotype of CDK5RAP2 depletion was very reminiscent of that observed upon depletion of CP148, another scaffolding protein of the corona. BioID interaction assays revealed an interaction of CDK5RAP2 not only with the corona markers CP148, gamma-tubulin, and CP248, but also with the core components Cep192, CP75, and CP91. Furthermore, protein localization studies in both depletion strains revealed that CP148 and CDK5RAP2 cooperate in corona organization. KW - centrosome KW - centriole KW - Dictyostelium KW - microtubules KW - mitosis Y1 - 2018 U6 - https://doi.org/10.3390/cells7040032 SN - 2073-4409 VL - 7 IS - 4 PB - MDPI CY - Basel ER - TY - JOUR A1 - van Velzen, Ellen A1 - Gaedke, Ursula T1 - Reversed predator-prey cycles are driven by the amplitude of prey oscillations JF - Ecology and evolution N2 - Ecoevolutionary feedbacks in predator-prey systems have been shown to qualitatively alter predator-prey dynamics. As a striking example, defense-offense coevolution can reverse predator-prey cycles, so predator peaks precede prey peaks rather than vice versa. However, this has only rarely been shown in either model studies or empirical systems. Here, we investigate whether this rarity is a fundamental feature of reversed cycles by exploring under which conditions they should be found. For this, we first identify potential conditions and parameter ranges most likely to result in reversed cycles by developing a new measure, the effective prey biomass, which combines prey biomass with prey and predator traits, and represents the prey biomass as perceived by the predator. We show that predator dynamics always follow the dynamics of the effective prey biomass with a classic 1/4-phase lag. From this key insight, it follows that in reversed cycles (i.e., -lag), the dynamics of the actual and the effective prey biomass must be in antiphase with each other, that is, the effective prey biomass must be highest when actual prey biomass is lowest, and vice versa. Based on this, we predict that reversed cycles should be found mainly when oscillations in actual prey biomass are small and thus have limited impact on the dynamics of the effective prey biomass, which are mainly driven by trait changes. We then confirm this prediction using numerical simulations of a coevolutionary predator-prey system, varying the amplitude of the oscillations in prey biomass: Reversed cycles are consistently associated with regions of parameter space leading to small-amplitude prey oscillations, offering a specific and highly testable prediction for conditions under which reversed cycles should occur in natural systems. KW - coevolution KW - ecoevolutionary dynamics KW - predator-prey dynamics KW - top-down control Y1 - 2018 U6 - https://doi.org/10.1002/ece3.4184 SN - 2045-7758 VL - 8 IS - 12 SP - 6317 EP - 6329 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Lukan, Tjaša A1 - Machens, Fabian A1 - Coll, Anna A1 - Baebler, Špela A1 - Messerschmidt, Katrin A1 - Gruden, Kristina T1 - Plant X-tender BT - an extension of the AssemblX system for the assembly and expression of multigene constructs in plants JF - PLOS ONE N2 - Cloning multiple DNA fragments for delivery of several genes of interest into the plant genome is one of the main technological challenges in plant synthetic biology. Despite several modular assembly methods developed in recent years, the plant biotechnology community has not widely adopted them yet, probably due to the lack of appropriate vectors and software tools. Here we present Plant X-tender, an extension of the highly efficient, scar-free and sequence-independent multigene assembly strategy AssemblX, based on overlap-depended cloning methods and rare-cutting restriction enzymes. Plant X-tender consists of a set of plant expression vectors and the protocols for most efficient cloning into the novel vector set needed for plant expression and thus introduces advantages of AssemblX into plant synthetic biology. The novel vector set covers different backbones and selection markers to allow full design flexibility. We have included ccdB counterselection, thereby allowing the transfer of multigene constructs into the novel vector set in a straightforward and highly efficient way. Vectors are available as empty backbones and are fully flexible regarding the orientation of expression cassettes and addition of linkers between them, if required. We optimised the assembly and subcloning protocol by testing different scar-less assembly approaches: the noncommercial SLiCE and TAR methods and the commercial Gibson assembly and NEBuilder HiFi DNA assembly kits. Plant X-tender was applicable even in combination with low efficient homemade chemically competent or electrocompetent Escherichia coli. We have further validated the developed procedure for plant protein expression by cloning two cassettes into the newly developed vectors and subsequently transferred them to Nicotiana benthamiana in a transient expression setup. Thereby we show that multigene constructs can be delivered into plant cells in a streamlined and highly efficient way. Our results will support faster introduction of synthetic biology into plant science. Y1 - 2018 U6 - https://doi.org/10.1371/journal.pone.0190526 SN - 1932-6203 VL - 13 IS - 1 PB - Public Library of Science CY - San Fransisco ER - TY - JOUR A1 - Kolora, Sree Rohit Raj A1 - Weigert, Anne A1 - Saffari, Amin A1 - Kehr, Stephanie A1 - Walter Costa, Maria Beatriz A1 - Spröer, Cathrin A1 - Indrischek, Henrike A1 - Chintalapati, Manjusha A1 - Lohse, Konrad A1 - Doose, Gero A1 - Overmann, Jörg A1 - Bunk, Boyke A1 - Bleidorn, Christoph A1 - Grimm-Seyfarth, Annegret A1 - Henle, Klaus A1 - Nowick, Katja A1 - Faria, Rui A1 - Stadler, Peter F. A1 - Schlegel, Martin T1 - Divergent evolution in the genomes of closely related lacertids, Lacerta viridis and L. bilineata, and implications for speciation JF - GigaScience N2 - Background Lacerta viridis and Lacerta bilineata are sister species of European green lizards (eastern and western clades, respectively) that, until recently, were grouped together as the L. viridis complex. Genetic incompatibilities were observed between lacertid populations through crossing experiments, which led to the delineation of two separate species within the L. viridis complex. The population history of these sister species and processes driving divergence are unknown. We constructed the first high-quality de novo genome assemblies for both L. viridis and L. bilineata through Illumina and PacBio sequencing, with annotation support provided from transcriptome sequencing of several tissues. To estimate gene flow between the two species and identify factors involved in reproductive isolation, we studied their evolutionary history, identified genomic rearrangements, detected signatures of selection on non-coding RNA, and on protein-coding genes. Findings Here we show that gene flow was primarily unidirectional from L. bilineata to L. viridis after their split at least 1.15 million years ago. We detected positive selection of the non-coding repertoire; mutations in transcription factors; accumulation of divergence through inversions; selection on genes involved in neural development, reproduction, and behavior, as well as in ultraviolet-response, possibly driven by sexual selection, whose contribution to reproductive isolation between these lacertid species needs to be further evaluated. Conclusion The combination of short and long sequence reads resulted in one of the most complete lizard genome assemblies. The characterization of a diverse array of genomic features provided valuable insights into the demographic history of divergence among European green lizards, as well as key species differences, some of which are candidates that could have played a role in speciation. In addition, our study generated valuable genomic resources that can be used to address conservation-related issues in lacertids. KW - sister species KW - PacBio and Illumina KW - de novo hybrid assembly KW - transcripts KW - noncoding RNA KW - zinc fingers KW - positive selection KW - UV response KW - inversions KW - gene flow Y1 - 2018 U6 - https://doi.org/10.1093/gigascience/giy160 SN - 2047-217X VL - 8 IS - 2 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Beermann, Jan A1 - Westbury, Michael V. A1 - Hofreiter, Michael A1 - Hilgers, Leon A1 - Deister, Fabian A1 - Neumann, Hermann A1 - Raupach, Michael J. T1 - Cryptic species in a well-known habitat BT - applying taxonomics to the amphipod genus Epimeria (Crustacea, Peracarida) JF - Scientific reports N2 - Taxonomy plays a central role in biological sciences. It provides a communication system for scientists as it aims to enable correct identification of the studied organisms. As a consequence, species descriptions should seek to include as much available information as possible at species level to follow an integrative concept of 'taxonomics'. Here, we describe the cryptic species Epimeria frankei sp. nov. from the North Sea, and also redescribe its sister species, Epimeria cornigera. The morphological information obtained is substantiated by DNA barcodes and complete nuclear 18S rRNA gene sequences. In addition, we provide, for the first time, full mitochondrial genome data as part of a metazoan species description for a holotype, as well as the neotype. This study represents the first successful implementation of the recently proposed concept of taxonomics, using data from high-throughput technologies for integrative taxonomic studies, allowing the highest level of confidence for both biodiversity and ecological research. Y1 - 2018 U6 - https://doi.org/10.1038/s41598-018-25225-x SN - 2045-2322 VL - 8 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Mumm, Rebekka A1 - Godina, Elena A1 - Koziel, Slawomir A1 - Musalek, Martin A1 - Sedlak, Petr A1 - Wittwer-Backofen, Ursula A1 - Hess, Volker A1 - Dasgupta, Parasmani A1 - Henneberg, Maciej A1 - Scheffler, Christiane T1 - External skeletal robusticity of children and adolescents BT - European references from birth to adulthood and international comparisons JF - Journal of biological and clinical anthropology JF - Anthropologischer Anzeiger ; Mitteilungsorgan der Gesellschaft für Anthropologie N2 - Background: In our modern world, the way of life in nutritional and activity behaviour has changed. As a consequence, parallel trends of an epidemic of overweight and a decline in external skeletal robusticity are observed in children and adolescents. Aim: We aim to develop reference centiles for external skeletal robusticity of European girls and boys aged 0 to 18 years using the Frame Index as an indicator and identify population specific age-related patterns. Methods: We analysed cross-sectional & longitudinal data on body height and elbow breadth of boys and girls from Europe (0-18 years, n = 41.679), India (7-18 years, n = 3.297) and South Africa (3-18 years, n = 4.346). As an indicator of external skeletal robusticity Frame Index after Frisancho (1990) was used. We developed centiles for boys and girls using the LMS-method and its extension. Results: Boys have greater external skeletal robusticity than girls. Whereas in girls Frame Index decreases continuously during growth, an increase of Frame Index from 12 to 16 years in European boys can be observed. Indian and South African boys are almost similar in Frame Index to European boys. In girls, the pattern is slightly different. Whereas South African girls are similar to European girls, Indian girls show a lesser external skeletal robusticity. Conclusion: Accurate references for external skeletal robusticity are needed to evaluate if skeletal development is adequate per age. They should be used to monitor effects of changes in way of life and physical activity levels in children and adolescents to avoid negative health outcomes like osteoporosis and arthrosis. Y1 - 2018 U6 - https://doi.org/10.1127/anthranz/2018/0826 SN - 0003-5548 VL - 74 IS - 5 SP - 383 EP - 391 PB - Schweizerbart CY - Stuttgart ER - TY - JOUR A1 - Donat, Stefan A1 - Lourenco, Marta Sofia Rocha A1 - Paolini, Alessio A1 - Otten, Cecile A1 - Renz, Marc A1 - Abdelilah-Seyfried, Salim T1 - Heg1 and Ccm1/2 proteins control endocardial mechanosensitivity during zebrafish valvulogenesis JF - eLife N2 - Endothelial cells respond to different levels of fluid shear stress through adaptations of their mechanosensitivity. Currently, we lack a good understanding of how this contributes to sculpting of the cardiovascular system. Cerebral cavernous malformation (CCM) is an inherited vascular disease that occurs when a second somatic mutation causes a loss of CCM1/KRIT1, CCM2, or CCM3 proteins. Here, we demonstrate that zebrafish Krit1 regulates the formation of cardiac valves. Expression of heg1, which encodes a binding partner of Krit1, is positively regulated by blood-flow. In turn, Heg1 stabilizes levels of Krit1 protein, and both Heg1 and Krit1 dampen expression levels of klf2a, a major mechanosensitive gene. Conversely, loss of Krit1 results in increased expression of klf2a and notch1b throughout the endocardium and prevents cardiac valve leaflet formation. Hence, the correct balance of blood-flow-dependent induction and Krit1 protein mediated repression of klf2a and notch1b ultimately shapes cardiac valve leaflet morphology. Y1 - 2018 U6 - https://doi.org/10.7554/eLife.28939 SN - 2050-084X VL - 7 PB - eLife Sciences Publications CY - Cambridge ER - TY - JOUR A1 - Olmer, Ruth A1 - Engels, Lena A1 - Usman, Abdulai A1 - Menke, Sandra A1 - Malik, Muhammad Nasir Hayat A1 - Pessler, Frank A1 - Goehring, Gudrun A1 - Bornhorst, Dorothee A1 - Bolten, Svenja A1 - Abdelilah-Seyfried, Salim A1 - Scheper, Thomas A1 - Kempf, Henning A1 - Zweigerdt, Robert A1 - Martin, Ulrich T1 - Differentiation of Human Pluripotent Stem Cells into Functional Endothelial Cells in Scalable Suspension Culture JF - Stem Cell Reports N2 - Endothelial cells (ECs) are involved in a variety of cellular responses. As multifunctional components of vascular structures, endothelial (progenitor) cells have been utilized in cellular therapies and are required as an important cellular component of engineered tissue constructs and in vitro disease models. Although primary ECs from different sources are readily isolated and expanded, cell quantity and quality in terms of functionality and karyotype stability is limited. ECs derived from human induced pluripotent stem cells (hiPSCs) represent an alternative and potentially superior cell source, but traditional culture approaches and 2D differentiation protocols hardly allow for production of large cell numbers. Aiming at the production of ECs, we have developed a robust approach for efficient endothelial differentiation of hiPSCs in scalable suspension culture. The established protocol results in relevant numbers of ECs for regenerative approaches and industrial applications that show in vitro proliferation capacity and a high degree of chromosomal stability. KW - virus infection KW - progenitor cells KW - in vitro KW - telomere dysfunction KW - cord blood KW - cardiomyogenic differentiation KW - angiogenesis KW - efficient KW - aberrations KW - expression Y1 - 2017 U6 - https://doi.org/10.1016/j.stemcr.2018.03.017 SN - 2213-6711 VL - 10 IS - 5 PB - Springer CY - New York ER - TY - JOUR A1 - Taron, Ulrike H. A1 - Lell, Moritz A1 - Barlow, Axel A1 - Paijmans, Johanna L. A. T1 - Testing of Alignment Parameters for Ancient Samples BT - Evaluating and Optimizing Mapping Parameters for Ancient Samples Using the TAPAS Tool JF - Genese N2 - High-throughput sequence data retrieved from ancient or other degraded samples has led to unprecedented insights into the evolutionary history of many species, but the analysis of such sequences also poses specific computational challenges. The most commonly used approach involves mapping sequence reads to a reference genome. However, this process becomes increasingly challenging with an elevated genetic distance between target and reference or with the presence of contaminant sequences with high sequence similarity to the target species. The evaluation and testing of mapping efficiency and stringency are thus paramount for the reliable identification and analysis of ancient sequences. In this paper, we present ‘TAPAS’, (Testing of Alignment Parameters for Ancient Samples), a computational tool that enables the systematic testing of mapping tools for ancient data by simulating sequence data reflecting the properties of an ancient dataset and performing test runs using the mapping software and parameter settings of interest. We showcase TAPAS by using it to assess and improve mapping strategy for a degraded sample from a banded linsang (Prionodon linsang), for which no closely related reference is currently available. This enables a 1.8-fold increase of the number of mapped reads without sacrificing mapping specificity. The increase of mapped reads effectively reduces the need for additional sequencing, thus making more economical use of time, resources, and sample material. KW - ancient DNA KW - short-read mapping KW - palaeogenomics KW - paleogenomics KW - alignment sensitivity/specificity Y1 - 2018 U6 - https://doi.org/10.3390/genes9030157 SN - 2073-4425 VL - 9 IS - 3 PB - MDPI CY - Basel ER - TY - JOUR A1 - Martin-Creuzburg, Dominik A1 - Massier, Tamara A1 - Wacker, Alexander T1 - Sex-Specific differences in essential lipid requirements of Daphnia magna JF - Frontiers in Ecology and Evolution N2 - Sex-specific differences in nutritional requirements may crucially influence the performances of the sexes, which may have implications for sexual reproduction and thus is of great ecological and evolutionary interest. In the freshwater model species Daphnia magna, essential lipid requirements have been extensively studied. Dietary deficiencies in sterols and polyunsaturated fatty acids (PUFA) have been shown to constrain somatic growth and parthenogenetic reproduction of female Daphnia. In contrast, nutrient requirements of male Daphnia have not been studied yet. Supplementation experiments were conducted to investigate differences in sterol (cholesterol) and PUFA (eicosapentaenoic acid, EPA) requirements between female and male D. magna. Thresholds for sterol-limited juvenile growth were higher in females than in males, suggesting that females are more susceptible to dietary sterol deficiencies than males. Sex-specific differences in maximum somatic growth rates were evident primarily in the presence of dietary EPA; females could not exploit their generally higher growth potential in the absence of dietary PUFA. However, the thresholds for EPA-limited growth did not differ between sexes, suggesting that both sexes have similar dietary EPA requirements during juvenile growth. During a life history experiment, the gain in body dry mass was higher in females than in males, irrespective of food treatment. In both sexes, the gain in body dry mass increased significantly upon EPA supplementation, indicating that both sexes benefited from dietary EPA supply also later in life. However, the positive effects of EPA supplementation were most pronounced for female reproduction-related traits (i.e., clutch sizes, egg dry masses, and total dry mass investment in reproduction). The high maternal investment in reproduction resulted in a depletion of nutrients in female somata. In contrast, the comparatively low paternal investment in reproduction allowed for the accumulation of nutrients in male somata. We conclude that males are generally less susceptible to dietary nutrient deficiencies than females, because they can rely more on internal body stores. Our data suggest that the performances of the sexes are differentially influenced by lipid-mediated food quality, which may have consequences for sexual reproduction and thus the production of resting eggs and the maintenance of Daphnia populations. KW - allocation KW - cholesterol KW - eicosapentaenoic acid KW - food quality KW - male Daphnia KW - polyunsaturated fatty acids KW - sterols KW - lipid limitation thresholds Y1 - 2018 U6 - https://doi.org/10.3389/fevo.2018.00089 SN - 2296-701X VL - 6 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Zurell, Damaris A1 - von Wehrden, Henrik A1 - Rotics, Shay A1 - Kaatz, Michael A1 - Gross, Helge A1 - Schlag, Lena A1 - Schäfer, Merlin A1 - Sapir, Nir A1 - Turjeman, Sondra A1 - Wikelski, Martin A1 - Nathan, Ran A1 - Jeltsch, Florian T1 - Home range size and resource use of breeding and non-breeding white storks along a land use gradient JF - Frontiers in Ecology and Evolution N2 - Biotelemetry is increasingly used to study animal movement at high spatial and temporal resolution and guide conservation and resource management. Yet, limited sample sizes and variation in space and habitat use across regions and life stages may compromise robustness of behavioral analyses and subsequent conservation plans. Here, we assessed variation in (i) home range sizes, (ii) home range selection, and (iii) fine-scale resource selection of white storks across breeding status and regions and test model transferability. Three study areas were chosen within the Central German breeding grounds ranging from agricultural to fluvial and marshland. We monitored GPS-locations of 62 adult white storks equipped with solar-charged GPS/3D-acceleration (ACC) transmitters in 2013-2014. Home range sizes were estimated using minimum convex polygons. Generalized linear mixed models were used to assess home range selection and fine-scale resource selection by relating the home ranges and foraging sites to Corine habitat variables and normalized difference vegetation index in a presence/pseudo-absence design. We found strong variation in home range sizes across breeding stages with significantly larger home ranges in non-breeding compared to breeding white storks, but no variation between regions. Home range selection models had high explanatory power and well predicted overall density of Central German white stork breeding pairs. Also, they showed good transferability across regions and breeding status although variable importance varied considerably. Fine-scale resource selection models showed low explanatory power. Resource preferences differed both across breeding status and across regions, and model transferability was poor. Our results indicate that habitat selection of wild animals may vary considerably within and between populations, and is highly scale dependent. Thereby, home range scale analyses show higher robustness whereas fine-scale resource selection is not easily predictable and not transferable across life stages and regions. Such variation may compromise management decisions when based on data of limited sample size or limited regional coverage. We thus recommend home range scale analyses and sampling designs that cover diverse regional landscapes and ensure robust estimates of habitat suitability to conserve wild animal populations. KW - 3D-acceleration sensor KW - biotelemetry KW - Ciconia ciconia KW - home range selection KW - resource selection Y1 - 2018 U6 - https://doi.org/10.3389/fevo.2018.00079 SN - 2296-701X VL - 6 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Omidbakhshfard, Mohammad Amin A1 - Fujikura, Ushio A1 - Olas, Justyna Jadwiga A1 - Xue, Gang-Ping A1 - Balazadeh, Salma A1 - Mueller-Roeber, Bernd T1 - GROWTH-REGULATING FACTOR 9 negatively regulates arabidopsis leaf growth by controlling ORG3 and restricting cell proliferation in leaf primordia JF - PLoS Genetics : a peer-reviewed, open-access journal N2 - Leaf growth is a complex process that involves the action of diverse transcription factors (TFs) and their downstream gene regulatory networks. In this study, we focus on the functional characterization of the Arabidopsis thaliana TF GROWTH-REGULATING FACTOR9 (GRF9) and demonstrate that it exerts its negative effect on leaf growth by activating expression of the bZIP TF OBP3-RESPONSIVE GENE 3 (ORG3). While grf9 knockout mutants produce bigger incipient leaf primordia at the shoot apex, rosette leaves and petals than the wild type, the sizes of those organs are reduced in plants overexpressing GRF9 (GRF9ox). Cell measurements demonstrate that changes in leaf size result from alterations in cell numbers rather than cell sizes. Kinematic analysis and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay revealed that GRF9 restricts cell proliferation in the early developing leaf. Performing in vitro binding site selection, we identified the 6-base motif 5'-CTGACA-3' as the core binding site of GRF9. By global transcriptome profiling, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) we identified ORG3 as a direct downstream, and positively regulated target of GRF9. Genetic analysis of grf9 org3 and GRF9ox org3 double mutants reveals that both transcription factors act in a regulatory cascade to control the final leaf dimensions by restricting cell number in the developing leaf. Y1 - 2018 U6 - https://doi.org/10.1371/journal.pgen.1007484 SN - 1553-7404 VL - 14 IS - 7 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Otten, Cecile A1 - Knox, Jessica A1 - Boulday, Gwenola A1 - Eymery, Mathias A1 - Haniszewski, Marta A1 - Neuenschwander, Martin A1 - Radetzki, Silke A1 - Vogt, Ingo A1 - Haehn, Kristina A1 - De Luca, Coralie A1 - Cardoso, Cecile A1 - Hamad, Sabri A1 - Igual Gil, Carla A1 - Roy, Peter A1 - Albiges-Rizo, Corinne A1 - Faurobert, Eva A1 - von Kries, Jens P. A1 - Campillos, Monica A1 - Tournier-Lasserve, Elisabeth A1 - Derry, William Brent A1 - Abdelilah-Seyfried, Salim T1 - Systematic pharmacological screens uncover novel pathways involved in cerebral cavernous malformations JF - EMBO molecular medicine N2 - Cerebral cavernous malformations (CCMs) are vascular lesions in the central nervous system causing strokes and seizures which currently can only be treated through neurosurgery. The disease arises through changes in the regulatory networks of endothelial cells that must be comprehensively understood to develop alternative, non-invasive pharmacological therapies. Here, we present the results of several unbiased small-molecule suppression screens in which we applied a total of 5,268 unique substances to CCM mutant worm, zebrafish, mouse, or human endothelial cells. We used a systems biology-based target prediction tool to integrate the results with the whole-transcriptome profile of zebrafish CCM2 mutants, revealing signaling pathways relevant to the disease and potential targets for small-molecule-based therapies. We found indirubin-3-monoxime to alleviate the lesion burden in murine preclinical models of CCM2 and CCM3 and suppress the loss-of-CCM phenotypes in human endothelial cells. Our multi-organism-based approach reveals new components of the CCM regulatory network and foreshadows novel small-molecule-based therapeutic applications for suppressing this devastating disease in patients. KW - angiogenesis KW - CCM KW - ERK5 KW - indirubin-3-monoxime KW - KLF2 Y1 - 2018 U6 - https://doi.org/10.15252/emmm.201809155 SN - 1757-4676 SN - 1757-4684 VL - 10 IS - 10 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Hochrein, Lena A1 - Mitchell, Leslie A. A1 - Schulz, Karina A1 - Messerschmidt, Katrin A1 - Müller-Röber, Bernd T1 - L-SCRaMbLE as a tool for light-controlled Cre-mediated recombination in yeast JF - Nature Communications N2 - The synthetic yeast genome constructed by the International Synthetic Yeast Sc2.0 consortium adds thousands of loxPsym recombination sites to all 16 redesigned chromosomes, allowing the shuffling of Sc2.0 chromosome parts by the Cre-loxP recombination system thereby enabling genome evolution experiments. Here, we present L-SCRaMbLE, a lightcontrolled Cre recombinase for use in the yeast Saccharomyces cerevisiae. L-SCRaMbLE allows tight regulation of recombinase activity with up to 179-fold induction upon exposure to red light. The extent of recombination depends on induction time and concentration of the chromophore phycocyanobilin (PCB), which can be easily adjusted. The tool presented here provides improved recombination control over the previously reported estradiol-dependent SCRaMbLE induction system, mediating a larger variety of possible recombination events in SCRaMbLE-ing a reporter plasmid. Thereby, L-SCRaMbLE boosts the potential for further customization and provides a facile application for use in the S. cerevisiae genome reengineering project Sc2.0 or in other recombination-based systems. Y1 - 2018 U6 - https://doi.org/10.1038/s41467-017-02208-6 SN - 2041-1723 VL - 9 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Heim, Wieland A1 - Eccard, Jana A1 - Bairlein, Franz T1 - Migration phenology determines niche use of East Asian buntings (Emberizidae) during stopover JF - Current zoology N2 - Stopover niche utilization of birds during migration has not gained much attention so far, since the majority of the studies focuses on breeding or wintering areas. However, stopover sites are crucial for migratory birds. They are often used by a multitude of species, which could lead to increased competition. In this work, we investigated niche use of 8 migratory and closely related Emberiza bunting species at a stopover site in Far East Russia, situated on the poorly studied East Asian fly-way. We used bird ringing data to evaluate morphological similarity as well as niche overlap on the trophic, spatial, and temporal dimension. Bill morphology was used as a proxy for their trophic niche. We were able to prove that a majority of the species occupies well-defined stopover niches on at least one of the dimensions. Niche breadth and niche overlap differ between spring and autumn season with higher overlap found during spring. Morphological differences are mostly related to overall size and wing pointedness. The temporal dimension is most important for segregation among the studied species. Furthermore, all species seem to exhibit a rather strict and consistent phenological pattern. Their occurrence at the study site is highly correlated with their geographic origin and the length of their migration route. We assume that buntings are able to use available resources opportunistically during stopover, while trying to follow a precise schedule in order to avoid competition and to ensure individual fitness. KW - bird migration KW - Emberiza KW - habitat use KW - non-breeding KW - phenology KW - stopover Y1 - 2018 U6 - https://doi.org/10.1093/cz/zoy016 SN - 1674-5507 SN - 2396-9814 VL - 64 IS - 6 SP - 681 EP - 692 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Prahl, Boris F. A1 - Boettle, Markus A1 - Costa, Luís Fílípe Carvalho da A1 - Kropp, Jürgen A1 - Rybski, Diego T1 - Damage and protection cost curves for coastal floods within the 600 largest European cities JF - Scientific Data N2 - The economic assessment of the impacts of storm surges and sea-level rise in coastal cities requires high-level information on the damage and protection costs associated with varying flood heights. We provide a systematically and consistently calculated dataset of macroscale damage and protection cost curves for the 600 largest European coastal cities opening the perspective for a wide range of applications. Offering the first comprehensive dataset to include the costs of dike protection, we provide the underpinning information to run comparative assessments of costs and benefits of coastal adaptation. Aggregate cost curves for coastal flooding at the city-level are commonly regarded as by-products of impact assessments and are generally not published as a standalone dataset. Hence, our work also aims at initiating a more critical discussion on the availability and derivation of cost curves. Y1 - 2018 U6 - https://doi.org/10.1038/sdata.2018.34 SN - 2052-4463 VL - 5 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Bizic-Ionescu, Mina A1 - Ionescu, Danny A1 - Grossart, Hans-Peter T1 - Organic Particles: Heterogeneous Hubs for Microbial Interactions in Aquatic Ecosystems JF - Frontiers in microbiology N2 - The dynamics and activities of microbes colonizing organic particles (hereafter particles) greatly determine the efficiency of the aquatic carbon pump. Current understanding is that particle composition, structure and surface properties, determined mostly by the forming organisms and organic matter, dictate initial microbial colonization and the subsequent rapid succession events taking place as organic matter lability and nutrient content change with microbial degradation. We applied a transcriptomic approach to assess the role of stochastic events on initial microbial colonization of particles. Furthermore, we asked whether gene expression corroborates rapid changes in carbon-quality. Commonly used size fractionated filtration averages thousands of particles of different sizes, sources, and ages. To overcome this drawback, we used replicate samples consisting each of 3–4 particles of identical source and age and further evaluated the consequences of averaging 10–1000s of particles. Using flow-through rolling tanks we conducted long-term experiments at near in situ conditions minimizing the biasing effects of closed incubation approaches often referred to as “the bottle-effect.” In our open flow-through rolling tank system, however, active microbial communities were highly heterogeneous despite an identical particle source, suggesting random initial colonization. Contrasting previous reports using closed incubation systems, expression of carbon utilization genes didn’t change after 1 week of incubation. Consequently, we suggest that in nature, changes in particle-associated community related to carbon availability are much slower (days to weeks) due to constant supply of labile, easily degradable organic matter. Initial, random particle colonization seems to be subsequently altered by multiple organismic interactions shaping microbial community interactions and functional dynamics. Comparative analysis of thousands particles pooled togethers as well as pooled samples suggests that mechanistic studies of microbial dynamics should be done on single particles. The observed microbial heterogeneity and inter-organismic interactions may have important implications for evolution and biogeochemistry in aquatic systems. KW - particle-associated bacteria KW - microbial communities KW - inter- and intra-species interactions KW - antagonism KW - phage KW - transcriptome Y1 - 2018 U6 - https://doi.org/10.3389/fmicb.2018.02569 SN - 1664-302X VL - 9 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Garcia, Sarahi L. A1 - Buck, Moritz A1 - Hamilton, Joshua J. A1 - Wurzbacher, Christian A1 - Grossart, Hans-Peter A1 - McMahon, Katherine D. A1 - Eiler, Alexander T1 - Model communities hint at promiscuous metabolic linkages between ubiquitous free-living freshwater bacteria JF - mSphere N2 - Genome streamlining is frequently observed in free-living aquatic microorganisms and results in physiological dependencies between microorganisms. However, we know little about the specificity of these microbial associations. In order to examine the specificity and extent of these associations, we established mixed cultures from three different freshwater environments and analyzed the cooccurrence of organisms using a metagenomic time series. Free-living microorganisms with streamlined genomes lacking multiple biosynthetic pathways showed no clear recurring pattern in their interaction partners. Free-living freshwater bacteria form promiscuous cooperative associations. This notion contrasts with the well-documented high specificities of interaction partners in host-associated bacteria. Considering all data together, we suggest that highly abundant free-living bacterial lineages are functionally versatile in their interactions despite their distinct streamlining tendencies at the single-cell level. This metabolic versatility facilitates interactions with a variable set of community members. KW - community KW - interactions KW - metagenomics KW - microbial ecology KW - mixed cultures KW - promiscuous Y1 - 2018 U6 - https://doi.org/10.1128/mSphere.00202-18 SN - 2379-5042 VL - 3 IS - 3 PB - American Society for Microbiology CY - Washington ER -