@article{StoofLeichsenringBernhardtPestryakovaetal.2014,
  author    = {Stoof-Leichsenring, Kathleen Rosemarie and Bernhardt, Nadine and Pestryakova, Luidmila Agafyevna and Epp, Laura Saskia and Herzschuh, Ulrike and Tiedemann, Ralph},
  title     = {A combined paleolimnological/genetic analysis of diatoms reveals divergent evolutionary lineages of Staurosira and Staurosirella (Bacillariophyta) in Siberian lake sediments along a latitudinal transect},
  series = {Journal of paleolimnolog},
  volume    = {52},
  journal   = {Journal of paleolimnolog},
  number    = {1-2},
  publisher = {Springer},
  address   = {Dordrecht},
  issn      = {0921-2728},
  doi       = {10.1007/s10933-014-9779-1},
  pages     = {77 -- 93},
  year      = {2014},
  abstract  = {Diatom diversity in lakes of northwest Yakutia (Siberia) was investigated by microscopic and genetic analysis of surface and cored lake sediments, to evaluate the use of sedimentary DNA for paleolimnological diatom studies and to identify obscure genetic diversity that cannot be detected by microscopic methods. Two short (76 and 73 bp) and one longer (577 bp) fragments of the ribulose 1,5-bisphosphate carboxylase/oxygenase (rbcL) gene, encoding the large subunit of the rbcL, were used as genetic markers. Diverse morphological assemblages of diatoms, dominated by small benthic fragilarioid taxa, were retrieved from the sediments of each lake. These minute fragilarioid taxa were examined by scanning electron microscopy, revealing diverse morphotypes in Staurosira and Staurosirella from the different lakes. Genetic analyses indicated a dominance of haplotypes that were assigned to fragilarioid taxa and less genetic diversity in other diatom taxa. The long rbcL_577 amplicon identified considerable diversification among haplotypes clustering within the Staurosira/Staurosirella genera, revealing 19 different haplotypes whose spatial distribution appears to be primarily related to the latitude of the lakes, which corresponds to a vegetation and climate gradient. Our rbcL markers are valuable tools for tracking differences between diatom lineages that are not visible in their morphologies. These markers revealed putatively high genetic diversity within the Staurosira/Staurosirella species complex, at a finer scale than is possible to resolve by microscopic determination. The rbcL markers may provide additional reliable information on the diversity of barely distinguishable minute benthic fragilarioids. Environmental sequencing may thus allow the tracking of spatial and temporal diversification in Siberian lakes, especially in the context of diatom responses to recent environmental changes, which remains a matter of controversy.},
  language  = {en}
}
@article{ZorHeiskanenCavigliaetal.2014,
  author    = {Zor, K. and Heiskanen, A. and Caviglia, Claudia and Vergani, M. and Landini, E. and Shah, F. and Carminati, Marco and Martinez-Serrano, A. and Ramos Moreno, T. and Kokaia, M. and Benayahu, Dafna and Keresztes, Zs. and Papkovsky, D. and Wollenberger, Ursula and Svendsen, W. E. and Dimaki, M. and Ferrari, G. and Raiteri, R. and Sampietro, M. and Dufva, M. and Emneus, Jenny},
  title     = {A compact multifunctional microfluidic platform for exploring cellular dynamics in real-time using electrochemical detection},
  series = {RSC Advances},
  volume    = {4},
  journal   = {RSC Advances},
  number    = {109},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {2046-2069},
  doi       = {10.1039/c4ra12632g},
  pages     = {63761 -- 63771},
  year      = {2014},
  abstract  = {Downscaling of microfluidic cell culture and detection devices for electrochemical monitoring has mostly focused on miniaturization of the microfluidic chips which are often designed for specific applications and therefore lack functional flexibility. We present a compact microfluidic cell culture and electrochemical analysis platform with in-built fluid handling and detection, enabling complete cell based assays comprising on-line electrode cleaning, sterilization, surface functionalization, cell seeding, cultivation and electrochemical real-time monitoring of cellular dynamics. To demonstrate the versatility and multifunctionality of the platform, we explored amperometric monitoring of intracellular redox activity in yeast (Saccharomyces cerevisiae) and detection of exocytotically released dopamine from rat pheochromocytoma cells (PC12). Electrochemical impedance spectroscopy was used in both applications for monitoring cell sedimentation and adhesion as well as proliferation in the case of PC12 cells. The influence of flow rate on the signal amplitude in the detection of redox metabolism as well as the effect of mechanical stimulation on dopamine release were demonstrated using the programmable fluid handling capability. The here presented platform is aimed at applications utilizing cell based assays, ranging from e.g. monitoring of drug effects in pharmacological studies, characterization of neural stem cell differentiation, and screening of genetically modified microorganisms to environmental monitoring.},
  language  = {en}
}
@misc{ZorHeiskanenCavigliaetal.2014,
  author    = {Z{\´o}r, K. and Heiskanen, A. and Caviglia, Claudia and Vergani, M. and Landini, E. and Shah, F. and Carminati, Marco and Mart{\´i}nez-Serrano, A. and Ramos Moreno, T. and Kokaia, M. and Benayahu, Dafna and Keresztes, Zs. and Papkovsky, D. and Wollenberger, Ursula and Svendsen, W. E. and Dimaki, M. and Ferrari, G. and Raiteri, R. and Sampietro, M. and Dufva, M. and Emn{\´e}us, J.},
  title     = {A compact multifunctional microfluidic platform for exploring cellular dynamics in real-time using electrochemical detection},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-99492},
  pages     = {11},
  year      = {2014},
  abstract  = {Downscaling of microfluidic cell culture and detection devices for electrochemical monitoring has mostly focused on miniaturization of the microfluidic chips which are often designed for specific applications and therefore lack functional flexibility. We present a compact microfluidic cell culture and electrochemical analysis platform with in-built fluid handling and detection, enabling complete cell based assays comprising on-line electrode cleaning, sterilization, surface functionalization, cell seeding, cultivation and electrochemical real-time monitoring of cellular dynamics. To demonstrate the versatility and multifunctionality of the platform, we explored amperometric monitoring of intracellular redox activity in yeast (Saccharomyces cerevisiae) and detection of exocytotically released dopamine from rat pheochromocytoma cells (PC12). Electrochemical impedance spectroscopy was used in both applications for monitoring cell sedimentation and adhesion as well as proliferation in the case of PC12 cells. The influence of flow rate on the signal amplitude in the detection of redox metabolism as well as the effect of mechanical stimulation on dopamine release were demonstrated using the programmable fluid handling capability. The here presented platform is aimed at applications utilizing cell based assays, ranging from e.g. monitoring of drug effects in pharmacological studies, characterization of neural stem cell differentiation, and screening of genetically modified microorganisms to environmental monitoring.},
  language  = {en}
}
@article{BrothersKoehlerAttermeyeretal.2014,
  author    = {Brothers, Soren M. and Koehler, J. and Attermeyer, Katrin and Grossart, Hans-Peter and Mehner, T. and Meyer, N. and Scharnweber, Inga Kristin and Hilt, Sabine},
  title     = {A feedback loop links brownification and anoxia in a temperate, shallow lake},
  series = {Limnology and oceanography},
  volume    = {59},
  journal   = {Limnology and oceanography},
  number    = {4},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {0024-3590},
  doi       = {10.4319/lo.2014.59.4.1388},
  pages     = {1388 -- 1398},
  year      = {2014},
  abstract  = {This study examines a natural, rapid, fivefold increase in dissolved organic carbon (DOC) concentrations in a temperate shallow lake, describing the processes by which increased DOC resulted in anoxic conditions and altered existing carbon cycling pathways. High precipitation for two consecutive years led to rising water levels and the flooding of adjacent degraded peatlands. Leaching from the flooded soils provided an initial increase in DOC concentrations (from a 2010 mean of 12 +/- 1 mg L-1 to a maximum concentration of 53 mg L-1 by June 2012). Increasing water levels, DOC, and phytoplankton concentrations reduced light reaching the sediment surface, eliminating most benthic primary production and promoting anoxia in the hypolimnion. From January to June 2012 there was a sudden increase in total phosphorus (from 57 mg L-1 to 216 mg L-1), DOC (from 24.6 mg L-1 to 53 mg L-1), and iron (from 0.12 mg L-1 to 1.07 mg L-1) concentrations, without any further large fluxes in water levels. We suggest that anoxic conditions at the sediment surface and flooded soils produced a dramatic release of these chemicals that exacerbated brownification and eutrophication, creating anoxic conditions that persisted roughly 6 months below a water depth of 1 m and extended periodically to the water surface. This brownification-anoxia feedback loop resulted in a near-complete loss of macroinvertebrate and fish populations, and increased surface carbon dioxide (CO2) emissions by an order of magnitude relative to previous years.},
  language  = {en}
}
@article{BaetenWartonVanCalsteretal.2014,
  author    = {Baeten, Lander and Warton, David I. and Van Calster, Hans and De Frenne, Pieter and Verstraeten, Gorik and Bonte, Dries and Bernhardt-R{\"o}mermann, Markus and Cornelis, Johnny and Decocq, Guillaume and Eriksson, Ove and Hedl, Radim and Heinken, Thilo and Hermy, Martin and Hommel, Patrick and Kirby, Keith J. and Naaf, Tobias and Petrik, Petr and Walther, Gian-Reto and Wulf, Monica and Verheyen, Kris},
  title     = {A model-based approach to studying changes in compositional heterogeneity},
  series = {Methods in ecology and evolution : an official journal of the British Ecological Society},
  volume    = {5},
  journal   = {Methods in ecology and evolution : an official journal of the British Ecological Society},
  number    = {2},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {2041-210X},
  pages     = {156 -- 164},
  year      = {2014},
  language  = {en}
}
@misc{ShapiroHofreiter2014,
  author    = {Shapiro, B. and Hofreiter, Michael},
  title     = {A paleogenomic perspective on evolution and gene function: new insights from ancient DNA},
  series = {Science},
  volume    = {343},
  journal   = {Science},
  number    = {6169},
  publisher = {American Assoc. for the Advancement of Science},
  address   = {Washington},
  issn      = {0036-8075},
  doi       = {10.1126/science.1236573},
  pages     = {7},
  year      = {2014},
  abstract  = {The publication of partial and complete paleogenomes within the last few years has reinvigorated research in ancient DNA. No longer limited to short fragments of mitochondrial DNA, inference of evolutionary processes through time can now be investigated from genome-wide data sampled as far back as 700,000 years. Tremendous insights have been made, in particular regarding the hominin lineage. With rare exception, however, a paleogenomic perspective has been mired by the quality and quantity of recoverable DNA. Though conceptually simple, extracting ancient DNA remains challenging, and sequencing ancient genomes to high coverage remains prohibitively expensive for most laboratories. Still, with improvements in DNA isolation and declining sequencing costs, the taxonomic and geographic purview of paleogenomics is expanding at a rapid pace. With improved capacity to screen large numbers of samples for those with high proportions of endogenous ancient DNA, paleogenomics is poised to become a key technology to better understand recent evolutionary events.},
  language  = {en}
}
@article{AudisioClineSolanoetal.2014,
  author    = {Audisio, Paolo and Cline, Andrew R. and Solano, Emanuela and Mancini, Emiliano and Lamanna, Francesco and Antonini, Gloria and Trizzino, Marco},
  title     = {A peculiar new genus and species of pollen-beetle (Coleoptera, Nitidulidae) from eastern Africa, with a molecular phylogeny of related Meligethinae},
  series = {Systematics and biodiversity},
  volume    = {12},
  journal   = {Systematics and biodiversity},
  number    = {1},
  publisher = {Routledge, Taylor \& Francis Group},
  address   = {Abingdon},
  issn      = {1477-2000},
  doi       = {10.1080/14772000.2013.877539},
  pages     = {77 -- 91},
  year      = {2014},
  language  = {en}
}
@article{BiancoKetmaier2014,
  author    = {Bianco, Pier Giorgio and Ketmaier, Valerio},
  title     = {A revision of the Rutilus complex from Mediterranean Europe with description of a new genus, Sarmarutilus, and a new species, Rutilus stoumboudae (Teleostei: Cyprinidae)},
  series = {Zootaxa : an international journal of zootaxonomy ; a rapid international journal for animal taxonomists},
  volume    = {3841},
  journal   = {Zootaxa : an international journal of zootaxonomy ; a rapid international journal for animal taxonomists},
  number    = {3},
  publisher = {Magnolia Press},
  address   = {Auckland},
  issn      = {1175-5326},
  pages     = {379 -- 402},
  year      = {2014},
  abstract  = {By combining morphology, ecology, biology, and biogeography with the available molecular (sequence variation of the entire mitochondrial cytochrome b gene; cyt-b) and karyology data, the taxonomy of several species of the Rutilus complex inhabiting southern Europe is revised. Rutilus stoumboudae, new species, is described from Lake Volvi, Greece. It differs from Rutilus rutilus in possessing more total GR and less branched rays in both dorsal and anal fins and in its placement in the cyt-b based phylogeny of the genus. The resurrected genus Leucos Heckel, 1843 (type species Leucos aula, Bonaparte, 1841), which according to molecular data diverged from Rutilus more than 5 million years ago, during the Messinian salinity crisis, includes five species of small size, without spinous tubercles on scales and head in reproductive males, pharyngeal teeth formula 5-5, and all show a preference for still waters. Leucos aula is the Italian species endemic in the Padany-Venetian district: L. basak is widespread in Croatia, Albania, Montenegro and former Yugoslav Republic of Macedonia (FYROM); L. albus, recently described from Lake Skadar, Montenegro, is also found in rivers Moraca and Zeta (Montenegro). L. albus differs from L. basak, its closest relative, in having more scales on the LL and less anal-fin rays; L. panosi is endemic to the western-Greece district, and L. ylikiensis is endemic to lakes Yliki and Paralimni in eastern Greece (introduced in Lake Volvi). Among the nominal species examined, Rutilus karamani, R. ohridanus, R. prespensis and R. prespensis vukovici are all junior synonyms of Leucos basak. Rutilus vegariticus is definitively regarded as junior synonym for R. rutilus. Sarmarutilus n.gen. is a monotypic genus, with Sarmarutilus rubilio as the type species. According to phylogenetic data, Sarmarutilus rubilio is basal to a cluster of species that includes Leucos basak, L. albus, L. aula, L. panosi and L. ylikiensis. Sarmarutilus possibly evolved in pre-Messinian time, in the Lago Mare, entered the Mediterranean area during the Messinian Lago Mare phase of the Mediterranean Sea and survived only in the Tuscany-Latium district. This genus differs from Leucos in having large pearl organs on the central part of head and body scales in mature males and for the habitat preference, being a riverine-adapted species. It differs from Rutilus in pharyngeal teeth formula (5-5 in Sarmarutilus and 6-5 in Rutilus), size (small in Sarmarutilus and large in Rutilus) and for the preferential habitat (riverine vs. still water). Finally, lectotypes for Leucos basak, Leucos aula, and Sarmarutilus rubilio are designated.},
  language  = {en}
}
@article{OmidbakhshfardWinckArvidssonetal.2014,
  author    = {Omidbakhshfard, Mohammad Amin and Winck, Flavia Vischi and Arvidsson, Samuel Janne and Riano-Pachon, Diego M. and M{\"u}ller-R{\"o}ber, Bernd},
  title     = {A step-by-step protocol for formaldehyde-assisted isolation of regulatory elements from Arabidopsis thaliana},
  series = {Journal of integrative plant biology},
  volume    = {56},
  journal   = {Journal of integrative plant biology},
  number    = {6},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {1672-9072},
  doi       = {10.1111/jipb.12151},
  pages     = {527 -- 538},
  year      = {2014},
  abstract  = {The control of gene expression by transcriptional regulators and other types of functionally relevant DNA transactions such as chromatin remodeling and replication underlie a vast spectrum of biological processes in all organisms. DNA transactions require the controlled interaction of proteins with DNA sequence motifs which are often located in nucleosome-depleted regions (NDRs) of the chromatin. Formaldehyde-assisted isolation of regulatory elements (FAIRE) has been established as an easy-to-implement method for the isolation of NDRs from a number of eukaryotic organisms, and it has been successfully employed for the discovery of new regulatory segments in genomic DNA from, for example, yeast, Drosophila, and humans. Until today, however, FAIRE has only rarely been employed in plant research and currently no detailed FAIRE protocol for plants has been published. Here, we provide a step-by-step FAIRE protocol for NDR discovery in Arabidopsis thaliana. We demonstrate that NDRs isolated from plant chromatin are readily amenable to quantitative polymerase chain reaction and next-generation sequencing. Only minor modification of the FAIRE protocol will be needed to adapt it to other plants, thus facilitating the global inventory of regulatory regions across species.},
  language  = {en}
}
@article{LukasWacker2014,
  author    = {Lukas, Marcus and Wacker, Alexander},
  title     = {Acclimation to dietary shifts impacts the carbon budgets of Daphnia magna},
  series = {Journal of plankton research},
  volume    = {36},
  journal   = {Journal of plankton research},
  number    = {3},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0142-7873},
  doi       = {10.1093/plankt/fbu018},
  pages     = {848 -- 858},
  year      = {2014},
  abstract  = {Daphnia responds to low availability of carbon (food quantity) or limiting concentrations of nutrients relative to carbon (C) in excess (food quality) by respectively saving or discharging C via different pathways. We investigated which kind of food limitation leads to a faster regulation in Daphnia C budgets, and whether the pre-assimilative C pathways, ingestion and faeces egestion and the post-assimilative C pathways, excretion and respiration, are regulated concurrently. Daphnia magna were exposed to dietary shifts in different food quantities or qualities; food quality was varied in terms of the essential component, cholesterol. After acclimation to the new diet ranging from 0 to 96 h, C budgets were measured by a radiotracer technique. Dietary shifts in quantity and quality caused Daphnia to quickly adjust their C budgets within 6 h, but different C pathways were affected. A shift to low food quantity reduced Daphnia respiration indicating C retention. In contrast, sudden low quality food caused increased faeces egestion to discharge excess C. Furthermore, we observed a delayed increase in excretion but no change in respiration within the time frame studied. Such time-shifted responses appear to be an appropriate means to keep the costs of physiological adjustments relatively low, which in turn would benefit Daphnia performance.},
  language  = {en}
}
@unpublished{LendleinNeffeJerome2014,
  author    = {Lendlein, Andreas and Neffe, Axel T. and Jerome, Christine},
  title     = {Advanced functional polymers for medicine},
  series = {Advanced healthcare materials},
  volume    = {3},
  journal   = {Advanced healthcare materials},
  number    = {12},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {2192-2640},
  doi       = {10.1002/adhm.201400718},
  pages     = {1939 -- 1940},
  year      = {2014},
  language  = {en}
}
@article{KindMusterStaroskeetal.2014,
  author    = {Kind, Barbara and Muster, Britta and Staroske, Wolfgang and Herce, Henry D. and Sachse, Rene and Rapp, Alexander and Schmidt, Franziska and Koss, Sarah and Cardoso, M. Cristina and Lee-Kirsch, Min Ae},
  title     = {Altered spatio-temporal dynamics of RNase H2 complex assembly at replication and repair sites in Aicardi-Goutieres syndrome},
  series = {Human molecular genetics},
  volume    = {23},
  journal   = {Human molecular genetics},
  number    = {22},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0964-6906},
  doi       = {10.1093/hmg/ddu319},
  pages     = {5950 -- 5960},
  year      = {2014},
  abstract  = {Ribonuclease H2 plays an essential role for genome stability as it removes ribonucleotides misincorporated into genomic DNA by replicative polymerases and resolves RNA/DNA hybrids. Biallelic mutations in the genes encoding the three RNase H2 subunits cause Aicardi-Goutieres syndrome (AGS), an early-onset inflammatory encephalopathy that phenotypically overlaps with the autoimmune disorder systemic lupus erythematosus. Here we studied the intracellular dynamics of RNase H2 in living cells during DNA replication and in response to DNA damage using confocal time-lapse imaging and fluorescence cross-correlation spectroscopy. We demonstrate that the RNase H2 complex is assembled in the cytosol and imported into the nucleus in an RNase H2B-dependent manner. RNase H2 is not only recruited to DNA replication foci, but also to sites of PCNA-dependent DNA repair. By fluorescence recovery after photobleaching, we demonstrate a high mobility and fast exchange of RNase H2 at sites of DNA repair and replication. We provide evidence that recruitment of RNase H2 is not only PCNA-dependent, mediated by an interaction of the B subunit with PCNA, but also PCNA-independent mediated via the catalytic domain of the A subunit. We found that AGS-associated mutations alter complex formation, recruitment efficiency and exchange kinetics at sites of DNA replication and repair suggesting that impaired ribonucleotide removal contributes to AGS pathogenesis.},
  language  = {en}
}
@misc{LecourieuxKappelLecourieuxetal.2014,
  author    = {Lecourieux, Fatma and Kappel, Christian and Lecourieux, David and Serrano, Alejandra and Torres, Elizabeth and Arce-Johnson, Patricio and Delrot, Serge},
  title     = {An update on sugar transport and signalling in grapevine},
  series = {Journal of experimental botany},
  volume    = {65},
  journal   = {Journal of experimental botany},
  number    = {3},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0022-0957},
  doi       = {10.1093/jxb/ert394},
  pages     = {821 -- 832},
  year      = {2014},
  abstract  = {In addition to their role as a source of reduced carbon, sugars may directly or indirectly control a wide range of activities in plant cells, through transcriptional and post-translational regulation. This control has been studied in detail using Arabidopsis thaliana, where genetic analysis offers many possibilities. Much less is known about perennial woody species. For several years, various aspects of sugar sensing and signalling have been investigated in the grape (Vitis vinifera L.) berry, an organ that accumulates high concentrations of hexoses in the vacuoles of flesh cells. Here we review various aspects of this topic: the molecular basis of sugar transport and its regulation by sugars in grapevine; the functional analysis of several sugar-induced genes; the effects of some biotic and abiotic stresses on the sugar content of the berry; and finally the effects of exogenous sugar supply on the ripening process in field conditions. A picture of complex feedback and multiprocess regulation emerges from these data.},
  language  = {en}
}
@phdthesis{Girbig2014,
  author    = {Girbig, Dorothee},
  title     = {Analysing concerted criteria for local dynamic properties of metabolic systems},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-72017},
  school      = {Universit{\"a}t Potsdam},
  year      = {2014},
  abstract  = {Metabolic systems tend to exhibit steady states that can be measured in terms of their concentrations and fluxes. These measurements can be regarded as a phenotypic representation of all the complex interactions and regulatory mechanisms taking place in the underlying metabolic network. Such interactions determine the system's response to external perturbations and are responsible, for example, for its asymptotic stability or for oscillatory trajectories around the steady state. However, determining these perturbation responses in the absence of fully specified kinetic models remains an important challenge of computational systems biology. Structural kinetic modeling (SKM) is a framework to analyse whether a metabolic steady state remains stable under perturbation, without requiring detailed knowledge about individual rate equations. It provides a parameterised representation of the system's Jacobian matrix in which the model parameters encode information about the enzyme-metabolite interactions. Stability criteria can be derived by generating a large number of structural kinetic models (SK-models) with randomly sampled parameter sets and evaluating the resulting Jacobian matrices. The parameter space can be analysed statistically in order to detect network positions that contribute significantly to the perturbation response. Because the sampled parameters are equivalent to the elasticities used in metabolic control analysis (MCA), the results are easy to interpret biologically. In this project, the SKM framework was extended by several novel methodological improvements. These improvements were evaluated in a simulation study using a set of small example pathways with simple Michaelis Menten rate laws. Afterwards, a detailed analysis of the dynamic properties of the neuronal TCA cycle was performed in order to demonstrate how the new insights obtained in this work could be used for the study of complex metabolic systems. The first improvement was achieved by examining the biological feasibility of the elasticity combinations created during Monte Carlo sampling. Using a set of small example systems, the findings showed that the majority of sampled SK-models would yield negative kinetic parameters if they were translated back into kinetic models. To overcome this problem, a simple criterion was formulated that mitigates such infeasible models and the application of this criterion changed the conclusions of the SKM experiment. The second improvement of this work was the application of supervised machine-learning approaches in order to analyse SKM experiments. So far, SKM experiments have focused on the detection of individual enzymes to identify single reactions important for maintaining the stability or oscillatory trajectories. In this work, this approach was extended by demonstrating how SKM enables the detection of ensembles of enzymes or metabolites that act together in an orchestrated manner to coordinate the pathways response to perturbations. In doing so, stable and unstable states served as class labels, and classifiers were trained to detect elasticity regions associated with stability and instability. Classification was performed using decision trees and relevance vector machines (RVMs). The decision trees produced good classification accuracy in terms of model bias and generalizability. RVMs outperformed decision trees when applied to small models, but encountered severe problems when applied to larger systems because of their high runtime requirements. The decision tree rulesets were analysed statistically and individually in order to explore the role of individual enzymes or metabolites in controlling the system's trajectories around steady states. The third improvement of this work was the establishment of a relationship between the SKM framework and the related field of MCA. In particular, it was shown how the sampled elasticities could be converted to flux control coefficients, which were then investigated for their predictive information content in classifier training. After evaluation on the small example pathways, the methodology was used to study two steady states of the neuronal TCA cycle with respect to their intrinsic mechanisms responsible for stability or instability. The findings showed that several elasticities were jointly coordinated to control stability and that the main source for potential instabilities were mutations in the enzyme alpha-ketoglutarate dehydrogenase.},
  language  = {en}
}
@article{KuekenshoenerHagemannWohlwendetal.2014,
  author    = {Kuekenshoener, Tim and Hagemann, Urs B. and Wohlwend, Daniel and Raeuber, Christina and Baumann, Tobias and Keller, Sandro and Einsle, Oliver and Mueller, Kristian M. and Arndt, Katja Maren},
  title     = {Analysis of Selected and Designed Chimeric D- and L-alpha-Helix Assemblies},
  series = {Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences},
  volume    = {15},
  journal   = {Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences},
  number    = {9},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {1525-7797},
  doi       = {10.1021/bm5006883},
  pages     = {3296 -- 3305},
  year      = {2014},
  abstract  = {D-Peptides have been attributed pharmacological advantages over regular L-peptides, yet design rules are largely unknown. Based on a designed coiled coil-like D/L heterotetramer, named L-Base/D-Acid, we generated a library offering alternative residues for interaction with the D-peptide. Phage display selection yielded one predominant peptide, named HelixA, that differed at 13 positions from the scaffold helix. In addition to the observed D-/L-heterotetramers, ratio-dependent intermediate states were detected by isothermal titration calorimetry. Importantly, the formation of the selected HelixA/D-Acid bundle passes through fewer intermediate states than L-Base/D-Acid. Back mutation of HelixA core residues to L-Base (HelixLL) revealed that the residues at e/g-positions are responsible for the different intermediates. Furthermore, a Val-core variant (PeptideVV) was completely devoid of binding D-Acid, whereas an Ile-core helix (HelixII) interacted with D-Acid in a significantly more specific complex than L-Base.},
  language  = {en}
}
@article{BrustLehmannFettke2014,
  author    = {Brust, Henrike and Lehmann, Tanja and Fettke, J{\"o}rg},
  title     = {Analysis of the functional interaction of arabidopsis starch synthase and branching enzyme isoforms reveals that the cooperative action of SSI and BEs results in glucans with polymodal chain length distribution similar to amylopectin},
  series = {PLoS one},
  volume    = {9},
  journal   = {PLoS one},
  number    = {7},
  publisher = {PLoS},
  address   = {San Fransisco},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0102364},
  pages     = {14},
  year      = {2014},
  abstract  = {Starch synthase (SS) and branching enzyme (BE) establish the two glycosidic linkages existing in starch. Both enzymes exist as several isoforms. Enzymes derived from several species were studied extensively both in vivo and in vitro over the last years, however, analyses of a functional interaction of SS and BE isoforms are missing so far. Here, we present data from in vitro studies including both interaction of leaf derived and heterologously expressed SS and BE isoforms. We found that SSI activity in native PAGE without addition of glucans was dependent on at least one of the two BE isoforms active in Arabidopsis leaves. This interaction is most likely not based on a physical association of the enzymes, as demonstrated by immunodetection and native PAGE mobility analysis of SSI, BE2, and BE3. The glucans formed by the action of SSI/BEs were analysed using leaf protein extracts from wild type and be single mutants (Atbe2 and Atbe3 mutant lines) and by different combinations of recombinant proteins. Chain length distribution (CLD) patterns of the formed glucans were irrespective of SSI and BE isoforms origin and still independent of assay conditions. Furthermore, we show that all SS isoforms (SSI-SSIV) were able to interact with BEs and form branched glucans. However, only SSI/BEs generated a polymodal distribution of glucans which was similar to CLD pattern detected in amylopectin of Arabidopsis leaf starch. We discuss the impact of the SSI/BEs interplay for the CLD pattern of amylopectin.},
  language  = {en}
}
@article{HornProstStilleretal.2014,
  author    = {Horn, Susanne and Prost, Stefan and Stiller, Mathias and Makowiecki, Daniel and Kuznetsova, Tatiana and Benecke, Norbert and Pucher, Erich and Hufthammer, Anne K. and Schouwenburg, Charles and Shapiro, Beth and Hofreiter, Michael},
  title     = {Ancient mitochondrial DNA and the genetic history of Eurasian beaver (Castor fiber) in Europe},
  series = {Molecular ecology},
  volume    = {23},
  journal   = {Molecular ecology},
  number    = {7},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {0962-1083},
  doi       = {10.1111/mec.12691},
  pages     = {1717 -- 1729},
  year      = {2014},
  abstract  = {After centuries of human hunting, the Eurasian beaver Castor fiber had disappeared from most of its original range by the end of the 19th century. The surviving relict populations are characterized by both low genetic diversity and strong phylogeographical structure. However, it remains unclear whether these attributes are the result of a human-induced, late Holocene bottleneck or already existed prior to this reduction in range. To investigate genetic diversity in Eurasian beaver populations during the Holocene, we obtained mitochondrial control region DNA sequences from 48 ancient beaver samples and added 152 modern sequences from GenBank. Phylogeographical analyses of the data indicate a differentiation of European beaver populations into three mitochondrial clades. The two main clades occur in western and eastern Europe, respectively, with an early Holocene contact zone in eastern Europe near a present-day contact zone. A divergent and previously unknown clade of beavers from the Danube Basin survived until at least 6000years ago, but went extinct during the transition to modern times. Finally, we identify a recent decline in effective population size of Eurasian beavers, with a stronger bottleneck signal in the western than in the eastern clade. Our results suggest that the low genetic diversity and the strong phylogeographical structure in recent beavers are artefacts of human hunting-associated population reductions. While beaver populations have been growing rapidly since the late 19th century, genetic diversity within modern beaver populations remains considerably reduced compared to what was present prior to the period of human hunting and habitat reduction.},
  language  = {en}
}
@article{RoderHille2014,
  author    = {Roder, Phillip and Hille, Carsten},
  title     = {ANG-2 for quantitative Na+ determination in living cells by time-resolved fluorescence microscopy},
  series = {Photochemical \& photobiological sciences},
  volume    = {13},
  journal   = {Photochemical \& photobiological sciences},
  number    = {12},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {1474-905X},
  doi       = {10.1039/c4pp00061g},
  pages     = {1699 -- 1710},
  year      = {2014},
  abstract  = {Sodium ions (Na+) play an important role in a plethora of cellular processes, which are complex and partly still unexplored. For the investigation of these processes and quantification of intracellular Na+ concentrations ([Na+](i)), two-photon coupled fluorescence lifetime imaging microscopy (2P-FLIM) was performed in the salivary glands of the cockroach Periplaneta americana. For this, the novel Na+-sensitive fluorescent dye Asante NaTRIUM Green-2 (ANG-2) was evaluated, both in vitro and in situ. In this context, absorption coefficients, fluorescence quantum yields and 2P action cross-sections were determined for the first time. ANG-2 was 2P-excitable over a broad spectral range and displayed fluorescence in the visible spectral range. Although the fluorescence decay behaviour of ANG-2 was triexponential in vitro, its analysis indicates a Na+-sensitivity appropriate for recordings in living cells. The Na+-sensitivity was reduced in situ, but the biexponential fluorescence decay behaviour could be successfully analysed in terms of quantitative [Na+](i) recordings. Thus, physiological 2P-FLIM measurements revealed a dopamine-induced [Na+](i) rise in cockroach salivary gland cells, which was dependent on a Na+-K+-2Cl-cotransporter (NKCC) activity. It was concluded that ANG-2 is a promising new sodium indicator applicable for diverse biological systems.},
  language  = {en}
}
@article{RadchukJohstGroeneveldetal.2014,
  author    = {Radchuk, Viktoriia and Johst, Karin and Groeneveld, J{\"u}rgen and Turlure, Camille and Grimm, Volker and Schtickzelle, Nicolas},
  title     = {Appropriate resolution in time and model structure for population viability analysis: Insights from a butterfly metapopulation},
  series = {: an international journal},
  volume    = {169},
  journal   = {: an international journal},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0006-3207},
  doi       = {10.1016/j.biocon.2013.12.004},
  pages     = {345 -- 354},
  year      = {2014},
  abstract  = {The importance of a careful choice of the appropriate scale for studying ecological phenomena has been stressed repeatedly. However, issues of spatial scale in metapopulation dynamics received much more attention compared to temporal scale. Moreover, multiple calls were made to carefully choose the appropriate model structure for Population Viability Analysis (PVA). We assessed the effect of using coarser resolution in time and model structure on population dynamics. For this purpose, we compared outcomes of two PVA models differing in their time step: daily individual-based model (dIBM) and yearly stage-based model (ySBM), loaded with empirical data on a well-known metapopulation of the butterfly Boloria eunomia. Both models included the same environmental drivers of population dynamics that were previously identified as being the most important for this species. Under temperature change scenarios, both models yielded the same qualitative scenario ranking, but they quite substantially differed quantitatively with dIBM being more pessimistic in absolute viability measures. We showed that these differences stemmed from inter-individual heterogeneity in dIBM allowing for phenological shifts of individual appearance. We conclude that a finer temporal resolution and an individual-based model structure allow capturing the essential mechanisms necessary to go beyond mere PVA scenario ranking. We encourage researchers to carefully chose the temporal resolution and structure of their model aiming at (1) depicting the processes important for (meta)population dynamics of the species and (2) implementing the environmental change scenarios expected for their study system in the future, using the temporal resolution at which such changes are predicted to operate.},
  language  = {en}
}
@article{StiefAltmannHoffmannetal.2014,
  author    = {Stief, Anna and Altmann, Simone and Hoffmann, Karen and Pant, Bikram Datt and Scheible, Wolf-R{\"u}diger and B{\"a}urle, Isabel},
  title     = {Arabidopsis miR156 regulates tolerance to recurring environmental stress through SPL transcription factors},
  series = {The plant cell},
  volume    = {26},
  journal   = {The plant cell},
  number    = {4},
  publisher = {American Society of Plant Physiologists},
  address   = {Rockville},
  issn      = {1040-4651},
  doi       = {10.1105/tpc.114.123851},
  pages     = {1792 -- 1807},
  year      = {2014},
  abstract  = {Plants are sessile organisms that gauge stressful conditions to ensure survival and reproductive success. While plants in nature often encounter chronic or recurring stressful conditions, the strategies to cope with those are poorly understood. Here, we demonstrate the involvement of ARGONAUTE1 and the microRNA pathway in the adaptation to recurring heat stress (HS memory) at the physiological and molecular level. We show that miR156 isoforms are highly induced after HS and are functionally important for HS memory. miR156 promotes sustained expression of HS-responsive genes and is critical only after HS, demonstrating that the effects of modulating miR156 on HS memory do not reflect preexisting developmental alterations. miR156 targets SPL transcription factor genes that are master regulators of developmental transitions. SPL genes are posttranscriptionally downregulated by miR156 after HS, and this is critical for HS memory. Altogether, the miR156-SPL module mediates the response to recurring HS in Arabidopsis thaliana and thus may serve to integrate stress responses with development.},
  language  = {en}
}