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201.
Protein interaction networks are important for the understanding of regulatory mechanisms, for the explanation of experimental data and for the prediction of protein functions. Unfortunately, most interaction data is available only for model organisms. As a possible remedy, the transfer of interactions to organisms of interest is common practice, but it is not clear when interactions can be transferred from one organism to another and, thus, the confidence in the derived interactions is low. Here, we propose to use a rich set of features to train Random Forests in order to score transferred interactions. We evaluated the transfer from a range of eukaryotic organisms to S. cerevisiae using orthologs. Directly transferred interactions to S. cerevisiae are on average only 24% consistent with the current S. cerevisiae interaction network. By using commonly applied filter approaches the transfer precision can be improved, but at the cost of a large decrease in the number of transferred interactions. Our Random Forest approach uses various features derived from both the target and the source network as well as the ortholog annotations to assign confidence values to transferred interactions. Thereby, we could increase the average transfer consistency to 85%, while still transferring almost 70% of all correctly transferable interactions. We tested our approach for the transfer of interactions to other species and showed that our approach outperforms competing methods for the transfer of interactions to species where no experimental knowledge is available. Finally, we applied our predictor to score transferred interactions to 83 targets species and we were able to extend the available interactome of B. taurus, M. musculus and G. gallus with over 40,000 interactions each. Our transferred interaction networks are publicly available via our web interface, which allows to inspect and download transferred interaction sets of different sizes, for various species, and at specified expected precision levels. Availability:
http://services.bio.ifi.lmu.de/coin-db/. 相似文献
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203.
Jean-Yves Zimmer Fran?ois Smeets Grégory Simonon Jean Fagot Eric Haubruge Frédéric Francis Bertrand Losson 《PloS one》2013,8(6)
Several species of Culicoides (Diptera: Ceratopogonidae) biting midges serve as biological vectors for the bluetongue virus (BTV) and the recently described Schmallenberg virus (SBV) in northern Europe. Since their recent emergence in this part of the continent, these diseases have caused considerable economic losses to the sheep and cattle industries. Much data is now available that describe the distribution, population dynamics, and feeding habits of these insects. However, little is known regarding the presence of Culicoides in unusual habitats such as peaty marshes, nor their potential vector capacity. This study evaluated Culicoides biting midges present in the bogs of a Belgian nature reserve compared to those residing at a nearby cattle farm. Culicoides were trapped in 2011 at four different sites (broadleaved and coniferous forested areas, open environments, and at a scientific station) located in the Hautes Fagnes Nature Reserve (Belgium). An additional light trap was operated on a nearby cattle farm. Very high numbers of biting midges were captured in the marshy area and most of them (70 to 95%) were Culicoides impunctatus, a potential vector of BTV and other pathogens. In addition, fewer numbers of C. obsoletus/C. scoticus species, C. chiopterus, and C. dewulfi were observed in the bogs compared to the farm. The wet environment and oligotrophic nature of the soil were probably responsible for these changes in the respective populations. A total of 297,808 Culicoides midges belonging to 27 species were identified during this study and 3 of these species (C. sphagnumensis, C. clintoni and C. comosioculatus) were described in Belgium for the first time. 相似文献
204.
Sina Alexa Trautmann-Lengsfeld Judith Domínguez-Borràs Carles Escera Manfred Herrmann Thorsten Fehr 《PloS one》2013,8(6)
A recent functional magnetic resonance imaging (fMRI) study by our group demonstrated that dynamic emotional faces are more accurately recognized and evoked more widespread patterns of hemodynamic brain responses than static emotional faces. Based on this experimental design, the present study aimed at investigating the spatio-temporal processing of static and dynamic emotional facial expressions in 19 healthy women by means of multi-channel electroencephalography (EEG), event-related potentials (ERP) and fMRI-constrained regional source analyses. ERP analysis showed an increased amplitude of the LPP (late posterior positivity) over centro-parietal regions for static facial expressions of disgust compared to neutral faces. In addition, the LPP was more widespread and temporally prolonged for dynamic compared to static faces of disgust and happiness. fMRI constrained source analysis on static emotional face stimuli indicated the spatio-temporal modulation of predominantly posterior regional brain activation related to the visual processing stream for both emotional valences when compared to the neutral condition in the fusiform gyrus. The spatio-temporal processing of dynamic stimuli yielded enhanced source activity for emotional compared to neutral conditions in temporal (e.g., fusiform gyrus), and frontal regions (e.g., ventromedial prefrontal cortex, medial and inferior frontal cortex) in early and again in later time windows. The present data support the view that dynamic facial displays trigger more information reflected in complex neural networks, in particular because of their changing features potentially triggering sustained activation related to a continuing evaluation of those faces. A combined fMRI and EEG approach thus provides an advanced insight to the spatio-temporal characteristics of emotional face processing, by also revealing additional neural generators, not identifiable by the only use of an fMRI approach. 相似文献
205.
Gunnar Ottleben Luigi Messori Heinz Rüterjans Robert Kaptein Michèle Granger-Schnarr Manfred Schnarr 《Journal of biomolecular structure & dynamics》2013,31(3):447-461
Abstract A synthetic half-operator DNA-duplex, d(GCTACTGTATGT), containing a portion of the proposed recognition sequence (CTGT) of serveral “SOS” genes, has been synthesized. The dodecamer has been characterized through 1H-NMR spectroscopy. Complete assignment of exchangeable hydrogen bonded imino protons has been acheived by applying 1D NOE techniques and an analysis of the temperature dependence of the chemical shifts. In order to determine the specific role of the CTGT consensus sequence in the overall recognition process, the oligonucleotide duplex has been titrated with the amino terminal DNA binding domain of the LexA repressor. The observation of substantial changes of 1H-NMR chemical shifts in the imino proton region upon interaction with the protein strongly suggests that the protein binds specifically to the operator DNA. The largest deviations of 1H-NMR chemical shifts upon protein binding have been observed for protons assigned to the CTGT segment, thus strongly suggesting a direct involvement of this sequence in the binding process. At high potassium chloride concentrations the 1H-NMR chemical shift deviations are reverted which is consistent with the known drop in the affinity constant of LexA for operator DNA at high salt concentrations. 相似文献
206.
Marc Zimmer 《Journal of biomolecular structure & dynamics》2013,31(5):787-797
Abstract A thorough conformational search of all the conformations available to oxygen-bound urea within wild-type urease was carried out. Identical low energy urea conformations were obtained by a Ramachandran type plot for the NHis272-Ni1-O-Curea and Ni1-O-Curea-Nurea dihedral angles. Ramachandran plots, with active sites and protonation states modified to model the different urease mechanisms, were used to evaluate the different mechanisms. Based upon the low energy conformations available to urea in the active site of wild-type urease one can conclude that the traditional “His320 acts as a base” mechanism is unlikely, while the N,O urea bridged and the reverse protonation mechanisms cannot be ruled out. A consensus hydrogen-bonding network that does not favor any of the mechanisms has been reconfirmed by the extensive conformational search. 相似文献
207.
Birgit Ploier Melanie Scharwey Barbara Koch Claudia Schmidt Jessica Schatte Gerald Rechberger Manfred Kollroser Albin Hermetter Günther Daum 《The Journal of biological chemistry》2013,288(50):36061-36072
Saccharomyces cerevisiae, as well as other eukaryotes, preserves fatty acids and sterols in a biologically inert form, as triacylglycerols and steryl esters. The major triacylglycerol lipases of the yeast S. cerevisiae identified so far are Tgl3p, Tgl4p, and Tgl5p (Athenstaedt, K., and Daum, G. (2003) YMR313c/TGL3 encodes a novel triacylglycerol lipase located in lipid particles of Saccharomyces cerevisiae. J. Biol. Chem. 278, 23317–23323; Athenstaedt, K., and Daum, G. (2005) Tgl4p and Tgl5p, two triacylglycerol lipases of the yeast Saccharomyces cerevisiae, are localized to lipid particles. J. Biol. Chem. 280, 37301–37309). We observed that upon cultivation on oleic acid, triacylglycerol mobilization did not come to a halt in a yeast strain deficient in all currently known triacylglycerol lipases, indicating the presence of additional not yet characterized lipases/esterases. Functional proteome analysis using lipase and esterase inhibitors revealed a subset of candidate genes for yet unknown hydrolytic enzymes on peroxisomes and lipid droplets. Based on the conserved GXSXG lipase motif, putative functions, and subcellular localizations, a selected number of candidates were characterized by enzyme assays in vitro, gene expression analysis, non-polar lipid analysis, and in vivo triacylglycerol mobilization assays. These investigations led to the identification of Ayr1p as a novel triacylglycerol lipase of yeast lipid droplets and confirmed the hydrolytic potential of the peroxisomal Lpx1p in vivo. Based on these results, we discuss a possible link between lipid storage, lipid mobilization, and peroxisomal utilization of fatty acids as a carbon source. 相似文献
208.
Benjamin Gennequin David-Marian OtteAndreas Zimmer 《Biochemical and biophysical research communications》2013
The CRISPR/Cas technology has been successfully used to stimulate the integration of small DNA sequences in a target locus to produce gene mutations. However, many applications require homologous recombination using large gene-targeting constructs. Here we address the potential of CRISPR/Cas-mediated double-strand breaks to enhance the genetic engineering of large target sequences using a construct for “humanizing” the mouse Cnr2 gene locus. We designed a small-guide RNA that directs the induction of double strand breaks by Cas9 in the Cnr2 coding exon. By co-transfection of the CRISPR/Cas system with the 10 kb targeting construct we were able to boost the recombination frequency more than 200-fold from 0.27% to 67%. This simple technology can thus be used for the homologous integration of large gene fragments and should greatly enhance our ability to generate any kind of genetically altered mouse models. 相似文献
209.
210.