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cc-by | , 2006). At the end of summer 1991, the 5300-year-old Tyrolean Iceman mummy emerged from the ablating ice field of the Tisenjoch, a saddle at 3210 m near the Italian-Austrian border in the eastern Alps (Seidler et al. , 1992). The excellent state of preservation of the Tyrolean Iceman provides strong evidence for the ... | 10.5194/tc-10-2779-2016 | article | en | 2,016 | true | false | false | false | Earth and Planetary Sciences | https://openalex.org/fields/19 |
cc-by | Bedrock topography Ground penetrating radar (GPR) was used to determine the bedrock topography (e. g. Binder et al. , 2009; Moran et al. , 2000) and to infer information about possible englacial features (e. g. Blindow and Thyssen, 1986; Konrad et al. , 2013). GPR profiles of 50 MHz were collected with a GSSI SIR 3000... | 10.5194/tc-10-2779-2016 | article | en | 2,016 | true | false | false | false | Earth and Planetary Sciences | https://openalex.org/fields/19 |
cc-by | e. increased potential for contamination due to a higher number of steps during sample processing). 14 C analyses were conducted using the compact radiocarbon Accelerator Mass Spectrometer (AMS) system "MI-CADAS" at the University of Bern (LARA laboratory). For details about sample preparation, WIOC separation, blank c... | 10.5194/tc-10-2779-2016 | article | en | 2,016 | false | true | false | false | Earth and Planetary Sciences | https://openalex.org/fields/19 |
cc-by | Acknowledgments This review was presented in part at the 15th Annual World Vaccine Congress 2015, Washington, DC, and to United Nations High-Level Panel on Access to Medicines in March 2016. The authors thank Grenville Marsh ( Sanofi Pasteur ) and Phillip Leventhal ( 4Clinics, Paris, France ) for editorial suppor... | 10.1080/21645515.2016.1172162 | review | en | 2,016 | false | false | true | false | Social Sciences | https://openalex.org/fields/33 |
cc-by | DREAM challenges are community competitions designed to advance computational methods and address fundamental questions in system biology and translational medicine. Each challenge asks participants to develop and apply computational methods to either predict unobserved outcomes or to identify unknown model parameters ... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Amendments from Version 1 One issue about the first version of the paper was related to the installation of the software itself. Indeed, dependencies on several (established) Python scientific software required long compilation time and sometimes compilation failure. This is a general issue but following comments and d... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Scoring methods developed by challenge organizers are reported in the publications that describe the challenges, but the corresponding code is typically provided only in pseudo-code or at best as a script in an arbitrary language (R, Python, Perl. ) and syntax by different developers leading to a set of heterogeneous c... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | We also provide a standalone executable for end-users and the ability to share and re-use existing code within a common framework to ease the development of new scoring functions for future challenges. DREAMTools does not provide code to generate the data or to manage leaderboards (which happens within Synapse), but fo... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Methods The diversity of challenges proposed by DREAM (see Available challenges section) and the plethora of languages that have been used in past challenges has led to a fragmentation of the software designed to score submissions. In order to tackle this problem, we chose Python as a glue language. In addition to a cl... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Note that all challenges follow the same structure with three main functions: to retrieve a template example, to retrieve a gold standard, and to score a prediction. In addition, dreamtools may give access to more functions. For example, the D5C2 challenge 6 has a plot method to compare a prediction with the official s... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | The downloaded files are stored locally in a standard place (e. g. , /home/user/. config/dreamtools directory under Linux systems). Users can retrieve the location of the templates and gold standards with the dreamtools application as follows: dreamtools --challenge D3C1 --downloadtemplate If sub-challenges are availab... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | dreamtools-layout --challenge D10C10 This command creates a directory named after the challenge nickname. Inside the directory, sub-directories are created to store the templates, gold standards and possibly other data sets. For instance, data to compute p-values may be stored in the data directory. Code related to tra... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Here is an example of such a file, which needs to be filled by the developer: Using the code above, the challenge will be automatically available in the standalone application without extra costs to the developer. The download_template( ) method is not strictly speaking required; it helps a user to create a prediction ... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Installation and dependencies The DREAMTools source code is available on GitHub. It can be downloaded and installed as follows: > git clone git@github. com:dreamtools/ dreamtools. git > cd dreamtools > python setup. py install The source code gives access to the latest version but releases are also provided on the Pyth... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Consequently, we also provide a pre-compiled version of DREAMTools within the bio channel (http://bioconda. github. io), which is a channel of Anaconda (https://www. continuum. io/downloads). The latter provides about 400 scientific packages including Numpy and Pandas aforementioned. Finally, note that in order to keep... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Scoring metric: As in the D7C1 challenge (See D7C1 section), submissions were scored based on a combination of their parameter and prediction distances (Equation 13 ). The parameter distance was computed as the average log ratio of the estimated and true parameter values (Equation 11 ). The prediction distance was co... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | DREAM8. 5 D8dot5C1: Rheumatoid Arthritis Responder Description: The goal of this challenge was to use a crowd-based competition framework to develop a validated molecular predictor of anti-TNF response in Rheumatoid Arthritis (RA). We used the whole genome SNP data derived from two cohorts: 2,706 anti-TNF treated RA pa... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | true | false | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Scoring metric: In sub-challenge 1, the scoring methods are the AUROC and balanced accuracy (BAC), defined in Section 1. 1. In sub-challenge 2 and 3, the scoring methods are the concordance index (CI) and Pearson correlation coefficient (see Section 1. 2. 5). The Pearson correlation coefficient is used to measure corre... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | true | false | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | DREAM10 D10C1: ALS Stratification Prize4Life Description: This challenge is a follow-up on to the DREAM 7 ALS Prize 4 Life Challenge (see D7C3 for details). It focuses on predicting the progression and survival of ALS patients. One objective of the challenge is to leverage the PRO-ACT database of more than 8,000 cases ... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | true | false | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Conclusions The organization of a collaborative competition such as the DREAM challenges is a complex task that starts by identifying a currently important and unresolved scientific problem, acquiring relevant data sets, engaging a community of participants, and implementing an appropriate scoring methodology. Particip... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | true | false | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | In this paper, we presented DREAMTools to provide a uniform framework where researchers can easily assess and compare new methods against benchmarks. DREAMTools gathers most of the scoring functions used in previous DREAM challenges. DREAM-Tools uses Python as a glue language known for its flexibility and ability to ca... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | The gold standards are also available together with the relevant scoring functions. Since DREAMTools makes use of an object oriented approach, it will ease the integration of future challenges thereby facilitating scoring in upcoming challenges. DREAMTools can also be used as a place to retrieve metadata and informatio... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | ( , ) ( , , , ) d d i j i j i j c G R h g g r r N N < = = -∑ c -index ( 1) where > < ∨ < > = = > > ∨ < < 1, if ( & ) ( & ) ( , , , ) 0. 5, if ( ) 0, if ( & ) ( & ) i j i j i j i j i j i j i j i j i j i j i j g g r r g g r r h g g r r g g g g r r g g r r (40) In the previous formulation of the c-index, t... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Acknowledgements The authors would like to thank all DREAM participants, organisers and data providers for their contributions to the DREAM challenges. | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | false | true | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | documentation Availability: DREAMTools are available at. The source code is http://pypi. python. org/pypi/dreamtools available at. http://github. com/dreamtools/dreamtools This article is included in the DREAM Challenges channel. | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Software availability Software releases are available from the Pypi website https://pypi. python. org/pypi/dreamtools Latest source code is hosted on GitHub website http://github. com/dreamtools/dreamtools Archived source code at the time of publication http://www. dx. doi. org/10. 5281/zenodo. 47949 37 g report and f... | 10.12688/f1000research.7118.2 | preprint | en | 2,016 | true | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Small-angle scattering measurement and analysis SAXS experiments were carried out at the European Molecular Biology Laboratory beamlines X33 and P12 of DORIS and PETRAIII storage rings respectively, using the X-ray wavelengths of 1. 54 and 1. 24 Å and a sample-to-detector distance of 2. 7 and 3. 0 m, respectively (38)... | 10.1093/nar/gkw1183 | article | en | 2,016 | true | false | false | false | Materials Science | https://openalex.org/fields/25 |
cc-by | The forward scattering intensity, I(0), and the radius of gyration, R g , were evaluated using Guinier's approximation (40) , assuming that at very small angles (s < 1. 3/R g ), the intensity can be well represented as I(s) = I(0) exp(-(sR g ) 2 /3). The P(r) distribution function of free PCNA was calculated by indire... | 10.1093/nar/gkw1183 | article | en | 2,016 | false | true | false | false | Materials Science | https://openalex.org/fields/25 |
cc-by | We first removed translations and rotations for the whole molecule and then calculated the rotational correlation function with GROMACS utilities trjconv and rotacf respectively (48, 60). For each residue, three C(t) functions were computed, corresponding to each of the protomers of PCNA, and subsequently averaged. Th... | 10.1093/nar/gkw1183 | article | en | 2,016 | false | true | false | false | Materials Science | https://openalex.org/fields/25 |
cc-by | Short explicit-solvent MD simulations for WAXSiS calculations The SAXS predictions for the structural ensembles were based on a short explicit-solvent MD simulation conducted for each conformation of the different ensembles. Accordingly, each structure of the ensembles of p15, PCNA and PCNA-p15 complexes were pre-proce... | 10.1093/nar/gkw1183 | article | en | 2,016 | false | true | false | false | Materials Science | https://openalex.org/fields/25 |
cc-by | This reconstruction displayed the expected ring-shape of the protein and precisely enveloped the crystallographic structure of PCNA (PDB code: 4D2G) (27). The high quality of the reconstruction reflects the wealth of information encoded in the 1D scattering pattern of PCNA. Before analyzing the SAXS curves of the PCNA... | 10.1093/nar/gkw1183 | article | en | 2,016 | true | false | false | false | Materials Science | https://openalex.org/fields/25 |
cc-by | WAXSiS analysis of the intrinsically discorded protein p15 The local structural information contained in Residual Dipolar Couplings (RDCs) and the global features reported by SAXS were recently combined to study the intrinsic conformational flexibility of p15 in solution (37). Here, we tested the performance of WAXSiS... | 10.1093/nar/gkw1183 | article | en | 2,016 | false | true | false | false | Materials Science | https://openalex.org/fields/25 |
cc-by | 1 M (27). For K d values much lower than the total concentration of PCNA (i. e. K d < 1 M), most of the p15 molecules are bound to PCNA, thereby explaining the lack of sensitivity of 2 to the K d. However, at such high affinities there was poor agreement with the experimental data, presumably because the model does not... | 10.1093/nar/gkw1183 | article | en | 2,016 | true | false | false | false | Materials Science | https://openalex.org/fields/25 |
cc-by | In particular, our model captured the smearing of the SAXS features upon addition of increasing amounts of p15. At the optimal K d , the averaged collective 2 value of the com- plete dataset was 0. 95, and the individual collective 2 values varied between 0. 91 and 0. 98. All titration points at a K d of 30 M containe... | 10.1093/nar/gkw1183 | article | en | 2,016 | true | false | false | false | Materials Science | https://openalex.org/fields/25 |
cc-by | p15 crosses the PCNA ring In all the models built for the structural analysis of the SAXS data for the PCNA-p15 complex, the disordered N-terminal region of p15 was modeled to cross the ring and emerge on the back face. This model, which we call in-model (see Figure 6A ), is supported by previous NMR and X-ray crystal... | 10.1093/nar/gkw1183 | article | en | 2,016 | true | false | false | false | Materials Science | https://openalex.org/fields/25 |
cc-by | While MD simulations probe fast dynamics on globular proteins, the conformational exploration of disordered proteins such as p15 and its complexes requires other approaches. Applying integrative strategies, we used previous non-overlapping NMR and crystallographic information to build accurate models for these highly f... | 10.1093/nar/gkw1183 | article | en | 2,016 | true | false | false | false | Materials Science | https://openalex.org/fields/25 |
cc-by | In line with this hypothesis, in a recent SAXS/SANS study using three mutants of the green fluorescent protein with very different net charges (+36, -6 and -29), it was demonstrated that the hydration shell is locally denser around acidic residues than around basic and hydrophobic ones (81). Our study also shows that,... | 10.1093/nar/gkw1183 | article | en | 2,016 | false | true | false | false | Materials Science | https://openalex.org/fields/25 |
cc-by | At the concentrations normally used in SAXS experiments, the K d value for stronger affinities cannot be precisely determined and, in this scenario, SAXS can detect only the formation of the complex. The continuous improvement of SAXS beam lines and commercial detectors will decrease the amount of protein required to a... | 10.1093/nar/gkw1183 | article | en | 2,016 | true | false | false | false | Materials Science | https://openalex.org/fields/25 |
cc-by | Conversely, structural models where p15 does not cross the ring but places its N-and C-termini on the front face of PCNA presented a lower agreement with the SAXS dataset. NMR chemical shift perturbation experiments and the crystallographic structure of PCNA with an enlarged version of p15 PIP region already suggested ... | 10.1093/nar/gkw1183 | article | en | 2,016 | true | false | false | false | Materials Science | https://openalex.org/fields/25 |
cc-by | ACKNOWLEDGEMENTS We gratefully acknowledge the use of the European Molecular Biology Laboratory BioSAXS X33 and P12 beamlines at DESY Hamburg and also the GWDG computing cluster for SAXS-profile calculations of PCNA-p15 ensembles. We acknowledge supercomputing facilities from the Catalan CSUC. | 10.1093/nar/gkw1183 | article | en | 2,016 | false | false | true | false | Materials Science | https://openalex.org/fields/25 |
cc-by | FUNDING SPIN-HD -ANR Chaires d'Excellence 2011; ATIP-Avenir; French Infrastructure for Integrated Structural Biology Nucleic Acids Research , 2017, Vol. 45, No. 3 1513 [FRISBI -ANR-10-INSB-05-01 to P. B. , CTQ2014-56966-R] from the Spanish Ministerio de Economía y Competitividad (to F. J. B. ); Deutsche Forschun... | 10.1093/nar/gkw1183 | article | en | 2,016 | false | false | true | false | Materials Science | https://openalex.org/fields/25 |
cc-by | Agar-grown colonies were microscopic and translucent with a mean diameter of 1 μm. Bacterial cells were Gram-positive cocci, ranging in length from 300 to 500 nm. Strain FC2 was catalase and oxidase negative. The 16S rRNA gene was sequenced using the fD1-rP2 primers as previously described [4] , using a 3130-XL sequen... | 10.1016/j.nmni.2016.07.017 | article | en | 2,016 | true | false | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | nov. (u. ri. na. coc'cus, N. L. masc. n. composed of u. ri. na, L. N. gen. fem. urina, from urina, the Latin name of urine and coc'cus. L. N. gen. masc. coccus, from coccus, the Latin name of bacterium having a spherical or spheroidal shape) as strain FC2 is a coccus and was first isolated from a paediatric urine sampl... | 10.1016/j.nmni.2016.07.017 | article | en | 2,016 | true | false | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | ACKNOWLEDGMENTS We thank all speakers for their contribution to the meeting. We also wish to thank the Center for Research in Agricultural Genomics (CRAG) , B-Debate , and the National Science Foundation for funding the meeting, and Semillas Fitó , Sequentia Biotech , the Xarxa de. | 10.1534/g3.115.025502 | article | en | 2,016 | false | false | true | false | Agricultural and Biological Sciences | https://openalex.org/fields/11 |
cc-by | evasion indirectly provides a gateway at the host-tick interface for pathogens such as Borrelia spp. and tick-borne encephalitis virus. A profile during viral infection showed that nymphal I. scapularis salivary gland lipocalin genes are differentially expressed when compared to mock infections 14. There are currently... | 10.1038/srep32372 | article | en | 2,016 | true | false | false | false | Immunology and Microbiology | https://openalex.org/fields/24 |
cc-by | Results and Discussion Identifying three lipocalins from the European tick disease vector, Ixodes ricinus. The most frequent transcripts from the I. ricinus salivary gland transcriptome shotgun assembly (TSA: GADI00000000. 1) are lipocalins (5. 76% of the entire transcriptome) and most (~90%) are putative histamine-bin... | 10.1038/srep32372 | article | en | 2,016 | true | false | false | false | Immunology and Microbiology | https://openalex.org/fields/24 |
cc-by | 29. Many identified I. ricinus lipocalins are also highly glycosylated 31 ; however, according to Schwarz et al. 26 , only three of the eight have glycosylation sites. These include, JAA70260 (4 sites), JAA70156 (1 site) and JAA67401 (1 site). The Illumina data from the Schwarz et al. 26 publication was compiled to... | 10.1038/srep32372 | article | en | 2,016 | true | false | false | false | Immunology and Microbiology | https://openalex.org/fields/24 |
cc-by | ricinus lipocalins with other tick lipocalins, we performed a second phylogenetic analysis that included 1748 tick lipocalins available in GenBank. After applying some selection criteria to the lipocalins (see methods), the final alignment contained 803 sequences. The NJ phylogenetic tree obtained from this analysis is... | 10.1038/srep32372 | article | en | 2,016 | true | false | false | false | Immunology and Microbiology | https://openalex.org/fields/24 |
cc-by | Sequences are labeled with species names, GenBank accession numbers and PDB ID (when crystal structures were available). and Monotonin (Fig. 4 ). The substitutions, however, may prevent the three I. ricinus lipocalins maintaining monoamines within their binding cavity or may provide alternative binding modes. Mans et a... | 10.1038/srep32372 | article | en | 2,016 | true | false | false | false | Immunology and Microbiology | https://openalex.org/fields/24 |
cc-by | Concluding remarks A new approach is presented here to predict the substrate(s) for highly divergent, uncharacterized proteins. Biophysical simulations, such as the stochastic approach employed by the PELE software, permit a robust analysis on the all-atom energy landscape exploration and interaction between a ligand a... | 10.1038/srep32372 | article | en | 2,016 | false | true | false | false | Immunology and Microbiology | https://openalex.org/fields/24 |
cc-by | Materials and Methods Sequences. The protein sequence dataset for the global tree of lipocalins comprised 146 sequences. These lipocalins included 113 sequences analyzed by Ganfornina et al. 1 , 30 new sequences reported since 2000 with experimentally determined 3D structures, and 3 lipocalins described herein from th... | 10.1038/srep32372 | article | en | 2,016 | true | false | false | false | Immunology and Microbiology | https://openalex.org/fields/24 |
cc-by | We did not use PAGAN (see below) at this stage, as it would be computationally expensive. The selection using MaxAlign resulted in an alignment of 788 sequences. Since MaxAlign excluded tick lipocalins with known ligands, we used the "add" option from the MAFFT package 45 to include them. The final tick lipocalins al... | 10.1038/srep32372 | article | en | 2,016 | true | true | false | false | Immunology and Microbiology | https://openalex.org/fields/24 |
cc-by | Global tree of lipocalin amino acid sequences. The three alignments produced by the methods described in the previous section were used to infer maximum likelihood (ML), neighbor joining (NJ) and maximum parsimony (MP) phylogenetic trees. The best-fit model of sequence evolution was selected based on the Corrected Akai... | 10.1038/srep32372 | article | en | 2,016 | false | true | false | false | Immunology and Microbiology | https://openalex.org/fields/24 |
cc-by | These PDBs included Japanin (PDB: 4BOE) and Ra-HBP2 (PDB: 1QFT) from R. appendiculatus, Monotonin from the soft tick A. monolakensis (PDB: 3BRN), and the bilin-binding protein (BBP; PDB: 1BBP) from the butterfly P. brassicae. The three I. ricinus salivary lipocalins were modelled using the Robetta server 52. All struc... | 10.1038/srep32372 | article | en | 2,016 | true | false | false | false | Immunology and Microbiology | https://openalex.org/fields/24 |
cc-by | Metropolis Monte Carlo exploration simulations for ligand screening. The Metropolis Monte Carlo-based PELE server was used for the biophysical simulations. The PELE software can demonstrate, step-by-step, the entrance or exit pathway of a ligand to/from the active site of a protein. Since lipocalins maintain ligands wi... | 10.1038/srep32372 | article | en | 2,016 | false | true | false | false | Immunology and Microbiology | https://openalex.org/fields/24 |
cc-by | Molecular dynamics studies on lipocalins indicate that the overall conformation of the beta-barrel is maintained while larger changes occur for the open-end beta-hairpin loops 55. Confirmed by NMR, these large conformational changes are present for open-end beta-hairpin loops in bound and unbound lipocalin structures ... | 10.1038/srep32372 | article | en | 2,016 | false | true | false | false | Immunology and Microbiology | https://openalex.org/fields/24 |
cc-by | Statistical analysis of ligand exploration simulations. A two-way ANOVA was performed to test the differences in the response variable of the distance (in Å) from the active site and binding energy (in kcal/mol), as calculated by PELE, and for the categorical explanatory variables 'lipocalin' and 'ligand'. An ANOVA, wh... | 10.1038/srep32372 | article | en | 2,016 | false | true | false | false | Immunology and Microbiology | https://openalex.org/fields/24 |
cc-by | Relative quantitative RT-PCR analyses. Total RNA was isolated from eggs, larvae, nymphs (non-infected and infected with B. afzelii CB43) and adult tick homogenates as well as from dissected tissues (salivary glands, guts and ovaries) from semi-engorged I. ricinus females, as previously described 65. For the qPCR, the ... | 10.1038/srep32372 | article | en | 2,016 | false | true | false | false | Immunology and Microbiology | https://openalex.org/fields/24 |
cc-by | Acknowledgements This work was supported by the European Union Seventh Framework Programme ( FP7/2077-2013 under grant agreement no. 316304 to JJV) and with financial support from the Ministry of Education, Youth and Sports of the Czech Republic under the Národní program udržitelnosti I program (project LO1218... | 10.1038/srep32372 | article | en | 2,016 | false | false | true | false | Immunology and Microbiology | https://openalex.org/fields/24 |
cc-by | Acknowledgements We thank P. Paoletti , V. Klippenstein , S. Edelstein , D. Baigl , S. Supplisson , S. Zhu and J. Lehmann for suggestions. We also thank Dr. Philippe Rondard at the University of Montpellier for the generous gift of the HA-GluN1 construct. We are grateful to the Proteomic Resource Center a... | 10.1038/srep34751 | article | en | 2,016 | false | false | true | false | Neuroscience | https://openalex.org/fields/28 |
cc-by | FUNDING GC is funded by the Fondation ARC pour la recherche sur le cancer , the European Research Council ( ERC-2010-StG 243312 , RETROGENOMICS), the French Government (National Research Agency, ANR) through the "Investments for the Future" (LABEX SIGNALIFE , ANR-11-LABX-0028-01 ), and the Fondation pour la Rec... | 10.3389/fcell.2016.00014 | review | en | 2,016 | false | false | true | false | Agricultural and Biological Sciences | https://openalex.org/fields/11 |
cc-by | The DNA present in the environment is a unique and increasingly exploited source of information for conducting fast and standardized biodiversity assessments for any type of organisms. The datasets resulting from these surveys are however rarely compared to the quantitative predictions of biodiversity models. In this s... | 10.1038/srep35644 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | In this study, we ask how the parameter estimates of Hubbell's neutral theory, one of the most prominent quantitative biodiversity models of the last decade 3, 8, 9 , are affected by noise in taxa-abundance datasets. We focus on the type of noise generated in DNA-based surveys, and specifically in DNA metabarcoding s... | 10.1038/srep35644 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | Some studies have also applied neutral models to environmental DNA data to interpret the composition of microbial communities. Sloan et al. 26, 27 and Woodcock et al. 28 developed a continuous approximation to Hubbell's model adapted to large-sized bacterial populations. They focused on estimating the rate of immigra... | 10.1038/srep35644 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | This type of noise can be regarded as simulating the noise generated in the sequencing step. To illustrate our modelling choices with empirical data, we produced a benchmark dataset obtained by mixing the DNA of 16 plant species in known quantities. The experiment and its results are detailed in the Supplementary Metho... | 10.1038/srep35644 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | For each set of parameters and noise intensity, we generated 100 simulated samples. We reported the mean and standard deviation of the relative biases θ θ θ -( )/ and Î I log ( / ) 10 over the 100 realizations. In the absence of dispersal limitation, the Ewens distribution permits the inference of θ by likelihood maxim... | 10.1038/srep35644 | article | en | 2,016 | false | true | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | Discussion Although they provide an unparalleled amount of information, biodiversity studies based on environmental DNA also have limitations. One of them is that the abundance of sequence reads corresponding to a given molecular taxonomic unit does not necessarily reflect the true population abundance of the correspon... | 10.1038/srep35644 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | Estimating the parameters θ and m of the neutral model is useful in interpreting biodiversity patterns even if the community is not governed by purely neutral mechanisms 62. Indeed, θ is closely related to Fisher's biodiversity index, and is an unbiased index of biodiversity, while m quantifies how the local sample is... | 10.1038/srep35644 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | However, these methods do not guarantee a complete filtering of artifactual MOTUs from empirical datasets. In particular, chimeric sequences formed at the PCR stage may be misconstrued as MOTUs. Because these sequences are generated by rare PCR replication errors, they should be predominantly represented by few reads. ... | 10.1038/srep35644 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | 1a , see also Fig. S3 in Supplementary Methods). Thus, the adequate subsample size for an empirical dataset may be chosen so as to trim out the MOTUs with abundances below an observed break in the ranked log-abundance curve. Another finding of our study is that for the same proportion of artifactual MOTUs, the θ estim... | 10.1038/srep35644 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | This threshold was found to be lower for larger θ values. For instance, the empirical noise intensity σ log = 1. 2 measured on our benchmark dataset was near or below the threshold σ log,th for θ values up to ca. θ = 20, while for larger θ values, it was responsible for a moderate underestimation of θ (20% for θ = 500)... | 10.1038/srep35644 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | We also simulated a Gaussian additive noise on abundance data and found that it had a disproportionate effect on the least abundant MOTUs, thus distorting the taxa-abundance distribution: parameter inference was biased if the standard deviation of the noise was larger than the abundance of the least abundant MOTUs. Her... | 10.1038/srep35644 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | However, these sources of bias may be generally seen as the accumulation of mutations during replication. In ecology, the only type of replication taken into consideration is demography, but DNA metabarcoding data are also the result of cellular and PCR replication processes. Since the assumptions of the neutral theory... | 10.1038/srep35644 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | We tested this hypothesis for a range of biologically plausible noise terms on simulated metabarcoding data, and we provide guidance for neutral parameter inference from such data. Our results indicate that whether an environmental DNA dataset really reflects the sampled community depends on noise intensity. They also ... | 10.1038/srep35644 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | Acknowledgements We thank Ryan Chisholm , Fabien Laroche and James O'Dwyer for fruitful discussion. This work has benefited from " Investissement d'Avenir " grants managed by the French Agence Nationale de la Recherche (CEBA, ref. ANR-10-LABX-25-01 and TULIP, ref. ANR-10-LABX-0041 ) and from anadditional ANR ... | 10.1038/srep35644 | article | en | 2,016 | false | false | true | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | 0. 1 pM), and is present in all mammalian body fluids including cerebrospinal fluid 7. Its concentration (in normal conditions B10 mM in serum) increases on inflammation. The X-ray structure of rabbit haem-haemopexin has been solved (PDB codes 1QHU and 1QJS). It is made up of two homologous halves (four-bladed b-prope... | 10.1038/ncomms11590 | article | en | 2,016 | true | false | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Data analysis showed that a ca. 1:1 complex was formed in the latter case, and that the heat evolved during the interaction was almost equal to that observed with the full-length protein ( À 48. 5 versus À 52. 7 kcal mol À 1 in this particular experiment). This indicates that NtHpx likely provides most, if not all, of ... | 10.1038/ncomms11590 | article | en | 2,016 | true | false | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | 5200005 keV, l ¼ 1. 775520 Å), as determined by an X-ray fluorescence scan. Two Eu sites were located using the programme SHELXD (ref. 43). Phasing was done with the programme Phaser 44 , and initial automatic model building proceeded with ARP/WARP (ref. 45). The model was then improved through iterative cycles of ma... | 10.1038/ncomms11590 | article | en | 2,016 | true | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | 5% (742/769) of all residues are in favoured (98%) regions, and 100. 0% (769/769) of all residues are in allowed (499. 8%) regions. Regarding HxuA in complex with N-ter haemopexin, 94. 7% (908/959) of all residues are in favoured (98%) regions, and 99. 7% (956/959) of all residues are in allowed (499. 8%) regions. Atom... | 10.1038/ncomms11590 | article | en | 2,016 | true | false | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | In total, 35 individual 7 ml aliquots were injected from the 250 ml syringe into the 1. 41 ml titration cell, with a 6-min interval between injections, unless otherwise stated. Heat signals were corrected for the respective heat of dilution and normalized to the amount of compound injected. The enthalpy of binding (DH)... | 10.1038/ncomms11590 | article | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Besides, as there are conformational changes in the interactants on interaction the values should be taken as apparent Ka's. TEM and image processing. For negative stain TEM, the protein solution was diluted at 10-20 mg ml À 1 in PBS buffer. Immediately afterwards, 4 ml aliquot was adsorbed onto glow discharged carbon ... | 10.1038/ncomms11590 | article | en | 2,016 | false | true | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Acknowledgements we thank Andrew Thompson from the PROXIMA-1 beamline at SOLEIL for data collection and help for initial model building, Franc¸oise Baleux from the Unitede Chimie des Biomolecules from Institut Pasteur for expert technical assistance in aminoacid analysis and mass spectrometry, Emmanuel Frachon ... | 10.1038/ncomms11590 | article | en | 2,016 | false | false | true | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | After generating the output data (m 2 , σ m2 ) by simulating the circuit's dynamics via the GA, the optimal input distribution will be constructed according to Eq. (19). We shall then let the circuit process an input signal sampled from that distribution and calculate the MI for both the transcriptional and posttranscr... | 10.1371/journal.pcbi.1004715 | article | en | 2,016 | true | false | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | In particular, MAML1 and MEF2C (coding for transcription factors that activate musclespecific gene expression) compete with linc-MD1 for miR-133 and miR-135 respectively [39]. Taken together, the available evidence indicates that miRNA activity depends on the miRNA:target ratio, on miRNA target site abundance and on m... | 10.1371/journal.pcbi.1004715 | article | en | 2,016 | true | false | false | false | Biochemistry, Genetics and Molecular Biology | https://openalex.org/fields/13 |
cc-by | Perturbed thyroid development and altered T3 to T4 ratio reported in the current study (Table 1 ) may therefore operate through a similar mechanism. Since all fetal ovaries were collected at Day 140, the profile of transcripts and proteins expressed at this stage reflects a snapshot of mechanistic changes that, by vir... | 10.1038/srep22279 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | At slaughter, data and tissues were collected and processed as described previously 11. In brief, fetal anogenital distance (AGD) was measured and fetal ovary weights recorded. Ovaries were either fixed in neutral buffered formalin (NBF) for histological analysis or snap frozen in liquid nitrogen and stored at -80 °C ... | 10.1038/srep22279 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | Antibodies used were (i) Lamin A/C 1/200, mouse (ab49721, Abcam); (ii) UCHL1, 3 μg/ml, rabbit (LS-B489/9526, Lifespan Biosciences), (iii) PD1A3 (ERP57); 1:1000 rabbit (ab13507, Abcam); (iv) TAGLN, 1 μg/L, goat (AHP2034, ABD Serotec) (v) GSTM3, 1:100 rabbit (15214-1-AP, ProteinTech), (vi) GSN, 1 μg/ml mouse (ab55070, Ab... | 10.1038/srep22279 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | chem. agilent. com/earray/) using the default options (Base Composition Methodology, one oligo par target, 60bp length, 3′ Bias Design). The array was enriched with transcripts isolated and identified in the fetal developing sheep ovary by subtractive cDNA library construction (SSH) 48 and completed with control gene... | 10.1038/srep22279 | article | en | 2,016 | false | true | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | Labeling and hybridization were carried out using the Quick Amp Labeling kit for one-color labeling (Agilent, 5190-0442) and the One-Color RNA Spike-in Kit (Agilent, 5188-5282) according to the manufacturer's instructions with 200 ng of total RNA starting quantities. Arrays were scanned with the Agilent DNA Microarray ... | 10.1038/srep22279 | article | en | 2,016 | false | true | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | In brief, RNA was treated using RQ1 RNase-free DNase (Promega, Southampton UK) prior to cDNA synthesis using the Transcriptor First Strand cDNA Synthesis Kit (Roche, Welwyn Garden City, UK) following the manufacturers instructions. Standard curves were generated using 1:5 serial dilutions of pooled cDNA. The cDNA sampl... | 10.1038/srep22279 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | The 20 μl reaction vol- umes contained 1 × Probes Master mix, 0. 5 μM of each primer, 0. 1 μM probe and 5 μl cDNA sample. The thermal cycling conditions were 10 minutes at 95 °C (initial denaturing), 45 to 55 cycles of 15 seconds at 95 °C, 30 seconds at 60 °C and 1 second at 72 °C (data acquisition). The housekeeping g... | 10.1038/srep22279 | article | en | 2,016 | true | true | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | A linear mixed model was used to account for litter size effects [fixed effects: number of fetuses and treatment, random effect: ewe]. Tissue EDC concentration data were log 10 transformed prior to analysis. Mean concentrations were compared using ANOVA, with the main effects being treatment and age (maternal vs fetal)... | 10.1038/srep22279 | article | en | 2,016 | true | true | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | Functional analysis was conducted on transcripts and proteins that exhibited statistically significant, differential expression, using Ingenuity Pathway Analysis (IPA, http://www. ingenuity. com/). | 10.1038/srep22279 | article | en | 2,016 | false | true | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | for details). Mass lists in the form of Mascot Generic Files were created automatically and used as the input for Mascot MS/MS Ions searches of the NCBInr database using the Matrix Science web server (www. matrixscience. com). The default search parameters used were: Enzyme = Trypsin, Max. Missed cleavages = 1; Fixed m... | 10.1038/srep22279 | article | en | 2,016 | true | false | false | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | Acknowledgements We thank George Corsar and Jim MacDonald for the management of experimental animals. We thank Ms Evelyn Argo , Mr Ian Davidson ( Proteomics Facility ), Ms Gillian Milne ( Histology & Electron Microscopy Facility ) and Mrs Margaret Fraser ( Institute of Medical Sciences ) at the University o... | 10.1038/srep22279 | article | en | 2,016 | false | false | true | false | Environmental Science | https://openalex.org/fields/23 |
cc-by | To overcome all these issues, the following two strategies have been proposed: the development of analytic techniques that can reliably detect HFOs in continuous wide bandwidth EEGs recorded from microelectrodes and conventional clinical electrodes and the creation of infrastructure projects that facilitate the sharing... | 10.1371/journal.pone.0158276 | article | en | 2,016 | true | false | false | false | Neuroscience | https://openalex.org/fields/28 |
cc-by | Consequently, some groups have developed customized interfaces to test their own algorithms [25, 26] , or they have joined professional EEG companies to develop proprietary software [27]. Unfortunately, these applications currently remain insufficiently documented or non-available to the general public, restricting t... | 10.1371/journal.pone.0158276 | article | en | 2,016 | false | true | false | false | Neuroscience | https://openalex.org/fields/28 |
cc-by | RIPPLELAB also proposes a common procedure to share HFO analyses in order to promote collaborations across research centers. This tool was designed to be manipulated by researchers and clinicians with no programming skills, and users do not require any programming abilities to execute an analysis. More seasoned scienti... | 10.1371/journal.pone.0158276 | article | en | 2,016 | false | true | false | false | Neuroscience | https://openalex.org/fields/28 |
cc-by | Broadly speaking, HFO detection methods can be classified in three groups: manual review, supervised detection and unsupervised detection. Manual review is performed by visual inspection of an expert with required knowledge on electrophysiological recording and signal processing to distinguish putative events from filt... | 10.1371/journal.pone.0158276 | article | en | 2,016 | true | false | false | false | Neuroscience | https://openalex.org/fields/28 |
cc-by | Originally, this detection methodology was implemented with 1-min segments of EEG signal. In addition to this, we included the possibility to process the data thresholds in epochs of time specified by the user. The flowchart of the MNI algorithm is presented in Fig 4. of electrophysiological data, especially at high f... | 10.1371/journal.pone.0158276 | article | en | 2,016 | false | true | false | false | Neuroscience | https://openalex.org/fields/28 |
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