dataesr/scientific-paragraphs-categorization huggingface dataset:
A randomization test (a resampling statistical technique called 'permutation test,' i. e. a statistical significance test in which the distribution of the test statistic under the null hypothesis was obtained by calculating all possible values of the test statistic under rearrangements of the labels on the observed data points) was used with 10 000 replications (method described by  Adams and Anthony, 1996)  as in our previous study  (Destrez et al. , 2014). Cortisol concentrations, blood cell count, antibody response to Chlamydia vaccine, Hp, AGP, SAA and temperatures met the requirements for parametric tests to test factor interactions. These data were analyzed using a repeated measures SAS ProcMixed analysis (a mixed procedure in which the variables 'day,' 'treatment' and 'day × treatment' interaction were fixed effects and 'animals' was a random effect and lamb was specified as experimental unit).
Acknowledgments The authors thank  D. Chassaignes  and  B. Viallard  from the experimental farm for their assistance on animal care and the experiment as a whole. MSD's Animal Health division (France)  provided the Ovilis ® Chlamydia vaccine, and  ID-VET (France)  provided the ID  Screen ® Chlamydophila  abortus Indirect ELISA kits. This study was performed with grant support from the  French National Research Agency  (grant no:  ANR-09-BLAN-0339-01 ) and from the  Auvergne region.
Epithelial cell culture Source, origin and characteristics of bovine epithelial cells used in this study are provided in Table  1. The epithelial origin of all cell lines deployed was confirmed by detection of cytokeratin and zonula occludens protein (ZO-2) via fluorescence microscopy and western blot analysis (data not shown). Cell culture media were obtained from Life Technologies (Darmstadt, Germany). The basis culture medium of the bovine udder epithelial cells (PS) was supplemented with Insulin-like growth factor 1 (10 ng/mL; Peprotech, Hamburg, Germany), Fibroblast growth factor (5 ng/mL Peprotech), Epidermal growth factor (5 ng/mL; Sigma, Taufkirchen, Germany), Hydrocortisone (1 µg/mL; Sigma), 20 mM HEPES buffer (Fisher Scientific, Schwerte, Germany) and 2 mM l-Glutamine (Life Technologies)  [17].
Some CCV were densely packed with C. burnetii. Most of them were mainly filled with LCV, but in a few CCV both LCV and SCV were present. Small amounts of cellular debris were regularly admixed with C. burnetii. Intestinal epithelial cells were characterized by numerous, sometimes large phagolysosomes. Small numbers of LCV and SCV were present in very few of these phagolysosomes only (Figure  6 ). They were obscured by the large amounts of cellular debris. No extracellular C. burnetii were detected. Epithelial cells infected with NMI or NMII retained their typical cell morphology after 7 days of infection and displayed no signs of cell death processes, e. g. , disrupted cell membrane or fragmented nuclei. These observations could be confirmed by cell vitality assays. Independent of the C. burnetii strain, infection neither affected metabolic activity nor cytoplasmic membrane integrity of any of the epithelial cell lines after 1 and 7 days of inoculation compared to uninfected control cells (data not shown).
1 Nickel-response pleiotropic regulator, metal (copper, iron, and nickel) homeostasis, acid adaptation, iron uptake/storage, motility, chemotaxis, stress response, and mouse colonization  Contreras et al. , 2003; Bury-Mone et al. , 2004; Ernst et al. , 2005b; Muller et al. , 2011  crdR (hp1365) CrdR/NP_208157. 1 Copper resistance, survival under nitrosative stress, and mouse colonization  Panthel et al. , 2003; Waidner et al. , 2005; Hung et al. , 2015 Hung et al. , et al. , 2010)) ]. Sequence data and loci annotations from 260 H. pylori genomes were retrieved from the NCBI database 1 by a series of custom Perl scripts. In addition, the genomes of 57 Helicobacter non-pylori strains were included in the comparative analysis (Supplementary Table  S1 ). Each putative transcriptional factor was queried using PSI-BLAST  (Altschul et al.
Bacterial Strains and Culture Conditions H. pylori 26695 was grown for 3 days on blood agar plates containing 10% defibrinated sheep blood, at 37   (Contreras et al. , 2003; Wen et al. , 2003; Vannini et al. , 2014; Cardenas-Mondragon et al. , 2016). Fold-changes in transcription were determined by calculating the relative expression of transcription regulator genes under different environmental conditions as compared to expression in BB + FBS. Experiments were performed in triplicate on three different days and the results shown are the mean of the data produced.
The pellets were resuspended in 100 µL of DEPC-treated water. Purification of RNA was performed using the TURBO DNA-free kit (Ambion, Inc. ). Quality of RNA was assessed using a NanoDrop (ND-1000; Thermo Scientific) and a bleach 2% agarose gel as previously described  (Aranda et al. , 2012). qRT-PCR was performed as previously reported  (Ares et al. , 2016). Specific primers were designed -R TGT TGG GGG CTA GAT CAA AG rpoN-F CAG CGG GTT GAA TAA TGA GG rpoN rpoN-R ACG CTT GCG CAC TTT TTC fliA-F TCG TCT AAA AGA GCG CTT GC fliA fliA-R CTT CGC ATA CCC CCA AAA AG hrcA-F TTT CTT GCG CAC TGG GTT AC hrcA hrcA-R GAA AGA AGC AGC GAT TGA GC arsR-F GAG CGA GTT TTT GCT CCA AC arsR arsR-R GCC CGT CTA AAT TAG GCA AAG hp0222-F CTA GGA CGC AAA CCA AAA GC hp0222 hp0222-R CCC ACG CTT TCT TCT TCT TC hp0564-F GTC GCT GTA GAT GAG CTG AAA C hp0564 hp0564-R GGC GTT TGA CAA AAG AAT TG flgR-F CAG GCC TTA AAA GTC GCA AG flgR flgR-R CGC TAT AAA AGG GTG CTT GG hup-F GTG GAG TTG ATC GGT TTT GG hup hup-R TTA GGC ACC CGT TTG TCT TC hp1021-F GTT GCG CAA GAT CCA ATA CC hp1021 hp1021-R AGG GCG TGT GGA TGA TAA AG hspR-F CGG GCG TGG ATA TTA TCT TG hspR hspR-R TGT TTG TGC AGA GCG TCT TG fur-F GAA GAA GTG GTG AGC GTT TTG fur fur-R CCT TTT GGC GGA TAG AAT GC hsrA-F GGA AGA AGT CCA TGC GTT TG hsrA hsrA-R CAA ACG AGC CTC AAT CCT TG cheY-F TGG AAG CTT GGG AGA AAC TG cheY cheY-R CAG AGC GCA CCT TTT TAA CG nikR-F CAT CCG CTT TTC GGT TTC nikR nikR-R CAT GTC GCG CAC TAA TTC TG crdR-F CTT AGG CGT GGC TAA AAT GC crdR crdR-R CAA ACG CCC CAA AAA CAC with the Primer3Plus software 2  and are listed in Table  2.
Heatmap Construction To show the fold-changes in gene expression, we selected the "heatmap. 2" function of the R software, using the "gplots" package. The rows (culturing conditions) were hierarchically clustered ("hclust" function, "ward. D" method) according to the absolute fold-changes in gene expression. In order to illustrate the presence/absence of transcription factors in all Helicobacter genomes, an amino acid sequences content matrix ("heatmap" function) was built using the R software 3  (v3. 2. 4). 260 H. pylori and 57 H. non-pylori genomes were retrieved from the NCBI database 4  by a series of custom Perl scripts. These paired loci were hierarchically clustered ("hclust" function, "ward. D" method) according to their loci-content using a sidelong dendrogram.
Transcriptional Regulator Genes Are Highly Conserved in H. pylori Strains We performed a Blast search in genomes deposited in GenBank 5  using the amino acids sequences of the 16 transcriptional regulators identified in H. pylori 26695. The transcription factors were highly prevalent and well conserved among different H. pylori isolates (Figure  5 ). We studied the occurrence of these genes in other Helicobacter species, and found that their presence changed from one species to another. Two species that are phylogenetically closely related to H. pylori, H. acinonychis (isolated from big cats), and H. cetorum (isolated from marine mammals), encoded all 16 transcriptional regulators with high identities to those of H. pylori strains, and clustered closer to the H. pylori strains (Figure  5 ).
Ungulate management databases An important goal of a vision for European ungulate management is to increase the scientific basis of wildlife management, rather than to rely only on opinion/experience-based management systems. To achieve this, consistent long-term monitoring and systematically collected data are essential. Tools for the remote capture, digital storing and processing of largescale data related to ungulate management (e. g. observations, harvest, mortality and recruitment rates) have become available and are commonly used in several European countries  (Ueno et al. 2014; Zaragozí et al. 2015; Helle et al. 2016; Bubnicki et al. 2016). As accurate spatial data accumulates, it will provide valuable information for e. g. preventing forest or agricultural damage and/or implementing mitigation measures to reduce ungulate-traffic collisions.
Therefore, careful analysis of disease and conservation risks, as well as economic issues, should be taken into account when considering feeding. Many feeding programmes should be reviewed accordingly. 8. Citizen science is a powerful source of data for wildlife management. Online, remotely accessible databases with spatial and temporal information on ungulate harvests, distribution and abundances should be developed and implemented to provide data on interactions of ungulates with the environment and human activities at national and pan-European scales. Data persistence, standardization and accessibility (including linguistic accessibility) should be promoted. 9. Wildlife management should recognise the impacts of hunting beyond simply reducing population densities. Hunting may lead to changes in both behaviour and social organization of ungulates and affect movements over short and long distances.
Acknowledgements The position statement presented in this article has been undertaken by participants of the  International Conference BUngulates  in a changing worldconsequences for population dynamics, migration and management^, 19-21 September 2016,  Krasny Bor , Belarus. We are grateful to two anonymous reviewers for comments that have helped to substantially enrich the statement. Open Access This article is distributed under the terms of the Creative Comm ons Attribution 4. 0 International License (http:// creativecommons. org/licenses/by/4. 0/),which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Among such organisms, sequencing the 16 S rRNA, rpoB and hsp65 genes suggested that strain M26, isolated from sputum collected in August 2011 from an 86-year-old French Polynesian man living in Taravao (17 44' S, 149 18' W) was representative of a new species. Strain M26 displayed 91. 47% rpoB gene sequence similarity with Mycobacterium rhodesiae CIP 106806 T (GenBank: EU109302), 98. 93% 16 S rRNA gene sequence similarity with Mycobacterium smegmatis ATCC 19420 T (GenBank: NR115233) and 95. 59% hsp65 gene sequence similarity with Mycobacterium conceptionense CIP 108544 T (GenBank: AY859678) 3. Since strain M26 was regarded as a potentially undescribed species of the genus Mycobacterium, it was further characterized. For phenotype, we observed that strain M26 exhibited yellow-orange, circular, convex, smooth colonies on Middlebrook 7H10 medium.
2 ). In particular, results of catalase, growth at 5% NaCl, Tween 80 hydrolysis, nitrate reductase, gelatin hydrolysis distinguish strain M26 from M. smegmatis  4. Also, the absence of scotochromogenic colonies, negative catalase activity and negative Tween hydrolysis at 37 °C all distinguished strain M26 from M. rhodesiae, the closest species by rpob sequencing  4  (Fig. 2 ). Accordingly, M26 strain exhibited a reproducible matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) profile that did not match any of the profiles entered in the Bruker database (version December, 2015). Furthermore, strain M26 was susceptible to rifabutin (minimal inhibitory concentration (MIC) < 0. 015 mg/L), rifampicin (MIC, 0. 06 mg/L), ethambutol (MIC, 1 mg/L), clarithromycin (MIC, 2 mg/L), azithromycin (MIC, 2 mg/L), linezolid  (MIC, 0.
5 mg/L), amikacin (MIC, 0. 25 mg/L), ciprofloxacin (MIC, 0. 125 mg/L), levofloxacin (MIC, 0. 06 mg/L), moxifloxacin (MIC, < 0. 03 mg/L), sulfamethoxazole (MIC, 1 mg/L) and resistant to penicillin G (MIC, 256 mg/L), imipenem (MIC, 64 mg/L), doxycyclin (MIC, 4 mg/L) and minocyclin (MIC, 1 mg/L). This antibiotic susceptibility profile also distinguished strain M26 from M. rhodesiae, which is resistant to rifampicin with a MIC of 25 mg/L. Phenotypic traits therefore suggested that strain M26 was a representative strain of a previously undescribed Mycobacterium species. Further, we found that the genome of strain M26 comprised one 5,732,017-bp long chromosome without plasmid and a 67. 54% GC content (Fig. 3 ). The genome of strain M26, comprising 12 contigs assembled into nine scaffolds, was ordered using Mauve software and Mycobacterium gilvum genome as nearest sequenced complete genome reference.
The ordered scaffolds were then assembled into one complete sequence. Analyzing the replication origin in strain M26 genome using Ori-Finder  5, 6  predicted two OriC regions splited by the dnaA gene and located at scaffold00008 (508 and 368 bp) (Supplementary File 1). The 368 bp predicted OriC region showed homology sequence with Mycobacterium rhodosiae NBB3 and Mycobacterium avium 104 in DoriC database  7  (Supplementary File 1). The genome of strain M26 encodes 5,500 protein-coding genes and 52 RNAs including two complete rRNA operons and 46 tRNA. A total of 4,086 genes (74. 29%) were assigned as putative function (by COGs or by NR blast), whereas 166 genes (3. 02%) were identified as ORFans. The remaining genes were annotated as hypothetical proteins (989 genes, 18%). A total of 2,876 proteins were found to be associated with mobilome.
Some manual refinements using CLC Genomics v7 software (CLC bio, Aarhus, Denmark) and homemade tools made in Python improved the genome. Finally, the draft genome of strain M26 consists into nine scaffolds. The replication origin in strain M26 genome was predicted using Ori-Finder  5, 6  (http://tubic. tju. edu. cn/Ori-Finder/) and homology with other OriC regions was predicted using blast algorithm in DoriC database  7  (http://tubic. tju. edu. cn/doric/). The 16 S rRNA gene sequence of strain M26 was deposited in GenBank under accession number LN909503 and its complete genome under accession number FAXD00000000. Genome annotation. Non-coding genes and miscellaneous features were predicted using RNAmmer 28 , ARAGORN  29  , Rfam 30 , PFAM  31  , and Infernal 32. Coding DNA sequences (CDSs) were predicted using Prodigal  33  and functional annotation was achieved using BLAST+  34  and HMMER3  35  against the UniProtKB database 36.
To refine the search of mobile genetic elements in the genome of strain M26, PHAST software predicted prophage  37  completed by the Actinobacteriophage Database at phageDB. org and the online plasmid search tool: https:// plasmid. med. harvard. edu/PLASMID/Home. xhtml. Phylogenomic tree was constructed using an identity matrix based on Mauve program genome alignment  38. Average Nucleotide Identity values were calculated between strain M26 and sequenced Mycobacterium species genomes using BLASTN and a home-made software, following the algorithm described by Goris et al. 39. The genomes of 32 Mycobacterium species were downloaded from Genbank (Table  2 ). The ORFeome of these species, in addition to M26 genome, were annotated using Prodigal  33  in order to normalize ORFs predictions. The Pangenomic analyses were computed using OrthoMCL software with > 60% amino acid identiy in all-against-all BLASTP algorithm  40.
COG Functional Group Analysis The COG (cluster of orthologous groups) classification of CDS of the B. suis genome was based on the database of Comprehensive Microbial Resource (CMR) or on that of Genoscope found at http://www. genoscope. cns. fr/agc/microscope/mage/. All genes induced or repressed by RegA in the wild-type strain, having respectively a ratio WT/ regA mean value of ≥ 2-fold or ≤ 0. 5fold, were classified according to the functional category to which they belong.
RT-qPCR Analysis Five hundred nanograms of the RNA samples used for microarray hybridizations were reverse-transcribed as reported in  Abdou et al. (2013) , and quantitative PCR experiments (RT-qPCR) were performed using the Light Cycler 480 with SYBR green chemistry (Roche). Primers (Sigma Genosys) were designed using Primer 3 Software (Table  S5 ). Aliquots of cDNA samples were diluted 20-and 2,000-fold to quantify expression of the selected mRNAs and of the constitutively expressed 16S rRNA, respectively, the latter being used to normalize expression values. For the three biological replicates, normalized threshold cycles Ct from averaged three technical replicates were used for calculating the fold change using the Ct method (Table  S3 ) and the relative fold change (WT/ regA) = 2 -Ct.
Using these 11 PWM, putative RegA-binding motifs were searched for in DNA sequences either 1 kb upstream or within 200 bp upstream and downstream of the start codon of RegAdependent individual genes or of the first gene in each operon. The structures of operons were obtained from the literature or from predictions based on the transcription directions of the genes and their intergenic sequence lengths as indicated in DOOR  (Mao et al. , 2014)  and BioCyc databases  (Romero and Karp, 2004). The MAST program was used to scan the target sequences to search for the motifs. (G/C)-C-G-G-(C/G)- N (0-10) -G-(T/A)-C-(G/A)-(C/A).
For tandem mass spectrometry, the same instrument was used and fragmentation was based on Collision-Induced Dissociation (CID). The raw spectra were processed with the Data Explorer software (version 4. 9, AB Sciex) or the GPS Explorer software (version 3. 6, AB Sciex). The measured monoisotopic peptide masses and the tandem MS spectra were combined and compared to all sequences of B. suis in a customized database using the software Mascot (Table  S7 ). The database consisted of the combination of four fasta files (NC_004310, NC_004311, NC_010167, NC_010169). Furthermore, all sequences were randomized and added to the database for evaluation of false positive rate.
Protein Identification by Mass Spectrometry Using LC-ESI-MS/MS For nano-LC-ESI (Electrospray ionization)-MS/MS, peptides were separated on an analytical column (C18, 25 cm length, 35 • C) with a linear gradient of 5-50% solution B (A: 0. 1% formic acid, B: 80% ACN, and 0. 1% formic acid). Mass spectrometry was performed on a linear ion trap mass spectrometer (LTQ Orbitrap Velos, Thermo Scientific) operating in positive polarity mode online coupled to the nano-LC system. The MS method consisted of a cycle combining one full MS scan (Mass range: 300-1,500 m/z) with 10 data-dependent MS/MS events (CID; 35% collision energy). Splitting of the three biological replicates in separate MS runs allowed further statistical data analysis.
ICPL Quantification and Database Queries The raw data were converted to mzXML format using a software tool from the Trans-Proteomic Pipeline. Peak detection, deconvolution, deisotoping, and quantification of the peaks were done using ICPL-ESIQuant. The quadruplet detection was performed for each run separately. Four separate database queries were done using the Mascot software as in 2D-DIGE analysis (see above). For each biological replicate, about 165 proteins were found for which the quantification was based on at least two different quadruplets and had a coefficient of variance below 40%. Furthermore, the ratios between the technical duplicates were very similar. The threshold for a regulated protein was set to 1. 5 and 0. 66-fold. For statistical evaluation of the biological data, the average and standard deviation of all three biological data were calculated using all four combinations of the wild-type to regA ratio.
Measurement of In vitro Sensitivity to Superoxide Production Triplicates of bacterial cultures were harvested at day 3 of our in vitro model of persistence, and adjusted to a density of ∼10 7 CFU/ml in PBS. O - 2 was produced during the xanthine oxidase reaction in cell suspensions, according to a procedure, adapted in  Hanna et al. (2013). At specific time points after initiating the reaction, the number of surviving bacteria was determined. The means from three independent platings of each bacterial cell suspension were calculated, and the data obtained were expressed as log10 CFU/ml at each sampling time, ± standard deviations.
We also confirmed that RegA induced expression of both ubiquinol and cytochrome c oxidases under these conditions  (Abdou et al. , 2013). In fact, strong induction of cytochrome bc1 components (complex III of the respiratory pathway; operon BR1543/1541) (Tables  S1-S3 ), of cytochrome c itself (BR0039), as well as of genes participating in its biogenesis (BR0096 and BR0607/0608, category O) (Tables  S1, S3 ), indicated that B. suis may use an electron transport chain terminating with a cytochrome c oxidase. Nevertheless, the only cytochrome c oxidase under strong positive control of RegA was the aa 3 -type (BR0467 and BR0468) (Tables  S1, S3 ), a quite unexpected finding given that it possesses a lower oxygen affinity than the cbb 3 -type  (Ekici et al. , 2012). The operon encoding the latter (BR0363/0360) was, however, also well-expressed in the WT strain (microarray data, GEO accession number GSE87538).
The complementation of aceA (C-aceA in Figure  7A ) allowed the restoration of the WT phenotype, and of the enzymatic activity (see above and data not shown). These results confirmed the loss of ICL activity as a direct consequence of aceA inactivation and the requirement of a functional ICL for optimal bacterial persistence under anoxia in the presence of low fatty acid concentrations. The behavior of WT, aceA and complemented aceA strains was similar during infection of both resting or IFNγ-and LPSactivated J774A. 1 murine macrophage-like cells  (Loisel-Meyer et al. , 2006) , under standard and microaerobic conditions. A possible role of aceA in pathogenesis in vivo was then assessed in a murine model of infection. In contrast to the WT strain, aceA did not display bacterial growth during the acute phase (day 7), a phenotype possibly correlated to the lower oxygenation inside the target organs than in the first step of our in vitro model  (Jiménez de Bagüés et al.
suis, unable to produce sufficient ribose via the PPC, may attempt to import this precursor possibly for residual biosynthetic needs, such as DNA repair (see results) and/or specific RNA synthesis for adaptation. The RegA-dependent repression of RNA polymerase subunits and of genes involved in DNA replication and transcription is compatible with their residual activity in the WT strain (GEO accession number GSE87538). During persistence, the PPC may become less central in B. suis physiology, as restricted gluconeogenesis provides less PPC substrates, and potential use of the DHAP-pathway produces glycolysis intermediates (Figure  6B ). In B. suis, glycerol may represent an important carbon source to partially support the energy metabolism needed for bacterial survival under conditions of persistence, despite RegA-dependent down-regulation of the downstream genes and proteins (Figure  6B ).
Each animal was studied only once per season; 1 h before the start of experiments, animals were weighed and housed individually in order to reduce the stress induced by handling. The meteorological data were obtained from the Algerian meteorological center. Blood samples (3 ml) were collected from the jugular vein by trained personnel using heparinized Vacutainer ® tubes (lithium heparinate, Venoject Terumo; Leuven, Belgium) and kept on ice until centrifugation at 3000 × g for 10 min at 4°C. Plasma samples were stored at -25°C until assayed. The rectal temperature of each buck was measured at 0800 and 2000 h using a digital clinical thermometer (Eco Temp Smart, MC-341-E; Omron Healthcare, Hoofddorp, Netherlands) inserted about 3 cm into the rectum in contact with the mucosal wall of the rectum.