dataesr/scientific-paragraphs-categorization huggingface dataset:
A future study could assess food intake in pet cats. However, such a study would be difficult to undertake in a field setting, since fewer factors can be controlled, and collection of data may be tricky. Most notably, it might be difficult to measure food intake accurately, and to ensure that other food sources are not available. There would also be great diversity in environment, most notably ambient temperature, access to outdoors, provision of artificial light and household temperature. Thus, a large population of pet cats would need to be studied to ensure that such increased variability did not mask any genuine effects. In conclusion, a seasonal effect on voluntary food intake exists in domesticated cats, whereby food intake is greater in winter and less in summer. These changes in food intake are likely to be the result of changes in ambient temperature, daylight length, or both, and the fact that they do not cause bodyweight changes suggest that they occur in response to changes in energy requirements.
5 mm 2. All these characteristics allowed us to identify the isolate as belonging to the genus Phialemoniopsis, despite that conidiomata were not observed. Molecular identification was ascertained by PCR amplification and sequencing of the ITS1-5. 8S-ITS2 region, the D1-D2 domains of the ribosomal DNA and two fragments of the actin and tubulin genes  [6]. The nucleotide sequence European Nucleotide Archive (ENA) accession numbers and the percentage of identity for each locus with the type strain of P. ocularis (IHEM 19077) were HG933293/98. 8%, HG933292/ 100%, HG933291/98. 3% and HG933290/99. 2% respectively. Antifungal susceptibility testing was assessed by broth microdilution EUCAST  [7]  method with some modifications. Briefly, testing of amphotericin B was performed on AM3 medium and MIC endpoints were determined on an automated microplate reader spectrophotometer  [6, 7].
Acknowledgements We thank  Christophe Eizaguirre  and  Miguel Soares  for inviting us to contribute to this special issue, and two anonymous referees for helpful comments on earlier draft of this manuscript. We would like to thank  Mikael Puurtinen  for valuable discussion about the revised version of the manuscript and his great advice for the mind map. RC was funded by the  Academy of Finland  and the  Centre of Excellence in Biological Interaction Research. CT was funded by the  Agence Nationale de la Recherche  (grant  ANR-12-ADAP-0006-02-PEPS ), and ML was supported by the  Swedish Research Council  ( VR 2013-3634 ).
Results Identification of unc-29, acr-8, unc-38 and unc-63 homologues from O. dentatum and phylogenetic comparison to related nematode species Taking advantage of the phylogenetic closeness of O. dentatum, C. elegans and H. contortus in clade V of the nematode phylum, we used a candidate gene approach to identify full-length subunit cDNAs from O. dentatum of unc-63, unc-29 and acr-8 homologues. The previously available O. dentatum unc-38-like full-length cDNA sequence (Accession number GU256648) allowed the rapid cloning of the Ode-unc-38 subunit cDNA. The UNC-38 and UNC-63 subunits being closely related in the UNC-38 ''core'' group  [28] , multi-alignment of unc-63 and unc-38 cDNA sequences from different nematode species allowed the design of degenerate primers that were able to specifically amplify the unc-63 homologue from O.
We show that the receptor structure and pharmacology can be plastic, and depends on subunit composition and stoichiometry. The factors that affect the diversity of the receptor may contribute to anthelmintic resistance. Our results demonstrate the presence of acetylcholine receptor subtypes that may serve as anthelmintic targets and suggest that pyrantel, tribendimidine and/or derquantel may still be effective on levamisole-resistant worms. S1A-D). The Ode-UNC-38, Ode-UNC-63 and Ode-ACR-8 subunits contained in their N-terminal part the Yx(x)CC motif characteristic of the a-type subunits whereas the Ode-UNC-29 subunit sequence lacked these vicinal di-cysteines. The different nAChR subunit sequences, accession numbers, characteristics and closest levamisole subunit homologues of C. elegans and H.
Positive identifications were made by BLAST analysis against all Haemonchus contortus entries in the H. contortus information resource data base. Primers designed on unc-29 sequence from H. contortus and C. elegans (unc-29-F0 GGACGAGAAAGATCAAGT-TATGCA, unc-29-XR2 TCATCAAATGGGAAGAAYTCGA-CG) allowed PCR amplification of a 288 bp fragment corresponding to partial O. dentatum unc-29 homologue. New gene specific primer sets were designed on this sequence for the 59-and 39-RACE-PCR providing the full-length cDNA sequence of Odeunc-29. To identify the unc-63 homologue from O. dentatum, degenerate primers were designed based on the Ode-unc-38 mRNA sequence (accession number GU256648) and the unc-63 and unc-38 sequences of cDNAs available from multiple nematode species (Ode-unc-63-F1 GCGAATCGCGAYGCGAATCGKCT, F2 AARAGYATGTGYCAAATWGAYGT, R3 ATATCCCAYTC-GACRCTGGGATA, R4 TAYTTCCAATCYTCRAT-SACCTG).
An 861 bp partial coding sequence of Ode-acr-8 cDNA was amplified using a sense primer (Hco-acr-8-FT1 TATGGT-TAGAGATGCAATGGTT) and an antisense primer (Hco-acr-8-RE8 GTGTTTCGATGAAGACAGCTT) from H. contortus Hcoacr-8. The product of this reaction was cloned and sequenced, and the data were used to design primers to get the 59 and the 39 ends of the target transcript. To amplify the full-length coding sequence of Ode-unc-38, Ode-unc-63, Ode-unc-29 and Ode-acr-8, we used the Phusion DNA polymerase (Finnzymes) and gene specific primer pairs containing HindIII or XhoI and ApaI restriction enzyme sites (Table  S1  in Text S1) to facilitate directional cloning into the pTB-207 expression vector that is suitable for in vitro transcription. PCR products were then digested with XhoI and ApaI restriction enzymes (except Ode-unc-29, digested with HindIII and ApaI), purified using the NucleoSpin Gel and PCR Clean-up kit (Macherey-Nagel), ligated into the respective corresponding sites of the pTB-207 expression vector with T4 DNA Ligase (New England Biolabs), and resulting constructs were transformed into E.
Sequence analysis and accession numbers Database searches, prediction of conserved motifs and phylogenetic analyses for the cDNAs were carried out as already described  [16]. Maximum likelihood analysis was performed on full-length AChR subunit cDNA sequences as follows: sequences were aligned with Geneious 6. 1. 6 (Biomatters Ltd) using the translation align MAFFT plugin  [41]  that aligns the nucleotide sequences as codons based on amino acid sequences. The resulting nucleotide alignment was used to generate phylogenetic trees with the PhyML plugin for Geneious  [42]. The HK85 substitution matrix was selected in order to optimize the tree topology and branch lengths. Branch support was evaluated using the chi2 option of PhyML. The accession numbers for cDNA and protein sequences mentioned in this article are C.
Recording and incubation solutions used are reported in  [26]. Incubation solution was supplemented with Na pyruvate 2. 5 mM, penicillin 100 U/mL and streptomycin 100 mg/ml. All drugs applied, except tribendimidine and derquantel, were purchased from Sigma Aldrich (St Louis, MO, USA). Oocytes were voltageclamped at 260 mV with an Axoclamp 2B amplifier; all data were acquired on a desktop computer with Clampex 9. 2.
Data analysis Acquired data were analyzed with Clampfit 9. 2 (Molecular Devices, Sunnyvale, CA, USA) and Graphpad Prism 5. 0 software (San Diego, CA, USA). The peak of currents in BAPTA-soaked oocytes was measured. The response to 100 mM ACh was normalized to 100% and the responses to the other agonists normalized to that of ACh. For all dose-response relationships, the mean 6 s. e of the responses is plotted. Dose-response data points were fitted with the Hill equation as described previously  [26]. To calculate the pK B values, the graphs were fitted with the Gaddum/ Schild EC 50 shift and the bottom of the curves were set to zero. Text S1 Supplementary information indicating how the calcium permeability measurements were conducted and the equation used for calculating the P Ca /P Na ratio.
Acknowledgments We are grateful to  Debra J Woods ,  Zoetis Animal Health, Kalamazoo, MI  for the generous supply of derquantel. We would like to thank  Prof. Shu Hua Xiao ,  National Institute of Parasitic Diseases, Shanghai, Peoples' Republic of China  for the gift of tribendimidine. The authors would like to thank  Dr. Robin Beech ,  McGill University, Canada  for his help and comments concerning the phylogenetic analysis. We particularly thank  Elise Courtot ,  INRA, Nouzilly, France  and  Dr. Jeff Beetham ,  Department of Vet Pathology, Iowa State University  for assistance cloning the receptor subunits.
There was one teat per pen. A narrow corridor that ends with a wood board with a hole of the size of the lambs head was built in front of each teat. Thus, only one lamb could access the teat at a time. When a lamb went to the teat, its identification number was read by a radio frequency identification (RFID) reader with an antenna. The time (month/day/year-hour/minute/second) and the identification of the lamb were then recorded in a database. When the lamb had finished sucking and left the teat, the quantity of milk consumed by the lamb as well as the time it left the teat was recorded in the database. The accuracy of milk consumption measurements was ± 4 g. To distribute milk, the Förster feeder necessitated a higher suction pressure than the Legrain feeder. The lambs adapted to this feeding technology within 1 day.
e. different repeatability). Furthermore, to evaluate the relationship between variables, we calculated the phenotypic correlations between individual feeding traits. We calculated the FCR for lambs from the normal growth class as the ratio of the quantity of Solvor Perfo milk replacement powder ingested per day (i. e. the quantity of milk consumed per day (in l) × 167) to the ADG for the three periods of age (0 to 15, 15 to 21 and 21 to 28 days). We selected the fixed effects influencing FCR in the same step-wise manner as previously described for individual feeding traits except that the lamb random effect was not included in the model. Although the feeding behaviour of the lambs was not observed directly, the automatically recorded data was used to try to determine whether the animals in a pen competed and/or motivated each other when sucking.
Statistical analysis The Proc Mixed model (SAS Inst. Inc. , Cary, NC) was used to test the effects of temperature and hydration level on all response variables. Daily feed and water intakes (14 measurements/animal) were analyzed with a model including the effects of temperature (2 levels), water restriction (2 levels), days of exposure within temperature effect (14 levels), and interactions. The model had a repeated structure for day of exposure, which allowed the incorporation of heterogeneity of variances across days. Contrasts were generated to compare data recorded from D0 to D7 (i. e. , 32uC) to average value of data between D-6 and D-1 (i. e. , thermoneutral condition considered as a reference value). Thermoregulation, hematological and hemorheological parameters (6 measurements/animal) were analyzed with a similar previous model.
Acknowledgments We sincerely thank the '' Institut National de la Recherche Agronomique '' ( INRA -PigChange  project  2012-2015 ) for his financial support. The authors thank  C. Anais ,  K. Benony ,  D. Be  ´ramis,  M. Bructer ,  M. Giorgi ,  J. L. Gourdine ,  J. Fleury ,  L. Tel ,  F. Silou  ( INRA, URZ ) for their skillful technical assistance and helpful collaboration.
The Horse-Genopole Microarray is the control Horse Gene Expression Microarray (AMAMID 021322, Agilent Technologies, Massy, France) enriched with 384 equine transcripts  [27]. The slides were washed as recommended by the manufacturer and scanned on an Agilent G2565CA scanner, at 5-micron resolution in 20-bit scan mode (Agilent Technologies, Massy, France). The resulting images were processed using the Feature Extraction software (version 10. 7). Raw data were deposited as Gene Expression Omnibus series GSE50623 on the website of the National Center for Biotechnology Information (NCBI).
Statistical and bioinformatic analyses Behavioral and physiological data hapiro-Wilk tests of the collected data revealed a deviation from normality; thus, we used nonparametric statistics. Groups were compared using two-tailed Mann-Whitney tests. Intragroup comparison was conducted using Wilcoxon tests. The x 2 test was used to compare proportions between groups. All calculations were performed using the XLSTAT software (Addinsoft Software, Paris, France). The results are presented as a median and an interquartile range. The level of statistical significance was set to P,0. 05.
Transcriptomic data The data were normalized for interarray comparison and analyzed using the BRB-ArrayTools package (version 4. 2. 0, http://linus. nci. nih. gov/BRB-ArrayTools. html). As recommended by Agilent Technologies, we chose the percentile method for the normalization, and adjusted the 75 th percentile of all noncontrol probes to 500. We identified genes that were differentially expressed between the two groups using a random-variance t test (Class Comparison Between Groups of Arrays Package, BRB-ArrayTools). Gene expression differences were considered statistically significant if they were showing a §20% difference in mean expression levels between samples from the EE and the control conditions, and if the resulting P value was ,0. 005. Details of the bioinformatic analyses using TELiS, oPOSSUM, and Ingenuity Pathway Analysis are provided in File S1.
001. This program highlights transcription factor-binding motifs that are over-or under-represented in a set of genes (e. g. , genes encoding transcripts either upregulated or downregulated under specific conditions). Figure  4  shows a summary of the results obtained using the human JASPAR and TRANSFAC databases and the transcriptional shift analysis of TELiS. There is clear overrepresentation of GATA and CREB/ATF transcription factors in promoters of the genes upregulated in the control group and overrepresentation of the NF-kB family (c-REL, NFKB) and AP1 and MZF transcription factor motifs in the promoters of genes upregulated in the EE-treated animals. To extend this analysis, we used another bioinformatic software package, oPOSSUM  [29] , which analyzes the data in a different way (see File S1 for details).
The binding motifs of the NF-kB family of transcription factors were found to be over-represented in the genes encoding transcripts that are upregulated in the EE-treated group (as in the TELiS analysis) along with other transcription factors such as Myc/Myf, Egr-1, INSM1, PLAG1, and Zfx. As for the control group, IRF1-binding sites were found to be over-represented, but CREB/ATF and GATA transcription factors were not detected at a significant level. Factors such as ARID3A, NKX3, and FoxD3, were activated more in the control group. To gain insight into the function of the differentially expressed genes, we used the Ingenuity Pathway Analysis (IPA) software. In order to build significant networks, we used the set of 400 differentially expressed genes at P,0. 005. The top score networks, biological functions, and canonical pathways calculated by the IPA software are presented in Tables  S3  and S4.
Nonetheless, EE also attenuates avoidance reactions toward tactile stimuli, human presence, and handling. Thus, these changes reflect broader effects than the classic effects on anxiety. Taken together, these observations seem to demonstrate a more positive perception of the environment, whether it concerns potentially frightening stimuli (novel or sudden) or nonfrightening ones (harmless tactile stimuli) or the human presence. In contrast, control horses. Illustration of the top gene network upregulated in the environmentally enriched (A) and control (B) groups. These data were generated by the Ingenuity Pathway Analysis (IPA) software using the 400 genes differentially expressed at P,0. 005. The genes marked with a red symbol are from the list of differentially expressed genes, whereas the genes marked with a white symbol are intermediary genes of the network added by the software.
The second result concerns the transcriptomic fingerprint of EE. The availability of a horse-specific microarray and of the horse genome sequence has opened up the opportunities for further research into the biological impact of EE on horses. By coupling gene expression data with several bioinformatic analyses, we can show that EE and control conditions have divergent effects on gene expression in blood cells. According to the TELiS analyses, there is pronounced activation of CREB/ATF and GATA families of transcription factors in the control group. In the EE-treated horses, there was a tendency for upregulation of target gens of NF-kB (NF-kB and REL factors), MZF, and AP1. Overrepresentation of the CREB transcription factors in chronically isolated versus socially integrated people has been observed previously  [45].
Here, this hypothesis is not supported by our data because control animals are isolated most of the time but display activation of IRF-1. Rather, activation of IRF-1 in the control group supports the notion that interferon induces a loss of appetite and sickness-like behavior because 4 out of 9 animals in the control group lost their appetite at the end of the experiment. A vet evaluated the animals with eating problems for infectious disease using standard clinical metrics (mostly core body temperature) and found no evidence of an active infection that might explain the observed transcriptomic alterations in immune cells. The oPOSSUM analysis showed overrepresentation of such factors as ARID3, NKX3-1, Foxq1, and FoxD3 (in addition to IRF-1) which are all involved in cell cycle regulation.
Figure5. Illustration of the top gene network upregulated in the environmentally enriched (A) and control (B) groups. These data were generated by the Ingenuity Pathway Analysis (IPA) software using the 400 genes differentially expressed at P,0. 005. The genes marked with a red symbol are from the list of differentially expressed genes, whereas the genes marked with a white symbol are intermediary genes of the network added by the software.
Outcome probabilities and cost inputs were derived from the published literature, clinical trials, expert panels and local database costs. In the base case, patients who failed to respond to first-line therapy were assumed to experience a single switch between comparator drugs or the other drug was added as second-line treatment. Base-case evaluation included only drug-management costs and additional hospitalisation costs due to severe AEs associated with first-and second-line therapies. Sensitivity analyses were conducted to assess the robustness of the results. Cost estimates were inflated to 2011 euros (€). Results: Based on clinical trial success rates of 52. 8% (voriconazole) and 50. 0% (liposomal amphotericin B), voriconazole had lower total treatment costs compared with liposomal amphotericin B in both Germany (€12,256 versus €18,133; length of therapy [LOT] = 10-day intravenous [IV] + 5-day oral voriconazole and 15-day IV liposomal amphotericin B) and Spain (€8,032 versus €10,516; LOT = 7-day IV + 8-day oral voriconazole and 15-day IV liposomal amphotericin B).
In Spain, the Third European Conference on Infections and Leukaemia  [12]  and the Spanish Society of Infectious Diseases and Clinical Microbiology  [13]  provide specific therapies and disease-management strategies. Voriconazole (Vfend®, Pfizer Inc) and liposomal amphotericin B (Ambisome®, Gilead Sciences) are licensed for the treatment of IFD, including IA. In a prospective, randomised trial of voriconazole versus amphotericin B deoxycholate for the primary treatment of IA, voriconazole demonstrated superior efficacy and improved survival, and resulted in fewer side effects, compared with amphotericin B  [14]. Health economic-based models are designed to address questions of economic relevance, and integrate efficacy and safety data from clinical trials with medical resource use and quality of life information from the published literature, expert opinion and database analysis.
To estimate the potential therapy costs of voriconazole versus liposomal amphotericin B, a decision analytic model based on a decision tree was developed (Figure  1 ). Each pathway in the model was defined by the probability of an event occurring and the costs associated with each clinical outcome defined as: (1) treatment success or (2) treatment failure, which included add-on treatment due to lack of response, switching to second-line therapy due to serious AEs or for other reasons, and mortality. The model inputs were treatment options, length of therapy (LOT), additional LOS in hospital, other efficacy and safety inputs, and drug costs. Outcome measures were the total hospital costs (e. g. drug and hospitalisation costs) associated with each therapy in 2011 euros (€). Outcome probabilities and cost inputs were derived from the published literature, clinical trials, expert panel discussions and local database costs.
Key model assumptions The model time horizon was the 30-day inpatient follow-up period based on the mean LOS for HSCT patients with IA and haematological malignancy in a United States claims database analysis  [16]. In the base-case scenario, patients who failed to respond to first-line therapy were assumed to undergo a single switch between comparator drugs or the other drug was added as a second-line therapy. Drug dosages were based on patients having an average weight of 70 kg, as defined in the key randomised clinical trials of voriconazole  [14]  and liposomal amphotericin B  [15]. Voriconazole was administered intravenously at doses of 6 mg/kg twice daily (BID; Day 1) and 4 mg/kg BID (Day 2+), and orally at a dose of 200 mg BID. Intravenous (IV) liposomal amphotericin B was administered at a dose of 3 mg/kg once daily.
Costs of medical resource and drug acquisition Hospitalisation costs and outpatient IV administration costs were based on economic research on the treatment of IA in Germany  [1, 18, 19]  and Spain  [20]  (Table  2 ). Drug acquisition costs in Germany were derived from the LAUER-Taxe, Pharmindex for Germany drug costs (Table  3 )  [21]. Drug acquisition costs in Spain were derived from the Bot Plus database (Table  3 )  [22].
e. arena test, corridor test, isolation box test, shearing test). A broad range of behaviors including vocalizations, locomotion, vigilance and flight distance, as well as the cortisol response to handling, were collected. All lambs were genotyped using the Illumina OvineSNP50 BeadChip. QTL detection was performed by linkage, association and joint linkage and association analyses using the QTLmap software. Five main QTL regions were identified on sheep chromosomes (Ovis Aries Region, OAR) 12, 16, 19, 21 and 23 among many other QTLs with small to moderate effects. The QTLs on OAR12, 16 and 21 showed significant associations with social reactivity. The QTLs on OAR19 and 23 were found to be associated with reactivity to humans. No overlapping QTLs were identified for the different traits measured in the behavioral tests, supporting the hypothesis that different genetic factors influence social reactivity and tolerance to humans.