dataesr/scientific-paragraphs-categorization huggingface dataset:
The equivalent loop, 308 -315, located in the first of the duplicated sequence elements, was not included in SmTK-TSA chain B. The quality of the final crystal structures was assessed with MOLPROBITY  (51)  prior to deposition at the PDB under the codes 4WO8 (SmTK), 4WOD (SmTK-Arg), and 4WOE (SmTK-TSA). Molecular images were generated with PyMOL (Schrödinger, LLC, New York). Secondary structure elements were assigned with DSSP  (52). Figures of sequence alignments were prepared using ESPript/ENDscript  (53). Data collection and final refinement statistics are presented in Table  1. SAXS-All scattering data were collected at the BM29 European Synchrotron Radiation Facility beamline. For every experimental condition (including buffers), the temperature was maintained at 277 K, and 10 frames (with 2-s time exposure) were collected to monitor radiation damages before being merged.
The predicted scattering profiles of crystal structures were calculated using the program CRYSOL for comparison with SAXS data  (58). Low resolution shape envelopes were generated with the ab initio bead-modeling program DAMMIF (59) by performing 10 independent reconstructions, aligning all with the most probable model with DAMSEL and DAMSUP, averaging models with DAMAVER, and adjusting to correspond with the experimentally determined excluded volume with DAMFILT  (60). The final bead model was superimposed upon the x-ray crystal structure coordinates with SUPCOMB (61). For SAXS experiments, SmTK in the concentration range of 0. 5-4. 2 mg/ml was analyzed in the presence or absence of substrates (taurocyamine, 10 mM taurocyamine; MgCl 2 , 10 mM MgCl 2 ; Mg(NO 3 ) 2 , 10 mM Mg(NO 3 ) 2 ; MgADP, 10 mM MgCl 2 , 10 mM ADP; MgATP, 10 mM MgCl 2 , 10 mM ATP; ADP, 10 mM ADP; TSA, 10 mM taurocyamine, 10 mM Mg(NO 3 ) 2 , 10 mM ADP; pre-TSA, 10 mM taurocyamine, 10 mM MgCl 2 , 5 mM AMPPNP).
Enzymatic reactions were followed by the decrease in absorbance at 340 nm of NADH on a Tecan Infinite M1000 spectrophotometer thermostated at 303 K. Samples where preincubated at this temperature for 30 min before adding the enzyme. Apparent kinetic constants were determined under pseudo-single substrate conditions by varying one substrate (taurocyamine or ATP, maximal tested concentration 5 mM) while holding the remaining substrate at constant and saturating concentration (5 mM). Apparent kinetic parameters (k cat(app) and K m(app) ) for wild-type enzyme and single reactive-cysteine mutants were determined from a nonlinear least-squares best fit of the data to the Michaelis-Menten equation using the program GraphPad Prism version 6. 05 (GraphPad Software, San Diego, CA). The apparent catalytic constant for double mutant was determined at single and saturating concentrations of ATP and taurocyamine (5 mM).
RESULTS Solution Characterization and Crystal Structure of Substrate-free SmTK-The duplicated structure of SmTK was investigated by combining SAXS and x-ray crystallography approaches (see "Experimental Procedures"). This enzyme is monomeric in solution, as assessed by the estimation of its molecular mass by SAXS, which indicated values close to the expected 80 kDa at the maximal protein concentration tested (4. 2 mg/ml). Similarly, a PISA analysis  (63)  detected no biological interface in the crystal packing of the 2. 2 Å resolution crystal structure. The calculated SAXS envelope has a slightly twisted U shape into which the atomic structure of SmTK fits perfectly, with a normalized spatial discrepancy value of 0. 94 (Fig. 1B ). Moreover, deconvolution into secondary structural components of the circular dichroism spectra recorded for the wild-type enzyme agrees well with the percentages obtained from a DSSP analysis of the crystal structure (data not shown).
Interestingly, the two monomers, termed A and B, provide different structural information. The 2. 3 Å resolution electron density maps clearly show that all TSA components are bound in each active site of A, whereas nitrate is absent from B. The TSA is firmly attached in lobe D2 of A and induces a global closure of the active site. A hinged rotation of 14º of the terminal region (residues 642-716) around an axis nearly parallel to the nucleotide-binding site cleft was calculated using the program DynDom (66) (Fig. 1C ). This rigid body motion facilitates the stabilization of the flexible loop Gly 670 -Gly 681 that folds over the active site toward the phosphagen specificity loop (Fig. 3  and supplemental Video 1). A significant displacement, which affects helix ␣-8 and adjacent loop 544 -552 on the other side of the active site crevice of D2, further constrains the bound nucleotide (Figs.
Microcalorimetric and Enzymatic Investigations of a Putative Cooperative Mechanism-Because a significant structural asymmetry was observed between the liganded lobes of SmTK-TSA, the enzyme was examined by ITC for evidence of inter-  lobe cooperativity in TSA complex formation by direct titration of SmTK with ADP with or without other TSA components. In the presence of TSA components, ADP binding to wild-type SmTK was characterized by a monophasic sigmoidal titration curve, which enabled us to determine the stoichiometry of binding as 1. 53 sites per SmTK protein (Fig. 6A ). In the absence of TSA components, a clearly distinct binding isotherm was recorded with a binding pattern typical of a weak binding event, and no dissociation constant could be determined (data not shown). The same experiments were performed using the active-site cysteine single mutants, for which structural integrity was controlled by CD spectroscopy (Table  2 ).
* The crystallization work in the study benefited from the  IBCP/UMS   3444/ US8  crystallogenesis facilities of  SFR Biosciences. This work was supported by the  European Community 's  Seventh Framework Program  ( FP7/2007-2013 ) under Grant Agreement 283570 (BioStruct-X). The atomic coordinates and structure factors (codes  4WO8 ,  4WOD , and  4WOE ) have been deposited in the Protein Data Bank (http://wwpdb. org/). □ S This article contains supplemental Video 1.
Acknowledgements The work was supported by the  Agence Nationale de la Recherche  ( ANR PPAIN R0809688  to  NV , and  ANR-12-BSV1-0030-01  to NV and PL). JPM was supported by a studentship from  INSERM/ Région Midi-Pyrénées , and by  Ph. D thesis awards from  GREMI (Group for Research and studies on Mediators of Inflammation)  and  CECED (Digestive epithelial cells study group ). CA was supported by the grant  ANR-12-BSV1-0030-01.
Data collection Mothers were interviewed to obtain socio-demographic, biographic, and clinical variables. These pregnant women were tested using both blood films (thin and thick blood smear) and polymerase chain reaction (PCR) for the presence of Plasmodium, responsible for malaria cases. Study participants who were positive for malaria were treated. All mothers were provided a standard counseling and were systematically screened for the presence of HIV antibody by using Determine HIV 1/2 rapid test kits (Abbott Diagnostic Division, Hoofddorp, The Netherlands). At the delivery, birth weights of newborns were recorded using standard methods.
Acknowledgments We greatly appreciate the immense contributions of students of  Université Prostestante du Congo (UPC) :  Mpangi Mumvunga Sarah ,  Mpetshi Okar Margot ,  Muamba Matanda Marie Paul ,  Mujinga wa Mudumbi Tatiana  and  Mukandi Tshimpaka Carine. This work was supported by the  Institute of Parasitology, Infectious Diseases and Tropical Medicine of Kinshasa, Congo. The  Protestant University of Congo (UPC)  provided a grant for the first two years of study, but had no role in the study design, data collection, analysis, or writing of the report.
Introduction: The dietary intake is an important factor that can influence weight gain and promote the accumulation of fat, especially in the abdominal area Objectives: To evaluate the effect of qualitative nutritional advice on anthropometric and dietetic changes in overweight individuals. Method / Design: Anthropometric (weight and WC) and dietary (24-hour diet recall) data of 101 overweight members of the university community were collected before and after 15 days. The individuals had qualitative nutritional guidance, with a primary focus on reducing the intake of fried foods, sweets, alcohol and on increasing the quantity of meals, intake of fruits and vegetables and whole foods. To quantify the intake of energy and macronutrients, the data were tabulated in the NDSR software. For qualitative assessment of food intake the food-based classification of eating episodes model was used.
Milli-Q water was provided ad libitum. Food intake per group was measured daily throughout the study by weighing each food cup and subtracting this weight from the previously measured weight. Residue in the food cup was not discarded and the daily ration was added to it. The body weight of each rat was measured weekly. On day 21, body weight as well as lean mass, bone mass content and fat mass under anaesthesia were measured using DEXA (Hologic, Discovery A, Quantitative Digital Radiography) with software (Hologic Apex Software, Version 13. 3) for small animal analysis. For the in vivo DEXA scanning, the rats were anaesthetised with an i. p. injection at an overdose rate of 0. 12 ml/100 g body weight using the injectable anaesthetic mixture: 2 mg/ml ACP (2 parts), 100 mg/ml Ketamine (5 parts), 10% Xylazine (1 part) and sterile water (2 parts).
Acknowledgments All the authors were involved in the experimental design and data collection. FKA and JC conceived the ComFa formulations for complementary feeding, particularly for infants in lowincome countries. FKA analysed the data and wrote the first draft. All authors read and approved the final version submitted for peer-review and publication. We acknowledged the  Nutricia Research Foundation , the  Netherlands  (Project number:  2012-E6 ), for funding for the development of the sweetpotato-based complementary foods, and payment of some laboratory analysis. We are indebted to  Delta Produce Co-op Ltd, Dargaville, New Zealand  for providing the sweetpotato and  Nestlé Malaysia , for donating the  Nestlé Cerelac Infant Cereal Wheat & Ikan Bilis.
Cichlid TAAR repertoires We carried out a TBLASTN search of the five cichlid genome sequences determined by the BROAD Institute  [23] , with a set of 199 sequences corresponding to 109 zebrafish, 27 medaka, 50 stickleback and 13 fugu annotated TAAR genes retrieved from the GenBank and ENSEMBL databases  [8]  (Additional file 1). This initial search, with a cut-off of 1e -50 , identified a number of candidate receptors; false candidates were identified by a second TBLASTN search with 247 fish class A non-TAAR GPCR sequences (Additional file 2) and were excluded. Finally, we performed a TBLASTX search against the fish database (NCBI, taxiD: 7898). Table  1  shows the number of TAAR genes identified in the five cichlid genomes (this work) and in the genome sequences of zebrafish, medaka and fugu  [8].
Tetraodon and stickleback TAAR gene sequences were extracted from the ENSEMBL database and curated by hand (this work). Direct comparison of gene content Cichid TAAR genes were retrieved from the genome sequences determined by the BROAD Institute  [23] , as explained in the Methods section. Medaka, stickleback, fugu and zebrafish TAAR genes were obtained from Hashiguchi and Nishida  [8]. The stickleback and medaka repertoires were updated for this work. The first numbers in brackets correspond to the gene numbers retrieved from Hashiguchi and Nishida  [8]  and the second number is the gene number assigned in this work. The tetraodon TAAR genes were retrieved from ENSEMBL and further characterized in this work. between different genome sequences could be biased by the differences in completeness and accuracy of the sequence data.
Additional evidence was provided by BLASTX and phylogenetic analyses, which demonstrated that these genes encoded true TAARs and not other GPCRs, which are generally encoded by more than one coding exon. All the candidate TAAR genes identified by the TBLASTN search against the positive and negative query sets were analyzed further, by a TBLASTX search against the non-redundant NCBI protein database. We retained only proteins giving a strong hit with TAAR proteins and no hit or a meaningless hit with other GPCRs. Finally, a phylogenetic tree was constructed with all the cichlid TAARs identified in this study and 753 class A GPCRs (247 non-TAAR GPCRs and 506 ORs). All of the TAAR sequences clustered in clades independent of those formed by all class A non-TAAR GPCRs (Figure  3 ).
Conserved amino-acid motifs and other features TAARs are GPCRs of the rhodopsin or class A superfamily. They are characterized by a number of features, such as a specific two-dimensional structure involving seven transmembrane domains, with an extracellular N terminus and an intracellular C terminus  [32] , and several amino-acid motifs; these motifs include the MAYDRY or, more precisely, the DRY motif, which plays a key role in regulating the conformational state of GPCRs and is responsible for G-protein coupling  [33] [34] [35]. This DRY motif, located at the junction of the third transmembrane domain and the second internal loop, is the most emblematic motif. We used the MEME program  [36]  to search for the five best motifs in each of the five cichlid TAAR repertoires and in the D. rerio TAAR repertoire.
This variability in the number of TAAR genes is similar to that observed for OR repertoires  [14, 46] , but is less consistent with the higher rate of gene duplication in East African cichlids than in other teleosts as revealed by genome sequence analysis  [23]. All mammalian and zebrafish TAAR genes have a single exon and no intron. In contrast, introns were found in 86% of stickleback, 74% of medaka and 61% of fugu TAAR genes  [8]  (Table  1 ). A re-analysis of the data in the Genbank database revealed the presence of spliced TAAR genes in the genome of tetraodon, albeit at a much lower frequency (16%). The numbers of TAAR subfamilies shared between some of the 10 species (stickleback, medaka, fugu, tetraodon, zebrafish and five species of the cichlid family) and the percentage of spliced TAAR genes have evolved in parallel (Table  4 ).
To assess the specificity of copper-induced protein expression, gel slices of identical sizes were also excised from the soluble protein fraction of unstressed bacteria. Comparative analyses of Mascot search results showed that CopI (17 kDa) and CopJ (14 kDa) were specifically identified under copper stress conditions. While the number of identified peptides  (CopI, 5; CopJ, 7)  and protein coverage (CopI, 44%; CopJ, 69%) were acceptable, N-terminal characterization was rather poor. Since predicted signal peptides (SignalIP and SMART) for periplasm localization are present in sequences of both proteins, we reviewed the LC-MS/MS datasets using the Mascot Error Tolerant Search software to identify nontryptic peptides. N-terminally processed CopJ peptides could not be found, whereas the CopI peptide 23 DAGHDHGSAH AGAHAHDADTPYGRPGDAAK 52 was unambiguously identified (Fig.
To determine whether CopI was thus present in these bands, the proteins were electroeluted from the MICS-BN-PAGE and subjected to Western blotting for CopI detection. CopI was detected only in the gel fractions where a high concentration of copper was detected, i. e. , in WT cells grown with 1,200 M CuSO 4 (Fig. 3 ). Accordingly, these data strongly suggest that CopI strongly binds copper in the periplasm. CopI is required for copper resistance under both aerobic and anaerobic conditions. A copI deletion strain was constructed to analyze the role of CopI in copper homeostasis. The copper sensitivity of the ⌬copI strain was investigated by growing the strain with increasing CuSO 4 concentrations in comparison with the WT and the copA mutant. First, on solidified medium, growth of both ⌬copI and copA strains was affected at 120 M and inhibited beyond 300 M CuSO 4 with aerobic respiration, unlike the WT (Fig.
We therefore questioned whether deletion of copI can give rise to the same phenotype. First, we visually compared the photosynthetic pigment content of the cells grown under microaerobic conditions with two copper concentrations. In contrast to the WT and copA strains, the ⌬copI culture exhibited different pigmentation at 100 M CuSO 4 (data not shown). Then, the pigment content of each culture was analyzed by UV-visible (UV-Vis) absorption. In the ⌬copI and copA cells, the bacteriochlorophyll (peak at 770 nm) and carotenoid (430 to 520 nm) contents were reduced when copper concentration was increased, in sharp contrast with the WT, where the photopigments were not affected (Fig. 5B ). Interestingly, in ⌬copI cells and medium, no trace of coproporphyrinogen III (peak at 395 nm) was observed, in sharp contrast with copA cells (Fig.
Peptide mass measurements were corrected during data processing, and peak lists were generated by PLGS (ProteinLynx Global Server; Waters). Processed data were submitted to Mascot searching using the following parameters: data bank, NCBInr; taxonomy, bacteria; peptide tolerance, 20 ppm; fragment tolerance, 0. 1 Da; digestion, reagent trypsin; variable modification, oxidation (methionine); fixed modification, carbamido-methylation (cysteine). Validation criteria for protein identification were two peptides with a Mascot individual ion score of Ͼ43. Nucleotide sequence accession number. The copI and copJ sequences reported in this paper were deposited in GenBank (accession number KF938602. 1).
The genome contains coding sequences related to fibronectin/ fibrinogen binding protein; translation elongation factor Tu; mucus binding factor and adhesin involved in aggregation, adhesion, and biofilm formation; lipoprotein; lipoteichoic acids; a bacteriocin biosynthetic protein; and a bile salt hydrolase. Those functions likely contribute to the gastric survival of the strain and promote its interactions with the intestinal mucosa and microbiota, such as competitive exclusion of pathogenic bacteria and modulation of the immune system  (12, 13). A more detailed analysis aiming at evaluating the stability, safety, functional, and metabolic aspects of this strain is in progress. Nucleotide sequence accession numbers. This whole-genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession no.
Acknowledgements This experiment has been produced with the financial assistance of the  European Union  through the " PROCAMED" Project: Promotion des systèmes camelins innovants et des filières locales pour une gestion durable des territoires sahariens : reference number: I. B/1. 1/493. The contents of this document are the sole responsibility of  IRA Médenine  and can under no circumstances be regarded as reflecting the position of the  European Union.
Calculations and Statistical Analysis Calculations and statistical analysis were performed on measurements made on 12 cows and 14 goats due to the removal of 1 goat early in the experiment. Milk FA melting point was calculated as the sum of melting points for constituent FA weighted by their respective molar percentages  (Jensen and Patton, 2000). For each individual FA, the melting point was obtained from  Gunstone et al. (1994)  and, failing that, from the Lipid Bank database (http://www. lipidbank. jp). For FA not reported in the literature, melting point was estimated on the basis of structural similarities with isomers of known melting point. Apparent transfer of 20:5n-3, 22:5n-3, and 22:6n-3 from FO into milk were calculated as [grams of milk FA yield × (% FA in milk fat -% in control milk fat)/(DMI × % FA in the diet)] × 100.
All data were subjected to ANOVA for a 3 × 3 Latin square design  (Kaps and Lamberson, 2009)  using the MIXED procedure of the SAS (version 9. 2, SAS Institute Inc. , Cary, NC). The statistical model included the fixed effects of period, species, experimental diet, and their interaction, as well as the order in which treatments were allocated to each animal and the random effect of animal nested within treatment order. For FA found exclusively in milk of cows and goats fed the FO treatment, data were analyzed by the same model, with the exception that fixed effects due to diet and diet by species interaction were removed. Differences between means were tested based on least square differences using the default pairwise t-test in the pdiff option in the lsmeans statement, and declared significant at P < 0.
ACKNOWLEDGMENTS P. G. Toral was granted a post-doctoral fellowship from  Fundación Alfonso Martín Escudero (Madrid, Spain). The authors gratefully acknowledge the staff of  Unité Expérimentale des Ruminants de Theix  ( INRA, Saint-Genès-Champanelle, France ) for the diligent care of the experimental animals, and  D. Bany ,  C. Delavaud ,  E. Tixier , and  M. Tourret  from  UMR 1213 Herbivores (INRA ) for assistance in sampling collection and laboratory analysis. The contribution of  Laura Ventto  and  Minna Aalto  ( Natural Resources Institute Finland, Jokioinen, Finland , formerly  MTT Agrifood Research Finland)  to the analysis of milk fat composition is acknowledged and appreciated.
(iii) Atypical scrapie and ovine BSE. The WB and ELISA failed to identify the presence of BSE in the dilution series when its concentration in the mixture dropped below 10% (Table  3 ). Therefore, the inoculum with 1% BSE concentration relative to scrapie was subjected to bioassays. The incubation period data in tg338 indicate that the agent isolated from these mixtures was compatible with the agent isolated from the atypical scrapie source; in tg110 mice, the incubation period data indicate that agent isolated from the mixtures was compatible with the agent isolated from the BSE source (Fig. 7A ). The lesion profiles from tg338 (Fig. 7B ) and tg110 mice (Fig. 7C ) provide further support to the incubation period data although it was not possible to construct lesion profiles from the scrapie source in tg110, as all of the mice challenged with this source were TSE negative.
ACKNOWLEDGMENTS We thank the many staff in the  Pathology, Virology , and  Animal Services Departments of APHA  without whose technical expertise and support this work would not have been possible. This work was funded by the  European Commission  through its support of the  TSE EU Reference Laboratory , and  Defra  through its support of the  TSE National Reference  Laboratory. M. J. O. was funded by a  BBSRC   DTP studentship.
Statistical analyses Descriptive statistics are presented as means ± standard deviations by sex for the characteristics and fatty acid compositions of erythrocytes and plasma of patients. Eighteen fatty acids and the following ratios (18:3(n-6)/18:2(n-6), 20:4(n-6)/20:3(n-6), 22:6(n-3)/20:5(n-3), 20:3(n-6)/18:3(n-6), 22:6(n-3)/22:5(n-3) and 18:1(n-7)/16:1(n-7)) were analyzed in plasma CE and in TPL and PE of erythrocytes. For dysglycemia and LDL-C, pairwise comparisons were derived using Tukey test. In case of interactions between sex and syndromes or variables, the analysis of variance was realized by sex. Transformation was used for distributional reasons. Statistical analyses were performed by using SAS software, release 9. 3.
, 2005) , SignalP  (Petersen et al. , 2011)  was used for the prediction of signal peptides. BlastP  (Altschul et al. , 1990)  was used for sequence similarity search against the nr database, conserved protein domains were searched in the Pfam database version 27. 0  (Punta et al. , 2012). The prediction of domain linkers was performed with the DLP-SVM web service  (Ebina et al. , 2009).