dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgements We thank  Thomas J. Buckhout  ( Humboldt University, Germany ) for valuable suggestions and critical comments on the manuscript. Proteomic mass spectrometry analyses and in-gel digestion was performed by the  Proteomics Core Laboratory  sponsored by the  Institute of Plant and Microbial Biology (IPMB)  and the  Agricultural Biotechnology Research Center (ABRC) ,  Academia Sinica. Libraries for RNA-seq analysis were constructed by the  Affymetrix Gene Expression Service Laboratory  (http://ipmb. sinica. edu. tw/affy/)supported by  Academia Sinica. We acknowledge the  Small Molecule Metabolomics Core Facility , sponsored by IPMB and the  Scientific Instrument Center, Academia Sinica , for providing technical assistance and support with data acquisition and analysis of Synapt HDMS experiments.
We further thank  Wen-Dar Lin  from the  Bioinformatics Core Lab at IPMB  for bioinformatics support and the laboratory of  Dr. Kuo-Chen Yeh  ( ABRC ) for experimental and technical help with ICP-OES analysis. The study was supported by a bilateral grant from the  Ministry of Science and Technology (MoST)  and the  Agence Nationale Recherche (ANR)  to C. C. and  W. S. (grant Nr. 101-2923-B-001-001-MY3 ). The mass spectrometry proteomics data have been deposited to the  ProteomeXchange Consortium  via the PRIDE partner repository with the dataset identifier PXD003309.
Patients and methods We collected retrospectively clinical, biochemical, imaging and electrophysiological data from thirteen genetically confirmed CTX patients followed at La Pitié-Salpêtrière University Hospital. In order to delineate the natural history of the disease, we selected only patients whose diagnosis was made in adolescence or adulthood. Values are expressed in mean ± SD and/or median. For the Kaplan-Meier analyses, we assumed that patients are determined to have CTX at birth. Therefore all time to event data (e. g. time to diarrhea, time to cataract) assumed that the initial time was the date of birth. The censoring time was the age at latest neurological exam. The symptoms were communicated via the caregiver or the patient directly. Each patient gave a written informed consent to participate in the study.
In humans, two different subtypes of OCA1 have been clinically identified, OCA1A and OCA1B. Mutations completely abolishing tyrosinase activity result in OCA1A, while mutations that leave some residual enzyme activity result in OCA1B, allowing accumulation of some melanin pigment over time  [11]. Therefore, cases with the OCA1A type suffer from complete lifelong absence of melanin, while OCA1B patients retain the ability to tan  [13]. By exploring the Human Gene Mutation Database  [14] , 234 pathogenic missense/nonsense mutations have been identified in OCA1 patients, affecting 169 unique amino acids, of which 53 are targeted by two or more mutations. Particularly, a subset of OCA1B mutations, including R402Q  [15, 16] , P406L  [17] , and R422Q  [18, 19] , cause the so-called temperature-sensitive oculocutaneous albinism (OCA1-TS), which leads to a temperature-sensitive form of TYR with optimal enzymatic activity at a temperature lower than 37°C; as a result, pigmentation is generally more prominent in the extremities (ears, face, and legs), where the temperature is cooler than in other parts of the body  [20].
Yet, the full-length sample contains the single α-helical trans-membrane domain, and the flexible C-terminal domain, both of which are likely detrimental for crystallization. In this study, we set up an easy protocol to overproduce active TYR, in which only two purification steps are needed to obtain highly pure protein sample. The protocol provides a consistent high expression yield of 4-6 mg per litre of culture, which is not only useful for crystallization screening, but also can be applied to carry out high-throughput screening for skin whitening agents. Another major challenge in crystallizing TYR is likely the presence of N-linked carbohydrate residues due to their intrinsic flexibility and heterogeneity. Indeed, glycoproteins are troublesome for crystallization in general, as evidenced by the dearth of human glycoproteins in the Protein Data Bank  [54].
Acknowledgements. The author acknowledges Pr. Philippe Legrand  ( Head of the laboratory of Biochemistry and Human Nutrition, Agrocampus Ouest-INRA USC 1378, Rennes, France ), his former D304, page 5 of 8 Dossier V. Rioux: OCL 2016, 23(3)  D304  Ph. D. students  Dr. Erwan Beauchamp  and  Dr. Hélène Ezanno  and his current Ph. D. student  Fanny Lemarié  for their great contributions to researches described in this review.
Statistical Analysis Mortality was expressed by the Kaplan Meier method and compared with the log-rank test. The inter-group comparison of hemodynamic parameters was performed by ANOVA for repeated measures; the pairwise comparison was made using a Tukey-Kramer adjustment for p values. A nonparametric analysis by a Kruskal Wallis test with a Dunn post hoc test was used for protein, °NO, O 2 °-and prostacyclin analysis. All statistics was performed with Statview™ software (version 5. 0, SAS Institute, Cary, NC, USA). All values were presented as mean ± SD for n experiments, with n representing the number of rats. A p value < 0. 05 was considered statistically significant.
S1C ). We further confirmed that the TLR activation was responsible for the observed NF-κB response. We pretreated cells with either an antibody antagonist of one TLR (TLR2) or its isotype control prior TLR2 stimulation. The anti-TLR2 blocking antibody specifically inhibited NF-κB response to TLR2/6 ligand but not to Il-1β (Fig. 1C ). We could therefore demonstrate that NCI-h716 cells expressed functional TLRs that can respond to microbial motifs by inducing the NF-κB pathway. TLR agonists induced a NF-κB-dependent expression of Pyy Promoter gene analysis using Jaspar database  (Mathelier et al. , 2014)  revealed that Pyy promoter contains two putative NF-κB binding domains in position -978 (GGGGTACCTCCC) and -833 (TGGGGTCCCCCA). Thus, we hypothesised that Pyy expression may be increased consequently to NF-κB activation.
NF-κB activity and cell viability NCI-h716 pNiftySEAP2 cells were seeded at 5. 10 4 per well in 96 well-plates and incubated for 24 h in 100 μl RPMI with TLR agonist or control. Secreted alkaline phosphatase (SEAP) in supernatant was quantified by reaction with Quantiblue reagent (Invivogen) during 6 h incubation at 37°C by measuring OD 655 nm using a microplate reader (Infinite 200, Tecan) accordingly to the manufacturer's instructions. Data were normalised to non-treated cells for each experiment and analysed using Student's t test. Cell viability was assayed using the CellTiter 96 Aqueouscell proliferation assay (Promega) following the manufacturer's instructions.
Measurement of the production of the pro-inflammatory cytokine IL-6 IL-6 production was quantified with standard ELISA kit (R&D system, San Diego, CA, USA) in the supernatants of synoviocytes exposed to cytokines and Zn at day 1, 5 and 8. Statistical analysis and modeling. Statistical significance of changes in data (mean ± standard error of the mean, SEM) was determined by GraphPad Prism™ using nonparametric statistical methods. A two-way ANOVA test was used in the case of exposure to both Zn and cytokines. A Mann-Whitney test or Wilcoxon matched-pairs signed rank test were used in the case of single exposure. p-values inferior or equal to 0. 05 were considered statistically significant. A model of diffusion-controlled Zn transport was constructed to describe the variation of Zn flux through the cells with or without IL-17 and TNF-α addition.
This project and PB have received funding from the  7th Framework program  of the  EU ,  SP3-People , support for training and career development for researchers ( Marie Curie), Network for Initial Training (ITN ),  FP7-PEOPLE-2011-ITN , under the  Marie Skłodowska-Curie grant  agreement  N°2 89903. This work has been supported in part by grants from the  IHU prometteur OPERA  and the " Cluster 1 region Rhône-Alpes. "PM is a senior member of and supported by the  "Institut universitaire de France. ".
1%, sucrose 5% and saccharine 0. 13%; Experiment 1). In Experiment 2, rats were killed 90 min after sucrose intra-oral infusion to investigate c-Fos brain expression. Berridge, 2000). Hedonic reactions were classified as tongue protrusions and paw licks. Negative reactions were classified as forelimb flails, gapes, head shakes and face wipes. Neutral reactions were classified as small mouth movements and passive drips. Gapes, forelimb flails and head shakes were counted as discrete events. Repetitive actions were counted in time bins: tongue protrusions (2 s), paw licks (5 s), face wipe (5 s), mouth movements (5 s) and passive drip (5 s). This analysis allows the harmonization of different types of reaction which could be summed into total hedonic, aversive or neutral scores. Data are expressed as number of events per minute.
Digital microphotographs of the region of interest in each hemisphere were examined with 59 virtual lens. Quantification was performed using an automated method developed in the laboratory with IMAGEJ software with the same threshold applied for each section. c-Fos-positive nuclei were quantified in the NAc (core and shell, from bregma +2. 5 to +1. 0 mm), the VP (from bregma +0. 4 to À0. 2 mm), the basolateral and central amygdaloid nuclei (BLA and CEA respectively; from to bregma À2. 3 to À3. 0 mm), the lateral hypothalamus (LH; from bregma À2. 3 to À3. 0 mm) and the ventral tegmental area (VTA; from bregma À5. 3 to À6. 0 mm) according to the atlas of  Paxinos & Watson (2007). Moreover, we also quantified c-Fos-positive cells in the gustatory part of the insular cortex (GCx, from bregma +2.
Data analysis All values are expressed as mean AE SEM. Behavioural data were analyzed using two-way ANOVAs with Group as between-subjects factor and Age (sucrose exposure), Bottle (Consumption tests) and Reactions (Taste reactivity tests) as within-subjects factors. The c-Fos data were analyzed using two-way ANOVAs with Group as between-subjects factor and Region as within-subjects factor. Bonferroni post hoc tests were performed when required. Linear regression and Pearson's correlation tests were used to investigate relationships between positive orofacial reactions and c-Fos levels. All the analyses were performed using GRAPHPAD PRISM (v 6. 01). The alpha risk for the rejection of the null hypothesis was 0. 05.
Study sample The Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study (HELENA-CSS) is a multicenter study for the assessment of the nutritional and lifestyle status of adolescents in 10 European cities  [12]. A random cluster sampling of 3528 European adolescents (target number) aged 12. 5e17. 5 years, stratified for geographical location, age and socioeconomic status, was carried out. Adolescents were excluded from the analysis a posteriori; if participating simultaneously in another clinical trial, if aged <12. 5 or !17. 5 years or if they suffered from an acute infection less than 1 week before the inclusion. All data were collected via standardized procedures. Details on the sampling and recruitment process and quality control procedures can be found elsewhere  [13].
Ethical issues and respect for good clinical procedures have also been discussed previously  [14]. Informed consent was obtained from all participating adolescents and their parents. Sensitivity analyses were performed in the sample by comparing the levels of BP and HR among adolescents who had complete dietary data (n Z 2283) and those who did not (n Z 1148). We found no significant differences in both levels of BP and in heart rate between the two aforementioned subgroups (p > 0. 05) and finally 2283 subjects were included in the current study.
Dietary assessment Dietary intake was assessed using a computerized 24-hour recall on 2 non-consecutive days, excluding weekend days, and within a time-span of 2 weeks. The 24-hour recall was performed using a validated computer-based tool for selfreported 24-hour recalls, HELENA-DIAT (Dietary Assessment Tool), based on a previous version developed for Flemish adolescents, called Young Adolescents' Nutrition Assessment on Computer (YANA-C)  [15]. Difficulties in obtaining comparable estimates of the energy and nutrient content of foods across countries precluded the use of country specific food composition tables to calculate energy and nutrient intakes. For pragmatic reasons, the data of the HELENA-DIAT were linked to the German Food Code and Nutrient Date Base (BLS (Bundeslebensmittelschlüssel), version II.
3. 1, 2005) , as this food composition database contained the largest number of nutrients and food items in Europe: approximately 12,000 coded foods and it has been demonstrated good accuracy in estimating nutrient intake in European adolescents  [16]. If a food item was missing in the German food composition table, calculations were made via recipes or a local food composition table for the specific country. All food groups were estimated in grams per day. Dairy products included milk, yoghurt, cottage cheese and milk and yoghurt beverages. High-sugar foods included sugar, honey, jam, cakes, pies, biscuits, confectionery and carbonated drinks. Savoury snacks included chips, salty biscuits, crackers and pop corns. of automated digital BP device for clinical use (OMRON MODEL hem 7001) approved by the European Hypertension Society  [17].
These data collection procedures have been previously described  [18]. Briefly, participants were seated in a separate, quiet room for 10 min with their backs supported and feet on the ground. The between-device coefficient of variation was <5% for measurements of SBP, DBP and heart rate. Two BP and heart rate readings were taken with a 10 min interval between; the lowest reading was recorded. MAP was calculated as ((2*DBP) þ SBP)/3. Interobserver coefficients of variation were 2. 1% and 3. 6% for SBP and DBP, respectively.
Socioeconomic status and physical activity questionnaires A self-reported socio-demographic, economic and lifestyle questionnaire about the adolescent and its family was collected  [18]. Parental educational level was defined as one of four levels (elementary, lower secondary, higher secondary or tertiary education). To assess physical activity of the last 7 days, an adolescent-adapted version of the International Physical Activity Questionnaire (IPAQ) was used, namely the IPAQ-A  [20] , assessing the different domains of physical activity (school, transport, housework and leisure time). For each of the four domains, total physical activity, moderate, vigorous and moderate to vigorous physical activity (MVPA) (expressed as minutes per week) were computed and summed to be used in the analyses, based on the guidelines for data processing and analyses of the IPAQ.
Statistical analyses The Statistical Package for the Social Sciences for Windows version 20 (SPSS Inc, Chicago, IL, USA) was used to carry out all statistical analyses. Only adolescents with complete two 24-hour recalls, BP and heart rate data were included in the study (n Z 2283). Underreporters of energy intake were calculated using Goldberg's cut-offs, 15% of the final sample were categorized as underreporters and finally included since the results from descriptive and correlation analyses were very similar when including or excluding the underreporters (p < 0. 05). Individual usual food and nutrient intakes, resulting from the two 24-hour recalls were estimated using the Multiple Source Method (MSM)  [21]. This method removes the effect of day-to-day variability and random error in both 24-hour recalls.
Moreover the absence of SFB (Candidatus arthromitus) in the ileum of HF-fed mice (4. 98% ± 3. 50% in SD-fed mice vs. undetectable in HF-fed mice) confirmed FISH analysis (Fig. 1A  and Fig. S4 ). HF Diet Differentially Alters AMP Gene Expression in the Duodenum, Jejunum, and Ileum. AMP gene expression was analyzed by RT-qPCR following 30 d of HF diet consumption (Dataset S1). Interestingly, in HF-fed mice, AMP gene expression was significantly different in the duodenum and jejunum, compared with the ileum (Fig. 2A ). Whereas Reg3γ was down-regulated by 2. 8and 5. 2-fold, respectively, in the duodenum and jejunum in HFfed mice compared with SD-fed mice, its expression remained unchanged in the ileum (Fig. 2A ). Moreover quantification of the immunofluorescence staining intensity of Reg3γ showed a significant decrease by 43% and 34% in the duodenum and jejunum, respectively, whereas it remained unchanged in the ileum (Fig.
4 B  and C ). Shift to SD After 30 d of HF Diet Reverses the Observed Phenotypes. After 30 d on HF diet, mice were returned to SD for 30 d (HFrev mice) and re-evaluated in comparison with littermates kept for 2 mo under an HF-diet. We observed a restoration of the spatial distribution of the microbiota in the ileum of HF-rev mice as observed in SD-fed mice (Fig. 5A ). The ileal gene-expression pattern of HF-rev mice showed that the shift to SD allowed gene expression of Cftr and Ppar-γ to return to the values previously observed in SD-fed mice (Fig. 5B ). Moreover, analysis of the microbiota composition of HF-rev mice showed that the bacterial relative abundance returned to levels similar to those observed in SD-fed mice, as shown by the PCoA clustering (Fig. 5C  and Dataset S1). At the phylum and family levels, the relative abundance of Bacteroidetes (S24-7 family), Verrucomicrobia, and Desulfovibrionales was similar to those of SD-fed mice (Dataset S1).
7B ). If the staining of Meprin-β in HF-rosi mice did not reach the level of SD-rosi mice (Fig. 7C ), it appeared stronger than that of HF-fed mice (Fig. 4C ). Concerning the microbiota composition, treatment with rosiglitazone did not restore the microbiota composition of HF-fed mice to that of SD-fed mice, as the relative abundance of the main bacterial families in HF-fed mice and HF-rosi mice remained very similar. For example, the relative abundance of the S24-7 family, which was 36. 54% ± 3. 59% in the feces of SD-fed mice and 6. 74% ± 1. 33% in HF-fed mice, reached 11. 21% ± 5. 32% in HF-rosi mice (Dataset S1). To validate the involvement of PPAR-γ in both spatial distribution of bacteria and AMP gene expression, experiments were performed with PPAR-γVillinCre + mice and their littermate controls, PPAR-γ VillinCre -mice, both fed with SD.
RT-qPCR Analysis of Intestinal Cell Gene Expression. Intestinal RNAs were analyzed by RT-qPCR. The list of the genes detected using the SYBR Green PCR system and the primers associated are listed in Dataset S1. Differences were calculated using the comparative 2-ΔΔCt method  (81). Results obtained with the QuantStudio 7 Flex Real-Time PCR System, 384-well (Life Technologies) were normalized to those for the Gapdh gene (Table  S2 ) and compared with the mean target gene expression in SD mice. LCM and Sample Collection for Intestinal Microbiota Analysis. Duodenum, jejunum, and ileum were embedded in OCT compound 4583 (Sakura), frozen in isopentane cooled with dry ice, and stored at -80 °C. Frozen blocks were cut with a thickness of 8 μm using a CM 3050S cryostat (Leica), and sections were collected on Superfrost plus slides (VWR) and stored at -20 °C.
8 16S rRNA genes sequence database  (86). To build the phylogenic tree of representative sets, the multiple-alignment was generated using PyNAST (87) based on default similarity of 75%. The phylogenic tree was constructed using make_phylogeny. py with tree_method_default parameter using the FastTree algorithm  (88). The resulting phylogenic tree was further processed to calculate core diversity metrics, including β-diversity [based on weighted/unweighted unifrac metrics  (89) ] and α-diversity (for different depth of rarefactions) measures. Moreover we carried out taxonomic group diversity analysis and differential taxonomy abundance (scripts of Qiime). The intergroup high similarity and intra group low similarity of microbiota in the contexts of HF diet and SD are proven by β-diversity, PCoA (Generated By Qiime using unweighted unifrac metrics)  (84, 89).
DNA was stained with DAPI revealing both eukaryotic and bacterial cells. Image Acquisition and Analyses. Structured illumination microscopy was used to observed fluorescent signals and for photography (IX81 Olympus). The intensity of IF staining were evaluated with the software MacBiophotonics ImageJ. Tissue-Conductance Measurements. Segments of duodenum, jejunum, and terminal ileum were mounted in Ussing chambers (Easy Mount Physiologic Instruments) with an exposed area of 0. 2 cm 2. The tissues were bathed at 37 °C, pH 7. 4 with carbogen-gassed Krebs-Ringer bicarbonate solution (92) containing 10 mM of glucose and mannitol in the basolateral and mucosal compartment, respectively. Electrogenic ion transport was monitored as shortcircuit current (Isc) by using an automated voltage clamp apparatus (DVC 1000; WPI) linked through Lab-Trax-4/16 to a PC computer.
At steady-state (30 min), potential difference and Isc were measured and total ionic conductances were calculated according to Ohm's law. Tissues were then challenged serosally with 10 μmol/L forskolin and ΔIsc was registered. Statistical Analysis. Data are reported as means ± SEM. Mann-Whitney test or one-way ANOVA (Prism 5. 0, GraphPad software) were used and significance was set at *P < 0. 05, **P < 0. 01, ***P < 0. 001.
ACKNOWLEDGMENTS. We thank  Laurence Motreff  for her help with the Illumina libraries preparation and the MiSeq run;  Eeswari Paramalingam  for animal handling and tissue preparation;  Jacques Ravel  for editing the manuscript; and  Nathalie Bechon  for her contribution during her fellowship. J. T. was in part funded by the  Contrat Jeune Scientifique  from the  Institut National de la Recherche Agronomique  (Jouy-en-Josas, France). This work was supported in part by the  Société Française de Nutrition ; the  Fondation des Treilles  created by  Anne Gruner Schlumberger  (www. les-treilles. com); the  French Government 's  Investissement d'Avenir program ,  Laboratoire d'Excellence "Integrative Biology of Emerging Infectious Diseases"  (Grant  ANR-10-LABX-62-IBEID ); the  European Research Council Advanced Grants 339579-DECRYPT  (to P.
In the Carbohydrate-Active Enzyme (CAZy) database, glycoside hydrolase family 5 (GH5) is a large family with more than 6,000 sequences. Among the 51 described GH5 subfamilies, subfamily GH5_26 contains members that display either endo-␤(1,4)-glucanase or ␤(1,3;1,4)-glucanase activities. In this study, we focused on the GH5_26 enzyme from Saccharophagus degradans (SdGluc5_26A), a marine bacterium known for its capacity to degrade a wide diversity of complex polysaccharides. SdGluc5_26A displays lichenase activity toward ␤(1,3; 1,4)-glucans with a side cellobiohydrolase activity toward ␤(1, 4)-glucans. The three-dimensional structure of SdGluc5_26A adopts a stable trimeric quaternary structure also observable in solution. The N-terminal region of SdGluc5_26A protrudes into the active site of an adjacent monomer.
Although ␤(1,3;1,4)-glucanases are encountered in several GH 2 families of the Carbohydrate-Active Enzyme (CAZy) database (4) (www. cazy. org), most are found in families GH5 and GH16. To date, with more than 6,600 available sequences in the CAZy database, family GH5 is one of the largest. Enzymes in this family are retaining glycoside hydrolases that operate via a classical Koshland double-displacement mechanism  (5). The first crystallographic structure of the GH5 family was solved in 1995  (6). It revealed a (␤/␣) 8 barrel found in other GH families that belong to the structural clan GH-A. Even if enzymes from family GH5 are predicted to be mainly involved in plant cell wall degradation, assignment of enzyme specificity is still complex. Indeed, up to 20 different activities have been reported for this large family  (7).