dataesr/scientific-paragraphs-categorization huggingface dataset:
Animal mobility to get pasturages, livestock markets and the the period in the year when religious ceremonies are celebrated on the top of abnormal climatic events may play a key role in the occurrence and the severity of RVF outbreaks  [32, 34]. Based on maximum likelihood trees, our data showed that Mauritanian 2020 strains clustered with Mauritanian 2015 and Niger 2016 strains  [33]  as well as with South African 2009-2010 strains, closely related to Egyptian strains, suggesting close proximity between the 2015 and 2020 RVF epidemics that occurred in Mauritania. The origins of the 2020 outbreak are likely due to animal mobility between neighbouring countries as commercial animal exchanges exist between countries, although the last reported outbreak of RVF in Senegal was in 2013  [9]  and unfortunately no sequences of the 2013 outbreak were available in the database to allow the comparison and to suggest either the introduction of the isolates from Senegal, or from Egypt to Mauritania, which are both neighbouring countries where animal mobility is likely  [34].
Acknowledgements We would like to thank  Dr. Lemrabotrott Ould Mekhalla , coordinator of the regional project  REDISSE  project for partial financing of the biological reagents and personal protection safety equipment and  Dr. Mohamed Gueya  from the  Ministry of Livestock of Mauritania  for the logistical support during the field missions. We also thank  FLI  for the molecular biology support by providing the RT-qPCR kits. We thank  Abdellahi El Ghassem  for the genome detection analysis.
• Efforts to harmonize patient monitoring across multiple centres following CAR-T cell infusion would be desirable (i. e. , reference labs, shared databases, and collaborations with dedicated centres for 'next generation' research). Successful implementation of these joint efforts will greatly advance our understanding of the biology involved in transferring CAR-T cells and, most importantly, serve our patients. Open Access This chapter is licensed under the terms of the Creative Commons Attribution 4. 0 International License (http://creativecommons. org/licenses/by/4. 0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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.
Rosé Wine Diversity Two hundred and sixty-eight commercial rosé wines were selected from the Rosé du Monde collection 2011, so as to obtain a diverse set of color styles and origins. These wines were analyzed by targeted UHPLC-QqQ-MS in the MRM mode targeting phenolic composition. Enological and color data were also collected. The variable list and codes used and the data presented in this study are provided as Supplementary Materials (Table  S1  and Table  S2 , respectively).
Analysis of Phenolic Composition Polyphenol composition was determined by UHPLC-MS/MS in the MRM mode, using an Acquity UHPLC system coupled to a triple quadrupole (QqQ) mass spectrometer (Waters, Saint-Quentin-en-Yvelines, France) with an electrospray ionization (ESI) source operated in both positive and negative modes. MassLynx software (Waters, Milford, MA, USA) was used to control the instruments and to acquire the data. Then, data were processed using TargetLynx software (Waters, Milford, MA, USA). The method described by Lambert et al. [14]  was applied to detect and quantify 135 phenolics, including 99 anthocyanins and derivatives (native anthocyanins, anthocyanin dimers, pyranoanthocyanins, carboxypyranoanthocyanins, phenylpyranoanthocyanins (i. e. , catechyl, hydroxyphenyl, and guaiacylpyranoanthocyanins), flavanyl-pyranoanthocyanins, flavanolanthocyanin (F-A) and anthocyanin-flavanol (A-F) dimer adducts and methylmethinelinked anthocyanin flavanol adducts (F-ethyl-A dimers); 15 phenolic acids (hydroxybenzoic acids, hydroxycinnamic acids and their methyl esters), six stilbenes, five flavonols, two dihydroflavonols, nine flavanol monomers, dimers and trimers and two F-ethyl-F dimers.
Chemometrics Principal Component Analysis and ANalysis Of VAriance with a Student-Newman-Keuls post-hoc test were performed with RStudio software (www. rstudio. com, Boston, MA, USA, accessed on 30 January 2022) using Factoextra, Agricolae and Stats package. ANOVA results were considered significant at p-value < 0. 05. The correlation network was performed using Cytoscape 3. 9. 0 (https://cytoscape. org/ accessed on 30 January 2022).
Funding: This research was initially funded by  IFV  ( Institut Français de la Vigne et du Vin ) and  Conseil Interprofessionnel des vins de Provence. It was also supported by  CASDAR  under the grant agreement N •  18ART1807 , by  ANRT  under the grant agreement  CIFRE 2018/1412 , and by  Actia (French Ministry of Food)  through funding of  UMT Qualinnov  (2006-2015) that performed oenological analysis and spectrophotometric analysis.
METHOD Several sources of information were used to summarize the literature on this subject, and PubMed, the Cochrane Database of Systematic Reviews, and the Web of Science were used to search scientific articles. The most recent studies conducted in humans (within the last 20 years) were preferentially analyzed, although no strict selection over the period was made. Observational and interventional studies were included, along with literature reviews, systematic reviews, and meta-analyses. Other inclusion criteria were: (1) studies in English or French, (2) containing data on the future mother's nutrition during the preconception period or during pregnancy, and (3) including data on pregnancy outcomes or fetal development. We also looked at articles of interest in scientific journals specialized in food, obstetrics, environmental epidemiology, and obesity.
Moreover, between 25 and 50% had insufficient intake for iodine and iron, between 50 and 75% for fish, seafood, and dietary folic acid, and more than 75% for fruit and vegetables. The study also reported that, for iron, only 55% of women had an intake equal to or above the nutritional benchmark. This high proportion of women with insufficient intake of iodine, iron, and vitamin B9 has previously been reported. 18 The dietary guidelines were retrieved directly from the ANSES report. We have chosen to focus on the recommendations for which data from the literature show that intake was insufficient and on those modified by the 2019 dietary guideline guidelines.
ACKNOWLEDGMENTS The authors thank: the coordinators ( Chloé Barasinski ,  Clermont-Ferrand ;  Rémi Béranger , Rennes;  Catherine Salinier , Gradignan;  Cécile Zaros , Paris) and the experts in the working group ( Julie Bercherie , Paris;  Jonathan Bernard , Paris;  Nathalie Boisseau ,  Clermont-Ferrand ;  Aurore Camier , Paris; Corinne Chanal, Montpellier;  Bérénice Doray , la Réunion;  Romain Dugravier , Paris;  Anne Evrard , Lyon;  Anne-Sophie Ficheux , Brest;  Ronan Garlantézec , Rennes;  Manik Kadawathagedara , Rennes;  Anne Laurent-Vannier ,  Saint-Maurice ;  Marion Lecorguillé , Paris;  Cécile Marie ,  Clermont-Ferrand ;  Françoise Molénat , Montpellier;  Fabienne Pelé ,  Rennes ;  Brune Pommeret de Villepin, Lille; Mélie Rousseau, Loos; Virginie Rigourd, Paris; Laurent Storme, Lille; Stéphanie Weiss, Chambéry ), who contributed the discussions, as well as Journal of Midwifery & Women's Health r www.
A General Chol-Binding Motif in Mammalian Membrane Proteins To determine if the chol-binding motif identified in the IFN-R2 TMD is a general motif present in other proteins, we generated a "relaxed" motif to search for other chol-binding membrane protein candidates. We allowed different permutations of the -branched amino acid Val and the nonbranched amino acids Leu and Gly in the lipid-binding crevice and the polar uncharged amino acid Gln in the interface position: (Q/N)XX(V/I/T/L)(V/I/T/L)XX(G/A)XXX(V/I/T/L) (Fig-  ure 6A ). This new relaxed motif corresponds to 256 different possible motifs (2 × 4 × 4 × 2 × 4), generating a vast number of candidate proteins if directly used to screen an extensive set of mammalian proteins. To overcome this issue, we used a simple motif-probability algorithm named MOtif PRObability (MOPRO) that identifies membrane proteins containing the putative chol-binding motif in a database containing proteomes from mammalian organisms (see Experimental Section for further details).
[40] We applied MOPRO to search for putative chol-binding candidates in single-span membrane proteins in a homology-reduced mammalian protein dataset, and we identified eight over-represented chol-binding motifs with a stringent p-value ≤ 0. 05 and z-score > 2. 5 (Table  S1 , Supporting Information) that fulfill the "relaxed" motif defined in Fig-  ure 6A. These over-represented motifs were then used to search for candidates, this time in a non-homology reduced-mammalian dataset. In this way, a total of 12 novel single-span membrane proteins were found (Table  S2 , Supporting Information). Next, we tested whether IFN-R2-like chol-binding domains are not only restricted to single-span membrane proteins but are also found in multispan membrane proteins. To this end, we repeated the same procedure described above and identified ten over-represented motifs (Table  S1 , Supporting Information) and 38 novel cholbinding proteins (Table  S2 , Supporting Information) in a dataset comprising all predicted transmembrane spanning membrane proteins in complete proteomes from mammalian organisms.
4) for 30 min to avoid unspecific antibodies binding. After blocking, cells were incubated with the primary antibody in 1% BSA, PBS pH 7. 4 for 1 h. Finally, cells were rinsed three times with PBS and incubated with the secondary antibody in 1% BSA, PBS pH 7. 4 for 30 min, washed three times with PBS, and coverslip mounted. All imaged were acquired with a Zeiss Apotome microscope equipped with an argon laser beam. Image processing was performed using FIJI-ImageJ software. IFN-R2 Variants Plasma Membrane Localization: CHO and HAP1 IFN-R2KO cells were grown on glass coverslips, and transfected with GFP-tagged IFN-R2WT or IFN-R2 TM constructs. 24 h after transfection cells were washed three times with PBS and incubated for 10 min at 37 °C with 5 μg mL -1 WGA-Alexa Fluor 647 in PBS. After labeling, cells were washed three times with PBS, and fixed with 4% PFA for 15 min at RT.
After washing with PBS three times, cells were subjected to a second round of permeabilization using 0. 4% Triton X-100 for 15 min. After permeabilization, cells were rinsed with PBS, incubated in blocking buffer for 30 min, and incubated with primary antibody anti-pSTAT1 for 1 h at room temperature. Finally, cells were rinsed three times with PBS and incubated with the secondary antibody in 1% BSA, PBS pH 7. 4 for 30 min, and coverslips mounted in media containing DAPI. pSTAT1 nuclear translocation was quantified with FIJI-ImageJ software by calculating the pSTAT1 nuclear signal (nuclei mask was realized with DAPI staining). Docking Experiments: 3D energy-minimized structure of the TMDs was obtained using the Biochemical Algorithms Library (BALL) viewer 1. 4. 2 software employing the MMFF94 force field.
[49] The solvent excluded (van der Waals) surfaces were simulated, and the structure was set to a maximum energy difference of 0. 0001 kJ mol -1 (15 000 interactions). Cholesterol structure was obtained from the PubChem Compound Database (PubChem CID: 5997). Docking experiments between the acceptor transmembrane receptor and the cholesterol ligand were performed using the AutoDock Vina software (Scripps Research Institute),  [50]  and binding energies were calculated. The ligand and the target transmembrane protein were prepared following the standard procedure of ligand and protein preparation. Finally, the prepared files were submitted to AutoDock Vina. For blind docking experiments, the grid box covers the complete proteins, whereas, for biased assays, the grid box wraps only the target region in the protein.
The docked complexes were analyzed using Discovery Studio 3. 1 visualizer or Chimera UCS software. Besides, blind protein-protein docking experiments were performed using the Swarm-Dock software (Francis Crick Institute). [51] The lowest 3D energy structure of the TMDs was obtained as described above. Bioinformatical Analysis: The amino acid sequence of IFN-R2 was obtained in FASTA format from UniProt. A search for chol-binding domain CRAC and CRAC-like motifs was performed using EMBROSS fuzzpro program, sequences given as a motif search pattern were: [LV]-X (1-5) -Y-X (1-5) - RK], [LV]-X (1-5) -F-X (1-5) -[RK], and [RK]-X (1-5) -F-X (1-5) -[LV]. Protein Sequence Alignment: All IFN-R2 protein sequences from different mammalian species were downloaded in FASTA format from Uniprot. [52] Multiple sequence alignment was performed using the ClustalW program.
Then, the number of occurrences of motif "i" in the randomized TMD data set, Ri, was obtained. Next, the randomization procedure was repeated 10 000 times to obtain the exact Ri value distribution expected for motif "i" over a TMD data set with randomized sequences. From this distribution, the p-value and z-score for motif "i" were calculated. Finally, the motifs that were found to be over-represented were used to screen for chol-binding protein candidates. Candidates were acquired from a 90% homology reduced mammalian data set containing 9981 proteins. This homology reduction was performed using cd-hit. [40, 53] he 8 and 12 novel motifs for single-and multi-span membrane proteins, respectively, were used. TMDs were predicted using SCAMPI by extending the predicted TMDs by three amino acids upstream and downstream.
Raster Imaging Correlation Spectroscopy: HAP1 IFN-R2KO cells were seeded onto imaging dishes (Ibidi 81156) in IMDM media and transfected with GFP-tagged IFN-R2WT or IFN-R2 TM. RICS acquisitions were recorded on a commercial LEICA SP8 3X STED SMD confocal microscope (Leica Microsystems, Manheim, Germany), with an HCX PL APO 63x/1. 2NA CORR CS2 water immersion objective and using a WLL as pulsed laser source. Relative power, as it appears in the LAXs software, was always below 2%. The images shown were representative of the experiments used for quantification out of a larger set of time lapses that were also analyzed for statistical purposes. Diffusion analysis by RICS was examined using SimFCS 4 software (G-SOFT Inc. ), as previously described in ref. [32]. Point spread function was determined as described elsewhere.
Cell PM was stained with WGA-Alexa Fluor 647, and coverslips mounted in media containing DAPI. PD-L1 cell surface expression was quantified with FIJI-ImageJ software by calculating the PD-L1 PM signal (PM mask was realized with WGA-Alexa Fluor 647 staining). Interaction-Dependent Probe Incorporation Mediated by Enzymes: pAz ligation to cell-surface IFN-R2 protein was performed using exogenous LplA W37V. HEK cells were grown on glass coverslips to 80% of confluency and transiently transfected with 400 ng of HA-LAP2-IFN-R2 construct for 24 h. Cell surface labeling of the protein of interest was performed by adding 10 μm LpIAW37V, 200 μm pAz, 1 mm ATP, and 5 mm magnesium acetate heptahydrate in growth medium for 30 min at 37 °C. Negative controls were performed by omitting either pAz or the LpIA W37V ligase in the reaction mixture during cell surface protein labeling.
Three rinses with PBS with 0. 1% Tween-20 was applied between each antibody incubation step. Confocal images were acquired using a Zeiss Apotome. 2. To quantify cell surface interaction-dependent pAz labeling, ROIs were manually drawn on transfected cells by visually inspecting the anti-HA immunofluorescence images. Intensities of cell surface pAZ were computed and normalized on HA intensity. Background fluorescence was measured by drawing a ROI on an untransfected cell. Statistical Analysis: OriginPro was used for plotting data and statistical analyses. No data were considered outliers. One-way ANOVA with Bonferroni´s multiple comparison test was used to determine statistical significance. ***p < 0. 001; **p < 0. 01; **p < 0. 05, ns: not significant.
Acknowledgements This work was supported by grants from the  Spanish Ministry of Science, Innovation, and Universities  ( BFU-2015-68981-P  and  PID2020-117405GB-I00 ) and the  Basque Government  ( IT1264-19 ,  IT1625-22 ) to F. -X. C. and M. L. F. -X. C. acknowledge the generous support of  Fundación Ramón Areces  (grant  CIVP20S11276 ). O. T. was supported by a  Basque Government  grant ( IT1270-19 ) I. R. -B. , O. M. , J. A. N. -G. , and D. C. were supported by the  Fundación Biofisica Bizkaia. The Lamaze laboratory was supported from  Agence Nationale de la Recherche  grants  ANR-11-LABX-0038 ,  ANR-10-IDEX-0001-02 , and  ANR NanoGammaR-15-CE11-0025-01. The  Bernardino de la Serna Lab  acknowledges support from  Belinda and Bill Gates Foundation  and  BBSRC  ( INV-016631  and  BB/V019791/1 , respectively).
Except for SOX2, gene expression changes for SEMA6B, MCAM, and H19 in MCF-7 cells treated with the hypomethylating agent decitabine ((33), GSE74036) were similar to those observed upon TET2 CD expression, validating the hypothesis that these genes are regulated by DNA methylation (Fig  S1B ). Finally, consistent with a lower tumorigenicity of TET2 CD cells, interrogation of proteomic data obtained from a panel of various breast cancer cell lines  (34)  showed that TET2 CD cells activated genes encoding proteins enriched in the proteome of low tumorigenic cells and repressed genes encoding proteins that accumulate in highly tumorigenic cells (Fig S1C  -F ). Similar gene expression changes were also observed in decitabine-treated MCF-7 cells (Fig  S1G ). As a whole, this set of data indicates a lower aggressiveness of TET2 CD cells, which correlates with a down-regulation of master regulators of cell growth and migration, likely contributing to their lower tumorigenic potential.
Altogether, these data indicate that 5mC oxidation dynamics at TSS-CGIs per se is not a robust predictor of the directionality of gene expression changes. To further explore CGI chromatin remodeling upon TET2 CD expression, changes in the distribution of the active promoter mark H3K4me3 and the PRC2-mediated repression mark H3K27me3 were investigated by ChIP-seq in MCF-7 clones. Quite few genomic regions gained H3K4me3 (n = 254) in TET2 CD cells compared with regions gaining H3K27me3 (n = 1,939). However, 55. 1% (140 of 254) of these H3K4me3-up regions overlapped with CGIs compared with 11. 3% (220 of 1,939) of H3K27me3-up regions (Fig  2I ). Contrary to 5mC oxidation, changes in the levels of histone modifications reflected gene expression changes in TET2 CD cells versus EV cells, with CGIs gaining H3K4me3 being associated with activated genes and CGIs gaining H3K27me3 with repressed genes (Fig  2J ).
TET2 regulates lysosome function Innate immune response triggered by viral infection is associated with an RNase L-dependent autophagy of viral particles  (63). Although autophagy was not a term enriched by gene ontology analysis of our RNA-seq data, a significant association of TET2 CD down-regulated genes (FC ≥ 2) with lysosome annotation was evidenced, and this association was even more pronounced when using a less stringent threshold of a 1. 5-fold decrease (Figs  5A  and S4A ). As already suggested in Fig  2N-P , these data indicate that TET2 CD cells are endowed with altered lysosomal function. Downregulation of CLN3, CTSD, and NAGLU in TET2 CD cells was further confirmed by RT-qPCR analysis, and expression of these three genes was shown to be anticorrelated with TET2 expression levels in the breast cancer TCGA cohort of patients (n = 1,218), validating our in vitro observations (Figs 5B and C and S4B and C).
By using siRNAs targeting all three TETs, expression of CTSD and CLN3 was shown to be specifically repressed by TET2 in MCF-7 and T47D breast cancer cells and, to a lower extent, in HEK293T kidney cancer cells (Fig  S4D ). Using the Pan-Cancer TCGA dataset gathering RNA-seq data from 11,060 patients, an anticorrelation between TET2 expression and mRNA levels of lysosome proteins was confirmed for CLN3, CTSD, CTSF, CTSZ, IFI30, and NAGLU, suggesting TET2 might down-regulate lysosomal genes in various types of cancer (Fig S4E). To interrogate a possible impact of TET2 CD expression on lysosome activity, acidic   (64). Data showed that acidic vesicle size was higher in TET2 CD cells, indicating a potential engorgement of lysosomes (Fig  5D  and E ). Lysosomes often position next to the centrosome where they have a high probability to fuse with autophagosomes guided by molecular motors  (65).
SRT1720 has also been shown to enhance TET2 enzymatic activity in myelodysplastic syndrome hematopoietic stem/progenitor cells  (72). Thus, the impact of SRT1720 on global 5hmC levels in MCF-7 cells was first analyzed by dot blot. Data indicated that SRT1720, in MCF-7 cells, did not increase 5mC oxidation (Fig S4G ), ruling out a possible regulation of TET activity by SRT1720 in these cells. At a concentration of 2. 5 μM, SRT1720 induced the appearance of cytoplasmic vacuoles as soon as 4-h posttreatment and these vacuoles were cleared after 24 h in the EV and TET2 mCD cells whereas they remained visible, together with hyper-vacuolated dead cells, in TET2 CD cells (Fig  5K ). After 4 d of treatment with daily doses of SRT1720, marked differences in cell survival were detected between clones, with a drastic reduction in viable TET2 CD cells compared with TET2 mCD cells (Fig  5L ).
Cell cycle analysis, migration, and clonogenic assays The cell cycle was analyzed by flow cytometry. Briefly, 2,000,000 cells were plated on 10-cm dishes in DMEM supplemented with 10% FBS. After 72 h, the cells were trypsinized and fixed with 70% ethanol before being stained with propidium iodide in the presence of RNAse A. The cells were acquired on a Fortessa Becton Dickinson cytometer (Flow Cytometry, Biosit facility), and cell cycle analysis was performed with BD FACSDiva software. For 5-ethynyl-29deoxyuridine (EdU) labeling of S-phase cells, 250,000 cells were plated on coverslips in six-well plates. After 24 h, the cells were incubated with the serum-and steroid-deficient medium and then treated with 10 nM E 2 or vehicle for 24 h in a 0. 5% serumsupplemented medium. Incorporated EdU was then fluorescently labeled with Alexa Fluor 488 by click chemistry (Click-iT EdU Imaging Kit; Invitrogen) according to the manufacturer's instructions.
RT-qPCR analyses Total RNAs were isolated from 5 × 10 7 cells using TRIzol reagent (15596018; Thermo Fisher Scientific) according to the manufacturer's protocol. Reverse transcription was performed using 500 ng of total RNAs as template, 200 units of M-MLV reverse transcriptase (28025013; Thermo Fisher Scientific), and 250 ng of Pd(N)6 random hexamers (PM-301L; Euromedex). Real-time qPCR of reversed-transcribed RNAs was run with SYBR Green Master Mix (1725006CUST; Bio-Rad) in a Bio-Rad CFX96. Data were normalized to the positive control CDK8 using the 2 -ΔΔCt method. Primers were designed using Primer3 software (http://frodo. wi. mit. edu/primer3/; (90)) and were synthetized by Sigma-Aldrich. Primer sequences are listed in Table  S2.
Quantification and statistical analyses RNA-seq reads were mapped to hg19 with Bowtie (91), and transcripts were quantified with RSEM  (92). Differentially expressed genes were identified from RNA-seq data by the R package DESeq2  (93)  after filtering the raw data using the R package HTSFilter  (94). Online tools (GREAT,  (95) ; http://bejerano. stanford. edu/great/ public/html/; Panther,  (38) ; http://www. pantherdb. org/) were used for interpretation and functional annotation. ChIP-seq reads were mapped to hg19 using Bowtie  (91). SAMtools (96) generated bam files, which were processed with MACS (97) to generate wig files. Peak calling was followed a previously described procedure  (79). Sequencing reads from publicly available datasets were mapped and treated following the same procedure as described earlier.