dataesr/scientific-paragraphs-categorization huggingface dataset:
Funding This study was supported by financial support to CESAM ( UID/AMB/50017/2019 ), to FCT/MCTES through national funds, and the co-funding by the  FEDER , within the  PT2020 Partnership Agreement and Compete 2020. This study was also supported by a  Pew Marine Fellowship (USA) , the  National Geographic Channel  through project  Deep Reefs , a  National Geographic/Waitt  grant (no. W153-11 ), the  InAqua Conservation Fund (Oceanário de Lisboa) , the  European Regional Development Fund  ( COMPETE program ) and the  Foundation for Science and Technology (FCT)  of Portugal through postdoctoral fellowship  SFRH/BPD/111003/2015  and programs  CCMAR/Multi/04326/2013 ,  UID/MAR/04292/2013  and  PTDC/BIA-BIC/114526/2009  (DiverseShores-Testing associations between genetic and community diversity in European rocky shore environments).
Data Availability The following information was supplied regarding data availability: Microsatellite data for Paramuricea clavata samples are provided in Dataset S1. The data are available in GEN format and can be used in GENEPOP software package (http://genepop. curtin. edu. au). Each sample is named after the initials of the sampling location, where the last letter ''S'' stands for shallow populations and ''D'' stands for deep populations.
T. , Gautron, J. (Auteur de correspondance) (2019). The glycoproteins EDIL3 and MFGE8 regulate vesicle -mediated eggshell calcification in a new model for avian biomineralisation. Journal of Biological Chemistry, 294  (40) , 14526-14545. , DOI : 10. 1074/jbc. RA119. 009799 EDIL3/MFGE8 in avian shell calcification 2 interactions determine the orientation of calcite crystals, which results in the complex ultrastructure of the eggshell, its texture and consequently its mechanical properties. Over the last couple of decades, numerous studies have defined the chicken eggshell matrix proteome  (11) (12) (13) (14) (15) (16) (17) (18). Currently, the entire dataset of reported proteins contains around 900 nonredundant proteins for the chicken eggshell and more than 600 for the UF  (19, 20). Amongst them, EDIL3 (EGF-like repeats and discoidin Ilike domains 3) and MFGE8 (Milk fat globule-EGF factor 8), are reported in the majority of transcriptomics and proteomics studies associated with chicken eggshell biomineralisation  (11, (13) (14) (15) (16) (17) (18) 21, 22).
2 ). We first investigated the presence of the two proteins in eukaryotes. Blast analysis revealed that EDIL3 and / or MFGE8 were absent from protozoans to sponges. Consequently, the phylogenetic reconstruction was performed with EDIL3 / MFGE8 protein sequences from eumetazoan species (Fig. 2 ). The NCBI database contains a large number of EDIL3 / MFGE8 orthologues. To perform this analysis, we loaded 34 EDIL3 / MFGE8 sequences from 19 different species representing different taxa. These sequences belong to non-vertebrates (1 cnidarian, 1 platyhelminthe, 2 molluscs, 1 arthropod, 1 echinoderm and 1 cephalochordate) and vertebrates (2 fishes, 1 amphibian, 3 reptiles, 3 birds and 3 mammals; Table  S3 ). MFGE8 sequences were often annotated as lactadherin in various databases (Table  S3 ). For consistency during our analysis, all lactadherin sequences were renamed MFGE8 (Fig.
The Gallus gallus mfge8 gene is located on chromosome 10 and is made of 10 exons (Fig. 4 ). As is the case for edil3, mfge8 also exhibited two transcripts of 2588 and 2570 bases, which encode proteins of 474 and 468 amino acids, respectively (NCBI). The shorter transcript is the result of an 18-nucleotide deletion at the onset of the last exon, which induces a loss of six amino acids between two F5/8C domains of the corresponding protein. The remaining sequence is not affected by this deletion. EDIL3 and MFGE8 Gallus gallus proteins were aligned with MEGA7 software, and protein domains were investigated using PROSITE (Fig. 5 ). Both proteins exhibited three EGF-like domains at the N-terminus (Fig. 5 , protein 1 in Fig. 4 ). Residues 22-60 and 24-62 correspond to EDIL3 and MFGE8 EGF-like 1 domains, respectively.
3 and I-TASSER program server. Twenty-two β-sheets and two α-helix were predicted for EDIL3, and 25 β-sheets and two α-helix for MFGE8 proteins, with good correspondence between the 22 β-sheets of EDIL3 and those in MFGE8. We also observed that EGF-like domains are made up of two β-sheets in each protein. The first F5/8C contains 11 β-sheets in MFGE8 and nine in EDIL3, whereas the second is similar in both proteins with seven β-sheets. The 3D structures of EDIL3 and MFGE8 were also predicted with I-TASSER program server (molecular homology modelling) and the spatial arrangement of amino acids involved in each binding function (ITG, Ca 2+ and PS) was highlighted on the 3D structure models using PyMOL Molecular Graphics system (Fig. 6A, C ). A close spatial proximity among residues was observed in accordance with their ability to interact with their substrates and consequently we predicted that these domains are functional.
Eggshell CaCO3 requires bicarbonate ions in addition to calcium to form ACC. This role of HCO3 -supplier inside the vesicles could be ensured by carbonic anhydrases (CAs), which transform soluble CO2 into bicarbonate ions (Fig. 7 ). Indeed, the UF has a high partial pressure of CO2 (100 mm Hg) which is 2-fold elevated compared to plasma  (93, 102). Amongst the members of the CA family, CA4 is present in the eggshell proteome of chicken, duck, quail, turkey and guinea fowl  (25, 101). CA4 is a GPI-anchored protein that is attached to plasma membrane, and consequently we predict that it is present in the extracellular vesicles. Ovocleidin-17 (OC-17), ovalbumin (OVAL) and lysozyme (LYZ) are three chicken eggshell proteins described as ACC stabilisers  (103) (104) (105). Finally, we used the Vesiclepedia database (106) to explore vesicular markers amongst chicken shell proteins already identified (Table  1 ).
Total RNA samples (1 µg) were reversetranscribed using RNase H-MMLV reverse transcriptase (Superscript II, Invitrogen, Carlsbad, USA) and Oligo (dT)™ primers (Invitrogen, Carlsbad, USA). Primers to detect expression of Gallus gallus edil3, mfge8 and eight housekeeping genes (b2m, eif3i, gapdh, gusb, stag2, tbp, sdha, and ppia) were designed using Primer-BLAST (NCBI, https://www. ncbi. nlm. nih. gov/) (Table  S4 ) and synthesised (Eurogentec, Lièges, Belgium). Their efficiencies were evaluated by real-time quantitative RT-PCR using LightCycler ® 480 SYBR Green I Master and LightCycler ® 480 instrument II (Roche, Bâle, Switzerland). Edil3, mfge8 and housekeeping gene expressions were quantified using the Biomark microfluidic system from Fluidigm, in which every sample-gene combination was quantified using a 96.
96 Dynamic Array™ IFCs (BMK-M-96. 96, Fluidigm, San Francisco, USA) at the Get-Genotoul platform (Toulouse, France). After specific pre-amplification and according to manufacturer specifications, the PCR was performed using the following thermal protocol: Thermal Mix of 50 °C, 2 min; 70 °C, 30 min; 25°C, 10 min, Hot Start at 50 °C, 2 min; 95°C, 10 min, PCR Cycle of 35 cycles of (95 °C, 15 s; 60 °C, 60 s), and melting analysis (60°C, 30s; 95°C,1°C/3s). RT-qPCR results were analysed using Fluidigm real-time PCR analysis software v. 4. 1. 3 (https://www. fluidigm. com/software). Six biological replicates and two technical replicates were performed for each sample. GenNorm software was used for validation of housekeeping gene stabilities. Edil3 and mfge8 normalised quantities were calculated using the following formula: gene efficiency (ctcalibrateur- ctsample) / geometric average quantity of housekeeping genes.
Synteny and phylogeny of EDIL3 and MFGE8 Synteny of edil3 and mfge8 genes were analysed using the Genome data viewer of NCBI for 8 vertebrate species (3 mammals, 2 birds, 1 non-avian reptile, 1 amphibian and 2 fishes). EDIL3 and MFGE8 protein sequences of 12 vertebrate and 7 non-vertebrate species (Table  S3 ) were aligned using clustalΩ multiple alignment in MEGA7  (108). The appropriate substitution model, determined using MEGA7 substitution model, was LG model. The phylogenetic tree was built with MEGA7 using Maximum Likelihood method (LG substitution model) with 1,000 repetitions and the bootstrap method to evaluate branch robustness. Additionally, phylogenetic analysis using Bayesian inference was performed using BEAST v1. 10. 4 (109) with 10,000,000 generations and a sampling of tree each 1,000 steps.
Trees were then summarised with TreeAnnotator (distributed with BEAST v1. 10. 4) and displayed using FigTree v1. 4. 4 (http://tree. bio. ed. ac. uk/software/figtree/). Divergence times between species were determined using Timetree (www. timetree. org/) and are reported on the generated phylogenetic tree. Distinct protein domain conservation throughout the evolution of eumetazoans was investigated with HomoloGene (NCBI) and domain sequence analysis in several databases and genome browsers (ExPASy-PROSITE, https://prosite. expasy. org/; Ensembl, https://www. ensembl. org/index. html; SMART, http://smart. embl-heidelberg. de/).
Analysis of gene and protein sequences of EDIL3 and MFGE8 in Gallus gallus Gallus gallus edil3 and mfge8 gene, mRNA and protein sequences were collected from the NCBI database (edil3 Gene ID: 427326; edil3 transcripts: XM_424906. 6 and XM_004949448. 3; EDIL3 proteins: XP_424906. 3 and XP_004949505. 1; and mfge8 Gene ID: 415494; mfge8 transcripts: NM_001277110. 1 and NM_001277111. 1; MFGE8 proteins: NP_001264039. 1 and NP_001264040. 1). NCBI Genome data viewer was used in order to identify the exon / intron boundaries, and alternative splicing of each gene. EDIL3 / MFGE8 (XP_424906. 3 / NP_001264039. 1), HAPLN1 / HAPLN3 (XP_015136083. 1 / XP_413868. 3) and VCAN / ACAN (XP_015136071. 1 / XP_015147464. 1) pairwise alignments were performed using ClustalΩ in MEGA7. BioEdit software (http://www.
Journal of Biological Chemistry, 294 (40), 14526-14545. , DOI : 10. 1074/jbc. RA119. 009799Proteinsinvolved in the proposed vesicular transport. All proteins have been reported in proteomic studies of chicken eggshell (ES) or uterine fluid (UF)(11,15,19,21). ANX and CA can provide Ca 2+ or HCO3 -, respectively. ACC can be stabilised by LYZ(103), OC17(105)or OVAL(104). Extracellular vesicle (EV) markers are from the Vesiclepedia database(106).
Acknowledgements: The authors are grateful to  Jacky Ezagal  for his technical skills and his help in molecular biology experiments. The authors also thank the experimental unit ( UE-PEAT ) for the care of birds, the  GeT-GenoToul plateform Toulouse  for performing the real time quantitative PCR with the  Biomark Fluidigm system and Pierre-Ivan Raynal  and  Sonia Georgeault  from electronic microscopy Platform of the  Université François Rabelais de Tours  for the microscopic observations. MH's participation was partially supported by the  Canadian Natural Sciences and Engineering Research Council (NSERC ,  Discovery program   RGPIN-2016-04410 ). The authors wish to thank the  Université François Rabelais de Tours  and the  Région Centre Val de Loire  for financial support of  Lilian Stapane 's doctoral studies.
Journal of Biological Chemistry, 294 (40), 14526-14545. , DOI : 10. 1074/jbc. RA119. 009799Proteinsinvolved in the proposed vesicular transport. All proteins have been reported in proteomic studies of chicken eggshell (ES) or uterine fluid (UF)(11,15,19,21). ANX and CA can provide Ca 2+ or HCO3 -, respectively. ACC can be stabilised by LYZ(103), OC17(105)or OVAL(104). Extracellular vesicle (EV) markers are from the Vesiclepedia database(106). EDIL3/MFGE8 in avian shell calcification Comment citer ce document : Stapane, L. , Le Roy, N. , Hincke, M. T. ,Gautron, J. (Auteur de correspondance) (2019). The glycoproteins EDIL3 and MFGE8 regulate vesicle -mediated eggshell calcification in a new model for avian biomineralisation. Journal of Biological Chemistry, 294 (40), 14526-14545. , DOI : 10.
For short days (Figs. 3  and 4 ), T°C was kept constant (25 °C) from the beginning of the day 3 light phase until the end of the experiment. The day 3 light phase was shortened by 8 h and red light was used instead of white light, followed by RD 8 cycles, then constant darkness (6 DD cycles). For standard (high light) LD phase delays, T°C was kept constant (25 °C) from the beginning of the day 2 light phase until the end of the experiment. Between days 2 and 3, the dark phase was lengthened by 8 h followed by LD 8 cycles (400 nm-680 nm LEDs at ~2000 lux), then constant darkness (6 DD cycles). Data analysis was done with the FaasX 1. 21 software, which is derived from the Brandeis Rhythm Package  67, 68. FaasX runs on Apple Macintosh OSX and is freely available (http://neuro-psi. cnrs. fr/spip.
php?article298&lang=en). Bin size was 30 min. The data are shown as average double-plotted actograms from n flies. All behavioral experiments were done at least three times (except when indicated) with similar results. The statistical analysis of the phase data was done as follows. For each day, the ZT that corresponds to the peak value of evening activity (second half of the day) in LD/RD cycles was determined from the averaged activity data (n flies). These values were used to generate phase plots that are shown next to the corresponding actograms to better visualize the daily phase during all experiments. Entrainment was then estimated by comparing the peak ZT values of the last 5 days of the shifted LD/RD regime to those of Canton S controls. A genotype was considered entrained when this series of five values was not significantly different from the control one in a one-way analysis of variance (ANOVA) Dunnett′s multiple comparisons test (GraphPad Prism 7 software).
Acknowledgements We thank the  Bloomington Drosophila Stock Center  and the  Vienna Drosophila Research Center (VDRC)  for fly stocks,  M. Boudinot  for the FaasX software, as well as  A. Chatterjee  and  J. Carcaud  for discussions and insightful comments on the manuscript. D. V. acknowledges funding from  European Union   7th Framework Program  ( Marie Curie Career Integration Grant ). F. R. acknowledges funding from  Agence Nationale de la Recherche  (ClockEye and TEFOR grants),  Fondation pour la Recherche Médicale (Equipe FRM  grant), and  European Union   6th  ( EUCLOCK Integrated  Project) and 7th ( INsecTIME Initial Training Network) Framework Programs. D. V. and F. R. are supported by  Institut National de la Santé et de la Recherche Médicale (INSERM).
Analytical approaches We employed a machine learning approach to analyze the suite of indicators. Specifically, we used the gradient forest method (R package gradientForest, available online at http://gradientforest. r-forge. rproject. org/) to explore the responses of ecological indicators to changes in fishing pressure and primary productivity alone or in combination. The gradient forest method builds upon random forests and thus has all the functionalities of random forests  (Ellis et al. , 2012). Random forests are essentially regression tree techniques that do not pre-specify relationships between the response and predictors but rather construct a set of decision rules to recursively partition the data into successively smaller groups with binary splits based on a single predictor variable x  (Breiman 2001).
Funding This is a contribution to the IndiSeas Working Group, co-funded by  IOC-UNESCO  (www. ioc-unesco. org)and EuroMarine (http:// www. euromarinenetwork. eu), to the project EMIBIOS (FRB, contract no. APP-SCEN-2010-II) and to the  IOC-UNESCO GOOS Program  and  GOOS Biology and Ecosystems Panel. The work on Canada West Coast ecosystem was sponsored by  Fisheries & Oceans Canada  under the  Aquatic Climate Change and Adaptation Services Program. YJS and LV were supported by the project EMIBIOS (FRB, contract no. APP-SCEN-2010-II). AG was supported by  NOAA 's  Integrated Ecosystem Assessment (IEA) program  (http://www. noaa. gov/iea/). LJS was supported by  IRD, France , and through the  South African Research Chair Initiative , funded through the  South African Department of Science and Technology (DST)  and administered by the  South African National Research Foundation (NRF).
Optical mapping and measurement Progression of tissue assembly was observed using a fluorescence microscope (Olympus IX71; Olympus, Tokyo, Japan) equipped with a charge-coupled device (CCD) camera (Exiblue; Qimaging, Surrey, BC, Canada; or DP74; Olympus). GCaMP3 was excited from 450 nm to 490 nm, and fluorescence images of GCaMP3-positive CMs were recorded with 8 × 8 binning of CCD pixels at 30 frames/s. Images were processed to obtain data using ImageJ (NIH, Bethesda, MD, USA) and MATLAB (R2014b; MathWorks, Natick, MA, USA) using a customized program. Activation-time mapping was performed using a custom plug-in in ImageJ, as previously described  57.
Transient and electrophysiological Ca 2+ characterization Ca 2+ transience was recorded by fluorescence imaging of GCaMP3-positive CMs with the same experimental setup as that described for optical mapping and measurement. To characterize the spontaneous beating of SOTRs, TWs were removed from the SOTRs 1 day before recording by emerging the SOTRs into medium at room temperature for 1 min. The Ltype Ca 2+ -channel blocker verapamil (1 mM; Sigma-Aldrich) and 5 mM caffeine (Wako Pure Chemical Industries, Ltd. Osaka, Japan) were added directly to the chamber containing the SOTRs during imaging, as described in the figure legends. Extracellular recording of field potentials (FPs) was performed using an MEA dataacquisition system (USB-ME64; Multi Channel Systems). Signals were recorded from days 5 and 6 after CM seeding, and data were collected and processed using MC_Rack (Multi Channel Systems) or LabChart (ADInstruments, Dunedin, New Zealand).
Cycling conditions were set as follows: initial denaturation at 95°C for 10 min, followed by 40 cycles at 95°C for 15 s and 60°C for 70s. Reactions were performed in a StepOnePlus real-time PCR system (Life Technologies). Gene expression was determined using the 2 -∆∆Ct method and relative to glyceraldehyde 3-phosphate dehydrogenase expression. Heatmaps were created by the "pheatmap" package (https://cran. r-project. org/web/packages/pheatmap/index. html), and clustering order was produced using the Ward. D clustering algorithm (https://stat. ethz. ch/Rmanual/R-devel/library/stats/html/hclust. html).
Clustering and sequencing Clustering of the Index-coded samples was performed on a cBot cluster generation system using a HiSeq 4000 PE cluster kit (Illumia, San Diego, CA, USA) according to manufacturer instructions. After cluster generation, the library preparations were sequenced on an Illumina Hiseq 4000 platform (Illumina), and 150-bp paired-end reads were generated. After quality control, the paired-end reads were aligned to the hg19 human reference genome (UCSC; https://genome. ucsc. edu/) using TopHat (v2. 0. 12; https://ccb. jhu. edu/software/tophat/index. shtml)  48. We quantified the relative expression level as log2(FPKM + 1) to perform PCA analysis and hierarchical clustering. Uniquely mapped reads counted by HTSeq  49  were used to conduct differential-expression analysis in DEseq2  50.
Applied to adolescence, such an analysis offers a non-invasive window into cortical architecture, which may recapitulate and expand classical histological findings showing overall increases in cortical myelin in adolescence  (Kaes, 1907)  as well as transcriptional analyses suggesting that laminar signatures reflect cortical development  (Miller et al. , 2014). In addition to studying regional variations in cortical architecture, depth-dependent profiling theoretically lends a framework to tap into the large-scale coordination of different brain areas. One such approach, known as microstructure profile covariance (MPC), quantifies inter-regional similarity in microstructure at a single subject-level  (Paquola et al. , 2019). Previous research has demonstrated the utility of MPC for understanding large-scale patterns of cortical architecture, specifically illustrating a sensory-fugal gradient of microstructural differentiation in both post mortem and in vivo datasets  (Paquola et al.
, 2019). This axis describes gradual transitions from primary sensory and motor regions with high laminar differentiation, through association cortex toward paralimbic areas with increasingly dysgranular appearance  (Mesulam, 1998). Given prior evidence that microstructural similarity predicts cortico-cortical connectivity  (Barbas and Rempel-Clower, 1997) , tracking age-related changes in MPC provides an unprecedented way to probe coordinated maturation of microstructural networks during the critical adolescent period, moving towards a network perspective of structural brain development  (Alexander-Bloch et al. , 2013; Vasˇa et al. , 2018). The present study examined adolescent maturation of cortical architecture and microstructure using an accelerated longitudinal NeuroScience in Psychiatry Network dataset  (Kiddle et al.
Characterization of intracortical MT profiles We studied the NSPN dataset, an accelerated longitudinal cohort that aggregates multimodal imaging data from 234 adolescents and young adults aged 14-27 (for details on cohort selection, processing, and quality control, see Materials and methods). Briefly, we generated cortical surface models based on T1-weighted MRI and co-registered the corresponding MT volumes to these surfaces. We systematically generated equivolumetric intracortical surfaces and sampled MT intensities along matched vertices perpendicular to the cortical mantle to build intracortical MT profiles (Figure  1A ). Our vertex-wise technique leverages equivolumetric transformations that critically adjust surface placement in accordance to the folded cortical sheet  (Wagstyl et al.
, 2010). The pattern of age-related change in skewness showed a significant and specific transcriptomic signature (for unthresholded lists, see Data Availability). Cell specific expression analysis  (Dougherty et al. , 2010)  suggested enrichment exclusively with oligodendrocytes (p<0. 001 [at a specificity index threshold of 0. 0001]; Figure  3A ), confirming the association between myelination and decreased MT skewness. Developmental expression analysis  (Dougherty et al. , 2010)  showed selective enrichment for adolescence and young adulthood (Figure  3B ). Both analyses thus confirmed a spatial overlap of our findings from NSPN with genes associated with myelin processes, that are also enriched during adolescence. It should be noted however that individual gene expression assays only provide a snapshot of inherently dynamic processes (ArnatkevicIu ¯te ˙et al.
, 2019). We detected enrichment of adolescent-linked genes based on cross-sectional developmental gene expression data. Specifically, genes showing significant spatial overlap in adult post-mortem brains from the AIBS were identical to those showing significant expression differences during adolescence in the BrainSpan dataset. While there was evidence for an adolescent developmental signal results are nevertheless indirect, also given that glial and oligodendrocyte associated genes may undergo expression changes during other periods of the lifespan  (Soreq et al. , 2017). Furthermore, we performed gene ontology analysis using a modified Fishers exact test, which captures the deviation from the expected gene rank  (Kuleshov et al. , 2016) , on genes associated with decreasing skewness. This indicated a negative association with demyelination (Z = À2.