dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgments We acknowledge  Montpellier Biocampus  facilities: the imaging facility (MRI), the " Réseau d'Histologie Expérimentale de Montpellier" -RHEM  facility supported by  SIRIC Montpellier Cancer  Grant  INCa_Inserm_DGOS_12553 , the  european regional development foundation  and the  Occitanian region  ( FEDER-FSE 2014-2020   Languedoc Roussillon ) for processing some of our animal tissues. We acknowledge the  MGX facility  for the RNAseq analysis, and the MRI imaging platform. We are grateful to  Olivier Coux  and  Aymeric Bailly  for their help in producing FGF19 and Aldafermin recombinant proteins, and to  Geun-Joong Kim 's Lab for advice. We thank  Georges-Philippe Pageaux  for helpful discussions and  Michael Hahne  for support. This work was funded by  EVA-Plan cancer INSERM THE ,  Association Française pour l'Etude du Foie (AFEF)   AAP_2021  and supported by  SIRIC Montpellier Cancer  Grant  INCa_Inserm_DGOS_12553 ,  Fondation ARC and INCa  ( 2019-134 ).
05 for each comparison. Correlation plot of the mean log10(CPM) of the Aldafermin+MYC and FGF19 +MYC tumors. Each point represents one gene, and the black line is a linear regression over the whole dataset. Equation of the linear regression and its Pearson's correlation coefficient are indicated. Mann-Whitney test statistical significance is indicated. Abbreviations: HES: Hematoxylin & Eosin & Saffron.
The citrullinating enzymes found in human parasites and microbes are highly divergent in sequence and have different substrate specificities. These include pPAD, which is an extended agmatine deiminase found in Porphyromonas gingivalis, and giardia ADI, which is an extended form of the free L-arginine deiminase gADI found in the human parasite Giandia lamblia  (35, 36). Previous small scale phylogenetic analysis of the PADI family has shown that PADI2 is the most conserved family member. Mammalian PADIs comprise three structural domains; the Nterminal domain (NTD) (PADI_N, Pfam annotation: PF08526), the middle domain (PADI_M, Pfam annotation: PF08527), and the catalytic C-terminal domain (PADI_C, Pfam annotation: PF03068)  (37) (38) (39) (40). Of note, there is a closer relationship between PADI1 and PADI3, and between PADI4 and PADI6, than between any member and PADI2  (5) , suggesting that PADI2 could be the original founder within the PADI family and that the others arose by gene duplication.
Multiple sequence alignments All of the homolog PADI sequences available in the OMA database were downloaded  (53). The species for the study were selected using three criteria: (i) a good representation of the different mammalian lineages, (ii) good sequence quality, and (iii) the presence of a full PADI2 sequence. Three outgroups of bird species (chicken, turkey, and duck) were also used. The protein sequences were aligned using the software PRANK (54) and a pruned mammalian guide tree with branch distances  (55). This program uses an evolutionary model to place insertions and deletions, minimizing the over-alignment of non-homologous regions, and has been shown to improve dN/dS estimates  (56). Local realignments of two regions were done using MAFFT  (57)  within AliView  (58). Another MSA using only one-to-one orthologous PADI2 sequences was also built.
TrimAI  (59)  was applied to the PADI family MSA, enabling the -automated1 option, as recommended before a phylogenetic reconstruction. The PADI2 protein MSA was then converted into a nucleotide alignment using the script Pal2Nal. The corresponding cDNA sequences for each species were gathered from the OMA database and converted using the script Pal2Nal  (60). The MSAs generated and the trees used are available as Supplementary Material S1.
Structural modeling of PADI2-CDK9/CCNT1 and selection of putative interface residues. The structure of the trimer complex the PADI2-CDK9 was derived using protein docking as follows. The crystal structure of PADI2 (PDB code: 4n2a) (24) and CDK9/CCNT1 (PDB code: 3blr)  (66)  were available. The protein docking was performed using VD 2 OCK (67), generating the ensemble of over 10000 docking poses. Docking conformers were clustered using the GROMACS  (68)  and sorted by the ES3DC potential  (69). The top 200 poses were selected to identify the top 10 putative interface residues as shown next. For this, a composite score was calculated using the docking information, the MVORFFIP score and sequence conservation. Among the top 200 docking poses as shown above a normalized score (Z score) was calculated for each exposed residue in PADI2.
AlphaFold-Multimer modeling of PADI2-CDK9/CCNT1 complex Structural models of the trimer PADI2-CDK9/CCNT1 were generated using AlphaFold-Multimer (71) as follow. The sequences were retrieved as mentioned above, PADI2 (PDB code: 4n2a)  (24)  and CDK9/CCNT1 (PDB code: 3blr) (66). The structure was derived using the model parameters corresponding to "model_1_multimer".
Evolutionary analysis of the PADI family To obtain a global picture of evolutionary relations within the PADI family, we first searched for all PADI family members with sequence homology to the human PADI2 in the OMA (Orthologous MAtrix) database  (53)  and gathered all the available sequences in mammals (see Materials and Methods). After close inspection, we discarded partial sequences and low-quality genomes and selected 185 confident sequences originating from 25 mammalian species and 3 bird species (Supplementary Figure  S1 ). With these sequences, we built a multiple sequence alignment (MSA, Supplementary Material File S1) and reconstructed a phylogenetic tree using the software RaxM, rooting the tree using the bird sequences as outgroups (Supplementary Figure  S2 , see.
PADI2 is highly conserved As PADI2 is likely to be the ancestral copy, we decided to focus on the most recent changes occurring in its sequence. With the phylogenetic selection of species, we aimed to identify changes that have occurred since the common amniote ancestor, with a good resolution in different mammals. Our dataset contains representatives in all the three extant major groups in the Mammalia class and the principal orders or infraclasses: primates, rodents, carnivores, cetartiodactyla, lagomorphs, proboscidea, and marsupials. We built a multiple sequence analysis with all 28 PADI2 sequences (see Materials and Methods, Supplementary Material File S1) and computed the ratio of substitution rates at non-synonymous sites and synonymous sites (dN/dS; also termed Ka/Ks) to infer the direction and magnitude of natural selection acting on protein-coding genes  (73).
Judging by the structural microenvironment, these residues could also play a role in protein-protein interactions, in line with the high scores assigned by MVORFFIP (Figure  3D , Table  1 )  (65). Finally, D507 and M663 are both located in helix cappings. Conservation in helix capping is important for the stability and integrity of the helix; in the case of M663, it also might play a role in the packing of the C-terminal tail. A search on the CAPS Database  (76)  showed that other helices with the same capping structure present a conserved small hydrophobic in the same position by including M, V, or L. It is noteworthy that M663 was indeed strictly conserved across all human PADIs. These observations suggested that most of these positively selected amino acids most likely have key functions in facilitating and stabilizing the protein -protein interactions.
Discussion We characterized the evolution of the PADI gene family by using the most complete dataset of mammalian orthologous sequences to date. There are three extant major groups in the Mammalia class, which are organized into two subclasses: Prototheria which includes monotremes (platypus and echidnas), and Theria, which includes the infraclasses Methatheria (marsupials), and Eutheria (placental mammals). According to  Jones et al. 2009 (81) , there are 5416 species divided into 29 orders. Most of the species described belong to the 7 biggest orders (4865 species), and all of them have at least one representative in our used phylogeny. The functional relevance of PADI2 is highlighted by its high sequence conservation across species, with very low dN/dS values. We took advantage of the natural experiments performed by evolution and applied sensitive methodologies such as the branch-site test of positive selection.
Data Availability The OMA is an open-source available database for the inference of orthologs among complete genomes https://omabrowser. org/oma/home/. The ETE3 was used for the reconstruction, analysis, and visualization of phylogenetic trees is freely available at http://etetoolkit. org. Other open-source programs used here were GROMACS, VD2OCK, MVORFFIP and al2co, which are available at http://www. gromacs. org, http://www. bioinsilico. org/VD2OCK, http://www. bioinsilico. org/MVOR.
Toxin-Antitoxin landscape in Sedentary Chromosomal Integrons determined by comparative genomics To assess if a correlation could exist between the number of TAs and the size of the SCI cassette arrays, we used IntegronFinder 2. 0  [4]  to detect all of the sedentary integrons in complete genomes of the RefSeq NCBI database. We identified 398 genomes with at least one SCI (defined as an integron comprising strictly more than 10 cassettes, as suggested in  [4] ) or one large CALIN (BigCALIN, defined as a SCI lacking a functional integrase). In each of these genomes, we screened TA systems with TASmania  [40] , a predictor with very low false negative rate. Our goal was to retrieve even unusual TA systems that would be rarely found outside SCIs and hence missed by more conservative predictors.
SI inverted strain constructions Two DNA fragments were inserted respectively upstream and downstream of the SI in a N16961 hapR + strain (WT). The upstream fragment contained a kanamycin resistance gene and the 5' end of a carbenicillin resistance gene associated with the attRHK site. The downstream fragment contained a zeocin resistance gene and the partner 3' end of the carbenicillin resistance gene associated with the attLHK site. The strain containing the upstream and downstream fragments prior to inversion is referred to as the parental strain (Par). The expression of the HK022 integrase and excisionase (as a directional factor) in the parental strain led to the attRHK × attLHK reaction resulting in the inversion of the SI and to the reconstitution of the full copy of the bla gene, making it possible to select on carbenicillin for clones with an inverted SI.
As a control for the following experiments, the SI was re-inverted to its original orientation using the HK022 integrase to perform the attPHK × attBHK reaction in the SI inv strain. The high frequency of that recombination reaction allowed an easy screening of the re-inversion events by PCR. We used a genetic tool developed in the lab and designed to target the relocation of chromosomal DNA using bacteriophage attachment sites. Prophage excision from the host chromosome relies on site-specific recombination between to sequences flanking the phage, (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint this version posted August 7, 2022. ; https://doi. org/10. 1101/2022. 08. 03. 502626 doi: bioRxiv preprint termed attachment sites attL and attR.
Genomes dataset and SCI/BigCALIN annotation To study the enrichment of TA systems within SCI across bacterial genomes, we used the dataset and integron predictions of IntegronFinder 2. 0  [4]. Briefly, this dataset consists of 21,105 complete genomes retrieved from NCBI RefSeq on 30 March 2021. We defined SCIs as complete integrons with at least 11 predicted attC sites. Several isolates of Vibrio cholerae appeared to be devoid of any SCI, carrying instead a large (>10 attC sites) CALIN (cluster of attC sites lacking an integrase), that we called BigCALIN. A closer investigation showed that these BigCALIN were preceded by a pseudogenized integrase, which makes them similar to the SI found in Vibrio cholerae. These elements could have been recently inactivated, or the putative pseudogenes could result from sequencing artifacts.
Vibrio genus cladogram To identify a potential evolutionary trend explaining the TA enrichment within SCI/BigCALIN across the Vibrio genus, we reconstructed a cladogram grouping Vibrio species together. More precisely, we took as basis the phylogeny published by Sawabe and coll. [41]  and removed the species that did not harbor any SCI/BigCALIN. The species comprised in our dataset that were absent of the phylogeny were then added as a sister branch of its closest relative species.
Acknowledgements We thank  Jun Teramoto  and  Akihiko Kondo  for sharing their construct for base-editing. We thank  Marc Monot ,  Laurence Ma ,  Juliana Pipoli Da Fonseca  and  Thomas Cocklaer  from the  Biomics platform ,  C2RT ,  Institut Pasteur, Paris, France. EQU202103012569 ), the  ANR Chromintevol  ( ANR-21-CE12-0002-01 ), the  French Government 's  Investissement d'Avenir program Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'  [ ANR-10-LABX-62-IBEID] , the  Ministère de l'Enseignement Supérieur et de la Recherche  and the  Direction Générale de l' Armement (DGA).
Sensor platforms for vegetation productivity monitoring Over the last two decades, the optical EO domain has seen an increasing number of space missions with various sensors aboard, complemented by airborne campaigns and in situ measurements from widespread ground-based networks. This increase in the abundance of EO data has contributed to the establishment of consistent global databases with quality-checked optical data, which can be used to estimate vegetation productivity metrics at almost any spatial and temporal scales  (Kuenzer et al. , 2015). The relevant sensor platforms serving to collect observations for deriving vegetation productivity information are graphically illustrated in Fig. 2  and described in the following sections.
Based on some of those methods within TimeStats, predefined workflows were implemented in a web interface called EOTSA (Earth Observation Time Series Analysis) Toolbox  (Leopold et al. , 2020). EOTSA allows online access to satellite data archives (currently the full PROBA-V database) without the need for local data storage. Fig. 6  shows two examples where NDVI TS were analysed at the continental scale using EOTSA. In the first example, seasonal characteristics (mean NDVI, annual magnitude, peaking time) were derived (step 1), followed by a trend analysis (step 2) (Fig. 6B ). The colour composite of the trends for the seasonal characteristics reveals spatiotemporal patterns. Fig. 6C  shows an example of multivariate TS analysis in which NDVI was regressed against lagged rainfall using distributed lag modelling after pre-whitening the TS.
To address data consistency and allow cross-site comparisons, FLUXNET was established in 1997, which is a 'network of networks' and has led to harmonised methods and datasets. The latest dataset of FLUXNET, the FLUXNET2015, contains gap-filled time series of GPP, Re and meteorological data for 1500 site years, along with an estimation of uncertainties  (Pastorello et al. , 2020). However, there are concerns around the spatial and temporal representative of EC data, due to the disproportionate predominance of flux towers being located in North America and Europe  (Chu et al. , 2017). To scale from the footprint of individual flux tower sites to gridded, spatially-and temporally-explicit products, a variety of machine-learning techniques have been employed, including neural networks, regression trees and kernel methods  (Beer et al.
Systematic literature review The systematic literature review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)  (Page et al. , 2021). The SCOPUS and Web of Science web catalogues were queried for published, peer-reviewed publications. In SCOPUS, the title, abstract and keywords were searched with the query "time AND series AND productivity AND 'remote sensing' AND (vegetation OR forest OR crop)", while the topic field in the Web of Science catalogue was searched for "'time series' AND (vegetation OR forest OR crop) AND productivity". The resulting 915 records of the two databases were merged into one database by omitting duplicated records as identified by their DOI (Fig. 8 ). The records were further screened to include research articles and conference contributions in the English language, excluding review studies.
In this period, only 21 studies (3. 7 %) were published. Second, a rising contribution of MODIS and Landsat marked the period from 2005 until 2017 (e. g. ,  Boisvenue et al. , 2016). During this period also the number of studies per year increased from 6 (1. 1 %) in 2005 to 52 (9. 2 %) in 2017. In Fig. 10 , the years 2013 and 2016 appeared to be outliers with the highest portion of studies with larger than 1000 m resolution. The 2016 outlier can be explained with the publication of the Global Inventory Monitoring and Modeling System (GIMMS) third generation NDVI (NDVI3g) long-term TS dataset based on AVHRR  (Pinzon and Tucker, 2014). The last phase started in 2017 and is marked by an increasing trend towards sub-1000 m resolution studies driven by the increased availability of longer-term Landsat and MODIS TS.
Key challenges Efficient use of increasingly available and longer time-series datasets: Over the past few decades, there has been an increasing number of TS datasets made available, with enhanced spatial details as depicted in Fig. 3. Despite this progress, there may still be limitations in terms of the spatial and temporal resolutions for specific objectives and applications. Some of these limitations include gaps in available long-term datasets due to persistent cloud cover, and discontinuity of sensors, leading to uncertainties in variable retrievals being relevant for vegetation productivity metrics. While with the advent of cloud-computing platforms access to EO data TS has never been as easy as nowadays, access to other RS resources (local airborne campaigns) is more fragmented and not always open.
Processes and factors affecting vegetation productivity: One important goal will be to adopt TS datasets to develop and test methods for heterogeneous natural environments, as the current focus is largely on croplands (see Fig. 12 ). Satellite TS data streams can effectively capture, characterize, and quantify the spatiotemporal variation of natural processes. However, some approaches (discussed in Sect. 3) may only provide a relative characterization of vegetation productivity. To increase our understanding, process-based models (i. e. , DVMs) are required to provide the mechanistic basis (linking to modelling domains) necessary to capture productivity variations in natural environments. Integrated modelling is a potential approach to address this need.
The abundance of ways to derive such variables makes it difficult to find the most effective set of predictors for the automated identification of disturbances in vegetation productivity. Deep learning (DL) has been identified as a powerful method that can learn the most appropriate data transformations to get the most relevant data features for solving a specific problem  (Kattenborn et al. , 2021; Cherif et al. , 2023). However, a key condition is the availability of a large training dataset, i. e. , if the dataset is small, then conventional ML methods may be more suitable. For analysing data streams of temporal dynamics, recurrent neural networks (RNN) are of particular interest because they can recognize temporal patterns regardless of data gaps due to missing images or cloud cover. Similar to convolutional neural networks (CNN) for spatial patterns, RNNs make a selection of temporal features (e.
By using satellite data to estimate the amount of carbon stored in vegetation, we can better understand the impact of land use changes (e. g. , deforestation) and other human activities on the global carbon balance, and thus climate change. The availability of long-term satellite TS datasets with improved spatial and temporal detail has increased steadily over the past decades. More recently, the emergence of routinely-acquired SIF products proved to provide a more direct linkage towards photosynthetic activity and became increasingly integrated into vegetation productivity processing chains. Validation efforts in ensuring the accuracy, robustness, and reliability of RS-based productivity estimates are another essential aspect of the processing chains. Validation can be performed in several ways, including in situ measurements, local sensor networks, and inter-comparisons of available productivity products or models.
Cell cycle analysis Cells were seeded in 6-well plates at optimized densities, allowed to attach overnight and treated with CAPE (IC 50 ) for 24 h. Cells were incubated with 10 μM BrdU (Sigma-Aldrich) for 30 min (NSCLC) or 1 h (lung fibroblasts), and stained for BrdU and propidium iodide (PI) (Supplementary material). Fluorescence intensity was measured by flow cytometry (BD FACS Canto II), and data was analysed using FlowJo software (v10. 8. 1).
Despite both NSCLC types carry a high percentage of mutations, no differences in the mutation profile were found within adenocarcinoma nor non-adenocarcinoma cell lines, or between the cancer types upon review of the COSMIC and DepMap databases  [31] [32] [33]. The differences in CAPE-induced radiosensitivity might be explained by the differential effects in NF-κB activity in adenocarcinoma and non-adenocarcinoma cell lines. NF-κB is a transcription factor involved in the regulation of pro-inflammatory genes as well as cell survival, proliferation and cell death  [34]. We observed that CAPE slightly diminished NF-κB activity in adenocarcinomas, while increased its activity in non-adenocarcinomas. Increased basal levels of NF-κB activity have been reported in cancer cells as a mechanism of resistance to treatment via increased cell survival and decreased cell death, as well as promoting metastasis and de novo angiogenesis  [35, 36].
Given the inefficiency of LDH1  4, 26  , functional mitochondria turn essential for neurons to regenerate cytosolic NAD +32 via the malate and glycerol phosphate shuttles  33. Thus, the impaired mitochondria of glycolytically active neurons hinder their ability to avoid NAD + depletion, causing autophagy impairment. Neurons are thus metabolically inflexible cells unable to adapt to sustained active glycolysis, unlike their neighbor astrocytes  34  , which explains the aberrant neuronal glycolysis found in neurodegeneration  9, 10, 11  and metabolic-like syndrome where neuron-specific inhibition of Pfkfb3 may be considered as a therapeutic opportunity. Data Availability. Source data are provided with this paper. The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.
by the European Regional Development Fund, Agencia Estatal de Investigación (PID2019-105699RB-I00 / AEI / 10. 13039/501100011033 and RED2018-102576-T to JPB; SAF2017-90794-REDT to AA), Instituto de Salud Carlos III (CB16/10/00282 to JPB; PI18/00285; RD16/0019/0018 to AA), Junta de Castilla y León (CS/151P20 and Escalera de Excelencia CLU-2017-03 to JPB and AA). MetaToul is part of the national infrastructure MetaboHUB, and is funded by the French National Research Agency (ANR) with grant number MetaboHUB-ANR-11-INBS-0010.
Acknowledgements We acknowledge the technical assistance of  Monica Resch ,  Monica Carabias-Carrasco ,  Lucia Martin  and  Estefania Prieto-Garcia , from the  University of Salamanca. Staff members ( Amandine Rocher ,  Hanna Kulyk ,  Nina Lager-Lachaud ,  Lara Gales ,  Floriant Bellvert ) of  MetaToul (Toulouse, France , www. metatoul. fr) are gratefully acknowledged for technical support and access to mass spectrometry facilities. This work was funded.