dataesr/scientific-paragraphs-categorization huggingface dataset:
e. higher expression before RYGB and in the insulin resistant state; or lower expression two years post-RYGB and in the insulin-sensitive state) (Fig. 1a  and Supplementary Table  3 ). ADIPINT (CATG00000106343. 1) displayed the greatest fold change in both cohorts of the twelve genes and the second largest fold change of all lncRNAs two years post-RYGB (Fig. 1a ). In addition, the changes in total fat mass and adipocyte cell volume correlated positively with the change in ADIPINT expression post-RYGB (Fig. 1b ). These data suggests that ADIPINT is a promising candidate and further study was devoted to this lncRNA. ADIPINT is intergenic and located on chromosome 9 (Fig. 1c ). None of the three transcripts in the ADIPINT loci have protein coding potential according to CPAT, RNACode, phyloCSF, and sORF riboseq coding prediction softwares.
ADIPINT is not conserved between phylogenetically distant species at the sequence or genome synteny level. RNA-seq and CAGE-seq  18  in human adipose-derived stem cells (hADSC) from subcutaneous WAT revealed that transcript 2 of ADIPINT is the dominant isoform expressed in mature adipocytes (Fig. 1c ). Transcript 2 is 4. 8 kb long and contains two exons (Fig. 1c ); the junction was validated by qPCR and Sanger sequencing (data not shown). Upregulation of ADIPINT expression during differentiation in hADSC and enrichment in mature adipocytes isolated from WAT were confirmed by qRT-PCR (Fig. 1d, e ). Analysis of RNA expression in different human cell types in the FANTOM5  7  database demonstrated that ADIPINT is exclusively expressed in adipocytes (Fig 1f). Subcellular fractionation studies and RNA-fluorescence in situ hybridization (FISH) revealed ADIPINT to be predominantly localized in the cytoplasm of adipocytes (Fig.
3a ). The interphase is cleaned, sonicated and used for targeted pulldown of ADIPINT with short antisense oligonucleotides. After UV crosslinking, ADIPINT became enriched at the interphase, indicating its binding to a protein partner (Extended Data Fig. 2 ). Using two distinct sets of oligonucleotides, each tiled along ADIPINT, we enriched the lncRNA 3. 5-4. 8 fold compared to the input material (Fig. 3b ). No ADIPINT expression was detected after pulldown using probes targeting Lac Z mRNA or using the ADIPINT-targeting probes with RNase. Mass-spectrometry analyses revealed that pyruvate carboxylase (PC) was significantly enriched with ADIPINT pulldown (Fig. 3c ). No differences in PC abundance were found in the RNase-treated or Lac Z probe sets. All detected proteins in each experiment are listed in Supplementary Table  11.
We confirmed the interaction with PC by western blot analysis (Fig. 3d ). GADPH, another enzyme known to bind RNA  24  , was used as a control for pulldown and interaction specificity. To validate the ADIPINT interaction, we performed immunoprecipitation of PC in hADSCs. ADIPINT was enriched when compared to IgG and this enrichment was significantly higher than that of 18S, PC, and U1 RNA (Fig. 3e ). We examined the specificity of the ADIPINT and PC interaction by Gel Filtration Chromatography. Both the RNA and protein could be distinguished using a Sepharose column filtration system, establishing their specific elution volumes (Extended Data Fig. 3a ). When ADIPINT and PC were combined and the resulting mixture loaded, PC and ADIPINT eluted together at the RNA elution volume (Fig. 3f , Extended Data Fig.
3b ). PC when ran alone or with ADIPINT anti-sense did not elute at the RNA elution volume to any significant degree (Fig. 3f ). Furthermore, we found ADIPINT and PC to exist in the same compartments within the cell after performing subcellular fractionation (Fig. 3g ) for mitochondrial and cytoplasmic fractions (Extended Data Fig. 4a-b ). RNA-FISH with immunofluorescence staining for ADIPINT and PC in tandem confirmed the localization overlap (Fig. 3h ). Together these data suggest a physical ADIPINT-PC interaction.
Chemical inhibition of pyruvate carboxylase perturbs lipid metabolism and the bioenergetic rate in fat cells Inhibiting PC activity in mouse adipocytes reduces lipid synthesis and triglyceride accumulation  29. To determine if a selective targeted reduction in PC activity in human fat cells could lead to the same alterations in lipid metabolism as with ADIPINT knockdown, we incubated hADSCs with the PC inhibitor oxalate  30, 31. Oxalate reduced glycerol release, intracellular triglyceride and insulin-stimulated lipid synthesis (Fig. 5a-c ). At 500 µM of oxalate the reduction of lipid metabolism was similar to ADIPINT knockdown in parallel experiments using GapmeR 1. We next assessed the effect of PC inhibition on adipocyte bioenergetics. Oxalate administration reduced basal and ATP-linked OCR as well as glucose-stimulated ECAR and a similar decrease was seen following ADIPINT knockdown (Fig  5d-f , Extended Data Fig.
ADIPINT expression correlates with adipose pyruvate carboxylase activity and clinical phenotypes Finally, we examined a possible physiological role of ADIPINT. A correlation between ADIPINT and PC was examined in abdominal subcutaneous adipose tissue of 19 apparently healthy women (clinical data are given in Supplementary Table  13 ). They were subdivided according to obesity status with body mass index of 30 kg/m 2 used as the cut-off value (9 were obese). ADIPINT expression was increased in obesity in the first examined cohort (Fig. 1a ), which was confirmed in this second cohort as well (Fig. 6a ). PC protein expression did not differ between groups (Fig. 6b ), however PC activity was higher in women with obesity (Fig. 6c ). Furthermore, ADIPINT expression and PC activity were positively correlated (Fig.
6d ), while no correlation between PC protein expression and ADIPINT was observed (Extended Data Fig 7). The physiological role of ADIPINT was further examined through its association with other clinical traits in this cohort. ADIPINT expression correlated positively with fasting serum insulin and plasma triglyceride levels but not with fasting plasma cholesterol (Fig. 6e-g ). Also the level of in vivo insulin resistance (measured by the homeostasis assessment method) correlated positively with ADIPINT expression (Fig  6h ). In agreement with the results of the cohort used in Fig. 1 , ADIPINT expression, in the current cohort, correlated strongly with fat cell volume and ADIPINT expression (Fig. 6i ). Up to 33% of the variation in fat cell volume between subjects could be explained by variations in ADIPINT expression (i.
Clinical cohort We included women with obesity who were subjected to Roux-en-y gastric bypass (RYGB) and have been described previously for other type of studies  16, 17  (DEOSH, trial registration number NCT01785134). Clinical data extracted from previous publications are presented in Table  S1  and Figure  1a. They were investigated before, 2 and 5 years after RYGB. Presently we focused on first (n=50) and second examination (n=49) when there was a substantial bodyweight loss. Three had type-2 diabetes pre-surgery treated with metformin and/or diet only. Diabetes was absent following RYGB. Sixteen women had hypertension at baseline and treated with ACE-or angiotensin 2 receptor blockers, beta-blockers, thiazide diuretics and/or calcium channel antagonists; 9 women remained on antihypertensive treatment at two years follow up.
6 m/z and normalized collision energy to 30%. The raw files were imported to Proteome Discoverer v2. 3 (ThermoFisher) and analyzed using the SwissProt protein database with Mascot v 2. 5. 1 (MatrixScience Ltd) search engine. Parameters were chosen as follows: up to two missed cleavage sites for trypsin, peptide mass tolerance 10 ppm, 0. 02 Da for the HCD fragment ions. Carbamidomethylation of cysteine was specified as a fixed modification, whereas oxidation of methionine and deamidation of asparagine was defined as variable modifications.
Gel filtration analysis ADIPINT or ADIPINT anti-sense cDNA was cloned out of a plasmid containing the full length cDNA sequence for ADIPINT transcript 2 (MICT00000363691. 1) using KOD Hot Start Polymerase (Sigma-Aldrich) as previously described  59. The PCR product was confirmed by size and EcoRI-HF (NEB) restriction digest, bands were excised from the agarose gel and purified using the NucleoSpin Gel and PCR Clean-up kit (Machery-Nagel). The RNAMaxx Transcription Kit (Agilent) was used as per manufacturers instructions to synthesize RNA, with 1 µg of template DNA product used per reaction. The reaction was carried out for two hours at 37 o C before RNA was purified using the NucleoSpin RNA Isolation Kit (Machery-Nagel). For RNA-PC binding, RNA was added to purified bovine PC (0. 3 µg/µL Sigma-Aldrich) in a 110 uL reaction containing 10mM HEPES (pH 7.
Statistical analyses GraphPad Prism v8. 0 was used for all statistical comparisons unless otherwise stated. The specific statistical test used for each comparison mentioned in the figure legend. All data are expressed as mean ± S. D for experiments with sample size n < 6 and S. E. M when n was higher. All n represent biologically independent experiments. For ANOVA, Dunnett post-test was used for comparisons of all samples to a particular sample and Holm-Sidak was used for comparisons of all samples to one another. Comparisons between ADIPINT knockdown and control samples in microarray and proteomic studies were carried out using the Bioconductor R package Limma  61. An FDR ≤ 0. 05 was used to select for significant genes and FDR ≤ 0. 1 for proteins in all comparisons. Pearson correlation was used to assess significance between the change in ADIPINT expression versus weight/adipocyte cell volume and ADIPINT versus PC mRNA expression at all time points.
Acknowledgements The expert technical assistance of  Katarina Hertel ,  Ana Maria Suzuki  and  Thais De Castro Barbosa  is greatly acknowledged. This study was supported with grants from the  Swedish Research Council ,  Novo Nordisk Foundation , the  Strategic Diabetes Research Program at Karolinska Institutet , EMIF ( Stockholm County ) and the  European Research Council (ERC)   Synergy Grant SPHERES  (agreement No. 856404 ) under the European Union's  Horizon 2020 research and innovation programme  (erc-spheres. univ-tlse3. fr). A  Human Frontier Science Program  grant ´( RGY0074/16 ) awarded to C. M. The  China Scholarship Council  ( CSC) program  awarded to  Z. W. AG Kerr ,  KHM Kwok  and  A Ludzki  were sponsored by the  Novo Nordisk   Postdoctoral Fellowship program  at  Karolinska Institutet.
Protein identification, quantification, in-gel digestion, mass spectrometric analysis and database searches for protein identification was carried out at the  Proteomics Biomedicum core facility ,  Karolinska Institute, Stockholm. (https://ki. se/en/mbb/proteomics-biomedicum). RNA sequencing and microarray was carried out at BEA core facility at  Karolinska Institute, Stockholm  (https. bea. ki. se). We thank the  Live Cell Imaging facility ,  Karolinska Institutet  , Stockholm (https://ki. se/en/bionut/welcome-to-the-lci-facility)for microscopy imaging analysis.
g. , geological, physical, chemical, biological) at high temporal resolution and over years to decades. Repeated submersible visits to study sites, combined with observatory maintenance, have documented submarine volcanic eruptions and associated changes to hydrothermal vent fields (e. g. ,  Chadwick et al. , 2012; Fornari et al. , 2012; Chadwick et al. , 2013; Nooner and Chadwick, 2016; Wilcock et al. , 2016; Chadwick et al. , 2022; Barreyre et al. , 2022) , changes in community structure and activity  (Shank et al. , 1998; Fortunato et al. , 2018; Rommevaux et al. , 2019)  as well as interactions with other nearby chemosynthetic and peripheral surrounding ecosystems  (Levin et al. , 2016). Together, these data contribute to answering a number of questions across various disciplines from geophysics to microbiology: • How are hydrothermal heat, mass and chemical fluxes to the ocean impacted by seismicity, volcanic activity and ground deformation at a diverging plate boundary? • Does tectonic setting impact the long-term stability or temporal variability of these systems? • How do steep axial valley topography and hydrothermal buoyancy flux affect the dynamics of water masses, and how do local dynamics impact the dispersion of hydrothermal effluents? • How do species compositions differ between habitats, geological settings, and ridges? • How do pioneering species colonise new sites and which processes are involved? • What are the impacts of telluric, climatic, and anthropogenic changes on deep seafloor ecosystems and hydrothermal communities? There are currently three observatory installations at hydrothermally active MOR systems.
IR aims to (i) facilitate interdisciplinary, international collaboration; (ii) coordinate scientific exchange -including information, technology and facilities; (iii) encourage the protection and environmental management of ridge environments; and (iv) promote communication between scientists and members of the society through coordinated outreach efforts. InterRidge Working Groups (WGs) are formed to support the implementation of these objectives in priority areas. The IMOVE WG was formed to advance multi-disciplinary research within and across the three MOR observatories. A large volume of temporally-and spatially-variable multidisciplinary data has been collected at the three presently active MOR vent observatories (Figure  1 ), requiring considerable support from funding agencies. One of the goals of the IMOVE WG is to advance the integration of data from different disciplines into quantitative, cross-disciplinary models relevant to hydrothermal processes on the global MOR system.
An High-Definition (HD) video camera module  (Sarrazin et al. , 2007) , chemical sensor  (Laës-Huon et al. , 2020) , and thermistor string, support studies of the dynamics of mussel assemblages and their environment. Biological and chemical properties of hightemperature fluids are monitored with the microbial colonization module CISICS (Connected In Situ Instrumented Colonizing System), and the in situ automated sampling of hightemperature hydrothermal fluid device DEAFS (DEep sea Autonomous Fluid Sampler). The two nodes are acoustically linked to a surface relay instrumented buoy, ensuring satellite communication to the land base station in Brest, France. Data are archived, published with a DOI, and available on the EMSO-Azores web page (Box 1). In addition to these nodes, the observatory setup comprises several sets of autonomous instruments, with data recovered during yearly maintenance cruises.
The EMSO-Azores observatory is maintained annually during the MoMARsat cruises  (Cannat and Sarradin, 2010). All seafloor system components are recovered, serviced onboard and redeployed by either the Remote Operated Vehicle (ROV) Victor 6000 or the Human Occupied Vehicle (HOV) Nautile. Each dataset is linked to the relevant cruises, which are listed in the data DOI, and each cruise DOI includes a list of the available data with their DOIs (Box 1).
Expansion of the observing system began in 2016 with the installation of extension optical cables to connect the Endeavour node to the Mothra vent field and a site north of the High Rise field. Installation of new sensors and camera systems began in 2019 and are scheduled for completion in 2022. All data are available for download and visualization through an online query interface linked to the data archive and GIS database (Box 1). During the deployment of the 840 km backbone NEPTUNE cable, a spur cable (with a cable termination assembly) was extended to the Middle Valley hydrothermal area, to the north of the Endeavour Segment (Figure  3 ). This installation could support future development of a node and instruments to contrast the hydrothermal activity at the sedimented Middle Valley, with the sediment-starved spreading centre at Endeavour.
Crustal Processes While MOR's represent the world's largest hydrothermalvolcanic system, we still lack an in-depth understanding of the complex interplay of magmatic, tectonic, and hydrothermal processes that take place along the ~65,000 km of ridge axis. Comprehensive databases acquired in recent decades show that hydrothermal fluids expelled at vents along magmatically robust sections of a MOR have a large spatial and temporal variability in exit fluid velocity, temperature, and chlorinity (e. g. ,  Scheirer et al. , 2006; Larson et al. , 2007; Sohn, 2007; Sarrazin et al. , 2009; Barreyre et al. , 2014b; Germanovich et al. , 2015; Xu et al. , 2017). Monitoring seafloor deformation and seismic activity at active volcanoes provided insights into magma movement at depth  (Chadwick et al. , 2016; Nooner and Chadwick, 2016; Wilcock et al.
TOWARDS A COORDINATED UNDERSTANDING OF MID-OCEAN RIDGES (MOR) HYDROTHERMAL VENTS AND THEIR ECOSYSTEMS The IMOVE working group seeks to refine common processoriented research questions that can be addressed with data in hand, and identifying what is needed to address questions raised by today's societal challenges, in order to help and foster interoperability across vent observatory platforms. The locations of the three observatories permits the study of hydrothermal processes in contrasting environments and settings. Each is representative of different dynamics of seafloor spreading and volcanism, from slow (MAR) to intermediate (JdFR) spreading rates, and the relative importance of tectonic (Endeavour) and volcanic (Lucky Strike, Axial Volcano) processes. They also provide contrasting examples of hydrothermal plume behaviour: with episodic megaplume generation during eruptions at Axial volcano, (e.
Ocean Networks Canada has recently collaborated with WoRMS and the US National Oceanic and Atmospheric Administration (NOAA) Office of Ocean Exploration & Research (OER) to develop a standardized video annotation system. The SeaTube interface allows users at sea or via telepresence to annotate live video streams, and permits post cruise annotation of ROV video recordings. Annotations may be entered as freeformat text or structured annotations adhering to custom or standard taxonomies (such as WoRMS, CMECS, etc. ). Ancillary data from both ROV and ship mounted sensors are also displayed in conjunction with the video, all synchronised with the video timestamp (Figure  6 ). Live links to the WoRMS database while annotating allows for near-real-time validation of species identifications against known geographic distributions, and the flagging of potential new occurrences or identification errors.
g. ,  Picheral et al. , 2021). New imaging techniques are currently under development to document spawning or larval settlement events in conjunction with multi-parameter sensors to identify environmental cues or oceanographic patterns driving life cycles in the deep sea. Machinelearning can allow for rapid identification of high-volume image samples, as well as enable the collection of higher-resolution samples following detection of an anomaly (adaptive sampling). While such technological innovation could greatly accelerate our knowledge on deep-sea benthic and planktonic communities, most deep-sea species are still undescribed in their adult form, and this is only amplified for their larval forms. Therefore, their identification from images still requires the collection of physical specimens for morphological or genetic analyses, which will feed biodiversity baseline databases and provide training sets for machine learning (e.
A Tool to Inform Environmental Managers and Policy Makers Because observatories constitute technological development platforms, they can support the design, testing and implementation of environmental monitoring strategies and evolve with new emergent technologies and the innovation of instrumentation for sustained, systematic data acquisition (e. g. ,  Danovaro et al. , 2017a). The Endeavour nodes of ONC and EMSO-Azores are both located within an MPA. Together, these seafloor infrastructures constitute an essential tool to inform MPA management and efficiency for the benefits of the local governments but also of international instances such as the International Seafloor Authority (ISA) which is currently developing the standards and guidelines of the international mining code. As an example, ONC has developed SeaTube (Box 1), a software system for assembling ROV dive navigation logs and video records, including real-time annotations, into an online archive and a GIS database.
The database can be queried to generate maps for researchers and MPA managers that illustrate the spatial distribution of seafloor features of interest. Juniper et al. (2019)  provide examples of how this geodatabase can be used to analyse the distribution of species of interest, debris, and human pressures resulting from research activity. All observatory sensor data and ROV expedition video and navigation records from the Endeavour Hydrothermal Vent MPA are archived and made publicly available by ONC (Box 1). The combined data archive therefore has the potential to support adaptation of the EHV MPA management plan and conservation objectives to a growing understanding of natural and scales of environmental and ecosystem change, and the spatial distribution of research activity. To standardize and implement these conservation objectives at a larger scale, regular workshops should be organized with various stakeholders, including the ISA, State environmental ministries, Non-Governmental Organisations (NGOs), Business/Industry, Science Networks and the civil society to identify their respective needs and work towards the co-design, co-development and co-delivery of commonly defined monitoring approaches and tools.
In addition to live interactions during cruises, other original actions have been developed including, among others, participative science and art & science projects. AbyssBox, the first permanent public exhibition of live deep-sea hydrothermal fauna maintained at in situ pressure (170 bars,  Shillito et al. , 2015) , is a first step towards maintaining a variety of deep-sea fauna year-round, serving both scientific and public purposes. The Deep Sea Spy (DSS) project (Box 3), developed by Ifremer allows society to be involved in the research process by contributing to the annotation of deep-sea hydrothermal vent imagery acquired by seafloor observatories. To date, over 1300 citizens annotated almost 50,000 images through the DSS platform building a reference database for machine algorithms developments.
ACKNOWLEDGMENTS The authors acknowledge the support of the InterRidge office in Paris,  Nadine Lebris ,  Jeŕome Dyment  and  Kamil Szafrański. Thanks  to  Jina Mousseau  ( ONC ) for creating Figure 3. We thank the captains and crews of the research vessels that enabled infrastructure maintenance: RV Pourquoi Pas?,  RV L'Atalante ,  RV Thalassa ,  CCGS John P. Tully, RV Thomas G Thompson, EV Nautilus. We are also grateful to the pilots of the submersible Nautile, Victor6000,  ROPOS, Hercules, Argus, Odysseus. The work reviewed in this paper would have not been possible without the help of all mechanical, electric and computer engineers and technicians from Ifremer (RDT and RIC),  ONC  and  OOI. The working group was supported by  InterRidge  (2017InterRidge ( -2020)). Other participants in IMOVE Working Group:  Lise Artigue ,  Loïc Van Audenhaege ,  Valeŕie Ballu ,  Catherine Borremans ,  Greace Crystle ,  Cećile Cathalot ,  Jerome Dyment ,  Aida Farough ,  Anne Godfroy ,  Sabine Gollner ,  Zhikui Guo ,  Orest Kawka ,  NoéLahaye ,  Marie Eide Lien ,  Anna Lim ,  Jean-Arthur Olive ,  Giuliana Panieri ,  Rolf Birger Pedersen ,  Eoghan Reeves ,  Celine Rommevaux ,  Guillaume Roullet ,  Lars Rüpke ,  Ben Snook ,  Adam Soule ,  Kamil Szafranski ,  Julie Tourolle ,  Benjamin Wheeler.