dataesr/scientific-paragraphs-categorization huggingface dataset:
, 2013). Our group noted a 50% reduction of rectovaginal plaque volume after 12 months of dienogest therapy  (Razzi et al. , 2007a) , whereas another cohort study saw no volumetric change in deep lesions of intestine or posterior fornix with the same treatment  (Leonardo-Pinto et al. , 2017) , although symptoms improved leading to a better quality of life. Indeed, intestinal endometriosis can be so resistant to medical therapy   (Ferrero et al. , 2009)  and in women with ovarian endometrioma  (Ferrero et al. , 2014)  treated with norethisterone acetate for 6 months. Data were extracted from published tables of two separate studies and plotted together for better visualisation. that in some cases it keeps growing and invading the organ wall despite continuous medication  (Millochau et al. , 2016).
Small-angle X-ray scattering SAXS data were collected at the beamline P12, operated by EMBL Hamburg at the PETRA III storage ring (DESY, Hamburg, Germany)  (37). Measurements were done at 20 °C in 20 mM MES, pH 6. 5, 75 mM NaCl and 0. 5 mM TCEP in flow cell mode at 1. 24 Å. For each sample and buffer 20-100 frames with 0. 05-0. 195 s exposure time were acquired and frames showing radiation damage manually removed. Data analysis was done using the ATSAS package version 2. 8. 3  (38). PRIMUS was used for frame averaging and buffer subtraction  (39). The radius of gyration, R g , was estimated using the Guinier approximation in PRIMUS. Pair-wise distribution functions were calculated using GNOM  (40). Collection statistics for SAXS measurements are summarized in Supplementary Table  S1.
Cooperative binding of PRY/SPRY and CC domain to RNA induces conformational change in TRIM25 We noted that in the crystal structure of the CC-PRY/SPRY dimer (PDB:6FLN) binding-site-1 is part of a larger positively charged surface that extends onto the CC (Figure  2B ). Together, the PRY/SPRY domain and CC seem to form a joint interaction surface that could explain the tighter binding of RNA as observed by ITC and filter binding assays. The CC is not suitable for NMR studies due to its size and extended conformation, which causes slow molecular tumbling and NMR resonance line broadening beyond detection. Instead, to test the CC's putative RNA-binding capacity  (12, 44) , we used ITC to characterize its RNA binding properties (Table  1 ). We found that the CC binds pre-let-7 with low micromolar affinity (8.
Figure2. CC and PRY/SPRY domains bind RNA cooperatively: (A) Binding isotherms of TRIM25 CC-PRY/SPRY (B) and PRY/SPRY (C) titrated by pre-let-7 show that the PRY/SPRY alone is not sufficient to explain the nanomolar affinity of the longer CC-PRY/SPRY construct. The CC binds prelet-7 similarly to the PRY/SPRY with micromolar affinity. The thermodynamic parameters of all ITC measurements can be found in Table1. (B) The surface potential of the CC dimer with bound PRY/SPRY (PDB:6FLN) shows that they share a positively charged interface in close proximity to RNA binding-site-1 marked by H505 and K508. (C) SAXS curves and pairwise distance distributions for the free TRIM25 CC-PRY/SPRY (black) and its complex with pre-let-7 RNA (red). The distance distribution of the free protein features two maxima, indicating independence of the two domains, whereas the distribution for the RNA-bound complex is much narrower and contains only one peak, indicating a conformational change towards a more compact form.
ACKNOWLEDGEMENT We thank the  ESRF Grenoble  (beamline  BM29 ),  EMBL/DESY Hamburg PETRA-III  (P12 beamline), and the ILL (D22 beamline) local contacts for support ( Taisiia Cheremnykh ,  Andrey Gruzinov ,  Al Kikhney ,  Gabriele Giachin  and  Anne Martel ). We also thank  Lucía Alvarez  for critical reading of the manuscript. This work was supported by the  Francis Crick Institute  which receives its core funding.
cellular biology, editorial/personal viewpoint, graft survival, innate immunity, tissue (nonvascularized) transplantation ACK N OWLED G M ENTS We would like to acknowledge receipt of support from the Société Française de Transplantation, the ANR project BIKET (ANR-17-CE17-0008), the University Hospital Institute (IHU)-European Center for Transplantation and Immunotherapy Services (CESTI), the DHU Oncogreffe, the LabEX IGO financial support managed by the "Investment into the Future" program (ANR-10-IBHU-005 and ANR-11-LABX-0016-01), the CENTAURE foundation (www. fonda tion-centa ure. org), and the COST Action: CA17138.
, 2001)  affecting mainly humans and horses  (Benjelloun et al. , 2016; Johnson et al. , 2018; Papa, 2019). In Morocco, several outbreaks of WNV have been reported: (i) in 1996 with 94 equine cases including 42 deaths and only one human case  (El Harrack et al. , 1997; Tber Abdelhaq, 1996) , (ii) in September and October of 2003 when WNV circulated among horses in Kenitra  (Schuffenecker et al. , 2005) , (iii) in 2010 in horses  (World Animal Health Information Database, 2010 ; Benjelloun et al. , 2017; Durand et al. , 2016; El Rhaffouli et al. , 2013). The two strains of  WNV (outbreaks in 1996 and 2003)  belonged to clade 1a of lineage 1  (schuffenecker et al. , 2005). The principal vector of WNV in Europe, Northern USA and North Africa is Culex pipiens which is the most widespread vector in temperate regions including North Africa  (Amraoui et al.
Seroneutralization tests Flaviviruses identified by MIA and all undetermined ELISA-positive flavivirus samples were investigated using MNT against WNV and USUV. Neutralizing antibody titers against WNV and USUV were determined by MNT on Vero cells in 96-well cell culture plates, following the protocol described in  (Beck et al. , 2015) , using WNV strain IS-98-ST1 (Genbank ID AF481864. 1, provided by P. Desprès, IPP) and USUV strain France 2018. The MNT results were interpreted according to the following rules: (i) A serum was considered positive if cells were protected at the 1:10 serum dilution for WNV and USUV. Owing cross-neutralization between flaviviruses especially in the same serocomplex, we identified the infecting flavivirus by considering the virus with the highest neutralization capacity, and with neutralization titers that differ by at least a four-fold factor  (Beck et al 2015).
, 2004; Beck et al. , 2015)  and by MNT against WNV and USUV. A significant proportion of horses (23/28) were found to be WNV positive by the two technics. Two samples were found positive against USUV in MIA but positive for WNV in MNT. Such discordant results could originate from a lower specificity of the flavivirus EDIII MIA technique. The fact that these sera were tested by MIA with WNV and USUV nonstructural protein 1 (NS1) and were found positive for WNV (data not given) supports this hypothesis. We did not identify the flavivirus involved in 9. 7% (3/31) of horse infections evidenced by positive cELISA reactions. As already mentioned by several authors  (Beck et al. , 2015) , WNV cELISA tests lack specificity in the diagnosis of WNV infection. Of 31 sera tested positive for anti-WNV IgG by ELISA, only 28 had specific neutralizing antibodies.
Mass spectrometry analysis The mass spectrometry (MS) analysis was performed using a Q Exactive™ HF Orbitrap with BioPharma option (Thermo Fisher Scientific, Waltham, MA, USA) operating in the high mass range. The mass spectrometry spectra were deconvoluted using the Protein Deconvolution Software (Thermo Fisher Scientific, Waltham, MA, USA). UPLC was also performed on the samples. The separation was done using the MAbPAC SEC-1 column, 5 μm, 300 Å, 4 × 150 mm (Thermo Fisher Scientific, Waltham, MA, USA), and ammonium acetate 50 mM pH 7. 0 at 0. 3 mL/min as mobile phase. By knowing the average mass of the antibody and the center of the conjugated antibody average mass distribution (broader peak in MS spectrum than the unconjugated form), an average number of chelators linked to the antibody was calculated.
HPLC HPLC analyses were performed using an Ultimate 3000 SD System (Thermo Fisher Scientific, Waltham, MA, USA) coupled to a GabiStar detector (Raytest, Straubenhard, Germany). Compound were separated with a size exclusion column, XBridge protein BEH 200 Å SEC 3. 5 μm, dimension 7. 8 × 300 mm (Waters, Baden-Dättwil, Switzerland). Elution was performed using phosphate buffer pH 6. 8 (1 mL/min) as mobile phase and was monitored via absorbance at 220/280 nm or γ detection. iTLC iTLC analysis were performed using dried iTLC-SG Glass microfiber chromatography paper impregnated with silica gel (Agilent Technologies, Folsom, CA 95630). Detection of the radioactivity were obtained on a mini-GITA scanning device (Raytest, Straubenhard, Germany) using the Gina star software after manual integration of the peaks.
Radio-immunoreactivity The immunoreactive fraction was assessed using Lindmo assay  [26]. A fixed concentration of radiolabeled 1C1m-Fc (0. 07 μg/mL) was incubated with increasing numbers (0. 25-8 x 10 6 ) of SK-N-AS cells in PBS containing 0. 5% BSA (PBS/BSA) for 3 h at 37 °C on a shaking platform. Nonspecific binding was evaluated by the addition of an excess of native non-radiolabeled 1C1m-Fc (> 100-fold excess). Unbound activity was washed away twice with PBS/BSA after centrifugation for 5 min at 300 g. The cell-bound activity was measured with a gamma counter (AMG Automatic Gamma Counter, Hidex, Turku, Finland). All conditions were tested in triplicate. The binding curve was extrapolated to an infinite number of cells using nonlinear regression from the Graphpad Prism 8. 0 software (GraphPad Software, San Diego, CA, USA).
For two animals belonging to group 2, imaging at 72 h was performed and then the mice were sacrificed to allow a biodistribution study. The image reconstruction methods were for SPECT: ordered subset expectation-maximization algorithm, 2 iterations and with scatter correction, and for CT: filtered back-projection algorithm with de-ringing correction. The tumor volumes of interest (VOI) were obtained by manual segmentation on axial CT slices using the PMOD software (PMOD technologies, version 3. 709, Zurich, Switzerland).
1 (HERMES Medical Solution AB, Stockholm, Sweden). We derived timeintegrated activity coefficients (TIACs) by analytical time-integration of fitted source organ nTACs obtained with the average nA, nA + SD and the nA-SD values, respectively. A specific absorbed dose estimated was obtained for the uterus, this organ, in fact, exhibited an important specific tracer uptake, but was not among the source/ target organs available in the murine model of the OLINDA/EXM 2. 1 software. In the liver, the stomach, the bladder, the uterus, and in the TEM-1 positive tumor, the radioactivity was still in the uptake phase 48 h post-injection. For these tissues, the TIAC was obtained by trapezoidal integration using the Matlab software (release 2017a, The MathWorks, Inc. , Natick, Massachusetts, USA), between t = 0 and t = 6 days, whereas a mono-exponential analytical integration to infinity was calculated after the last measure (t > 6 days) considering the 177 Lu physical decay constant.
Finally, the TIACs were entered into the OLINDA/ EXM® 2. 1 software kinetic module for organ absorbed dose estimates considering the 25 g murine model where the phantom source organ masses were adjusted to the average organ masses obtained from the mice population used in our experiment. In this process, the TIAC of the uterus was part of the remainder of the body. A specific absorbed dose estimate for the uterus was obtained using the sphere model of OLINDA/EXM 2. 1 where the average organ TIAC and the average organ mass were applied.
These hypotheses will be tested in future experiments using fluorescence microscopy. Biodistribution data were used for dosimetry calculations. The organ receiving the highest absorbed dose would be the liver (2. 23 Gy/MBq) followed by the uterus (1. 5 Gy/MBq), the spleen (1. 2 Gy/MBq), and the stomach (1. 15 Gy/MBq). The total body dose would be (0. 4 Gy/ MBq) and the tumor dose 1. 82 Gy/MBq. In particular, a specific dose estimate was performed for the uterus using the spherical model available in the OLINDA/ EXM 2. 1 software. This approach does not consider the specific morphology of the organ but it is at present the best approximation we can provide without applying  specific Monte Carlo dose calculations which are beyond the scope of this study. To evaluate the organ radiotoxicity after therapy administration in humans it would be necessary to extrapolate the human dosimetry to from the pre-clinical model.
IAPs appeared as pleiotropic proteins with cell type-specific functions. Accordingly, they have been involved in diverse human pathologies, including immune deficiencies, cancers, and inflammatory disorders  [200] , and IAP antagonists have entered into clinical trials for diverse clinical applications. It will be important to decipher further the specific functions and regulation mechanisms of IAPs in immune or non-immune cell subsets and to determine the impact of IAP antagonists on specific cell populations. Funding: Our work is supported by grants from "La Ligue contre le cancer" Comité de la Côte d'Or », the "Conseil Regional de Bourgogne-Franche-Comté", the French National research Agency, ("Investissements d'Avenir" program ANR-11-LABX-0021), the European Union program FEDER, and fellowships from the "Ministere de l'Enseignement Supérieur et de la Recherche" of France (AZ) and the "Fondation ARC" (BD).
Iphisa elegans Gray, 1851 is a lizard of the family Gymnophthalmidae distributed throughout Amazonia. The taxonomy of I. elegans is not well resolved, since several mitochondrial lineages and morphotypes suggested the existence of undescribed species currently embedded in a single taxon  (Nunes et al. 2012). Molecular data can significantly contribute in resolving the systematics and species boundaries within this genus but available genomic data are still scarce. Here, we describe the complete mitochondrial genome of Iphisa elegans. A male of Iphisa elegans was collected in the Nouragues Reserve in French Guiana (N4. 0716, W52. 7325). Genomic DNA was isolated from liver tissue using the Wizard Genomic extraction protocol (Promega, Madison, WI). We then used 200 ng of DNA to create a DNA sequencing library at the Genotoul-GeT-PlaGe sequencing platform of Toulouse (France) with TruseqNano LT kit Illumina (Illumina Inc.
, San Diego, CA). The library was hybridized and sequenced on a 1/24th of lane of an Illumina HiSeq 3000 flow cell. Over 32 million paired-end read of 150 bp were obtained. The mitochondrial genome was assembled using an iterative mapping strategy  (Besnard et al. 2014). We obtained a circular sequence of 18,622 bp in length. The overall base composition was as follows: A (31. 3%), C (20. 3%), G (18. 8%), and T (29. 7). We annotated the mitogenome with the MITOS webserver  (Bernt et al. 2013). We validated the coding regions using Geneious version 9. 0. 5  (Kearse et al. 2012). The annotated sequence was deposited in GenBank (accession no. MT472615). We then used MAFFT v. 7  (Katoh and Standley 2013)  to align the mitogenome of Iphisa elegans with all available mitochondrial genomes of Squamata retrieved from GenBank.
Data availability statement The data that support the findings of this study are openly available in figshare at https://doi. org/10. 6084/m9. figshare. 12349988. v1. The complete sequence can be accessed in GenBank at https://www. ncbi. nlm. nih. gov/ nuccore/MT472615. 1. The DNA sample is stored in the EDB collection (Laboratoire Evolution et Diversit e Biologique, Toulouse, France) curated by Antoine Fouquet under accession number IPHFG.
The assay was carried out in the presence of Benzonase to eliminate all nucleic acid-mediated protein interactions. The processed affinity eluates were subjected to liquid chromatography coupled to tandem MS (LC-MS/MS) and the resulting peptide mass fingerprint data were searched in the Swiss-Prot human protein sequence database using the Mascot software search engine (www. matrixscience. com). The screening identified 270 proteins with a score >20 and confirmed 15 proteins previously reported to interact with S-HDAg in HEK293 cells expressing a Flag-Tag-S-HDAg bait  17  (www. imexconsortium. org; identifier IM-27520). BAZ2B appeared among the proteins with the highest Mascot score co-purifying with S-HDAg and was hence chosen for further studies. The peptide mass fingerprinting analysis identified 24 unique peptides spanning across the full length of the BAZ2B protein (Supplementary Fig.
HDV RNA was detected by qRT-PCR using HDVspecific primers. Values represent the mean ± SEM (n = 3). g Pull-down assay of Strep-Tagged S-HDAg and BAZ2B BRD. Strep-Tactin® magnetic beads bound ST S-HDAg was mixed with his-tag BAZ2B BRD (5 µM) or his-tag GFP (5 µM). Input corresponds to 0. 2 µM of recombinant protein and 30% of the SDS eluate was subjected to immunoblotting with anti-His-Tag antibody, whereas 5% of the SDS eluate was subjected to immunoblotting with anti-Strep-Tag antibody. Source data are provided as a Source Data file. endogenous cellular H4 for incorporation into chromatin and alters host immune-associated genes expression  35. The adenovirus protein VII, which resembles cellular histones, complexes with nucleosomes to sequester the high-mobility-group protein B1, making it unable to signal danger and activate immune responses  36.
e Wt S-HDAg and R75A S-HDAg protein stability was compared in Huh7 cells treated with cycloheximide (CHX: 100 μg/ml). Left panel: Total cell extracts were analyzed by western blotting using the indicated antibodies. Right panel: Densitometric values expressed as ratio over wt S-HDAg or R75A S-HDAg controls (time 0). f Co-immunoprecipitation of S-HDAg and GFP-Tag-BAZ2B BRD. Parental Huh7 cells and Huh7 cells stably expressing wt or R75A S-HDAg were transfected with the pGFP-Tag-BAZ2B BRD plasmid coding for a GFP-BAZ2B BRD fusion protein targeted to the nucleus. Nuclear extracts were subjected to IP with GFP-Trap® beads. Input and elutions were analyzed by IB using the indicated antibodies. Source data are provided as a Source Data file. AB_2576217 or Cat#: A-21070, RRID: AB_2535731, dilution 1:1000) diluted in PBS/BSA.
Uncropped and unprocessed scans of all relevant blots are included in the Source Data file. Co-immunoprecipitation. For co-immunoprecipitation assays cell media were supplemented with 5 mM Sodium Butyrate 24 h prior collection. RIP was performed using 10  were detected by chemiluminescence. For co-immunoprecipitation assays involving the GFP-TRAP®_M beads (Chromotek), the nuclei lysates were obtained as described above and incubated with 25 µl of GFP-TRAP®_M beads overnight at 4 °C. After thorough washing with RIPA buffer, beads were resuspended in Laemmli (2×) and incubated at 95 °C for 10 min prior to electrophoresis. shRNA-mediated silencing/shRNA interference for BAZ2B. Lentiviruses containing shRNA for BAZ2B were obtained from GenTarget, Inc. , in the pLenti-H1-shRNA-puro lentivector.
BAZ2B shRNA sequences were designed using the Gentarget's software to knockdown human BAZ2B gene (Locus ID 29994), for all its transcripts variants (NM_001289975. 1; NM_001329857. 1; NM_001329858. 1; NM_013450. 3). The target sequences of the shRNA used are: shRNA BAZ2B #1 (5′-GATAGTGATTCAGGCACATCA-3′), shRNA BAZ2B #2 (5′-ATCCTGTTG GCTTAAATCCAT-3′), shRNA BAZ2B #3 (5′-GTATGGAGAAGGGCATTAT CA-3′), shRNA Scramble (5′-GTCTCCAGGCGCAGTACATTT-3′). Lentiviruses were transduced into PHHs overnight in the presence of 10 ng/ml of EGF (Gibco, Cat#: PHG0311L) and 8 µg/ml of Polybrene (Sigma Aldrich, Cat#: TR-1003-G). Cell medium was refreshed 24 h post transduction. Knockdown efficiency of BAZ2B mRNA expression was analyzed by RT-qPCR 12 days post transduction. Analysis of HDAg proteins in HDV viral inoculum.
Acknowledgements We thank  Alan Campbell Kay  for the gift of anti-delta antibodies and  Michel Rivoire  ( Centre Léon Bérard, Lyon ) for providing HBV, HCV, and HIV negative human liver resections. We thank  Christophe Combet  for bioinformatic support. We thank  Sebastien Violot  ( IBCP, Lyon, France ),  Georges Abou-Jaoudé  ( INTS, Paris, France ),  Alan Campbell Kay , and  Fabien Zoulim  ( CRCL, Lyon, France ) for fruitful discussions and advice. We thank  Sophie Clement  for her help in confocal microscopy imaging. P. D. was supported by an  INSERM Interface  Contract (2007-2011). N. A. S. was the recipient of a PhD grant from the  French Ministry of Research and Technology  ( 2013-2016 ) and a fellowship from the  ANR@RACTION  ( 2017-2018 ). This work was supported by grants from the  Agence Nationale pour la Recherche sur le SIDA et les hépatites virales (ANRS)  to P.
Data availability The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD016880 and to the IMEx consortium (www. imexconsortium. org) through IntAct  49  , and assigned the identifier IM-27520. All other data, materials, and reagents are available on request from the corresponding author (M. L. ). The source data underlying Fig. 1.
14 eurotoxicity was also induced by chemical depolarization with an exposure to 50 mM KCL for 30 min. 15 ultures were washed and returned to standard neurobasal medium. Neuronal death was estimated 24 h after the onset of the insult. Assessment of neuronal death. Death of cultured neurons was quantified by trypan blue staining 24 h after exposure with an automatic counter (Life technologies) or using PI/Hoechst staining. PI-positive neurons were quantified with ImageJ software and expressed as a ratio of PIþ neurons/Hoechstþ nuclei.
TMRE and MitoSOX TM fluorescence intensity in individual neuron were analyzed with an image analysis software (n ¼ 12 neurons and 3 separate neuronal cultures). Briefly, the area in each confocal micrograph occupied by each neuron was defined using the ImageJ 'threshold' function based on Hoechst staining, and the average fluorescence intensity derived from the indicator dyes (TMRM or MitoSOX Red) was measured within this area.
Electrophysiology Membrane potentials were measured on cortical neurons. Cells were incubated during 12 h in the presence of vehicle (neurobasal) or GC7 (30 mM), with or without K ATP channel blocker glibenclamide (10 mM), the mitochondrial K ATP blocker 5-hydroxydecaoate (5-HD, 10 mM), apamin (100 nM), or charybdotoxin (100 nM). After the incubation period, cells were patched and membrane potentials were immediately measured using the whole cell patch clamp configuration (Hamill et al. , 1981). 16 Each membrane potential was evaluated by using a RK 400 patch clamp amplifier (Axon Instrument), low-pass filtered at 3 kHz and digitized at 10 kHz using a 12-bit analog-to digital converter digidata (1322 series, Axon Instrument, USA). Patch clamp pipettes were pulled using vertical puller (PC-10, Narishige) from borosilicate glass capillaries and had a resistance of 3-5 MX.
The pipette solution contained (in mM) 155 KCl, 3 MgCl 2 , 2. 5 Na 2 -ATP, 5 EGTA, 2. 1 CaCl 2 , and 10 HEPES adjusted to pH 7. 2 with KOH. All experiments were performed at room temperature (21-22 C). Stimulation protocols and data acquisition were carried out using a microcomputer (Dell Pentium) which used a commercial software and hardware (pClamp 8. 2).
Swim pattern of the probe test at D18 was recorded by ANY-maze software (Version 5. 6; Stoelting Co. , Wood Dale, Il). Statistical analyses. Statistical analysis was performed using GraphPad Prism 6. 0 (GraphPad Software, La Jolla, CA, USA). Results are presented as means AE 95% confidence intervals (CI) for the in vitro experiments and as mean AE SD for the in vivo experiments. Unpaired t test and Mann-Whitney test were performed to assess the difference between groups as appropriate. Two-way ANOVA was performed when two groups (first factor) were compared over the time (second factor). This test was used to compare the GC7 effect on motor recovery and cognitive recovery. Statistically significant value was set to p < 0. 05, *p < 0. 05, **p < 0. 01, ***p < 0. 001.