dataesr/scientific-paragraphs-categorization huggingface dataset:
25, 27  Again, we found a significant decrease in Fmo3 hepatic gene expression in response to PB in both datasets (Fig. 5G  and 5H ). It is worth noting that all publicly available studies were conducted in male mice only, which could explain why the decrease in Fmo3 expression seen upon CAR activation by PB or CITCO was of lower magnitude than that seen in our own in vivo experiments in females. Finally, we took advantage of the only available ChIP-seq analysis of hCAR binding in vivo to date  28  and observed that, among the 6,364 unique genes associated with high-confidence hCAR-binding genes, Fmo3 was found as a hCAR-direct binding gene with a p value = 1. 26 × 10 -29 (Fig. 5I ). Thus, in females, CAR activation by TCPOBOP perturbated the metabolism of TMAO from TMA by inhibiting the expression of Fmo3 (Fig.
Financial support MH is the recipient of a PhD grant from the French Ministry of Research. This work was supported by Région Occitanie (Hepatomics to NL) the Fondation pour la Recherche Médicale (grant number ENV202109013962 to HG) and grants from the French National Research Agency (Hepatomorphic ANR-20-CE14-0035 to HG; Gadget ANR-22-CE34-0005-01 to SE-S).
Next, noninfected tumoral cells could be targeted with the expression of therapeutic genes by bystander effect, and nally, they could stimulate an immune cell response as foreign microorganisms  9. We have developed the oncolytic vaccinia virus TG6002, deleted of thymidine kinase and ribonucleotide reductase to enhance tumor-selective viral replication  10, 11. TG6002 expresses FCU1, a bifunctional chimeric protein that combines cytosine deaminase and uracil phosphoribosyltransferase activities and e ciently catalyzes the direct conversion of the non-cytotoxic prodrug 5-uorocytosine (5-FC) into the chemotherapeutic compound 5-uorouracil (5-FU)  12. TG6002 has recently entered clinical development in patients with advanced gastrointestinal tumors (NCT03724071, NCT04194034). These clinical trials are phase 1 studies evaluating the safety and tolerability of multiple-ascending doses of TG6002 administered intravenously in combination with oral 5-FC.
RNA-seq analysis RNA-seq data have been previously published  (18)  and deposited on NCBI GEO under the accession number GSE123752. Briefly, poly-A transcripts were extracted at 48h post-transfection from 293T-LTR-GFP cells transfected with pSG5M-Tax or pSG5M empty vectors. RNA-seq libraries were prepared from biological triplicates and sequenced using the illumina HiSeq 2500. Paired-end pairs of reads were then analyzed using the pipeline FaRLine and the FasterDB database  (47). HTSeq-count (v0. 7. 2)(48) and DESeq2 (v1. 10. 1) (49) were used calculating gene expression level and for computing differential gene expression levels, respectively. The significance thresholds were set to 5% for ΔPSI (differential percentage of spliced-in sequence) (p < 0. 01, Fisher's exact test) and 0. 6 for log2-gene expression changes (p<0.
The ratio between short-range and long-range contacts was computed using hicPlotSVL with the threshold distance set to 1e6 nucleotides. The inference of A/B compartments and changes in compartmentation between Tax and CTL matrices were analyzed using the pipeline dcHiC with matrices at a resolution of 100k  (53). The full genome compartment strength was calculated as (AA + BB) / (AB + BA) from the log2 ratio of observed versus expected contacts sorted by their eigen vector values (hicCompartmentalization). A saddle plot was generated with cooltools (https://github. com/open2c/cooltools) using cis-contacts from matrices at a resolution of 50k. The eight subcompartments were assigned by the pipeline CALDER with matrices at a resolution of 10k and the binning variable set to 50k  (54). The Deeptools' PlotEnrichment  (55)    EDTA and supplemented with protease inhibitor cocktail).
ACKNOWLEDGEMENTS We gratefully acknowledge support from  Laurent Modolo  at the  LBMC  for bio-informatic advice, and from the  PSMN (Pôle Scientifique de Modélisation Numérique)  of the  ENS de Lyon  for computing resources. FM thanks  Chloé Journo ,  Daniel Jost , and  Aurele Piazza  for their valuable discussions and insightful comments.
subcompartments A. 1. 1 and A. 1. 2 in control cells were markedly enriched in active marks H3K27ac and H3K4me3, while compartments B. 2. 1 and B. 2. 2 corresponded to H3K9me3 embedded regions (Sup Fig 3E). We then compared the subcompartment annotations between the two experimental conditions by considering 4 large subcompartments: A. 1 (A. 1. 1 + A. 1. 2), A. 2 (A. 1. 1 + A. 1. 2), B. 1 (B. 1. 1 + B. 1. 2), and B. 2 (B. 2. 1 + B. 2. 1). Subcompartment transitions were observed in Tax expressing cells, as demonstrated in Figure 1E and Sup Fig 3F. These transitions involved shifts from active to inactive subcompartments, with some coinciding with differential trans-chromosomal interactions (Figure 3 E-F). Using publicly available ChIP-seq datasets for HEK 293T cells, we confirmed that the predicted.
(2). Since then, technical improvements (e. g. , the advent of cryoelectronic microscopy) led to the deposition of hundreds of NCP structures on the Protein Data Bank (PDB), gathering from mono-to 6-mer NCP assemblies  (3)  and large NCP-protein complexes. This accumulation of data also allowed to start unraveling the finely-tuned epigenetic regulation of chromatin dynamics by histone PTM and variants exchange, resorting to both experimental and theoretical approaches  (4, 5). Yet, structures of NCP harboring PTM marks are rare, and a lot of aspects remain to be uncovered in order to get a better understanding of epigenetic regulation at the molecular level. It is only recently that oxidative PTM (oxPTM) have gained interest from the biochemical community due to their importance in disease onset and for the development of redoxbased therapies.
System preparation The α-satellite nucleosome starting structure for MD simulations was taken from Davey et al. crystal structure of the nucleosome featuring an α-satellite DNA sequence and histone tails (PDB ID 1KX5 (1)). Crystallographic waters and ions were removed. Force field parameters were taken from ff14SB  (26) , and bsc1  (27)  and CUFIX  (28)  corrections were applied to improve DNA and the disordered tails description. The sulfonylated nucleosome starting system was created from the canonical nucleosome by mutating in silico the cysteine 110 of the first copy of histone H3. The modified residue name was set to OCS, consistently to what is found in the literature. Considering the very low pKa (∼2) of sulfonated cysteines  (29) , the deprotonated form of OCS was used, with a total charge of -1.
Long-read DNA sequencing (ONT) and methylation base-calling DNA was extracted from approximately 100 mg of young plant tissue from rdr1;2;6 ddm1, rdr1;2;6 Cen5-ATHILA5 ddm1 (hp5) and their corresponding DDM1 wild-type siblings with the DNeasy Plant Pro Kit (Qiagen). From each sample, 600 ng -1 ug of purified DNA was taken as input for ligation library preparation with the Native Barcoding Kit 24 v14 (ONT -SQK-NBD114. 24) with equimolar pooling following barcode ligation. 35 ng of the multiplexed library was sequenced on an R10. 4. 1 a Marie Curie fellowship (REP-658900-2) and a grant from the Agence Nationale de la Recherche (ANR-12-BCV2-0013). T. K. was supported by the Japanese Ministry of Education, Culture, Sports, Science, and Technology (26221105 and 15H05963). The Arabidopsis pericentromere is maintained by DNA methylation and H3K9 methylation, and is essential for sister chromatid cohesion.
Acknowledgements We thank the late  Simon Chan  and  Taku Sasaki  for sharing seeds;  Soichi Inagaki ,  Mayumi Takahashi  and  Akiko Terui  for experimental support;  Paul Fransz  for training in cytogenetics, and  Joe Simorowski ,  Benjamin Roche  and  Jean-Sébastien Parent  for helpful suggestions. A. S. was supported by  JSPS  postdoctoral fellowships. Research in the  Martienssen Laboratory  is supported by a grant from the  National Institutes of Health  ( RO1GM067014 ) and by the  Howard Hughes Medical Institute. D. G. was supported by.
Statistical analysis Plasma immune markers, histological parameters and gene expressions were statistically analyzed using the Rcmdr package of R software (version 4. 1. 2). For each dataset, normality of the distributions and homogeneity of the variances were assessed using a Shapiro-Wilk's test and a Levene's test, respectively. When these prerequisites were met, the effects of the diet and duration of refeeding (days 2, 5 and 8) were analyzed using two-way analysis of variance (ANOVA) by excluding the fasted fish. Then, the influence of time (i. e. sampling day) was tested independent of the diet by analyzing the datasets from day 0 (fasted fish) to day 8 using one-way ANOVA. Differences were considered statistically significant at the 5 % threshold.
ACKNOWLEDGMENTS The authors acknowledge the use of the supercomputing machine Nandadevi at The  Institute of Mathematical Sciences, Chennai. Priyotosh Sil  would like to thank  Velmurugan S  for discussions. Ajay Subbaroyan  would like to thank  Ajaya Kumar Sahoo  for discussions. Areejit Samal  acknowledges support from the  Max Planck Society, Germany , through the award of a  Max Planck Partner Group in Mathematical Biology , and the  Department of Atomic Energy, Government of India. IPS2 benefits from the support of  Saclay Plant Sciences-SPS  ( ANR-17-EUR-0007 ).
Oxidation-sensitive cysteines act as redox switches to control IL-38 aggregation in vitro and in cells Next, we further investigated the molecular mechanisms underlying oxidation-dependent IL-38 amyloid formation. In the IL-38 crystal (PDB: 5BOW) and in the AlphaFold-modelled IL-38 protein, the two ACs mostly fall into β-sheets buried inside the protein (Fig  3a ). Intriguingly, although IL-38 has a remarkably high cysteine content (7 cysteines, amounting to 4. 6% of its 152 aa sequence) (Fig  2a ), the IL-38 crystal does not show any disulfide bonds. Based on the high structural homology within the IL-1 family and the presence of disulfide bridges in other family members  (Cohen et al. , 2015; Schreuder et al. , 1997) , we hypothesized that IL-38 might nevertheless be able to form intramolecular S-S bonds and measured the distances between the sulfurs of its 7 cysteine residues along a 1 μs accelerated molecular Altogether, these data support a role for the C37-C38 disulfide bond in facilitating conformational changes and modification of the biochemical properties of IL-38 in response to oxidation.
Acknowledgements We would like to thank  Ali Modarressi  ( University Hospitals, Geneva, Switzerland ) for providing healthy human skin samples used in this study. We would like to thank  Sergei Startchik  and  Nicolas Liaudet  ( Bioimaging Core Facility, Faculty of Medicine, University of Geneva, Switzerland ) for their help with microscopy image analysis. We would like to thank the  Protein Platform (Faculty of Medicine , University of Geneva, Switzerland ) for their help with the production of recombinant IL-38 proteins and the  Proteomics Core Facility (Faculty of Medicine, University of Geneva, Switzerland)  for their help with the analysis of N-terminal IL-38 peptides. This work was supported by grants from the  Swiss National Science Foundation  ( 310030_188470  to GP), the  Rheumasearch Foundation , the  Kurt and Senta Herrmann Foundation , the  Medicor Foundation , and by a generous donor advised by  Carigest SA.
Nematodes are keystone actors of soil, freshwater and marine ecosystems, but the complexity of morphological identification has limited broad-scale monitoring of their biodiversity. DNA metabarcoding is increasingly used to assess nematode biodiversity but requires universal primers with high taxonomic coverage and high taxonomic resolution. Several primers have been proposed for the metabarcoding of nematode diversity, many of which target the 18S rRNA gene. In-silico analyses have a great potential to assess key parameters of primers, including their taxonomic coverage, resolution and specificity. Based on a recently-available reference database, we tested in-silico the performance of fourteen commonly used and one newly optimized primer for nematode metabarcoding. Most primers showed very good coverage, as amplified most of sequences in the reference database, while four markers showed limited coverage.
2010). In-silico tests allow cheap and rapid comparisons of a very large number of primers and often provide a good estimate of the actual performance of primers across various taxa, that can later be confirmed by in-vitro assays on real-worlds samples  (Ficetola et al. 2010 , Epp et al. 2012 , Clarke et al. 2014 , Collins et al. 2019 , Kawanobe et al. 2021 , Van Nynatten et al. 2023). Accurate in-silico assessments of primers for DNA metabarcoding require the availability of extensive, highquality reference databases over which primers can be tested  (Ficetola et al. 2010 , Collins et al. 2019). The recent publication of a curated 18S rRNA database of nematode sequences (18S-NemaBase;  Gattoni et al. 2023)  poses the basis for such assessments. In this study, we built upon the 18S-NemaBase to compare the performance of 15 primers proposed for the metabarcoding of nematodes (Table  1 ).
Primer selection All 15 primers selected for our analyses target the 18S rRNA region of nematodes (Table  1 ). Among these primers, 13 were selected because they have been identified by a previous review as the primers more commonly used in nematode metabarcoding  (Gattoni et al. 2023). One additional primer, Euka02  (Guardiola et al. 2015)  is often used for metabarcoding of eukaryotic eDNA and it has been suggested to provide a good estimate of nematode diversity  (Guardiola et al. 2015 , Ohlmann et al. 2018 , Rosero et al. 2021 , Calderón-Sanou et al. 2022). Furthermore, we developed a new primer pair (Nema02; see Table  1 ) by optimizing primer pair F548_A / R1912 from  Kawanobe et al. (2021). More specifically, we performed in silico PCRs on the public sequence database GenBank v249 with the ecoPCR program  (Ficetola et al.
In-silico PCR The availability of high-quality, curated databases is pivotal to test the performance of metabarcoding primers. We based our analyses on the 18S-NemaBase  (Gattoni et al. 2023) , which represents the most complete and high-quality available reference database of nematode 18S rRNA. The original 18S-NemaBase includes 5 231 sequences identified at family level or better, representing 214 families and 2734 species  (Gattoni et al. 2023). The performance of primers was tested using the ecoPCR program  (Ficetola et al. 2010). EcoPCR allows in-silico assessment of amplification of a sequence on the basis of its match with a selected primer pair in a region of a specified length  (Ficetola et al. 2010 ). The sequence is selected from a given reference database. To work, the program requires the reference database in the ecoPCR format.
Thus, we converted the 18S-NemaBase from the fasta to the ecoPCR format using the obiconvert command of the OBITools command suit  (Boyer et al. 2016). The original 18S-NemaBase database consisted of 5231 sequences. However, 283 sequences (i. e. 5,4%) were excluded because they showed problems during the conversion from the fasta to the ecoPCR format (268 sequences) or because they were they were assigned to non-nematode taxa in 18S-NemaBase (15 sequences), thus we based our analyses on a total of 4948 sequences. For in-silico PCR, we allowed a maximum of 3 mismatches between each primer and the sequences in the database. For each primer pair, the length of amplified fragments was selected based on the literature and of preliminary trials (Table  1 ). Running ecoPCR on the curated 18S-NemaBase allowed us to calculate two measures of primer performance: -Taxonomic coverage, as the percentage of amplified sequences within the reference database -Resolution, i.
2021). We used a linear regression to test whether there is a positive relationship between taxonomic resolution and the log-transformed average length of the amplified fragments. This analysis was run at the species-level resolution because all the primes showed excellent resolution at the genus-and family level (see results). Furthermore, we assessed the specificity of the tested primers using the whole GenBank database (version 249) instead of the 18S-NemaBase as reference database in the ecoPCR program. This time, we only retained one sequence per species, to avoid biased due to the overrepresentation of model species (e. g. Caenorhabditis elegans for nematodes). Then, specificity was measured as the percentage of nematodes amplified over non target organisms  (Ficetola et al. 2010). Primers showing high specificity are in principle preferable because they have a higher probability of detecting target taxa, including rare species  (Ficetola et al.
Taxonomic coverage The taxonomic coverage (proportion of amplified sequences compared to the 18S-NemaBase database) was highly variable across primers. The majority of primers showed very good to excellent coverage, amplifying >90% of sequences in the reference database, while four primers showed a limited coverage (Table  2 , Fig. 1 ). The three primers with the highest coverage were 3NDf-1132rmod, EcoF-EcoR and Euka02, all showing coverage ≥ 97%. These primers amplified fragments with very different lengths, spanning from 100 bp (Euka02) to more than 800 bp (1813F_2646R; Table  2 ).
Specificity When tested on the whole GenBank, primers showed specificity values that ranged between 1% or less (FO4-R22, SSU_F04-SSU_R22) and ~7% (1813F-2646R, Nema02; Fig. 4a ). These values indicate that all the markers amplify a very large number of non-nematode sequences. Nevertheless, some of the primers with high specificity only amplified a limited number of nematode taxa (Fig. 1 , Fig. 4b ). The primers with the best compromise between specificity and coverage of nematodes included 18SILVOmidF-18SILVOmid, Euka02 and Nema02 (Fig. 2 , Fig. 4 ).
2015 , Fonseca 2018 , Marquina et al. 2019). A few mismatches probably are less problematic in phylogenetic studies, where the DNA of just one species is extracted at each time directly from specimens  (Blaxter et al. 1998 , Holterman et al. 2006). In-silico assessments of primer coverage, like the one performed here, have their own limitations, as they may both miss some taxa that would be amplified in-vitro and vice versa. In-silico analyses focusing on curated databases can also miss key issues, such as non-specific amplification  (Collins et al. 2019 ). Nevertheless, several in-vitro tests have confirmed the appropriateness of primers studied with in-silico analyses  (Epp et al. 2012 , Clarke et al. 2014 , Kartzinel and Pringle 2015 , Collins et al. 2019 , Waeyenberge et al. 2019 , Kawanobe et al.
g. , Nema02, but se  Kawanobe et al. 2021  for analyses confirming the good performance of similar primers). All primers showed good to excellent resolution on the considered reference database. Even the shortest primer (Euka02) showed a reasonably good ability to discriminate between species (Fig. 2 ) and, for all primers, the frequency of genera sharing the same metabarcode was ≤5% (i. e. genus-level resolution was always 95% or higher). These findings are highly promising for the use of metabarcoding for nematode analyses. However, it is important to acknowledge some caveats. The use of high quality, curated databases is fundamental for all the metabarcoding analyses, being pivotal for assessments of marker performance, and for accurate taxonomic identification  (Taberlet et al. 2018 , Leray et al.
2019 , Morinière et al. 2019 , White et al. 2020 , Williams et al. 2023). Our analyses were run on a large, curated database containing about 5000 sequences from 214 families, 668 genera and 2734 species  (Gattoni et al. 2023). Unfortunately, this database only represents the currently described species and genera, but most nematodes inhabiting the Earth still require description  (Hodda 2022a , Hodda 2022b). We stress that all measures of taxonomic resolution strongly depend on the available data  (Weigand et al. 2019). For instance, if the reference database only includes one species within a given genus, analyses would return a species-level resolution, despite unanalysed species within that genus may share the same metabarcodes  (Ficetola et al. 2021). Within the primers with good taxonomic coverage, resolution was clearly related to the length of the amplified fragment (Fig.
3 ). This is not unexpected, as longer fragments include more variable sites and thus are well known to provide a better resolution  (Taberlet et al. 2018 ). Nevertheless, even the shortest fragments allow an excellent genus-level resolution. Many functional analyses of nematodes are performed at the genus level. For instance, Nemaplex (http://nemaplex. ucdavis. edu) is a major database of nematode traits, and provides traits at the genus-level resolution. Ensuring that primers provide robust identification at the genus level is thus extremely important for all the studies focusing on nematode traits and functional diversity. A key issue of the analyzed primers is that they are not specific to nematodes, and amplify a broad range of eukaryotes (Fig. 4 ). A-specific amplification can reduce the detection of rare taxa, and can even increase false positives  (Wilcox et al.
This was followed by 5 acetone washes for 5 minutes each. Ovaries were infiltrated with Polybed resin in a series of steps as follows: 1:3 resin to acetone overnight, 1:1 resin to acetone for 6 hours, 3:1 resin to acetone overnight, 100% resin for 6 hours followed by embedment in molds in fresh 100% resin and curation at 60C for 2 days. Polymerized samples were then trimmed using an ultramicrotome to get the entire cross-section of the ovary. Serial 60 nm sections were collected using an Automated Tape-Collecting Ultramicrotome, mapped, and imaged with a Zeiss Sigma FE-SEM as described previously  S15. Homology search. Canonical human GRASP (GRASP65 and GRASP55) and Golgin amino acid sequences (Data S1A) were used as initial queries. Homologs were searched in the target species using Basic Local Alignment Search Tool, BLAST, (BLASTp and TBLASTn) in available databases (Uniprot, NCBI, Ensembl).
For specific target species, the search was carried out in dedicated databases (Amphiura filiformis: http://www. echinonet. org. uk/blast/; Mnemiopsis leidyi: https://research. nhgri. nih. gov/mnemiopsis/sequenceserver/; Nematostella vectensis: http://marimba. obs-vlfr. fr/blast; unicellular holozoans: https://protists. ensembl. org). Target genomes and, whenerver available, transcritpomes were interrogated. Hits with the lowest E-value and highest query coverage were selected as candidate homologs and validated when by reverse BLAST on the human proteome the query was retrieved as the highest scoring. If this approach did not return a hit, homologs of evolutionarily closer species were used as queries. Further validation of homology was obtained by subjecting the hits to sequence and structural analysis with InterProScan (https://www.
Emanuele Astoricchio is supported by a PhD fellowship funded by the Stazione Zoologica Anton Dohrn (Open University -Stazione Zoologica Anton Dohrn PhD Program). With the aim of expanding our survey, we would be grateful to researchers willing to contribute examples of Golgi morphology (electron and light micrographs) in tissues, species or phyla not covered by the present report. To this purpose, please contact Francesco Ferraro at the following email addresses: francesco. ferraro@szn. it or f. ferraro. uk@gmail. com. Author contributions Conceptualization: F. F. Methodology: F. F. , M. I. A. , S. D. , S. L. Investigation: F. F. , G. B. , S. L. , E. A. , S. Bo. Resources: S. J. , M. K. , K. M. , V. H. , V. B. , H. E. , S. Be. , C. L. , J. U-L. , B. S. , P. B. , I. R-T. , G. J. , E. D. Writing original draft: F.