dataesr/scientific-paragraphs-categorization huggingface dataset:
ACKNOWLEDGMENTS We deeply thank  Geraldine Toutirais  ( PTME, Plateau Technique de Microscopie Électronique et de Microanalyses du Museum National d'Histoire Naturelle, Paris ) for assistance with SEM imaging. We thank  Jasmine Kirati  ( UMR BIPAR, Anses, ENVA, INRA ) for help with in vivo assays and  Olivier Berteau  ( Micalis Institute, INRA ) for assistance in protein purifications.
johnsonii La1 (Q74JG0_LACJO); BSH12, L. johnsonii La1 (Q74LX7_LACJO); CBAH-1, C. perfringens strain 13 (P54965. 3); BSHA, L. acidophilus LA4 (ACL98173. 1); BSHB, L. acidophilus LA4 (ACL98173. 1); BSHA, L. acidophilus LA11 (ACL98175. 1); BSHB, L. acidophilus LA11 (ACL98176. 1); BSHA, L. acidophilus NCFM (YP_193782. 1); BSHB, L. acidophilus NCFM (AAV42923. 1); BSH, L. gasseri AM1 (ACL98172. 1); BSH-α, L. johnsonii 100-100 (AAG22541. 1); BSH-β, L. johnsonii 100-100 (AAC34381. 1); BSHA, L. johnsonii pf01 (EGP12224. 1); BSHB, L. johnsonii pf01 (EGP13287. 1); BSHC, L. johnsonii pf01 (EGP12391. 1); pCBH1, L. plantarum 80 (AAB24746. 1); BSH1, L. plantarum WCSF (CCC80500. 1); BlBSH, B. longum subsp. longum (2HF0); BSH, L. acidophilus PF01 (ABQ01980. 1); BSH, L. plantarum CK 102 (Ha et al. , 2006) ; Penicillin V Acylase (PVA), Bacillus sphaericus (3PVA).
marinus individuals studied here; the differences between these three sequences were confined to only four SNPs (SI Appendix, Fig. S5B ), indicating that they are orthologous sequences. Notably, the P. marinus CDA1L2 gene exhibits several insertion/deletion mutations and a large internal deletion, compared with the seemingly functional L. planeri and L. japonicum CDA1L2 genes. However, another sequencing study identified a complete version of CDA1L2 in a P. marinus individual (referred to as CDA4 in GenBank accession no. ALO81575. 1; SI Appendix, Fig. S3A ) that is closely related to the sequence of L. japonicum CDA1L2_2, suggesting that like CDA1L1 genes, the CDA1L2 genes are also subject to pseudogenization or loss. Predicted Biochemical Features and Structures of Lamprey CDA Proteins. The lamprey deaminases comprise a distinct clade of the AID/APOBEC sequences that are exclusively found in jawed vertebrates (SI Appendix, Fig.
Interestingly, unlike other CDA1L1 proteins in lampreys, the CDA1L1_4 protein, encoded by the CDA1L1_4 gene, shares a unique chemical property with PmCDA1 and AID, namely, a high net positive surface charge. This positively charged surface is a feature of AID that distinguishes it from related APOBEC3 proteins, which have neutral or net negative charges  (3). We speculate that as in human AID, this highly positive surface charge modulates the efficiency of ssDNA substrate on/off binding kinetics  (50) , functionally distinguishing CDA1L1_4 from the other CDA1-like proteins. Combined with its cytidine deamination activity, our data are consistent with the evolution of CDA1L1_4 toward a similar DNA editing function in vivo as PmCDA1. Therefore, our findings raise the intriguing possibility that lampreys have found different solutions for VLRA/C assembly; the gene conversion process might be governed by either a canonical CDA1 gene in P.
The average size of sequenced DNA fragments (∼400-500 bp) allowed us to fuse the paired reads into single contigs. Generation of BLAST Databases from WGS. Illumina adapter sequences were trimmed off the read ends using cutadapt in paired-end mode  (64). Lowquality bases were removed using prinseq  (65)  with minimum base quality 20 in a window of three bases with a step size of two bases, retaining reads of at least 30-nt length. For lower quality libraries, window and step size were increased. Reads with mean quality below 26 were removed as appropriate. Forward and reverse mates were merged using flash  (66) , allowing for up to 300 bases overlap. Spaces in read names were replaced with underscores using the sed command. The resulting merged as well as unmerged read files were formatted into one nucleotide blast database allowing for read name parsing.
CDA Contig Assembly from BLAST Databases. Genomic sequence collections were searched for CDA-like sequences using the BLASTn algorithm on the SequenceServer BLAST server (version 1. 0. 9) (67), installed in-house. BLAST parameters were set to an expectation cutoff of 1E -5 , allowing a maximum number of 1,000 returned sequences. From the resulting hits, contigs were assembled with SeqMan Pro (version 13. 0. 0, DNASTAR) using a match size of 25 nucleotides and a minimum match percentage of 99% with otherwise default parameters. Contigs were manually curated and used as queries against the nonredundant National Center for Biotechnology Information protein database using the BLASTx algorithm to identify bona fide CDAencoding sequences. Phlyogenetic Comparison of AID/APOBEC Family Members with Lamprey CDAs.
Phylogenetic relationships were derived using an approximate maximum likelihood (ML) method as implemented in the FastTree program  (68)  and the full ML method implemented in MEGA7  (69). To increase the accuracy of topology in FastTree, we increased the number of rounds of minimumevolution subtree-prune-regraft (SPR) moves to 4 (-spr 4) as well as utilized the options -mlacc and -slownni to make the maximum-likelihood nearestneighbor interchanges (NNIs) more exhaustive. Southern Filter Hybridizations. Southern filter hybridizations were carried out as described  (39). Final wash conditions were 0. 1 × SSC/0. 1% SDS at 60 °C. PCR of CDA Genes with Version-Specific Primers. PCR was carried out on genomic DNA using the proof-reading Phusion polymerase (New England Biolabs) as described  (39).
Libraries were sequenced at 2 × 100 bp paired end using HiSeq2500 (Illumina). Trimmomatic (version 0. 30)  (70) , Trim Galore! (version 0. 3. 3) (www. bioinformatics. babraham. ac. uk/projects/trim_galore/), and fastx-toolkit (hannonlab. cshl. edu/fastx_toolkit/) program suites were used to trim adapters and low-quality bases and remove reads that were too short for assembly or had overall low quality. The reads from each organ were combined per individual for de novo transcriptome assembly. We additionally applied in silico fragment normalization to 30× coverage using the normalize_by_kmer_coverage. pl utility from Trinity. The assembly was performed using Trinity (version r20131110)  (71)  with default settings. The best ORFs were subsequently extracted using the Transdecoder tool from Trinity; ORFs with identical amino acid sequences were collapsed together using CD-Hit (version 4.
6. 1-2012-08-27) (72). Collections of unique ORFs for each animal were converted into BLAST databases as described above. RNA-Seq Expression Analysis. Using the trimmed and processed reads described above as an input, reads were aligned from each organ from L. planeri specimen Lp#131 and Lp#132 against the different CDA gene variants using HiSAT2 (Galaxy version 2. 0. 5. 1) (73) with default parameters and alignments with a quality score of less than 30 filtered out. Read counts per gene were extracted using Samtools IdX Stats and converted to log 2 counts per million (log 2 cpm). Expression of CDA Variants. The newly identified CDA variants were expressed in bacterial and eukaryotic cells as previously described for human and bony fish AID  (21, 24, 25, 74). Briefly, for expression in 293T cells, amplicons containing ORFs of CDA variants were obtained and KpnI and EcoRV restriction sites were added to the 5′ and 3′ ends, respectively, of each ORF by PCR, followed by cloning into the expression vector pcDNA3.
Following addition of loading dye and denaturation, electrophoresis was performed on a 14% denaturing acrylamide gel. The gels were exposed to a Kodak Storage Phosphor Screen GP (Bio-Rad) and visualized using a PhosphorImager on Quantity One software (Bio-Rad). Percent deamination of each substrate (d)C was calculated for each CDA variant using Quantity One software (Bio-Rad) and averaged between two independent duplicate preparations of each variant. Bacterial Resistance Assays. cDNA sequences corresponding to MmAID, PmCDA1, and LpCDA1L1_4 were cloned into the pTrc99A vector (Pharmacia; a kind gift from Cristina Rada, MRC Laboratory of Molecular Biology, Cambridge, UK) using NcoI/HindIII restriction sites and transformed into the ung-1 derivative of the KL16 E. coli strain, BW310 (a kind gift from Cristina Rada).
Six independent cultures per construct were grown overnight at 37 °C to saturation in LB medium supplemented with 100 μg/mL ampicillin and 1 mM IPTG. Mutagenic activity is expressed as the number of colony-forming units grown on LB agar plates containing 100 μg/mL rifampicin per 10 9 viable cells grown on LB agar plates containing 100 μg/mL ampicillin relative to a vector only control as previously described  (53). Structure Prediction of CDA Variants. For structural modeling and substrate docking, we used the same strategy as previously described for determination of AID's functional and breathing structure  (3, 50) , which has since been confirmed by a partial AID crystal structure  (51). Briefly, five homologous APOBEC structures were chosen as templates for homology modeling: mouse A2 NMR (PDB: 2RPZ), A3A NMR (PDB: 2M65), A3C (PDB: 3VOW), A3F-CTD X-ray (PDB: 4IOU), and A3G-CTD X-ray (PDB: 3E1U).
APOBEC structures were obtained from the Protein Data Bank (www. rcsb. org) and visualized using PyMOL v1. 7. 6 (https://pymol. org/2/). Using I-TASSER (https://zhanglab. ccmb. med. umich. edu/I-TASSER/), full-length orthologous AID and CDA protein structures were modeled at pH 7 from APOBEC templates to generate 9-25 models for each (variability due to model convergence), for a total of 145 models. Nonhomologous regions between the target and APOBEC template, such as the N and C termini, were modeled ab initio. The catalytic pocket was defined by the solvent accessible cavity containing the Zncoordinating and catalytic residues. Protein charge and pI were predicted for each protein structure using the PARSE force field in PROPKA 3. 0. DNA substrates were docked to each AID or CDA model using Swiss-Dock (www.
7 (https://www. cgl. ucsf. edu/chimera) (75). Deaminationconducive CDA-DNA complexes were defined by the accessibility of the (d)C-NH 2 substrate group to the catalytic Zn-coordinating and the glutamic acid residues within the putative catalytic pockets. Sequence Deposition. Whole genome reads (accession nos. SAMN08109814-SAMN08109820) and raw transcriptome reads (accession nos. SAMN08109821-SAMN08109828) were submitted to the Sequence Read Archive at the NCBI. cDNA sequences were submitted to GenBank at the NCBI (accession nos. MG495252-MG495272).
Tamami Hirai for expert technical assistance; Dr. Cristina Rada for reagents; Dr. Max Cooper for insightful discussion of his unpublished data on the CDA gene family in lampreys; and the Experimental Unit of Aquatic Ecology and Ecotoxicology (U3E), Institut National de la Recherche Agronomique 1036, which is part of the research infrastructure Analysis and Experimentations on Ecosystems-France, for help with the provision of animals. S. J. H. and T. B. are supported by the Max Planck Society, the Deutsche Forschungsgemeinschaft through SFB 746, and the European Research Council (ERC) under the European Union's Seventh Framework Programme (FP7/2007-2013), ERC Grant agreement 323126. M. L. is supported by a Canadian Cancer Society Research Institute innovation grant and Natural Sciences and Engineering Research Council (NSERC) Discovery Grant 2015-047960.
ACKNOWLEDGMENTS We thank  A. Rongvaux ,  L. Evangelisti ,  J. Stein ,  C. Hughes , and  L. Borelli  for help with generating Gpr183 À/À mice. We also thank  L. Zenewicz  for providing cDNA and  G. Eberl  ( Pasteur Institute ) for providing Rorc(gt) GFP transgenic work was supported by a  Sir Henry Dale Wellcome Trust  Fellowship ( 105644/Z/14/Z ) to M. R. H. ,  NIH  grant  RO1AI113040  to J. P. P. ,  Swiss National Science Foundation  grant  159188  to B. L. , and a  Junior Investigator Research Grant  from the  Center for Innovative Medicine at the Karolinska Institutet  and a grant from the  A ˚ke Wiberg Foundation  to T. W.
For intracellular staining, cells were stimulated with SIINFEKL 100 nmol/L 37 C for 5 hours, adding Golgi Stop (BD Biosciences) to allow accumulation of intracellular cytokines. After viability and surface marker staining, cells were fixed and permeabilized using Cytofix/Cytoperm solution (BD Biosciences) following the manufacturer's instructions, and then stained with anti-IFNg. Flow data were acquired with a FACS Celesta (BD Biosciences) and analyzed with Diva software (BD Biosciences) or FlowJo software (Tree Star, Inc. ).
IFNa production was measured by ELISA. Data are presented as mean AE SEM of two independent experiments. B, In vitro T-cell activation assays. After 2 hours of conditioning with 3LL TCM (1:2), wt and MyD88 À/À FL-DCs were pulsed with OVA class I peptide for 3 hours. DCs were then coincubated 48 hours with OT-I T cells and IFNg production was quantified by ELISA. Data represent the mean AE SEM of two independent experiments. D, FL-DCs were conditioned 24 hours with 3LL TCM in the presence of aIL10R (10 mg/mL) or aTGFb (10 mg/mL) or both, as indicated. After treatment, cells were washed and stimulated overnight with CpG-B (1 mg/mL), polyI:C (10 mg/mL), or DMXAA (25 mg/mL). IFNa and IL12p70 were measured by ELISA. Data represent mean AE SEM of one experiment out of two. Significance was determined by an unpaired t test.
Our data show that these subset-specific functions, analyzed in bulk, are both targeted when the lung is infiltrated by a tumor. In parallel, we exposed DCs to medium conditioned by a whole-tumor extract, that includes cancer cells and their surrounding stroma. Using both approaches and measuring independently cytokine production and T-cell priming, we found that conditioning blocks the ability to secrete IL12 and type-I interferon in response to agonist of TLR9, TLR3, and STING. Inability to respond to LPS or IFNg/CD40 was previously shown to depend on tumor derived PGE-2, IL10, or miRNA reprogramming  (3, 8, 46, 47). Our data extend the concept of innate suppression showing that tumor-exposed DCs become refractory to stimulation by agonist of TLR3 and STING and, importantly, become unable to secrete IFNI.
Type-I interferon in DCs is critical for immunosurveillance of nascent tumors, cross-priming and tumor rejection  (7, 48, 49). In established tumors, however, plasmacytoid DCs were shown to silence IFNI production, suggesting the existence of an escape mechanism that targets the IFN axis  (50). Our data show that also conventional DCs lose the ability to respond to exogenous nucleic acids, indicating that crippling cytosolic sensing and the ensuing IFNI in crosspresenting DCs may be a further mechanism to avoid T-cell recognition. Innate immune memory is emerging as a key feature of myeloid cells that, depending on the type and concentration of ligand encountered, respond with enhanced or decreased cytokine production upon restimulation  (51). Maturation and early cytokine induction upon TCM exposure suggest triggering of innate sensors by soluble factors, which in turn may induce tolerance to further stimulation.
After treatment, cells were washed and stimulated overnight with CpG-B (1 mg/mL), polyI:C (10 mg/mL), or DMXAA (25 mg/mL). IFNa and IL12p70 were measured by ELISA. Data represent mean AE SEM of one experiment out of two. Significance was determined by an unpaired t test. Ã , P 0. 05; ÃÃ , P 0. 01. NS, not stimulated.
Acknowledgments This work was supported by grant  IG2013 14414  from the  Italian Association for Cancer Research (AIRC ; to  F. Benvenuti ) and grant  14-0320  from  Worldwide Cancer Research  (WWCR; to  F. Benvenuti ). We are grateful to  Vasilena Gocheva  and members of the  Tyler Jacks's laboratory  for providing the LG tumor cell line and to  D. Fearon  for providing LLC/1 tumor cell line transduced with OVA (3LL-OVA) cells. We thank  V. M. Dixit  ( Genetech ) for Asc À/À mice and  Cecilia Garlanda  for shipping MyD88 À/À bone marrow. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U. S. C. Section 1734 solely to indicate this fact.
The following annealing temperatures were chosen: LINE-1: 53 °C; LINE-1 control: 60 °C; Alu: 58 °C and Alu control: 61 °C. The amplification conditions were denaturation at 95 °C for 10 min, followed by 40 cycles of 95 °C for 30 s, T M °C for 40 s, and 72 °C for 15 s. DNA Methylation levels were calculated by the DDC T method using StepOne Software 2. 2 (Applied Biosystems).
Acknowledgements In Memoriam and in Gratitude to  Professor Rolf Ackermann. The authors are grateful to  Wolfgang Schulz  ( Department of Urology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany ) for revising the paper. They thank  Johannes Fischer  ( Institute of Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany ) for providing blood samples. This study has been supported by:  Stiftung für Altersforschung, Heinrich-Heine-Universität Düsseldorf. Prof. Dr. Rolf Ackermann ,  Wissenschaftliche Urologische Gesellschaft  e. V. M. J. A-B. has been supported by grants  DFG10/15 ,  DFG15/15  and  DFG141/16  from  Diputación Foral de Gipuzkoa, Spain, Ministry of Economy and Competitiveness, Spain ,  MINECO  grants  PI16/01430  and  BFU 2016-7798-P  and funds from  Ikerbasque, Basque Foundation for Science, Spain.
The Brown Ring Disease (BRD) caused high mortality rates since 1986 in the Manila clam Venerupis philippinarum introduced and cultured in Western Europe from the 1970s. The causative agent of BRD is a Gram-Negative bacterium, Vibrio tapetis, which is also pathogenic to fish. Here we report the first assembly of the complete genome of V. tapetis CECT4600 T , together with the genome sequences of 16 additional strains isolated across a broad host and geographic range. Our extensive genome dataset allowed us to describe the pathogen pan-and core genomes and to identify putative virulence factors. The V. tapetis core genome consists of 3,352 genes, including multiple potential virulence factors represented by haemolysins, transcriptional regulators, Type I restriction modification system, GGDEF domain proteins, several conjugative plasmids, and a Type IV secretion system.
Genome Annotation, Comparative Genomics, and Core Genome Phylogeny Expert annotation of the reference strain CECT4600 T was done using the MaGe tools of the MicroScope platform  (Vallenet et al. , 2017). The other 16 draft genomes were then aligned on the complete genome sequence of V. tapetis CECT4600 T using ABACAS  (Assefa et al. , 2009)  and annotations were collected from MicroScope  (Vallenet et al. , 2017). Orthologous clusters were computed using GET_HOMOLOGUES (Contreras-Moreira and Vinuesa, 2013), a software relying on three clustering algorithms. We defined the core genome as the consensus of these three algorithms, using a maximal e-value of 1e-05 and a minimum coverage of 75% in pairwise alignments. The pangenome was defined using the sole OrthoMCl clustering algorithm instead of the three implemented in GET_HOMOLOGUES  (Contreras-Moreira and Vinuesa, 2013).
Circular comparison of the genomes was carried out to identify the genome architecture and the highly conserved and divergent regions using V. tapetis CECT4600 T as reference and the BRIG software with results plotted as series of lanes, all colored according to BLAST alignment of coding sequences  (Alikhan et al. , 2011). To perform phylogenetic analyses, we retrieved the single-only copy of core genes following alignment of each individual orthologous gene cluster with Muscle v6. 1  (Edgar, 2004). The concatenated alignment was used to construct a core genome maximum-likelihood (ML) phylogenetic tree using the LG amino acid evolutionary model with an estimated gamma distribution with four categories using PhyML  (Guindon et al. , 2010). Robustness of branching was estimated with 1000 bootstrap pseudoreplicates.
ACKNOWLEDGMENTS This project received grants from the  Region Bretagne , from the  CNRS ,  IFREMER , and  MENSR (Biological Resource Center, CRB 2002) "collection of pathogenic bacteria of marine aquaculture species ", the  FP7 European project Bivalife  (grant agreement  N • 266157 ),  GIS EUROPOLE MER "VIVREM", CNRS INEE APEGE "PaleoCOQ", CAPES-COFECUB "MICROBIV" (Sv   818-14 ),  PVE Brésil  ( N • 03/2014 ), the cluster of excellence  LabexMER  ( ANR-10-LABX-19 ), and  ArcheoSHELL  ( Danish Council for Independent Research, Natural Sciences (FNU ,  4002-00152B ), and  H2020   VIVALDI  project (grant agreement  N • 678589 ). Acknowledgement to the LABGeM and the  National Infrastructure "France Genomique" Special  thanks to  Philippe Maes , who isolated, together with CP, all bivalve V. tapetis strains from 1988 to 1992 in Brittany and Galicia and  Jean Louis Nicolas  for his inestimable collaboration in microbial ecology.
The Thai national AIDS program database, which includes data on DM incidence, related mortality and prevalence of related complications, provided a unique opportunity to assess the importance of DM in a South-East Asian HIV infected adult population. Since Fiscal Year (FY) 2005 (October 1, 2004 to September  30, 2005) , Thailand has provided free health services, including ART and laboratory monitoring to HIV-infected patients through the Thailand National AIDS Program (NAP), under the National Health Security Office (NHSO). At each visit, or at the end of each month for hospitalizations, data from HIV-infected patients covered by these schemes are entered into the NAP database. We estimated the incidence of DM diagnosis, investigated associated risk factors and clinical outcomes using the data from adults registered with the NAP under the Universal Coverage Scheme (UCS), which covers about three-quarters of the Thai population  [7].
Methods This study was a retrospective cohort study and an analysis of secondary data of the NHSO. A total of 199,707 HIV infected adults (≥18 years old) with no history of DM registered between FY2007 to FY2013 and follow up until September 30,2014 (end of FY2014) for care with the NAP and received care under UCS in 1035 hospitals throughout Thailand. We extracted the following patient characteristics from the NHSO database: sex, date of birth, weight, height, fasting plasma glucose (FPG), triglycerides, hepatitis C virus infection, absolute CD4 cell count (including nadir) and date of ART initiation  [7]. A patient not showing up for at least 7 months after last visit was considered lost to follow up (LTFU). The number of PYFU was calculated from date of NAP registration (baseline) to censoring date, i.
05). We tested the proportional hazards assumption of each model based on Schoenfeld residuals  [20]  and considered time-updated DM diagnosis as a time-varying variable  [21, 22]. Analyses were performed using Stata software, version 13. 1 (Stata Corp, College Station, Texas, USA). Patient identifiers were encrypted by NHSO prior data management and analysis. The analysis plan was approved by the Ethical Committee of the Faculty of Medicine, Chiang Mai University, Thailand on March 18, 2014 (114/2014, Research ID: COM-2557-02140).
Study population and follow up All 199,707 HIV-infected adults (54. 2% male) with no history of DM, registered with the NAP through the UCS from FY2007 to FY2013, were included in the analysis. Baseline median age was 36. 2 years (IQR 30. 5 to 42. 6), BMI 20. 2 kg/m 2 (IQR 18. 2 to 22. 4), absolute CD4 cell count 120 cells/mm3 (IQR 33 to 324) and nadir CD4 cell count 119 cells/mm 3 (IQR 33 to 323); and 1408 of 199,707 (0. 7%) had a history of hepatitis C infection. Of the 11,763 patients with available records, 2511 (21. 4%) had triglycerides ≥200 mg/dl. Data from a total of 763,666 PYFU were available from FY2007 to FY2014 (median follow-up time was 3. 8 years [IQR 1. 6 to 6. 1]); 15,114 patients (7. 6%) were lost-to-follow up, 8383 (4. 2%) were diagnosed with DM and 44,062 (22. 1%) died (Fig.