dataesr/scientific-paragraphs-categorization huggingface dataset:
In vivo anti-tumoural and anti-metastatic effect of N6L polyplexes In vivo anti-tumour activity of N6L polyplexes was then analysed using subcutaneous tumor xenograft of PANC-1 cells. As shown in Figure  3 , treatments with N6L alone had no significant effect on PANC-1 xenograft tumour growth. In sharp contrast, N6L polyplexes significantly inhibited tumour growth by 85% (p<0. 05) (Figure  3 ). No significant effect of CS-C alone could be observed. Immunohistological analysis of tumour indicated that treatment with N6L polyplexes significantly decreased Ki67 positive cells by 53 % (p<0. 001) (Figure  4A ). Moreover, the area occupied by the tumour vasculature decreased by 70 % (p<0. 001) (Figure  4B ). All animals were closely monitored during the treatment and no toxicity could be evidenced in the various groups involved in the experiments, including the group treated with the N6L polyplexes (data not shown).
Design of N6L polyplexes for structural characterization Dynamic light scattering measurements were obtained at a 173° angle with a Nano-ZS Zetasizer from the Malvern company, equipped with a 4 mW He-Ne laser at 633 nm. Measurements were obtained in triplicate (each measurement was the average of fifteen 10 seconds runs). The data were analyzed using Malvern Zetasizer Series Software v7. 11. A Malvern Instruments dip cell was used for zeta potential measurements, each sample being measured in automatic mode, with an imposed maximum of 100 runs. For the DLS experiments, samples were prepared as follows. Stock solutions of N6L (2. 8 mM in water), of heparin (19. 6 mg/mL in water), and of Cs-C under three conditions (20 mg/mL in water, 1 mg/mL in water, and 1 mg/mL in a culture medium) were prepared.
Acknowledgements This work was supported by the  Ministry for Education and Science of the Russian Federation , in the framework of the  Increase Competitiveness Program  of the  National University of Science and Technology MISIS  under contract numbers  K4-2015-031  and  K2-2016-051 , the  Russian Foundation for Basic Research  (Grant Agreements No. 16-32-50139  and No. 16-02-00789 ) and by  LABEX WIFI (Laboratory of Excellence  within the  French Program Investments for the Future ,  ANR-10-LABX-24  and  ANR-10-IDEX-0001-02 PSL ). We wish to thank the referees who referred us to the new works about toroidal response.
In silico survey 2. 1. 1 Genome screen Twenty-four Anopheles genomes (full list and accession numbers are provided in Table  1 ) were screened by tBLASTn (BLASTþ 2. 2. 28)  (Camacho et al. 2009)  for the presence of flavivirus-derived EVEs using a collection of 50 full flavivirus polyprotein queries (full list and accession numbers are provided in Supplementary Table  S1 ) representing the currently known diversity of the Flavivirus genus. The sequences of hits whose E-value was < 10 À4 were extracted using an in-house bash shell script. In order to reconstruct putative flavivirusderived EVEs, BLAST hits were clustered using CD-HIT v. 4. 6. 1  (Li and Godzik 2006)  and aligned using MAFFT v7. 017  (Katoh et al. 2002). Putative EVEs were extracted and used as query for a reciprocal tBLASTn (BLASTþ 2.
2. 30) against the National Center for Biotechnology Information (NCBI) nucleotide database (Evalue < 10 À4 ). Genetic features of identified EVE were analyzed using the NCBI Conserved Domain Database  (Marchler-Bauer et al. 2015). Nucleotide sequence data reported are available in the Third Party Annotation Section of the DDBJ/ENA/GenBank databases under the accession numbers TPA: BK009978-BK009980.
Acknowledgements The authors thank  Inge Holm  and  Guillaume Carissimo  for providing An. stephensi nucleic acids,  Albin Fontaine  for help with the in silico screen,  Davy Jiolle  and  Elliott Miot  for technical assistance,  Clement Gilbert  for advice and critical reading of an earlier version of the article, and members of the  Lambrechts lab  for insightful comments and discussions. We also thank  Aris Katzourakis ,  Oliver Pybus  and two anonymous reviewers for constructive comments on an earlier version of the article.
Funding This work was supported by the  French Government 's  Investissement d'Avenir program Laboratoire d ' Excellence Integrative Biology of Emerging Infectious Diseases  grant  ANR-10-LABX-62-IBEID , and the  City of Paris Emergence (s) program in Biomedical Research. S. L. was supported by a doctoral fellowship from  University Pierre and Marie Curie. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
1 An. minimus A APHL01 AminM1 GCA_000349025. 1 An. nili ATLZ01 Anili1 GCA_000439205. 1 An. punctulatus JXXA01 APwgs2 GCA_000956255. 1 An. quadriannulatus A APCH01 AquaS1 GCA_000349065. 1 An. sinensis: Sinensis (Korean strain) AXCK02 AsinS2 GCA_000472065. 2 An. sinensis: China (Chinese strain) ATLV01 AsinC2 GCA_000441895. 2 An. stephensi: Indian ALPR002 AsteI2 GCA_000300775. 2 An. stephensi: SDA-500 APCG01 AsteS1 GCA_000349045. 1 WGS, whole-genome shotgun sequencing.
DNA was extracted using All Prep DNA/RNA Mini Kit (Qiagen, Hilden, Germany) following the manufacturer's instructions. EVE pres- ence in genomic DNA was assessed by 35 cycles of PCR using Taq Polymerase (Invitrogen, Thermo Fisher Scientific, Waltham, MA, USA) (Supplementary Table 30 cm screened cages under controlled insectary conditions (28 6 1 C, 75 6 5% relative humidity, 12:12 h light-dark cycle). They were provided with cotton soaked in a 10% (m/v) sucrose solution ad libitum. An. stephensi nucleic acids, used as a reaction control, were kindly provided by the Genetics and Genomics of Insect Vectors unit, Institut Pasteur, Paris. (Li et al. 2009)lzberg 2012)ptome sequence read archive was found under accession number SRX265162. Six An. sinensis transcriptome sequence read archives were found under accession numbers SRX448985, SRX449003, SRX449006, and SRX277584 for experiments using Illumina sequencing technology, and SRX218691 and SRX218721 for experiments using Roche 454 sequencing technology.
Construction of an M81 recombinant virus that constitutively expresses the luciferase gene We constructed a recombinant M81 strain with constitutive luciferase activity (B1129) by introducing a luciferase gene (pGL4. 5, Promega) into the M81 BAC  [56]  via homologous recombination  [57]  at the SmaI restriction site of the BXLF1 coding region (coordinate 131,127 on the M81 genome, GenBank accession number KF373730. 1). The expression of the luciferase gene on this virus is driven by a CMV early enhancer/chicken beta actin (CAG) promoter. The disruption of BXLF1 gene has previously been confirmed not to interfere with the growth of LCLs  [58]. Infectious virions were harvested from 293 cells (ATCC) stably infected with M81-Luc virus.
Xenograft studies NSG mice were injected subcutaneously in the flanks with 5 × 10 6 M81-Luciferase (M81-Luc) lymphoblastoid cells. Mice were treated with 20 mg/ kg teriflunomide intraperitoneally three times a week, beginning on day 8 and sacrificed on day 21 post-infection (a total of six injections). To determine tumor size, mice were injected intraperitoneally with the luciferase substrate luciferin (150 mg/kg; Gold Biotechnology) and scanned using an IVIS Spectrum in vivo imaging system. The light produced by the luciferase was quantified using Living Image software (PerkinElmer).
Allele-specific silencing was demonstrated by reduced mutant/WT ratio using RT-PCR and EcoNI digestion profile  (Fig 3C). Specific silencing of the mutant transcript was also shown by the quantification of the digested products corresponding to mutant and WT mRNAs relative to Gapdh expression  (Appendix Fig S4A)  and for sh9 by a second RT-PCR assay using primers designed for specific amplification of either WT or mutant alleles (Appendix Fig  S4B  and C ). These data confirmed that sh9, and to a lesser extent sh10, maintained allelespecific silencing properties in vivo. We evaluated capacity of 3-month sh9 and sh10 treatments to alleviate muscle atrophy, morphological abnormalities and contractile properties. When compared to WT muscle, HTZ TA muscles showed a significant 28% decrease in mass  (Fig 4A).
Data analysis and statistics Graphics and statistical analyses were performed with GraphPad Prism software version 5. 00. Values were expressed as means AE SEM. The number of samples (n), representing the number of independent biological replicates, was indicated in the figure legends. For molecular analysis, the experiments were repeated at least three times per biological replicate and averaged. We used nonparametric statistical tests to analyse our data since the normality could not be assumed or tested (n too small) or the variance was not equal between groups. Statistical comparisons between two groups were performed using unpaired one-or two-tailed Mann-Whitney Utest as specified. Statistical tests applied are indicated in the figure legends. P < 0. 05 were considered as statistically significant.
Page ruler prestained protein ladder (ThermoFisher Scientific, France) was used as molecular weight marker. Membranes were blocked for 1 h at room temperature in PBS containing non-fat dry milk 5% and Tween-20 0. 1% and then exposed to rabbit polyclonal anti-Dynamin 2 antibody (1:400, Abcam ab3457, United Kingdom) or rabbit polyclonal anti-GAPDH antibody (1:2,000, Santa Cruz, France) in PBS-Tween-20 0. 1%, milk 1% overnight at 4°C. Membranes were rinsed in PBS-Tween-20 0. 1% and incubated 1 h with horseradish peroxidase-conjugated secondary antibody (1:20,000, anti-rabbit from Jackson ImmunoResearch, United Kingdom) in PBS-Tween-20 0. 1%. Chemiluminescence was detected using ECL detection Kit (Merck-Millipore, Germany) in a G-Box imaging system (Ozyme, France), and signal quantification was performed using ImageJ software.
Light microscopy was performed using an upright microscope (DMR, Leica), and images were captured using a monochrome camera (DS-Ri1, Nikon) and NIS-Elements BR software (Nikon, France). Exposure settings were identical between compared samples and viewed at room temperature. For quantification of the frequency of fibre size, the maximum diameter was calculated for each fibre on TA muscle sections labelled with antilaminin antibody (1:500, ab11575 Abcam, United Kingdom) using ImageJ software and the normal distribution of the values was plotted using Microsoft Excel software. Histomorphological abnormalities were counted on DPNH staining (two sections per animals) using ImageJ software.
Acknowledgments We thank the  Pitié-Salpêtrière Imaging Platform (PICPS)  for light microscopy imaging facilities, the  Penn Vector Core ,  Gene Therapy Program  ( University of Pennsylvania, Philadelphia, USA ) for providing pAAV1 plasmid (p0001) and  Stéphanie Buart  for mouse embryonic fibroblast preparation. This work was supported by the  Institut National de la Santé et de la Recherche Médicale (INSERM) , the  Association Institut de Myologie (AIM) , the  Université Pierre et Marie Curie (UPMC) , the  Centre National de la Recherche Scientifique (CNRS) , and the  Agence Nationale de la Recherche  (grant  ANR-14-CE12-0009  to M. B. and  Young Researcher  grant  ANR-14-CE12-0001-01  to S. V. ).
Background Around two-thirds of patients with psoriasis do not adhere to topical treatment. The Topical Treatment Optimization Programme (TTOP), a fiveelement tool, includes guidance for the conversation between dermatologists/ nurses and patients, patient information material, telephone/e-mail helpdesks and treatment reminders. It has been developed by patients and dermatologists to help increase adherence to treatment in psoriasis. Objectives To compare TTOP with standard of care ('non-TTOP') within a large European investigator-initiated study, PSO-TOP (clinicaltrials. gov NCT01587755). Methods Patients with mild-to-moderate psoriasis received calcipotriol/betamethasone dipropionate gel as standardized study medication and were randomized 1 : 1 to either TTOP or non-TTOP management. Study medication was applied once daily for 8 weeks followed by 'as needed' application for an additional 56 weeks.
Study design PSO-TOP was a phase IV, 64-week, randomized controlled study (EudraCT number 2011-001697-26). It was an investigator-led (K. R. ) study, designed, developed and conducted by dermatology experts from Denmark, France, Germany, Italy, the Netherlands, Spain, Sweden and the U. K. , with additional input from patient focus-group interviews. 12 During the first 8 weeks, all patients applied Cal/BD gel once daily, then on an 'as needed' basis in the following 56 weeks as per the SmPC. 14 At baseline, patients were randomly assigned 1 : 1 to either the TTOP or non-TTOP intervention. 12 An electronic randomization list was generated by an independent third party using the software RandList 1. 2, and was stored in the electronic case report form so that a randomization number was automatically assigned in ascending order as soon as the investigator confirmed the randomization of the patient.
Objectives and assessments The primary objective was to demonstrate a difference in treatment responses to study medication in the TTOP and non-TTOP arms. The primary efficacy end point was PGA response after 8 weeks of treatment, with a responder having a PGA of 0 (clear) or 1 (almost clear). Visits were planned at weeks 4 and 8 (AE 3-day and AE 7-day window at each visit, respectively), then every 8 weeks during the 'as needed' period up to week 64. PGA and affected BSA were assessed at all visits. 15, 16 Patient-reported outcomes -Patient's self Global Assessment (PsGA),  12  Dermatology Life Quality Index (DLQI)  17  and the Topical Therapy Adherence Questionnaire (TTAQ)  18  were collected at baseline, weeks 8, 40 and 64 (Data S1; see Supporting Information). At weeks 8 and 64, patients randomized to the TTOP arm were asked to rank the five TTOP elements from one (most important) to five (least important).
Acknowledgments This study was supported by a grant from  LEO Pharma  to K. R. , who designed the study with help from I. Z. , C. O. and U. M. The experts originally involved in developing the TTOP intervention were K. R, I. Z, C. O, U. M. , E. H. B. , E. M. G. J. J. , P. G. , L. P. and R. B. W. The TTAQ was developed by patient-reported outcome specialists at SCIderm. The data were collected and analysed by SCIderm, with input from K. R. and U. M. The manuscript was prepared by K. R. , I. Z. , U. M. and C. O. , with input from all authors. Writing assistance and editorial support were provided by  Andrew Jones PhD  from  Mudskipper Business Ltd , which was funded by  LEO Pharma. We thank all participating sites for their support and are grateful to all patients who took part in the trial.
Representative downregulated genes at 4 h and 8 h are presented Fig 3D. The list of differentially expressed genes between the WT and the bdf1-Y187F-Y354F mutant strain was established for each time-point using the DESeq2 R-package (Fig 3C  , S5 Table, p value < 0. 05 and |Fold change| > 2). Of the genes analysed, none showed a statistically significant difference in expression before sporulation induction between the WT and bdf1-Y187-F-Y354F strains. The same analysis was performed on the data obtained 4 and 8 hours after inducing sporulation; in these conditions large numbers of deregulated genes were identified, 473 and 1,098, respectively (Fig 3C  and 3D , S5 Table ). Notably, NDT80, AMA1 and late genes such as DIT1 and DIT2 failed to induce when Bdf1 bromodomains were mutated (Fig  3D).
This difference with the data obtained in the Bdf1 complex and the published structure of the SWR complex could be explained if the SWR complex is present in vivo in several forms. This hypothesis is strengthened by results from structural studies using cosslinking reagents to obtain a homogeneous population of the complex  [51]. Interestingly, Bdf2 was never identified in SWR complex. This result suggests that Bdf1 could form two exclusive complexes, one with the SWR complex and another one with Bdf2. Finally, Bdf1-TAP was purified from a strain lacking YAF9, the subunit of the SWR complex responsible for recruiting Bdf1  [52]. In the yaf9Δ strain, Bdf1 still associated with Bdf2, but its interaction with the SWR complex was completely abolished (Fig 5D ). Taken together, these results suggest that Bdf1 can be part of two exclusive complexes: one with the SWR complex or a Bdf1 / Bdf2 complex whose function remains to be characterised (Fig 5E ).
Meiotic recombination analysis The frequency of meiotic recombination between the heteroalleles his4-N/his4-G was quantified by plating sporulated yeast cultures on YPD and SC-HIS plates. The number of yeasts growing on SC-HIS plates was counted and normalised to the total number of cells growing on YPD. reads were quality-checked using FastQC before and after cleaning by Trimmomatic applying default parameters  [71]. Reads were then aligned to S. cerevisiae S288c genome build R64-1-1. 82 using Bowtie2  [72]. The attribute file was downloaded from Ensembl website and modified to include yeast intronic sequences, obtained from Yeastmine. Raw read counts for each gene were calculated using HTSeqCount using defaults parameters  [73]. Read count data was normalised using the DESeq2 R-package (S5 Table,  [74] ).
DESeq2 normalised read counts were used to identify differentially expressed genes with an adjusted p-value < 0. 05 and a fold change below -2 or above 2 (S5 Table ). Gene ontology analysis was performed using the generic GO-term mapper developed by the Max Planck Institute (http://cpdb. molgen. mpg. de/ YCPDB). Pscan tool was used to explore the promoter of the genes which are downregulated in bdf1-Y187F-Y354F 4 and 8h after sporulation induction (http://159. 149. 160. 88/pscan/, [75] ). Binding motifs for yeast transcription factors were obtained from the JASPAR 2016 database  [76]  and researched in the promoter of each gene (-500 to 0 bp upstream each transcription start side). A binding motif was considered significantly over-represented when the p-value was inferior to 0. 001 (Fig 4A ).
Protein preparation and mass spectrometry-based proteomic analyses were carried out as described in  [79]. Briefly, eluted proteins were stacked as a single band in a SDS-PAGE gel (NuPAGE 4-12%, Invitrogen) and submitted to in-gel digestion using trypsin (Promega, sequencing grade). Resulting peptides were analysed by online nanoLC-MS/MS (UltiMate 3000 and Q-Exactive Plus or LTQ-Orbitrap Velos Pro, Thermo Scientific) using a 120-min gradient. Peptides and proteins were identified and quantified using MaxQuant (version 1. 5. 3. 30, [80] ) and the SGD database (November 2015 release). Proteins were quantified based on the iBAQ value  [81]  calculated by MaxQuant. Only proteins identified with a minimum of two unique + razor peptides were taken into account. For statistical analysis of results obtained with Bdf1-TAP triplicates, we used ProStaR  [82] : proteins identified in the reverse and contaminant databases and proteins exhibiting fewer than 6 iBAQ values in a single condition (2 conditions and 2 analytical replicates per biological replicate) were discarded from the list.
RT-qPCR Reverse transcription was performed by following manufacturer instructions using kits iScript RT Supermix and Universal SYBR Green Supermix (Bio-Rad) on a CFX384 Touch qPCR machine (Bio-Rad). Primers are presented (S4 Table ). At least three biological replicates were performed to determine the standard errors for each experiment. RT-qPCR data were then normalised relative to the reference gene, NUP85  [19].
This work was supported by the  Fond d'Intervention of the University Grenoble Alpes  [to JG], the  Agence Nationale de la Recherche  [ ANR-11-PDOC-0011  to JG]; the  European Union   FP7 Marie Curie Action  " Career Integration Grant " [304003 to JG] and the  Fondation pour la Recherche Medicale  [ SPF20140129159  to EGO]. transcription program and of the expression of the master regulator  NDT80. This study received financial support from the  French National Research Agency   ANR-10-INBS-08  ProFI,  Proteomics French Infrastructure. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
RNA-Seq enables the generation of extensive transcriptome information providing the capability to characterize transcripts (including alternative isoforms and polymorphism), to quantify expression and to identify differential regulation in a single experiment. To reveal the capacity of new anti-HIV ABX464 candidate in modulating the expression of genes, datasets were generated and validated using RNA-seq approach. This comprehensive dataset will be useful to deepen the comprehensive understanding of the progression of human immunodeficiency virus (HIV) associated with mucosal damage in the gastrointestinal (GI) tract and subsequent inflammation, providing an opportunity to generate new therapies, diagnoses, and preventive strategies.
To this end the data from three distinct group of BMDM cultures were analyzed for different gene expression levels using RNA-seq. We performed a high-resolution transcriptome analysis of ABX464-treated BMDMs stimulated or unstimulated with LPS. In this work, the RNA-seq libraries were sequenced using the BGISEQ-500 platform which use the DNA nanoball technology. Approximately 1 billion 50-bp single-end RNA-seq reads were generated, with an average of over 45 million sequence reads per sample. 24 intestinal macrophages mRNA profiles of three distinct group of BMDM cultures from mice were generated by deep sequencing, using Illumina protocol. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: HISAT  10  and Bowtie2 (ref. 11) followed by genes expression quantification using a software package called RSEM  12.
Using an optimized data analysis workflow, about 45 million sequence reads per sample were mapped to the mouse genome (build mm9) and identified 1,383 expressed genes in the LPS-stimulated BMDMs among which 439 and 397 genes increased and decreased in expression > = 1. 5 log2-fold, respectively. Altered expression of some genes was confirmed with qPCR, demonstrating the high degree of sensitivity of the RNA-seq method. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to inflammatory function. Data analysis with HISAT  10 / Bowtie2 (ref. 11)  and RSEM  12  workflows revealed a significant overlap yet provided complementary insights in transcriptome profiling. A comprehensive RNA-seq data resource was provided on the antiinflammatory properties of ABX464 that warrant exploration in both HIV and inflammatory ulcerative colitis (UC) disease.
The library was amplified with phi29 to make DNA nanoball (DNB) which have more than 300 copies of one molecular. The DNBs were load into the patterned nanoarray and single end 50 bases reads were generated in the way of sequenced by synthesis. Then, RNA-seq libraries were sequenced using the BGISEQ-500 sequencer. Base-calling was performed by the BGISEQ-500 software version 0. 3. 8. 1111.
Data filtering 'Dirty' raw reads were defined as reads which contain the sequence of adaptor, high content of unknown bases and low quality reads. These reads were removed before downstream analysis to decrease data noise. Filtering steps are as follows: The quality of the RNA-seq libraries was first evaluated using the FastQC v0. 11. 5 software. Then, the reads were subjected to standard quality control (QC) criteria according to the following parameters: (1) trimming and cleaning reads that aligned to primers and/or adaptors, (2) reads with over 50% of low-quality bases (quality value ≤5) in one read, and (3) reads with over 10% unknown bases (N bases). After filtering, the remaining reads are called 'clean reads' and stored as FASTQ format  13.