dataesr/scientific-paragraphs-categorization huggingface dataset:
Mirror tree analysis Using Artemis40, 79 fam-m and fam-l doublets that were confidently predicted as being paired-up were manually selected on the basis of their dispersal throughout the subtelomeres of different chromosomes. The Mirrortree64 web server (http://csbg. cnb. csic. es/mtserver/) was used to construct mirror trees for these 79 doublets. 35 doublets with recent branching from another doublet were manually selected to enrich for genes under recent selection (Extended Data Fig. 5c ). To control for chance signals of co-evolution on the basis of their subtelomeric location, the same methodology was repeated by choosing 79 pir genes in close proximity of fam-m genes as 'pseudo-doublets' for analysis and paired up in the Mirrortree64 web server (Extended Data Fig. 5d ).
Reticulocyte-binding protein (RBP) phylogenetic plot Full-length RBP genes were manually inspected using ACT41 and verified to either be functional or pseudogenized by identification of sequencing reads in other samples that confirm mutations inducing premature stop codons or frameshifts. All functional RBPs were aligned using MUSCLE21 and cleaned using GBlocks46 with default parameters. PhyML50 was used to construct a phylogenetic tree of the different RBPs (Extended Data Fig. 4a ). Figtree was used to colour the tree (http://tree. bio. ed. ac. uk/software/figtree/).
Finally, we filtered sites that were masked using Dustmasker53 to remove repetitive and difficult to map regions. The same methodology was also applied to two P. vivax samples (SRR3400910 and SRR332566) and two P. falciparum Pf3K field samples (PF0066-C and PF0038-C, see https://www. malariagen. net/projects/pf3k) for comparative purposes.
To calculate the average K a /K s ratio68, we took the cleaned alignments of the MK test, extracting the pairwise sequences of P. malariae and P. malariae-like (and of P. o. curtisi and P. o. wallikeri). The 'Bio::Align::DNAStatistics' module was used to calculate the K a /K s values for each pair70, averaging across samples within a species. Using existing RNA sequencing data from seven different life-cycle stages in P. falciparum71, reads were mapped against spliced gene sequences (exons, but not UTRs) from the P. falciparum 3D7 reference genome18 using Bowtie2 (ref. 72)  v2. 1. 0 (-a -X 800x). Read counts per transcript were estimated using eXpress v1. 3. 0 (ref. 73). Genes with an effective length cutoff below 10 in any sample were removed. Summing over transcripts generated read counts per gene.
Numbers were averaged for all gametocyte stages and for all blood stages. Genes with no stage having 10 or more reads were classified as being expressed elsewhere. Genes in P. malariae and P. ovale were classified by the maximum expression stage of their P. falciparum orthologue if the difference between the maximum expression stage and the second highest stage was larger than the difference between the second and third highest stage, otherwise the gene was classified as having no peak expression. The Gene Ontology term enrichment analysis was performed in R, using TopGO74. As a Gene Ontology database, the predicted Gene Ontology terms from the P. falciparum 3D7 genes orthologous to the P. malariae and P. o. curtisi genes included in the analysis were used. Collated tables for all molecular evolution measures for all genes can be found in Source Data File 1 for P.
Data deposition statement All raw data has been deposited as described in Supplementary Information. Assembled genome sequences can be found under the study PRJEB14392 (http://www. ebi. ac. uk/ena/ data/view/PRJEB14392). The individual accession numbers are as follows for PmUG01 (contig accession: FLRL01000001-FLRL01000047; chromosome accession: LT594622-LT594637), PocGH01 (contig accession: FLRI01000001-FLRI01000638; chromosome accession: LT594582-LT594597), PowCR01 (contig accession: FLRJ01000001-FLRJ01000771; chromosome accession: LT594505-LT594520) and PmlGA01 (contig accession: FLRK01000001-FLRK01000035; chromosome accession: LT594489-LT594503). similarities. Functional genes are in red and pseudogenes in grey. This compares to only 17 Pfg27 copies described previously7, which were found on six separate contigs, while all Pfg27 copies described here are found on the same contig.
Extended Data Table 2 Samples positive for different Plasmodium species in the Pf3K data set The first column shows country of origin for the different samples, with the second column showing the total number of samples collected in that country. The following five columns show the number of these samples that are positive for the different Plasmodium species. All samples are positive for P. falciparum, which is expected because all the samples were initially identified as P. falciparum infections. We do not see any samples positive for P. knowlesi, because it has a very limited geographic range and isn't found in any of the sampled countries to our knowledge. Presence and absence of P. malariae (red), P. ovale (blue) or both (purple) by country on the basis of a literature review (Supplementary Information).
Acknowledgements This work was supported by the  Medical Research Council  ( MR/J004111/1 ;  MR/L008661/1 ) and the  Wellcome Trust  ( 098051 ). S. A. and R. N. P. are funded by the  Wellcome Trust  ( 091625 ). F. R. , B. O. and F. P. are financed by the  ANR JCJC 2012 ORIGIN , the  LMI Zofac , as well as by  CNRS ,  IRD , and  CIRMF. C. I. N. is funded by a  Wellcome Trust   Investigator Award  ( 104792/Z/14/Z ). A. A. D. is funded as a Sanger International Fellow. J. S. M. and N. M. A. are supported by  NHMRC Practitioner Fellowships  ( 1041802 ;  1042072 ). The authors thank  E. Willaume  from the  Park of La Lékédi  and the people involved in the sanitary controls of the chimpanzees. The authors also thank  P. Griffin  and  S. Sekuloski  for assistance in collection of P. malariae isolate PmGN01.
| RESULTS We first evaluated by flow cytometry the level of human hematopoietic cell (hCD45 + ) engraftment in the skin as compared to various organs of NSG-HLA-A2-HIS mice. We observed a high level of hCD45 + engraftment in the spleen, liver, lymph node (Figure  1A ) and thymus of the animals (data not shown). The lung and bone marrow exhibited good to intermediate level of human hCD45 + cells engraftment (Figure  1A ), whereas the vagina and intestine (data not shown) were moderately colonized by human hematopoietic cells. This data were confirmed by histology (Fig. S1 ). In comparison, the skin from the flank and the ear was moderately engrafted with human CD45 + cells, which were mostly located in the dermis (Figure  1B, C ). The engraftment efficiency of human cells in the skin was time-dependent, with increasing human cell density in the skin of older animals (23-26 weeks old, Figure  1C ) as compared to younger ones (12-13 weeks old, Figure  1B ).
ACKNOWLEDGEMENTS MC, MP, AJH, MD and AS performed research; DB and MM provided human materials. MC and BC designed the research, analysed data and wrote the manuscript. Dr Centlivre was supported by a  FRM postdoctoral fellowship  ( SPF20121226281 ) and  Dr Combadière  received  Eu-FP7 CuTHIVAC  (no. 241904 ) and FRM fundings. We thank  Dr Morosan  for animal facility and  Dormeur Foundation ,  Vaduz , for providing AID EliSpot Reader and Cryostat HM550 apparatus and  Dr Verrier  for providing MVA.
Histological Evaluation Skin samples embedded in paraffin were sliced into serial 4-µm sections. Dermal thickness at the injection site was assessed by performing a May-Grünwald-Giemsa (MGG) staining and measuring the distance between the epidermal-dermal junction and the dermal-subcutaneous fat junction at a 40-fold magnification using the ImageJ morphometic software (U. S. National Institute of Health)  (22). Ten random measurements per section were performed by two blinded investigators and averaged for each section. Collagen deposition in the skin was evaluated by performing a picrosirius-red staining and delineating the stained area using a color deconvolution method  (23). This allowed a precise quantification of the total area occupied by collagen deposits in each section. Expression of α-smooth muscle actin (α-SMA) in the skin was assessed by immunofluorescence with a specific anti-α-SMA antibody (clone 1A4, cat.
Flow Cytometry Immediately after collection, spleen cells were counted using an automated method (Flow-Count Fluorospheres, cat. #7547053, Beckman Coulter); and their viability was assessed with propidium iodide staining. Approximately 1 million spleen cells were incubated with mouse anti-Fc receptor antibody (FcBlock, clone 2. 4G2; cat. #553142, BD Biosciences) for 15 min at 4°C protected from light to limit non-specific antibody binding. They were next incubated with different antibody mixes for membrane staining (Table  S2  in Supplementary Material) for 20 min at 4°C protected from light. Data were then acquired on a 3-laser cytometer (Navios, Beckman Coulter) and analyzed with a dedicated software (Kaluza, Beckman Coulter).
Splenic B Cell Production of Pro-inflammatory Cytokines Is Increased in HOCl Mice Based on data from a preliminary work (not shown), we selected two candidate proteins, IL-6 and CCL3, to assess the proinflammatory properties of B cells in the HOCl model. First we measured IL-6 and CCL3 mRNA levels in splenic B cells ex vivo (just after collection and sorting). IL-6 mRNA levels did not differ at day 21 (p = 0. 83); but there was a trend for a significant increase in the HOCl group at day 42 (p = 0. 06) (Figure  9A ). CCL3 production was significantly higher in HOCl mice at both time points (p = 0. 02 in both cases) (Figure  10A ). As to further explore these anomalies, we then studied the secretion of IL-6 and CCL3 in splenic B cells cultured with various stimulation conditions. Without immunostimulation, there was only negligible basal secretion of both cytokines at both time points.
Flow Cytometric Analysis. Immediately after the liver biopsy procedure, cells were recovered by mechanical disruption and stained for flow cytometric analysis as described previously  [7]. Similarly, peripheral blood cells were immunostained. Live/dead cells were discriminated by a Zombie UV™ Fixable Viability Kit. The following antibodies were used for surface staining: CD45 (APC/Cy7, Clone HI30, Bio-Legend), CD3 (PerCP/Cy5. 5, Clone UCHT1, BioLegend), and CD56 (APC, Clone HCD56, BioLegend). Surface staining of CD107a (Pacific Blue, LAMP-1, Clone H4A3, 0. 25 μg/sample) was used to study degranulation activity  [8] [9] [10] [11] [12] [13]. Data were acquired on BD-LSRII flow cytometer (BD Biosciences), collected with BD FACSDiva 6. 3. 1 software, and analyzed using FCS Express V3 and V6 software.
2. 5. Measurements of Hormone Levels. Levels of estradiol and testosterone were measured in serum by commercially available ELISA kits (Abcam, UK), according to manufacturer's protocols. 2. 6. Statistical Methods. Analyses were performed using the statistical software GraphPad Prism 6 (GraphPad Software, CA, USA). Gaussian distribution was tested by the D'Agostino-Pearson omnibus normality test. The t-test was used in the case of normal distribution of data and the nonparametric Mann-Whitney test in the case of nonnormality. The Wilcoxon matched-pairs signed-rank test was used to test differences between K562 nonstimulated and K562 stimulated cells. Pearson's correlation coefficients were used for the linear relationship between two variables.
Acknowledgments The authors would like to thank the patients enrolled in this study for their participation. The authors are grateful to  Caroline Aspord  for scientific discussion and  Emilie Fugier  for the technical assistance. This work was supported by grants from the  Institut National de la Santé et de la Recherche Médicale (INSERM)  and the  Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS). Zuzana Macek Jilkova  was supported by 2014-1  ANRS  fellowship.
In this case, high viral doses and a short time analysis of infected cells post challenge were used to appreciate in as much as possible the antiviral effects on a single cycle basis (Fig  7C ). Under these conditions and as expected from data in the field, expression of IFITM3 was associated to a statistically significant protection of target cells (from 1. 3 to 4. 3 fold). Very variable inhibition rates have been reported for different viruses across different studies, in some instances higher than what we describe here. We believe these differences are mainly due to the heterogeneity of the experimental systems used (cell types, IFITM expression levels, use of pseudovirions versus replication-competent viruses, time of analysis, etc). Finally, the effects played by IFITM3 in the production of infectious virions was assessed by harvesting cell free supernatants at late time points during spreading infections.
Given their high identity, the antiviral effects of IFITM2 and 3 are presented together, separately from those of IFITM1. Variations in the magnitude of the antiviral effects reported in the different studies have not been taken into account here, as they are likely influenced by the specific experimental conditions used, so that the effects of IFITMs on viral infectivity are presented as negative, absent (none), or controversial, even when a single conflicting report exists. When data in the literature was not directly comparable to ours (i. e. the same virus was not used), data was compared to its closest relative, marked in italicus. The effects of the expression of IFITMs in target cells against AAV and MeV were measured in this study and are presented in Supplementary S6 members, our results indicate that even the most internally distributed IFITM members (IFITM2 and 3) are clearly present at the plasma membrane of non-permeabilized cells.
Acknowledgments We are indebted to  Steve Goff  ( Columbia University, New York, USA ),  Francois-Loic Cosset  ( CIRI, Lyon, France ) and  Gilles Querat  ( Faculty of Medecine, Marseille, France ) for sharing MPMV-GFP,  HCV E1/E2  and WNV-GFP coding plasmids, respectively; to  Philippe Despres  ( University of Reunion Island, La Reunion, France ),  Jane McKeating  ( University of Birmingham, UK ) and the  Armed Forces Biomedical Research Institute , ( IRBA, France ) for providing anti-E, anti- E1/2  and anti-Dugbe antibodies, respectively; to  Marie Flamand  ( Pasteur Institute ) and  Richard Elliott  ( CVR-Glascow, UK ) for the RVFV anti-Gn, -N and -NSs antibodies, respectively; to  Yusuke Yanagi  ( Kyushu University, Fukuoka, Japan ) for providing Vero-hSLAM cells and to  Francis V. Chisari  for the subclone Huh-7.
Work in the laboratory of AC is supported by grants from  Sidaction , the  ANRS ,  Finovi , as well as from an internal grant from the  ENS-L. Work in the laboratory of FA  was partly funded by the  Ecole Pratique des Hautes Etudes , the  Institut National de la Recherche Agronomique , the  University of Lyon 1. Work in the laboratory of VV  was supported by in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
, among which those infecting the African great apes  (Liu et al. , 2010; Prugnolle et al. , 2010; Rayner, Liu, Peeters, Sharp, & Hahn, 2011). Recently, we reported the results of a longitudinal survey carried out in the rainforest of Gabon with the aim of identifying mosquitoes involved in the transmission of great ape malaria parasites  (Makanga et al. , 2016) , as well as of other haemosporidians infecting wildlife  (Boundenga et al. , 2016). During this survey, more than 2,000 individual anophelines were collected, among which only seven were engorged with blood, and 74 were infected with haemosporidian parasites. Here, we used this dataset to gain insights about mosquito trophic behavior, as a proof of concept of such indirect approach. Specifically, we first analyzed the origin of the blood meals and then inferred the blood-feeding behavior of unfed mosquitoes from the haemosporidians they were carrying.
| Blood meal analysis Host DNA was extracted from the blood contained in female mosquito guts using the Qiagen DNeasy Blood and Tissue kit  (Makanga et al. , 2016)   et al. , 2008) , 1 μL of 10 μmol/L dNTPs, 0. 3 μL of DNA polymerase (Qiagen, Germany) and 3 μL of template DNA using a GeneAmp 9700 thermal Cycler (Applied Biosystems, USA) under the following cycling conditions: 95°C for 1 min; 35 cycles at 95°C for 30 s, 52°C for 50 s, 72°C for 1 min, and final extension at 72°C for 5 min. PCR-amplified products (10 μL) were run on 1. 5% agarose gels in 1× TBE buffer for quality control and then sent to Beckman Coulter Genomics (France) for sequencing both strands after purification. Nucleotide sequences were edited and aligned using BioEdit 7. 0. 9. 0  (Hall, 1999)  and compared with homologous host sequences contained in GenBank using the basic local alignment search tool (BLAST; http://www.
) originated from forest ungulates belonging to the families of the Bovidae and Tragulidae: Cephalophus ogilbyi (Ogilby's duiker, recovered from An. gabonensis), Cephalophus callipygus (Peters's duiker, recovered from An. obscurus), Cephalophus sylvicultor (yellow-backed duiker, recovered from An. moucheti), Tragelaphus spekii (sitatunga, recovered from An. moucheti), Syncerus caffer (African buffalo, recovered from An. moucheti and An. marshallii), and Hyemoschus aquaticus (water chevrotain, recovered from F I G U R E 1 Phylogenetic position of the Cyt-b sequences amplified from the blood meal of field-collected anopheline mosquitoes (in red: the name is composed from the mosquito species it was recovered and the abbreviation of the collection site, LOP, Lopé National Park; LEK, La Lékédi game reserve) relative to reference sequences for different host species (in black; GenBank sequence number and name of the vertebrate host).
ACKNOWLEDGMENTS We thank the  Agence Nationale des Parcs Nationaux (ANPN)  and the  Centre National de la Recherche Scientifique et Technologique of Gabon (CENAREST)  that authorized this study and facilitated access to the  Lopé National Park , the  Société d'Exploitation du Parc de la Lékédi  for its support in the park of  La Lékédi. This work was funded by the  Institut de Recherche pour le Développement (Laboratoire Mixte International ZOFAC) , the  Centre National de la Recherche Scientifique ,  Centre International de Recherches Médicales de Franceville , as well as the  Agence Nationale de la Recherche (ANR) programme Jeunes Chercheuses Jeunes Chercheurs (JCJC) Sciences de la Vie, de la Santé  et des Ecosystèmes 7-2012 project  ORIGIN  ( ANR JCJC SVSE 7-2012 ORIGIN ).
Whether this sex bias was due to estrogens was not addressed specifically, but it was independent from Irf-4 expression, in agreement with the currently accepted notion that CD103 + cDCs in the skin belong to the Batf-3-dependent cDC1 subset. By contrast, the Irf-4-dependent CD11b + cDC subsets showed no such sex bias  (124). Thus, despite strong evidence that E2-ERα-signaling strongly regulates Irf-4-dependent cDC subsets in the in vitro Csf-2 differentiation model, it is still unclear how this relates to particular cDC subsets found in lymphoid or non-lymphoid tissues in vivo, at the steady state, or during inflammation. Our search of the ImmGen database at http://www. immgen. org  (128)  showed that lung CD11b + CD103 neg DCs display the highest levels of Esr1 expression among DC subsets.
ACKNOwLeDGMeNTS This work was supported by grants from  Arthritis Fondation Courtin, Fondation ARC pour la Recherche sur le Cancer ,  Fondation pour la Recherche Médicale  ( DEQ2000329169 ),  Conseil Régional Midi-Pyrénées , and the  French National Agency for Research on AIDS and Viral Hepatitis (ANRS). SL has been supported by fellowships from  Association pour la Recherche sur la Sclérose en Plaques (ARSEP). CS is supported by fellowship and grant from the  National Health and Medical Research Council (NHMCR ,  APP1123000  and  APP1098832 ). We wish to thank  Dr. JE Méjia  for critical readings of the manuscript.
As shown in Fig. 1 , in BALB/c mice the bioluminescence signal increased and peaked at approximately 20 min after luciferin injection. We decided to measure the bioluminescence signal for all subsequent experiments 18 min after luciferin injection, when the bioluminescence signal was shown to be high and the exposure time was short. In addition, the optimal settings for the IVIS machine for all drug testing studies was examined through iterative testing, and the most effective settings were found to be medium binning and automatic exposure. In GSH, the signal continued to increase over time and reached a plateau approximately 30 min after luciferin injection (data not shown), but for the same reasons mentioned above, we decided to measure the bioluminescence signal 20 min after luciferin injection with settings of medium binning and a 5-min exposure time.
Dark crusts started to appear on the surface of Leishmania lesions at approximately 18 to 25 days postinfection, and this crust could easily quench the bioluminescence signal and thus attenuate the bioluminescence measured. As shown in Fig. 3 , when the dark crust that covered the lesion was removed, the bioluminescence signal increased significantly (P Ͻ 0. 05). Moreover, the accumulation of necrotic tissue at the site of infection might further reduce the bioluminescence signal. For this reason, the bioluminescence signal data observed for each animal were collected and followed as a means for evaluating the presence (or lack thereof) of parasites at the infection site, but the bioluminescence signal was not used as an experimental endpoint in the lesion cure models.
There was a strong correlation (R 2 ϭ 0. 80) between suppression of the bioluminescence signal on the first day after the end of treatment and suppression of the lesion size in late-stage CL disease in BALB/c mice. These data support our hypothesis that a lesion suppression assay conducted with in vivo imaging technology is capable of predicting whether a CL lesion will actually develop and, if it does, what the approximate mean lesion size in the treated group will be. Assessment of efficacy of treatment with topical antileishmanial creams with in vivo imaging technology. We utilized the in vivo imaging technology to assess the efficacy of a topical antileishmanial investigational cream (WR279396, which is a combination of paromomycin and gentamicin) and a cream with paromomycin only, which is currently being tested in humans under investigational new drug application IND 50098.
p. ) into BALB/c mice and GSH at a concentration of 200 mg/kg at 18 min before bioluminescence analysis. Animals were anesthetized in a 2. 5% isoflurane atmosphere (MWI Veterinary Supply, Harrisburg, PA) for 7 min and maintained in the imaging chamber for analysis. Emitted photons were collected by automatic acquisition with a charge-coupled-device (CCD) camera (PerkinElmer IVIS Spectrum in vivo imaging system) using the medium-resolution (medium-binning) mode. Analysis was performed after a region of interest (ROI) that delimited the surface of the affected area was defined. The total photon emission from the infected area at the base of the tail was quantified with Living Image software (Xenogen Corporation, Alameda, CA), and results were expressed in numbers of photons per second. Establishment of a first-tier Leishmania lesion suppression screening model using in vivo imaging in BALB/c mice infected with luciferase-expressing L.