dataesr/scientific-paragraphs-categorization huggingface dataset:
1b ), which suggests preservation of protein function. As the model 4zi5 is also annotated as a phosphotriesterase in PDB, we tested this activity on LmjF. 36. 6540. Supplemental Fig. S1  shows that no phosphotriesterase activity could be detected for LmjF. 36. 6540. In the TriTrypDB database, this protein is annotated as similar to the endo-1-like protein (http://tritrypdb. org/tritrypdb/app/record/ gene/LmjF. 36. 6540). However, when having a more detailed look at the surface charges, no positive patch that would bind DNA was identified. On the contrary, the surface of LmjF. 36. 6540 is generally negative, especially where the catalytic triad is localized (Fig. 1c ). When analyzed with the PsortII prediction software (https:// psort. hgc. jp/form2. html), a mitochondrial localization is predicted at 39.
36. 6540. a Alignment of the LmjF. 36. 6540 protein sequence and the PDB ID 4zi5, which is the crystal structure of dienelactone hydrolase-like promiscuous2 phospotriesterase p91 from metagenomic libraries, as done with the software Phyre2 (www. sbg. bio. ic. ac. uk/phyre2). The red stars indicate the three catalytic amino acids: C130, H204 and D175. b Tertiary structure of LmjF. 36. 6540 done with the UCSF Chimera software from the structural model from Phyre2. The catalytic triad is indicated in green. c LmjF. 36. 6540 electrostatic potential visualization: red for negative, white for neutral and blue for positive potentials (UCSF Chimera software, coulombic surface coloring). The catalytic triad is circled in green, highlighting the negative potential of the surface near the triad. d Alignment of the amino-acid sequences of the LmjF.
Structural analysis of LmjF. 36. 6540 and amino-acid sequence alignment The three-dimensional structure of LmjF. 36. 6540 was obtained using the software Phyre2 (www. sbg. bio. ic. ac. uk/ phyre2). With this structure, the electrostatic potential was obtained using the Coulombic surface coloring option from UCSF Chimera software  28. The amino-acid sequences of the different Leishmania species were.
Calcein and PI labeling Cells were washed once in PBS and resuspended in 1 mL of calcein (LIVE/DEAD® Viability/Cytotoxicity Kit for mammalian cells, Molecular Probes, OR, USA) diluted 1/80 in DMSO and 5 µL PI at 0. 5 mg/mL. The mixed sample was then incubated for 15-20 min at room temperature and protected from light. The cells were analyzed by flow cytometry using 488 nm excitation and measuring green fluorescence emission for calcein (530/30 bandpass) and red fluorescence emission for PI (610/20 bandpass) on the BD LSRFortessa™ cell analyzer. Data were exported and analyzed with Flowjo software for evaluation of the percentage of calcein-and PI-positive cells.
Acknowledgements We want to thank  Lucile Pinault  ( Aix-Marseille University ) for purification of the LmjF. 36. 6540 protein,  Eva Gluenz  ( University of Oxford ) for the Cas9/T7 L. major expressing strain and for the pPLOT and pT plasmids for CRISPR/Cas9 constructions, as well as  Patrick Bastien , from the  University of Montpellier , for the pTH6nGFPc expression vector and the  CNR Leishmania (Montpellier, France)  for the L. major strain. We also thank  Eric Chabrière  ( Aix-Marseille University ) for discussing protein structure and function with us. This study was supported by the  Institut Hospitalo-Universitaire (IHU) Méditerranée Infection , the  National Research Agency  under the program « Investissements d'avenir », reference  ANR-10-IAHU-03 , the  Région Provence Alpes Côte d'Azur and European funding FEDER PRIMI.
Introduction: Endovascular therapy has been shown to be an effective and safe treatment for tandem occlusion. The endovascular therapeutic strategies for tandem occlusions strokes have not been adequately evaluated and the best approach is still controversial. The TITAN (Thrombectomy in TANdem occlusions) registry was a result of a collaborative effort to identify the best therapeutic approach for acute ischemic stroke due to tandem lesion. In this review, we aim to summarize the main findings of the TITAN study and discuss the challenges of treatment for tandem occlusion in the era of endovascular thrombectomy. Methods: A review of the data from the multicenter international observational and non-randomized TITAN registry was performed. The TITAN registry included acute ischemic stroke patients with tandem lesions (proximal intracranial occlusion and cervical carotid artery occlusion or stenosis>90%) who were treated with thrombectomy with or without carotid artery stenting.
The TITAN Collaboration The TITAN (Thrombectomy In TANdem lesions) international collaboration pooled individual data of nonrandomized thrombectomy databases from 18 comprehensive stroke centers for all consecutive anterior circulation tandem patients who underwent emergent thrombectomy between January 2012 and September 2016. Patients were included if they presented with acute ischemic stroke due to anterior circulation tandem occlusion and were treated with modern endovascular devices such as second-generation stent retriever and/or contact aspiration. Tandem lesion was defined as a proximal intracranial occlusion (distal ICA, and/or M1 and/or M2 segment of the middle cerebral artery) and an extracranial ICA lesion (complete occlusion or stenosis ≥90% North American Symptomatic Carotid Endarterectomy Trial).
Treatment of the extracranial ICA lesion was left at the discretion of the operators. Four therapeutic strategies for the cervical steno-occlusive lesion were possible: (1) acute stenting with antithrombotic agents, (2) acute stenting without antithrombotic agents, (3) acute balloon angioplasty without stenting, and (4) no treatment. Intravenous thrombolysis was administered for eligible patients according to the international guidelines. Intravenous sedation and general anesthesia were permitted. All patients included had a computed tomography or magnetic resonance imaging at 24 h after treatment onset to assess for hemorrhagic complications. The local ethics committees approved the use of patient data for the retrospective analysis and waived the need for patient consent. All data were retrospectively collected and scored by one neuro-interventionist in each center.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/ licenses/by/4. 0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. (Anonymous, 2018). Only in the Indian Ocean the stock of bigeye tuna is estimated to be in good condition  (International Seafood Sustainability Foundation, ISSF, 2017). Stock assessment requires a substantial amount of information. Data on retained catch, discards, catch per unit of effort, and size compositions of the catches from different fishery are typically used. Several assumptions regarding processes such as growth, recruitment, movement, natural mortality, and fishing mortality, are also done. The interpretations of stock status are strongly dependent on those assumptions.
Data collection The cruise took place in May 2014 in the central Pacific Ocean aboard the Albatun 3, a 115 m and 4406 GT Spanish-flagged purse-seiner. The cruise started in Christmas Island (Kiribati) on 3rd May and ended in Tarawa Island (Kiribati) on 31st May. Meteorological and oceanographic information was obtained from the CLS (Collecte Localisation Satellites, France, https:// www. cls. fr). During the selected sets the conditions were 7-10 knot of wind (Beaufort 3) and 1-1. 5 m of swell. Acoustic data were registered during the purse-seine sets at 20 different FADs, followed by intensive spill sampling  (Lawson, 2009)  to compare acoustic data and species composition caught. The strategy to collect the data from the purse-seiner is thoroughly detailed in  Boyra et al. (2018). Here, in this second work, in contrast to the previous one, no recorded sonar data were available, so we only used echosounder data.
Catch data collection Purse-seine sets, performed with a 1800 m length Â 310 m height gear, were followed by intensive sampling of the catch (between 1 and 2 tonnes per set) once the aggregation was lifted on-board. Fish samples were selected randomly to avoid bias. Species were identified and each fish in the sample measured to the nearest centimetre on flat measuring boards. The weights of sampled individuals were estimated using length-weight relations available for each species  (Parks et al. , 1982; Caveriviere, unpublished data). These proportions by weight were then extrapolated to the total tonnage of each set, as estimated by the fishing master. The sets with more than 90% in weight (about >75%) of bigeye (Table  2 ) were selected for acoustic analysis to obtain TS-length relationship and acoustic frequency response.
Data analysis Acoustic data were processed from the beginning of the set until the moment in which the net was visible in the echogram. To reduce echoes from bycatch fish species, S V and TS data were excluded if shallower than 25 m  (Muir et al. , 2012; Forget et al. , 2015). Then, the TS echograms at each frequency were processed using a single target detection algorithm  (Simrad, 1996; Soule et al. , 1997)  with the following settings: minimum threshold ¼ À80 dB; normalized pulse durations ¼ 0. 9 to 1. 5; maximum off-axis angles ¼ 3 ; and maximum standard deviations of phase ¼ 0. 6. A series of target selection filters (a school masking, a fish tracking, and a high-density filter) was applied to retain single targets of tuna and remove the echoes attributed to plankton and micronekton. The single target detection algorithm, the school processing, and the fish tracking were applied using Echoview (Myriax Inc.
Acknowledgements We thank the following organizations and people for their support of this work: the governments of Kiribati, Tuvalu, and Tokelau, which permitted this research in their EEZs; Albacora for allowing this work aboard F/V ALBATUN TRES;  Fishing Master Euken Mujika ; the captain and crew; the divers and scientists  J. Filmalter  and  F. Forget  are thanked for invaluable insight about fish behaviour, vertical stratification, and non-target species composition at FADs. Simrad is thanked for technical assistance during this work. Sonia Sanchez  and  Andres Uriarte  are thanked for help concerning mixtures of Gaussian distributions. We thank two anonymous reviewers as well as both editors  Richard O'Driscoll  and  Olav Rune Godø  for careful and constructive criticism of the manuscript.
Results Phylogenomic relationships of lacertid lizards. The phylogenomic analyses reconstructed the evolutionary relationships among the main groups of lacertid lizards with high support. Concordant results were obtained from analyses of two largely independent, newly acquired datasets (Fig. 1 ): (i) 6269 protein-coding nuclear loci for 21 lacertid species obtained by adding novel RNA sequencing (RNAseq) data to a previously established set of vertebrate loci  29  , and (ii) 324 anonymous nuclear loci for 65 species obtained by anchored hybrid enrichment sequencing (AHE)  30. Importantly, partitioned maximum likelihood (ML) concatenation and coalescent species tree analyses, performed separately on each dataset, recovered largely congruent tree topologies (Fig. 1 , Supplementary Fig. 2S ).
6  and 7 ). Gene jackknifing thus indicated these clades were not strongly supported by the data. However, their recovery by both AHE and RNAseq analysis, and partly by both concatenated and summary coalescent approaches, suggests they might correctly reflect evolutionary relationships. To increase species-level representation, we built a large-scale lacertid phylogenetic tree by combining the RNAseq and AHE datasets with DNA sequences of four mitochondrial and one nuclear loci traditionally used in lacertid phylogenetics, selected to maximize taxon coverage. The new dataset, totaling 11,175,421 aligned nucleotide positions (6598 loci) for 262 species (see Supplementary Table  10  for further alignment details and amount of missing data) was analyzed by partitioned ML. Based on a newly compiled set of 89 morphological characters that were in part obtained via newly generated CT-scans, we estimated the phylogenetic position of seven fossil lacertid taxa and subsequently time-calibrated this 262-species tree (Supplementary Figs.
1a ). We then calculated the same regression for each of the gene trees deriving from those 5878 protein-coding nuclear loci in the RNAseq dataset for which the outgroup was available. In 5728 genes the regression slope was positive (linear regression, statistically significant at P < 0. 05 in 3499 genes), in 150 genes it was negative (significant in only seven genes). In gene trees reconstructed from the respective amino acid sequences, the slope was positive in 4745 (significant in 1387) and negative in 1132 (significant in 26). None of the seven genes with deviant signal at the nucleotide level was under selection (Codon-based Z test of selection of overall averages; non-neutrality rejected at P < 0. 0001), and visual inspection of the alignments of these genes did not reveal any amino acid substitutions common to unrelated species from cold or hot environments, respectively.
In our study, Podarcis likewise was among the taxa with relatively short root-to-tip paths. We hypothesize that this condition is derived, and indicative of a genome-wide slowdown of substitution rates in those lacertids that adapted to cooler conditions, rather than an acceleration in heat-adapted species, which contrasts with previous findings in a cold-adapted agamid lizard that has accelerated substitution rates in several genes  49. Taking advantage of our phylotranscriptomic dataset, we verified that the positive correlation between environmental temperature and substitution rates affects the vast majority of coding genes across the genome, with only very few genes showing an inverse relationship (i. e. , accelerated rates in cool environments; Fig. 2e ). This pattern most likely can be explained by an influence of metabolic rate on mutation rate  47  , and we did not find any indication that deviations from the overall pattern were caused by selection.
non-coding loci warrant further study. In comparison with the very clear temperature-related patterns encountered in our dataset, the signal of humidity regimes appeared weaker. Precipitation-related variables usually played a secondary role predicting physiological and genomic traits or range sizes, and we found that IWL was phylogenetically less conserved than T pref (as indicated by the absence of a significant phylogenetic signal in IWL), despite IWL being correlated to climate. This may indicate a stronger selection pressure on and faster adaptation of this key physiological trait, which might be less efficiently buffered by behavior than thermal preferences. This hypothesis would predict that intraspecific local adaptation of widespread lacertids should be more strongly reflected in variation of IWL than T pref , which could be easily tested in future meta-analyses.
Despite their low T pref, they will rarely be able to behave as full thermoconformers in temperate environments. This could explain declines detected in species such as Algyroides marchi and Podarcis carbonelli  58. In the viviparous populations of Z. vivipara, the species with highest IWL in our dataset, we speculate that this handicap could be exacerbated in gravid females as these require optimal thermoregulation to ensure embryonal development for a longer period of time than oviparous species. Many cold-adapted species furthermore are restricted to very small ranges with an associated increased extinction risk, as revealed by the overall correlation of range size to temperature we observed. Hence, we hypothesize that not only tropical lizards, but also some lacertids from mesic and temperate zones might be "toast" in the face of climate change  59  , although they are able to cope with substantial annual and diurnal variation in temperature and humidity, and may not operate near their critical thermal safety margins just yet.
Methods Phylogenomics. We assembled two main datasets (AHE and RNAseq) to resolve lacertid phylogeny and combined these with five gene fragments commonly used in lacertid phylogenetics. The amphisbaenian Blanus, a representative of the sister group of lacertids  60  was used as outgroup. AHE sequencing followed established methods for squamates  30, 61. For RNAseq, RNA was trizol-extracted from pooled samples of different organs (skin, muscle, and liver of single individuals per species). Libraries were prepared following the Illumina TruSeq mRNA protocol, and sequenced on an Illumina NextSeq platform. After read pre-processing, transcriptomes were assembled de novo with Trinity v. 2. 1. 0 (ref. 62 ). Ortholog sequences were selected, translated to amino acids and aligned to a previously compiled set of markers across vertebrates  29  using the software Forty-Two (https:// bitbucket.
org/dbaurain/42/). Sequences from non-vertebrate sources, cross-contaminations, misaligned and possibly paralogous sequences were removed  29  (Supplementary Methods) and nucleotide sequences for the retained amino acid alignments recovered from the original assemblies. A third dataset was compiled with sequences from previous studies for the nuclear proto-oncogene mos gene (cmos) and the mitochondrial genes for 12S and 16S rRNA, Cytochrome b, and NADH-dehydrogenase subunit 4. For those species included in the phylogenomic dataset we assembled full mitochondrial genomes, and extracted the four mitochondrial target genes. Phylogenetic analyses. Maximum likelihood trees were inferred separately for the AHE and RNAseq datasets using IQTREE v. 1. 5. 4 (ref. 63 ). Best-fitting partitioning schemes and substitution models were selected based on the Akaike Information Criterion (AIC) using the heuristic algorithms implemented in IQTREE and branch support was assessed by 1000 replicates of ultrafast bootstrapping.
For computational feasibility, the combined dataset was analyzed using the best-fit partitions previously selected for the three datasets and best-fit models were selected among JC, HKY, or GTR models, with or without gamma parameter, and assuming edge-proportional partitions ("-spp" option). For the combined dataset containing AHE, RNAseq and the five additional gene fragments, the ML tree was estimated as above except for the constraint to satisfy the topologies recovered by AHE and RNAseq ML trees. For the AHE and RNAseq datasets, we estimated summary coalescent species trees under the multi-species coalescent with ASTRAL II  64  with node support measured by multilocus bootstrapping with gene and site resampling  64. Single-locus trees were first estimated under the best-fitting model and 1000 replicates of ultrafast bootstrapping.
Gene jackknife analyses  31  were performed to more stringently test tree topologies and understand the amount of data required to recover each bipartition with confidence (>75 GJP). We generated 100 alignment replicates by randomly sampling loci, without replacement, to ca. 10K, 100K, 1000K, and 10,000K nucleotide positions (RNAseq), or 5K, 10K, 50K, 100K, and 500K nucleotide positions (AHE). Each replicate was analyzed by locus-wise partitioned ML and gene jackknife proportions were estimated as the number of times a given bipartition is recovered per replicate length. Phylogenetic placement of fossils and molecular dating. To generate a lacertid timetree based on phylogenetically tested fossil calibrations, we compiled a morphological dataset of 89 characters, based on published data  14, 19  and novel microCT scans for 250 specimens of 82 lacertid species of 36 genera.
Added to this were data from nine fossil taxa selected according to fossil completeness and stratigraphic reliability (see Supplementary Methods). We pruned our molecular tree for those taxa represented by morphological data and used it as topological constraint in a maximum parsimony analysis of the morphological data in TNT 1. 5. 3 (ref. 65 ), using 100 replicates of traditional and "new technology" tree searches. After excluding two fossils that could not be reliably placed due to their low number of scored characters, we obtained 70 (traditional) and 11 (new technology) equally parsimonious trees (tree length: 1166 steps; Consistency Index: 0. 105; Retention Index: 0. 484). The consensus topology obtained was used to define the following fossil calibration points (detailed rationale in Supplementary Methods): (i) Lacertidae, 40.
4 Ma minimum age (oldest record of Plesiolacerta lydekkeri), 150. 0 Ma maximum age. (ii) Lacertinae, minimum 33. 9 Ma (placement of Succinilacerta specimens within Eremiadini), maximum 61. 6 Ma (oldest-known, Paleocene lacertid fossils). (iii) Gallotiinae: minimum 28. 1 Ma (placement of the fossil clade containing Dracaenosaurus, Pseudeumeces, and Janosikia sister to Gallotia), maximum 61. 6 Ma; (iv) Lacerta s. str. : minimum 4. 4. Ma (oldest reliable fossil of the Lacerta agilis lineage), maximum 61. 6 Ma; (v) Acanthodactylus erythrurus -A. lineomaculatus 18 : minimum 0. 8 Ma (oldest record of A. erythrurus), maximum 61. 6 Ma. These calibrations were implemented in a penalized likelihood timetree inference, using TreePL 1. 0 (ref. 66 ) on the full ML phylogram derived from the combined molecular dataset.
We compiled a curated dataset of georeferenced data points for lacertid lizards by combining (i) data from the Global Biodiversity Information Facility (www. gbif. org), (ii) our own published and unpublished datasets, and (iii) literature data. To obtain an approximation of bioclimatic conditions characterizing the overall range of species, we extracted 29 bioclimatic variables (http://www. worldclim. org) at 30 arc seconds of spatial resolution  33. We calculated yearly hours above 30 °C at 1 cm above the ground, rock surface, and at full sun exposure from the Microclim dataset  35  at a spatial resolution of ~18 × 18 km, as well as yearly hours >4 °C and with solar radiation of >100 W/m 2. This computation is conceptually similar to the one used to predict the observed extinctions of lizards at global scales  16  , differing slightly in y and x-variable scales.
To analyze the disparity between T pref and the temperatures a species experiences within its range we extracted from Worldclim the monthly maximal and minimal temperatures (T max , T min ), as an average value for each occurrence record for the years 1950-2000. We then excluded months with T min <5 °C, averaged T max across remaining months for each occurrence record, and subtracted this value from the T pref of the respective species. Comparative and diversification analyses. Bioclimatic and physiological variables were mapped onto the lacertid timetree (pruned for species with missing data for each variable), estimating states in internal nodes by ML, assuming a Brownian model of evolution and interpolating them along branches (function contMap in the R package phytools  69  ). We explored the relationship between IWL, T pref and bioclimate by means of phylogenetic linear and second order polynomial regression models (PRM) with the R package phyloml  70  selecting a fixed-root Ornstein-Uhlenbeck (OU) model based on AIC scores.
Three values (body size, distribution range, and hours >4 °C and >100 W/m 2 ) were log-transformed before analysis. We used Blomberg's K statistic  71  to estimate phylogenetic signal. This was done with the function phylosig in phytools  69  , estimating P-values by 1000 simulations. To visualize trends of T pref and hours >30 °C over time, we estimated these variables for each branch as the average between the two contacting nodes, and averaged the values for all lineages (branches) existing at a certain time. To explore the dynamics of species diversification we fitted 15 alternative models of species diversification to the lacertid phylogeny using the R package RPANDA  39. Of these models six assumed covariation between speciation rates and time, six others assumed covariation between speciation rates and paleotemperature across the Cenozoic and three models assumed constant speciation rates.