dataesr/scientific-paragraphs-categorization huggingface dataset:
Proteomic data analysis Raw data collected during nano-LC-MS/MS analyses were processed and converted into *. mgf peak list format with Proteome Discoverer 1. 4 (Thermo Fisher Scientific). MS/MS data were interpreted using search engine Mascot (version 2. 4. 1, Matrix Science, London, UK) installed on a local server. Searches were performed with a tolerance on mass measurement of 0. 02 Da for precursor and 10 ppm for fragment ions, against a composite target decoy database (189,576 total entries) built with Plasmodium berghei UniProt database (TaxID = 5,823, December 3, 2015, 13,853 entries), Mus musculus UniProt database (TaxID = 10,090, December 3, 2015, 78,986 entries) fused with the sequences of recombinant trypsin and a list of classical contaminants (117 entries). Methionine oxidation and protein N-terminal acetylation were searched as variable modifications, and no enzyme was indicated.
1, 1/300 Biolegend), CD8a APC-Cy7 (53-6. 7, 1/200 BD Pharmingen), or XCR1-PE (REA707, 1/100 Miltenyi). Cells were sorted on a BD AriaSorp (BD Biosciences) with purity routinely higher than 95%. Expression of MHC II was assessed in a separate mix since the anti-I-A b AF700 (M5/114, 1/500 BD Pharmingen) is a blocking antibody. For experiments with Karma mice in which cDC1 are Tomato + , CD11b-PerCP-Cy5 (M1/70, 1/200 BD Pharmingen) was used. All flow cytometry samples were run on a Fortessa (BD Biosciences) and analyzed using FlowJo software.
Acknowledgements  F. L'Faqihi-Olive ,  V. Duplan-Eche ,  A. -L. Iscache , and  P. Menut  for technical assistance at the  CPTP-INSERM U1043  flow cytometry facility,  R. Balouzat  and the zootechnicians at INSERM UMS006-CREFRE mouse facility,  J. F. Franetich ,  M. Tefit , and  T. Houpert  for mosquito breeding,  E. Bassot  and  F. de Giorgi  for technical help, the  Blanchard team  for helpful discussions,  H. Acha-Orbea  for the MutuDC,  M. Rescigno  for the E. coli-OVA,  A. -M. Lennon-Duménil  and  D. Lankar  for the JV2 antibody. This work was supported by  Human Frontier Science Program Organization  ( CDA00047/2011  to NB),  PIA   PARAFRAP Consortium  ( ANR-11-LABX0024  to NB and OS),  PIA ANINFIMIP equipment  ( ANR-11-EQPX-0003  to NB),  Région Occitanie PhD co-funding (MD), "Ministère de l'Education Nationale, de la Recherche et de la Technologie" (AH) ,  Idex Toulouse "Attractivity Chair" Program (NB).
It is also important to note that, on average, over the street network the morning peak of emissions data occurs 1 h later than in Boulevard Alsace-Lorraine. It means that the delay in simulated concentrations is introduced by a transport process (advection in the street network or turbulent exchange with the background atmosphere). In addition to NO 2 concentrations, NO x concentrations (NO 2 equivalent) were measured at the monitoring stations at Boulevard Alsace-Lorraine. The comparison of the measured and simulated concentrations with MU-NICH shows a large underestimation in the NO x concen-Y. Kim et al. :  Multi-scale modeling of urban air pollution (SinG) a FB (fractional bias), NMSE (normal mean square error), MFE (mean fractional error), VG (geometrical mean squared variance), MG (mean geometrical bias), FAC2 (fraction in a factor of 2), and R (correlation coefficient)  (Chang and Hanna, 2004; Yu et al.
Among those, 471 ticks were randomly selected for molecular and proteomic analyses. Tick legs submitted to MALDI-TOF MS revealed a concordant morpho/molecular identification of 99. 6%. The inclusion in our MALDI-TOF MS arthropod database of MS reference spectra from ethanol-preserved tick leg specimens was required to obtain reliable identification. When tested by molecular tools, 76. 6%, 37. 6%, 20. 8% and 1. 1% of the specimens tested were positive for Rickettsia spp. , Coxiella burnetii, Anaplasmataceae and Borrelia spp. , respectively. These results support the fact that MALDI-TOF is a reliable tool for the identification of ticks conserved in alcohol and enhances knowledge about the diversity of tick species and pathogens transmitted by ticks circulating in Mali.
Molecular tools have been used as an alternative to overcome the limitations of morphological identification  [15]. Sequencing of several genes has been used, including ribosomal sub-units (e. g. , 12S, 16S or 18S), the cytochrome c oxidase unit I (COI), or the internal transcribed spacer  [16]. These techniques are generally time-consuming, laborious and can be expensive, preventing their use in large scale studies  [17] [18] [19] [20]. Moreover, the absence of a consensus gene target sequence for tick identification and/or the comprehensiveness of genomic databases are additional factors hampering their use  [16]. Recently an alternative tool based on the analysis of protein profiles resulting from matrixassisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis has been explored to identify arthropods  [21].
MALDI-TOF MS has been used to identify tick species  [22] [23] [24]  and to determine tick infectious status  [25] [26] [27]. However, tick collection usually takes place far from analytical laboratories and therefore requires proper storage of samples. Ticks are generally stored either alive, at -20˚C, or in alcohol. Although alcohol storage is cheaper and easier, especially in African countries, previous studies reported that the use of fresh (i. e. , recently dead) or frozen specimens led to more reproducible and better MS spectra compared to the alcohol preservation mode for ticks  [24]  [28], and also for other arthropod families  [29, 30]. In a recent study, it was demonstrated that long-term tick storage in alcohol altered MS profiles, which did not provide conclusive identification following in-house MS reference spectra database-querying containing MS spectra from counterpart fresh tick species.
Nevertheless, the upgrading of the in-house MS reference spectra database of specimens stored in alcohol allowed correct identification of ticks at the species level, also underlining the reproducibility and specificity of MS profiles for tick specimens stored in alcohol  [31]. The goal of the present work was to determine tick population diversity and associated pathogens from alcohol stored specimens collected on cattle in Mali by using MALDI-TOF MS and molecular approaches with specimens collected in the field. First, optimized sample preparation conditions for ticks stored in ethanol for MALDI-TOF MS analysis were established. Second, based on morphological and molecular identification of ticks, an MS reference spectra database was created and tested blindly using new tick specimens. In addition, tickassociated bacterial pathogens were screened by molecular biology on half-tick body parts and leg MS spectra from ticks mono-infected or not by bacterial pathogenic agents, and they were compared to assess the efficiency of this proteomic tool for classification of ticks according to their infectious status.
Molecular identification of ticks Standard PCR, using an automated DNA thermal cycler amplifying a 405-base pair fragment of the mitochondrial 12S RNA gene (Table  1 ), was used for tick identification to the species level, as described previously  [31]. The 16S RNA gene was used to confirm all Rhipicepalus (Boophilus) microplus identification. DNA from Am. variegatum specimens reared at the laboratory was used as positive control. PCR products of the positive samples were purified and sequenced as described previously  [31]. The sequences were assembled and analyzed using the ChromasPro software (version 1. 34) (Technelysium Pty. Ltd. , Tewantin, Australia), and were then blasted against GenBank (http://blast. ncbi. nlm. nih. gov).
MALDI-TOF MS parameters Protein mass profiles were obtained using a Microflex LT MALDI-TOF mass spectrometer (Bruker Daltonics, Germany) using parameters previously described  [31]. The spectrum profiles obtained were visualized with Flex analysis v. 3. 3 software and exported to ClinProTools software v. 2. 2 and MALDI-Biotyper v. 3. 0. (Bruker Daltonics, Germany) for analysis  [25].
Spectra analysis The reproducibility of spectra was evaluated by analyzing ten Am. variegatum specimens from Kolleper sample preparation protocol as previously described  [29]. The selected protocol was analyzed using an unsupervised statistical test classifying specimens according to MS spectra (i. e. , Principal Component Analysis, PCA test, ClinProTools v2. 2 software). The Composite Correlation Index (CCI) tool (MALDI-Biotyper v3. 0. software, Bruker Daltonics), was used to assess spectra variations within each sample group according to protocol tested, as previously described  [37]. CCI was computed using the standard settings of mass range 3000-12000 Da, resolution 4, 8 intervals and autocorrelation off. Higher the log score values (LSVs) and correlation values (expressed by mean ± standard deviation [SD]) reflect higher reproducibility of MS spectra and were used to determine the best protocol for sample preparation.
Reference database creation Based on the correlation of morphological and molecular results of tick identification, two to five specimens per species were used to assess MS spectra reproducibility from specimens of the same tick species, and the MS spectra specificity from specimens of distinct tick species. These analyses were performed with the average spectral profiles (MSP, Main Spectrum Profile) obtained from the four spots of each individual tick specimen using Flex analysis v. 3. 3 and ClinProTools 2. 2 softwares (Bruker Daltonics). Tick species exhibiting reproducible and specific MS spectra were then included in-house MS spectra reference database. To upgrade the database, MSP reference spectra were created using spectra from at least 2 specimens per species of both genders by the automated function of the MALDI-Biotyper software v3.
Blind tests A blind test was performed with new tick specimens collected in Mali stored in 70% alcohol or frozen. A total of 451 MS spectra from tick legs, including 340 stored in alcohol and 111 frozen specimens were tested successively against the in-house MS reference spectra database (Database 1) and its upgraded version, which includes the 20 MS spectra from specimens of the 6 tick species collected in Mali and alcohol-preserved (Database 2). Among the 451 ticks tested 51 Am. variegatum and 23 Rh (B) microplus were fully engorged. Database 1 was composed of specimens of fresh or frozen arthropods (Table  2 )  [16, 24, 30, 31, 39]. Database 2 includes database 1 plus MS spectra of tick legs from 6 species stored in ethanol from the present study (Tables  3  and 4 ). The reliability of species identification was estimated using the LSVs obtained from the MALDI-Biotyper software v.
Validation of morphological identification by molecular tools on a subgroup of ticks A total of 20 specimens, including 2 to 5 specimens per species and all specimens of Rh (Bo. ) microplus, were randomly selected for molecular analysis. A GenBank query revealed that 12S gene sequences were available for the 6 tick species. BLAST analysis indicated high identity (i. e. , a range from 99% to 100%) of 12S rRNA gene sequences among specimens classified per species according to morphological identification (Table  4 ). BLAST analysis revealed that these 6 tick species and all specimen of Rh (B) microplus had high sequence identity with their respective homolog species available in GenBank (i. e. , range 96. 5% to 100%; Table  4 ).
Fifty-seven ticks, 20. 8% (57/274) were positive in qPCR targeting the 23S rRNA of Anaplasmataceae. Among them, 23S rRNA amplification and sequencing was successful for 50 samples. The BLAST found broad agreement that 43 ticks were positive for E. ruminantium (GenBank accession number NR 077002. 1), 2 ticks were positive for Ehrlichia sp. urmitei TCI148 (GenBank ACCN KT 364334. 1) and 1 tick for Ehrlichia sp. rustica TCI141 (GenBank ACCN KT 364330. 1). A. marginale was detected in 3 ticks and A. sp. ivoriensis TCI50 (GenBank ACCN KT 364336. 1) in 1 specimen (Table  5 ). Borrelia spp. was detected in 1. 1% (3/274) of ticks by qPCR. However, all standard PCR for determination of Borrelia species failed. No Bartonella spp. was detected in the ticks tested.
The first comparison concerned the "de- alcoholization" and "dry" protocols (Fig  2A ). The visual comparison of MS profiles between these two groups using the gel view tool and the superimposition of average MS profiles in each condition using ClinProTools software (Bruker) did not reveal differences in peak position between the two protocols (Fig 3A  and 3B ). This reproducibility of the profiles was analyzed using an unsupervised statistical test classifying specimens according to MS spectra (i. e. , Principal Component Analysis, PCA test, ClinProTools software). The mixing of both groups on the graphical representation confirmed the absence of differences between both groups (Fig 3C ). Thus, the "dry" protocol was preferred compared to the "de-alcoholization" protocol, the latter considered to be more time-consuming and fastidious.
Intra-species reproducibility and inter-species specificity of MS spectra Twenty ticks, including several specimens per species coming from distinct localities, were identified by sequencing 12S tick gene. Their non-infected status was also controlled for the microorganisms tested in the present work by q PCR. These specimens were selected for evaluating intra-species reproducibility and inter-species specificity of MS spectra. Comparison of the MS spectra with Flex analysis software indicated reproducibility of the MS profiles between tick specimens from the same species (Fig  5A ). Moreover, the visual comparison of MS profiles indicated a clear distinction of spectra according to species. To reinforce the specificity of MS profiles according to tick species, MS profiles from these 20 specimens were used to generate a dendrogram and PCA (Fig 5B  and 5C ).
MS reference spectra database upgrading and blind test for tick identification To assess the efficacy of the in-house MS reference spectra database, named database 1 (DB 1) to correctly identify tick specimens preserved in alcohol, half of the MS spectra from ticks included in the present study were randomly selected. Then, MS spectra from 178 specimens including 60 Am. variegatum, 64 Hy. truncatum, 16 Hy. m. rufipes, 26 Rh. (Bo. ) microplus, 7 Rh. e. evertsi and 5 Rh. sanguineus sl were queried against the DB 1 spectra database. The blind test against DB 1 revealed correct identification for some specimens of Hy. truncatum (n = 5) and Hy. m. rufipes (n = 5), with LSVs > 1. 8 (Table  6 ). For the remaining ticks (n = 168), all LSVs were < 1. 8  [24]. Tick MS spectra from 20 specimens, including 6 species identified morphologically and molecularly in this work, were added to DB 1, which was then renamed DB 2 (Table  4 ).
To confirm the morphological identification of tick specimens that were used for creating the MALDI-TOF MS database, sequencing of the 12S rRNA gene was performed. The 12S rRNA gene was chosen to validate identification because this gene is known as a reliable tool for molecular identification of ixodid ticks  [16]. The coverage percentages and identity between the sequences of specimens of the same species were from 99 to 100% for all species of ticks. Percentages of identity and coverage of sequences Am. variegatum, Hy. m. rufipes, Rh. (Bo) microplus, Rh. e. evertsi and Rh. sanguineus sl were 99-100% with sequences of the same species available in GenBank. Interestingly, lower sequence identities (96-97%) of Hy. truncatum compared to the corresponding reference sequence in GenBank were observed.
It could be hypothesized that the sequence differences could correspond to genetic variation within ticks of the same species adapted to different geographic regions of a country or countries, as previously described  [56]. The difference between the sequences of 12S rRNA genes of Hy. truncatum collected in Mali and that available on GenBank tick collected in Zimbabwe  [57]  could explain these genetic variations. In the future, the sequencing of a second gene target, such as 16S or COI, could be performed to further study these variations  [58]. In this study, DNA from Rickettsia spp. was detected in 76. 6% of infected ticks collected from cattle, among which R. africae was found in 87. 6% (184/210). R. africae was detected in 92. 2% of Am. variegatum, a cattle tick found throughout sub-Saharan Africa.
Such high prevalence of R. africae in Am. variegatum has already been reported  [59] [60] [61]. R. africae was also detected in Rhipicephalus spp. and Hyalomma spp. , respectively 7. 9% and 9. 2%. Other recent studies have detected R. africae in other tick genera, including Rhipicephalus and Hyalomma  [59, 62, 63]. R. africae is the etiological agent of African tick-bite fever in humans (ATBF)  [64]. R. aeschlimannii have been observed in Hyalomma spp. , with 9% and 52. 6% respectively in Hy. truncatum and Hy. m. rufipes. These data are comparable with those of previous studies that reported 45% to 55% of Hy. m. rufipes and 6% to 7% of Hy. truncatum were DNA carriers of R. aeschlimannii in Senegal  [63] , and 44% and 11% in Ivory Coast  [59]. The sequences of R. aeschlimannii identified in our work were identical to those of R.
aeschlimannii, previously detected in Hy. truncatum collected in Senegal (GenBank accession number HM050276. 1). R. aeschlimannii is an agent of spotted fever in humans  [64]. R. aeschlimannii is found in sub-Saharan Africa, North Africa, Europe and Asia  [11, 65]. Our results confirm a large prevalence of this pathogen in Mali. For the first time, the presence of R. mongolitimonae was identified in Hy. truncatum from Mali. It had been previously detected in Hy. truncatum from the countries bordering Mali, including Niger  [11]  and Senegal  [63]. R. mongolitimonae 12S sequence of the present study were 99% identical with the same sequence fragment of a strain previously isolated from a patient from Algeria (GenBank DQ097081. 1). Until now, two Borrelia species have been identified in Mali, B.
To avoid bias, we choose to query the MS spectra of 178 specimens of ticks, including 6 species against DB 1 which includes several families of arthropods, including mosquitoes. We constantly improve it with new specimens collected in the field and find it more relevant to carry out a total interrogation without the knowledge without any filter on a specific family. The results of the blind test revealed correct identification in 10 specimens only with high log score values, even though this database contained the same tick species that were also preserved in alcohol. This misidentification could be attributed to several factors: (i) the method used for sample crushing (initially manually, and here an automatic apparatus was used as previously described  [28] , (ii) the difference in storage time (6 months here vs 3 years in the previous study), (iii) the geographical distance (Mali vs.
Ethiopia), which could have consequences on MS spectra profiles, as observed also at the genetic level. This last phenomenon had already been reported in other studies of sand flies  [71] , mosquito immature stages  [46]  and ticks  [31]. Conversely, when database 1 was upgraded with 20 spectra of the six tick species of our study, the blind test of all ticks revealed 95. 60% (325/340) correct identification for tick species stored in alcohol. However, the remaining fifteen ticks (4. 40%) with inconsistent identification between morphological and MALDI-TOF MS tools were subjected to molecular biology to determine the real identification of these specimens. The molecular biology results confirmed those of MALDI-TOF MS for 13 of these specimens. Two Hy. truncatum specimens were misidentified by MALDI-TOF MS.
The current limiting factors of MALDI-TOF MS analysis are the small diversity of tick species included in the MS spectra reference database and the relative elevate cost to acquire the machine. Nevertheless, it high-throughput and large application for microorganisms identification either in research or medical diagnosis, do of this emerging tool a highly competitive method also for medical entomology studies. It is likely that MALDI-TOF MS will realize similar revolution in medical entomology as it was occurred in microbiology. Our results confirm those of previous studies, according to which MALDI-TOF MS could be used for identification of ticks preserved in alcohol, but it requires the creation of a database with specimens stored in the same condition  [31]. In our work, MALDI-TOF MS analysis was not able to differentiate ticks which were infected or not by the bacteria that were screened.
Motor neuron recordings Sharp electrodes were made from thick-walled glass capillary tubes (1. 5 mm OD; Warner Instrument G150F-4) using a Sutter P-97 micropipette puller (Sutter Instrument) and filled with 1 M K-acetate. Then the electrodes were beveled (BV-10 microelectrode Beveler, Sutter Instrument) until the resistance dropped to 25-30 MW. Intracellular recordings of motor neurons were done in the discontinuous current clamp mode (DCC, switching rate 5-8 kHz, output bandwidth 5. 0 KHz) using an Axoclamp 2B intracellular amplifier (Axon Instruments, Burlingame, CA). Data were sampled at 10 KHz. Only motor neurons with a stable resting potential below À60 mV and action potentials of at least 70 mV of amplitude were included in the study. Motor neurons were identified by their location (20 to 200 mm under the ventral surface of the spinal cord), by their distinctive action potential (AP)/afterdepolarization-afterhyperpolarization shape and by orthodromic conduction of action potentials in the corresponding ventral roots (see Figure  3 -figure supplement 1).
Calcium imaging For visualizing activity in spinal interneurons we used crosses of Rosa26-GAG-GCaMP3' and Vglut2-Cre or VIAAT Cre mice. The spinal cords were isolated from acutely or chronically spinal cord transected mice. The cord was transversally cut at the level of S4/Co1 and placed in a chamber mounted on an epifluorescence microscope (Zeiss, Axioscope2) with the dorsal and ventral horns facing the objective (10x or 40x). The cord was illuminated with a 100 W Mercury light source for excitation (excitation filter, 470-490 nm) and visualization (emission filter, 520-560 nm). Activity-dependent changes in fluorescence were detected using a digital CMOS camera (Hamamatsu, Japan) at 10 and 20 frames/s and stored directly on the computer. Changes in fluorescence were analyzed off-line using an image processing software (ImageJ).
, 2008) , the  COPERNICUS program, (Copernicus, 2017) , as well as in many air quality networks. In this paper, the CHIMERE-2017 model version is presented. All new developments made since the CHIMERE-2013 version  (Menut et al. , 2013a)  are presented. This mainly consists in an extension of input databases, model grid management, optimization and chemical mechanism. The changes for the grid management are dedicated to build a CTM able to run over a hemispheric domains as well as for smaller regions anywhere in the world. These developments required important changes in the model, as well as the improvement of many processes already included in the previous version: the Fast-JX module for realistic evaluation of the photolysis rates has been added and allows for the calculation of updated photolysis rates at each physical time step, including the optical effects of clouds and aerosols.