dataesr/scientific-paragraphs-categorization huggingface dataset:
To test if tissue damage accounts for the NADPH oxidase-dependent attraction of neutrophils to the hindbrain ventricle upon C. albicans infection, we performed mock injections of buffer into vehicle (DMSO) or DPI-treated larva and measured neutrophil recruitment. We found that there was a small increase in hindbrain ventricle neutrophils in mock-injected larvae (from 0. 75 to 2 neutrophils), although this was not significantly affected by DPI (2. 05 vs 1. 98) (Fig. S7 ). Thus, in contrast to the NADPH oxidase-dependent phagocyte recruitment to infection, the minor recruitment induced by this injection method is not NADPH oxidase-dependent. Our data demonstrate that NADPH oxidase(s) direct the early immune response to fungal infection in the zebrafish hindbrain ventricle, tissue in the central nervous system.
) or treated the same but not injected; post-injection, fish were incubated in 0. 8% DMSO or 0. 8% DMSO+100 mM DPI and neutrophil numbers were quantified by confocal microscopy at 4 hours post-injection. For a-tocopherol experiments, larvae were immersed in 100 mM a-tocopherol (Sigma-Aldrich, St. Louis MO) in 1% DMSO or 1% DMSO (control) from two hours pre-infection and throughout imaging. Fish were imaged from 3-6 hpi by confocal microscopy as described above. Data on GFP-Lc3 localization from all experiments were pooled and analyzed by Fisher's exact test.
albicans. Further imaging with dihydrorhodamine gave similarly negative results in two independent experiments (data not shown). Scale bars represent 100 mm. One group of fish was imaged from 0 to 9 hpi, while the other was imaged only at 9 hpi. Imaging performed with 543 nm He-Ne laser at 88% power, using a 406 0. 75NA objective, with slices at 1. 5 mm spacing. Pixel dwell time was 4 ms, each image dimension was 102461024, and total number of slices ranged from 32-40, with total active imaging time of 5-7 minutes per stack and 45-63 minutes for each fish total over the course of the experiment. (A) Image panels of a fish imaged from 0 to 9 hpi with florid fungal filamentation. Scale bar = 10 mm. (B) The number of C. albicans cells per fish was quantified at 9 hpi for each imaging group (N = 3) with no statistical significance (p.
Acknowledgments We would like to acknowledge  Alex Hopke ,  Kim lab  members,  Henry  lab members and  Mark Nilan  for technical assistance throughout the project. We thank  C. Henry  and  C. Kim  for comments on the manuscript. We thank  Graham Lieschke  for the Tg(mpeg1:Gal4; UAS:Kaede) line,  Daniel Klionsky  for the Tg(GFP-Lc3) line, and  Steve Renshaw  for the Tg(mpx:GFP i114 ) fish line.
Five microliters of each sample were loaded onto a C 18 precolumn (300 m inner diameter ϫ 5 mm; Dionex) at 20 l/min in 2% ACN and 0. 05% TFA. After 5 min of desalting, the precolumn was switched online with the analytical C 18 column (75 m inner diameter ϫ 15 cm; PepMap C 18 , Dionex) equilibrated in 100% solvent A (5% ACN, 0. 2% formic acid) and 0% solvent B (80% ACN, 0. 2% formic acid). Peptides were eluted by using a 0%-50% gradient of solvent B for 60 min at a flow rate of 300 nl/min. The LTQ-Orbitrap XL was operated in data-dependent acquisition mode with Xcalibur software (version 2. 0 SR2, Thermo Fisher Scientific). Survey scan MS spectra were acquired in the Orbitrap in the 300 -2000 m/z range with the resolution set to a value of 60,000 at m/z 400. Up to five of the most intense multiply charged ions (2 ϩ and 3 ϩ ) per survey scan were selected for collisioninduced dissociation fragmentation, and the resulting fragments were analyzed in the linear trap (LTQ).
Dynamic exclusion was used within 60 s to prevent repetitive selection of the same peptide. Database Search and Data Analysis-Mascot Daemon software (version 2. 3. 2, Matrix Science, London, UK) was used to perform database searches in batch mode with all of the raw files acquired for each sample. To extract peak lists automatically from Xcalibur raw files, the Extract msn. exe macro provided with Xcalibur was used through the Mascot Daemon interface. The following parameters were set for the creation of the peak lists: parent ions in the mass range of 300 -4500, no grouping of MS/MS scans, and no threshold. A peak list was created for each analyzed fraction (i. e. gel slice), and Mascot searches were performed for each fraction. Data were searched against all entries in the International Protein Index human protein database (v3.
86, released September 7, 2011; 91,522 sequences). Cysteine carbamidomethylation was set as a fixed modification; methionine oxidation and protein N-terminal acetylation were set as variable modifications for all Mascot searches. Proteins were digested by trypsin, and two missed trypsin cleavage sites were allowed. The mass tolerances in MS and MS/MS were set at 10 ppm and 0. 6 Da, respectively, and the instrument setting was specified as "ESI-Trap. " To calculate the false discovery rate (FDR), the search was performed using the "decoy" option in Mascot. Mascot results were parsed and quantified with the in-house-developed software Mascot File Parsing and Quantification (MFPaQ), version 4. 0. 0  (24). Peptide identifications extracted from Mascot result files were validated at a final peptide FDR of 1 (at least one peptide with a score of 40, or at least two peptides with a score of 20).
The FDR was calculated at the protein level (FDR ϭ number of validated decoy hits/number of validated target hits ϫ 100). If the same set of peptides belongs to several proteins, the first protein listed is the one that contains the most peptides. Unambiguous protein identification is provided by a proteotypic peptide (i. e. a peptide with a unique amino acid sequence among all proteins). Known contaminants excluded were keratins and trypsin. Label-free Quantification-The quantification of proteins was performed using the label-free module implemented in the MFPaQ v4. 0. 0 software  (25). Briefly, for each sample, the software used the validated identification results and extract ion chromatograms of the identified peptide ions in the corresponding raw nano-LC/MS files, based on their experimentally measured retention time and monoisotopic m/z values.
7% paraformaldehyde, permeabilized, blocked, and incubated for 2 h with rhodamine-conjugated phalloidin (Molecular Bioprobes, Eugene, Oregon, USA) in phosphate-buffered saline (PBS) containing 1% BSA (PBS-BSA). Subsequently, the coverslips were washed with PBS-BSA, air dried, and embedded in Dako Cytomation Fluorescent Mounting Medium. Fluorescence was detected using a Leica microscope (Leitz DMRB; 100ϫ objective). Images were acquired as sets of color images and prepared using Photoshop software. Cell Migration and Invasion Assays-Equal numbers of cells (1 ϫ 10 5 ) in serum-free RPMI were added to the upper compartments of the chamber (ThinCerts ® , 12 wells, 8-m pores (Greiner Bio-One, Frickenhausen, Germany)) and kept in an incubator at 37 °C for 20 h. As a chemoattractant, the lower compartment contained RPMI supplemented with 10% FCS.
The remaining IP fractions were subjected to analytical SDS-PAGE. The gel was cut into slices and subsequently treated with trypsin. Peptides were extracted and analyzed via nano-LC-MS/MS on an LTQ-Orbitrap-XL. The identification of peptides was performed using the Mascot Daemon software for searching databases, combined with a label-free protein quantification analysis with in-house-developed MFPaQ software  (24). Prior to quantification, a list of proteins exhibiting an FDR lower than 1% was automatically validated. Protein quantification was then performed using the listed proteins. Label-free quantification is based on a comparison of the PAI of each protein in two different conditions. The PAI (average of area under the curve) is calculated from the three most intense peptides of each protein.
Acknowledgments-We acknowledge  Dr. Irwin Davidson  for his suggestions of MITF target genes and  Dr. Lionel Larue  for providing melanoma cell lines and for very useful discussions about this project. We also thank  Pamela Houston  for critical reading of the manuscript and  Francoise Viala  and  David Bouyssie  ´for, respectively, iconographic and bioinformatics assistance. * Studies performed in our laboratories were supported by the  University of Toulouse  ( AO CS 2008  to L. N. ) and the  Centre National de la Recherche Scientifique (CNRS) , the  Advanced Technology Institute in Life Sciences  ( ALMA  project to M. E. ), the  Association contre le Cancer  ( ARC 2008-1102  to C. M. ), and the  Radioprotection Committee of EDF  (C. M. ). O. S. and B. M. were supported by grants from the  Agence Nationale de la Recherche  ( ANR Plates -formes technologiques du vivant),  Fondation pour la Recherche Medicale  ( Programme Grands Equipements ), Region Midi-Pyrenees, and  Infrastructures en Biologie Santeet Agronomie (IBISA).
Recombinant clones with multimeric arrays of satellite DNA were sequenced by Macrogen (Korea). Monomers and HORs sequences from M. chitwoodi and M. fallax as well as Box 1-containing sequences from M. incognita sequenced genome were deposited in EMBL databank under Accession Numbers: JX186757-JX186849, JX186850-JX186855, JX186856 -JX186877, JX186878 -JX186996, KC968979 -KC969073.
Sequence Analyses DNA sequence data were compared to the GenBank databases by using the BLAST version 2. 0 server at the National Center for Biotechnology Information. The BLAST servers of M. incognita (http://meloidogyne. toulouse. inra. fr/blast/blast. html) and M. hapla (http://www. pngg. org/cbnp/index. php) genome were used to search for Box 1-containing sequences in the sequenced genomes. Initial sequence manipulations were done by using BioEdit v. 7. 0. 5. 3  [24]. Multiple alignments and pairwise sequence identity of monomers and HOR sequences were extracted from ClustalW Output (version 1. 83)  [25]. Lasergene software package v. 7. 0. 0 (DnaStar) was used in further analyses of repetitive sequences including pairwise alignments, dot plot analyses and PCR primer design. Monomers from cloned multimeric arrays were extracted using Key-String Algorithm (KSA)  [26].
A large number of studies have emphasized the spatial proximity of economic activity and its relation to the spatiality of knowledge creation in various types of connections. Far less attention has been paid to the understanding of the determinants of 'cultural' and geographical proximity in international R&D cooperation projects involving SMEs and the role of the quality of the Regional Innovation System (RIS). Using a database of completed European Cooperative Research projects, we conclude that: 1) technologically more complex projects are more likely to involve 'culturally' and geographically distant partners; 2) RIS related variables determine 'cultural' proximity but not geographical proximity; 3) at first sight surprisingly, international cooperation projects involving the 1st promoters of innovation-led regions (high patent propensity and high human capital levels) are culturally more distant.
Subjects or Participants Using a database of 118 international cooperation projects -'success stories' of completed CRAFT projects -, we aim at providing a contribution which may complement the existing literature on the relation between cooperation technology traits, RIS features and (cultural and geographical) proximity between cooperative participants. Thus, this study seeks to answer the following main questions: 1) What is the effect of technological complexity on the geographical and cultural distance of network participants?; 2) What is the effect of project size on the geographical and cultural distance of network participants?; and 3) What is the effect of the strength of the regional system of innovation on the cultural and geographical distance of network participants? CRAFTs are instruments of cooperative research, specially designed for SMEs.
In this study we analyze a sub-group of CRAFTs, those from the 3rd to 5th FP considered 'successful'. Based on this information, we constructed a database which contains general information on each project, mostly gathered from pdf files that describe the projects, and RIS-related variables (human capital, patent propensity and employment rate) taken from the main regional indicators published by the EUROSAT. Although success criterion is not explicit, some contacts with CRAFT national managers convey the information that 'successful' projects were those which the main performer reckons as well-succeeded, which are in general associated to a new product/service being commercialised or in a nearby market stage. Although the inclusion of non-successful projects could have generated interesting insights, no public information on the former is available.
The two countries with a higher number of participating companies, Germany and France, are also those that participate in a larger number of projects: 64 and 53, respectively. Generally, cooperation between research institutions of the same country is weaker than between same country SMEs. Austria is an exception, with 3 Austrian institutions per project. The 'successful' CRAFT database identifies the main region where each Project is developed. With few exceptions it is the region where the prime SMEs contractor is located. Although it was not possible to identify the region of origin for all the participating SMEs, we analyzed the regional origin of the first promoter in order to identify the regions with a higher 'promoting' ability. The regions with a higher promoting capacity, involved in successful CRAFTs (Table  4 ) are Noroeste (Spain) and Sud-Ouest (France) both with 7 projects each, Vlaams Gewest (Belgium), Baden-Württemberg (Germany) and West-Nederland (the Netherlands), with 6 projects each.
Estimation results The model was estimated using OLS. The number of projects included as valid observation is 114, as no regional data was available for one of the countries (Norway), and for the remaining three projects some variables are missing. Estimation results for the 'cultural' proximity proxy are presented in Table  6  and for the geographical distance proxy in Table  7. In general, all the estimated models present a reasonable fit. In fact, when considering jointly the adjusted R square, F-statistics, and the Durbin Watson, we have sufficient statistical evidence that the models reflect reality quite appropriately. With regard to the factors determining 'cultural' proximity, it is clear cut that regardless of the model specification (I-VI), the technological diversity variable is always highly statistically significant and negative.
Others (e. g. ,  Sonn and Storper 2008)  find that proximity in the creation of economically-useful knowledge appears to be becoming even more important than was previously the case. In the present study, with a view to complementing existing evidence in this field, using new data on successful international formal R&D alliances, we aimed to assess the determinants of 'cultural' proximity and geographical distance, highlighting the role of the quality of the regional innovation system (RIS). More specifically, we assessed the effect of project technological complexity, project size, and the strength of the regional system of innovation on the cultural and geographical proximity of network participants. We conclude that technologically more complex projects are more likely to involve 'culturally' and geographically more distant partners and that the 1st promoter's regional patent propensity and human capital endowments (proxies for RIS strength) determine 'cultural' proximity but not geographical proximity among network participants.
Genome sequencing was performed using the Roche 454 GS-FLX titanium (Beckman Coulter Genomics). The run generated 750,117 reads corresponding to 226 Mb of chromosomal sequence, as strain IP10393 had lost its pYV plasmid upon subcultures. The mean read length was ~300 bp. The data were assembled using Newbler assembler version 2. 3 (Roche) into 101 contigs grouped into 8 scaffolds. Most of the gaps between the contigs were manually closed by Sanger sequencing of PCR products, yielding a final set of 12 contigs with a size ranging from 34,829 bp to 1,531,738 bp (N50 ϭ 870,086 bp). The resulting draft genome had a size of 4,463,212 bp and a GϩC content of 47. 0%, which is similar to that of other Y. enterocolitica genomes  (8) (9) (10) (11). Genome annotation using Rapid Annotation using Subsystem Technology (RAST) (http://rast.
nmpdr. org/) (12) predicted 4,181 coding sequences (CDS), 64 tRNA genes, and 5 rRNA genes. The average GϩC content for each predicted CDS was 48. 1%. Numerous copies of insertion sequences were present: 52 of IS1667, 8 of ISsod5, 7 of IS1668, and 3 of ISPsy4. The known virulence determinants ail, inv, and yst were also present. The availability of this new chromosomal sequence of a Y. enterocolitica 4/O:3 isolate may help in the identification of the core genome of these strains and a variable pool that differentiates subgroups. Nucleotide sequence accession numbers. The IP10393 sequence has been deposited at DDBJ/EMBL/GenBank under the accession numbers CAOV01000001 to CAOV01000012 and Bio-Project accession number PRJNA177695. The version described in this paper is the first version.
Synaptic profiles were then counted in a total of 308 photomicrographs (153 from control and 155 from rora-depleted mice). Synaptic profiles crossing two sides of a picture were excluded, whereas those intersecting the two other sides were included. PF synaptic profiles were identified as presynaptic varicosities containing at least three synaptic vesicles and facing a postsynaptic density, and were easily differentiated from CF profiles that contain a higher density of synaptic vesicles in a darker matrix  (Palay and Chan-Palay, 1974). The length of postsynaptic densities was measured using ImageJ software  (Rasband, 2008). Anterograde tracer labeling. After behavioral testing, eight mutant (Pcp2::Cre ϩ/Ϫ ;Rora fl/fl ) and three control (Pcp2::Cre Ϫ/Ϫ ;Rora fl/fl ) mice received an injection of anterograde tracer into the inferior olive, as previously described  (Sugihara et al.
Synaptic currents were further analyzed using Igor Pro (Wavemetrics) and the NeuroMatic program developed by Jason Rothman (University College London). Amplitudes and rise times for the CF-EPSCs were measured. Several parameters were also evaluated for PF-EPSCs recorded from control and mutant PCs, including the increase in PF-EPSC amplitude with increased stimulus intensity (input-output relationship), and short-term paired-pulse facilitation. After electrophysiological recordings, slices were fixed in 4% paraformaldehyde in PB 0. 1 M and processed for immunohistochemistry. Slices were incubated with streptavidin-Cy3 (1:800, Sigma) for 4 h, and then with anti-ROR␣ overnight to further confirm that the recorded PCs, filled with biocytin, lacked ROR␣. Analysis of PC dendritic trees and spines: image acquisition and morphological analysis.
The biocytin-filled PCs from the electrophysiological study were used for morphological analysis. Image stacks were obtained with a Confocal Laser Scanning Microscope (SP5, Leica) equipped with a 1. 4 NA objective (oil-immersion, 63ϫ, Leica) and with the pinhole aperture set to 1 Airy unit. Images coded in 16 bits depth were acquired in the 570 -620 nm emission range and 2 images were taken and averaged for each z-step. For whole neuron observation, the pixel size was 240 nm and z-step of 1 m was used. Images stacks were deconvolved using a Maximum Likelihood Estimation algorithm performed with Huygens 3. 6 software (Scientific Volume Imaging) with 50 iterations using theoretical PSF. For dendritic spine analysis, the pixel size was set to 60 nm and z-step to 0. 2 m. The images were deconvolved with 100 iterations using an experimental PSF, obtained from images of 170 nm diameter fluorescent latex beads (PS-Speck, Invitrogen)  (Heck et al.
, 2012). For analysis of PC morphology, a 3D model of the dendritic tree was reconstructed using Neuronstudio  (version 9. 92; Rodriguez et al. , 2008)  (http://research. mssm. edu/cnic/tools. html) and saved in swc file format. First, the ImageJ plugin tubeness ( value of 0. 8; http://rsb. info. nih. gov/ij/index. html) was applied to the image stack to reinforce tubular structures (i. e. , dendrites), and the tree was semiautomatically reconstructed with Neuronstudio; then the 3D model obtained was refined on the original image stack. Dendrite branches were labeled according to Strahler order with Neuronstudio. Order 1 corresponds to terminal branches, and the order number increases toward the soma. Quantitative morphological parameters of the whole neuron were extracted using Lmeasure software  (Scorcioni et al.
, 2008)  (http://cng. gmu. edu:8080/ Lm/). Sholl analysis was performed with the plugin Simple Neurite Tracer in Fiji program (http://pacific. mpi-cbg. de). For dendritic spine analysis, segments from the upper part of the dendrites were reconstructed so a total of 150 -200 m dendrite length per neuron was analyzed. Automated spine detection followed by manual correction was performed using Neuronstudio. Spine density is defined as the number of spines for 10 m of dendrite length. Recombinant lentiviral vectors and production. Recombinant lentiviral vectors expressing Cre or GFP under the control of the CMV promoter were used to prepare stocks of LV-CMV-Cre and LV-CMV-GFP viral particles as previously described  (Zennou et al. , 2001). Briefly, HEK 293T cells were transiently cotransfected with the p8.
Using ImageJ software, the number of VGLUT2 puncta directly apposed on the soma or on the stem dendrite (first 20 m) were counted through the stack of images. For the soma, we assigned PCs to three groups: PCs with  (1) 0 -2, (2) 3-6,  and ( 3) Ͼ6 VGLUT2 puncta on their soma. For the stem dendrite, we assigned PCs to four groups as follows: PCs with  (1) 0 -5, (2) 6 -10, (3) 11-15,  and (4) Ͼ16  VGLUT2 puncta on the first 20 m of dendritic shaft. The distribution in the different groups of the PCs transduced with LV-CMV-GFP (2-6 weeks), LV-CMV-Cre (2-4 weeks), and LV-CMV-Cre (6 weeks) was calculated. Statistical analysis. All variables were initially analyzed with the Shapiro-Wilk test to determine whether the data varies significantly from the pattern expected if the data were drawn from a population with a normal distribution.
9K ). To determine whether the remaining PF synapses were functional, we measured the input-output relationship and the maximum PF-EPSC amplitudes recorded in control and mutant PCs. There were no significant differences in these parameters between the two groups (data not shown), indicating that, although PF synaptic contacts are differently organized on the mutant PCs, they are still functional. As reported above with light microscopy, the CFs innervating the mutant PCs did not reach the upper half of the thinner molecular layer. They rather showed characteristics of the immature "capuchon" stage (Chedotal and  Sotelo, 1992) , with CF contacts on the PC cell body. At the ultrastructural level, CF varicosities were easily identified by several morphological parameters  (Larramendi and Victor, 1967) , including the tight packing of spherical synaptic vesicles, filling almost the entire surface of the varicosity, together with the occurrence of large granulated vesicles and the dense appearance of the axoplasm (Fig.
This work was supported by the  CNRS, UPMC , and  ANR-07-NEURO-043-01. C. S. was supported in part by the  Spanish Ministry of Science and Innovation  Grant  BFU2010 -27326. We thank  Richard Schwartzmann  ( Plateform Imagerie ,  IFR83 ) and  David Godefroy  ( Cellular Imaging Facility of the Institut de la Vision, Paris ) for help with confocal and Nanozoomer slides scanning, respectively. The authors declare no competing financial interests.