dataesr/scientific-paragraphs-categorization huggingface dataset:
To study the distribution of transposons in the genome, we used Repeatmaske (with RM-BLAST as searching engine, the rice transposon sequence database was downloaded in Repbase (http://www. girinst. org/repbase/) to analyze the MSU6. 0 version of the rice genomic sequence in high sensitivity. A transposon is considered to have H3K9 acetylation if located inside a peak. We used 2-fold cut-off in analyzing H3K9 acetylation. For TEs numbers less than 100, Fisher's exact tests were used to test the enrichment. Hyper geometric distribution tests were used for TE numbers greater than 100. We set the p-value cut-off as 0. 01. We used MEME (mod anr -nmotifs 5 -minw 5 -maxw 50) to analyze the binding motif of OsSRT1 ChIP-seq peak sequences. MAST software was used to analyze the distribution of the motifs in the MSU6.
Effect of OsSRT1 RNAi on Genome-wide Histone H3K9 Acetylation in Rice To study the effect of OsSRT1 down-regulation on histone acetylation in rice, a high-resolution map of the genome-wide distribution of H3K9ac in 11-day old wild type and OsSRT1 RNAi seedlings was determined by chromatin immunoprecipitation (ChIP) assays followed by high-throughput Illumina/Solexa sequencing (Fig. S1 ). Values of normalized strand correlation (NSC) and relative strand correlation (RSC) indicated a high quality of the sequence data (Fig. S2 ). Sequencing reads were mapped to the reference genome of rice (Oryza sativa L. ssp. Japonica cv. Nipponbare) using MAQ software  [10]. About 8-9 million unique sequence reads per sample were identified and mapped to the reference genome (Fig. S2 ). Genomic regions or peaks associated with H3K9ac were identified using MACS 1.
Patients The study was approved by the Clinical Research Ethics Committee of Bellvitge University Hospital and all data were collected in an anonymized fashion (ref PR228  /12). We reviewed 604 medical records from patients with neurological signs attributed to spinal cord inflammation assessed at Bellvitge University Hospital (Barcelona, Spain) between January 1989 and December 2011. Among them, we found 487 patients diagnosed with MS who presented a spinal cord inflammation or a first spinal cord inflammation with cranial MRI suggestive of MS, 11 due to parainfeccious disease, systemic disease in 9, spinal cord infarction in 3 patients and ADEM, dural fistula and tumoral-related spinal cord in 2 patients respectively. One patient had simultaneous myelitis and optic neuritis (ON) as a part of the classic Devic Syndrome.
Epidemiological and clinical data Sex, age at symptoms onset, season of onset and time to reach maximum functional deficit were recorded. Hypertension, hypercholesterolemia, diabetes mellitus, smoking habit, traumatic events, and symptoms related to infection (eg, flu, gastrointestinal, or urinary tract symptoms) within one month before the onset of IATM symptoms were also collected. Clinical findings were noted, such as urinary sphincter dysfunction or anal sphincter dysfunction, and the treatment received. None of the patients were receiving immunosuppressants or corticosteroids before the acute spinal event or at the time immunological studies were performed. Disability was evaluated on admission and at last visit using the modified Rankin Scale  [8]. Rankin scores were categorized into <2 and ≥2 to distinguish functional disability.
Imaging data In all patients, baseline and follow-up MRI scans were performed on a 1. 5-Tesla system. MRI study included axial and sagittal images of the brain and spinal cord obtained by T1, T2, FLAIR and T1 post-contrast sequences. All patients had normal brain MRI findings at the first episode of IATM. All underwent spinal MRI on admission, and the number, location, and length of lesions were noted. Longitudinally extensive transverse myelitis (LETM) was defined as extension over three or more vertebral segments on MRI study.
Follow-up Patients were followed-up with a neurological evaluation every 6 months during the first year, and once a year thereafter. Follow-up time was established as the difference between the date of the last visit and the date of admission. Analysis of data was performed on December 2012. An additional neurological examination was performed when a relapse occurred. Relapse was defined as a second demyelinating event at the spinal cord (recurrence) or other central nervous system structure at least one month after the first event, sustained for a minimum of 24 hours. The date of MS conversion was noted in all patients in the MS group.
Mutational analysis After polymerase chain reaction (PCR) amplification of exons 1-8 of the AR using the Taq PCR Master Mix kit from Qiagen (Courtaboeuf, France), we performed direct sequencing using the BigDye terminator v1. 1 kit (Applied Biosystems, Foster City, CA) and an ABI Prism310 Genetic Analyzer (Applera, Courtaboeuf, France), as reported elsewhere  [3]. In cases of mutation, PCR and sequencing of the DNA sample were repeated twice to confirm the finding and rule out any PCR-generated errors. Every PCR product was sequenced with forward and reverse primers. When AR mutations were detected, SRD5A2 and MAMLD1 genes were also sequenced to rule out another cause of hypospadias  [10, 11]. The amino acid numbering for the AR was based on the NCBI reference sequence NM_000044. 2 and the AR database  [12].
Homology study and structure prediction When a mutation that had never been reported was found, the functional consequences of amino acid changes were predicted using in silico models. Regarding the homology study, ensembl. org detected the putative homologs of the human AR gene and alignments were made with the ClustalW software at http://www. ebi. ac. uk/Tools/ msa/clustalw2/. Regarding the structure prediction, the secondary structure for wildtype and variants was predicted using JPred software  [13]  (http://www. compbio. dundee. ac. uk/www-jpred/). The relative accessibility of amino acids was studied with Netsurf software  [14]  (http://www. cbs. dtu. dk/services/NetSurfP/). The three-dimensional structure was predicted by the Protein Homology/ analogY Recognition Engine (PhyreEngine) from the Structural Bioinformatics Group, Imperial College, London, at http:www.
It is notable that 7 out of 9 patients exhibited a mutation in exon 1 of the AR, whereas about 85% of the mutations reported in the AR mutations database  [39]  (http://www. mcgill. ca/androgendb/) are localized in exons 2 to 8. In contrast, the mutations responsible for minor phenotypes, as seen in our series, are mainly present in exon 1. Of the exon 1 mutations described in the AR database, 70% induced complete androgen insensitivity syndrome (CAIS), 14% induced partial androgen insensitivity syndrome (PAIS), and 16% were implicated in infertility. Exon 1 is an important regulatory region for AR activity. It encodes the N-terminal domain of the AR protein, which contains transactivation elements, dimerization zones, several cofactor binding sites, and two regions ( 25 FXXLF 27 and 433 WXXLF 437 ) involved in Nterminal and C-terminal domain interactions.
Loss of this domain results in inactivation of the AR since testosterone binding no longer leads to its conformational change and the subsequent interactions between helix H12 and helix H3  [40]. Exon 1 mutations are thus mainly associated with CAIS. In a recent report by Philibert et al. [3] , all these mutations led to a premature stop codon and totally disrupted AR transductional activity because the protein was truncated, explaining the severe phenotype. In our study, the phenotype was minor with isolated hypospadias and no nonsense mutation was identified. The functional studies of the D551H mutation demonstrating a slightly lowered transactivation of the receptor are in agreement with some level of genotypephenotype correlation. Such a correlation has not been demonstrated for the AR and there are important variations in phenotypes for a single AR mutation in the database (ranging from PAIS to infertility).
This study was funded by a  Programme Hospitalier de Recherche Clinique Inter-Re  ´gional (PHRC number  UF 8270 ) provided by the  CHU de Montpellier  and by a grant from the  Fondation pour la Recherche Medicale   FRM110309. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
14, 15 These patients could benefit from more intensive or innovative prophylactic strategies as opposed to a general pre-emptive strategy. To our knowledge no data are available in the literature about this issue. We have attempted to study CMV reactivation patterns in 99 consecutive patients with MM who underwent RIC Allo-SCT in our cancer centre at Marseille, where serial CMV monitoring has been done, to ascertain the risks of CMV reactivation. Patients and Methods. This is a retrospective analysis of MM patients who underwent RIC Allo-SCT at our centre between January 2000 and January 2012. The data were collected from the transplant database and individual medical records. A total of 99 patients (median age 53 years, range 27-67) underwent RIC Allo-SCT, including 59 males and 40 females.
Diffusion tensor imaging data acquisition Following the behavioral tests, the rats were sacrificed at three time points: 1 week, 3 weeks, and 2 months after surgery (only at 1 week for sham-operated animals). They were perfused with phosphate-buffered saline (PBS) intracardially and decapitated. Each brain was post-fixed in 4% formaldehyde (from paraformaldehyde) in PBS (pH 7. 4) for 30 min at 4°C. The fixed brain was rinsed with PBS and was then placed into the scanner within a plastic tube. The magnetic resonance (MR) experiments on rats were performed in a 4. 7 T scanner (Varian Associates, Palo Alto, CA) equipped with gradients of up to 60 mT/m. A 66-mm volume coil was used for both transmission and reception. A 2D diffusion-weighted (DW) spin-echo sequence was used with the following acquisition parameters: FOV = 30 × 30 mm 2 , image matrix = 128 × 128, slice thickness/gap = 1/0 mm, TR/TE = 3000/50 ms, NEX = 40.
5/0 mm, TR/TE = 2500/27 ms, NEX = 16. DW images were acquired in 12 directions with 2 b-values of 0 and 1500 s/mm 2. The total acquisition time was 19 h. For the DTI of both rats and mice, motion-probing gradients (MPGs) were applied as follows:  These sample preparation and DTI data acquisition methods were based on previous research with minor modifications  [19, 29]. g1 ¼ ffiffi ffi 5 p 5 201 ð Þ; g2 ¼ ffiffi ffi 5 p 5 012 ð Þ; g3 ¼ ffiffi ffi 5 p 5 120 ð Þ; g4 ¼ ffiffi ffi 5 p 5 210 ð Þ; g5 ¼ ffiffi ffi 5 p 5 021 ð Þ; g6 ¼ ffiffi ffi 5 p 5 102 ð Þ; g7 ¼ ffiffi ffi 5 p 5 20-1 ð Þ; g8 ¼ ffiffi ffi 5 p 5 012 ð Þ; g9 ¼ ffiffi ffi 5 p 5 -120 ð Þ; g10 ¼ ffiffi ffi 5 p 5 2-10 ð Þ; g11 ¼ ffiffi ffi 5 p 5 02-1 ð Þ and g12 ¼ ffiffi ffi 5 p 5 -102 ð Þ ** * * A B.
Image and data analysis The six independent elements of the 3 × 3 diffusion tensor were calculated from each series of DW images. The tensor was diagonalized to obtain three eigenvalues (λ 1-3 ), which corresponded to the three eigenvectors (ν 1-3 ). The DTI index Trace(D), which is a scalar measurement of the total diffusion within a voxel, was derived from the DTI-studio software  [30]. Trace D ð Þ ¼ λ 1 þ λ 2 þ λ 3 The mean diffusivity (MD) is a measure of the average motion of water molecules independent of directionality, which was obtained from the Trace(D). For the color-coded MD maps, MATLAB (Math Works, Natick, MA, USA) was used. The MD value range was defined as 0 to 5. 0 × 10 -4 mm 2 /sec. MD ¼ λ 1 þ λ 2 þ λ 3 3 ¼ Trace D ð Þ 3 Regions of interest (ROIs) were semi-automatically defined in the images generated from DTI Studio, by ROI Editor  [30].
Images obtained via confocal microscopy were analyzed with ImageJ software, as reported in our previous study  [32]. A custom plugin was used to automatically establish the overall fluorescence from the image (> 0. 28 mm 2 ) at the dentate gyrus (DG)/hilus, the CA2 and CA3 (CA2/3) regions, or the CA1 region, and to calculate the percentage of the image covered by staining.
Long-lasting deficit in cognitive function after middle cerebral artery occlusion in rats We tested the cognitive function of rats 1 week, 3 weeks, and 2 months after MCAO, and observed a clear decrease in the freezing time in the contextual conditioned test at all the time points tested, compared to the control rats 1 week after the sham operation (n = 6 in each group; P <0. 05, Figure  1A ). In contrast, in a cue test, we did not observe a significant difference in the freezing behavior among the groups (data not shown). We also evaluated the time course of sensory-motor function after MCAO. A sensory-motor neurological test was conducted in a different cohort of MCAO and sham-operated rats (n = 6 in each group) every day from 1 to 28 days after the operation. As shown in Figure  1B , we detected significant recovery in the sensory-motor function of the MCAO rats, suggesting the regeneration and/or functional repair of the damaged neural networks.
A B Next, we quantitatively analyzed the change in the MD value at the affected hippocampus. For this analysis, we used DTI Studio for the MD calculation, with semiautomatic morphometric identification of the hippocampus by ROI Editor. We detected a significant reduction in the MD value of the ipsilateral hippocampus (P <0. 05) after MCAO, compared to the intact or sham group (Figure  3C ). The contralateral hippocampus did not show a significant MD decrease after MCAO (data not shown). For a more precise verification of the decreased MD value, we performed a voxel-based morphometric (VBM) analysis, as a fully automatic digital comparison of imaging data between the MCAO and sham-operated rats. The T-contrast map image revealed a significant reduction in the MD value after MCAO (Figure  3D ).
Database Searching MS n data were processed (smoothing, background subtraction, and centroiding) using the program DTASuperCharge (Source-Forge, Inc. ). The processed files were subsequently searched against the human sequence library in the International Protein Index (IPI) and UniProtKB/Swiss-Prot protein sequence databases using an in-house Mascot server (Matrix Science Ltd. ,London, UK). The databases searches were performed choosing trypsin as enzyme and one miss cleavage was allowed. Carbamidomethyl (Cys) was considered as the fixed modification. Oxidation (Met), N-acetylation (protein) and phosphorylation (STY) were chosen as variable modifications. The data were searched with a peptide mass tolerance of 630 ppm and a fragment mass tolerance of 60. 6 Da.
p140Cap is a Substrate of the Abelson Tyrosine Kinase In order to identify the tyrosine kinases involved in phosphorylation of the EPLYA and EGLYA sequences, we first performed in silico analysis. Based on the fact that three different tyrosine kinases, namely Abl, Alk, and Src displayed the highest scores (data not shown), we took advantage of the KinaseFinder service package (see Materials and Methods) to find out whether the EPLYA and EGLYA peptides could function as substrates for these three recombinant protein tyrosine kinases in an in vitro system. As shown in Figure  5A , when different amounts of the synthetic peptide SIIKIYRKEPLYAAFPGSHLTNGDL includ- ing the EPLYA sequence, were incubated with recombinant purified kinases, only the Abl kinase was able to significantly trigger peptide phosphorylation at both 0,5 and 1 micromolar substrate concentrations.
This study was funded by  Associazione Italiana Ricerca Cancro (AIRC), Ministero UniversitaRicerca (MIUR)  and  University of Torino Compagnia San Paolo , Torino;  Progetto d'Ateneo. The authors also received financial support from the following:  Regione Piemonte ,  Progetto Druidi. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
EXPERIMENTAL PROCEDURES Cloning of DENV NS5FL and RdRp Fragments-cDNAs encoding the NS5FL proteins from DENV1-4 (GenBank TM accession number EU848545. 1, GenBank accession number AF038403. 1, MY00-22366 strain, and MY01-22713 strain) were cloned in pET28a. cDNAs encoding the RdRp domains from DENV3 and DENV4 were cloned into a modified pET28a vector comprising a PreScission protease cleavage site inserted downstream of the vector N-terminal His tag sequence. Sitedirected alanine mutations of DENV4 NS5FL were performed using pET28-D4-MY01-22713 NS5FL  (12)  as a template according to the manufacturer's protocol (Stratagene). A list of primers used for cloning and mutagenesis are available in supplemental Table  1. Reverse Genetic Analysis of the DENV4 T269A Linker Mutation-A cDNA fragment containing the DENV4 (GenBank accession number AF326825) T269A mutation (ACA to GCC) was isolated from a synthetic gene construct (containing DENV4 nucleotides 8121-9340; GenScript) by PstI/SacII digest and substituted with the corresponding wild-type sequence in the DENV4 infectious cDNA clone p4 (a kind gift from Stephen Whitehead, National Institutes of Health).
5, 10 mM KCl, 1 mM MgCl 2 , 0. 3 mM (DENV2 and -4) or 1 mM (DENV1 and -3) MnCl 2 , 0. 001% Triton X-100, and 10 M cysteine. 4 The reactions were allowed to proceed for up to 3 h at room temperature. At the indicated time points, 30 l of 2. 5ϫ STOP buffer (200 mM NaCl, 25 mM MgCl 2 , 1. 5 M diethanolamine, pH 10; Promega) with 25 nM calf intestinal alkaline phosphatase (New England Biolabs) was added to the wells to terminate the reactions. The plate was shaken and centrifuged briefly at 1200 rpm followed by incubation at room temperature for 60 min and then read on a Tecan Saffire II microplate reader at excitation max and emission max wavelengths of 422 and 566 nm, respectively. All data points were collected in triplicate wells in 96-well black opaque plates (Corning), and the experiments were performed at least three times.
After incubation at room temperature for 2 h, 2. 5ϫ STOP buffer containing calf intestinal alkaline phosphatase was added to terminate the reactions, and the plate was processed as described above. All data points were performed in triplicate wells in 96-well black opaque plates (Corning), and the experiments were performed three times. Amounts of Atto-Phos (2Ј-[2-benzothiazoyl]-6Ј-hydroxybenzothiazole phosphate; nM) released from Atto-CTP incorporation were calculated from a standard curve comprising 10 points of 2-fold serially diluted Atto-Phos reagent (500 -0. 98 nM; Promega). K m values were obtained by plotting the observed 2Ј-[2-benzothiazoyl]-6Ј-hydroxybenzothiazole production (nM/min or velocity, v) as a function of nucleotide or RNA concentrations, and the data were fitted to the equation v ϭ V max ϫ [S]/(K m ϩ [S]) or v ϭ V max ϫ [S]/(K m ϩ [S] ϫ (1 ϩ [S]/K i )) where [S] is the substrate concentration for RNA and NTP, respectively, using GraphPad Prism software.
Thermofluorescence Assay-Each reaction mixture comprised 2. 5 M protein and 62. 5ϫ SYPRO Orange dye (Invitrogen) in 1ϫ assay buffer (50 mM Tris, pH 7. 5, 100 mM KCl, 0. 001% Triton X-100, 0. 1 mM MnCl 2 , 0. 1 mM MgCl 2 ) in a total volume of 20 l in a 96-well PCR white opaque plate (Bio-Rad). The plate was sealed and heated from 25 to 85 °C with increments of 0. 5 °C using an iQ TM 5 Multicolor Real-Time PCR Detection System (Bio-Rad). Fluorescence was detected at an excitation max of 485 nm and an emission max of 625 nm. Signals were recorded as relative fluorescence units (RFU) with respect to temperature, and their derivatives (ϪdRFU/dT) were plotted using GraphPad Prism software. Melting temperatures for each protein were measured in triplicate wells. Crystallization and Structure Determination-Crystallization trials were set up at 20 °C using a Phoenix crystallization robot using sitting drop vapor diffusion.
RdRp265-900 (or RdRp263-900) from DENV3 (GenBank accession number AY662691. 1) was concentrated to 7-10 mg/ml in 20 mM Hepes, pH 7. 0, 300 mM NaCl, 5 mM tris(2-carboxyethyl)phosphine and screened against 96 unique conditions from the Hampton Research index screen and crystal screen II. Crystals were obtained in numerous conditions including conditions 33 and 34 (Index HT Screen HR2-134, Hampton Research) and in condition 30 (crystal screen II, Hampton Research). Larger crystals of size 100 ϫ 100 ϫ 300 m 3 were obtained over 2-4 days by mixing a volume of 1 l of RdRp265-900 (or RdRp263-900) with 1 l of condition 34 (1. 0 M succinic acid, 0. 1 M Hepes, pH 7, 1% (w/v) PEG monomethyl ether 2000). For cryoprotection, crystals were transferred to the crystallization solution supplemented with 20% glycerol.
Diffraction data, collected on an R-Axis IVϩϩ mounted on a rotating anode (Rigaku FRE), were integrated using MOSFLM  (15)  and scaled and truncated to structure factor amplitudes using SCALA/TRUNCATE from the CCP4 suite  (16). The structure was determined by molecular replacement using the previously determined structure of RdRp272-900 (Protein Data Bank code 2J7U (8) as a search probe. Residues from the linker region were built using the computer graphics program Coot  (17) , and the structure was refined using REFMAC5  (16).
b, schematic diagram of the N-terminal extended DENV4 RdRp domain proteins that were expressed and tested for activity (MY01-22713 strain). The longest RdRp construct (264 -900) contains all 9 amino acid residues from the linker region. The other deletion constructs tested have 7, 5, and 3 amino acids of the linker sequence (RdRp266 -900, RdRp268 -900, and RdRp270 -900) respectively. RdRp273-900 denotes the RdRp domain devoid of residues from the linker region. c, graphical representation of results obtained from a typical activity assay obtained for DENV4 NS5FL and RdRp proteins in the de novo initiation FAPA assay measured over a period of 3 h. The data shown are the average RFU obtained from triplicate wells. d, representative thermofluor experiments showing the increased thermostability for DENV4 RdRp264 -900 (red curve) compared with DENV4 NS5FL (black curve) and DENV4 RdRp273-900 (blue curve) proteins.
Like the structure of RdRp272-900 reported earlier at 1. 79-Å resolution (Protein Data Bank code 4HHJ)  (11) , residues 407-419 (loop 3) and 455-469 from the finger domain are not visible in the electron density map, confirming their intrinsic mobility in the absence of an RNA template regardless of specific crystal packing contacts. The asymmetric unit comprises two RdRp265-900 molecules assembled as a head-to-tail dimer related by a non-crystallographic dyad (Fig. 5 ). The interface area between both polymerase molecules extends over 1,604 Å 2 and is stabilized via seven hydrogen bonds involving residues 296, 316 -319, and 584 from the finger domain as well as residues 747 and 876 from the thumb domain (Fig. 5 ). Although RdRp265-900 appears to be predominantly monomeric in solution, dimerization modes    have been put forward for the RdRp from poliovirus and from hepatitis C virus  (18, 19).
DISCUSSION The crystal structure of the MTase domain from DENV2 reveals ordered residues up to amino acid 267 (Protein Data Bank code 1L9K)  (23). The segment comprising amino acids 268 -296 is disordered, but it is included in the protein fragment used for crystallization. Likewise, the structure of the MTase domain from DENV3 (comprising residues 1-272) determined at 1. 7-Å resolution (Protein Data Bank code 3P8Z) (7) reveals the polypeptide chain up to residue Arg 262 , which has been strictly conserved during flavivirus evolution (Fig. 1a ). Interestingly, in both structures, the guanidinium group of the arginine side chain establishes a strong hydrogen bond with the main-chain carbonyl oxygen of Val 97. Thus, the C-terminal subdomain of the DENV3 MTase consisting of strand ␤3 spanning residues 259 -262 belongs to the MTase core domain, whereas residues beyond 263 extend away from it.