dataesr/scientific-paragraphs-categorization huggingface dataset:
The ''touch down'' program consisted of 15 s at 95uC, 5 s at 68uC, and 8 s at 72uC followed by a progressive decrease of the annealing temperature which was reduced by 0. 5uC every successive cycle until 62uC (13 cycles). A generic PCR amplification of up to 27 cycles was then performed using the final annealing temperature reached in the ''touch down'' phase. A melting curve step was used to examine each sample for purity. Quantitative PCR analysis was performed in triplicate. Primers were designed with Primer-Blast software (National Centre for Biotechnology Information/NCBI, Bethesda, USA) and purchased from MWG (Germany). All primers had Tms between 59 and 61uC and all the products were 100-200 bp. The primers used were as follows: HPRT1 (forward, 59-TCTGTGGCCATCTGCTTAGTAGAGC-39; reverse, 59-ACAATCCGCCCAAAGGGAACTGA-39), FAM110B (forward, 59-GCGCAAGCATGATCAGCTCAGAC-39; reverse, 59-TGGCAGAAATGCCATACGGCAC-39), HIPK2 (forward, 59-ACAAGACATTCCAGCCCCAGGGA-39; reverse, 59-CACA-GACAGGGAATGAAGCCTGCA-39), SMC6 (forward, 59-TCTTTCCCTGTGGTCCATCGCAGA-39; reverse, 59-ACGCTGGGAATCTGCCATCTTCAG-39), THRA (forward, 59-ATGCCCTCAACTCACCCCCTACA-39; reverse, 59-CCAAGCCAAGCCGTTCTTTGCAC-39) and TOP1 (forward, 59-ATGAGTGGGGACCACCTCCACA-39; reverse, 59-CGGAAATCCGCTTCGATCTGGGA-39).
Characteristics of Genes Exhibiting Altered Translational Efficiencies on BRCA1 Depletion Distinct categories of mRNAs that displayed either increased or decreased translatability (RR $1. 50 or RR #0. 67) in BRCA1depleted cells were identified. A gene ontology analysis conducted with Ingenuity Pathway analysis (IPA) software was used to determine whether translationally deregulated genes are significantly enriched in particular functions (Figure  2C ). Interestingly, the most enriched function is cellular maintenance, the function considered today as the major role of BRCA1 contributing to its tumour suppressor activity. We also noticed that the second and third enriched functions, namely embryonic development and lipid metabolism, are two cellular processes previously linked to BRCA1  [21]   [22].
Since translation is the last step in the flow of expression of genetic information, BRCA1-dependent regulation at the translational level would allow for an immediate and rapid response to changes in physiological conditions such as DNA damage without the involvement of mRNA synthesis and transport. We previously showed that BRCA1 regulates global translation in a PABP1-dependent manner. We demonstrate here that BRCA1 regulates the translation of a limited number of mRNAs. Because PABP1 acts as a general translational factor, we asked how BRCA1 selectively impacts the translation of only some mRNAs species. We first examined whether the proteins encoded by these mRNAs present some common features. Using IPA software, we found that these proteins participate in many cellular pathways, and are not restricted to any particular gene ontology function such as transcription regulators or kinases.
Using IPA software, we found a number of drug targets to be regulated in the BRCA1-depleted cells (Table  S5 ). They include the up-regulated HDAC8, THRA, TOP1 and CDK6 that participate to the 5 main functions depicted for BRCA1. HDAC8 is involved in chromatin remodelling by histone deacetylation. Inhibition of HDAC8 results in a-tubulin acetylation and therefore sensitizes breast cancer cells to tubulinpolymerizing agents  [59]. Several kinases are up-regulated in the absence of BRCA1, including CDK6 and PIK3CB. CDK4/6 inhibitors that interrupt cell cycle have therapeutic efficacy in combination with endocrine-based therapy in patients with steroid hormone receptor positive breast cancer  [60]. The PIK3CB kinase belongs to the well-investigated PI3K pro-proliferative pathway and is a target of several inhibitory drugs currently under trial  [61].
The sign specifies the RR value: (2) #0. 67, (+) $1. 50. The number indicates how many mRNAs are deregulated. : mRNAs translationally deregulated through change in polysome mRNA abundance only; : mRNAs translationally deregulated through change in total mRNA abundance only; : mRNAs translationally deregulated through change in polysome abundance together with opposite changes in total mRNA C/Functional distribution of differentially translated known genes in BRCA1-depleted versus control MCF7 cells. Gene functions were established based on the annotation provided by the IPA database. The number of genes enriched in each function is shown in brackets. doi:10. 1371/journal. pone. 0067313. g002.
50. The RRs are annotated with a sign and a number. The sign specifies the RR value: (2) #0. 67, (+) $1. 50. The number indicates how many mRNAs are deregulated. : mRNAs translationally deregulated through change in polysome mRNA abundance only; : mRNAs translationally deregulated through change in total mRNA abundance only; : mRNAs translationally deregulated through change in polysome abundance together with opposite changes in total mRNA C/Functional distribution of differentially translated known genes in BRCA1-depleted versus control MCF7 cells. Gene functions were established based on the annotation provided by the IPA database. The number of genes enriched in each function is shown in brackets. doi:10. 1371/journal. pone. 0067313. g002.
nidulans) 0,9 1,4 0,6 NM_001143979 RECQL RecQ protein-like (DNA helicase Q1-like) 1,4 0,8 1,8 NM_002907 TPR translocated promoter region (to activated MET oncogene) 1,8 0,7 2,5 NM_003292 Genes are clustered into functional groups. Each gene is annotated in the table with the gene symbol, the gene name, the fold change in abundance in polysomal RNA (polyRNA), the fold change in mRNA abundance (totRNA), the relative translatability (poly/tot) and the GenBank accession number. doi:10. 1371/journal. pone. 0067313. t001.
To that end, one interspecific cross of Eucalyptus urophylla x E. grandis was planted in three different field trials in the Republic of Congo where contrasting environmental conditions in term of water availability (rainy vs. dry seasons), were suitable for observing the effect of drought on growth. We used two complementary types of growth trait: integrative traits (cumulative growth, growth curve parameters) and responsive traits (sub-annual growth increments) in combination with climatic data to characterize growth response to changes in water availability and reveal its genetic component. This comprehensive dissection of growth enabled us to characterize the genetic determinism of primary (height) and secondary (circumference) growth using conventional quantitative genetics and QTL detection approaches.
Broad-sense heritability of growth Broad-sense heritabilities were estimated using trial P98 which corresponded to a clonal test with 10 replicates of 60 full-sibs. Analyses were conducted using Markov Chain Monte Carlo methods implemented in the R MCMCglmm package  [73]. The following mixed effects model was used for each trait: y ¼ μþRow i þ Col j þ G k þ ε where y is the individual tree measurement, μ is the general mean, Row i is the fixed effect of the row, Col j is the fixed effect of the column, G k is the random effect of the genotype e N O; σ 2 G À Á and ε is the residual random effect e N O; σ 2 ε À Á. The intersection between individual tree coordinates in the trial (row and column) represented the spatial position of each tree. Broad-sense heritability for the full-sib family (H 2 ) was estimated for each trait using the following formula: H 2 ¼ σ 2 G = σ 2 G þ σ 2 ε À Á Where σ 2 G is the genetic variance and σ 2 G þ σ 2 ε À Á is the phenotypic variance  [74].
QTL analysis QTL mapping Quantitative trait locus (QTL) analyses were performed with R software using the qtl package  [82]. We carried out simple and composite interval mapping using the multiple imputation method of Sen and Churchill  [83]  with a step interval of 1 cM, a genotyping error rate of 0. 001 and 512 imputations per genotypes. It has been shown that this imputation method performs better with missing genotypic data  [83]. The whole-genome significance thresholds for all traits were determined with 10,000 permutations  [84]. QTLs that met or exceeded 95 th and 90 th percentiles were assessed to be significant or suggestive, respectively. Confidence intervals for each QTL position were obtained using Bayes credible intervals (BCI). Genetic maps and QTL positions were drawn using MapChart  [85].
Trend in the genetic control of growth traits Broad-sense heritabilities (H 2 ) were estimated for cumulative growth traits, growth increment, and the GCP based on the data from P98. For all traits, H 2 values were small to medium. Although standard errors associated with H 2 were high (± 0. 1 on average), we observed a regular increase in heritability with time for cumulative growth: Ht [0. 06-0. 33], Cir [0. 12 to 0. 38] (Figure  5 , Additional file 7). The heritabilities for the Asym parameter (Asym_h: 0. 35 and Asym_c: 0. 44) were only slightly higher than those obtained for final Ht and Cir, which is consistent with the strong correlation between these pairs of traits. H 2 for growth increments were more heterogeneous than H 2 for cumulative traits (Figure  5 , Additional file 7), even though the variation ranges were similar (Ht_Inc [0-0.
Acknowledgements The authors would like to thank the technicians at  CRDPI  ( Centre de Recherches sur la Durablilité des Plantations Industrielles located in the Republic of Congo ) for trial establishment and follow-up. The authors acknowledge two anonymous reviewers for their constructive comments and suggestions on the manuscript. This study was supported by grants from  FEDER  ( Fonds Européen de Développement Régional ,  ABIOGEN  project, n°Presage  32973 ). JB received a PhD fellowship from the  BIOS department of CIRAD (Centre de coopération Internationale en Recherche Agronomique pour le Développement).
Target Gene and Primers Design Snapback and reverse primers were designed to target the 30 kDa RNA polymerase subunit (RPO30) gene of CaPVs  [13, 17, 27]. Primers were designed to allow the amplification, in all CaPVs, of a 96 base pair (bp) fragment corresponding to position 27875 to 27970 of the SPPV A genome (AY077833). These primers were selected using AlleleIDH version 6 software (Premier Biosoft International, Palo Alto, CA, USA). Within this amplicon, a snapback tail of 16 bases length was designed manually to match 100% with GTPV and presented a T:A mismatch with SPPV and a T:G mismatch with LSDV (Figure  1 ). This snapback tail, whose sequence is complementary to the extension product of the forward primer, was added to the 59 end of the forward primer. Two nucleotides (GG) not relevant to the extension product of the forward primer were added to the 59 end of the snapback tail (Table  1 ) to prevent it from being extended once it anneals to its complementary sequence.
0 (Bio-Rad) and the correspondent curves were displayed as negative first-derivative plots of fluorescence with respect to temperature. High-Resolution Melting (HRM) analysis, a post-PCR melting analysis method used to identify variations in nucleic acid sequences, was also used to plot the melting profile of the three genotypes using the Precision Melt Analysis TM software (Bio-Rad). Normalized melt curves and difference in curves were acquired by selecting pre-and post-melt regions for snapback hairpin and full-length amplicons separately. Alternatively, the current method was tested using different PCR machines to evaluate the possibility of performing the assay using the available PCR platforms. Thus, PCR was performed on a conventional PCR machine (C1000, Bio-Rad) and the PCR product transferred to the CFX96 real-time PCR machine (Bio-Rad) for melting acquisition.
Limit of Detection for Each Genotype The analytical sensitivity of the method was assessed by amplifying five different concentrations (200, 160, 120, 80 and 40 copies/reaction) of each plasmid containing GTPV Denizli, SPPV Denizli and LSDV Ismalia RPO30 gene. The limit of detection (LOD) of each genotype was evaluated by testing the diluted plasmids in pentaplicate separately at different days on five separate occasions. The data from each PCR reaction was recorded and subjected to probit regression analysis using the STATGRAPHICS Centurion XV Version 15. 2. 12 software package (StatPoint Technologies, Warrenton, VA, USA). Because this method aims simultaneously detecting and genotyping the CaPVs, the criteria for a PCR to be considered as positive for the LOD determination were taking into account both amplification plot and the shape of the melting peak of the snapback stem.
Furthermore, 8 additional samples from suspected capripox cases and 20 swab samples from healthy goats tested negative in the snapback assay. All these negative samples were also confirmed to be negative by dual hybridization probe assay; hence the specificity was 100%. To further confirm the virus host origin discriminating power of the current genotyping method, the melting data of the PCR product duplexes acquired using CFX TM Manager software were analysed using the Precision Melt Analysis TM software. Since the assay produced two PCR amplicons duplexes representing the snapback hairpin and the full-length amplicons, the HRM analysis was done separately for each melting region. The normalized melt curves and difference curves were acquired by selecting the preand post-melt regions for the PCR amplicons duplexes by shifting on the two different melting temperature regions, thus for the fulllength amplicons the data analysis window was gagged between 70uC-74.
Cross-platform Compatibility To evaluate the cross-platform compatibility of the assay, we performed the assay under the conditions described in the Material and Methods section using plasmids containing each of the three CaPV genotypes in the following instruments: the 7500   The melting of both amplicons and snapback stems were obtained for a successful genotyping in all instruments except the 7500 Fast Real-Time PCR System, where only the melting of the amplicons could be observed. Indeed, the fixed data-acquisition capabilities (3 data points/uC) of the 7500 Fast Real-Time PCR System and the supplied version of the software (version 1. 4) were not adequate for evaluating the snapback melting  [24]. There was a small shift in the Tm values of both amplicons and snapback stems from one instrument to another.
These were two samples from Kenya (Kitengela/O58/ 2011 and Kitengela/O59/2011), and three from Ethiopia (Chagni/O06/2012, Akaki/O01/2008 and Metekel/O01/2010), both collected from sheep, but identified as GTPV using our new assay. These genotyping results were in complete agreement with those of the dual hybridization probes assay  [14]  and the phylogenetic reconstruction using the CaPV RPO30 gene (data not shown). Additionally, two samples collected from Springbok antelope were detected as LSDVs (Table  2 ) which was in agreement with our previous characterization data  [13]. The snapback primer technology was first established as a closed tube genotyping method with saturating dye having a similar specificity to a probe without the need to use any covalent label  [26]. It was successfully applied for the genotyping of Factor V Leiden  [26] , Gilbert Syndrome UGT1A1 (TA) n promoter polymorphism  [24]  and for the enrichment and detection of rare alleles  [25].
Acknowledgments The authors would like to thank  Mr. Christian Hollub  for his technical assistance and,  Dr. Emmanuel Albina  and  Mr. Christian Le Goff  (CIRAD),  Dr. David Wallace  (OVI),  Dr. Vely ´Gulyaz  ( VCRI-Pendik ),  Dr. Hafsa Madani  ( INMV-LCV ),  Dr. Mehdi El Harrak  (Biopharma),  Mr. Badian Kamissoko  and  Dr. Mamadou Niang  (LCV) and  Dr. Jacqueline Kasiiti Lichoti-Orengo  ( CVL ) for providing samples. We also thank  Prof. Lukas Mach  for helpful discussions.
Homology modeling The amino acid sequence was submitted to the homology modeling and threading server I-TASSER with or without specifi ed restraints  (28) (29) (30). The protonation state of the resulting top rated model was predicted utilizing the H++ server  ( 31 ). Subsequently, the models were parameterized, solvated, and equilibrated for 10 ns at 310 K in the presence of 0. 15 mM KCl utilizing the NAMD software package  ( 32 )  and the CHARMM 36 force fi eld  ( 33 ). The bonded interactions were calculated every timestep, full range electrostatic interactions every other time-step, short-range nonbonded interaction cutoff was set to 12 Å and a smoothing function employed at 10 Å, and pair-lists were recalculated every 10 time-steps with a pair-list distance of 14 Å. The temperature and pressure (1 bar) were maintained utilizing Langevin dynamics and Langevin piston method, respectively.
RESULTS Two mushroom-derived aegerolysins, Ply and Oly, have been reported to bind SM/Chol membranes  ( 22, 23 ). In order to fi nd a new SM/Chol binding protein, we screened for proteins that bind liposomes composed of SM and Chol (1:1) using extracts of P. eryngii. The mushroom extract was incubated with SM/Chol (1:1) liposomes for 30 min at 37°C, centrifuged, and the pellet and supernatant were subjected to SDS-PAGE ( Fig. 1A  ). The liposome-bound pellet gave a low molecular weight single band ( Fig. 1A  , lane 4, arrow). The bound protein was extracted from the gel and subjected to amino acid sequencing as described in Materials and Methods. The N-terminal amino acid sequence of the protein was determined as AYAQXVIIII. Then, using an in-house P. eryngii transcriptome database, the protein was identifi ed to be a 138 amino acid polypeptide which exhibits two amino acid substitution (K22V and T100A) from the PlyA from P.
ostreatus ( 35 ) ( Fig. 1B , triangles ). This was an identical protein to the protein that we recently identifi ed in the transcriptome of P. eryngii as a homolog of PlyA  ( 36 ). We designated the gene as Pe. Pleurotolysin A (Pe. PlyA) (Accession number AB777517). Here we name the protein PlyA2. PlyA2 belongs to the aegerolysin family and exhibits a high homology to other family members, EryA and ostreolysin sonication (Misonix). Insoluble protein and cell debris were removed by centrifugation at 9,000 g at 4°C for 20 min. For purifi cation of EGFP-proteins, a Ni-NTA (Qiagen) column was used according to the supplier's protocol. The resulting fractions were concentrated, followed by exchanging buffer (PBS, pH 7. 5) using an Amicon Ultra-15 Ultracel®-30K centrifugal unit (Millipore). The protein concentration was determined using the Bradford assay.
In contrast, in model 1, the reduced binding affi nity after W28 mutation is diffi cult to rationalize. Superimposition of the ␤ -sheet core of both models with Stl2 (PDB code 1O72) in the presence of choline phosphate (CP) revealed the close proximity of W112 in model 2 to the superimposed CP binding site of Stl2. In contrast, loss of binding of the W112A mutant cannot be explained in terms of model 1. In summary, model 2 appears to be in better agreement with experimental results compared with model 1. (model 2) with a C-score of Ϫ 1. 76 and a TM -score of 0. 5 ( Fig. 10  ). In line with CD spectral data of Oly  ( 45 ) , both models exhibit a high degree of ␤ -structure. In contrast, only model 2 matched the ␣ -helix content of the CD data, despite omission of the ␣ 2-helix of the template structure.
process based on protein threading, amino acid charge prediction, and molecular dynamic simulation as described in Materials and Methods. The fi rst model (model 1) was generated by unrestrained submission of the PlyA2 amino acid sequence to I-TASSER (supplementary Figs. I, II) and was based on chain A of 3VSF (exo-␤ -1,3-galactanase from Clostridium thermocellum ). Model 1 achieved a confi dence score (C-score) of Ϫ 2. 05 on a scale of Ϫ 5 to 2 of low to high confi dence respectively, where a C-score of about Ϫ 1. 5 and higher is considered to indicate a correct fold of the model ( 43 ). Interestingly, the second ranked template structure, 3LIM_A (FraC from sea anemone Actinia fragacea ), is a member of the actinoporin family of pore forming toxins. Actinoporins, such as equinatoxin II (Eqt2) [Protein Data Bank (PDB) code 1IAZ, 1O72] and sticholysin II (Stl2) (PDB code 1GWZ), are known to bind to SM-rich membranes.
The source of the Crozet plume is also a matter of debate. Based on tomography, the Crozet and Kerguelen plumes have a common source in the deep lower mantle  (Montelli et al. , 2006 (Montelli et al. , , 2004)). However, this tomographic modeling is controversial (van der Hilst and de  Hoop, 2005). The petrographic description of the Crozet Archipelago is limited to a few samples  (Gunn et al. , 1970). Several studies include Pb, Sr and/or Nd isotopic data  (Dupré and Allègre, 1983; Giret et al. , 2002; Hedge et al. , 1973; Mahoney et al. , 1996; Salters and White, 1998; Zhou, 1996) , however the total number of analyses (N = 27) remains limited and often, for a given sample, one of the elements (Pb, Nd or Sr) of the isotopic dataset is not available. As a consequence, lavas from the Crozet Archipelago are poorly known compared to those of other islands in the Indian Ocean such as the Reunion or Kerguelen.
, 2002; Mahoney et al. , 1996). In this study, we present a new geochemical dataset for the Crozet Islands that includes major and trace elements, as well as Sr, Nd, Pb and He isotopes, and a detailed petrography of the studied samples. This dataset was obtained on new samples from the Possession, East and Penguins Islands. In particular, we present the first helium isotopes and high-precision Pb isotopes data for the Crozet Archipelago. These new data allow us to show that the basalts of the archipelago mainly derive from two deep mantle components. Mixing with small amounts of a third component, the local DMM, is invoked to fully explain the data. We also show that the geochemical signature of the SWIR between the Indomed and Gallieni transform faults can be explained by local contamination of the upper mantle by material derived from the Crozet plume.
, 2000). NBS 981 was measured every two samples to monitor machine performance. The measured ratios were subsequently normalized by linear interpolation using the values of  Galer and Abouchami (1998)   Cantagrel et al. , 1980)  and parent/daughter ratios are relatively low (e. g. , Rb/Sr = 0. 05, Sm/Nd = 0. 2 and U/Pb = 0. 4 in average), yielding measured isotopic ratios close to initial isotopic ratios. Thus in the following discussion, the Pb isotopic data are not corrected from radioactive decay. Helium concentrations and isotopic ratios were determined using noble gas mass-spectrometer (Noblesse, Nu Instruments) at the Institut de Physique du Globe de Paris, France. Between 0. 3 and 1. 1 g of olivine crystals were picked from the samples and subsequently cleaned with distilled water and ethanol in an ultrasonic bath.
Isotope compositions Isotope compositions in Nd, Sr, Pb and He are reported in Table  1  and Figs. 3  and 5. East and Possession Islands have homogeneous Sr isotopic ratios (0. 704029 to 0. 704488) and 143 Nd/ 144 Nd (0. 512822 to 0. 512857) (Fig. 3A ). Our Sr and Nd isotopic data are in agreement with the results of previous studies for both East Island ( 87 Sr/ 86 Sr = 0. 7039-0. 7045 and 143 Nd/ 144 Nd = 0. 51274-0. 51286) (Giret et al. , 2002; Mahoney et al. , 1996; Zhou, 1996)  and Possession Island ( 87 Sr/ 86 Sr = 0. 7040-0. 7041 and 143 Nd/ 144 Nd = 0. 51283-0. 51285) (Mahoney et al. , 1996). Samples from Penguins Island display less radiogenic Sr isotope ratios (0. 703211 to 0. 703324) than the other islands, and more radiogenic 143 Nd/ 144 Nd (0. 512931 to 0. 512960, Fig. 3A ). The same two groups of islands can be distinguished with Pb isotopic compositions.