dataesr/scientific-paragraphs-categorization huggingface dataset:
Notably, a neighboring sub-clade contains two genes, RBGD2 and RGBD4 (Figure  1B ), that encode for heat-inducible RBPs implicated in the response to heat stress in Arabidopsis  (Zhu et al. , 2022). MSIL1-4 proteins share a common domain architecture consisting of two N-terminal RNA recognition motifs (RRM1 and RRM2) that are followed by a poorly conserved, intrinsically unstructured, carboxy-terminal region (Figure  1A  and Figure  1 -figure  supplement 1A ). The survey of the gene expression ARAPORT11 databases (https://araport. org/; http://fgcz-pep2pro. uzh. ch) revealed that the MSIL1-4 genes are widely expressed in Arabidopsis, with MSIL1 showing the lowest levels of expression (Figure  1C ). Database searches further indicated that MSIL orthologs are widely distributed in land plants, from bryophytes to angiosperms (Figure  1 -figure supplement 1B).
, 2021 , using the complemented MSIL2F1 and MSIL4F1 lines. Consistent with their functional redundancy, MSIL2F1 and MSIL4F1 exhibit a similar protein interaction network,      with 27 proteins significantly enriched in both MS analyses (Figure  3A  and B, and Supplementary file 1). Examination of the PANTHER database (http://www. pantherdb. org) identified that MSIL2F1/4F1 are part of a protein-protein interaction network that was principally enriched in 4 categories of GO molecular functions, namely poly(A) binding protein (GO:0008143), mRNA 3-UTR binding (GO:0003730), single-stranded RNA binding (GO:0003727), and translation initiation factor activity (GO:0003743), highlighting the relationship between MSIL2/4 and the mRNA binding and regulatory proteome (Figure  3C ). Many of the proteins present in the MSIL2/4 interactome, such as PABs, PUMs, UBP1 are involved in translation regulation and are targeted to stress granule (SGs) components, a membraneless cytoplasmic organelle that formed consecutive to the global inhibition of translation caused by heat-stress  (Chantarachot and Bailey-Serres, 2018; Scutenaire et al.
, 2018). To assess the potential functional link between MSIL and those proteins, we crossed the MSIL2G/4 G plants with a functional PAB2-RFP/ PAB2R line  (Scutenaire et al. , 2018) , and assessed the localization of the fusion proteins before and after heat-stress in both parent and crossed lines. Fluorescence analysis revealed that MSIL2G/4 G, like PAB2R, show a dispersed cytoplasmic signal under normal condition, and are recruited to cytoplasmic granules that largely overlap with PAB2R-containing SG upon heat stress as judged by the yellow-orange appearance in the merged figure (Figure  3D  and Figure  3 -figure supplement 1), and by an independent analysis using the Colocalization Threshold plugin from ImageJ software (data not shown). Treatment with cycloheximide (CHX), a translation inhibitor that prevent SG assembly by trapping mRNAs at polysomes  (Mahboubi and Stochaj, 2017) , confirmed that those foci correspond to bonafide SGs (Figure  3E ).
MSIL2/4 proteins regulate the molecular architecture of SCW in Arabidopsis fibers Pendant stem inflorescence is a common phenotypic trait of Arabidopsis mutants defective in SCW biosynthesis, that results from a lack of mechanical support and rigidity  (Zhang et al. , 2018; Mitsuda et al. , 2007). Given the current lack of knowledge of the role of post-transcriptional mechanisms in the control of SCW biosynthesis in plants, we henceforth focused our analysis on the pendant stem phenotype of the msil2/4 double mutant. Survey of the Arabidopsis inflorescence stem tissue-specific transcriptome database  (Shi et al. , 2021)  indicated that the MSIL2/4 genes are highly expressed in the SCW-forming interfascicular fiber (if) and xylem vessel (xy) cells (Figure  4A ). Toluidine blue O staining and microscopic analysis of Col-0 and msil2/4 mutant stem cross-sections revealed no major changes in the architecture of both the interfascicular and xylary fibers in the mutant stem.
Representative fiber and xylary regions analyzed by immunofluorescence are outlined. Xy, xylem fibers; if, interfascicular fibers. Right: Quantification of the fluorescence was done using ImageJ software and processed according to Supplementary file 5. Significant differences are indicated by asterisks*, p-value <0. 01 according to Student's t test (n=5-12). The online version of this article includes the following figure supplement(s) for figure  5 :     6 ), suggesting that the MSIL2/4 mutations unleash the activity of the GXM1/3 in stem. RNA immunoprecipitation assays further confirmed that the GXM3 and GXM1 mRNAs are efficiently pulled-down from MSIL4G-3, but not MSIL4G RRM -3 plant extracts (Figure  6D ), suggesting that the MSIL2/4 interaction network controls the 4-O-methylation of glucuronoxylan by repressing the activity of the GXM1/3 mRNAs in stem.
Bottom panel (RT): Corresponding RT-PCR using GXM1 or GXM3 specific primers on RNA fractions. The online version of this article includes the following source data and figure supplement(s) for figure  6 : Source data 1. Uncropped Western gels of MSIL4-GFP, MSIL4-GFP RRM and UGP proteins from inputs or antiGFP immunoprecipitates. Source data 2. Uncropped gel of semi-quantitative RT-PCR performed on inputs or antiGFP immunoprecipitates. A penetrant developmental phenotype associated with the MSIL2/4 mutations is a loss in stem rigidity that we could trace back to a defect in SCW formation, an important reservoir of fixed carbon and a renewable resource of major environmental and economic importance  (Meents et al. , 2018 ). Yet, with the exception of few microRNAs involved in the control of lignin polymer synthesis  (Zhang et al.
RNASeq analysis For each library, 30-35x10 6 reads were obtained with 85-90% of the bases displaying a Q-score ≥30, with a mean Q-score of 38 as assessed with Fastqc (http://www. bioinformatics. babraham. ac. uk/projects/fastqc/). Reads were mapped against the TAIR 10 genome using gtf annotation file and default parameters of TopHat2 v2. 0. 7  (Langmead and Salzberg, 2012). Assembly and transcript quantification were performed with Cufflinks v2. 2. 1  (Kim et al. , 2013). Finally, the low expressed transcripts -less than 1 RPKM (reads per kilobase per million mapped reads) in one of the libraries were filtered out. The differential analysis was conducted by Cuffdiff software, belonging to the Trapnell suite. Foldchange (FC) was determined as the ratio between the normalized read counts between mutant and wild-type.
Spectra analyses were performed as described in  Dai et al. , 2020. Saccharification yield was estimated with or without alkali pretreatment, as described by  Acker et al. , 2016. Reducing sugar concentration was assessed with dinitrosalicylic acid (DNS) reagent using 10 µl of the supernatant after 9 hr of reaction. Enzyme activity was assessed at 0. 25 filter paper units (FPU) ml -1 in our conditions. The Boxplots were generated using ggplot2 R package (R v2022. 07. 1).
6 µm, IonOpticks). The MS and MS/MS data were acquired using Xcalibur 4. 4 (Thermo Fisher Scientific). Peptides and proteins were identified by Mascot (version 2. 8. 0, Matrix Science) through concomitant searches against the Viridiplantae database (from Uniprot, Arabidopsis thaliana (thale-cress) taxonomy, 136447 sequences) and a homemade database containing the sequences of classical contaminant proteins found in proteomic analyses (human keratins, trypsin. , 126 sequences). Trypsin/P was chosen as the enzyme and two missed cleavages were allowed. Precursor and fragment mass error tolerances were set at respectively at 10 and 20 ppm. Peptide modifications allowed during the search were: Carbamidomethyl (C, fixed), Acetyl (Protein N-term, variable) and Oxidation (M, variable). The Proline software  (Bouyssié et al.
, 2020; version 2. 2. 0)  was used for the compilation, grouping, and filtering of the results (conservation of rank 1 peptides, peptide length ≥6 amino acids, false discovery rate of peptide-spectrum-match identifications <1%  (Couté et al. , 2020) , and minimum of one specific peptide per identified protein group). MS data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository  (Perez-Riverol et al. , 2022). Proline was then used to perform a MS1 label-free quantification of the identified protein groups based on razor and specific peptides. Statistical analysis was performed using the ProStaR software  (Wieczorek et al. , 2017)  based on the quantitative data obtained with the four biological replicates analyzed per condition. Proteins identified in the contaminant database, proteins identified by MS/MS in less than two replicates of one condition, and proteins quantified in less than three replicates of one condition were discarded.
MALDI measurements were then performed on a rapifleX MALDI-TOF spectrometer (Bruker Daltonics, Bremen, Germany) equipped with a Smartbeam 3D laser (355 nm, 10,000 Hz) and controlled using the Flex Control 4. 0 software package. The mass spectrometer was operated with positive polarity in reflectron mode. Spectra were acquired in the range of 560-3200 m/z. The detected species correspond to ions in the form of sodium adducts.
Observations were carried out using a LeicaDM 6000microscope with a TCS SP8 scanning confocal system using a 40 x apochromatic oil immersion objective to visualized Alexa555 fluorescence (excitation: 561 nm; emission: 565-645 nm). Acquisition settings, including laser power,photomultiplier gain, field of view (X,Y dimension), Z-step, and pixel size of the image, were strictly identical to ensure reliable comparisons between plant material (i. e. the wild type versus mutants). The following datasets were generated:.
Acknowledgements We thank  Aurélie Le Ru  the histological staining and cell wall thickness measurements,  Hua Cassan-Wang  for helping to the preparation of stem sections for staining, and  Michele Laudié  for preparation of the mRNA libraries. This work was supported by the  Centre National de la Recherche Scientific (CNRS) , and grants  ANR-08-BLAN-0206  and  12-BSV6-0010  from  Agence National de la Recherche (ANR)  to TL. This study was supported by the  " Ecole Universitaire de Recherche (EUR)   TULIP-GS  ( ANR-18-EURE-0019 ), and the  EPIPLANT Groupement de Recherche (CNRS, France). The proteomic experiments performed by PH and DG from the  Interdisciplinary Thematic Institute IMCBio , as part of the  ITI 2021-2028 program  of the  University of Strasbourg ,  CNRS  and  Inserm , were supported by  IdEx Unistra  ( ANR-10-IDEX-0002 ), by  SFRI-STRAT'US  project ( ANR 20-SFRI-0012 ), and  EUR IMCBio  ( IMCBio   ANR-17-EURE-0023 ).
The proteomic experiments performed by LB and YC were partially supported by  Agence Nationale de la Recherche  under projects  ProFI (Proteomics French Infrastructure ,  ANR-10-INBS-08 ) and  GRAL , a program from the  Chemistry Biology Health (CBH) Graduate School of University Grenoble Alpes  ( ANR-17-EURE-0003 ). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the paper.
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In the longest follow-up, to our knowledge, for a KRAS G12C inhibitor, we assessed the long-term efficacy, safety, and biomarkers of sotorasib in patients with KRAS G12C-mutated advanced non-small-cell lung cancer (NSCLC) from the CodeBreaK 100 clinical trial (ClinicalTrials. gov identifier: NCT03600883). This multicenter, single-group, open-label phase I/phase II trial enrolled 174 patients with KRAS G12C-mutated, locally advanced or metastatic NSCLC after progression on prior therapies.
Patients The multicenter, single-group, open-label phase I/II CodeBreaK 100 trial (ClinicalTrials. gov identifier: NCT03600883) enrolled patients age 18 years and older with KRAS G12C-mutated locally advanced or metastatic NSCLC after progression on prior therapies (Data Supplement, online only). 16 Institutional review board approval before study initiation and participating country regulatory authority approval were received; all patients provided written informed consent.
Study Design Phase I primary end point was safety and tolerability (key secondary: DOR and PFS). Phase II primary end point was ORR (blinded independent central review; key secondary: DOR, PFS, OS, and safety). Late-onset toxicities were assessed (treatment-related adverse events [TRAEs] occurring after 1 year on treatment). Exploratory analyses evaluated molecular correlates with efficacy (Data Supplement). 16 PD-L1 and genomic alterations were correlated with long-term benefit (PFS $ 12 months) versus early progression (nonresponders with PFS # 3 months).
Safety Any-grade TRAEs were observed in 121 (70%) patients (Data Supplement), with grade 3 in 34 (20%), grade 4 in 2 (1%), and no fatal TRAEs; TRAEs led to treatment reduction or interruption in 39 (22%) and treatment discontinuation in 11 (6%). Most common TRAEs were diarrhea (53 [30%]), increased alanine aminotransferase level (31 [18%]), and increased aspartate aminotransferase level (31 [18%]). Median (range) time to grade $ 3 diarrhea and hepatotoxicity onset was 6. 1 (1. 7-11. 1) and 9. 1 (3. 1-18. 7) weeks. All grade $ 3 (median [range] duration, weeks) diarrhea resolved (2. 9 [0. 3-6. 0]); grade $ 3 hepatotoxicity resolved in all but three of 19 (16%; 5. 5 [0. 4-39. 1]). Trends toward increased hepatotoxicity in patients receiving checkpoint inhibitors # versus. 3 months before sotorasib initiation were observed (Data Supplement).
CONTEXT Key Objective To determine the long-term safety, tolerability, and efficacy of sotorasib 960 mg once daily in patients with KRAS G12Cmutated, locally advanced or metastatic non-small-cell lung cancer from the CodeBreaK 100 clinical trial (ClinicalTrials. gov identifier: NCT03600883). Exploratory analyses assessed the relationship of various biomarkers, such as PD-L1 expression level and genomic alterations, with efficacy. Knowledge Generated This 2-year pooled analysis of CodeBreaK 100, which is, to our knowledge, the largest clinical data set with the longest follow-up reported for patients treated with any KRAS G12C inhibitor to date, showed that sotorasib treatment provided long-term efficacy and was well tolerated, with no new safety signals detected. Long-term benefit with sotorasib (defined as progression-free survival of at least 12 months) was associated with lower baseline circulating tumor DNA levels and was observed across KRAS G12C variant allele frequency levels, PD-L1 expression levels, and in a proportion of patients with STK11 and/or KEAP1 comutations.
Biomarker Analysis Centrally measured PD-L1 and/or genomic data were available for 114 phase II patients (Data Supplement). Most prevalent alterations were TP53 (46%), LRP1B (36%), KDM6A (32%), and STK11 (32%). Albeit limited in sample size, long-term clinical benefit with sotorasib was observed across PD-L1 expression levels (Fig  2A ). There was a nonsignificant trend toward enrichment of longer benefit with PD-L1 tumor proportion score (TPS) ,1% versus $1% (odds ratio [OR], 0. 36 [0. 12 to 1. 12]), without significant differences between PD-L1 TPS 1%-49% and $50% (OR, 0. 83 [0. 07 to 9. 69]). Most significant enrichment in patients with early progression was with mutant KEAP1 (OR, 0. 22 [0. 06 to 0. 87] long-term benefit v early progression); although not significant, these patients were more likely to have ROS1 (single-nucleotide PD-L1 IHC Group Central Testing A 1% (n = 31) 1%-49% (n = 21) t50% (n = 4) Patients (%).
DISCUSSION 7] [18]  A substantial proportion of patients derived long-term clinical benefit (1-and 2-year OS rates, 51% and 33%, respectively). Once-daily oral sotorasib 960 mg did not result in cumulative late-onset severe or chronic lower-grade toxicities. 0] [21] [22] [23] [24]  Two-year OS rate (33%) with sotorasib was higher versus docetaxel (historically 14%). 2  In the phase III CodeBreaK 200 randomized controlled trial (Clinical-Trials. gov identifier: NCT04303780), sotorasib showed statistically significant improvement in PFS versus docetaxel in pretreated KRAS G12C-mutated advanced NSCLC, with a 34% decrease in the relative risk of disease progression or death with sotorasib (HR 0. 66; P 5. 0017). 25  There was no OS difference, although the study was not powered for OS, and docetaxel arm crossover was permitted  25  ; improved quality of life with sotorasib was observed.
ACKNOWLEDGMENT The authors thank the patients and their families for participating in this trial, as well as  Lisa R. Denny, PhD , and  Lee B. Hohaia, PharmD  (ICON,  Blue Bell , PA), whose work was funded by  Amgen Inc , for medical writing assistance in the preparation of this manuscript. The authors thank  Agnes Ang, PhD , who contributed to the biomarker analysis presented in this work,  Maya Shehayeb, PharmD , and  Jennifer Martucci  for operational planning assistance,  Bob Dawson  for graphics assistance,  Liz Leight, PhD , and  Brittany L. Phillips, PhD , for medical writing support (all employed by  Amgen Inc ,  Thousand Oaks , CA). Therapeutics,  AmMax Bio ,  Revolution Medicines Speakers' Bureau: Boehringer Ingelheim Research Funding: Mirati Therapeutics (Inst) ,  Revolution Medicines (Inst) ,  Amgen (Inst) ,  Boehringer Ingelheim (Inst) ,  Virtec Pharmaceuticals (Inst) Patents ,  Royalties , Other Intellectual Property: I am listed as an inventor on a patent application filed by MSKCC that describes an approach to treat BRAF mutant cancers (Inst), I am listed as an inventor on a patent application filed by MSKCC that describes an approach to treat KRAS mutant cancers ( Inst) Qui Tran Employment :  Amgen Stock and Other Ownership Interests: Amgen Simon Jones Employment: Amgen Stock and Other Ownership Interests: Amgen Travel, Accommodations, Expenses: Amgen Abraham Anderson Employment: Amgen Stock and Other Ownership Interests: Amgen Patents, Royalties , Other Intellectual Property: I am listed as an inventor on several Amgen patents.
Acknowledgements Work in the Keyes lab was supported in part by grants from  La Fondation pour la Recherche Medicale (FRM)  ( AJE20160635985 ),  Fondation ARC pour la Recherche sur le Cancer  ( PJA20181208104 ),  La Fondation Schlumberger pour l'Education et la Recherche  ( FSER 19 (Year 2018 )/FRM),  La Ligue Contre le Cancer , and  Agence Nationale de la Recherche (ANR)  ( ANR-19-CE13-0023-03 ). AK was supported by a fellowship from  Eur IMCBiO.
The data concerning the systems D, R and I were taken as presented in the work of Marzanov et al. [9]. The occurrence of alleles and genotypes at diallelic loci (D, R, I) was determined based on the Hardy-Weinberg equation  [5]. To study the BMP-15, BMPR1B and GDF9 genes linked to high ovulation rates, the blood samples were taken from 4-5 years old ewes. After DNA isolation from whole blood, the determination of normal and mutant alleles in the BMP-15 locus was carried out according to the method of Polley et al. [11]  and  Malyuchenko et al. [12]. For this purpose, the sequencing of these genes was undertaken using an ABIPrism 3130xl device. Regarding the BMP-15 polymorphism concerning the mutations FecX G [391 (C-T)], FecX H 544 (C-T), FecX I [579 (T-A)], FecX L [635 (G-A)] and FecX B [773 (G-T)], primers defined in  [13]  were selected so that each amplified fragment contained the sites of all the single nucleotide substitutions described (SNPs, or single nucleotide polymorphism).
Characteristics of the Romanov Breed According to Seven Systems of Blood Groups Table  1  presents a detailed description of the Romanov breed according to six blood group systems  [9]. It shows data on phenotypic classes, genotypes and alleles. For each system, the number of individuals is in brackets. The B blood group system is shown separately (Table  2 ). According to the data obtained, the B blood group system is as complex in sheep as it is in cattle and goats. As can be seen in Table  2 , it contains many more phenotypic classes, genotypes and alleles than the other A, C, M, D, R and I blood group system data above. System B distinguishes simple and complex alleles. Simples have six alleles (B b , B d , B e , B i , B g , B -) and complexes up to ten (B bde , B bdi , B bdg , B bei , B beg , B big , B dei , B deg , B dig , B eig ).
Sampling description: On top of the data given on the original label, we have added the department (French administrative division) and the coordinates of the center of the locality where each specimen was collected (columns decimalLatitude and decimalLongitude). This gives an approximation of ca. 5 km, depending on each locality size. All species names were checked with the most recent list of European bee species  (Nieto et al. 2014 ). If a species name given on the label was not found on this reference list, a search of a possible synonym was performed, mostly from http://westpalbees. myspecies. info and the current name mentioned in the scientificName column, whereas the name given by the original identifier was put into the previousIdentifications column.
2014). If the original species name did not appear in this reference list, a search was done on http://westpalbees. myspecies. info and https:// www. bwars. com/search/node/Caelioxis websites to find the name currently used for names recognized as synonyms. If the original name could not be assigned to a current name unambiguously or if no identification had been given, no current species name was given in the data set. As much as possible, the locality of origin of the specimen was identified, and its latitude and longitude given by the website https://www. geoportail. gouv. fr/ was input. In a few cases, such as passes or forests between neighbouring localities, the precise coordinates of the location were input. In the CSV dataset format, fields are seaprated by tabs, all encoding is UTF-8, which allowed for all diacritic signs to be retained.
The 4253 specimens with accurate collection data (day, month, year) date from 1881 to 2018. The temporal distribution of the data according to the IUCN criteria of the European fauna  (Nieto et al. , 2014)  shows that most specimens belonging to endangered species were collected in the years 2000-2018 (Fig. 3 , Fig. 4 ). Only one specimen captured between 1950 and 1999 belonged to an endangered species (Trachusa interrupta) whereas a total of seven endangered species specimens were collected since 2000 (belonging to the species Trachusa interrupta, Colletes collaris, Lasioglossum breviventre and Lasioglossum laeve). On the other hand, four endangered species have no data since 1950: From the recently checked 1301 Bombus specimens from MHNL, 713 did not bear any previous identification label at the species level.
This work is licensed under a Creative Commons Attribution (CC-BY) 4. 0 Licence. All work derived from the present study should cite it appropriately, including the Museum where the material is held. Darwin core, so that it could be transferred later into GBIF as the identifications are checked and more precise locations entered. The whole data set (Suppl. material 1) includes 9752 Apoidea specimens from the Muséum d'Histoire Naturelle d'Aix en Provence (MHNAix), the Musée des Confluences, Lyon (MHNL), the Muséum d'Histoire Naturelle de Marseille (MHNM) and the Muséum Départemental du Var, Toulon (MDV). This dataset uncludes 2741 recently identified individuals and 9256 with geolocalization within France (Table 1). basisOfRecord InstitutionCode Muséum d'Histoire Naturelle de Marseille (MHNM), The specific nature of the data record (i.