dataesr/scientific-paragraphs-categorization huggingface dataset:
HYPK promotes NatA activity in planta Selective staining of free protein N termini revealed that both hypk lines accumulated soluble proteins displaying free N termini in comparable amounts as NatA-depleted plants (Fig. 2A ). We applied the SILProNAQ global proteomics approach for proteome-wide assessment of the NTA frequency of individual proteins  (2, 32, 33). Of the 419 unique N termini quantified in the hypk lines, 405 (97%) resulted from the cytosolic translation of nuclear genes, and 14 (3%) resulted from the translation of plastid-encoded genes. A total of 166 N termini (41%) were subject to iMet excision (NME), 51 (13%) proteins retained the iMet, and the remaining 188 protein N termini (46%) were caused by internal cleavage of proteins, predominantly occurring during maturation of nuclear-encoded mitochondrial or plastid proteins Proteomics Identifications Database (PRIDE, www.
ebi. ac. uk/pride) (PRIDE ID: PXD023195). An evident global decline of N-terminal acetylation was observed in both hypk lines. The average acetylation yield of the whole dataset was decreased by 12 ± 1% (PXD023195). This increase of nonacetylated proteins in hypk lines was triggered by the significantly decreased NTA of NatA substrates (27 ± 3%), characterized by iMet excision before acetylation of the penultimate amino acid (Fig. 2B ). Loss of HYPK affected NatA substrates displaying either A, G, S, or T at the neogenerated N terminus. The extent of the impact of both hypk lines on single entries of the fully acetylated subset of the wild type is displayed in fig. S6A. The data indicate that the HYPK knockout is similar in each line within the error bar and that the decrease is similar in most entries.
Neither transcript nor protein levels of NAA10 and NAA15 were significantly decreased in both hypk lines when compared to wild type (Table  1  and fig. S4 ). The catalytically active NAA10 protein even accumulated approximately twofold in roots of both hypk lines, potentially because of a feedback mechanism trying to compensate for decreased in vivo NatA activity in these lines (Table  1  and Fig. 2B ; PRIDE ID: PXD023599). These findings demonstrate that loss of HYPK explicitly decreases the activity of the cotranslationally acting NatA complex but does not decrease the abundance of the core NatA subunits. Noticeably, HYPK depletion did not impair the NTA frequency of proteins addressed by the other ribosome-associated Nats.
Loss of HYPK induces the ubiquitin-proteasome system To test whether HYPK affects plant metabolism and development exclusively by lowering NatA activity, we compared the transcriptome changes of hypk-3 and hypk-1 with the transcriptome changes induced by depletion of the catalytically active subunit of the NatA complex (Gene Expression Omnibus accession: GSE158586). The depletion of NAA10 caused the most substantial perturbation in gene expression compared to wild type, with 1503 and 1641 genes significantly up-and down-regulated. Approximately 1000 genes were either significantly up-or down-regulated in both hypk lines (Fig. 4 , A and B, and table  S1 ). The vast majority of these regulated genes (~75%) were coregulated in hypk lines and amiNAA10 (Fig. 4 , A and B, intersection). We did not find any gene that was antagonistically regulated in both hypk lines when compared to amiNAA10 (Fig.
5A ). Despite the up to 5. 7-fold faster protein degradation, the total level of extractable soluble proteins and the abundance of distinct proteins were unaffected in hypk lines (fig. S10 ). A shotgun proteomics approach confirmed that of the 1253 proteins detected in the wild-type and hypk lines (table  S3 ; PRIDE ID: PXD022120), only 31 proteins were significantly [permutation-based false discovery rate (FDR) ≤ 0. 05] decreased (<0. 67-fold) in hypk-1 or hypk-3 (Fig. 5, C  and D ). Of these lower abundant proteins, 81 and 94% were canonical NatA substrates (table S4; Fisher's exact test, P < 0. 0001 for the enrichment of NatA substrates in the subset of lower abundant proteins in hypk lines), strongly suggesting that lowered NTA of these NatA substrates caused their destabilization. In a companion study  (18) , we demonstrated that decreased NatA activity resulted in a faster turnover of NatA substrates and identified the novel nonAc-X 2 / N-degron targeting nonacetylated NatA substrates for degradation.
Search for HYPK in Arabidopsis proteome The Homo sapiens HYPK protein [NP_057484;  (30) ] was used as a query in the blastp program (National Center for Biotechnology Information; https://blast. ncbi. nlm. nih. gov/Blast. cgi?PAGE=Proteins) to search for the HYPK protein in A. thaliana. Input settings of blastp were as follows: expect threshold, 10; word size, 6; alignment matrix score, BLOSUM62; gap costs, existence, 11; extension: 1.
Whole-transcriptome analysis For gene expression profiling, total RNA was extracted as described above and converted to biotinylated antisense cDNA according to the Affymetrix standard labeling protocol. The resulting cDNA was hybridized to the Arabidopsis AraGene-1_0-st-type (Affymetrix) as described in  (10). A Custom CDF Version 20 with TAIR-based gene definitions was applied for array annotation  (51). Raw intensity values were RMA background corrected and quantile normalized. One-way analysis of variance (ANOVA) was performed to identify differentially expressed genes using SAS JMP10 Genomics, version 6, from SAS (SAS Institute, Cary, NC, USA). A false-positive rate of a = 0. 05 with FDR correction was taken as the level of significance. Venn diagrams were created with the public available analysis tool of the Bioinformatic & Evolutionary Genomic server (http://bioinformatics.
9% ACN (acetonitrile) (Biosolve) and 0. 1% FA] with a flow rate of 300 nl min -1 in a linear gradient (acetonitrile gradient: 3 to 21. 5%, 20 min; 21. 5 to 35%, 4 min). NAA15 was quantified from data acquired in a data-dependent acquisition mode, automatically switching between MS, acquired at 60,000 [mass/charge ratio (m/z) 400] resolution, and MS 2 spectra, generated for up to 15 precursors with normalized collision energy of 27%, measured at 15,000 resolution. To quantify NAA10, MS 2 spectra were acquired for up to nine unspecified precursors with additional five MS2 scans targeted for NAA10. Precursors for targeted analysis of NAA10 were m/z 538. 2, 558. 8, 743. 3, 745. 9, and 881. 4. For HYPK, four additional MS2 scans were acquired in data-independent mode with m/z of 508. 9, 596. 3, 604.
3, and 762. 9. To identify and quantify the proteins, raw files were analyzed using Proteome Discoverer with the Sequest (Thermo Fisher Scientific, San Jose, USA; version 2. 2). Sequest was set up to search against A. thaliana databases (UP000006548_201709. fasta, 82,082 sequences and UP000006548 unreviewed_201709. fasta, 15,727 sequences), common contaminants (MaxQuant 1. 5. 3. 30), and target proteins (NAA15, NAA10, and HYPK) with trypsin as the digestion enzyme. Parent ion mass tolerance was set to 10 parts per million (ppm), and fragment ion mass tolerance was set to 0. 02 Da. Carbamidomethylation of cysteine was specified as a fixed modification. Oxidation of methionine and acetylation of the protein N terminus were specified as variable modifications. For MS1 quantification, protein abundances determined by Proteome Discoverer were used.
Global proteomics for quantification of protein steady-state levels The global proteomics approach has been performed as described in  (18). In brief, proteins were extracted from leaves of 6-week-old soil grown plants according to the in-StageTip protocol  (57)  and analyzed on an EASY-nLC 1200 UPLC system (Thermo Fisher Scientific) that was coupled to a Q Exactive HFX Orbitrap instrument. The resulting MS raw files were analyzed using the MaxQuant software, version 1. 6. 1. 13 (58) , and peptide lists were searched against the species level UniProt FASTA database. A contaminant database generated by the Andromeda search engine (59) was configured with cysteine carbamidomethylation as a fixed modification and N-terminal acetylation and methionine oxidation as variable modifications. We set the FDR to 0.
01 for protein and peptide levels with a minimum length of seven amino acids for peptides. The FDR was determined by searching a reverse database. Enzyme specificity was set as C-terminal to arginine and lysine as expected using trypsin and LysC as proteases. A maximum of two missed cleavages was allowed. Peptide identification was performed in Andromeda with an initial precursor mass deviation up to 7 ppm and a fragment mass deviation of 20 ppm. All proteins and peptides matching to the reversed database were filtered out. Bioinformatic analyses were performed using Perseus  (60).
Statistical analysis The Holm-Sidak one-way ANOVA or the unpaired Student's t test of the SIGMA Plot12 software suite was applied for the detection of statistically significant differences between sample groups. Asterisks (*P ≤ 0. 05, **P ≤ 0. 01, ***P ≤ 0. 001) or letters indicate individual groups identified by the Student's t test or pairwise multiple comparisons with the Kruskal-Wallis or the Holm-Sidak one-way ANOVA, respectively.
Data collection Patient's clinical and pathological data, retrieved retrospectively from an electronic patients records management system (Clinicom® computerized record software), were collected on a database managed using Ennov Clinical® software. Questionnaires responses were integrated to the same database. Incomplete questionnaires were handled as per the THYCA-QoL and EORTC QLQ-C30 developer's recommendation  [13, 19]. All data were controlled and validated by a Clinical Data Manager.
3%) had a vocal cord impairment and 71 (25. 4%) had a transient or permanent parathyroid insu ciency resulting from treatment. The median interval between surgery and questionnaire completion was 2. 7 years (range: 0. 2 to 26. 3 years). We analyzed acceptability, oor and ceiling effects, reliability, convergent and discriminant validities, multi-dimensionality and criterion validity of the F-THYCA-QoL. Acceptability of the questionnaire was assessed by the percentage of missing data (missing items and missing forms). A high proportion of missing data may indicate poor acceptability of the instrument  [22]. Floor and ceiling effects were estimated for each item. As in the original study, oor or ceiling effects were considered to be present if more than 80% of the responders achieved the lowest or highest possible score respectively  [13].
Statistics The Mann-Whitney and Chi-square tests were used to assess statistical differences between "toxicity" and "non-toxicity" groups for each biomarker, p-values < 0. 05 were considered significant. Discriminatory capability of the features was additionally assessed using ROC-curves and the corresponding area under the curves (AUCs). We report features with AUC > 0. 65 as discriminatory. Data analysis was performed with FlowJo V10 (TreeStar) software, GraphPad Prism 8. 0. 1 software and RStudio 1. 3. 1093 (Foundation for Statistical Computing). Principal-component analysis (PCA) was performed using RStudio v1. 3. 1093 with FactoMineR PCA and Factoextra fviz_pca_biplot functions on MFI ratio values.
] [54] [55]  Title and abstract screening was performed by two independent screeners with content expertise (S. O. , W. S. ), and full-text review of screened studies was performed independently. A list of all articles screened was compiled. Relevant studies were included in our final analysis if they respected our eligibility criteria. One reviewer (S. O. ) performed data abstraction, verified by a second reviewer (A. W. ). Authors removed duplicate participants. In cases of identical cohorts described in many articles, we considered only the most recent article. Corresponding authors of all included studies were systematically contacted, and additional data were used when supplied by the authors.
61 Ten complete datasets were imputed for each regression analysis, and parameters and standard errors from the analysis were pooled according to Rubin's rules. 62 o account for the variability in follow-up among included patients and heterogeneity between studies, a mixed-effects Cox proportional hazards model was constructed, with the study that the patient originated from acting as the random-effects variable, to perform a time-to-event analysis of seizure recurrence. Time-toevent analyses are advantageous for the evaluation of seizure outcomes because it accounts for both the dynamic nature of postoperative seizures and variability in follow-up across patients by placing an increasingly positive value on a longer delay to seizure recurrence or follow-up duration that is entirely seizure-free, and vice versa.
| Study selection and risk of bias Using the search strategy detailed above, 4567 citations were initially identified. After exclusion of duplicates, 2483 citations remained, of which 191 were reviewed in full text following title and abstract screening (unweighted κ = 0. 746). ] [26] [27] [28] [29] [30] [31] [32] 45, 47, [65] [66] [67] [68] [69] [70] [71] [72]  Contacting the corresponding authors leads to complementary data in 145 of the 293 participants and supplied 19 additional patients. 16, 37 Ultimately, 312 participants were included in the final analysis. Twenty-two articles were retrospective case series, while two were retrospective case-control studies. The evaluation of quality and risk of bias of all included studies is detailed in Table  S1. Table  S2  provides characteristics of all included studies.
| DISCUSSION We performed a systematic review of the literature and meta-analysis with IPD on the surgical treatment of drugresistant IE. This review included 312 participants from 24 studies. Compared with the surgical treatment of temporal  and other ETE, which have been carried out in epilepsy centers worldwide for over half a century, widespread surgery for IE is relatively new, and data regarding its safety and efficacy are limited. 4] [75] [76] [77] [78] [79] [80]  In this regard, Kerezoudis et al performed a recent meta-analysis of patients undergoing surgery for insular epilepsy that revealed rates of overall seizure freedom (64. 3%) and postoperative neurological deficits (43. 2%, most of which were transient) comparable to our study. While their assessment is valuable, the overall findings are limited by the fact that the heterogeneity between studies was not accounted for, multivariate analyses were not performed, missing data were not imputed, and predictors of postoperative neurological complications were not evaluated.
| Strengths and limitations Strengths of this review include: (a) We performed a comprehensive search; (b) we did not exclude studies based on language of publication; (c) we obtained IPD to perform our meta-analysis; and (d) corresponding authors of all included studies were contacted for additional data. This is a very robust and rigorous method for conducting meta-analyses especially given that the majority of studies are small with a fair amount of heterogeneity; (e) we accounted for heterogeneity in clinical practices and patient populations across institutions through mixed-effects modeling; and (f) we adjusted for the length of follow-up, which eliminated biases that would have resulted if putative predictive variables were associated with length of follow-up. The review also has limitations: (a) Although an exhaustive search strategy was utilized, it is possible that some studies were not identified due to inappropriate indexing or errors in screening; (b) non-standardized reporting affects the validity of data abstraction and assessment of risk of bias; (c) there is a lack of recognized criteria for assessment of bias in prognostic cohort studies.
databases: Africa-Wide Information [Ebsco], AMED [Ovid] (Allied and Complementary Medicine Database), BIOSIS [Ovid], CINAHL [Ebsco] (Nursing and Allied Health Literature), Cochrane [Wiley], Embase [Ovid], Global Health [Ovid], LILACS (Latin American and Caribbean Health Sciences), Medline [Ovid], PubMed [NLM], and Web of Science [Thomson Reuters] for relevant articles from database inception to January 19th, 2020, (performed by a librarian, E. G. ). The search was restricted to humans but with no language limitations.
Overall, PCA and perMANOVA of the entire morphological datasets run on all five TS-biotic treatments, four of which included prey, showed a clear evolutionary change in fruiting body morphology relative to Anc and morphological divergence among treatments (Fig. 4a, b ) (perMANOVA: F = 50. 5, R2 = 0. 95, P = 0. 001). As for the TS-abiotic analysis, PCA of the entire TS-biotic population data set revealed that the primary component explains a large majority of the variance (93%) (Supp. Fig. 4a ) and high overall levels of trait correlation, as reflected by the similar positioning of the four traits in the morphospace (Supp. Fig. 4b ). However, we again tested whether the character of trait relationships may have diverged as a function of MyxoEE-3 selective environments by estimating their morphological integration (see Methods: Morphological analysis).
Swarming assay. The swarming rates of all TS-biotic evolved populations and their ancestors were quantified by measuring the total area covered by the myxobacteria swarm plated the original MyxoEE-3 selective environment. The experimental conditions were equivalent to those used during MyxoEE-3, except that in this study, Bacto agar instead of Select agar was used (ref. 104 ). Plates containing either CTT-HA or TPM-HA were prepared 24 h prior to inoculation with M. xanthus. The two prey E. coli and B. subtilis were grown in CTT liquid to stationary phase before being spread over the plates. In all cases, 10 µl of myxobacteria cultures growing in CTT liquid were spotted on the plate at a final density of 5 × 10 9 cells/ml. Plates were incubated at 32 °C with 90% rH for 4 days, after which swarm areas were manually outlined and subsequently measured with the software ImageJ 109.
Acknowledgements We thank  Kaitlin Schaal  for her comments on the manuscript. This work was funded in part by two  EMBO Long-Term Fellowships ,  ALTF 1208-2017  to M. L. F. and  ALTF 1411-2012  to O. R. and  Swiss National Science Foundation (SNF)  grant  31003B_6005  to G. J. V.
Image acquisition, processing and quantification XZ and YZ stacks of discs were acquired with sections every 1 µm using the confocal SP5 AOBS, 40x objective. Microscope settings were chosen to allow the highest fluorescence levels to be imaged under non-saturating conditions. Image data were processed and quantified using ImageJ software (National Institute of Health). An ImageJ macro was designed to quantify SNAP-SMO fluorescence from the Z projections (average intensity) of the stack (8 sections). Firstly, the macro determines the shape and limits of the disc. It then asks the user to select a point in the disc (selected at the A/P boundary) from which rectangular regions from apical to basal, with the same width, will be drawn across the disc. Following this, each region is divided into three smaller ones: the apical/subapical, lateral and the basal subregions.
Statistics and data representation See also Figure  S1. The mean intensity is also shown for the whole epithelial column. N= 17 and 10 for shi + and shi ts flies, respectively. Note the weaker basal effect of SHI inactivation in presence of HH, which indicates that HH may slightly reduce SMO basal endocytosis. (D-E") XZ confocal images of wing imaginal discs from apGal4, Gal80 ts ; UAS SNAP-smo WT (D) or apGal4, Gal80 ts /UAS YFP-rab5 CA ; UAS SNAP-smo WT (E-E") flies put at restrictive temperature (to allow rab5 CA expression) before dissection and labeled for surface SNAP-SMO. In the latter case, E" is a merge image with Surf SNAP-SMO in green and YFP-RAB5 CA in red. Note that for a better visualization of SMO, imaging of rab5 CA and control discs were not done in the same conditions. SMO is initially targeted (curved arrow) from the Golgi compartment to the apical plasma membrane (presented in pink), where it is endocytosed (pink membrane vesicle).
ACKNOWLEDGMENTS We are grateful to  Drs. M. Crozatier ,  A. Guichet ,  D. Hipfner ,  J. Jian ,  P. Therond , F. Schweisguth for generously sharing their fly lines and reagents; to  A. Benhmerah ,  A. Guichet  and  S. Léon  and our colleagues from the  Institut Jacques Monod  for insightful discussions,  Andréa Mialet  and  Severine Nozownik  for their technical help. We are very grateful to  Drs. G. D'Angelo  and  R. Holmgren  for sharing their expertise and for their insightful advice. The Apa 1,  4D9 ,  4F3  and  20C6  monoclonal antibodies were obtained from the  Developmental Studies Hybridoma Bank , created by the  NICHD  of the  NIH  and maintained at The  University of Iowa, Department of Biology, Iowa City , IA 52242. Drosophila embryo injections were carried out by  BestGene Inc. We acknowledge the  ImagoSeine core facility of Institut Jacques Monod , member of  France-BioImaging  ( ANR-10-INBS-04 ) and certified  IBiSA.
RNA Sequencing RNA sequencing analysis was carried out for 12 (4 for each subgroup: low, medium and high, respectively) mouse kidney RNA samples and sent to AtlasBiolabs (Berlin, Germany) for processing. The RNA was adjusted to 100 ng RNA/ul and enriched by polyA affinity kits before sequencing. Subsequently, the samples were sequenced on an Ilumina Nova sequencing device ("paired-end" analysis), with a sequencing depth of more than 30 million base pairs (bp) with an average sequence length of 136 bp. Raw data were imported into ArrayStudio (Qiagen, Les Ulis, France) Omicsoft software. The "RNA-Seq-Pipeline" was used to align the sequence fragment of each sample to a mouse genome model and a reference library mouse gene. Standard normalization was performed which gave values in FPKM (fragments per kilobase million) for the mRNA of each gene and isoform detected in the sample, indicating a normalized expression value.
Acknowledgments: We thank  P. Wohlfart  from  Sanofi-Aventis (Diabetes Research) and AtlasBiolabs (Berlin, Germany ) for RNAseq analysis, the technical staff ( C. Kitou ,  L. Louedec ) of the Tenon animal facility for helping with animal handling, the biochemical platforms of  Centre de Recherche et de Inflammation (CRI) of Bichat Hospital  and the  Centre de Recherche des Cordeliers (CRC)  for the biochemical measurements.
Randomization and masking RCT: Each enrolled caregiver-child pair was randomly assigned to one of the study arms by study staff. Stratified block randomization was used with a block size of 56 and six strata based on enrollment vaccine cohort (BCG, penta-1, and penta-2) and sex. The randomization lists were generated by Dr. Rachel Glennerster and her team using the statistical software Stata. The allocation sequence was concealed from the study staff responsible for screening and enrolling participants through realtime phone-based access to the randomized sequence (see supplemental material). The final treatment assignment was not masked from the study staff responsible for enrollment or the participants. Serosurvey: The sub-sample was stratified on sex, enrollment vaccine cohort, study arm, and lottery status.
Study procedures and intervention RCT: All screening, enrollment, and follow-ups were conducted by study staff at the study immunization clinics via the Government of Sindh's Zindagi Mehfooz electronic immunization registry (EIR) with added studyspecific functionalities. Participants providing verbal consent were enrolled and assigned a unique study ID and Quick response (QR) code pasted on the government-issued EPI card. The QR code was scanned through the EIR to record the child's biodata, demographic information, and immunization history. Participant data was submitted to an electronic server in realtime, and the caregiver-child pair was allocated to a study arm via the pre-programmed randomized sequence. Airtime payments to caregivers' registered cellphone number were automatically generated by the EIR, approved by a dedicated study team member, and could be used instantly by participants.