dataesr/scientific-paragraphs-categorization huggingface dataset:
Isothermal titration calorimetry (ITC) The thermodynamic parameters of the molecular interactions between human centrins (full-length 1 and 2 and their C-terminal domains) and the target peptide were investigated via ITC using a MicroCal MCS instrument (MicroCal Inc. , Northampton, MA). The protein and peptide were equilibrated in the same buffer (50 mM MOPS, 100 mM NaCl pH 7. 5) supplemented with 1 mM CaCl 2 or 2 mM EDTA. The centrins (10 lM) in the calorimeter cell were titrated with the peptide-target (100 lM) by automatic injections of 8-10 lL at 30 °C. On some occasions, the centrin/peptide target ratio was 10-170 lM. The first injection of 2 lL was ignored in the final data analysis. Integration of the peaks corresponding to each injection and correction for the baseline were performed using the Origin-based software provided by the manufacturer.
Acknowledgements This work was supported by the  Centre National de la Recherche Scientifique , the  Institut National de la Santé et de la Recherche Médicale  and the  Institut Curie. Dora Grecu  acknowledges a PhD Grant from the  Université Pierre et Marie Curie. We thank the  Laboratoire de Spectrométrie de Masse Protéomique de l'Institut Curie.
05). SIRT2 expression after MM and fasting with red wine is significantly correlated with downregulation of CCL5 and upregulation of CAT ( < 0. 001). GPX1 increased significantly in the comparison between baseline and all conditions with red wine. We highlighted for the first time the positive effect of red wine intake combined with different but widely consumed meal types on ox-LDL and gene expression. Trial Registration. This trial is registered with ClinicalTrials. gov NCT01890070.
Bioelectrical Impedance Analysis (BIA). Resistance (), reactance (  ), impedance, and phase angle (PA) at 50 kHz frequency (single frequency, SF) were measured using BIA phase-sensitive system (BIA 101S, Akern/RJL Systems, Florence, Italy). Measurements were taken on the left side of the body with injection and sensor electrodes placed on the hand and foot in the reference position. TBW, extracellular water (ECW), intracellular water (ICW), Na/K ratio, PA, body cell mass (BCM), and body cell mass index (BCMI) were calculated from bioelectrical measurements and anthropometric data by applying the software provided by the manufacturer which incorporated validated predictive equations  [29].
Sample Collection and RNA Extraction. A fasting blood sample was collected and stabilized in PAXgene Blood RNA Tubes (PreAnalytiX Qiagen, Hombrechtikon, Switzerland) and stored at -80 ∘ C until RNA extraction. The total RNA of each collected sample was purified using the PAXgene Blood miRNA Kit according to the manufacturer's instructions (PreAnalytix Qiagen, Hombrechtikon, Switzerland). Aliquots of total RNA were then quantified and assessed for quality by spectrophotometry (Nanodrop, Wilmington, USA) and agarose gel electrophoresis. 2. 6. Quantitative Real Time PCR and Data Analysis. We used specific RT 2 Profiler PCR Arrays (Qiagen, Netherlands); for our study we focused on the Human Oxidative Stress (PAHS-065ZA) pathway, in particular SIRT2 CCL5SOD, CAT, and GPx. Each qRT-PCR experiment was performed in triplicate and repeated at least twice according to the manufacturer's instructions (Qiagen, Netherlands).
Acknowledgments Laura Di Renzo  designed the research and wrote the paper;  Alberto Carraro ,  Roberto Valente , and  Leonardo Iacopino  conducted the research;  Roberto Valente  analyzed the data;  Antonino De Lorenzo  had primary responsibility for the final content. All authors read and approved the final paper. The authors would like to thank  Francesca Sarlo ,  Daniela Minella ,  Guido Rillo ,  Anna Anzidei ,  Elaine Tyndall , and  Nicoletta Del Duca  for their contribution to the study. The authors have no financial or personal interests in any organization sponsoring the research at the time the research was conducted. This study was supported by Grants from the  Ministry of Agriculture, Food and Forestry  ( DM 18829/7818/2009 ).
The luciferase activity of pGL3-Enhancer-Myh2/1/4 was seven to twelve times higher for either of the promoters, than with pGL3-Myh2/1/4. Enhancer activity was not observed in plasmids with mutated MEF3 sites associated with either of the Myh promoters (Figure  1C ). Enhancer activity was neither observed with the promoters of the slow Sln (Figure  S3B ) or Tnni1 genes, or with the promoter of the ubiquitous b-actin gene (Figure  S3C ). A weak enhancer activity was observed with Myh4 promoter in primary embryonic fibroblasts, in which Six1 is expressed (Figure  S3D  and data not shown). These data showed that high MYH enhancer activity was only reached in vivo and required specific interactions with MYH promoter elements. To determine in vivo interactions between the enhancer and each Myh gene, we performed chromatin conformation capture (3C) assays of adult fast EDL (Extensor digitorum longus) myofibers.
lincRNAs can localize in cytoplasm  [16]  or as a single focus  [19]  or multiple foci  [20]  in nuclei. To analyze linc-MYH localization in skeletal muscle fiber, we performed fluorescent in situ hybridization (FISH), using linc-MYH sense and antisense RNA on isolated myofibers from fast EDL. Intranuclear localization of linc-MYH was observed with the antisense linc-MYH RNA probe, with approximately 10 linc-MYH foci per nucleus (n = 10, Figure  4C ), while the sense linc-MYH RNA probe gave no signal (data not shown). We concluded from these experiments that linc-Myh RNA accumulates at specific sites in the nucleus of fast myofibers.
ChIP experiments GP and TA muscles of 2 months old mice were minced with scissors just after sampling and fixed in 1% formaldehyde for 10 minutes. Formaldehyde was quenched by addition of 0. 125 M glycine, and muscles were washed twice in PBS. The muscles were incubated on ice in lysis buffer (10 mM Tris-HCl pH 7. 9, 85 mM KCl, 0. 5% NP40, protease inhibitors (cOmplete, Roche)) for 10 minutes and homogenized with a mortar and, subsequently with a Dounce homogenizer. The nuclei were obtained by centrifugation, incubated in SDS lysis buffer (50 mM Tris-HCl pH 8, 10 mM EDTA, 1% SDS, protease inhibitors) for 10 minutes, and sonicated in a Bioruptor apparatus (Diagenode). The debris were removed by centrifugation. The sonicated DNA was incubated with 1 mg of Six1 antibodies (HPA001893, Sigma) under agitation at +4uC overnight.
Cross-links were reversed, and DNA was then purified by phenol extraction and ethanol precipitation. To correct for the PCR amplification efficiency of different primer sets, a BAC clone containing the mouse Myh locus (RP23-61C14) was digested, ligated and used as control templates. Quantification of the data was performed by quantitative real-time PCR using the Lightcycler 480 probe master (Roche Diagnostic). The sequences of the oligonucleotides used in this study are given in Table  S3.
Acknowledgments We thank  V. Moncollin  at  ENS Lyon  for help with the adult muscle ChIP experiments, the imaging facility at  Institute Cochin  for technical assistance, the sequencing and genomic platform at  Institute Cochin  for microarray experiments and  F. Dumont  and  S. Jacques  for advice. We thank  P. Billuart  for the shRNA expression vector,  F. Le Grand  for teaching isolated myofibers isolation,  E. Perret  for his help with gene expression analysis,  D. Blanchot  for advice on the FISH experiment and  S. Gautron ,  C. Rougeulle ,  L. Dandolo ,  F. Le Grand  and  A. Sotiropoulos  for reading the manuscript.
IS is supported by  ANR ,  The Uehara Memorial Foundation  and  JSPS Postdoctoral Fellowships for Research Abroad. Financial support was provided by the  Institut National de la Santeet la Recherche Medicale (INSERM), the ''Association Francaise contre les Myopathies'' (AFM) , the  Centre National de la Recherche Scientifique (CNRS) , the Peps '' Bio-Math-Info '', and the  Agence Nationale pour la Recherche  ( ANR RPV09108KKA ). We also acknowledge a contribution to the  Institut Cochin animal care facility , made by the  Region Ile de France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
NMR spectroscopy All of the NMR experiments were performed on a 600 MHz Varian UNITY INOVA spectrometer at 299 K. DSS (4,4-dimethyl-4-silapentane-1-sulfonic acid) was used as reference. Spectra were processed using NMRPIPE  [16] , and analyzed with NMRVIEW  [17]. The 15 N and 1 H N chemical shifts for free MC1 have already been reported  [9]  and those for bound MC1 were assigned from a combination of 1 H- 15 N HSQC (heteronuclear single quantum coherence) and 2D 15 N NOESY-HSQC (mixing time of 150 ms) spectra. Chemical shift perturbation (CSP) data of the protein were calculated and analyzed with SAMPLEX  [18]. The 1 H NMR resonances of the free 15-mer dsDNA were assigned from a combination of NOESY (nuclear Overhauser effect spectroscopy) (mixing times of 150 and 300 ms) and TOCSY (total correlation spectroscopy) (mixing time of 60 ms) spectra.
Structure analysis The Adaptive Poisson-Boltzmann Solver (APBS) program  [19]  was used within PyMOL to display the results of the calculations as an electrostatic potential molecular surface. The Platinum software  [20]  was used to calculate and visualize molecular hydrophobic/hydrophilic properties using the concept of ''Molecular Hydrophobicity Potential'' (MHP). Sequence homology and alignment were performed using online Protein BLAST software (blast. ncbi. nlm. nih. gov). The structures of nucleic acids were analysed using the CURVES+ software  [21]. The figures were drawn with VMD  [22] , PyMOL  [23]  and MOLMOL  [24].
Docking of DNA onto the MC1 protein Several steps were used to obtain DNA/MC1 complexes and are schematically reported in Supplementary Figure  S1. Coarse-grained docking with BIOSPRING. An interactive docking experiment was performed using the BioSpring program  [25]. Flexible double-strand DNA was driven into the electrostatic potential of a static coarse-grained molecular shape of the free MC1 protein corresponding to the first model of the 2KHL PDB structures. DNA should be strongly curved in the final complex, as observed from electron microscopy experiments  [13]. Taking this into account and in order to obtain a better convergence of the simulation, two kinked-DNA conformers were extracted from DNA-protein complexes available in the PDB (1A74, recognition DNA sequence of I-PpoI  [26]  and 1YTB, yeast TATA-box) and were used as starting structures.
Determination of the DNA-binding surface of MC1 As attested by the superimposition of 1 H- 15 N HSQC spectra between the free and the DNA-bound form of MC1 (Supplementary Figure  S5 ), the overall structure of the protein is largely unchanged upon binding. Measurement of 1 H N and 15 N chemical shifts on both the free and bound forms of MC1 yielded the chemical shift perturbations (CSP) along the sequence of MC1. These CSP data were analyzed using the SAMPLEX software  [18]  and are reported in Supplementary Figure  S5. Significantly perturbed residues were located in five sites: the a-Helix from Pro24 to Arg34, three residues in the center of the b3-strand (Ile45-Leu47), six residues belonging to the b4-strand (Phe58-Glu63), part of the loop LP5 (Pro72-Pro76) and practically all of the residues constituting the b5-strand (Val84-Glu90).
We therefore performed a second docking with the commonly used HADDOCK program using the 15 free conformations of MC1 in solution and 10 15 bp DNA models extracted from the previous docking. Both the protein and DNA were considered semi-flexible molecules. Eight models of the DNA-MC1 complex were selected from the more populated clusters (,140/200 pdb). Their bound DNA is bent with an average curvature of 104621u (Supplementary Figure  S9 ). The angle of curvature depends on the position of the loop LP5 with regard to the core of MC1. As in the first models, the protein hangs on to the extremities of the DNA by inserting the expected residues Pro72, Trp74, Met75, Lys85, Lys86, Arg88 and Ile89 in the minor groove. The side chain of Lys22 is most probably involved in the minor groove interaction as well (Figure  4 ).
An important point to note is the complete conservation of the residues Pro24 to Lys30, belonging to the a-helix, which seems to ensure the correct positioning of the Arg25 side-chain. In our opinion, the proposed model built for Methanosarcina thermophila MC1 is representative of MC1 from Methanomicrobia and Halobacteria species and more generally from the Euryarchaeal subdomain (Figure  7 ). Bending proteins, used by all organisms across the three domains of life to compact genomic DNA, belong to distinct families of small, basic and abundant chromatin proteins (Figure  6 ). Many 3D structures of DNA complexes with bending proteins are deposited in the Protein Data Bank and most of them were obtained by crystallography: In Bacteria, 5 structures are known with HU  [52] [53] [54] , 11 with IHF  [52] [53] [54] [55] [56] [57] , and 12 with Fis  [58].
M. H. received support from Agence Nationale de la recherche bearing the reference ANR-09-BLAN-0234-01, and also acknowledges support from the Swedish research council (VR) and the Swedish National Space Board (SNSB). G. Ö. is a Swedish Royal Academy of Sciences research fellow supported by a grant from Knut and Alice Wallenberg foundation, and also acknowledges support from the Swedish research council (VR) and the Swedish National Space Board (SNSB). A. V. benefits from the fellowship 'Boursière d'excellence de l'Université de Genève'. Facilities: HST (ACS,WFC3).
I. O. was financed through the Sciex fellowship by the Rectors' Conference of Swiss Universities. H. A. and D. K. are supported by the Centre National d' Études Spatiales (CNES) and the Programme National de Cosmologie et Galaxies (PNCG). P. L. acknowledges support from the ERC-StG grant EGGS-278202. H. O. F. acknowledges financial support from CONACYT grant 129204, Spanish FPI grant BES-2006-13489, and was also financed through a postdoctoral UNAM grant. H. O. F. and J. M. M. H. are partially funded by Spanish MICINN grants CSD2006-00070 (CONSOLIDER GTC), AYA2010-21887-C04-02 (ESTALLIDOS) and AYA2012-39362-C02-01.
Data Sources UNICEF and the Ministry of Health performed a cross-sectional secondary analysis of the Cambodia Demographic Health Survey (CDHS)  [1, 12, 13]  to observe the trends in infant and young child feeding practices such as breastfeeding practices, early initiation of breastfeeding (within one hour after birth), pre-lacteal feeding, the use of BMS, and trends in bottle use. This secondary analysis was based on the three latest CDHS conducted in 2000, 2005 and 2010 and the authors used the most recently available Cambodia DHS datasets from 2000, 2005, to 2010. The CDHS collected data on demographics, socioeconomics and health, and this is a useful and valid source of information on IYCF from a nationally representative sample of households. A total of at least 15,000 households were selected for the survey.
Breastfeeding Indicators The rate of EBF was defined as the proportion of infants, aged 0-5. 9 months, who received only breast-milk and no other fluids or solids except for drops or syrups consisting of vitamins, minerals supplements or medicines  [14, 15]. The EBF rate was estimated according to the WHO recommended definition of this key IYCF indicator  [15]  with further categorization for the following age ranges 0-1, 2-3 and 4-5 months of age  [15]. It should be noted that EBF does not represent the proportion of infants who are exclusively breastfed from birth until sixth months of age, rather it is a snapshot of current practices for all children 0-5. 9 months of age. A wealth index was constructed from data collected in the household questionnaire, and was divided into five categories (from lowest to highest, Q1 to Q5 respectively).
To confirm this hypothesis, analysis was completed with near full-length sequencing of the HCV genome using next-generation sequencing (NGS) on the same sample. Results confirmed the presence of an RF2k/1b strain with a breakpoint between genomic regions of genotype 2k and 1b localised in the NS2 region between nucleotide position 3,189 and 3,200 on the H77 reference genome (Figure  1 ), as previously observed in the reference RF2k/1b genome sequence (GenBank accession number: AY587845)  [2].
Genotyping Following this identification, the virology laboratory in Lyon, as well as the collaborating laboratory in Grenoble, decided to perform two genotyping methods, namely NS3 sequencing and either LiPA 2. 0 or core sequencing, for each new genotyping request when one of the following criteria were met: patients with previous treatment failure infected with HCV genotype 2 (based on previous LiPA 2. 0 results), NS3 or NS5B sequence clustering with available RF sequences in GenBank or patients born in Russia or in the countries of the former Soviet Union, as these regions represent the major source of circulating HCV recombinants described to date. This strategy led to the detection of the RF2k/1b strain in nine additional patients (two in Grenoble and seven in Lyon). Of these 10 patients, six were born in Georgia, three in Armenia and one in Azerbaijan.
Core sequencing confirmed that the 5' fragment of these genomes belonged to genotype 2k (Figure  2a ), whereas NS3 sequencing led to the classification of the 3' fragment of the viral genome region as 1b (Figure  2b ). Overall, core and NS3 sequences from all strains clustered with previously described RF2k/1b and were distinct from reference sequences of non-recombinant genotype 2k and genotype 1b, respectively. GenBank accession numbers for all sequences obtained in this study are indicated in the Table. Since the beginning of 2014, HCV from 21 patients originating from the Caucasus (i. e. born in Armenia, Azerbaijan or Georgia) have been genotyped in the virology laboratory in Lyon: eight were RF2k/1b, eight were of genotype 1b, four of genotype 3a and one of genotype 4a. Patients in Grenoble are not described here in detail as some of their demographic data were incomplete.
Among our patients, the RF2k/1b strain was, along with 1b, the most frequent genotype detected in patients originating from the Caucasus area. Thus the recombinant RF2k/1b strain seems to have spread widely and appears to be one of the major strains infecting patients from these countries. Moreover, this RF was identified in 10 new patients during a single eightmonth period, whereas only 37 isolates of this particular strain have been reported in GenBank to date since the first description in 2002  [2, 4]. Based on these observations, it can be hypothesised that the number of patients infected with the RF2k/1b HCV strain (and maybe other recombinant HCV forms) is underestimated. During the study period, HCV genotyping has been verified by NS3 sequencing in 16 patients not born in the Caucasus region who were infected with HCV previously classified as genotype 2 by either LiPA or sequencing of the 5' non-coding region.
Epidemiological surveillance for rotavirus infection, data collection and analysis We studied RV laboratory detections from virological laboratory surveillance and all-cause GE consultations in under five year-olds from a Dutch sentinel General Practice (GP) network. The virological surveillance collects weekly numbers of virus detections from between 17 and 21 virological laboratories registered with the Dutch Working Group for Clinical Virology (NWKV), serving primary care, hospitals and long-term care facilities. RV diagnostic testing is not routinely recommended for suspected infectious GE, but stool tests are performed in approximately two-thirds of children admitted for GE and in 10% of children with GE visiting primary care  [3]. We analysed data from 1999 to 2014 by RV epidemiological year, defined as running from August to July of the following year.
We analysed GP consultations for all-cause GE in under five year-olds using routine electronic health record data from general practices participating in the NIVEL Primary Care Database (NIVEL-PCD). Here, data were available from August 2006 to July 2014. Consultations are coded according to the International Classification of Primary Care (ICPC)  [5]. Data are provided by 240 general practices covering a population of 1 million people, ca 5. 5% of the Dutch population. Every Dutch citizen is obliged to be registered with a general practice. The GP acts as a gatekeeper for specialised, secondary healthcare. The electronic medical records kept by the GP, therefore, provide the most complete picture of the population's health. Descriptive statistics were used to summarise data by RV epidemiological year and by seasonal month.
Timeseries analysis was performed to assess trends in weekly counts of RV detections and in GE consultations in under five year-olds, and to compare the 2013/14 RV season (January-April) to the same months in previous years. Negative binomial regression models were fitted to each data source separately. We adjusted the models for seasonal patterns (adding an indicator variable for month), for potential long-term linear trends and for variations in the number of reporting laboratories or person-time under observation, respectively. Both models were corrected for residual autocorrelation by adding lagged residuals.
Discussion We observed an exceptionally low number of RV detections and a low primary care GE consultation rate in children under five years of age, with nearly complete absence of winter excess, during the period of the typical RV season in 2014. This is a striking finding in the absence of RV vaccination in the Netherlands. The observation that the decrease was found in both datasets indicates that the low number of RV detections is not a surveillance artefact, and likely reflects reduced RV circulation. Our RV data did not include the number of RV tests performed. However, there have been no changes in diagnostic guidelines or reimbursement policy that could have impacted RV testing practices in 2014 compared to previous years. Potential contributing mechanisms for the reduced RV circulation in 2013/14 include the mild winter, the relatively high RV epidemic season in the previous year, a low birth rate and, possibly, RV vaccination programmes in the neighbouring countries  [6] [7] [8].
In seven HTs, staff cohorting and/or appointment of a unit casemanager nurse was adopted, while in the other 10 HTs neither of the two was adopted. Eight HTs out of 17 reported repeated observational audits of compliance with contact precautions based on a planned schedule, while seven HTs reported random audit activities and two HTs reported no audit activity. Data on use of hand hygiene products were also requested from the HT hospital pharmacies. The consumption rate of these products significantly increased  during the implementation of regional guidelines for CPE control, and the mean regional rates (litres/1,000 hospital days) were 5. 1, 6. 8 and 9. 4 in 2010, 2011 and 2012, respectively.
Between January and May 2013, 352 cases of HAV infection were notified in Italy corresponding to a 70% increase compared to the same period in 2012, and preliminary investigations indicated mixed frozen berries as the most likely vehicle of infection  [12]. Following these alerts, a decision was taken in Ireland to retrospectively and prospectively genotype and sequence all available samples from serologically confirmed cases of HAV infection since the beginning of 2013. In June 2013, three HAV cases from Ireland were identified as subgenotype IA, a strain identical to the one occurring in the Italian outbreak (GenBank accession number: KF182323)  [12]. None of the cases had a history of travel to Italy. An outbreak investigation commenced and a multidisciplinary outbreak control team was established.