dataesr/scientific-paragraphs-categorization huggingface dataset:
*p<0. 05 (one-way ANOVA followed by Bonferroni's test) vs C57Bl6/J and vs B6129SF2/J mice. B: The relative abundance of genes involved in placenta development and functions (proliferin, Gcm1, Mash2, CD31) was analyzed by real-time RT-qPCR in the 3 groups of mice (C57Bl6/J, B6129SF2/J and TRPC6 -/-). Data are normalized to C57Bl6/J mice with n= 4 per group. Mean ± SEM with *p<0. 05 (one-way ANOVA followed by Bonferroni's test) vs C57Bl6/J and vs B6129SF2/J mice. Zn were found in the 3 groups of mice (C57Bl6/J, B6129SF2/J and TRPC6 -/-) (Fig. 3B ). This showed that the deletion of TRPC6 was associated with a Zn enrichment in the placenta but not in the embryonic brain, indicating the existence of tissue specific alterations of the homeostasis of cations in TRPC6 -/-mice.
Discussion The placenta is a unique organ that plays key roles in the transport of minerals, oxygen and nutrients. Various pathophysiological conditions can alter its functions and therefore influence the success of pregnancy. Human and murine placentas express high amounts of TRPC6  [2, [11] [12] [13]  but the physiological contribution of this channel to placental functions is currently unknown. To address that question we used a TRPC6-deficient mice strain  [15]. TRPC6 -/-females delivered less pups when compared to C57BL6/J and B6129SF2/J females mice. For instance, C57Bl6/J mice had an average of 6-7 pups per litter (see Mouse Phenome Database, http://www. jax. org/phenome) whereas TRPC6 -/-mothers had 4-5. The number of pups at birth is an important physiological parameter with functional implications on various aspects of offspring development  [28]  such as age at sexual maturity and reproductive behaviors  [29].
Acknowledgements We also wish to acknowledge support from the  Centre National de la Recherche Scientifique (CNRS) ,  Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA) , l' Institut National de la Santé et de la Recherche Médicale (INSERM)  and the  Université de Grenoble Alpes (UGA). Subjects have given their written informed consent. Animal experiments were conducted in compliance with the French legislation and the  European Community Council Directive  of 24 November 1986 ( 86/609/EEC ). The experimental protocol was approved by the ethical committee of the  CEA's Life Sciences Division (CETEA). The study was supported by grants from l'  Agence Nationale de la Recherche  ( ANR-13-NEUR-0003-02  and  ANR-16-CE29-0024  to AB) and the  Fondation pour la recherche Médicale (FRM)  ( SPF20150934074  to RAN).
Affinity measurements Affinities of the different VHHs for the LR were determined in a similar plate-binding assay as described before: VHH-coated plates were incubated with a serial dilution of the mouse LR extracellular domain fused to SEAP (mLR EC -SEAP)  [50]  for 2 h. The GraphPad Prism software was used to calculate the affinities from the bound SEAP measurements.
Data points are the mean (± STDEV) of quadruple luciferase measurements (cps: counts/s). Both datasets are representative for at least three independent experiments ◂ upon reconstitution of STAT3 signalling. Luciferase data in Fig. 1d -f clearly illustrate that both EGFR and LR form homo-oligomers on the membrane, but also cluster with each other in the absence of any ligand, and that, in accordance with the co-immunoprecipitation data, this clustering does not depend on the LR IGD.
Two days after transfection, cells were stimulated with a serial dilution of leptin S120A-T121A (b) or wild-type leptin (c) as indicated. Mean luciferase counts (± STDEV. ) of quadruple measurements are plotted. Both datasets are representative for at least three independent experiments with the other two VHHs. To prolong half-life in circulation, VHHs were genetically fused to a VHH directed against mouse serum albumin (mAlb)  [50]. Healthy mice were treated with the resulting bispecific VHHs on a daily basis and food intake and body weight were measured throughout the duration of the experiment. Data in Fig. 4a  and b  show that treatment with 2. 17-mAlb and 4. 10-mAlb resulted in a significant increase in food intake and body weight, while 4. 80-mAlb does not seem to have any effect. Mice were killed on day 14 and fat pads (subcutaneous and visceral) were dissected and weighed.
p. at the start of the starvation and 24 h later with PBS, pegylated leptin or a combination of pegylated leptin and 4. 80-mAlb. Animals were killed, thymi (a, b) and spleens (c, d) isolated and weighed (a, c) and the total number of white blood cells (b, d), splenic lymphocytes (e), neutrophils (f) and monocytes (g) counted using the Hemavet instrument. Values represent mean ± SEM; *P < 0. 05, **P < 0. 01, ***P < 0. 005 vs. ad libitum-fed controls, unless stated otherwise. Data representative for three independent experiments to high incidence of early-onset obesity in the Nochurli population. Surprisingly, affected patients are still fertile and not more susceptible to infections (unpublished data). This latter is in strong contrast to earlier described human loss-of-function mutations in leptin or LR genes  [79].
Differential scanning calorimetry (DSC) The thermal characteristics during starch gelatinization were determined by using a Multi-Cell Differential Scanning Calorimeter (MC-DSC) -(TA Instruments, Lindon, UTAH, USA). Before analysis, the samples were weighed in the ampoules (total mass (starch + water) so that each contained 700 mg, keeping the relation of 10. 7 g starch / 100 g). An ampoule with alumina powder was used as reference and three runs for each sample were analyzed. The MC-DSC heating program consisted in going from 30 to 130 °C at a rate of 2 °C/min. The onset temperature (To), the peak temperature (Tp), the conclusion temperature (Tc), and the enthalpy (ΔH) associated with the starch gelatinization interval were calculated with the aid of the Universal Analyzer software (TA Instruments).
Acknowledgments The authors are grateful to the  Région Pays de la Loire / RFI "FOOD 4 TOMORROW"  for funding the  Post-doctoral fellowship  " STARCH-3D " of  B. Maniglia , to the  São Paulo Research Foundation  ( FAPESP, Brazil)  for funding project n°  2016/18052-5 , and to the  National Council for Scientific and Technological Development (CNPq, Brazil)  for funding the productivity grant of  P. E. D. Augusto  ( 306557/2017-7 ). This study was funded in part by the  "Coordenação de Aperfeiçoamento de Pessoal de Nível Superior -Brasil (CAPES)" -Finance Code 001 , through the D. C. Lima Ph. D. scholarship.
Immunoblots Aliquots of the collected fractions were treated with a final concentration of 50 µg/ml PK (1 hour, 37°C). Samples were then mixed in Laemmli buffer and denatured at 100°C for 5 min. The samples (15 µl) were run on 12% Bis-Tris Criterion gels (Bio-Rad, Marne la Vallée, France) and analyzed by immunoblots, using the Sha31 anti-PrP antibody (human PrP epitope at residues 145 to 152  [35] ). Immunoreactivity was visualized by chemiluminescence (GE Healthcare). The amount of PrP present per fraction and the PrPSc glycoforms ratios were determined with the GeneTools software after acquisition of chemiluminescent signals with a GeneGnome digital imager (Syngene, Frederick, Maryland, United States).
Conclusion Together, our data would expand the prion quasispecies concept to an ensemble of macromolecular assemblies, -not necessarily associated to different substrains-, that complement each other to adapt tissue-specific selection pressure and extend prion host range. Such 'epistatic' behavior may provide new fundamental principles for understanding prion distinctive properties to transfer between species  [54]  and can explain the relative inability of recombinant PrP to generate high-titer prions  [55] , unless submitted to intense mechanisms of polymerization/fragmentation which may generate aggregate polydispersity and/or a larger portfolio of conformations  [56]  for complementation. analyzed for PrPres content by immunoblot and for infectivity by an incubation time bioassay in tgOv and tgBov mice (tg110 line).
Microscopic images were obtained using a Leica TCS SP5 confocal microscope (Leica Microsystems, Wetzlar, Germany), and analyzed with FiJi, Leica light and Imaris software. Turbidity assay for fibrin formation. Washed platelets from WT, Unc13d -/-and Nbeal2 -/-mice were activated with 0. 1 U/mL or 1 U/mL thrombin in the presence or absence of 100 μM ZnCl 2 or apyrase (2 U/mL)   A, B ) Turbidity assay on (A) resting and (B) thrombin-activated platelets. (B) WT, Unc13d -/-and Nbeal2 -/-platelets were activated with 0. 1 U/mL thrombin in the presence or absence of 100 μM ZnCl 2 , and turbidity was measured at 405 nm in an ELISA reader, n = 3 mice per group, Mean ± SEM. (C-H) Citrated whole-blood from WT, Unc13d -/-or Nbeal2 -/-mice, labelled with DiOC 6 (0. 5 μg/mL) and AF647-fibrin(ogen), (8.
Platelet-mediated fibrin formation in recalcified mouse whole blood using a microfluidics flow chamber with microspots of collagen and tissue factor, at a shear rate of 1000 s -1 was measured, as described before  22. statistical analysis. Statistical significance was analyzed using SigmaPlot 11 software. Statistical difference of the means (Mean ± SEM) was determined using 2-way analysis of variance, followed by the stated test of variance for significance or an unpaired Student's t test. P values < 0. 05 were considered to be significant (*P < 0. 05, **P < 0. 01, ***P < 0. 001, ****P < 0. 0001).
Acknowledgements The authors thank  Mike Friedrich  from the  Bioimaging center (Rudolf Virchow Center, Würzburg ) for excellent technical support. This work was supported by grants from This study was supported by the  Interreg Euregio Meuse Rhine programme PolyValve  to M. N. , S. B. and J. W. M. H. ; and by the  Deutsche Forschungsgemeinschaft  project number  374031971-TRR 240/A09  to A. B. and H. M. H.
s c r i p t conference. The author also insists on the fact that all the research advances presented in this review are the result of a collective work, and therefore acknowledges all the persons involved. The complete financial disclosure is provided in the Supplementary Material S1. doi:10. 5061/dryad. ch4nr. Summary of 10 years of nutrition research (2008-2018) using in vivo brain imaging in the conventional pig ([Large White x Landrace] x Piétrain) and minipig models. All these studies were performed by our INRA research group on the PRISM imaging platform of Rennes, France. The approximate age of the animals at the time of brain imaging is indicated in the second column. All references were ordered chronologically. Main imaging techniques used: 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET) to map brain glucose metabolism; 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) single-photon computed tomography (SPECT) to map cerebral blood flow; functional magnetic resonance imaging (fMRI) based on blood-oxygenlevel dependent (BOLD).
| Study population The IeDEA global paediatric collaboration is part of the global IeDEA research consortium (https://www. iedea. org/), supported by the US National Institutes of Health since 2006, to describe HIV epidemiology and evaluate HIV outcomes using large patient-level observational databases. HIV care cohorts from sub-Saharan Africa (West, Central, Eastern and Southern Africa regions), the Asia-Pacific, and the Caribbean, Central and South America (CCASAnet) regions contributed data for this analysis. We merged data collected from HIV clinics in partnership with IeDEA from these six sub-regions between 2003 and 2016. Among patients who had at least one visit available during adolescence, with at least one height measurement during this period (i. e. age 10 to 19 years), inclusion criteria to assess growth throughout adolescence were as follows: reported perinatally acquired infection or entering HIV care before 10 years of age (proxy for perinatally acquired HIV when not documented); having a documented date of ART initiation, at least one height measurement between 10 and 16 years of age; and followed in care until at least 14 years of age.
| Variables and data management We studied growth using height-for-age, defined by the WHO child growth standards  [24, 25] , expressed in z-scores (HAZ). Stunting was defined as HAZ lower than À 2 standard deviations (SD), with moderate stunting between À 3 and À 2 SD and severe stunting lower than À 3 SD. Z-scores lower than À 10 or greater than + 10 were viewed as outliers and removed. Growth velocity defined as height gain in centimetre (cm) per year was compared to the reference population from the WHO child growth standards for a subset of adolescents having at least two height measurements. We calculated growth velocity per year by dividing the height gain in cm between two clinical visits by the time in years between these two visits. Velocities greater than 20 cm/year and below À 1 cm/year were excluded as outliers.
Wasting was defined using weight-for-height z-score (WHZ) for children under five years of age, and body-mass-index-for-age z-score (BAZ) for children aged more than five years. Immunodeficiency for age at ART initiation was defined following the 2006 WHO guidelines  [26]. The location of the clinic site (urban or mostly urban, rural or mostly rural) was also recorded. Follow-up for patients was analysed on a six-monthly basis, with data on immunologic, clinical, anthropometric status and ART regimen collected. Loss to follow-up was defined as having a last contact longer than six months before database closure in children not known to have died or transferred out, and transfer was documented when adolescents were transferred to another paediatric clinic or to adult care.
The model contained time-varying age (=10 years plus follow-up time) as a covariate which was included non-linearly using (penalized) splines  [28]. Age at ART initiation, stunting and wasting at ART initiation and at age 10 years, current CD4 count, CD4 count at age 10 years, CD4 count at ART initiation and at first visit as well as region and location of clinic site were considered as potential adjustment variables. To take into account missing data, especially at baseline, we conducted multiple imputation for stunting and wasting at age 10 years and ART initiation as well as CD4 count and location, using the Amelia II package in R  [29]. The imputation model contained all measured variables, as well as splines of time and lagged variables of CD4 count. Variable selection using the AIC criteria was applied to the imputed data sets  [30, 31].
| Selection and characteristics of the study population Between 2003 and 2016, 68,461 patients receiving care in the six IeDEA regional cohorts had at least one visit during adolescence. Of these, 50,469 (74%) had one available HAZ measurement during the same period, and 21,038 (42%) of them met criteria for perinatally acquired infection. Among APH on ART, the majority had at least one available HAZ measurement between 10 and 16 years of age. The median age at last follow-up was 14. 2 (interquartile range (IQR) 12. 1 to 16. 5 years), with 43% followed up until at least 14 years of age. Among the APH excluded for not being followed after 14 years of age, 73% had not yet reached age 14 years by the time the database was closed. The final study population included 8737 APH (Figure  1 ). APH excluded for three criteria (no information on ART initiation (A), no HAZ measurements between 10 and 16 years of age (B), no follow-up after 14 years of age (C), Figure  1 ) were compared to the final study population.
A study in Botswana showed that severe short stature among children and adolescents with HIV was associated with virologic failure  [44]. In a review on growth after ART initiation among children, the ART regimen used was not associated with growth evolution  [22]. Also, pregnancy data were not recorded in all regions and then not included. Metabolic data were also not available, but would have been valuable to better assess the effect of long-term ART on growth  [45, 46]  Our results could have been affected by selection bias, as they were driven by the large proportion of children from Southern Africa, which may not be representative of growth among APH worldwide. Excluding children who were not followed-up until at least 14 years of age substantially restricted our sample size and adolescents who were LTFU or died before age 14 were not included, leading to survivor bias, with the risk of underestimating the prevalence of stunting in this population.
A U T H O R S H I P JJ and M Schomaker conducted the analysis. JJ wrote the paper. MD, VL and M Schomaker supervised the analysis and the writing of the paper. KM contributed to the data management. DW and AK contributed and represent the cohort data from the Asia-Pacific region, SS and MM for the Southern Africa region, M Sylla and KK for the Western Africa region, SA and RV from the Eastern Africa region, CM for CCASAnet and MY for Central Africa region. All authors have read and approved the final manuscript.
O M P E T I N G I N T E R E S TAuthors have no conflict of interest to declare. F U N D I N GResearch reported in this publication was supported by the US National Institutes of Health. Asia-Pacific: The TREAT Asia Pediatric HIV Observational Database is an initiative of TREAT Asia, a program of amfAR, The Foundation for AIDS Research, with support from the US National Institutes of Health's National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Cancer Institute, National Institute of Mental Health, and National Institute on Drug Abuse as part of the International Epidemiology Databases to Evaluate AIDS (IeDEA; U01AI069907). Caribbean, Central and South America network for HIV epidemiology (CCASAnet) is a member cohort of the International Epidemiology Databases to Evaluate AIDS (leDEA) (U01AI069923; CMG is a PI).
C O M P E T I N G I N T E R E S TAuthors have no conflict of interest to declare. F U N D I N GResearch reported in this publication was supported by the US National Institutes of Health. Asia-Pacific: The TREAT Asia Pediatric HIV Observational Database is an initiative of TREAT Asia, a program of amfAR, The Foundation for AIDS Research, with support from the US National Institutes of Health's National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Cancer Institute, National Institute of Mental Health, and National Institute on Drug Abuse as part of the International Epidemiology Databases to Evaluate AIDS (IeDEA; U01AI069907). Caribbean, Central and South America network for HIV epidemiology (CCASAnet) is a member cohort of the International Epidemiology Databases to Evaluate AIDS (leDEA) (U01AI069923; CMG is a PI).
27 To our knowledge, this is the first international comparison of hypertension control   54. The respective 95% confidence intervals were 5 estimated with bias-corrected bootstrap methods. All adjustment variables were not available 6 for some of the participating studies, either because they were not collected or because they 7 were missing for ≥ 20% of participants (Table  S10 ). We used data from these 3 cohorts to conduct international comparisons of the prevalence of uncontrolled BP in adults F 4 with CKD before and after adjustment for well-known risk factors for poor hypertension 5 control. We also described patterns of antihypertensive therapy prescription by study cohort 6 and world region in this population. 1A  and Supp Tables  S31  and S42 ). In contrast, further adjustment for 9 history of cardiovascular disease, BMI, and most importantly for albuminuria (Figure  1B ) The number of antihypertensive drug classes prescribed was highest in the cohorts from 10 7 North America, where more than 6050% of individuals were usinghad 3 drug classes or more 8 (Figure  3 , Supp Table  9 ).
27 Although unstudied geographical specificities characteristics including genetics,  34  28 diet,  35  economic level,  28  and public health policies  36   12 For each study, we also asked for three datasets containing grouped information including 13 the number of participants having a particular profile, and respective number of participants 1 ratios correspond to the ratio of the true prevalence of uncontrolled BP for a given study 2 cohort according to the model (predicted mean), divided by the prevalence that would be 3 expected for a hypothetical cohort with the same case-mix and an intercept parameter equal 4 to the population average (marginal mean)  54. The respective 95% confidence intervals were 5 estimated with bias-corrected bootstrap methods. All adjustment variables were not available 6 for some of the participating studies, either because they were not collected or because they 7 were missing for ≥ 20% of participants (Table  S10 ).
Missing covariates, by study. : BP, blood pressure; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate. If missing values were more than 20% for covariates in a given cohort, these covariates were excluded from analyses. We acknowledge the KNOW-CKD investigators and the study coordinators for their dedication to this study. We also thank the Medical Research Coordinating Center, Seoul National University Hospital for the assistance with data acquisition and management and analysis. KNOW-CKD study was supported by the Research Program funded by the Korea Center for Disease Control and Prevention (2011E3300300, 2012E3301100, 2013E3301600, 2013E3301601, 2013E3301602, 2016E3300200, 2016E3300201, and 2016E3300202). We acknowledge the nephrologists of the NRHP-URU for submitting the data of their patients.
The NRHP-URU is funded by the Fondo Nacional de Recursos. PROVALID funding was provided in part by the European Union (grant agreement number 241544, Systems Biology towards Novel Chronic Kidney Disease Diagnosis and Treatment) and AbbVie. PSI BIND-NL We acknowledge the initial PSI BIND-NL investigator for establishing the cohort: Gerjan Navis, Peter J. Blankestijn, Jeroen Deegens, Johan W. De Fijter, Jaap J. Homan van der Heide, Ton Rabelink, Raymond T. Krediet, Arjan J. Kwakernaak, Gozewijn D. Laverman, Karel M. Leunissen, Pieter van Paassen, Marc G. Vervloet, Pieter M. TerWee, Jack F. Wetzels, Robert Zietse and Frans J. van Ittersum. PSI was funded by the Dutch Government (FES-funds), the NFU and the 8 UMCs of The Netherlands. contribution of the following co-investigators who contributed to the original RRID cohort study: Drs N.
J. McIntyre, A. Shardlow, S. D. S. Fraser, P. J. Roderick, R. J. Fluck and C. W. McIntyre. The RRID study was funded by a Research Project Grant (R302/0713) from the Dunhill Medical Trust, a joint British Renal Society and Kidney Research UK fellowship (to NJM) and an unrestricted educational grant from Roche Products Ltd. No pharmaceutical company had any input into study design, data collection or analysis. The data are wholly owned by the investigators.
Acknowledgements  iNET-CKD (International Network  of CKD cohort studies) is endorsed by the  International Society of Nephrology. Analysis were conducted at the  Inserm Center for Research in Epidemiology and Population Health (CESP), Villejuif, France. We acknowledge  Sandrine Damster  for the efforts in managing this project. We thank  Jo Ann Cahn  for editing the English version. The  International Network of Chronic Kidney Disease cohort studies (iNET-CKD) Acknowledgements iNET-CKD (International Network  of CKD cohort studies) is endorsed by the  International Society of Nephrology. Analysis were conducted at the  Inserm Center for Research in Epidemiology and Population Health (CESP), Villejuif, France. We acknowledge  Sandrine Damster  for the efforts in managing this project. We thank  Jo Ann Cahn  for editing the English version.