dataesr/scientific-paragraphs-categorization huggingface dataset:
) in prophylactic setting as well as a dose of 9. 5x103     PFU/mouse (Figure7D-F) in treatment setting. Mice were monitored daily for weight loss and any other signs of disease. Statistics All data are presented as mean ± s. d. or mean ± s. e. m. , unless specified in the figure legends. Student's t-tests were applied to determine the statistical significance between two datasets and one-way ANOVA was used to perform analyses between more than two datasets, unless specified in the figure legends. A value of p ≤ 0. 05 was considered significant (denoted * p ≤ 0. 05, ** p < 0. 01, *** p < 0. 001, **** p < 0. 0001). Graph Pad Prism Software 8 was used to produce the graphs and to perform statistical analyses. ACKNOWLEDGEMENT We thank Cezarela Hoxha, Laurent Audry, Yuen-Yan Chang, Sylvain Meunier (Institut Pasteur, Paris, France) and Imène Belhaouane (Institut Pasteur, Lille) for technical involvement as well as Caroline Stefani (Benaroya Research Institute, USA), Daniel Ladant (Inst.
Pasteur) and Jean-Nicolas Tournier (IRBA) for fruitful discussions. This work was funded by the joint ministerial program of Research and Development against Chemical, Biological, Radiological, Nuclear and Explosive risks (CBRNE), a grant from the Agence Nationale de la Recherche (ANR-19-ASTR-0001), Labex IBEID (ANR-10-LABX-62-IBEID), the French Alternative Energies and Atomic Energy Commission (CEA). N. M. , L. C. , F. V. and E. P. were supported by DGA-MRIS/AID scholarships with CEA and Pasteur, respectively. SIMoS and SCBM are members of the Laboratory of Excellence LERMIT, supported by a grant from the Agence Nationale de la Recherche (ANR-10-LABX-33).
, 2002b; Lukić et al. , 2014). Studies of LPSs from the CLP  (Ji et al. , 2002)  and the Danube Basin  (Lukić et al. , 2014; Obreht et al. , 2016)  demonstrated the strength of combining magnetic and colorimetric parameters. While many multi-proxy studies have been performed on archives covering the last glacial cycle, investigations of European LPSs spanning multiple glacialinterglacial cycles are fewer (e. g. ,  Jordanova et al. , 2007; Necula et al. , 2013; Basarin et al. , 2014; Marković et al. , 2015; Zeeden et al. , 2016; Sümegi et al. , 2018; Antoine et al. , 2019; Obreht et al. , 2019). In this study, we extend colorimetric data to about 430 kyr with the Zemun LPS record from the Middle Danube Basin (MDB), spanning from Marine Isotope Stage (MIS) 11 to MIS 5a. Besides a dominating amount of quartz, feldspar, phyllosilicate and carbonate grains, comprising the average composition of the upper continental crust, Eurasian loess consists of heavy minerals and measurable relevant ferromagnetic (s.
Samples were exposed to a saturating field of 500 mT, Hu (min, max) were selected after initial test-measurements to ± 80 mT, and Hc (min, max) to 0 and 100 mT. Averaging time was set to 300 ms, reducing measurement noise. For each diagram, 150 FORCs were acquired at a field increment of ca. 1. 9 mT. For weak samples originating from loess units, 2-9 series of FORC measurements were measured and averaged. The number of FORCs averaged for each sample is reported as n-values in Figure  6. FORC data analyses were carried out using FORCinel version 3. 06  (Harrison and Feinberg, 2008). The main pre-processing consisted in drift and high-field slope corrections, first point removal, and lower-branch subtraction. FORCs of loess samples, for which multiple FORC were measured, were averaged in FORCinel.
High-Resolution IRM Acquisition Complementary to FORC measurements, high-resolution stepwise isothermal remanent magnetizations (IRM) were acquired on the same samples using the VSM. Samples were demagnetized before IRM acquisition. The initial field was set to 15 µT, the final field to 1. 5 T, using 300 logarithmically spaced measurement steps. Tentative un-mixing of the IRM acquisition curves was carried out with aid of the MAX UnMix RShiny web-application  (Maxbauer et al. , 2016). Smoothing factors were set between 0. 5 and 0. 6, depending on measurement noise. Before using MAX UnMix, first derivatives of the raw IRM acquisition data were calculated, distributions of suspected tephra and bracketing loess samples compared to determine roughly the number and characteristics of geologically realistic components.
CONCLUSION AND SUMMARY In this study, we present a new high-resolution loess-paleosol paleoclimate record from the Middle Danube Basin based on the application of environmental magnetic and colorimetric techniques for the last four-interglacial-to-glacial cycles spanning from MIS 11 to MIS 4. Data stemming from the S2 pedocomplex reveals different stages of environmental change during an interglacial, reflected by different coercivities, magnetic grain sizes, and different magnetic mineralogies. The combination of rock-magnetic and colorimetric data for the Zemun loess profile confirms the proposed aridification trend by  Marković et al. (2009) ,  Buggle et al. (2013), and Obreht et al. (2016). Furthermore, our HGR dataset indicates a general decreasing summer heat or dryness over the last 430 kyr in the Middle Danube Basin.
ACKNOWLEDGMENTS We want to thank the Zemun sampling team. We want to thank  Kathrin Worm  ( LIAG Grubenhagen ) for the additional colorimetric measurements and  Eva Meier  ( University of Bayreuth ) for language improvements of this manuscript. DV was supported through a fellowship provided by  Alexander von Humboldt Foundation. All data will be made available on the Pangaea Data Repository. This is IPGP contribution 4210.
Embryo bisection and RNA extraction Using a binocular magnifying glass, collected embryos were immediately photographed with a size standard to subsequently determine embryo diameter using ImageJ® software (version 1. 52a; National Institutes of Health, Bethesda, MD, USA). Then embryos were washed 4 times in commercially available Embryo holding medium (IMV Technologies, France) at 34°C and bisected with a microscalpel under binocular magnifying glass to obtain a trophoblast (TE_part) and an inner cell mass enriched (ICMandTE) hemi-embryo. At this stage, the TE_part is composed of trophectoderm and endoderm whereas the ICM is composed of epiblast cells. Directly after bisection, RNA extraction of each hemiembryo was started in extraction buffer (PicoPure RNA isolation kit, Applied Biosystems, France) for 30 min at 42°C prior to storage at -80°C.
Data analysis All statistical analyses were performed by comparing ON to OM (set as reference group) using R version 4. 0. 2 [46]  on Rstudio software version 1. 3. 1056 [47]. Embryo were sexed using X Inactive Specific Transcript (XIST) expression as previously described  [23]. Seven embryos were determined as females (4 in the ON group and 3 in the OM group) while 4 were considered as males (1 in the ON group, and 3 in the OM group).
Thus, ICMandTE and TE_part RNA quantities were summed up. With embryo diameter, both variables were analyzed using a linear model of nlme package version 3. 1-148  [48]  including maternal age and embryo sex, followed by 1000 permutations using PermTest function from pgirmess package version 1. 6. 9 [49]. Variables were kept in models when statistically significant differences were observed. Differences were considered as significant for p < 0. 05.
Deconvolution of gene expression in ICMandTE using DeMixT The deconvolution method has already been described in equine embryos  [23]. Briefly, this method enables the estimation of the relative gene expression of TE and ICM cell types within the hemi-embryo ICMandTE which is composed of both trophoblast and inner cell mass in unknown relative proportions. After filtering out all genes with at least 3 null count values in at least one group (ON or OM) per hemiembryo (ICMandTE or TE_part), removing genes with a null variance in TE_part and adding the value "1" to all count values in ICMandTE and TE_part datasets, deconvolution was performed using the DeMixT R package version 1. 4. 0  [50, 51]. Output datasets were DeMixT_ICM_cells and DeMixT_TE_cells, corresponding to the deconvoluted gene expression in ICM cells and TE cells of ICMandTE, respectively.
Maternal parity comparison for gene expression All genes with an average expression <10 counts in both ON and OM per hemi-embryo (ICM or TE) were filtered out on the DeMixT_ICM_cells and TE_part datasets. Differential analyses were performed with Deseq2 version 1. 28. 1  [52]  with the OM group as reference, without independent filtering and taking into account embryo diameter and sex in the model. Genes were considered differentially expressed (DEG) for FDR < 0. 05 after Benjamini-Hochberg correction (also known as false discovery rate, FDR). Equine Ensembl IDs were converted into Human Ensembl IDs and Entrez Gene names using gorth function in gprofiler2 package version 0. 1. 9 [56]. Genes without Entrez Gene names using gprofiler2 were manually converted when Entrez Gene names were available, using Ensembl web search function  [57].
Gene set enrichment analyses (GSEA) After log transformation using RLOG function of DESeq2 version 1. 28. 1, gene set enrichment analyses (GSEA) were performed on expressed genes using GSEA software version 4. 0. 3 (Broad Institute, Inc. , Massachusetts Institute of Technology, and Regents of the University of California)  [58, 59]  to identify biological gene sets disturbed by maternal parity. Molecular Signatures Databases  [60]  version 7. 1 (C2: KEGG: Kyoto Encyclopedia of Genes and Genomes; REACTOME, C5: BP: GO biological process) were used to identify most perturbed pathways. Pathways were considered significantly enriched for FDR< 0. 05. When the normalized enrichment score (NES) was positive, the gene set was enriched in the ON group while when NES was negative, the gene set was enriched in the OM group.
05) between the ICMandTE and the TE_part (Figure  1A ). After deconvolution, the comparison between DeMixT_ICM_cells and DeMixT_TE_cells yielded 7,116 differentially expressed genes while the comparison DeMixT_ICM_cells vs TE_part yielded 5,615 differentially expressed genes, with 5,103 in common (74%). Moreover, all but one of the initially 303 differentially expressed genes before deconvolution were also identified as differentially expressed in both post-deconvolution analyses. On the PCA graph of individuals, Axis 1 (21. 8% of variance) separated well groups according to data origin. ICMandTE and TE_part were separated on axis 1 but very close before deconvolution (Figure  1B ). DeMixT_TE_cells and TE_part were partly superposed, indicating that datasets before and after deconvolution have a similar global gene expression; whereas the DeMixT_ICM_cells group is clearly separated from both, indicating that the deconvolution effectively enabled the separation of gene expression in the two cell types.
Acknowledgments The authors are grateful to the staff of the  Institut Français du Cheval et de l'Equitation (IFCE) experimental farm (Jumenterie du Haras du Pin, Exmes, France)  for care and management of animals. We acknowledge the high-throughput sequencing facility of  I2BC  for its sequencing and bioinformatics expertise. The bioinformatics analyses were performed thanks to  Core Cluster  of the  Institut Français de Bioinformatique (IFB)  ( ANR-11-INBS-0013 ). The authors thank  A. L. Lainé  and the staff of the  Phenotyping-Endocrinology laboratory  for the hormonal assays. Many thanks to  Matthias Zytnicki  and  Christophe Klopp  for their advice on RNA-seq de novo analysis. Many thanks to  Pablo Ross  who kindly provided the coordinates for the XIST gene.
The first sample consisted of 186 adult basketball players (106 males and 80 females), the vast majority of Caucasian origin. As the study of this cohort is cross-sectional, the stature, chronological age and pubertal stages between the ages of 160 and 164 months were identified for boys. The stature of the girls was measured between 159 and 178 months and the age at menarche was obtained by questionnaires. The actual adult stature of these individuals is known, with the females averaging 179. 2 cm and the males 194. 3 cm. These data were collected in 2013 and 2014 as part of a Figure  2. Polynomial curves of degree 2 in stature (y = cm) for males and females according to age (t = months). These curves were modelled over the age range of 120 to 216 months using average curves that represent growth kinetics as a function of biological maturation.
In the projection, average stature values converge at around 177 cm at the age of 216 months (18 years) for males and around 165 cm at the age of 17. 5 years for females. The standard deviation for stature is 6 cm in males and 5. 6 cm in females. research project with the French Basketball Federation ("Predictaille" software). All participants and their parents gave their oral and written consent to participate in the studies in accordance with the Helsinki Declaration. The second sample is made up of 40 individuals (26 females and 14 males) from Moange le Bosquet, a Baka pygmy village in south-eastern Cameroon. African pygmies, who include many different groups, live in equatorial rain forests and grow to an average adult stature of < 155 cm  41. Pygmies share a common ancestor and split from Bantu-speaking populations at around 60,000 years BP  42.
Acknowledgements The author thanks  X. Garde ,  B. Bordage  and all the staff at the  IRD in Yaounde  for their logistical support, and the nuns at the  Le Bosquet mission  for their kind hospitality. Special thanks to  P. Kalo ,  J. B. Etoa  and other Baka collaborators for their help, assistance and friendship. This study was supported by the  CNRS , the  IRD  and grants from the  Wenner-Gren Foundation  ( Gr7810 ),  National Geographic  (# 8863-10 ) and the  ANR Blanc   SVSE7-2011  'GrowinAP' programme.
(Trp82Valfs*4) InDel in exon 2 of CCDC51 (NM_001256964. 2) (will be submitted to https://databases. lovd. nl/shared/genes/CCDC51, accessed on 9 April 2021) remained on the list (Figures  1c  and 2 , Table  1 ). The 3 nucleotides 5 -TGG-3 at positions 244 to 246 were deleted and replaced by 17 nucleotides 5 -GTGGAGATATGAAGATA-3 in exon 2. This is predicted to lead to a shift in the coding frame and a shorter form of the protein or nonsense-mediated mRNA decay. The variant was validated in the index patient as well as in all available family members by Sanger sequencing and co-segregated with the phenotype in the three-generation family following an autosomal recessive mode of inheritance (Figure  1c ). Among these homozygous regions, the four largest had sizes of 25, 18, 20, and 13 Mb and mapped to chromosomes 2, 3, 12, and 15, respectively.
Together, screening results of CCDC51 revealed that this gene defect is an ultra-rare cause of autosomal recessive RCD as it has been previously found for other novel gene defects underlying IRD  [8] [9] [10]. Similarly, rare loss-of-function mutations in another mitochondrial gene, IDH3B, led to non-syndromic RCD in three families  [23, 24]  and was mentioned to be mutated in a patient with an unspecified syndrome  [25]. According to the American College of Medical Genetics and Genomics standards, the variant was classified as pathogenic (1a) (PVS1, PVS4, PM2, and PM3)  [21, 22]. This probably disease-causing variant is rare and is not reported in current variant databases including gnomAD. CCDC51, mapping to chromosome 3  (48, 473, 481 ,529 bps on GRCh37/hg19) contains 4 exons of which exons 2-4 are coding (Figure  2a ).
Expression Results of CCDC51, a Novel Candidate Gene Defect Underlying Mild arRCD To further investigate the potential role of CCDC51, alias MITOK, in the retina, never described before, expression studies were performed. Transcriptomic analysis in public database revealed that CCDC51 is ubiquitously expressed e. g. , in the adrenal gland, blood, bone, brain, intestine, kidney, muscle, ovary, pancreas, skin, testis, but also eye (Hs. 187657, found in former available UniGene database). This agrees with studies from others showing the presence of RNA and protein of MITOK in all tissues in humans and mice  [27, [32] [33] [34]. In addition, here, retinal expression was investigated using available human and mouse transcriptomic databases. Indeed, the human transcript of CCDC51 and more specifically the four exons of CCDC51 were found to be expressed in human retina  [20]  (Figure  2b ).
Interestingly, in mice, Ccdc51 showed high expression in rod and possibly cone photoreceptors of the retinal-cell-type comparative transcriptome atlas  [35, 36]  (Figure  3a ). Due to high variability of the experiments for this gene in this database, it is unclear if Ccdc51 is also expressed in horizontal, bipolar, amacrine, ganglion, and microglial cells (Figure  3a ). Indirectly, expression of Ccdc51 was also suggested in photoreceptors in the mouse model, rd1, where its relative expression decreases with age-dependent rod photoreceptor degeneration (Figure  3b ) and in the rod-less mouse, Nrl -/-at postnatal day 21, where the Ccdc51 transcript is less abundant compared to wild-type mice (Figure  3c ).
Genetic variation annotations were realized by an in-house pipeline (IntegraGen), and results were provided per sample or family in tabulated text files. Stringent filtering criteria were used to select the most likely pathogenic variant(s) as previously described  [13]. Only variants showing a minor allele frequency of ≤0. 5% in Exome Variants Server (EVS, http://evs. gs. washington. edu/EVS, accessed on 9 April 2021), HapMap (http://hapmap. ncbi. nlm. nih. gov, accessed on 9 April 2021), 1000Genomes (http://www. 1000genomes. org, accessed on 9 April 2021), Exome Aggregation Consortium (ExAC, http://exac. broadinstitute. org, accessed on 9 April 2021), and genome Aggregation Database (GnomAD, http://gnomad. broadinstitute. org, accessed on 9 April 2021), in these databases were kept. The variants had to be nonsense, missense, splice site variants, or represent a small InDels.
Gene Expression Analyses Putative candidate genes showing putative disease-causing variants were investigated for their expression in different transcriptomic databases including UniGene (http://www. ncbi. nlm. nih. gov/unigene, accessed on 9 April 2021), the retinal gene expression profile database provided by Farkas and colleagues for human retina  [20] ; the in-house rd1 mouse expression database (http://kbass. institut-vision. org/KBaSS/transcriptomics/index. php, accessed on 9 April 2021) to investigate if the gene is expressed in rod photoreceptors as these mice undergo early rod photoreceptor degeneration due to mutations in Pde6b  [37] ; a database based on transgenic mice, to see in which kind of retinal cells the candidate gene is expressed (https://www. fmi. ch/roska. data/index.
php, accessed on 9 April 2021)  [35, 36] , and the database of the "rod-less" Nrl -/-mouse (https://retseq. nei. nih. gov, accessed on 9 April 2021)  [57]  to acquire knowledge if the candidate gene is also expressed in cone photoreceptors. Expression of the candidate gene has been experimentally validated in human retina (Clonetech, Palo Alto, California), in human control cDNA (universal, multitissues, Clonetech), in human fibroblast, in blood, in COS-1 and HeLa cells with primers in exon 2 and 4 of CCDC51 (Ex2cDNAF: 5 -CACAGCATTCAGCAACGAGC-3 and Ex4aR: 5 -GGACTACCTGCCTGTGACC-3 ), and the sequence of the transcripts was validated by Sanger sequencing with the same primers (detailed conditions will be delivered on request).
Protein Localization Studies The following online sites were used to predict the protein domains and protein localization of the candidate protein, MitoMiner 4. 0, a database of mammalian mitochondrial localization evidence, phenotypes, and diseases (http://mitominer. mrc-mbu. cam. ac. uk/ release-4. 0/report. do?id=1003774, accessed on 9 April 2021), (https://www. proteinatlas. org/humancell/mitochondria, accessed on 9 April 2021) and (http://www. uniprot. org/ uniprot/Q96ER9, accessed on 9 April 2021).
Specificity of Antibody against CCDC51 To perform functional analysis in mammalian cell lines and retinal tissues a rabbit anti-CCDC51 (HPA010980, Sigma, Saint Quentin Fallavier, France) antibody, directed against the human protein, was validated for its ability to detect CCDC51 in COS-1 cells overexpressing c-myc-tagged human CCDC51 (GeneCust, Dubelange, Luxembourg) as previously described for other candidates  [58, 59]  using the rabbit anti-CCDC51 (1:100) and mouse anti-c-myc (1:500) (11667149001, Roche, Basel, Switzerland) antibodies and with secondary donkey anti-rabbit conjugated with Alexa Fluor 488 (green, 1:1000) (711-545-152, Jackson Immuno Research Laboratories, Baltimore, MD, USA) and donkey anti-mouse with Cy3 (red, 1:1000) (715-165-150, Jackson Immuno Research) antibodies. Nuclei were stained with DAPI (1:1000) and cells mounted with a mounting medium (Fluoromount-G, South-ernBiotech, Birmingham, AL, USA) using coverslips.
Immunolocalization Studies in Human Cells and Retinal Tissue Using Fluorescence Imaging The rabbit anti-CCDC51 antibody (1:100, HPA010980, Sigma) was used to stain HeLa and human fibroblast cells. Cells were washed with PBS, fixed in 4% formaldehyde for 10 min, rewashed with PBS, and most of the time quenched with 50 mM NH 4 Cl in PBS for 10 min. Subsequently cells were permeabilized for 10 min with 0. 1% Triton X-100 in PBS, washed with PBS and blocked in PBS containing 2% BSA for 1 h. Cells were then incubated with primary antibodies (the rabbit anti-CCDC51 antibody) for 3 h at room temperature and washed 3 times with 0. 1% Triton X-100 in PBS. CCDC51 was detected with the secondary donkey anti-rabbit conjugated with Alexa Fluor 488 (1:1000 green) (711-545-152, Jackson Immuno Research Laboratories).
Similarly, non-human primate (12 µm sections), human, and mouse (20 µm sections) retinas postfixed with acetone were stained with the validated rabbit anti-CCDC51 antibody (HPA010980, (1:1000) Sigma) and co-stained with the mitochondrial mouse anti-ATP-synthase beta antibody (1:1000) or the mitochondrion-selective probe (1:1000 red) (MitoTracker Probe, Molecular Probes, Thermo Fisher Scientific), using the same secondary antibodies and conditions as described for the human cell lines. Retinae stained only with the secondary antibodies or the isotype antibody (Rabbit (DA1E) mAb IgG XP ® Isotype Control #3900, Cell Signaling, Ozyme, Saint-Cyr-L'École, France) served as negative controls. Immunostainings were visualized with confocal microscopy (Olympus FV1200, Rungis, France).
Immunohistochemistry in Human Retinal Tissue Using Horseradish Peroxidase Human retinas (50 µm sections) were postfixed with acetone and endogenous peroxidase was inhibited with 0. 3% H 2 O 2 (H1009-100mL lot STBH1090, Sigma). Subsequently, the retina was incubated with the rabbit anti-CCDC51 antibody ((1:1000), HPA010980, Sigma) and the secondary horseradish peroxidase antibody ((1. 500) HTP goat anti-rabbit IgG(H + L), Jackson Immuno Research). The labeling was performed with a substrate (VIP peroxidase, SK-4600, Vector Laboratories, Inc. , Burlingame, CA, USA) and images taken with a microscope (Carl Zeiss Microscopy, imager. M1, Jena, Germany).
Funding: This research was funded by Fondation Voir et Entendre (CZ), Prix Dalloz for "La recherche en ophtalmologie" (CZ), LABEX LIFESENSES (reference ANR-10-LABX-65) supported by French state funds managed by the Agence Nationale de la Recherche within the Investissements d'Avenir program (ANR-11-IDEX-0004-0), IHU FOReSIGHT (ANR-18-IAHU-0001) supported by French state funds managed by the Agence Nationale de la Recherche within the Investissements d'Avenir program, Foundation Fighting Blindness center grant [C-CMM-0907-0428-INSERM04], grant (BR-GE-0619-0761-INSERM) Prix de la Fondation de l'OEil (IA), UNADEV (Union Nationale des Aveugles et Déficients Visuels) in partnership with ITMO NNP/AVIESAN (alliance nationale pour les sciences de la vie et de la santé) for research in visual disorders, and doctoral funding from the Ministère de l'Enseignement Supérieur et de la Recherche (MESR) and Fondation de France (CM).