dataesr/scientific-paragraphs-categorization huggingface dataset:
8 ± 0. 6 mm, N = 7) and was significantly different from wildtype (P < 0. 0001, one-way ANOVA with Bonferroni multiplecomparisons post-test; Figure  3B ). Complementation of fcpB - mutant restored wild-type colony size (16. 5 ± 0. 6 mm, N = 8), and no statistically significant difference was observed between the average colony diameter of the fcpB -/+ complemented strain and the wild-type (α = 0. 05, one-way ANOVA with Bonferroni multiple comparisons post-test; Figure  3B ). Because the inoculum was standardized and FcpB does not affect bacterial growth kinetics (data not shown), the difference in average colony diameter between the wild-type and mutant can be attributed to a difference in motility in semisolid media rather than a difference in growth kinetics. To determine whether FcpB affects motility in viscous liquid media, we performed dark field video microscopy of cells in late log phase in media containing 1% methyl-cellulose.
ACKNOWLEDGMENTS This work was supported by the  Institut Pasteur, Paris, France , and the  French Ministry of Research   ANR-08-MIE-018  and AK  NIH  grants  NIAID U01 AI088752 ,  Fogarty   R01 TW009504-05  and  NIAID R01 AI052473. AB acknowledges partial support from  ANII-Uruguay  (grants  FCE_3_2016_1_126797  and  ALI_1_2014_1_4982 ). We thank  Priscilla Oliveira de Giuseppe  and  Lucas Villasboas de Oliveira  for preliminary screening of the library of random mutants, as well as  Morven Graham  and  Xinran Liu  of the electron microscopy core facility at the  Yale School of Medicine (Center for Cellular and Molecular Imaging ) for assistance with the immunogold labeling and aiding in cryo-EM data acquisition, respectively. We thank staff in the  High-Performance Computing facility  for their maintenance of these facilities.
Familial data The family was enrolled at the Centre de Depistage et de Traitement de la Lèpre et de l'Ulcère de Buruli (CDTLUB) in Pobe, Benin, due to the unusual severity of the clinical course of the disease in patient P1 (details given in the case report section). The family consisted of two unaffected parents, two affected children and seven unaffected siblings living in the village of Tatonnonkon. This village is located in Adja-Ouèrè, a district of the Plateau department at the borders of the Zou and Ouemedepartments, with BU prevalence ranging from 10 to 18 per 1,000  [17]. Blood was obtained from the parents, the two affected and three unaffected siblings. DNA was extracted from whole blood according to the Nucleon BACC2 Genomic DNA extraction protocol (GE Healthcare), assayed with the QuantIt Picogreen dsDNA kit (Life Technologies) and processed for the genotyping of >900,000 single nucleotide polymorphisms (SNPs) used for both linkage and copy number variant (CNV) analysis and >900,000 monomorphic nucleotides used for CNV analysis by the Affymetrix Genome-Wide 6.
Whole-exome sequencing Whole-exome sequencing was performed on both affected patients. Genomic DNA was sheared with a Covaris S2 Ultrasonicator (Covaris). An adaptor-ligated library was prepared with the Paired-End Sample Prep kit V1 (Illumina). Exome capture was performed with the SureSelect Human All Exon v2 kit (Agilent Technologies), covering 38 Megabases (Mbs) of the genome. Single-end sequencing was performed on an Illumina Genome Analyzer IIx. The sequences were aligned with the human genome reference sequence (hg19/GRCh38 build), with BWA-MEM aligner  [21]. Downstream processing was carried out with the Genome Analysis Toolkit (GATK)  [22] , SAMtools  [23] , and Picard Tools (http://broadinstitute. github. io/picard/). Substitution and indel calls were both made with GATK HaplotypeCaller v3.
In our scenario (two affected siblings, three unaffected siblings, consanguinity loop involving second-degree cousins and a recessive genetic model with complete penetrance), this theoretical maximum LOD score was equal to 2. 8 (corresponding to a p-value of 3x10 -4 ). Eight regions spanning a total of 5. 7 Mbs and mapping to chromosomes 2 (linkage regions 2. 1 and 2. 2), 5, 7 (7. 1 and 7. 2) and 8 (8. 1, 8. 2 and 8. 3) reached or closely approached the theoretical maximum LOD score ((Fig  2 ). The second region on chromosome 2 (2. 2), and both regions on chromosome 7 (7. 1 and 7. 2) had LOD score of 2. 49, 2. 68 and 2. 35, respectively. All the other linked regions had a LOD score above 2. 75. The complete list of genes in each of these regions, retrieved from the Vega database as implemented in the Ensembl browser (vega.
archive. ensembl. org), is available in the S1 Table. Interestingly, two of the three linkage regions on chromosome 8, i. e. 8. 1 and 8. 2, contain clusters of genes encoding beta-defensins (S2 Fig). We screened the linkage regions for potential causal mutations by means of whole-exome sequencing of the two patients. We searched for homozygous variants predicted to have potential functional effect, i. e. missense, nonsense and splice site mutations, in-frame and out-offrame small insertions and deletions, common to both patients and located in the linkage regions. We filtered out population variants with a MAF above 1% from public databases such as the Exome Aggregation Consortium (ExAC; exac. broadinstitute. org). No candidate variants fitting these criteria were detected. However, the two linkage regions harboring clusters of beta-defensin genes (i.
Over this 37 kbs region the mean (interquartile range) coverage was 0. 47 X (0-0) in the two affected sisters homozygous for the deletion, 198. 5 X (94-274) in the unaffected heterozygote brother and 342. 8 X (196-515) in the seven wild-type homozygous controls (including one unaffected brother with a mean coverage of 330. 1 X). A brief description of this region-derived from the Vega database as implemented in the Ensembl genome browser (vega. archive. ensembl. org)-based on GRCh38 Assembly is given in Fig 4. Three genes of different biotypes have been identified so far including two processed pseudogenes AC068587. 5 (Ensembl id: ENSG00000255253; spanning 174bp from 12,638,428 to 12,638,602) and AC068587. 2 (ENSG00000244289; 780bps from 12,628,476 to 12,629,256), and one long non-coding RNA (lincRNA) gene AC68587.
Acknowledgments We thank the staff at the  Centre de Depistage et de Traitement de la Lèpre et de l'Ulcère de Buruli, Pobè, Benin ; staff of the  Laboratoire de Bacteriologie and Institut National de la Sante ét de la Recherche Medicale (INSERM)   U892 ,  CHU , Angers, France; and staff from the  INSERM U1163  for helpful discussions. We thank  Yoann Seeleuthner ,  Antoine Guerin , and  Maya Chrabieh  for technical help.
We acknowledge support from the  Fondation Raoul Follereau. QBV acknowledges support from the  'Fondation Bettencourt Schueller ' through the  MD/PhD program  of the  Imagine Institute. LM and AAl acknowledge support from the  Agence Nationale de la Recherche (ANR ; grant the skin. with severe BU in a large family supports the view of a key role of human genetics in the natural history of the disease. no. ANR-17-BSV3-0013-01 ). JM, LA and AAl acknowledge support from the  Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases  (grant no. ANR-10-LABX-62-IBEID ) and the  ANR  under the  "Investments for the Future" program  (grant no. ANR-10-IAHU-01 ). AAl acknowledges support from the  Fondation pour la Recherche Medicale  (grant no. DMI20091117308 ). JLC acknowledges support from  St.
In particular, the La Palma isolate (local isolate used in the present study) showed over 75% prevalence in sacrificed bovines and a mean of five alleles per analysed microsatellite locus with an observed heterozygosity of 0. 511  [15]. Unfortunately, no previous data on genetic diversity is available for the Dominican and French isolates used, but we can expect differences with Cuban flukes given the geographical isolation. Flukes were collected from the liver of infected cattle and kept alive for 6 h in a solution of 0. 85% NaCl (saline solution) and 5% glucose (Sigma-Aldrich, St. Quentin Fallavier, France) for egg laying. Eggs were preserved at 4 °C in the dark and in saline solution supplemented with gentamicin (Sigma-Aldrich, 40 mg/ml) until use. We used two susceptible P. columella populations, Negrines (Havana Province) and Aurora (Mayabeque Province), and two resistant populations, La Coca (Havana Province) and La Palma (Pinar del Río Province).
Results From 1997 to 2007 we captured 118 weasels, including 23 of M. n. vulgaris. Analysis of the live-trapping data showed a significant positive relationship between the summer-autumn share of M. n. nivalis in the weasel population inhabiting the study area and the number of days with snow cover during the preceding winter (LM, F 1,4 = 23. 93, R 2 = 0. 82, p < 0. 01, Fig. 1 ). During the field experiment, we recorded 138 model-predator encounters with a 31. 9% rate of detection. The red fox was the principal predator, followed by the raccoon dog. Avian predators were rarest, and were mainly buzzards (Buteo buteo and Buteo lagopus) and ravens (Corvus corax) (Table  1 ). We found that camouflage was the most significant factor affecting detection by a predator: weasel models with incompatible camouflage were detected more often than those matching the background colour (Table  2 ).
Moult progress. To analyse the progress of moulting in M. n. nivalis individuals we used data collected between 2002 and 2017, using 45 video-records and 85 trapping-records. For the video-records, we were unable to distinguish between individual animals, but for the trapping-records we included the same individuals (in total 64 different animals) if they were trapped at different stages of moult. From January 2014 till February 2016, twelve special camera traps were distributed evenly at the three different sites (Białowieża National Park, open grasslands and Narewka river valley). We placed the traps 500 meters apart at fixed locations, following linear features (roads, fences and riverbanks). Cameras (Bushnell Natureview HD MAX) were triggered by motion sensing and were programmed to record 15-second long videos.
Camera-traps worked continuously, and the data was retrieved every 2-3 weeks. For every video-recorded individual we recorded the date and time, type of morph (nivalis or vulgaris) and moulting stage (summer fur, winter fur, moulting). We classified all individuals into five groups: completely white (winter), dorsal part less than 25% brown, dorsal part 25-50% brown, dorsal part >75% brown, or completely brown dorsal part of the body (summer) (Fig. S2 ). Finally, we estimated the proportion of individuals at different moulting stages (5 groups) during every 10-day period of each month. Data on snow cover duration was collected from the meteorological station in Białowieża village. We used climate data collected between 1967 and 2017, which approximately corresponds with the records of weasel skins in the collection of the Mammal Research Institute PAS in Białowieża.
This has involved the acquisition of a battery of virulence factors followed by a toning down of virulence  (Wattam et al. , 2014). What is not understood is how the different species have adapted to their 'preferential' host, or the time line of this adaptation. Despite the strong sequence homogeneity within the genus (>94% nucleotide identity)  (Wattam et al. , 2009) , genome-wide studies suggest genetic variation, especially pseudogenization, i. e. , due to IS711 insertion and point mutations within marine Brucella genomes  (Suárez-Esquivel et al. , 2017) , might play a key role in Brucella host preference as the bacteria evolved with their respective preferential hosts  (Chain et al. , 2005). In a recent report, Ke and collaborators suggested that B. melitensis rapidly accumulates mutations during in vivo passage, however this observation is not supported by the high levels of sequence conservation seen between the genome sequences available in Genbank  (Ke et al.
9. Annotations were performed with Prokka  (Seemann, 2014)  and alignments with progressiveMAUVE  (Darling et al. , 2010)  and BLAST Ring Image Generator (BRIG) 0. 95  (Alikhan et al. , 2011). Genome assemblies were evaluated with QUAST 4. 6. 3 (Gurevich et al. , 2013). Single Nucleotide Polymorphism (SNP) and clustering (maximum-parsimony) analyses were performed using Bionumerics v7. 6. 2 (wgSNP-module). Applied filters removed indels, repeated regions and rRNAs with minimum ten bpdistance between SNPs. Non-synonymous, synonymous and intergenic SNPs were identified against 16M. Local alignment of interesting regions were done with ClustalW  (Thompson et al. , 1994)  via MEGA 6  (Tamura et al. , 2013). To functionally analyze genomes, Roary v3. 6. 1  (Page et al. , 2015)  was used to generate matrices of presence/absence of core (i.
Procedure A preliminary version of the survey was tested for understanding and duration with owners of ferrets that were not thereafter included in the survey. A validated questionnaire (Supplementary material) of ninety-one closed questions was developed and available online between June and October 2012. Each survey required 20-30 min to be completed. The first part of the questionnaire was dedicated to individual data regarding each ferret; the second part included more general questions about the household to identify owners' habits and applied to all ferrets living in the same household. The demographic characteristics of the sample were studied together with husbandry, reported medical care and feeding habits.
Statistics Descriptive analysis. Data analysis was run via epidemiology software (Epi Info 3; Centers for Disease Control and Prevention) and a statistical package (BiostaTGV). Descriptive data were reported as actual counts and the percentage of respondents. Differences between responses were determined by use of the χ 2 test and t test in the studied population. Differences were considered significant at values of P < 0•05. Associations between neuter status, sex, husbandry, food composition and distribution, mode of neutering and reported medical conditions were tested using univariate analysis. Then data were pooled as follows for the quantitative analysis for each outcome: lethargy, weakness, decreased activity, stand up only for food and declared insulinoma were pooled as lethargy ± insulinoma; diarrhoea and green or bird-seed stools pooled as diarrhoea ± bird-seed stools; dental problems including broken or impaired and injured teeth and teeth extraction pooled as dental problems; permanent tail alopecia, troncular alopecia and hair loss, and 'ferrets naked except on the head, adrenal disease, adrenal tumour' and ferrets declared with adrenal disease pooled as alopecia ± adrenal disease.
Acknowledgements Manuscript preparation and editorial assistance were provided by  Kurt Verkest of VetWrite  (vetwrite@gmail. com). The authors' contributions were as follows: all authors designed the study, and reviewed the results and manuscript; R. B. collected the data; G. B. , A. L. , B. -M. P. and J. -J. B. designed the study and epidemiology; M. M. performed the quantitative analysis; G. B. , M. M. and A. L. wrote the manuscript. The authors have no conflicts of interest to disclose.
Previous studies had demonstrated the genetic component of diseases affecting calves  (Heringstad et al. , 2008; Henderson et al. , 2011). Genetic and genomic selection therefore represent a potential strategy to increase resistance to these diseases, but necessitate the collection of additional phenotypic data beyond what is included in most of the national databases used for genetic evaluation. In addition, little research has been dedicated to the health of beef calves when compared to studies on dairy (and particularly Holstein) calves. Because French breeders were interested in improving the viability of Charolais beef calves, 16 herds were recruited for the purposes of this study, during which records were kept on calf health performance between birth and 1 mo of age. These records included birth weight (BW), calving ease (CE) score, vigor of the calf at birth [hereinafter referred to as neonatal vitality (NV)], survival, and all health events occurring between birth and 1 mo of age.
Data The herds included in this study were recruited from a network of 75 Charolais herds, mainly located in the regions of Burgundy and Vendée. These herds were participating in the on-farm DEGERAM project managed by the French Charolais breeding society in order to develop genomic selection schemes for new traits. The breeders recorded data on herd performance and transmitted it to the French Charolais breeding society during two successive birth campaigns, from August 2013 to July 2015. Data on the 30-d survival of all single newborn calves were extracted from the French national database which is used for on-farm genetic evaluations. For the present study, we selected records from the herds that: 1) had reported at least three health events per herd-year, and 2) were genetically connected to each other by the use of at least one artificial insemination sire with progenies in a minimum of three herds.
The final research dataset (Table  1 ) included data on 2,740 calves produced by 2,044 dams and 252 sires in 16 connected herds. The parent pedigrees of all calves had been registered for at least two generations of ancestors. Among the 252 sires, 112 bulls were also maternal grandsires of the calves, because they were sires of 839 dams. The two INRA experimental Charolais farms, located at Bourges (in the Berry region) and at Pin-aux-Haras (in Normandy) were among these 16 herds. All 16 herds were managed according to a standard suckler herd production system, in which calves were reared by their dams until 6 to 8 mo of age. With the exception of the INRA experimental unit in Bourges (where the animals were housed indoors throughout the year), the animals were indoors between late November and April and pastured outside for the other months of the year.
, 2014). Thus, the health events considered for the genetic analysis were umbilical infections occurring between 0 and 5 d of age (Umb1) or between 6 and 20 d of age (Umb2), and diarrhea occurring between 0 and 5 d of age (Diar1), between 6 and 20 d of age (Diar2), or between 21 and 30 d of age (Diar3). The frequency of navel illness between 21 and 30 d of age (Umb3) was too low (Table  1 ) to estimate genetic parameters; this was also the case for other diseases (including respiratory diseases) recorded in the 2 yr of data that we examined (Table  3 ). The incidence risk of diseases was calculated as the number of calves treated for the first time for a disease before 1 mo of age divided by the number of calves enrolled in the 24-mo period of the study. The incidence risk of disease within a given age category (birth to 5 d, 6 to 20 d, and 21 to 30 d) reflected the number of calves treated for the first time during that age interval divided by the number of calves eligible for treatment.
, 1995 (Gilmour et al. , , 2009)). Analyses were performed using a BLUP multitrait animal model. A preliminary univariate analysis was performed to select the best genetic model for each of the nine traits and obtain univariate estimates of genetic parameters. Because of the small size of the dataset and the strong genetic correlations between some of the nine traits, it was not possible to run a single nine-trait analysis; it was very difficult to achieve convergence of the REML log-likelihood in analyses containing more than five traits. As a result, 10 different fivetrait analyses were performed in order to obtain at least 2 different estimates of any of the two-by-two correlations between traits. Some correlations were fixed at the boundary value of 0. 999 or -0. 999 by the software in order to maximize the likelihood of the data.
In these cases, bi-variate analyses were performed to check that the results were unchanged and that corresponding correlations were at the boundaries of the parameter space. The results for a given parameter (and its standard error) were averaged over all the analyses performed on the corresponding trait. Estimates of correlations between direct and maternal effects (within or across traits) are always highly sensitive to any difference in data structure design, and it is difficult to distinguish a biased estimate from a true biological correlation between direct and maternal effects  (Robinson, 1996a,b). For this reason, we did not attempt to estimate these correlations using our small dataset.
Average BW values were similar to those recorded at a national scale in Charolais herds  (Guerrier and Leudet, 2015). The distributions of CE and NV scores in our dataset are shown in Table  2. Nearly 88% of calves were born without any assistance or only an easy pull (CE < 3) and 84. 5% were vigorous at birth (NV < 3). In the experimental herds, calving events not requiring assistance were 11 points below the rate of 68% observed at a national scale  (Guerrier and Leudet, 2015) , while the proportion of caesarians was close to the national average (4%). No health events were recorded for 1,947 of the 2,740 calves in the analyzed dataset, while 1,052 health events were recorded among the remaining 793 calves. In the current study, the total incidence risk of umbilical infections during the first month of life was about 6%, which is consistent with recent observations of U.
We therefore considered any random effect that might explain at least 1% of phenotypic variance (even with a large standard error) in the most parsimonious model with a log-likelihood very close to that of the full model. Our results showed that maternal genetic variance was null for all disease traits recorded during the period between 21 and 30 d. Nor was maternal genetic variance significant (less than 1% of phenotypic variance) for CE and NV in our dataset. As a result, the maternal genetic component was not considered for CE, NV and Diar3 in the final multitrait analysis. Our preliminary univariate analysis also showed that no common maternal environmental variance existed for any umbilical disease trait. This effect was not therefore considered in the model of resistance to umbilical infection.
Proportion of Phenotypic Variances Explained by Direct Genetic Effects and Maternal Genetic Effects Versus Common Environmental Effects The direct heritability values for BW and CE (Table  5 ) were low to moderate, with estimates within the range of most values that have previously been reported in different beef cattle breeds  (Varona et al. , 1999; Phocas and Laloë, 2004). In particular, a comparison with previous results from a large French Charolais dataset  (Phocas and Laloë, 2004)  revealed that the values for direct heritability were quite similar in both cases. However, our estimates of maternal heritability different markedly from published results: while the 2004 analysis of Charolais cattle obtained estimates of 12% and 3% for CE and BW, respectively, in the present study we detected no maternal heritability for CE and a value close to 6% for BW.
These differences could be explained by the limited number of years covered by the records in the current dataset and by our assumption of a genetic independence of direct and maternal genetic effects for all traits. The previous study had indeed estimated the correlation between direct and maternal genetic effects to be around -0. 4  (Phocas and Laloë, 2004). We did not find any maternal genetic variance regarding NV (Table  5 ), while the maternal common environmental variance component (Table  6 ) was quite a bit higher (16. 6% of phenotypic variance) than direct heritability (7. 8%). As far as we know, the only existing estimates of genetic parameters for calf vigor have been based on a binary trait (vigorous/weak calf during the first 24 h) in Brahman  (Riley et al. , 2004)  and Nelore  (Schmidek et al.