Genetic epidemiology and familial risk factors for paratuberculosis seropositivity in beef cattle

Paratuberculosis is an intestinal infection of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Genetic associations with paratuberculosis have been described in Holstein cattle. The objectives were to describe the association between paratuberculosis status of the dam and her offspring in beef cattle, develop methods to assess familial aggregation of paratuberculosis in cattle of unknown pedigree, and model the paratuberculosis status of beef cattle given familial and herdlevel covariates. Texas beef cattle were tested for paratuberculosis using serum antibody and microbiologic culture of feces. Available pedigree data were used to confirm familial relationships. The association between the paratuberculosis ELISA status of the dam and her offspring was assessed using mixed-effects models. Increased odds of being classified as a “suspect” or greater based on ELISA results were observed if the dam was classified as a “suspect” or greater. A positive linear association was observed between the ELISA value of the dam and her offspring. Analysis of pedigree data using conditional logistic regression identified ancestors associated with significantly increased odds of being classified as “low positive” or greater. Microsatellite markers were used to classify cattle into genetically similar groups using allele frequency data. Nine clusters of genetically similar cattle were identified among paratuberculosis test positive cattle, herd matched controls, and pedigreed cattle. Clusters were validated using animals of known pedigree. Increased odds of paratuberculosis seropositivity were observed for some clusters compared to the cluster with the lowest seroprevalence. A predictive model was developed using a Bayesian framework to assess the association between antibody status of the dam and her offspring adjusted for herd-level risk factors. Predictors associated with highly probable increased odds of seropositivity included herd seroprevalence and herd fecal prevalence of MAP. The association between dam and offspring ELISA status was small (OR 1.35) and not highly probable. The results of this work support familial aggregation of paratuberculosis ELISA status, but herd-level risk factors appear to be more important in predicting ELISA status. A large proportion of observed serological reactions were not supported by fecal culture results; therefore, observed associations might be limited to humoral responses to Mycobacterium spp

Influence de l'élasticité et de la plasticité cristallines sur la distribution des champs mécaniques à la surface des polycristaux

Cette étude vise, par une modélisation par éléments finis 3D, à évaluer les dispersions des champs mécaniques entre grains de surface d'un polycristal en acier inoxydable austénitique type AISI 316LN, en fonction de l'orientation du grain (configuration inter-orientations) et en fonction des orientations des grains environnants (configuration intra-orientation). Le comportement des grains est caractérisé par une élasticité linéaire, isotrope ou anisotrope (élasticité cubique), et une plasticité cristalline à écrouissage plus ou moins prononcé (structure Cubique à Face Centrée, écrouissage monotone ou cyclique). On montre que : - les amplitudes des distributions calculées en régime purement élastique sont supérieures ou égales que celles obtenues en régime élasto-(visco)plastique pour des déformations macroscopiques de plus 1%. L'effet de l'anisotropie de l'élasticité cristalline sur les champs locaux est sensible jusqu'à une déformation macroscopique de l'ordre de 0.2 % à 1% selon l'écrouissage macroscopique. - les distributions intra-orientation sont au moins aussi dispersées que les distributions inter-orientations

Somatostatin triggers rhythmic electrical firing in hypothalamic GHRH neurons

International audienc

Perceptions of veterinarians and producers concerning Johne’s disease prevalence and control in US beef cow-calf operations

BACKGROUND: Efforts to educate producers and veterinarians in the United States regarding the management, prevention and control of Mycobacterium avium subspecies paratuberculosis (MAP) infection have increased over recent years. While nationwide awareness about MAP infection is improving, current level of awareness among beef producers and veterinarians is largely unknown. This study compares the perceptions of beef producers and veterinarians on the burden of MAP infection in cow-calf herds and on measures to control new infections. Questionnaires were mailed to 989 US beef producers through state Designated Johne’s Coordinators and to 1080 bovine veterinarians belonging to a US nationwide professional association. RESULTS: Twenty-two percent (34/155) of producers reported having infected animals in their herds. The mean (minimum, median, maximum) prevalence reported by producers was 0.8% (0, 0, 10). Twenty-seven percent (27/100) of producers had at least one clinical animal during the previous year. Compared to the small herds (<50 head), the mean test-positive percentages and estimated prevalences were higher in medium (50–149) and highest in large (≥150) herds. Seedstock herds had a lower prevalence and these producers were more likely to enroll in Johne’s disease (JD) control programs and test their herds. Veterinarians reported a mean overall animal level prevalence in their client herds of 5% (0, 2, 60). Similarly, 26% (0, 10, 100) of client herds had at least one infected animal. Mean percentage of infected cows within infected herds was 9% (0.01, 5, 80). Producers generally performed activities to control MAP transmission more frequently than perceived by veterinarians. Compared to veterinarians’ opinions, producers were less likely to cull cows with signs consistent with JD (P < 0.01), but more likely to test purchased additions (P < 0.01). Testing recommendations by veterinarians (n = 277) for beef cow-calf herds were bacterial culture of feces (3%), PCR (14%), ELISA (35%) and a combination of these tests (47%). Seventy-nine percent of veterinarians recommended a 12-month interval between testing. CONCLUSIONS: Seedstock producers who had had JD risk assessments performed on their farms were more supportive of JD control programs and had a correspondingly lower prevalence. It is important to increase educational activities to provide relevant information to veterinarians and producers for better management and control of JD. Educational programs should target larger herds to maximize the impact

Comparison of calf weaning weight and associated economic variables between beef cows with and without serum antibodies against or isolation from feces of Mycobacterium avium subsp paratuberculosis

OBJECTIVE—To compare calf weaning weight and associated economic variables for beef cows with serum antibodies against Mycobacterium avium subsp paratuberculosis (MAP) or from which MAP was isolated from feces with those for cows that were seronegative for antibodies against or culture negative for MAP. DESIGN—Retrospective study. ANIMALS—4,842 beef cows from 3 herds enrolled in the USDA National Johne’s Disease Demonstration Herd Project. PROCEDURES—Individual cow ELISA and culture results were obtained from the project database. During each parity evaluated for each cow, the 205-day adjusted weaning weight (AWW) of its calf was calculated. The AWW was compared between test-positive and testnegative cows by use of multilevel mixed-effect models. The median value for feeder calves from 2007 to 2011 was used to estimate the economic losses associated with MAP test– positive cows. RESULTS—The AWW of calves from cows with strongly positive ELISA results was 21.48 kg (47.26 lb) less than that of calves from cows with negative ELISA results. The AWW of calves from cows classified as heavy or moderate MAP shedders was 58.51 kg (128.72 lb) and 40.81 kg (89.78 lb) less, respectively, than that of calves from MAP culture–negative cows. Associated economic losses were estimated as $57.49/calf for cows with strongly positive ELISA results and$156.60/calf and $109.23/calf for cows classified as heavy and moderate MAP shedders, respectively. CONCLUSIONS AND CLINICAL RELEVANCE—Calves from cows with MAP-positive test results had significantly lower AWWs than did calves from cows with MAP-negative test results, which translated into economic losses for MAP-infected beef herds. (J Am Vet Med Assoc 2013;243:1609–1615)http://avmajournals.avma.org/loi/javmaam2014ab201

Genome-wide association study provides insights into genes related with horn development in Nelore beef cattle.

Abstract The causal mutation for polledness in Nelore (Bos taurus indicus) breed seems to have appeared first in Brazil in 1957. The expression of the polled trait is known to be ruled by a few groups of alleles in taurine breeds; however, the genetic basis of this trait in indicine cattle is still unclear. The aim of this study was to identify genomic regions associated with the hornless trait in a commercial Nelore population. A total of 107,294 animals had phenotypes recorded and 2,238 were genotyped/imputed for 777k SNP. The weighted single-step approach for genome-wide association study (WssGWAS) was used to estimate the SNP effects and variances accounted for by 1 Mb sliding SNP windows. A centromeric region of chromosome 1 with 3.11 Mb size (BTA1: 878,631?3,987,104 bp) was found to be associated with hornless in the studied population. A total of 28 protein-coding genes are mapped in this region, including the taurine Polled locus and the IFNAR1, IFNAR2, IFNGR2, KRTAP11-1, MIS18A, OLIG1, OLIG2, and SOD1 genes, which expression can be related to the horn formation as described in literature. The functional enrichment analysis by DAVID tool revealed cytokine-cytokine receptor interaction, JAK-STAT signaling, natural killer cell mediated cytotoxicity, and osteoclast differentiation pathways as significant (P < 0.05). In addition, a runs of homozygosity (ROH) analysis identified a ROH island in polled animals with 2.47 Mb inside the region identified by WssGWAS. Polledness in Nelore cattle is associated with one region in the genome with 3.1 Mb size in chromosome 1. Several genes are harbored in this region, and they may act together in the determination of the polled/horned phenotype. Fine mapping the locus responsible for polled trait in Nelore breed and the identification of the molecular mechanisms regulating the horn growth deserve further investigation

Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection

Members of the Toll-like receptor (TLR) gene family occupy key roles in the mammalian innate immune system by functioning as sentries for the detection of invading pathogens, thereafter provoking host innate immune responses. We utilized a custom next-generation sequencing approach and allele-specific genotyping assays to detect and validate 280 biallelic variants across all 10 bovine TLR genes, including 71 nonsynonymous single nucleotide polymorphisms (SNPs) and one putative nonsense SNP. Bayesian haplotype reconstructions and median joining networks revealed haplotype sharing between Bos taurus taurus and Bos taurus indicus breeds at every locus, and specialized beef and dairy breeds could not be differentiated despite an average polymorphism density of 1 marker/158 bp. Collectively, 160 tagSNPs and two tag insertion-deletion mutations (indels) were sufficient to predict 100% of the variation at 280 variable sites for both Bos subspecies and their hybrids, whereas 118 tagSNPs and 1 tagIndel predictively captured 100% of the variation at 235 variable sites for B. t. taurus. Polyphen and SIFT analyses of amino acid (AA) replacements encoded by bovine TLR SNPs indicated that up to 32% of the AA substitutions were expected to impact protein function. Classical and newly developed tests of diversity provide strong support for balancing selection operating on TLR3 and TLR8, and purifying selection acting on TLR10. An investigation of the persistence and continuity of linkage disequilibrium (r2≥0.50) between adjacent variable sites also supported the presence of selection acting on TLR3 and TLR8. A case-control study employing validated variants from bovine TLR genes recognizing bacterial ligands revealed six SNPs potentially eliciting small effects on susceptibility to Mycobacterium avium spp paratuberculosis infection in dairy cattle. The results of this study will broadly impact domestic cattle research by providing the necessary foundation to explore several avenues of bovine translational genomics, and the potential for marker-assisted vaccination

Perceptions of veterinarians in bovine practice and producers with beef cow-calf operations enrolled in the US voluntary bovine Johne's disease control program concerning economic losses associated with Johne's disease

This study compares the perceptions of producers and veterinarians on the economicimpacts of Mycobacterium avium subspecies paratuberculosis (MAP) infection in cow-calfherds. Questionnaires were mailed to beef producers through the Designated Johne’sCoordinators and to veterinarians belonging to a nationwide professional organization.Important components of losses associated with MAP infected cows were used to estimatetotal loss per infected cow-year using an iterative approach based on collected survey data.Veterinarians were more likely to perceive a lower calving percentage in MAP infectedcows compared to producers (P = 0.02). Income lost due to the presence of Johne’s disease(JD) in an infected cattle herd was perceived to be higher by veterinarians (P < 0.01). Com-pared to veterinarians without JD certification, seedstock producers were more likely toperceive genetic losses due to culling cows positive for MAP (P < 0.01). There were mixedopinions regarding the magnitude of lowered weaning weight in calves from infected cowsand perceived differences in risk of other diseases or conditions in infected cows. An annualloss of $235 (95$89–$457) for each infected animal was estimated based on infor-mation from the producer survey. The analogous estimate using information inputs fromveterinarians was$250 ($82–$486). Mean annual loss due to JD in a 100 cow herd with a7% true prevalence was $1644 ($625–$3250) based on information provided by producers.Similarly, mean annual loss based on information collected from veterinarians was$1747($575–$3375).Program for the Study of Johne’s Disease in Texas and by a cooperative agreement with USDA-APHIS-VS.http://ww w.elsevier.com/locate/prevetmedhb2014ab201

Ghrelin Stimulation of Growth Hormone-Releasing Hormone Neurons Is Direct in the Arcuate Nucleus

International audienceGhrelin targets the arcuate nucleus, from where growth hormone releasing hormone (GHRH) neurones trigger GH secretion. This hypothalamic nucleus also contains neuropeptide Y (NPY) neurons which play a master role in the effect of ghrelin on feeding. Interestingly, connections between NPY and GHRH neurons have been reported, leading to the hypothesis that the GH axis and the feeding circuits might be co-regulated by ghrelin.Here, we show that ghrelin stimulates the firing rate of identified GHRH neurons, in transgenic GHRH-GFP mice. This stimulation is prevented by growth hormone secretagogue receptor-1 antagonism as well as by U-73122, a phospholipase C inhibitor and by calcium channels blockers. The effect of ghrelin does not require synaptic transmission, as it is not antagonized by gamma-aminobutyric acid, glutamate and NPY receptor antagonists. In addition, this hypothalamic effect of ghrelin is independent of somatostatin, the inhibitor of the GH axis, since it is also found in somatostatin knockout mice. Indeed, ghrelin does not modify synaptic currents of GHRH neurons. However, ghrelin exerts a strong and direct depolarizing effect on GHRH neurons, which supports their increased firing rate. Thus, GHRH neurons are a specific target for ghrelin within the brain, and not activated secondary to altered activity in feeding circuits. These results support the view that ghrelin related therapeutic approaches could be directed separately towards GH deficiency or feeding disorders

Autozygosity islands and ROH patterns in Nellore lineages: evidence of selection for functionally important traits.

Abstract Background The aim of this study was to assess genome-wide autozygosity in a Nellore cattle population and to characterize ROH patterns and autozygosity islands that may have occurred due to selection within its lineages. It attempts also to compare estimates of inbreeding calculated from ROH (FROH), genomic relationship matrix (FGRM), and pedigree-based coefficient (FPED). Results The average number of ROH per animal was 55.15&#8201;±&#8201;13.01 with an average size of 3.24 Mb. The Nellore genome is composed mostly by a high number of shorter segments accounting for 78% of all ROH, although the proportion of the genome covered by them was relatively small. The genome autozygosity proportion indicates moderate to high inbreeding levels for classical standards, with an average value of 7.15% (178.70 Mb). The average of FPED and FROH, and their correlations (&#8722;&#8201;0.05 to 0.26) were low. Estimates of correlation between FGRM-FPED was zero, while the correlation (&#8722;&#8201;0.01 to &#8722;&#8201;0.07) between FGRM-FROH decreased as a function of ROH length, except for FROH&#8201;>&#8201;8Mb (&#8722;&#8201;0.03). Overall, inbreeding coefficients were not high for the genotyped animals. Autozygosity islands were evident across the genome (n&#8201;=&#8201;62) and their genomic location did not largely differ within lineages. Enriched terms (p&#8201;<&#8201;0.01) associated with defense response to bacteria (GO:0042742), immune complex reaction (GO:0045647), pregnancy-associated glycoproteins genes (GO:0030163), and organism growth (GO:0040014) were described within the autozygotic islands. Conclusions Low FPED-FROH correlation estimates indicate that FPED is not the most suitable method for capturing ancient inbreeding when the pedigree does not extend back many generations and FROH should be used instead. Enriched terms (p <&#8201;0.01) suggest a strong selection for immune response. Non-overlapping islands within the lineages greatly explain the mechanism underlying selection for functionally important traits in Nellore cattle