Estimation of genetic parameters for maintenance energy requirements and residual feed intake in Nellore cattle.

We estimated heritabilities and genetic and phenotypic correlation estimates for maintenance energy requirements (NEmR), residual feed intake (RFI), growth, carcass and reproductive indicator traits, using data from 41 feed efficiency trials in Brazil, comprising 4381 males and females. Continuous traits were analysed using a linear animal model and threshold traits were analysed using a threshold animal model. The heritability estimates were low for RFI (0.190) and NEmR (0.193); other heritabilities were mainly moderate (growth and carcass traits) or high (sexual precocity traits). The genetic correlation of RFI with NEmR was high (0.701). The genetic correlations of NEmR were low with carcass and reproductive traits, and moderate with growth traits. Thus, selection to improve weaning weight and female sexual precocity indicator traits would not affect maintenance energy requirement. Genetic selection to reduce maintenance energy requirements is feasible and would also reduce DMI and RFI. Selection to improve RFI can be used to identify animals with lower maintenance energy requirements. Long-term selection to reduce RFI and NEmR would have favourable effects on yearling weight, carcass muscle indicator traits and female sexual precocity. Genetic (co)variance component estimates for NEmR, in conjunction with economic values of selection criteria, may be used to develop novel approaches for genetic selection to improve efficiency of beef production.

Strategies for genomic predictions of an indicine multi-breed population using single-step GBLUP.

Brazilian livestock breeding programmes strive to enhance the genetics of beef cattle, with a strong emphasis on the Nellore breed, which has an extensive database and has achieved significant genetic progress in the last years. There are other indicine breeds that are economically important in Brazil; however, these breeds have more modest sets of phenotypes, pedigree and genotypes, slowing down their genetic progress as their predictions are less accurate. Combining several breeds in a multi-breed evaluation could help enhance predictions for those breeds with less information available. This study aimed to evaluate the feasibility of multi-breed, single-step genomic best linear unbiased predictor genomic evaluations for Nellore, Brahman, Guzerat and Tabapua. Multi-breed evaluations were contrasted to the single-breed ones. Data were sourced from the National Association of Breeders and Researchers of Brazil and included pedigree (4,207,516), phenotypic (328,748), and genomic (63,492) information across all breeds. Phenotypes were available for adjusted weight at 210 and 450 days of age, and scrotal circumference at 365 days of age. Various scenarios were evaluated to ensure pedigree and genomic information compatibility when combining different breeds, including metafounders (MF) or building the genomic relationship matrix with breed-specific allele frequencies. Scenarios were compared using the linear regression method for bias, dispersion and accuracy. The results showed that using multi-breed evaluations significantly improved accuracy, especially for smaller breeds like Guzerat and Tabapua. The validation statistics indicated that the MF approach provided accurate predictions, albeit with some bias. While single-breed evaluations tended to have lower accuracy, merging all breeds in multi-breed evaluations increased accuracy and reduced dispersion. This study demonstrates that multi-breed genomic evaluations are proper for indicine beef cattle breeds. The MF approach may be particularly beneficial for less-represented breeds, addressing limitations related to small reference populations and incompatibilities between G and A22. By leveraging genomic information across breeds, breeders and producers can make more informed selection decisions, ultimately improving genetic gain in these cattle populations.

Genetic parameters for visual scores, growth and carcass traits in Nellore Cattle.

Growth and carcass traits are essential selection criteria for beef cattle breeding programs. However, it is necessary to combine these measurements with body composition traits to meet the demand of the consumer market. This study aimed to estimate the genetic parameters for visual scores, growth (pre and post-weaning weights), and carcass (rib eye area (REA), back and rump fat thickness) traits in Nellore cattle using Bayesian inference. Data from 12,060 animals belonging to the HoRa Hofig Ramos herd were used. Morphological traits were evaluated by the MERCOS methodology. The heritability estimates obtained ranged from low to high magnitude, from 0.15 to 0.28 for visual scores, 0.13 to 0.44 for growth, and from 0.42 to 0.46 for carcass traits. Genetic correlations between visual scores and growth traits were generally of moderate to high magnitudes, however, visual scores showed low correlations with carcass traits, except between sacral bone and structure and REA. Selection for visual score traits can lead to favorable responses in body weight and vice versa, but the same is not true for carcass traits. Morphological categorical traits can be used as complementary tools that add value to selection.

Genetic correlation estimates between calving ease in primiparous cows and economically important traits in Nellore cattle.

This study aimed to estimate (co)variance components and genetic parameters for calving ease (CE) and their genetic correlations with growth, reproductive, carcass, and feed efficiency traits in Nellore cattle. Phenotypes for CE are scored in two categories: normal calving and assisted calving. The traits considered were probability of precocious calving, age at first calving, stayability, adjusted scrotal circumference at 365 days of age, accumulated cow productivity, age at puberty of males, gestation length, birth weight, adjusted weights at 210 and 450 days of age, adult cow weight, frame score, hip height, rib eye area, subcutaneous backfat thickness, rump fat thickness, intramuscular fat percentage, residual feed intake and dry matter intake. The estimation of genetic parameters was performed using a two-trait threshold-linear animal model, except for CE, stayability, and probability of precocious calving, which were evaluated through a two-trait threshold animal model. The direct (0.27) and maternal (0.19) heritability estimates for CE in heifers primiparous Nellore indicated that selecting for this trait is feasible. The selection to improve the female sexual precocity should consider CE during the selection and mating decisions to reduce calving problems. Genetic correlation estimates between CE and BW suggest that selecting low birth weight to reduce calving problems is not an appropriate strategy to improve calving ease in heifers Nellore. Therefore, adopting a multi-trait selection model with CE and BW in the Nellore breed would reduce calving difficulties, particularly in sexually precocious heifers, without impairing the growth, reproductive, feed efficiency conversion, and carcass indicator traits.

Genotype-by-environment interactions for feed efficiency traits in Nellore cattle based on bi-trait reaction norm models.

BACKGROUND: Selecting animals for feed efficiency directly impacts the profitability of the beef cattle industry, which contributes to minimizing the environmental footprint of beef production. Genetic and environmental factors influence animal feed efficiency, leading to phenotypic variability when exposed to different environmental conditions (i.e., temperature and nutritional level). Thus, our aim was to assess potential genotype-by-environment (G × E) interactions for dry matter intake (DMI) and residual feed intake (RFI) in Nellore cattle (Bos taurus indicus) based on bi-trait reaction norm models (RN) and evaluate the genetic association between RFI and DMI across different environmental gradient (EG) levels. For this, we used phenotypic information on 12,958 animals (young bulls and heifers) for DMI and RFI recorded during 158 feed efficiency trials. RESULTS: The heritability estimates for DMI and RFI across EG ranged from 0.26 to 0.54 and from 0.07 to 0.41, respectively. The average genetic correlations (± standard deviation) across EG for DMI and RFI were 0.83 ± 0.19 and 0.81 ± 0.21, respectively, with the lowest genetic correlation estimates observed between extreme EG levels (low vs. high) i.e. 0.22 for RFI and 0.26 for DMI, indicating the presence of G × E interactions. The genetic correlation between RFI and DMI across EG levels decreased as the EG became more favorable and ranged from 0.79 (lowest EG) to 0.52 (highest EG). Based on the estimated breeding values from extreme EG levels (low vs. high), we observed a moderate Spearman correlation of 0.61 (RFI) and 0.55 (DMI) and a selection coincidence of 53.3% and 40.0% for RFI and DMI, respectively. CONCLUSIONS: Our results show evidence of G × E interactions on feed efficiency traits in Nellore cattle, especially in feeding trials with an average daily gain (ADG) that is far from the expected of 1 kg/day, thus increasing reranking of animals.

Weighted genomic prediction for growth and carcass-related traits in Nelore cattle.

This study aimed to assess the impact of differential weighting in genomic regions harboring candidate causal loci on the genomic prediction accuracy and dispersion for growth and carcass-related traits in Nelore cattle. The dataset contained 168 793 phenotypic records for adjusted weight at 450 days of age (W450), 83 624 for rib eye area (REA), 24 480 for marbling (MAR) and 82 981 for subcutaneous backfat thickness (BFT) and rump fat thickness (RFT). The pedigree harbored information from 244 254 animals born between 1977 and 2016, including 6283 sires and 50 742 dams. Animals (n = 7769) were genotyped with the low-density panel (Clarifide® Nelore 3.0), and the genotypes were imputed to a panel containing 735 044 markers. A linear animal model was applied to estimate the genetic parameters and to perform the weighted single-step genome-wide association study (WssGWAS). A total of seven models for genomic prediction were evaluated combining the SNP weights obtained in the iterations of the WssGWAS and the candidate QTL. The heritability estimated for W450 (0.35) was moderate, and for carcass-related traits, the estimates were moderate for REA (0.27), MAR (0.28) and RFT (0.28), and low for BFT (0.18). The prediction accuracy for W450 incorporating reported QTL previously described in the literature along with different SNPs weights was like those described for the default ssGBLUP model. The use of the ssGWAS to weight the SNP effects displayed limited advantages for the REA prediction accuracy. Comparing the ssGBLUP with the BLUP model, a meaningful improvement in the prediction accuracy from 0.09 to 0.63 (700%) was observed for MAR. The highest prediction accuracy was obtained for BFT and RFT in all evaluated models. The application of information obtained from the WssGWAS is an alternative to reduce the genomic prediction dispersion for growth and carcass-related traits, except for MAR. Furthermore, the results obtained herein pointed out that is possible to improve the prediction accuracy and reduce the genomic prediction dispersion for growth and carcass-related traits in young animals.

Genetic association between feed efficiency, growth, scrotal circumference, and carcass traits in Guzerat cattle.

The objective of this study was to estimate the genetic parameters for feed efficiency-related traits and their genetic correlations with growth, male fertility, and carcass traits using multi-trait analysis in Guzerat cattle. Further, it aimed to predict the direct and correlated responses for feed efficiency traits when selection was applied for growth, male fertility, and carcass traits. The evaluated traits were adjusted weight at 120 (W120), 210 (W210), 365 (W365), and 450 days of age (W450), adjusted scrotal circumference at 365 days of age (SC365) and at 450 days of age (SC450), scrotal circumference, ribeye area (REA), backfat thickness (BFT), rump fat thickness (RFT), residual feed intake (RFI), and dry matter intake (DMI). The genetic parameters were obtained by the restricted maximum likelihood method (REML), using an animal model in multi-trait analyses. The heritability estimates for W120, W210, W365, W450, SC365, and SC450 varied from low to high (0.17 to 0.39). The carcass traits, REA, BFT, and RFT, displayed low to moderate heritability estimates, 0.27, 0.10, and 0.31, respectively. The heritability estimates for RFI (0.15) and DMI (0.23) were low and moderate, respectively. The RFI showed low genetic correlations with growth traits, ranging from - 0.07 to 0.22, from 0.03 to 0.05 for scrotal circumference, and from - 0.35 to 0.16 for carcass, except for DMI, which ranged from 0.42 to 0.46. The RFI and DMI presented enough additive genetic variability to be used as selection criteria in Guzerat breed genetic improvement program. Additionally, the response to selection for RFI would be higher when selection is performed directly for this trait. The selection for residual feed intake would not promote unfavorable correlated responses for scrotal circumference, carcass (yield and finish), and growth traits. Therefore, the selection for more efficient animals would not compromise the productive, reproductive, and carcass performance, contributing to reduce the production costs, increasing the profitability and sustainability of beef cattle production in tropical areas.

Assessment of copy number variants in three Brazilian locally adapted cattle breeds using whole-genome re-sequencing data.

Further characterization of genetic structural variations should strongly focus on small and endangered local breeds given their role in unraveling genes and structural variants underlying selective pressures and phenotype variation. A comprehensive genome-wide assessment of copy number variations (CNVs) based on whole-genome re-sequencing data was performed on three Brazilian locally adapted cattle breeds (Caracu Caldeano, Crioulo Lageano, and Pantaneiro) using the ARS-UCD1.2 genome assembly. Data from 36 individuals with an average coverage depth of 14.07× per individual was used. A total of 24 945 CNVs were identified distributed among the breeds (Caracu Caldeano = 7285, Crioulo Lageano = 7297, and Pantaneiro = 10 363). Deletion events were 1.75-2.07-fold higher than duplications, and the total length of CNVs is composed mostly of a high number of segments between 10 and 30 kb. CNV regions (CNVRs) are not uniformly scattered throughout the genomes (n = 463), and 105 CNVRs were found overlapping among the studied breeds. Functional annotation of the CNVRs revealed variants with high consequence on protein sequence harboring relevant genes, in which we highlighted the BOLA-DQB, BOLA-DQA5, CD1A, ß-defensins, PRG3, and ULBP21 genes. Enrichment analysis based on the gene list retrieved from the CNVRs disclosed over-represented terms (p < 0.01) strongly associated with immunity and cattle resilience to harsh environments. Additionally, QTL associated with body conformation and dairy-related traits were also unveiled within the CNVRs. These results provide better understanding of the selective forces shaping the genome of such cattle breeds and identify traces of natural selection pressures by which these populations have been exposed to challenging environmental conditions.

Genomic evaluation of commercial herds with different pedigree structures using the single-step genomic BLUP in Nelore cattle.

The aim of this work was to evaluate the impact of applying genomic information in pedigree uncertainty situations on genetic evaluations for growth- and cow productivity-related traits in Nelore commercial herds. Records for accumulated cow productivity (ACP) and adjusted weight at 450 days of age (W450) were used, as well as genotypes of registered and commercial herd animals, genotyped with the Clarifide Nelore 3.1 panel (~29,000 SNPs). The genetic values for commercial and registered populations were estimated using different approaches that included (ssGBLUP) or did not include genomic information (BLUP), with different pedigree structures. Different scenarios were tested, varying the proportion of young animals with unknown sires (0, 25, 50, 75, and 100%), and unknown maternal grandsires (0, 25, 50, 75, and 100%). The prediction accuracies and abilities were calculated. The estimated breeding value accuracies decreased as the proportion of unknown sires and maternal grandsires increased. The genomic estimated breeding value accuracy using the ssGBLUP was higher in scenarios with a lower proportion of known pedigree when compared to the BLUP methodology. The results obtained with the ssGBLUP showed that it is possible to obtain reliable direct and indirect predictions for young animals from commercial herds without pedigree structure.

Estimates of genetic and phenotypic parameters for feeding behaviour and feed efficiency-related traits in Nelore cattle.

The objective of this study was to obtain (co)variance components, heritability, and genetic and phenotypic correlation estimates for feed efficiency and feed behaviour-related indicator traits. Further, it aimed to predict the direct and correlated responses for feed efficiency traits when selection was applied for feeding behaviour-related traits in Nelore cattle. Phenotypic records (n = 4840) from 125 feed efficiency tests (RFI: Residual feed intake and DMI: Dry matter intake) carried out between 2011 and 2018 were considered in this study. Animals belonged to five farms located in two Brazilian geographical regions (Midwest and Southeast). Animals under similar management and environmental conditions in the feedlot were evaluated when they attained an average of 13.5 ± 4.15 months of age. Feed behaviour-related traits were also obtained, including meal criteria (MC), meal frequency (MF), average meal duration (AMD), meal duration (MD), average consumption per meal (ACM), and consumption rate (CR) through the GrowSafe System® electronic bunk system. The contemporary groups for all traits were composed of farm, management group, feed efficiency test, sex, and birth year. The (co)variance components were estimated using the restricted maximum likelihood method considering a multi-trait (n = 8) animal model. The heritability estimates for RFI (0.23 ± 0.02), DMI (0.31 ± 0.02), MF (0.65 ± 0.02), AMD (0.29 ± 0.02), ACM (0.24 ± 0.02), MD (0.41 ± 0.02), MC (0.48 ± 0.02), and CR (0.42 ± 0.02) were moderate to high. The highest genetic correlation was obtained between CR and MD (-0.91 ± 0.04), MD and AMD (0.73 ± 0.03), CR and AMD (-0.68 ± 0.04), and RFI and DMI (0.81 ± 0.02). The highest phenotypic correlation was between ACM and AMD (0.76 ± 0.02), DMI and MD (0.77 ± 0.02), and DMI and RFI (0.77 ± 0.02). Genetic improvement for feed efficiency and feeding behaviour-related traits is feasible and the results obtained herein provided valuable information regarding the genetic background of Nelore feeding behaviour-related traits. The genetic association between feeding behaviour and feed efficiency-related traits suggested that animals spending less time feeding at a low feeding rate also had lower DMI and higher feed efficiency (RFI), and likely had lower energy maintenance requirements. The relative efficiency of selection showed that feeding behaviour-related traits were not adequate indicator traits to improve RFI and DMI. The DMI might be an effective selection criterion to improve RFI and reduce the herd's maintenance requirements.

Genomic prediction ability and genetic parameters for residual feed intake calculated using different approaches and their associations with growth, reproductive, and carcass traits in Nellore cattle.

This study aimed to estimate prediction ability and genetic parameters for residual feed intake (RFI) calculated using a regression equation for each test (RFItest) and for the whole population (RFIpop) in Nellore beef cattle. It also aimed to evaluate the correlations between RFIpop and RFItest with growth, reproductive, and carcass traits. Genotypic and phenotypic records from 8354 animals were used. An analysis of variance (ANOVA) was performed to verify the adequacy of the regression equations applied to estimate the RFItest and RFIpop. The (co)variance components were obtained using the single-step genomic best linear unbiased prediction under single and two-trait animal model analyses. The genetic and phenotypic correlations between RFItest and RFIpop with dry matter intake, frame, growth, reproduction, and carcass-related traits were evaluated. The prediction ability and bias were estimated to compare the RFItest and RFIpop genomic breeding values (GEBV). The RFIpop ANOVA showed a higher significance level (p < 0.0001) than did the RFItest for the fixed effects. The RFIpop displayed higher additive genetic variance estimated than the RFItest, although the RFIpop and RFItest displayed similar heritabilities. Overall, the RFItest showed higher residual correlations with growth, reproductive, and carcass traits, while the RFIpop displayed higher genetic correlations with such traits. The GEBV for the RFItest was slightly biased than GEBV RFIpop. The approach to calculate the RFI influenced the decomposition and estimation of variance components and genomic prediction for RFI. The application of RFIpop would be more appropriate for genetic evaluation purpose to adjust or correct for non-genetic effects and to decrease the prediction bias for RFI.

Genomic prediction for meat and carcass traits in Nellore cattle using a Markov blanket algorithm.

This study was carried out to evaluate the advantage of preselecting SNP markers using Markov blanket algorithm regarding the accuracy of genomic prediction for carcass and meat quality traits in Nellore cattle. This study considered 3675, 3680, 3660 and 524 records of rib eye area (REA), back fat thickness (BF), rump fat (RF), and Warner-Bratzler shear force (WBSF), respectively, from the Nellore Brazil Breeding Program. The animals have been genotyped using low-density SNP panel (30 k), and subsequently imputed for arrays with 777 k SNPs. Four Bayesian specifications of genomic regression models, namely Bayes A, Bayes B, Bayes Cπ and Bayesian Ridge Regression methods were compared in terms of prediction accuracy using a five folds cross-validation. Prediction accuracy for REA, BF and RF was all similar using the Bayesian Alphabet models, ranging from 0.75 to 0.95. For WBSF, the predictive ability was higher using Bayes B (0.47) than other methods (0.39 to 0.42). Although the prediction accuracies using Markov blanket of SNP markers were lower than those using all SNPs, for WBSF the relative gain was lower than 13%. With a subset of informative SNPs markers, identified using Markov blanket, probably, is possible to capture a large proportion of the genetic variance for WBSF. The development of low-density and customized arrays using Markov blanket might be cost-effective to perform a genomic selection for this trait, increasing the number of evaluated animals, improving the management decisions based on genomic information and applying genomic selection on a large scale.

Effect of Thermal Stress on Thermoregulation, Hematological and Hormonal Characteristics of Caracu Beef Cattle.

This study evaluated the influence of environmental temperature on thermoregulation, hormonal, and hematological characteristics in Caracu cattle. Blood samples, hair length, coat and muzzle colors, rectal (RT), and surface temperatures were collected from 48 males and 43 females before (morning) and after sun exposure for eight hours (afternoon). Infrared thermography (IRT) was used to identify superficial temperature that exhibits a high correlation with RT. Hematological parameters, hormone concentrations, RT, and the superficial temperature obtained by IRT that exhibited the highest correlation with RT were evaluated by variance analysis. Regarding IRT, the lower left side of the body (LS) showed the highest correlation with the RT. Interaction between period and sex was observed for LS, cortisol, and eosinophils. Cortisone, progesterone, and RT were influenced by period and sex. Neutrophils and segmented neutrophils were influenced by the period, which showed the highest concentrations after sun exposure. Platelets, leukocytes, lymphocytes, and monocytes were influenced by sex. Heat stress changes several physiological characteristics where males and females exhibited differences in their responses to heat stress. Furthermore, most characteristics evaluated remained within the regular values observed for taurine Creole breeds, showing that Caracu is adapted to tropical climates.

Detection of potential functional variants based on systems-biology: the case of feed efficiency in beef cattle.

BACKGROUND: Potential functional variants (PFVs) can be defined as genetic variants responsible for a given phenotype. Ultimately, these are the best DNA markers for animal breeding and selection, especially for polygenic and complex phenotypes. Herein, we described the identification of PFVs for complex phenotypes (in this case, Feed Efficiency in beef cattle) using a systems-biology driven approach based on RNA-seq data from physiologically relevant organs. RESULTS: The systems-biology coupled with deep molecular phenotyping by RNA-seq of liver, muscle, hypothalamus, pituitary, and adrenal glands of animals with high and low feed efficiency (FE) measured by residual feed intake (RFI) identified 2,000,936 uniquely variants. Among them, 9986 variants were significantly associated with FE and only 78 had a high impact on protein expression and were considered as PFVs. A set of 169 significant uniquely variants were expressed in all five organs, however, only 27 variants had a moderate impact and none of them a had high impact on protein expression. These results provide evidence of tissue-specific effects of high-impact PFVs. The PFVs were enriched (FDR < 0.05) for processing and presentation of MHC Class I and II mediated antigens, which are an important part of the adaptive immune response. The experimental validation of these PFVs was demonstrated by the increased prediction accuracy for RFI using the weighted G matrix (ssGBLUP+wG; Acc = 0.10 and b = 0.48) obtained in the ssGWAS in comparison to the unweighted G matrix (ssGBLUP; Acc = 0.29 and b = 1.10). CONCLUSION: Here we identified PFVs for FE in beef cattle using a strategy based on systems-biology and deep molecular phenotyping. This approach has great potential to be used in genetic prediction programs, especially for polygenic phenotypes.

Effects of Feeding and Drinking Behavior on Performance and Carcass Traits in Beef Cattle.

Feed and water efficiency are important traits to improve beef cattle production's economic and environmental sustainability. This study evaluated residual feed intake (RFI) and residual water intake (RWI) and their relationship with performance, ingestive behavior, and carcass traits in Caracu beef cattle. The data were analyzed using a generalized linear model with least squares means. The ingestive behavior, performance, and carcass traits were influenced by sex (p < 0.05). Males showed higher dry matter intake (DMI), average daily gain (ADG), mid-test metabolic weight (BW0.75), rib eye area, and rump fat thickness than females, besides spending more time drinking and eating. Low RFI animals exhibited higher DMI than high RFI animals. Low RWI animals ingested 3.89 L/d of water further than high RWI animals. The interaction between sex and RWI influenced the DMI, BW0.75, and backfat thickness. The ingestive behavior of low and high RFI animals was similar, although high RWI animals visited a smaller number of drinkers than low RWI animals. Water intake positively affects productive efficiency, and the combined use of RWI and RFI may help improve the selection of more efficient animals contributing to reducing the costs of beef cattle production and improving environmental sustainability.

Regular Use of Ivermectin as Prophylaxis for COVID-19 Led Up to a 92% Reduction in COVID-19 Mortality Rate in a Dose-Response Manner: Results of a Prospective Observational Study of a Strictly Controlled Population of 88,012 Subjects.

Background We have previously demonstrated that ivermectin used as prophylaxis for coronavirus disease 2019 (COVID-19), irrespective of the regularity, in a strictly controlled citywide program in Southern Brazil (Itajaí, Brazil), was associated with reductions in COVID-19 infection, hospitalization, and mortality rates. In this study, our objective was to determine if the regular use of ivermectin impacted the level of protection from COVID-19 and related outcomes, reinforcing the efficacy of ivermectin through the demonstration of a dose-response effect. Methods This exploratory analysis of a prospective observational study involved a program that used ivermectin at a dose of 0.2 mg/kg/day for two consecutive days, every 15 days, for 150 days. Regularity definitions were as follows: regular users had 180 mg or more of ivermectin and irregular users had up to 60 mg, in total, throughout the program. Comparisons were made between non-users (subjects who did not use ivermectin), and regular and irregular users after multivariate adjustments. The full city database was used to calculate and compare COVID-19 infection and the risk of dying from COVID-19. The COVID-19 database was used and propensity score matching (PSM) was employed for hospitalization and mortality rates. Results Among 223,128 subjects from the city of Itajaí, 159,560 were 18 years old or up and were not infected by COVID-19 until July 7, 2020, from which 45,716 (28.7%) did not use and 113,844 (71.3%) used ivermectin. Among ivermectin users, 33,971 (29.8%) used irregularly (up to 60 mg) and 8,325 (7.3%) used regularly (more than 180 mg). The remaining 71,548 participants were not included in the analysis. COVID-19 infection rate was 49% lower for regular users (3.40%) than non-users (6.64%) (risk rate (RR): 0.51; 95% CI: 0.45-0.58; p < 0.0001), and 25% lower than irregular users (4.54%) (RR: 0.75; 95% CI: 0.66-0.85; p < 0.0001). The infection rate was 32% lower for irregular users than non-users (RR: 0.68; 95% CI: 0.64-0.73; p < 0.0001). Among COVID-19 participants, regularusers were older and had a higher prevalence of type 2 diabetes and hypertension than irregular and non-users. After PSM, the matched analysis contained 283 subjects in each group of non-users and regular users, between regular users and irregular users, and 1,542 subjects between non-users and irregular users. The hospitalization rate was reduced by 100% in regular users compared to both irregular users and non-users (p < 0.0001), and by 29% among irregular users compared to non-users (RR: 0.781; 95% CI: 0.49-1.05; p = 0.099). Mortality rate was 92% lower in regular users than non-users (RR: 0.08; 95% CI: 0.02-0.35; p = 0.0008) and 84% lower than irregular users (RR: 0.16; 95% CI: 0.04-0.71; p = 0.016), while irregular users had a 37% lower mortality rate reduction than non-users (RR: 0.67; 95% CI: 0.40-0.99; p = 0.049). Risk of dying from COVID-19 was 86% lower among regular users than non-users (RR: 0.14; 95% CI: 0.03-0.57; p = 0.006), and 72% lower than irregular users (RR: 0.28; 95% CI: 0.07-1.18; p = 0.083), while irregular users had a 51% reduction compared to non-users (RR: 0.49; 95% CI: 0.32-0.76; p = 0.001). Conclusion Non-use of ivermectin was associated with a 12.5-fold increase in mortality rate and a seven-fold increased risk of dying from COVID-19 compared to the regular use of ivermectin. This dose-response efficacy reinforces the prophylactic effects of ivermectin against COVID-19.

Heritability and genetic correlations between marbling in longissimus dorsi muscle and conventional economic traits in Nellore beef cattle.

In Nellore beef cattle, studies addressing genetic correlations between ultrasound marbling content and other economically important traits are still incipient. Therefore, this work aimed to estimate heritability and genetic correlations between ultrasound marbling content in the longissimus dorsi muscle (MARB) and growth, reproductive, feed efficiency, and carcass-related traits in a Nellore beef cattle population from Brazil. Phenotypic records of 614,395 Nellore animals were used and included adjusted weight at 210 (W210) and 450 (W450) days of age, adult cow weight (AW), early heifer pregnancy (EH), stayability (STAY), adjusted scrotal circumference at 365 days of age (SC365), ribeye area (REA), subcutaneous backfat thickness (BF), rump fat thickness (RF), and marbling (MARB). The genetic parameters for all traits but EH and STAY were estimated considering a linear animal model, whereas for those two nonlinear traits, a threshold animal model was used. The direct and correlated response to selection for MARB versus the other traits, and the relative efficiency of selection, were also calculated. The heritability estimate for MARB was 0.31 and for the other conventional evaluated traits was low to moderate, with values ranging from 0.14 to 0.41. The genetic correlations between MARB and growth, reproductive, feed efficiency, and carcass-related trait were very low, with values close to zero, with similar correlated responses. The MARB displayed adequate genetic variability to respond to selection and crossbreeding programs looking forward to higher meat quality and differential market standards for the Nellore beef. The selection for growth, reproductive, feed efficiency, and carcass-related traits would not affect MARB in Nellore beef cattle and vice versa. Therefore, this trait should be included as a selection criterion in the Nellore breeding program.

Integration analyses of structural variations and differential gene expression associated with beef fatty acid profile in Nellore cattle.

This study aimed to integrate analyses of structural variations and differentially expressed genes (DEGs) associated with the beef fatty acid (FA) profile in Nellore cattle. Copy numbers variation (CNV) detection was performed using the penncnv algorithm and CNVRuler software in 3794 genotyped animals through the High-Density Bovine BeadChip. In order to perform the genomic wide association study (GWAS), a total of 963 genotyped animals were selected to obtain the intramuscular lipid concentration and quantify the beef FA profile. A total of 48 animals belonging to the same farm and management lot were extracted from the 963 genotyped and phenotyped animals to carry out the transcriptomic and differentially expressed gene analyses. The GWAS with extreme groups of FA profiles was performed using a logistic model. A total of 43, 42, 66 and 35 significant CNV regions (p < 0.05) for saturated, monounsaturated, polyunsaturated and omega 3 and 6 fatty acids were identified respectively. The paired-end sequencing of 48 samples was performed using the Illumina HiSeq2500 platform. Real-time quantitative PCR was used to validate the DEGs identified by RNA-seq analysis. The results showed several DEGs associated with the FA profile of Longissimus thoracis, such as BSCL2 and SAMD8. Enriched terms as the cellular response to corticosteroid (GO:0071384) and glucocorticoid stimulus (GO:0071385) could be highlighted. The identification of structural variations harboring candidate genes for beef FA must contribute to the elucidation of the genetic basis that determines the beef FA composition of intramuscular fat in Nellore cattle. Our results will contribute to the identification of potential biomarkers for complex phenotypes, such as the FA profile, to improve the reliability of the genomic predictions including pre-selected variants using differentiated weighting in the genomic models.

Refeeding ewes ad libitum after a moderate energy restriction during mid gestation did not affect the onset of breeding and ovulating rate of female offspring.

Sub-nutrition during pregnancy might affect the offspring´s reproductive performance through effects on the development and function of gonads. This study evaluated a maternal energy restriction in ewes from day 48-106 of gestation, on pre- and post-weaning female lambs` performance, onset of female lambs' breeding and ovulation rate during their first breeding season. Adult Polwarth ewes sired by Finnish rams bearing single or twin lambs were assigned to two dietary treatments from day 48 to day 106 of gestation: restricted (R; n = 60) at 60 % of their metabolizable energy (ME) requirements, or non-restricted (NR; n = 54) at 100 % of their ME requirements. After the restriction period, ewes grazed all together ad libitum until weaning. The ewe lambs were evaluated from birth to weaning, as well as during their first breeding season. Although NR ewes weighed 17.7 % more than R ewes (P < 0.05) at the end of the restriction period, the nutritional treatment of the dams had no effect on the weight of the ewe lambs at birth, weaning or final weight (P > 0.05). Fat depth, rib eye area, the percentage of ewe-lambs cycling and their ovulation rate during the first breeding season was not affected by the ewe´s dietary treatment. Ewes restricted at 60 % of their ME requirements in mid-gestation seemed to have the capacity to compensate any detrimental effects on growth and development as well as the reproductive potential of female lambs if adequate refeeding conditions are provided in late gestation, throughout lactation and post-weaning.

Integrating genome-wide association study and pathway analysis reveals physiological aspects affecting heifer early calving defined at different ages in Nelore cattle.

Heifer early calving (HC) plays a key role in beef cattle herds' economic sustainability and profitability by reducing production costs and generation intervals. However, the genetic basis of HC in Nelore heifers at different ages remains to be well understood. In this study, we aimed to perform a multi-trait weighted single-step genome-wide association (MT w-ssGWAS) to uncover the genetic mechanism involved in HC at 24 (HC24), 26 (HC26), 28 (HC28), and 30 (HC30) months of age in Nelore heifers. The MT w-ssGWAS pointed out four shared windows regions for HC24, HC26, HC28, and HC30 on BTA 5, 6, 14, and 16, explaining a larger proportion of genetic variation from 9.2% for HC30 to 10.6% for HC28. The shared regions harbored candidate genes related with the major gatekeeper for early puberty onset by controlling metabolic aspects related to homeostasis, reproductive, and growth (IGF1, PARPBP, PMCH, GNRHR, LYN, TMEM68, PLAG1, CHCHD7, KISS1, GOLT1A, and PPP1R15B). The MT w-ssGWAS and pathway analysis highlighted differences in physiological processes that support complex interactions between the gonadotropic axes, growth aspects, and sexual precocity in Nelore heifers, providing useful information for genetic improvement and management strategies.