2-Aminoethyl Dihydrogen Phosphate (2-AEH2P) Associated with Cell Metabolism-Modulating Drugs Presents a Synergistic and Pro-Apoptotic Effect in an In Vitro Model of the Ascitic Ehrlich Tumor.

The progression and maintenance of cancer characteristics are associated with cellular components linked to the tumor and non-cellular components with pro-tumoral properties. Pharmacological association with antagonists of the cellular components of the tumor, such as anti- and pro-apoptotic drugs, represents a novel adjuvant strategy. In this study, the antiproliferative, pro-apoptotic, and pharmacological effects of the combination of monophosphoester 2-AEH2P with Simvastatin, Coenzyme Q10, the chemotherapeutic drug paclitaxel, and colony-stimulating factor (GM-CSF) were evaluated. Tests were conducted to determine cytotoxic activity using the MTT method, cell cycle phases, and fragmented DNA by flow cytometry, mitochondrial membrane potential, expression of cell markers Bcl2, TNF-α/DR-4, Cytochrome c, caspase 3, and P53, and analysis of drug combination profiles using Synergy Finder 2.0 Software. The results showed a synergistic effect among the combinations, compared to individual treatments with the monophosphoester and other drugs. In addition, there was modulation of marker expression, indicating a pro-apoptotic and immunomodulatory effect of 2-AEH2P. Pharmacological analysis revealed that tumor cells treated with GM-CSF + 2-AEH2P exhibited a synergistic effect, while groups of tumor cells treated with paclitaxel, Coenzyme Q10, and Simvastatin showed additive effects. Furthermore, treatment with the paclitaxel + 2-AEH2P combination (12 h) resulted in a significant reduction in mitochondrial membrane potential. Pharmacological combinations for normal cells did not exhibit deleterious effects compared to mammary carcinomatosis tumor (EAT) cells.

Feed efficiency indexes and their relationships with carcass, non-carcass and meat quality traits in Nellore steers.

Five hundred and seventy-five Nellore steers were evaluated for residual feed intake and residual feed intake and gain and their relationships between carcass, non-carcass and meat quality traits. RFI was measured by the difference between observed and predicted dry matter intake and RIG was obtained by the sum of -1*RFI and residual gain. Efficient and inefficient animals were classified adopting ±0.5 standard deviations from RFI and RIG mean. A mixed model was used including RFI or RIG and contemporary group as fixed effects, initial age as covariate and sire and experimental period as random effects, testing the significance of the regression slope for each evaluated trait. RIG was positively related to longissimus muscle area. Efficient-RFI animals had lower liver and internal fat proportions compared to inefficient-RFI animals. Efficient-RFI and efficient-RIG animals had 11.8% and 11.2% lower extracted intramuscular fat, compared to inefficient-RFI and inefficient-RIG animals, respectively. Efficient-RFI animals had tougher meat compared to inefficient-RFI animals.

Eficiência produtiva ao desmame de vacas Nelore criadas no Pantanal / Productive efficiency to weaning of Nellore cows raised in the Pantanal

O trabalho objetivou avaliar a eficiência produtiva de vacas ao desmame de acordo com seu tamanho (peso) e estimar correlação fenotípica entre as características peso do bezerro ao desmame (PBD), peso da vaca ao desmame do bezerro (PVD) e relação desmame (RD = PBD/ PVD) de animais da raça Nelore criados no Pantanal de Mato Grosso do Sul. Foram utilizadas 706 observações para pares de dados de pesos de vacas e de bezerros da raça Nelore ao desmame criados em regime de pastejo. Foram formados seis grupos com base no peso de vaca ao desmame (GPVD) a partir dos desvios (40,73kg) de peso em relação à média geral do rebanho (420,56kg). Os grupos de vacas com menores pesos obtiveram maiores RD. As correlações fenotípicas entre PVD e PBD variaram de 0,05 a 0,26, enquanto para PVD e RD as correlações foram negativas e com variação de 0,11 a 0,25. As correlações fenotípicas entre PBD e RD apresentaram-se positivas e de alta magnitude (0,91 a 0,98). As maiores eficiências produtivas foram determinadas para vacas de pequeno a médio porte (327,20 a 438,62kg), além de estas serem menos exigentes quanto a nutrientes digestíveis totais (NDT). A seleção de vacas de tamanho médio (379, 83 a 461,29kg) apresenta-se mais vantajosa por gerar menor custo de mantença que as vacas maiores e produzir bezerros mais pesados que as vacas menores.(AU)

The study aimed to evaluate the productive efficiency of cow at weaning according to their size (weight) and estimated phenotypic correlation between the characteristics of weaning weight of calf and cow and weaning ratio of Nellore cattle raised in the Pantanal of Mato Grosso do Sul. 706 observations were used to weight data pairs of cow and calves at weaning. Six groups were formed based on the weight of cow at weaning from deviations (40.73kg) of weight in relation to the overall mean of the herd (420.56kg). The groups of cows with lower weaning weight have the highest weaning ratio. Phenotypic correlations of cow weight at weaning and weaning of calf weight ranged from 0.05 to 0.26, cow weight at weaning and weaning ratio were negative correlations ranging from -0.11 to -0.25. Phenotypic correlations between weaning of calf and weaning ratio were positive and of high magnitude (0.91 to 0.98). The highest efficiencies were determined for cows between 327.20 and 438.62kg, and are less demanding on total digestible nutrients (TDN). A selection of medium sized cows (379, 83 to 461.29kg) appears more interesting because it has lower maintenance costs than larger cows, and produces heavier calves than the smaller cows.(AU)

Eficiência produtiva ao desmame de vacas Nelore criadas no pantanal / Productive efficiency to weaning of Nellore cows raised in the pantanal

O trabalho objetivou avaliar a eficiência produtiva de vacas ao desmame de acordo com seu tamanho (peso) e estimar correlação fenotípica entre as características peso do bezerro ao desmame (PBD), peso da vaca ao desmame do bezerro (PVD) e relação desmame (RD = PBD/ PVD) de animais da raça Nelore criados no Pantanal de Mato Grosso do Sul. Foram utilizadas 706 observações para pares de dados de pesos de vacas e de bezerros da raça Nelore ao desmame criados em regime de pastejo. Foram formados seis grupos com base no peso de vaca ao desmame (GPVD) a partir dos desvios (40,73kg) de peso em relação à média geral do rebanho (420,56kg). Os grupos de vacas com menores pesos obtiveram maiores RD. As correlações fenotípicas entre PVD e PBD variaram de 0,05 a 0,26, enquanto para PVD e RD as correlações foram negativas e com variação de 0,11 a 0,25. As correlações fenotípicas entre PBD e RD apresentaram-se positivas e de alta magnitude (0,91 a 0,98). As maiores eficiências produtivas foram determinadas para vacas de pequeno a médio porte (327,20 a 438,62kg), além de estas serem menos exigentes quanto a nutrientes digestíveis totais (NDT). A seleção de vacas de tamanho médio (379, 83 a 461,29kg) apresenta-se mais vantajosa por gerar menor custo de mantença que as vacas maiores e produzir bezerros mais pesados que as vacas menores.

The study aimed to evaluate the productive efficiency of cow at weaning according to their size (weight) and estimated phenotypic correlation between the characteristics of weaning weight of calf and cow and weaning ratio of Nellore cattle raised in the Pantanal of Mato Grosso do Sul. 706 observations were used to weight data pairs of cow and calves at weaning. Six groups were formed based on the weight of cow at weaning from deviations (40.73kg) of weight in relation to the overall mean of the herd (420.56kg). The groups of cows with lower weaning weight have the highest weaning ratio. Phenotypic correlations of cow weight at weaning and weaning of calf weight ranged from 0.05 to 0.26, cow weight at weaning and weaning ratio were negative correlations ranging from -0.11 to -0.25. Phenotypic correlations between weaning of calf and weaning ratio were positive and of high magnitude (0.91 to 0.98). The highest efficiencies were determined for cows between 327.20 and 438.62kg, and are less demanding on total digestible nutrients (TDN). A selection of medium sized cows (379, 83 to 461.29kg) appears more interesting because it has lower maintenance costs than larger cows, and produces heavier calves than the smaller cows.

A genome-wide scan for selection signatures in Nellore cattle.

Brazilian Nellore cattle (Bos indicus) have been selected for growth traits for over more than four decades. In recent years, reproductive and meat quality traits have become more important because of increasing consumption, exports and consumer demand. The identification of genome regions altered by artificial selection can potentially permit a better understanding of the biology of specific phenotypes that are useful for the development of tools designed to increase selection efficiency. Therefore, the aims of this study were to detect evidence of recent selection signatures in Nellore cattle using extended haplotype homozygosity methodology and BovineHD marker genotypes (>777,000 single nucleotide polymorphisms) as well as to identify corresponding genes underlying these signals. Thirty-one significant regions (P < 0.0001) of possible recent selection signatures were detected, and 19 of these overlapped quantitative trait loci related to reproductive traits, growth, feed efficiency, meat quality, fatty acid profiles and immunity. In addition, 545 genes were identified in regions harboring selection signatures. Within this group, 58 genes were associated with growth, muscle and adipose tissue metabolism, reproductive traits or the immune system. Using relative extended haplotype homozygosity to analyze high-density single nucleotide polymorphism marker data allowed for the identification of regions potentially under artificial selection pressure in the Nellore genome, which might be used to better understand autozygosity and the effects of selection on the Nellore genome.

Candidate genes for production traits in Nelore beef cattle.

Meat quality is an important trait for the beef industry. Backfat thickness, ribeye area, and shear force are traits measured late in life, and the investigation of molecular markers associated with these traits can help breeding programs. In cattle, some polymorphisms have been related to production traits. Thus, the purpose of this study was to assess the presence of polymorphisms in the candidate genes insulin-like growth factor 1 (IGF1), fatty acid-binding protein 4 (FABP4), and peroxisome proliferative active receptor gamma coactivator 1 A (PPARGC1A) and associate them with production traits in reference families of Nelore cattle. We used 270 steers descendent from 20 sires that were chosen to represent variability in this breed. The investigation of marker effects on the traits was performed using a mixed model under the restricted maximum likelihood method. A significant allele substitution effect was found for IGF1 and yearling weight (P ≤ 0.017). The mean allele substitution effect was 6.9 kg, with the 229 allele associated with reduced yearling weight in this Nelore population.

A SNP in ASAP1 gene is associated with meat quality and production traits in Nelore breed.

The ASAP1 gene is located in a QTL region for meat production traits and to access the role of the ASAP1 gene, the association between a SNP in this gene and production traits in beef cattle was studied. For this, about 270 steers of reference families of Nelore breed were used. The investigation of marker effects on the traits was performed using a mixed model under the restricted maximum likelihood method. Novel association of a SNP in the ASAP1 gene and shear force measured at 24 h post mortem (P≤0.0083) was described in this population of Nelore cattle. This polymorphism accounted for 1.13% of the total additive variance and 17.51% of total phenotypic variance of the trait, suggesting that this marker could be used in marker assisted selection.

Estimativas de componentes de (co)variância para peso e escores visuais de conformação frigorífica em bovinos Nelore / Variance component estimates for weight and visual scores of slaughter conformation in Nellore cattle

Estimaram-se os componentes de (co)variância e herdabilidade da conformação frigorífica à desmama (CFD), conformação frigorífica ao sobreano (CFS), peso à desmama (PD) e peso ao sobreano (PS) de animais Nelore, e as correlações genéticas entre essas características. Um modelo animal multicaracterística foi proposto para analisar 6.397 informações de peso e escores visuais de conformação frigorífica, obtidas à desmama e ao sobreano. Esse modelo incluiu os efeitos aleatórios genético aditivo direto, genético aditivo materno, ambiente permanente materno e residual, além dos efeitos fixos de grupo contemporâneo e das covariáveis idade da mãe ao parto - para peso e conformação frigorífica à desmama e ao sobreano - e idade do animal à data da avaliação - para conformação frigorífica, à desmama e ao sobreano. As herdabilidades estimadas para CFD, CFS, PD e PS foram, respectivamente, 0,13, 0,25, 0,22 e 0,29. Correlações genéticas positivas e de alta magnitude entre as características de peso e as características de avaliação visual sugerem que a seleção para uma delas pode resultar em resposta indireta na outra. A característica de conformação frigorífica pode ser selecionada em idade mais precoce em razão da correlação genética alta e positiva entre mensurações feitas nas duas idades estudadas.(AU)

The aim of this study was to estimate variance components, heritability and genetic correlation for slaughter conformation at weaning (SCW), slaughter conformation at yearling age (SCY), weaning weight (WW) and yearling age weight (YW) of Nellore cattle. A total of 6,397 records of all traits measured at weaning and at yearling age were used in the analysis. A multiple trait animal model which included the direct genetic additive, maternal genetic additive, maternal permanent environmental and residual random effects, as well as the fixed effect of contemporary group and the covariates age at calving (for weight and slaughter conformation at weaning and yearling age) and age at the evaluation time (slaughter conformation at weaning and yearling age) was proposed. The heritability estimates for SCW, SCY, WW and YW were, respectively, 0.13, 0.25, 0.22 and 0.29. Positive and high genetic correlations between body weight traits and visual evaluation traits suggested that direct selection for one trait results in positive indirect response in the remaining trait. Slaughter conformation trait can be selected at earlier age due to the high and positive genetic correlation between conformation scores at different age.(AU)

Estimativas de componentes de (co)variância para peso e escores visuais de conformação frigorífica em bovinos Nelore / Variance component estimates for weight and visual scores of slaughter conformation in Nellore cattle

Estimaram-se os componentes de (co)variância e herdabilidade da conformação frigorífica à desmama (CFD), conformação frigorífica ao sobreano (CFS), peso à desmama (PD) e peso ao sobreano (PS) de animais Nelore, e as correlações genéticas entre essas características. Um modelo animal multicaracterística foi proposto para analisar 6.397 informações de peso e escores visuais de conformação frigorífica, obtidas à desmama e ao sobreano. Esse modelo incluiu os efeitos aleatórios genético aditivo direto, genético aditivo materno, ambiente permanente materno e residual, além dos efeitos fixos de grupo contemporâneo e das covariáveis idade da mãe ao parto - para peso e conformação frigorífica à desmama e ao sobreano - e idade do animal à data da avaliação - para conformação frigorífica, à desmama e ao sobreano. As herdabilidades estimadas para CFD, CFS, PD e PS foram, respectivamente, 0,13, 0,25, 0,22 e 0,29. Correlações genéticas positivas e de alta magnitude entre as características de peso e as características de avaliação visual sugerem que a seleção para uma delas pode resultar em resposta indireta na outra. A característica de conformação frigorífica pode ser selecionada em idade mais precoce em razão da correlação genética alta e positiva entre mensurações feitas nas duas idades estudadas.

The aim of this study was to estimate variance components, heritability and genetic correlation for slaughter conformation at weaning (SCW), slaughter conformation at yearling age (SCY), weaning weight (WW) and yearling age weight (YW) of Nellore cattle. A total of 6,397 records of all traits measured at weaning and at yearling age were used in the analysis. A multiple trait animal model which included the direct genetic additive, maternal genetic additive, maternal permanent environmental and residual random effects, as well as the fixed effect of contemporary group and the covariates age at calving (for weight and slaughter conformation at weaning and yearling age) and age at the evaluation time (slaughter conformation at weaning and yearling age) was proposed. The heritability estimates for SCW, SCY, WW and YW were, respectively, 0.13, 0.25, 0.22 and 0.29. Positive and high genetic correlations between body weight traits and visual evaluation traits suggested that direct selection for one trait results in positive indirect response in the remaining trait. Slaughter conformation trait can be selected at earlier age due to the high and positive genetic correlation between conformation scores at different age.

Genetic evaluation for large data sets by random regression models in Nellore cattle / Avaliação genética para grandes massas de dados por meio de modelos de regressão aleatória em gado Nelore

Expected progeny differences (EPD) of Nellore cattle estimated by random regression model (RRM) and multiple trait model (MTM) were compared. Genetic evaluation data included 3,819,895 records of up nine sequential weights of 963,227 animals measured at ages ranging from one day (birth weight) to 733 days. Traits considered were weights at birth, ten to 110-day old, 102 to 202-day old, 193 to 293-day old, 283 to 383-day old, 376 to 476-day old, 551 to 651-day old, and 633 to 733-day old. Seven data samples were created. Because the parameters estimates biologically were better, two of them were chosen: one with 84,426 records and another with 72,040. Records preadjusted to a fixed age were analyzed by a MTM, which included the effects of contemporary group, age of dam class, additive direct, additive maternal, and maternal permanent environment. Analyses were carried out by REML, with five traits at a time. The RRM included the effects of age of animal, contemporary group, age of dam class, additive direct, permanent environment, additive maternal, and maternal permanent environment. Different degree of Legendre polynomials were used to describe random effects. MTM estimated covariance components and genetic parameters for weight at birth and sequential weights and RRM for all ages. Due to the fact that correlation among the estimates EPD from MTM and all the tested RM were not equal to 1.0, it is not possible to recommend RRM to genetic evaluation to large data sets.(AU)

Compararam-se as diferenças esperadas nas progênies (DEPs) de gado Nelore, estimadas por meio de um modelo de características múltiplas (MTM), com um modelo de regressão aleatória (RRM). Foram utilizados 3.819.895 dados de peso corporal sequenciais para a avaliação genética de 963.227 animais, coletados do nascer aos 733 dias de idade. As características consideradas foram: peso ao nascer e pesos dos 10 aos 110, dos 102 aos 202, dos 193 aos 293, dos 283 aos 383, dos 376 aos 476, dos 467 aos 567, dos 551 aos 651, e dos 633 aos 733 dias. Sete amostras foram geradas. Duas amostras resultaram em estimativas de parâmetros mais consistentes do ponto de vista biológico, sendo, portanto consideradas representativas da população em estudo. A primeira amostra constituiu-se de 84.426 medidas, e a segunda, de 72.040. Os pesos pré-ajustados para as idades fixas foram analisados por meio de um MTM, com cinco características por processamento, no qual se incluíram efeito de grupo contemporâneo, classe de idade da vaca, aditivo direto, aditivo materno e ambiente materno permanente, utilizando-se a metodologia de máxima verossimilhança restrita (REML). Diferentes graus dos polinômios de Legendre foram utilizados em um RRM, para os efeitos aleatórios. As correlações entre as DEPs estimadas por meio do modelo para características múltiplas e de regressão aleatória não foram iguais a 1,0, portanto, não se recomenda a utilização dos modelos de regressão aleatória para avaliação genética para grande massa de dados.(AU)

Genetic evaluation for large data sets by random regression models in Nellore cattle / Avaliação genética para grandes massas de dados por meio de modelos de regressão aleatória em gado Nelore

Expected progeny differences (EPD) of Nellore cattle estimated by random regression model (RRM) and multiple trait model (MTM) were compared. Genetic evaluation data included 3,819,895 records of up nine sequential weights of 963,227 animals measured at ages ranging from one day (birth weight) to 733 days. Traits considered were weights at birth, ten to 110-day old, 102 to 202-day old, 193 to 293-day old, 283 to 383-day old, 376 to 476-day old, 551 to 651-day old, and 633 to 733-day old. Seven data samples were created. Because the parameters estimates biologically were better, two of them were chosen: one with 84,426 records and another with 72,040. Records preadjusted to a fixed age were analyzed by a MTM, which included the effects of contemporary group, age of dam class, additive direct, additive maternal, and maternal permanent environment. Analyses were carried out by REML, with five traits at a time. The RRM included the effects of age of animal, contemporary group, age of dam class, additive direct, permanent environment, additive maternal, and maternal permanent environment. Different degree of Legendre polynomials were used to describe random effects. MTM estimated covariance components and genetic parameters for weight at birth and sequential weights and RRM for all ages. Due to the fact that correlation among the estimates EPD from MTM and all the tested RM were not equal to 1.0, it is not possible to recommend RRM to genetic evaluation to large data sets.

Compararam-se as diferenças esperadas nas progênies (DEPs) de gado Nelore, estimadas por meio de um modelo de características múltiplas (MTM), com um modelo de regressão aleatória (RRM). Foram utilizados 3.819.895 dados de peso corporal sequenciais para a avaliação genética de 963.227 animais, coletados do nascer aos 733 dias de idade. As características consideradas foram: peso ao nascer e pesos dos 10 aos 110, dos 102 aos 202, dos 193 aos 293, dos 283 aos 383, dos 376 aos 476, dos 467 aos 567, dos 551 aos 651, e dos 633 aos 733 dias. Sete amostras foram geradas. Duas amostras resultaram em estimativas de parâmetros mais consistentes do ponto de vista biológico, sendo, portanto consideradas representativas da população em estudo. A primeira amostra constituiu-se de 84.426 medidas, e a segunda, de 72.040. Os pesos pré-ajustados para as idades fixas foram analisados por meio de um MTM, com cinco características por processamento, no qual se incluíram efeito de grupo contemporâneo, classe de idade da vaca, aditivo direto, aditivo materno e ambiente materno permanente, utilizando-se a metodologia de máxima verossimilhança restrita (REML). Diferentes graus dos polinômios de Legendre foram utilizados em um RRM, para os efeitos aleatórios. As correlações entre as DEPs estimadas por meio do modelo para características múltiplas e de regressão aleatória não foram iguais a 1,0, portanto, não se recomenda a utilização dos modelos de regressão aleatória para avaliação genética para grande massa de dados.