Unknown parent groups and truncated pedigree in single-step genomic evaluations of Murrah buffaloes.

Missing pedigree may produce bias in genomic evaluations. Thus, strategies to deal with this problem have been proposed as using unknown parent groups (UPG) or truncated pedigrees. The aim of this study was to investigate the impact of modeling missing pedigree under ssGBLUP evaluations for productive and reproductive traits in dairy buffalos using different approaches: 1) traditional BLUP without UPG (BLUP), 2) traditional BLUP including UPG (BLUP/UPG), 3) ssGBLUP without UPG (ssGBLUP), 4) ssGBLUP including UPG in the A and A22 matrices (ssGBLUP/A_UPG), 5) ssGBLUP including UPG in all elements of the H matrix (ssGBLUP/H_UPG), 6) BLUP with pedigree truncation for the last 3 generations (BLUP/truncated), and 7) ssGBLUP with pedigree truncation for the last 3 generations (ssGBLUP/ truncated). UPGs were not used in the scenarios with truncated pedigree. A total of 3,717, 4,126 and 3,823 records of the first lactation for accumulated 305 d milk yield (MY), age at first calving (AFC) and lactation length (LL), respectively were used. Accuracies ranged from 0.27 for LL (BLUP) to 0.46 for MY (BLUP), bias ranged from -0.62 for MY (ssGBLUP) to 0.0002 for AFC (BLUP/truncated), and dispersion ranged from 0.88 for MY (BLUP/ A_UPG) to 1.13 for LL (BLUP). Genetic trend showed genetic gains for all traits across 20 years of selection and the impact of including either genomic information, UPG or pedigree truncation under GEBV accuracies ranged among the evaluated traits. Overall, methods using UPGs, truncation pedigree and genomic information exhibited potential to improve GEBV accuracies, bias and dispersion for all traits compared with other methods. Truncated scenarios promoted high genetic gains. In small populations with few genotyped animals, combining truncated pedigree or UPG with genomic information is a feasible approach to deal with missing pedigrees.

Estimates of genetic parameters for rumination time, feed efficiency, and methane production traits in first-lactation Holstein cows.

The large-scale recording of traits such as feed efficiency (FE) and methane emissions (ME) for use in genetic improvement programs is complex, costly, and time-consuming. Therefore, heritable traits that can be continuously recorded in dairy herds and are correlated with FE and ME traits could provide useful information for genetic evaluation. Rumination time has been suggested to be associated with FE, methane production (MeP; ME in g/d), and production traits at the phenotypic level. Therefore, the objective of this study was to investigate the genetic relationships among rumination time (RT), FE, methane and production traits using 7,358 records from 656 first-lactation Holstein cows. The estimated heritabilities were moderate for RT (0.45 ± 0.14), MeP (0.36 ± 0.12), milk yield (0.40 ± 0.08), fat yield (0.29 ± 0.06), protein yield (0.32 ± 0.07), and energy-corrected milk (0.28 ± 0.07), but were low and nonsignificant for FE (0.15 ± 0.07), which was defined as the residual of the multiple linear regression of DMI on energy-corrected milk and metabolic body weight. A favorable negative genetic correlation was estimated between RT and MeP (-0.53 ± 0.24), whereas a positive favorable correlation was estimated between RT and energy-corrected milk (0.49 ± 0.11). The estimated genetic correlation of RT with FE (-0.01 ± 0.17) was not significantly different from zero but showed a trend of a low correlation with dry matter intake (0.21 ± 0.13). These results indicate that RT is genetically associated with MeP and milk production traits, but high standard errors indicate that further analyses should be conducted to verify these findings when more data for RT, MeP, and FE become available.

Development of an Anti-Acinetobacter baumannii Biofilm Phage Cocktail: Genomic Adaptation to the Host.

The need for alternatives to antibiotic therapy due to the emergence of multidrug resistant bacteria (MDR), such as the nosocomial pathogen Acinetobacter baumannii, has led to the recovery of phage therapy. In addition, phages can be combined in cocktails to increase the host range. In this study, the evolutionary mechanism of adaptation was utilized in order to develop a phage adapted to A. baumannii, named phage Ab105-2phiΔCI404ad, from a mutant lytic phage, Ab105-2phiΔCI, previously developed by our group. The whole genome sequence of phage Ab105-2phiΔCI404ad was determined, showing that four genomic rearrangements events occurred in the tail morphogenesis module affecting the ORFs encoding the host receptor binding sites. As a consequence of the genomic rearrangements, 10 ORFs were lost and four new ORFs were obtained, all encoding tail proteins; two inverted regions were also derived from these events. The adaptation process increased the host range of the adapted phage by almost 3-fold. In addition, a depolymerase-expressing phenotype, indicated by formation of a halo, which was not observed in the ancestral phage, was obtained in 81% of the infected strains. A phage cocktail was formed by combining this phage with the A. baumannii phage vB_AbaP_B3, known to express a depolymerase. Both the individual phages and the phage cocktail showed strong antimicrobial activity against 5 clinical strains and 1 reference strain of A. baumannii tested. However, in all cases resistance to the bacterial strains was also observed. The antibiofilm activity of the individual phages and the cocktail was assayed. The phage cocktail displayed strong antibiofilm activity.

PI3K inhibition by BKM120 results in anti-proliferative effects on corticotroph tumor cells.

PURPOSE: Cushing's disease is associated with significant morbidity; thus, additional tumor-directed drugs with the potential to exert antineoplastic effects on corticotroph adenoma cells are desired. The phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) pathway, which plays regulatory role in cell survival and proliferation, is activated in pituitary adenomas. The present study evaluated the effects of BKM120 (Buparlisib), an oral PI3K inhibitor, on cell viability, apoptosis, cell cycle phase distribution, and ACTH production in mouse corticotroph tumor cells. METHODS: AtT-20/D16v-F2 mouse pituitary corticotroph tumor cells were treated with increasing concentrations of BKM120 or vehicle. Cell viability was measured using an MTS-based assay. Apoptosis was evaluated by Annexin V staining. Cell cycle analysis was performed by propidium iodide DNA staining and flow cytometry. Gene expression of cell cycle regulators (Cdkn1b, Ccnd1, Ccne1, Cdk2, Cdk4, Myc, and Rb1) was assessed by qPCR. Protein expression of p27, total and phosphorylated Akt was assessed by Western blot. ACTH levels were measured in the culture supernatants by chemiluminescent immunometric assay. RESULTS: Treatment with BKM120 decreased AtT-20/D16v-F2 cell viability, induced a G0/G1 cell cycle arrest, reduced the phosphorylation of Akt at Serine 473, and increased p27 expression. Furthermore, BKM120 treatment diminished ACTH levels in the cell culture supernatants. CONCLUSION: In vitro inhibition of PI3K/AKT pathway by BKM120 resulted in anti-proliferative effects on corticotroph tumor cells, decreasing cell viability and ACTH production. These encouraging findings shape the path for further experiments with the inhibition of PI3K/AKT pathway in Cushing's disease.

Comparison of Stud- Retentor Versus Bar-Clip Attachment as Implant- Supported Systems Used in Overdentures: A Systematic Review and Meta-Analysis.

This study aimed to perform a systematic review and meta-analysis to analyze the results obtained clinically for bar-clip versus stud-retainers in overdentures. Three databases (PubMed Central, MEDLINE, and BvSalud) were used beyond a manual search. The study followed strictly the inclusion and exclusion criteria, considering the PICO strategy. For the risk of bias and quality assessment of studies, in the case of RCT, there were six domains of analysis, and for non-RCT studies, the Modified Newcastle-Ottawa Scale was performed. A meta-analysis was developed using the available data for marginal bone loss (MBL) and survival rate. 25 studies were included. The stud-retentor had the lowest implant SR (87.6%) and the greatest MBL (1.96 mm). For the bar-clip system, the mean survival rate was 95.91%, with only 4 studies included for this system, and the mean MBL was 1.13 mm. Only 3 studies directly compared both systems quantitatively, showing a significantly greater MBL toward the stud-retention group. The results may not allow determination of the best system for overdenture (stud retentor or bar-clip). Therefore, most of the studies suggested the stud-retentor as a more preferable system due to better distribution of forces, biological peri-implant behavior, low-cost, and ease for removal facilitating the sanitization and/or repair.

Activation of C-C motif chemokine receptor 2 modulates testicular macrophages number, steroidogenesis, and spermatogenesis progression.

The monocyte chemoattractant protein 1 (MCP-1) belongs to the CC chemokine family and acts in the recruitment of C-C motif chemokine receptor 2 (CCR2)-positive immune cell types to inflammation sites. In testis, the MCP-1/CCR2 axis has been associated with the macrophage population's functional regulation, which presents significant functions supporting germ cell development. In this context, herein, we aimed to investigate the role of the chemokine receptor CCR2 in mice testicular environment and its impact on male sperm production. Using adult transgenic mice strain that had the CCR2 gene replaced by a red fluorescent protein gene, we showed a stage-dependent expression of CCR2 in type B spermatogonia and early primary spermatocytes. Several parameters related to sperm production were reduced in the absence of CCR2 protein, such as Sertoli cell efficiency, meiotic index, and overall yield of spermatogenesis. Daily sperm production decreased by almost 40%, and several damages in the seminiferous tubules were observed. Significant reduction in the expression of important genes related to the Sertoli cell function (Cnx43, Vim, Ocln, Spna2) and meiosis initiation (Stra8, Pcna, Prdm9, Msh5) occurred in comparison to controls. Also, the number of macrophages significantly decreased in the absence of CCR2 protein, along with a disturbance in Leydig cell steroidogenic activity. In summary, our results show that the non-activation of the MCP-1/CCR2 axis disturbs the testicular homeostasis, interfering in macrophage population, meiosis initiation, blood-testis barrier function, and androgen synthesis, leading to the malfunction of seminiferous tubules, decreased testosterone levels, defective sperm production, and lower fertility index.

Lactobacillus plantarum Lp62 exerts probiotic effects against Gardnerella vaginalis ATCC 49154 in bacterial vaginosis.

The severe side-effects elicited by conventional antibiotic therapy and the recurrence of Bacterial vaginosis-associated bacteria and bacterial resistance have led to the development of novel alternative therapies, among which genital probiotics are widely used. In this study, we aimed to evaluate the antimicrobial activities of Lactobacillus plantarum Lp62 and its supernatant against Gardnerella vaginalis, using both in vitro and in vivo approaches. In vitro assays were used to evaluate the viability of the strain and the antimicrobial activities of the supernatant in different pH ranges. An in vivo assay was performed on female BALB/c mice, wherein the animals were divided into eight groups: four control groups and four treated groups (for curative and preventive therapies). After infecting and treating the mice, the animals were killed to quantify the bacterial load using qPCR, evaluate leucocyte cellular response, determine vaginal cytokine levels and perform cytokine tissue gene expression. Our analyses revealed significant activity of the strain and its supernatant against G. vaginalis. Preliminary in vitro tests showed that the strain grew with equal efficiency in different pH ranges. Meanwhile, the presence of halo and inhibition of pathogen growth established the significant activity of the supernatant against G. vaginalis. We observed that both micro-organisms are resident bacteria of mouse microbiota and that the lactobacilli population growth was affected by G. vaginalis and vice versa. We also observed that the treated groups, with their low bacterial load, absence of leucocyte recruitment, reduced cytokine levels in the vaginal lavage and normalized cytokine gene expression, successfully controlled the infection.

Cryptococcal Titan Cells: When Yeast Cells Are All Grown up.

Cryptococcus neoformans is a human pathogenic yeast that causes hundreds of thousands of deaths worldwide among susceptible individuals, in particular, HIV+ patients. This yeast has developed several adaptation mechanisms that allow replication within the host. During decades, this yeast has been well known for a very peculiar and unique structure that contributes to virulence, a complex polysaccharide capsule that surrounds the cell wall. In contrast to other fungal pathogens, such as Candida albicans or Aspergillus fumigatus, the role of morphological transitions has not been studied in the virulence of Cryptococcus neoformans since this yeast does not form hyphae during infection. However, in the last years, different groups have described the ability of this fungus to change its size during infection. In particular, Cryptococcus can form "titan cells," which are blastoconidia of an abnormal large size. Since their discovery, there is increasing evidence that these cells contribute, not only to long-term persistence in the host, but they can also actively participate in the development of the disease. Recently, several groups have simultaneously described different media that induce the appearance of titan cells in laboratory conditions. Using these conditions, new inducing factors and signaling pathways involved in this transition have been described. In this article, we will review the main phenotypic features of these cells, factors, and transduction pathways that induce cell growth, and how titan cells contribute to the disease caused by this pathogen.

Association of spontaneous abortion and Ureaplasma parvum detected in placental tissue.

Spontaneous abortion is considered a public health problem having several causes, including infections. Among the infectious agents, bacteria of the vaginal microbiota and Ureaplasma parvum have been associated with abortion, but their participation needs to be further elucidated. This study aims to evaluate the influence of Mollicutes on the development of spontaneous abortion. Women who underwent spontaneous abortion and those with normal birth (control) were studied. Samples of cervical mucus (CM) and placental tissue were collected to identify Mollicutes using the quantitative polymerase chain reaction methodology. Eighty-nine women who had a miscarriage and 20 women with normal pregnancies were studied. The presence of Mollicutes in placental tissue increased the chance of developing miscarriage sevenfold. The prevalence of U. parvum in women who experienced spontaneous abortion was 66.3% in placental tissue. A positive association was observed between the detection of U. parvum in samples of placental tissue and abortion. There was a significant increase in microbial load in placental tissue for M. hominis, U. urealyticum and U. parvum compared to the control group. Detection of U. parvum in CM in pregnant women can ascend to the region of the placental tissue and trigger a spontaneous abortion.

Short communication: Time-dependent genetic parameters and single-step genome-wide association analyses for predicted milk fatty acid composition in Ayrshire and Jersey dairy cattle.

Milk fat content and fatty acid (FA) composition have great economic value to the dairy industry as they are directly associated with taste and chemical-physical characteristics of milk and dairy products. In addition, consumers' choices are not only based on the nutritional aspects of food, but also on products known to promote better health. Milk FA composition is also related to the metabolic status and physiological stages of cows and thus can also be used as indicator for other novel traits of interest (e.g., metabolic diseases and methane yield). Genetic selection is a promising alternative to manipulate milk FA composition. In this study, we aimed to (1) estimate time-dependent genetic parameters for 5 milk FA groups (i.e., short-chain, medium-chain, long-chain, saturated, and unsaturated) predicted based on milk mid-infrared spectroscopy, for Canadian Ayrshire and Jersey breeds, and (2) conduct a time-dependent, single-step genome-wide association study to identify genomic regions, candidate genes, and metabolic pathways associated with milk FA. We analyzed 31,709 test-day records of 9,648 Ayrshire cows from 268 herds, and 34,341 records of 11,479 Jersey cows from 883 herds. The genomic database contained a total of 2,330 Ayrshire and 1,019 Jersey animals. The average daily heritability ranged from 0.18 (long-chain FA) to 0.34 (medium-chain FA) in Ayrshire, and from 0.25 (long-chain and unsaturated FA) to 0.52 (medium-chain and saturated FA) in Jersey. Important genomic regions were identified in Bos taurus autosomes BTA3, BTA5, BTA12, BTA13, BTA14, BTA16, BTA18, BTA20, and BTA21. The proportion of the variance explained by 20 adjacent SNP ranged from 0.71% (saturated FA) to 1.11% (long-chain FA) in Ayrshire, and from 0.70% (unsaturated FA) to 3.09% (medium-chain FA) in Jersey cattle. Important candidate genes and pathways were also identified, such as the PTK2 and TRAPPC9 genes, associated with milk fat percentage, and HMGCS, FGF10, and C6 genes, associated with fertility traits and immune response. Our findings on the genetic parameters and candidate genes contribute to a better understanding of the genetic architecture of milk FA composition in Ayrshire and Jersey dairy cattle.

Genomic analyses for predicted milk fatty acid composition throughout lactation in North American Holstein cattle.

Milk fat composition has important implications in the nutritional and processing properties of milk. Additionally, milk fat composition is associated with cow physiological and health status. The main objectives of this study were (1) to estimate genetic parameters for 5 milk fatty acid (FA) groups (i.e., short-chain, medium-chain, long-chain, saturated, and unsaturated) predicted from milk infrared spectra using a large data set; (2) to predict genomic breeding values using a longitudinal single-step genomic BLUP approach; and (3) to conduct a single-step GWAS aiming to identify genomic regions, candidate genes, and metabolic pathways associated with milk FA, and consequently, to understand the underlying biology of these traits. We used 629,769 test-day records of 201,465 first-parity Holstein cows from 6,105 herds. A total of 8,865 genotyped (Illumina BovineSNP50K BeadChip, Illumina, San Diego, CA) animals were considered for the genomic analyses. The average daily heritability ranged from 0.24 (unsaturated FA) to 0.47 (medium-chain and saturated FA). The reliability of the genomic breeding values ranged from 0.56 (long-chain fatty acid) to 0.74 (medium-chain fatty acid) when using the default τ and ω scaling parameters, whereas it ranged from 0.58 (long-chain fatty acid) to 0.73 (short-chain fatty acid) when using the optimal τ and ω values (i.e., τ = 1.5 and ω = 0.6), as defined in a previous study in the same population. Relevant chromosomal regions were identified in Bos taurus autosomes 5 and 14. The proportion of the variance explained by 20 adjacent single nucleotide polymorphisms ranged from 0.71% (saturated FA) to 15.12% (long-chain FA). Important candidate genes and pathways were also identified. In summary, our results contribute to a better understanding of the genetic architecture of predicted milk FA in dairy cattle and reinforce the relevance of using genomic information for genetic analyses of these traits.

Short communication: Genetic parameter estimates for caprine arthritis encephalitis in dairy goats.

Caprine arthritis encephalitis (CAE) is a chronic disease caused by a retrovirus from the Lentivirus genus. No effective vaccines or treatments exist, and therefore genetic selection for CAE resistance might be a feasible alternative. To our best knowledge, no other studies have investigated the genetic architecture of CAE resistance in dairy goats. In this context, this study was designed to estimate genetic parameters for CAE infection in Alpine and Saanen goats using a Bayesian threshold model. A total of 542 adult goats (and >3-generation pedigree), which were group-housed in a population with high CAE prevalence, were tested based on a serological infection assessment test (negative = 1 or positive = 2) and used for this study. Genetic parameters were estimated using the BLUPF90 family programs. There was considerable genetic variability for CAE resistance, and pedigree-based heritability was significantly different from zero (0.026 < heritability < 0.128). Our findings indicate that the prevalence of CAE in goat herds can be reduced or eliminated through direct genetic selection for CAE resistance in addition to proper management strategies.

Effect of carbodiimide and chlorhexidine on the bond strength longevity of resin cement to root dentine after radiation therapy.

AIM: To evaluate the effect of carbodiimide (EDC) and chlorhexidine (CHX) on the bond strength (BS) of resin cement to root dentine of teeth submitted to radiotherapy. METHODOLOGY: One hundred and twenty extracted maxillary canines were selected and assigned to 2 groups (n = 60): nonirradiated and irradiated (30 cycles of 2 Gy, total 60 Gy). Roots lengths were standardized, and canals were prepared and filled. Post spaces were then prepared, and the samples were redistributed according to dentine treatment (n = 20): saline solution (SF); CHX 2%; or EDC 0.5M. After drying the post space, fibreglass posts were cemented. Cross-sectioned slices were obtained, and in half of the specimens of each subgroup (n = 10), the analysis was performed immediately; the others (n = 10) were stored for 10 months before analyses. The most cervical slice of each third was subjected to a push-out test and failure pattern analysis (n = 10), and the most apical slice submitted to the analysis of the adhesive interface by SEM (n = 5). The bond strength data were submitted to anova and Tukey tests, the adhesive interface adaptation was submitted to Kruskal-Wallis and Dunn's tests, and the Chi-square test was used to evaluate the type of failure. RESULTS: The irradiated specimens had significantly lower bond strength (13.8 ± 4.3) than the nonirradiated (18.1 ± 3.1; P < 0.001). For the irradiated teeth, the bond strengths were significantly lower in the SF and CHX groups (P < 0.001). Also, the bond strengths reduced significantly after 10 months in the SF and CHX groups (P < 0.001). Cohesive failures occurred in dentine for irradiated specimens. Poorer interface adaptation, dentine fractures and microfractures were observed in irradiated specimens, and better adaptation was observed for specimens after EDC treatment. CONCLUSIONS: Radiotherapy was associated with lower bond strength and worse interface adaptation. Dentine treatment with EDC contributed to adhesive interface longevity during the cementation of glass fibre posts in nonirradiated and irradiated teeth.

Genetic evaluation for latent variables derived from factor analysis in broilers.

1. The aim of this study was to investigate the associations between several carcass, performance and meat quality traits in broilers through factor analysis and use the latent variables (i.e. factors) as pseudo-phenotypes in genetic evaluations.2. Factors were extracted using the principal components method and varimax rotation algorithm. Genetic parameters were estimated via Bayesian inference under a multiple-trait animal model.3. All factors taken together explained 71% of the original variance of the data. The first factor, denominated as 'weight', was associated with carcass and body weight traits; and the second factor, defined as 'tenderness', represented traits related to water-holding capacity and shear force. The third factor, 'colour', was associated with traits related to meat colour, whereas the fourth, referenced as 'viscera', was related to heart, liver and abdominal fat.4. The four biological factors presented moderate to high heritability (ranging from 0.35 to 0.75), which may confer genetic gains in this population.5. In conclusion, it seems possible to reduce the number of traits in the genetic evaluation of broilers using latent variables derived from factor analysis.

Effect of different solutions in reversing the damage caused by radiotherapy in dentin structure.

BACKGROUND: Previous studies have shown that radiotherapy of the head and neck region can cause direct changes in dental structure. This study evaluated the effect of different solutions on the dentin chemical composition and collagen structure of irradiated dentin. MATERIAL AND METHODS: Sixty maxillary canines were distributed in 2 groups (n=30): non-irradiated and irradiated (radiotherapy: X-rays of 6 MV in 30 cycles of 2 Gy to 60 Gy). The teeth were sectioned, sanded, and polished to obtain 3x3x2 mm fragments, which were redistributed in 3 subgroups (n=10) according to the treatment employed: chlorhexidine 2% (CL), chitosan 0.2% (QT), and 0.5 M carbodiimide (EDC). The samples were analyzed in FTIR at time zero (T0-control) and after 1 (T1), 3 (T3), and 5 (T5) minutes of immersion in the tested solutions. The data for the areas of the carbonate (C), amide I (AI) bands, and the ratio between the areas of the amide III/proline and hydroxyproline (AIII/PH) bands were analyzed using ANOVA and Tukey test (α=5%). RESULTS: QT showed lower C values at T1, T3, and T5 (P<0.0001), presenting lower values when compared to CL and EDC subgroups (P<0.05). AI values at T3 and T5 were higher than T0-control and T1, independently of the radiotherapy and dentin treatment factors (P<0.05). At T0-control, the AIII/PH ratio was lower in the irradiated group (P<0.05), whereas the EDC treatment at T1, T3, and T5 and QT at T3 and T5 increased these values (P<0.05), making them similar to non-irradiated subgroups (P>0.05). CONCLUSIONS: Radiotherapy changes the secondary structure of collagen, and EDC was able to restore collagen integrity after 1 minute of immersion, without changing dentin inorganic composition.

Moraxella bovis, Moraxella ovis and Moraxella bovoculi: biofilm formation and lysozyme activity.

AIMS: This study aimed to verify the formation of biofilms by Moraxella bovis, Moraxella ovis and Moraxella bovoculi isolates from ruminants. In addition, the lysozyme activity against the isolates of M. bovis, M. ovis and M. bovoculi in free form and in biofilms was determined. METHODS AND RESULTS: In this study, 54 isolates of Moraxella sp. obtained from bovine and ovine clinical samples were evaluated in vitro for capacity of biofilm formation and lysozyme susceptibility in planktonic and sessile cells. In addition, biofilms produced by four Moraxella sp. isolates were visualized under scanning electron microscope (SEM). It was possible to demonstrate, for the first time, the ability to form biofilms by M. ovis and M. bovoculi. The isolates of Moraxella sp. have the capacity to form biofilms in different intensities, varying among weak, moderate and strong. It was verified that the lysozyme shows activity on Moraxella sp. in planktonic form. However, on biofilms there was a reduction in the production, but without impairing its formation, and on consolidated biofilms the lysozyme did not have the capacity to eradicate the preformed biofilms. CONCLUSIONS: This work shows the capacity of biofilm formation by Moraxella sp. of veterinary importance. The lysozyme susceptibility of Moraxella sp. in planktonic form shows that this enzyme has bacteriostatic activity on this micro-organism and it reduced the production of biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: Based on the results, it is possible to infer that the biofilm formation capacity by Moraxella sp. and the resistance to lysozyme concentrations equal to or greater than the physiological levels of the ruminant tear may be linked not only to the capacity to colonize the conjunctiva, but also to remain in this place even after healing of the lesions, being a reservoir of Moraxella sp. in a herd.

Genomic prediction of lactation curves for milk, fat, protein, and somatic cell score in Holstein cattle.

Application of random regression models (RRM) in a 2-step genomic prediction might be a feasible way to select young animals based on the complete pattern of the lactation curve. In this context, the prediction reliability and bias of genomic estimated breeding value (GEBV) for milk, fat, and protein yields and somatic cell score over days in milk (DIM) using a 2-step genomic approach were investigated. In addition, the effect of including cows in the training and validation populations was investigated. Estimated breeding values for each DIM (from 5 to 305 d) from the first 3 lactations of Holstein animals were deregressed and used as pseudophenotypes in the second step. Individual additive genomic random regression coefficients for each trait were predicted using RRM and genomic best linear unbiased prediction and further used to derive GEBV for each DIM. Theoretical reliabilities of GEBV obtained by the RRM were slightly higher than theoretical reliabilities obtained by the accumulated yield up to 305 d (P305). However, validation reliabilities estimated for GEBV using P305 were higher than for GEBV using RRM. For all traits, higher theoretical and validation reliabilities were estimated when incorporating genomic information. Less biased GEBV estimates were found when using RRM compared with P305, and different validation reliability and bias patterns for GEBV over time were observed across traits and lactations. Including cows in the training population increased the theoretical reliabilities and bias of GEBV; nonetheless, the inclusion of cows in the validation population does not seem to affect the regression coefficients and the theoretical reliabilities. In summary, the use of RRM in 2-step genomic prediction produced fairly accurate GEBV over the entire lactation curve for all analyzed traits. Thus, selecting young animals based on the pattern of lactation curves seems to be a feasible alternative in genomic selection of Holstein cattle for milk production traits.

Invited review: Advances and applications of random regression models: From quantitative genetics to genomics.

An important goal in animal breeding is to improve longitudinal traits; that is, traits recorded multiple times during an individual's lifetime or physiological cycle. Longitudinal traits were first genetically evaluated based on accumulated phenotypic expression, phenotypic expression at specific time points, or repeatability models. Until now, the genetic evaluation of longitudinal traits has mainly focused on using random regression models (RRM). Random regression models enable fitting random genetic and environmental effects over time, which results in higher accuracy of estimated breeding values compared with other statistical approaches. In addition, RRM provide insights about temporal variation of biological processes and the physiological implications underlying the studied traits. Despite the fact that genomic information has substantially contributed to increase the rates of genetic progress for a variety of economically important traits in several livestock species, less attention has been given to longitudinal traits in recent years. However, including genomic information to evaluate longitudinal traits using RRM is a feasible alternative to yield more accurate selection and culling decisions, because selection of young animals may be based on the complete pattern of the production curve with higher accuracy compared with the use of traditional parent average (i.e., without genomic information). Moreover, RRM can be used to estimate SNP effects over time in genome-wide association studies. Thus, by analyzing marker associations over time, regions with higher effects at specific points in time are more likely to be identified. Despite the advances in applications of RRM in genetic evaluations, more research is needed to successfully combine RRM and genomic information. Future research should provide a better understanding of the temporal variation of biological processes and their physiological implications underlying the longitudinal traits.

Application of single-step genomic evaluation using multiple-trait random regression test-day models in dairy cattle.

Test-day traits are important for genetic evaluation in dairy cattle and are better modeled by multiple-trait random regression models (RRM). The reliability and bias of genomic estimated breeding values (GEBV) predicted using multiple-trait RRM via single-step genomic best linear unbiased prediction (ssGBLUP) were investigated in the 3 major dairy cattle breeds in Canada (i.e., Ayrshire, Holstein, and Jersey). Individual additive genomic random regression coefficients for the test-day traits were predicted using 2 multiple-trait RRM: (1) one for milk, fat, and protein yields in the first, second, and third lactations, and (2) one for somatic cell score in the first, second, and third lactations. The predicted coefficients were used to derive GEBV for each lactation day and, subsequently, the daily GEBV were compared with traditional daily parent averages obtained by BLUP. To ensure compatibility between pedigree and genomic information for genotyped animals, different scaling factors for combining the inverse of genomic (G-1) and pedigree (A-122) relationship matrices were tested. In addition, the inclusion of only genotypes from animals with accurate breeding values (defined in preliminary analysis) was compared with the inclusion of all available genotypes in the analyzes. The ssGBLUP model led to considerably larger validation reliabilities than the BLUP model without genomic information. In general, scaling factors used to combine the G-1 and A-122 matrices had small influence on the validation reliabilities. However, a greater effect was observed in the inflation of GEBV. Less inflated GEBV were obtained by the ssGBLUP compared with the parent average from traditional BLUP when using optimal scaling factors to combine the G-1 and A-122 matrices. Similar results were observed when including either all available genotypes or only genotypes from animals with accurate breeding values. These findings indicate that ssGBLUP using multiple-trait RRM increases reliability and reduces bias of breeding values of young animals when compared with parent average from traditional BLUP in the Canadian Ayrshire, Holstein, and Jersey breeds.

Single-step genome-wide association for longitudinal traits of Canadian Ayrshire, Holstein, and Jersey dairy cattle.

Estimating single nucleotide polymorphism (SNP) effects over time is essential to identify and validate candidate genes (or quantitative trait loci) associated with time-dependent variation of economically important traits and to better understand the underlying mechanisms of lactation biology. Therefore, in this study, we aimed to estimate time-dependent effects of SNP and identifying candidate genes associated with milk (MY), fat (FY), and protein (PY) yields, and somatic cell score (SCS) in the first 3 lactations of Canadian Ayrshire, Holstein, and Jersey breeds, as well as suggest their potential pattern of phenotypic effect over time. Random regression coefficients for the additive direct genetic effect were estimated for each animal using single-step genomic BLUP, based on 2 random regression models: one considering MY, FY, and PY in the first 3 lactations and the other considering SCS in the first 3 lactations. Thereafter, SNP solutions were obtained for random regression coefficients, which were used to estimate the SNP effects over time (from 5 to 305 d in lactation). The top 1% of SNP that showed a high magnitude of SNP effect in at least 1 d in lactation were selected as relevant SNP for further analyses of candidate genes, and clustered according to the trajectory of their SNP effects over time. The majority of SNP selected for MY, FY, and PY increased the magnitude of their effects over time, for all breeds. In contrast, for SCS, most selected SNP decreased the magnitude of their effects over time, especially for the Holstein and Jersey breeds. In general, we identified a different set of candidate genes for each breed, and similar genes were found across different lactations for the same trait in the same breed. For some of the candidate genes, the suggested pattern of phenotypic effect changed among lactations. Among the lactations, candidate genes (and their suggested phenotypic effect over time) identified for the second and third lactations were more similar to each other than for the first lactation. Well-known candidate genes with major effects on milk production traits presented different suggested patterns of phenotypic effect across breeds, traits, and lactations in which they were identified. The candidate genes identified in this study can be used as target genes in studies of gene expression.