Use of genomic recursions and algorithm for proven and young animals for single‐step genomic BLUP analyses – a simulation study

The purpose of this study was to examine accuracy of genomic selection via single‐step genomic BLUP (ssGBLUP) when the direct inverse of the genomic relationship matrix ( G ) is replaced by an approximation of G ^?1 based on recursions for young genotyped animals conditioned on a subset of proven animals, termed algorithm for proven and young animals (APY). With the efficient implementation, this algorithm has a cubic cost with proven animals and linear with young animals. Ten duplicate data sets mimicking a dairy cattle population were simulated. In a first scenario, genomic information for 20k genotyped bulls, divided in 7k proven and 13k young bulls, was generated for each replicate. In a second scenario, 5k genotyped cows with phenotypes were included in the analysis as young animals. Accuracies (average for the 10 replicates) in regular EBV were 0.72 and 0.34 for proven and young animals, respectively. When genomic information was included, they increased to 0.75 and 0.50. No differences between genomic EBV (GEBV) obtained with the regular G ^?1 and the approximated G ^?1 via the recursive method were observed. In the second scenario, accuracies in GEBV (0.76, 0.51 and 0.59 for proven bulls, young males and young females, respectively) were also higher than those in EBV (0.72, 0.35 and 0.49). Again, no differences between GEBV with regular G ^?1 and with recursions were observed. With the recursive algorithm, the number of iterations to achieve convergence was reduced from 227 to 206 in the first scenario and from 232 to 209 in the second scenario. Cows can be treated as young animals in APY without reducing the accuracy. The proposed algorithm can be implemented to reduce computing costs and to overcome current limitations on the number of genotyped animals in the ssGBLUP method.     

Effect of feeding different levels of wheat roti on nutrient utilization and blood metabolite profile in semi‐captive Asian elephants (Elephas maximus)

This experiment was conducted to study the effect of different levels of wheat roti (WR) on nutrient utilization and blood metabolites in Asian elephants fed roughages ad libitum. Nine (3 M, 6 F) Asian elephants (14–52 years of age, 1909–3968 kg BW) were used in an experiment based on replicated Latin square design. Animals in each group (n = 3) were assigned to one of the three dietary treatments in a manner that animals in all the three groups were exposed to all the three treatments in three different periods. Each feeding trial comprised 30 days (25 days of adaptation and 5 days collection period). The amount of WR fed to the elephants was 0.18, 0.12 and 0.06% of BW in groups I, II and III, respectively. They were allowed to forage in the nearby forests for 6 h/day and to bathe for 2 h/day. The animals had ad libitum access to cut Rohini (Mallotus philippensis) trees in their night shelter. Intake and apparent digestibility of dry matter (DM), crude protein (CP), gross energy (GE), Ca, P, Fe, Cu and Zn were measured. Feed consumption was not significantly different among the groups. Significant (p < 0.01) decrease in digestibility of DM and GE and blood glucose concentration was observed with decreased level of WR in the diet. Feeding of WR at 0.06% of BW supplied adequate amount of DE, CP, Ca, P, Fe, Cu and Zn to meet requirement for adult maintenance. Feeding of WR in excess of 0.06% of BW supplied DE in excess of requirement, increased blood glucose concentration which may cause obesity and other associated health problems. It was concluded that the amount of WR should be restricted to 0.06% of BW in the diet of captive Asian elephants.     

Influence of Disease Process and Duration on Acute Phase Proteins in Serum and Peritoneal Fluid of Horses with Colic

Background

The acute phase proteins (APP) serum amyloid A (SAA), haptoglobin, and fibrinogen are valuable blood biomarkers in equine inflammatory diseases, but knowledge of factors influencing their concentrations in blood and peritoneal fluid (PF) of horses with colic is needed.

Objectives

The objective of this study was to investigate the influence of demographics (age, sex, breed), disease process (simple obstruction, strangulating obstruction, inflammatory), disease location, disease duration, hypovolemia, and admission hospital on concentrations of APP, lactate and white blood cell counts (WBC) in horses with colic admitted to 2 referral hospitals.

Animals

The study included 367 horses with colic admitted at 2 referral hospitals.

Methods

Prospective multicenter observational study of clinical data, as well as blood and PF biomarkers. Associations between biomarker concentrations and clinical variables were analyzed using multivariate linear regression analysis.

Results

Increasing pre‐admission duration of colic was associated with increased concentrations of APP in blood and PF. Blood concentrations of SAA and fibrinogen were associated with disease process (inflammatory, strangulations, simple obstructions) in more colic duration groups (5–12 and >24 hours) than any of the other biomarkers. No relevant associations between demographic factors, hospital, or hydration status and the measured biomarkers were found.

Conclusions and Clinical Importance

In horses with colic, concentrations of APP are associated mainly with disease process and duration of colic and may thus be used for assessment of disease independently of demographic or geographic factors. Serum amyloid A may be a diagnostic marker for use in colic differential diagnosis, but further evaluation is needed.     

Single‐ and multiple dose pharmacokinetics and multiple dose pharmacodynamics of oral ABT‐116 (a TRPV1 antagonist) in dogs

Six dogs were used to determine single and multiple oral dose pharmacokinetics of ABT‐116. Blood was collected for subsequent analysis prior to and at 15, 30 min and 1, 2, 4, 6, 12, 18, and 24 h after administration of a single 30 mg/kg dose of ABT‐116. Results showed a half‐life of 6.9 h, k_el of 0.1/h, AUC of 56.5 μg·h/mL, T_max of 3.7 h, and C_max of 3.8 μg/mL. Based on data from this initial phase, a dose of 10 mg/kg of ABT‐116 (no placebo control) was selected and administered to the same six dogs once daily for five consecutive days. Behavioral observations, heart rate, respiratory rate, temperature, thermal and mechanical (proximal and distal limb) nociceptive thresholds, and blood collection were performed prior to and 4, 8, and 16 h after drug administration each day. The majority of plasma concentrations were above the efficacious concentration (0.23 μg/mL previously determined for rodents) for analgesia during the 24‐h sampling period. Thermal and distal limb mechanical thresholds were increased at 4 and 8 h, and at 4, 8, and 16 h respectively, postdosing. Body temperature increased on the first day of dosing. Results suggest adequate exposure and antinociceptive effects of 10 mg/kg ABT‐116 following oral delivery in dogs.     

Enantioselective pharmacokinetics of ketoprofen in calves after intramuscular administration of a racemic mixture

The pharmacokinetic properties of ketoprofen were determined in 4‐week‐old calves after intramuscular (i.m.) injection of a racemic mixture at a dose of 3 mg/kg body weight. Due to possible enantioselective disposition kinetics and chiral inversion, the plasma concentrations of the R(?) and S(+) enantiomer were quantified separately, using a stereospecific HPLC‐UV assay. A distinct predominance of the S(+) enantiomer was observed, as well as significantly different pharmacokinetic parameters between R(?) and S(+) ketoprofen. More in specific, a greater value for the mean area under the plasma concentration–time curve (AUC_0→∞) (46.92 ± 7.75 and 11.13 ± 2.18 μg·h/mL for the S(+) and R(?) enantiomer, respectively), a lower apparent clearance (Cl/F) (32.8 ± 5.7 and 139.0 ± 25.1 mL/h·kg for the S(+) and R(?) enantiomer, respectively) and a lower apparent volume of distribution (V_d/F) (139 ± 14.7 and 496 ± 139.4 mL/kg for the S(+) and R(?) enantiomer, respectively) were calculated for the S(+) enantiomer, indicating enantioselective pharmacokinetics for ketoprofen in calves following i.m. administration.     

Expression of Mitochondria‐Associated Genes (PPARGC1A,NRF‐1, BCL‐2 and BAX) in Follicular Development and Atresia of Goat Ovaries

Most follicles undergo atresia during the developmental process. Follicular atresia is predominantly regulated by apoptosis of granulosa cells, but the mechanism underlying apoptosis via the mitochondria‐dependent apoptotic pathway is unclear. We aimed to investigate whether the mitochondria‐associated genes peroxisome proliferator‐activated receptor‐gamma, coactivator1‐alpha (PPARGC1A), nuclear respiratory factor‐1 (NRF‐1), B‐cell CLL/lymphoma 2 (BCL‐2) and BCL2‐associated X protein (BAX) played a role in follicular atresia through this pathway. The four mitochondria‐associated proteins (PGC‐1α, which are encoded by the PPARGC1A gene, NRF‐1, BCL‐2 and BAX) mainly expressed in granulosa cells. The mRNA and protein levels of PPARGC1A/PGC‐1α and NRF‐1 in granulosa cells increased with the follicular development. These results showed that these genes may play a role in the regulation of the follicular development. In addition, compared with healthy follicles, the granulosa cell in atretic follicles had a reduced expression of NRF‐1, increased BAX expression and increased ratio of BAX to BCL‐2 expression. These results suggested that changes of the mitochondria‐associated gene expression patterns in granulosa cells may lead to follicular atresia during goat follicle development.     

Flow cytometric evaluation of ki67 for the determination of malignancy grade in canine lymphoma

Ki67 is a nuclear antigen significantly correlated with degree of malignancy in human non‐Hodgkin lymphomas. We wanted to assess the ability of flow cytometric evaluation of Ki67 index (Ki67I) in differentiating the grade of malignancy in canine lymphomas. Ki67I was determined on lymph node aspirates of 90 immunophenotyped lymphomas classified according to the updated Kiel classification: 80 high grade (HG, 62 B cell and 18 T cell) and 10 low grade (LG, 3 B cell and 7 T cell) lymphomas. HG lymphomas showed significantly higher Ki67I compared with LG lymphomas (P < 0.0001). A significant difference in HG lymphomas was detected between B‐ and T‐immunophenotypes. Receiver operating characteristic (ROC) curve highlighted a high accuracy of Ki67I in recognizing HG lymphomas [area under the curve (AUC) = 99.4] and a cut‐off value of 12.2% was established (sensitivity = 96.3% and specificity = 100%). Thus, we suggest the combination of Ki67I flow cytometric determination and immunophenotype as a reliable tool to classify canine lymphomas.