Standing in the canine precision medicine knowledge gap: Improving annotation of canine cancer genomic biomarkers through systematic comparative analysis of human cancer mutations in COSMIC

The accrual of cancer mutation data and related functional and clinical associations have revolutionised human oncology, enabling the advancement of precision medicine and biomarker-guided clinical management. The catalogue of cancer mutations is also growing in canine cancers. However, without direct high-powered functional data in dogs, it remains challenging to interpret and utilise them in research and clinical settings. It is well-recognised that canine and human cancers share genetic, molecular and phenotypic similarities. Therefore, leveraging the massive wealth of human mutation data may help advance canine oncology. Here, we present a structured analysis of sequence conservation and conversion of human mutations to the canine genome through a ‘caninisation’ process. We applied this analysis to COSMIC, the Catalogue of Somatic Mutations in Cancer, the most prominent human cancer mutation database. For the project's initial phase, we focused on the subset of the COSMIC data corresponding to Cancer Gene Census (CGC) genes. A total of 670 canine orthologs were found for 721 CGC genes. In these genes, 365 K unique mutations across 160 tumour types were converted successfully to canine coordinates. We identified shared putative cancer-driving mutations, including pathogenic and hotspot mutations and mutations bearing similar biomarker associations with diagnostic, prognostic and therapeutic utility. Thus, this structured caninisation of human cancer mutations facilitates the interpretation and annotation of canine mutations and helps bridge the knowledge gap to enable canine precision medicine.     

Duration of serologic response to three viral antigens in cats

OBJECTIVE: To determine whether vaccinated cats either remained seropositive or responded serologically to revaccination against 3 key viral antigens after extended periods since their last vaccination. DESIGN: Serologic survey. ANIMALS: 272 healthy client-owned cats. PROCEDURE: Cats were > or = 2 years old and vaccinated for feline panleukopenia virus (FPV), feline calicivirus (FCV), and feline herpesvirus (FHV). On day 0, cats were revaccinated with a vaccine from the same line of vaccines as they had historically received. Antibody titers were measured in sera collected on day 0 (prevaccination titer) and 5 to 7 days later (postvaccination titer). Cats were considered to have responded serologically if they had a day-0 hemagglutination inhibition titer to FPV > or = 1:40, serum neutralization (SN) titer to FCV > or = 1:32, SN titer to FHV > or = 1:16, or > or = 4-fold increase in antibody titer after revaccination. RESULTS: The percentage of cats that had titers at or above the threshold values or responded to revaccination with a > or = 4-fold increase in titer was 96.7% for FPV, 97.8% for FCV, and 88.2% for FHV. CONCLUSIONS AND CLINICAL RELEVANCE: In most cats, vaccination induced a response that lasted up to and beyond 48 months for all 3 antigens. Although not equivalent to challenge-of-immunity studies as a demonstration of efficacy, results suggest that revaccination with the vaccine used in our study provides adequate protection even when given less frequently than the traditional 1-year interval. The study provides valuable information for clinicians to determine appropriate revaccination intervals.     

Relationships between age at first calving and first lactation milk yield, and lifetime productivity and longevity in dairy cows

Lifetime records of 442 Holstein cows on one farm in North Queensland, Australia, were analysed to evaluate the effects of age at first calving (AFC) and first lactation milk yield on parities per lifetime, longevity, milk yield in subsequent lactations, lifetime milk production and the longevity index (LI), that is the proportion of a cow's life spent in active milk production. The mean daily yield in the first lactation was a reliable indicator of milk yield in subsequent lactations, estimated lifetime production, longevity and LI. The afc had no effect on lifetime days in milk. Neither the AFC nor the milk yield in the first lactation significantly affected the number of parities per lifetime. For the majority of cows, which produced less than 30 l/day in the first lactation, there was a significant positive relationship between longevity and AFC. However, none of the cows that produced more than 30 l/day in the first lactation survived for more than two lactations. The optimal AFC was thus two to two-and-a-half years, as these cows had the highest first lactation yield, estimated lifetime production and LI. The optimal mean daily yield in the first lactation was 20 to 30 l/day, as these cows lived longer and had a higher LI and lifetime production.     

Systemic Immunosuppression by Methylprednisolone and Pregnancy Rates in Goats Undergoing the Transfer of Cloned Embryos

The presence of the zona pellucida has been perceived as a requirement for the oviductal transfer of cloned embryos at early stages of development while protecting the embryo from an immune system response. We hypothesized that steroid hormone therapy could reduce a potential cellular immune response after the transfer of zona‐free cloned embryos into the oviduct of recipient female goats. In Experiment 1, seven does were used to study the systemic immunosuppressant effect of the methylprednisolone administration (for 3 days) on blood cell counts. Whole blood was collected prior to treatment with methyprednisolone and then on Days 1, 2, 3, 4, 7, 14, 21 and 28 after the first dose of methylprednisolone for the analysis of haematological parameters. Methylprednisolone treatment significantly reduced circulating white blood cells and neutrophils in comparison with pre‐treatment levels, demonstrating a systemic immunosuppressant effect. In Experiment 2, a group of 58 does were used as recipient females to study the effect of administration of methylprednisolone for 3 days on the establishment of pregnancies after the transfer of zona‐free cloned embryos into the oviducts. No effects on pregnancy rates on Day 30 were observed regarding the distinct treatment groups (control vs. methylprednisolone), the source of oocytes (in vivo‐ vs in vitro‐matured) or the presence or absence of the zona pellucida in embryos. In summary, methylprednisolone was effective at inducing a systemic immunosuppressed state in goats, but the treatment prior to embryo transfer did not affect pregnancy rates. Moreover, pregnancy rates were similar between zona‐free and zona‐intact goat cloned embryos.     

Sexual Precocity of Nellore Bulls that are Offspring of Super Precocious,Precocious and Normal Cows in Extensive Farming Conditions

The objective of this work was to verify that mothers classified as super precocious (M1) and precocious (M2) produce more precocious bulls than females classified as normal (M3). This study included 21 186 animals with an average age of 21.29 ± 1.77 months that underwent a breeding soundness evaluation from 1999 to 2008. Of these animals, 2019, 6059 and 13 108 were offspring of M1, M2 and M3 females, respectively. In the breeding soundness examination, the animals were classified as sound for reproduction, sound under a natural mating regime, unsound for reproduction and discarded. To compare the averages obtained for each category of mother within the individual breeding soundness classes, a chi‐square test with a 5% error probability was used, considering the effects of year and month of birth and farm. For the three classes of mothers (M1, M2 and M3), 67.26, 67.22 and 64.16% of bull calves were considered sound for reproduction and 19.71, 19.46 and 21.90% were considered unsound for reproduction, respectively. There was no difference in the frequency of animals that were sound for reproduction under the natural breeding regime between the three classes of mothers (8.87, 9.31 and 9.19%, respectively). There was a difference between the numbers of precocious and normal females that were discarded, with frequencies of 4.01 and 4.75%, respectively (p < 0.05). There were differences in year and month of birth and farm between super precocious and precocious cows in relation to the breeding soundness classification of the animals. It was concluded that the bull offspring of super precocious and precocious cows presented a higher percentage of approval in the breeding soundness examination than the bull offspring of normal cows, demonstrating that the selection for precocity of females has contributed to an increase in the sexual precocity of the herd in relation to the sexual maturity of bulls.     

Galileo Gravity Results and the Internal Structure of Io

Doppler data generated with the Galileo spacecraft's radio carrier wave were used to measure Io's external gravitational field. The resulting triaxial field is consistent with the assumption that Io is in tidal and rotational equilibrium. The inescapable conclusion is that it has a large metallic core. If the core is a eutectic mixture of iron and iron sulfide, it comprises 20.2 ± 7.4 percent of the satellite's total mass with a radius that is about 52 percent of Io's mean radius of 1821.3 kilometers; if the core is pure iron, it comprises 10.5 ± 3.7 percent of the total mass with a radius of about 36 percent of the mean radius.