👤 D Altieri

The Weibull proportional hazards model was used to identify the nongenetic effects that affect length of productive life (LPL) of the Italian Mediterranean buffalo. Data were provided by the Italian National Association of Buffalo Breeders and included records of reproductive, productive, and linear type traits from 59,943 buffalo with first calving from 2002 to 2019. Data were divided into 4 geographical regions to determine whether the relationship between the investigated effects and LPL varied by region. Length of productive life was defined as the number of days from the first calving to culling for those buffaloes that were culled (uncensored) or to the date of the last test-day for those that are still alive (censored). The Weibull model included time-dependent effects of herd-year-season of calving, parity and stage of lactation, production as within-herd deviations, as well as time-independent effects of age at first calving, year of birth, type of reproduction (natural mating vs. AI), classifier, and ten linear type traits. The average duration of productive life was 1,604 days. Both year of birth and production level had a significant effect on culling risk. Moreover, culling risk decreased linearly across parities. The reference point for age at first calving relative to other classes was set at 35 months. A significant relationship between linear type traits and relative culling risk was also observed, being highest for buffaloes with the lowest linear scores. The results show that the Weibull model provides consistent and robust risk estimates. Therefore, this model would be recommended for future implementation of the first genetic evaluation of LPL in the Italian Mediterranean buffalo. Show less

Previous SNP array analyses have revealed genomic alterations of the Notch pathway as being the most frequent abnormality in adrenocortical tumors (ACTs). The aim of the present study was to evaluate the expression of components of Notch signaling in ACTs and to correlate them with clinical outcome. The mRNA expression of JAG1, NOTCH1, and selected target genes of NOTCH1 (HES1, HES5, and HEY2) was evaluated in 80 fresh frozen samples (28 normal adrenal glands (NAGs), 24 adenomas (ACAs), and 28 carcinomas (ACCs)) by quantitative RT-PCR. Immunohistochemistry was performed in 221 tissues on paraffin slides (16 NAGs, 27 ACAs, and 178 ACCs) for JAG1, activated NOTCH1 (aNOTCH1), and HEY2. An independent ACC validation cohort (n=77) was then also investigated. HEY2 mRNA expression was higher in ACCs than it was in ACAs (P<0.05). The protein expression of all of the factors was high (H-score 2-3) in a larger proportion of ACCs as compared to ACAs and NAGs (JAG1 in 27, 15, and 10%; aNOTCH1 in 13, 8, and 0%; HEY2 in 66, 61, and 33% respectively, all P<0.001). High JAG1 expression was associated with earlier tumor stages and lower numbers of metastases in ACCs (both P=0.08) and favorably impacted overall and progression-free survival (PFS) (131 vs 30 months, hazard ratio (HR) 0.45, and 37 vs 9 months, HR 0.51, both P<0.005). This impact on overall survival (OS) was confirmed in the validation cohort. No such association was observed for aNOTCH1 or HEY2. In conclusion, different components of the Notch1 signaling pathway are overexpressed in ACCs, which suggests a role for the pathway in malignant transformation. However, JAG1 is overexpressed in a subgroup of ACCs with a better clinical outcome. Show less