Genetic and non-genetic factors associated with health and vitality traits in beef calves.

Awareness and interest in calf health and wellbeing is intensifying, prompting change in the management and breeding decisions of producers and associated policy-makers. The objectives of the present study were to 1) quantify the risk factors associated with subjectively measured scores of vigor and birth size as well as diagnoses of scour and pneumonia in a large national dataset of beef calves, and 2) to estimate the contribution of genetic variance to such phenotypic measures. After edits, the data consisted of health and birth size data subjectively scored by producers on 88,207 calves born in 6,126 Irish beef herds. Vigor was recorded on a scale of 1 (very poor) to 5 (very good). Birth size was also scored on a scale of 1 (very small) to 5 (very large). Scour and pneumonia were both scored independently based on the suspected number of occurrence of each (0 = no occurrence, 1 = one occurrence, or 2 = more than one occurrence). On average, 14.7% of calves were recorded as having had at least one occurrence of scour within the first 5 mo of life, whereas 6.4% of calves were recorded as having had at least one occurrence of pneumonia within the first 5 mo of life. Relative to female calves, male calves had a worse vigor score and a suspected greater incidence of both scour and pneumonia. Relative to singletons, twins were, on average, smaller at birth, they had a worse vigor score, and they were more prone to scour. Calves born in the later periods of the calving season (i.e., late and very late) had a greater incidence of scour relative to calves in the herd born earlier in the calving season. Heritability estimates for vigor, birth size, and pneumonia were 0.12 (0.02), 0.33 (0.03), and 0.08 (0.02), respectively; no genetic variance was detected for scour. Breeding for vigorous calves that are less susceptible to pneumonia could provide producers with an additional strategy to ensure consumer concerns regarding food quality, safety, and calf wellbeing are being met.

Methoxyethyl-modified intercellular adhesion molecule-1 antisense phosphorothiateoligonucleotides inhibit allograft rejection, ischemic-reperfusion injury, and cyclosporine-induced nephrotoxicity.

BACKGROUND: The addition of phosphorothioate (PS) groups to natural phosphodiester (PD) antisense oligodeoxynucleotides (oligo) prevents their in vivo hydrolysis by nucleases allowing an RNase-dependent elimination of targeted mRNA. To further improve oligo function 2'-methoxyethyl (ME) groups were attached to selected nucleotides at the 3'-end because ME groups block RNase activity. METHODS/RESULTS: ME modification of PS- or PD/PS-oligo targeting human intracellular adhesion molecule (ICAM)-1 mRNA significantly increased the degree and duration of the in vitro inhibitory effects without compromising selectivity and specificity. A 7-day intravenous or oral therapy with rat ME/PS-modified ICAM-1 antisense oligo extended the survivals of kidney allografts. In addition, ME/PS-modified ICAM-1 antisense oligo reduced ischemic-reperfusion injury in kidneys, as measured by glomerular filtration rate, creatinine levels, and infiltration with leukocytes. Finally, a 14-day treatment with cyclosporine (CsA)-induced nephrotoxicity in syngeneic kidney transplants correlated with both increased ICAM-1 protein expression and infiltration with leukocytes. Graft perfusion and treatment of recipients with ICAM-1 antisense ME/PS-oligo alleviated the nephrotoxic effect and decreased ICAM-1 expression and leukocyte infiltration. CONCLUSIONS: ME/PS-modified ICAM-1 antisense oligo is very effective in inhibiting the ICAM-1-dependent mechanism of graft infiltration and tissue damage involved in allograft rejection, ischemic-reperfusion injury, and CsA-induced nephrotoxicity.