Congenic strains represent an important resource for confirmation of previously identified QTLs, for identification and mapping of additional phenotypes, and for exclusion of candidate genes. QTL-marker-assisted selection rapidly stabilized the genetic background within four generations (based on phenotypic assessments); however, phenotypic selection during the backcrossing to generate congenic strains did not contribute to the successful capture of the ISS QTLs.

The physiological response of the preruminant calf to sustained exposure to moderate cold has not been studied extensively. Effects of cold on growth performance and health of preruminant calves as well as functional measures of energy metabolism, fat-soluble vitamin, and immune responsiveness were evaluated in the present study. Calves, 3 to 10 d of age, were assigned randomly to cold (n = 14) or warm (n = 15) indoor environments. Temperatures in the cold environment averaged 4.7 degrees C during the study. Frequent wetting of the environment and the calves was used to augment effects of the cold environment. Temperatures in the warm environment averaged 15.5 degrees C during the study. There was no attempt to increase the humidity in the warm environment. Preventative medications or vaccinations that might influence disease resistance were not administered. Nonmedicated milk replacer (20% crude protein and 20% fat fed at 0.45 kg/d) and a nonmedicated starter grain fed ad libitum were fed to all calves. Relative humidity was, on average, almost 10% higher in the cold environment. Warm-environment calves were moderately healthier (i.e., lower respiratory scores) and required less antibiotics. Scour scores, days scouring, and electrolyte costs, however, were unaffected by environmental temperature. Growth rates were comparable in warm and cold environments, although cold-environment calves consumed more starter grain and had lower blood glucose and higher blood nonesterified fatty acid concentrations. The nonesterified fatty acid and glucose values for cold-stressed calves, however, did not differ sufficiently from normal values to categorize these calves as being in a state of negative-energy balance. Levels of fat-soluble vitamin, antibody, tumor necrosis factor-alpha, and haptoglobin were unaffected by sustained exposure to moderate cold. These results support the contention that successful adaptation of the dairy calf to cold is dependent upon the availability of adequate nutrition.

Effects of neonatal vaccination on antigen-specific cellular and humoral immune responses of dairy calves have not been well described. The purpose of this study was to characterize the ontogeny of the adaptive immune response in calves sensitized to the attenuated strain of Mycobacterium bovis, bacillus Calmette-Guerín. Holstein bull calves were nonvaccinated (n = 6, vaccination controls) or vaccinated subcutaneously (n = 6) with bacillus Calmette-Guerín at 1 and 7 wk of age. Composition and functional capacities of blood mononuclear cell populations from calves were evaluated at 1 (prevaccination), 3, 6, 7, 8, 9, and 12 wk of age. Young adults (nulliparous heifers, n = 4) vaccinated in an identical manner were sampled concurrently to evaluate effects of animal maturity on the development of the adaptive immune response. Responses of nonvaccinated calves to recall antigen (Mycobacterium bovis purified protein derivative) ex vivo and in vivo (i.e., cutaneous delayed-type hypersensitivity) were minimal or nonexistent. Responses of cells from vaccinated calves and young adults to recall antigen, however, were evident as early as wk 2 after primary vaccination. Antigen-induced T cell subset proliferation, and secretion of interferon-gamma, nitric oxide, and tumor necrosis factor-alpha by cells from vaccinated calves were comparable to or greater than responses of vaccinated adults during the 11-wk study. Eleven weeks after primary vaccination, cutaneous responses of vaccinated calves and young adults to intradermal administration of antigen were pronounced and comparable, demonstrating the capacity of the bovine neonate to develop a vigorous cell-mediated immune response in vivo. Antibody responses (i.e., antibody concentrations in sera and in supernatants from antigen-stimulated cultures of blood mononuclear cells) of vaccinated calves, in contrast, were markedly lower than parallel responses of vaccinated adults. In conclusion, these results suggest that the bovine neonate can mount a vigorous, adult-like cell-mediated immune response when vaccinated at an early age.

In a two-lactation-gestation cycle experiment, 152 Holstein cows with low serum Se and vitamin E were fed total mixed rations and assigned at parturition to four groups (1, control; 2, 500 IU vitamin E/d; 3, 2 mg Se/d; 4, 500 IU vitamin E plus 2 mg Se/d). Supplements were not fed during dry periods. Serum Se and vitamin E were increased within 1 mo by oral supplements. Maximal mean serum Se in cycles 1 (67 ng/ml at 7 mo) and 2 (74 ng/ml at 4 mo) occurred in groups 3 and 4, respectively. Maximal mean serum vitamin E in cycle 1 (3.3 micrograms/ml at mo 8) and 2 (3.03 micrograms/ml at mo 2) occurred in groups 4 and 2, respectively. Selenium treatment of the dams increased Se in colostrum and in serum of presuckle calves. Vitamin E supplementation of dams did not affect vitamin E in serum of presuckled calves. Reproductive performance was not affected by supplement. In an 8-wk study, 24 lactating cows with low serum Se were assigned (6/group) to 0, 2.5, 5, and 10 mg supplemental Se/d. Maximal mean serum Se concentrations of 23, 56, 71, and 79 ng/ml were attained by wk 4 in the above respective groups. These data indicate that 2 to 2.5 mg supplemental Se/cow per d were inadequate for desirable serum Se concentrations and support recent changes in allowed Se supplementation for dairy cattle.

No abstract

Effects of increased protein and energy provided by an intensified milk replacer on the antigen-specific, cell-mediated immune response of the neonatal calf were examined. Calves were fed a standard (0.45 kg/day of a 20% crude protein, 20% fat milk replacer; n=11) or intensified (1.14 kg/day of a 28% crude protein, 20% fat milk replacer; n=11) diet from 0 to 6 weeks of age. All calves were vaccinated with Mycobacterium bovis bacillus Calmette-Guerin (BCG) at 1 week of age. The daily weight gain of intensified-diet calves (0.62 kg/day) was greater than the weight gain of standard-diet calves (0.29 kg/day). Liver, kidney, heart, thymus, and subcervical lymph nodes from intensified-diet calves were heavier than the same organs from standard-diet calves. Flow cytometric analysis of peripheral blood mononuclear cell (PBMC) populations indicated that CD4+ cells, gamma delta TCR+ cells, and monocyte percentages, although unaffected by diet during the first 5 weeks of the study, were higher in intensified-diet calves at week 6. The decline in gamma delta TCR+ cell percentages and increase in B cell percentages with increasing age seen in all calves are characteristic of the maturing immune system of the calf. CD8+ T cell or B cell percentages were not affected by diet. In intensified-diet calves, percentages of CD4+ expressing interleukin-2 receptor increased and percentages of gamma delta TCR+ cells expressing interleukin-2 receptor decreased with time. The same populations in standard-diet calves did not change with time. Percentages of CD4+ and CD8+ T cells, and B cells expressing MHC class II antigen, were unaffected by diet or age. Although mitogen-induced interferon (IFN)-gamma and nitric oxide (NO) secretion increased with age for all calves, PBMC from intensified-diet calves produced less IFN-gamma and more NO than did cells from standard-diet calves at week 6 of the study. Antigen-induced secretion of IFN-gamma and NO also increased with age but was unaffected by diet. Antigen-elicited delayed-type hypersensitivity was unaffected by diet, suggesting increased dietary protein and energy did not alter adaptive immunity in vivo. Overall, these results suggest that feeding calves a commercially available, intensified milk replacer affects minimally the composition and functional capacities of PBMC populations. Additional research is necessary to determine whether these subtle effects influence the calf's susceptibility to infectious disease.

Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Infection driven maternal immune activation (MIA) during pregnancy is a key environmental risk factor. However, little is known about how MIA during pregnancy could contribute to adult-onset schizophrenia. In this study, we investigated if maternal immune activation induces changes in methylation of genes linked to schizophrenia. We found that differentially expressed genes in schizophrenia brain were significantly enriched among MIA induced differentially methylated genes in the foetal brain in a cell-type-specific manner. Upregulated genes in layer V pyramidal neurons were enriched among hypomethylated genes at gestational day 9 (fold change = 1.57, FDR = 0.049) and gestational day 17 (fold change = 1.97, FDR = 0.0006). A linear regression analysis, which showed a decrease in gene expression with an increase in methylation in gestational day 17, supported findings from our enrichment analysis. Collectively, our results highlight a connection between MIA driven methylation changes during gestation and schizophrenia gene expression signatures in the adult brain. These findings carry important implications for early preventative strategies in schizophrenia.

No abstract