Effect of selected feed additives to improve growth and health of dairy calves.

The aim was to evaluate the effect of different feed additives on intake, performance, and fecal consistency index (FCI) of dairy calves from 6-60 d of age and its residual effect 15 d after weaning. Fifty Holstein calves (38 ± 1.0 kg BW) were fed 5 L/d of milk plus starter feed until weaning, and corn silage and concentrate after weaning. The treatments were: control (CON), monensin (MON; 30 mg/kg of starter), probiotic E. faecium (PROB; 70 mg/kg of starter), essential oils (EO; 300 mg/kg of starter), or PROB + EO (EOPROB). Fecal score and dry matter intake (DMI) were measured daily, and animals were weighed every 15 d. A DNA extraction from feces was performed to identify the presence of microorganisms (E. coli, Hafnia, Shiguella, Lactobacillus spp, Enterococcus spp, and Enterococcus faecium NCIMB 10415) by PCR. Two 72-h digestibility trials were performed at days 20-28 and 50-56, by total fecal collection. The DMI before weaning was greater for EO (903.0 g/d) compared with MON (794.3 g/d) and EOPROB (783.1 g/d). The FCI decreased during pre-weaning for EO and MON. Average daily gain (ADG) and feed efficiency (FE) did not differ among treatments before weaning. After weaning, DMI and FCI did not differ among treatments. The EO had greater ADG (917.5 g/d) compared with CON (615.8 g/d) and PROB (592.6 g/d). The FE improved with EO (0.72 g/g) over CON (0.36 g/g), MON (0.49 g/g), and PROB (0.36 g/g). The PCR results showed absence of E. faecium NCIMB 10415 in animals fed PROB and CON. Animals fed PROB had greater intake of CP and NDF than animals fed EOPROB. The EO can be added to the dairy calf ration to improve fecal score and increase DMI. The pre-weaning FCI decrease with MON and increase with PROB

Admixture Mapping in Lupus Identifies Multiple Functional Variants within IFIH1 Associated with Apoptosis, Inflammation, and Autoantibody Production

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease with a strong genetic component. African-Americans (AA) are at increased risk of SLE, but the genetic basis of this risk is largely unknown. To identify causal variants in SLE loci in AA, we performed admixture mapping followed by fine mapping in AA and European-Americans (EA). Through genome-wide admixture mapping in AA, we identified a strong SLE susceptibility locus at 2q22-24 (LOD=6.28), and the admixture signal is associated with the European ancestry (ancestry risk ratio ~1.5). Large-scale genotypic analysis on 19,726 individuals of African and European ancestry revealed three independently associated variants in the IFIH1 gene: an intronic variant, rs13023380 [P(meta) = 5.20×10(-14); odds ratio, 95% confidence interval = 0.82 (0.78-0.87)], and two missense variants, rs1990760 (Ala946Thr) [P(meta) = 3.08×10(-7); 0.88 (0.84-0.93)] and rs10930046 (Arg460His) [P(dom) = 1.16×10(-8); 0.70 (0.62-0.79)]. Both missense variants produced dramatic phenotypic changes in apoptosis and inflammation-related gene expression. We experimentally validated function of the intronic SNP by DNA electrophoresis, protein identification, and in vitro protein binding assays. DNA carrying the intronic risk allele rs13023380 showed reduced binding efficiency to a cellular protein complex including nucleolin and lupus autoantigen Ku70/80, and showed reduced transcriptional activity in vivo. Thus, in SLE patients, genetic susceptibility could create a biochemical imbalance that dysregulates nucleolin, Ku70/80, or other nucleic acid regulatory proteins. This could promote antibody hypermutation and auto-antibody generation, further destabilizing the cellular network. Together with molecular modeling, our results establish a distinct role for IFIH1 in apoptosis, inflammation, and autoantibody production, and explain the molecular basis of these three risk alleles for SLE pathogenesis