Fibroblast growth factor-21 (FGF21) administration to early-lactating dairy cows. I. Effects on signaling and indices of insulin action.

Modern dairy cows rely on hormonally driven mechanisms to coordinate the metabolic adaptations needed to meet the energy and nutrient deficits of early lactation. In the case of glucose, dairy cows cope with its scarcity during early lactation via reduced plasma concentrations of insulin and the insulin sensitizing hormone adiponectin and increased insulin resistance. Reduced insulin action promotes diversion of available glucose to the mammary gland but increases susceptibility to diseases if excessive. In earlier work, we reported that the insulin sensitizing hormone fibroblast growth factor-21 (FGF21) is increased in periparturient dairy cows and identified liver and adipose tissue as possible targets. These observations raised the possibility that FGF21 acts directly on these tissues to limit the insulin resistance of early lactation. To test this hypothesis, dairy cows were randomly assigned on d 12.6 ± 2.2 (± standard error) of lactation to receive either excipient (n = 6) or recombinant human FGF21 (n = 7), first as an FGF21 bolus of 3 mg/kg of body weight, followed 2 d later by a constant i.v. infusion of FGF21 at the rate of 6.3 mg/kg of metabolic body weight for 9 consecutive days. Biopsies of liver and adipose tissue were collected during the bolus phase of the experiment and used to analyze FGF21 signaling by Western blotting and expression of its receptor components by quantitative PCR. Bolus FGF21 administration caused a 4-fold increase in p44/42 MAPK (ERK1/2) activation in adipose tissue but had no effect on AKT and signal transducer and activator of transcription-3 (STAT3) signaling. The liver expressed negligible levels of the preferred FGF21 receptor FGFR1c and failed to mount any FGF21 signaling response. The FGF21 administered as a bolus had no effect on plasma glucose or insulin and did not stimulate an acute release of adiponectin from adipose tissue. Similarly, FGF21 infusion had no effect on plasma levels of glucose or insulin measured over the 9-d infusion or on glucose disposal during an i.v. glucose tolerance test performed on d 8 of infusion. Finally, the chronic FGF21 infusion had no effect on indices of adiponectin production, including plasma adiponectin and adipose tissue mRNA abundance of adiponectin and the endoplasmic reticulum chaperones ERO1A and DSBA-L involved in the assembly of adiponectin into multimeric complexes. These data show that human FGF21 does not act as an insulin sensitizer during the energy and glucose deficit of early lactation but do not rule out such a role in other physiological states.

Fagerstrom's Tolerance Questionnaire: clarification of item and scoring ambiguities.

Fagerstrom's Tolerance Questionnaire has often been used as a measure of physical dependence on nicotine. Inadequate delineation of scoring criteria has made reliability of scoring across users questionable. Standardized cutoffs and the correct translation of one item are presented with recommendations for future use.

Heritability and repeatability of Hereford show-ring placing and associated correlations with individual performance measurements and expected progeny differences.

Data associated with 1,531 Herefords shown at the National Western Stock Show at Denver from 1978 to 1984 were used to estimate heritability and repeatability of show-ring placing (SRP) and genetic, environmental and phenotypic correlations. The correlations were those between: SRP and individual measurements (IM) taken at the time of show and available to the judges, SRP and parents' SRP and IM, male SRP and their individual expected progeny difference values (EPD) and SRP and sire EPD. The IM were height, weight, backfat, weight per day of age and scrotal circumference. The estimation procedures were symmetric differences squared, analysis of variance and parent-offspring regression and correlation. Three similar estimates of SRP heritability averaged .39. Three similar estimates of SRP repeatability averaged .33 and suggested little effective selection for SRP based on first record and low permanent environmental variance. The phenotypic correlations indicated an individual's height (.63) had the most influence on its SRP followed by weight (.43). Genetic and environmental correlations between height and SRP averaged (three estimates) .78 and .37, respectively. Dam SRP, height and backfat had higher correlations with offspring SRP than those of the sire. Male SRP was moderately correlated with EPD values for weaning (.25) and yearling (.38) height and weaning (.33) and yearling (.32) weight. The correlations between SRP and sire EPD values were: .27 (birth weight), .16 (weaning weight), .33 (weaning height), .10 (yearling weight), .23 (yearling height) and .07 (maternal breeding value). The results did not support SRP as a criterion for improving growth performance traits.(ABSTRACT TRUNCATED AT 250 WORDS)

Purification and further characterization of phenol extract from Listeria monocytogenes.

A phenol-water extract of Listeria monocytogenes virulent strains 9-125 (serotype 4b) was purified by 3 cycles of ultracentrifugation. The purified extract reacted positively in Limulus amoebocyte lysate assay at a concentration of 1 microgram/ml. This value was 1,000 times higher than that for Salmonella abortus equi lipopolysaccharide. The phenol extract was toxic to chicken embryos (median lethal dose was 40.5 micrograms) and contained carbohydrates (heptose, hexose, hexosamine, methylpentose, 2-keto-3-deoxyoctanate, dideoxyhexose), lipid, 16 amino acids in the protein moiety, glucosamine, galactosamine, phosphorus, and ribonucleic acid.

Social punishment in the modification of a pre-school child's "autistic-like" behavior with a mother as therapist.

The mother of a 3-yr-old girl who showed "autistic-like" behavior was cued via an FM wireless microphone systematically to approve and disapprove of her child's behavior. After baselines were taken on two categories of problem behavior (Pre-Academic and Social Behavior), the social contingencies were applied successively to each category. The Pre-Academic task was quickly established in the child when the mother applied these social contingencies. This result was replicated with requests for social interaction. In the final phase, cueing was withdrawn from both situations and the mother was able to maintain the child's improved behavior. An analysis of the mother's behavior suggested that her increased use of social punishment for inappropriate behavior was the key factor in the child's increasing responsiveness. Follow-up seven months later indicated that the improvements maintained.