The impact of nutrition on lactation can be separated into acute effects, affecting day-to-day yield, and chronic effects, which govern the persistency of lactation and rate of decline of the lactation curve. A mathematical model of the mammary gland was constructed to investigate both acute and chronic effects. Mammary growth is expressed in terms of the dynamics of populations of active (secreting) and quiescent (engorged) alveoli. The secretion rate of active alveoli is expressed in terms of the energy status of the dam. The model was fitted to data from a 2 x 2 factorial trial in which lactation curves were measured for heifers of two different genotypes (North American and New Zealand Holstein-Friesians) fed two different diets [grass and total mixed rations (TMR)]. Total formation of alveoli during pregnancy and lactation was statistically the same across all groups despite differences between diets, in the rate of formation of alveoli at parturition. The senescence rate of alveoli was significantly higher for heifers fed grass compared with heifers fed TMR, which corresponds to better persistency for heifers fed TMR. Heifers fed TMR had a higher rate of reactivation of quiescent alveoli than heifers fed grass, which also contributes to increased persistence for heifers fed TMR. There was a genotype x diet interaction in the rate of quiescence of active alveoli: the North American-Grass group had a higher rate of quiescence than the other three groups, perhaps reflecting differences in selection pressures between the New Zealand and North American genotypes.

A mathematical model of biological mechanisms regulating lactation is constructed. In particular, the model allows prediction of the effect of milking frequency on milk yield and mammary regression, and the interaction of nutrition and milking frequency in determining yield. Possible interactions of nutrition with milking frequency on alveolar dynamics are highlighted. The model is based upon the association of prolonged engorgement (as a consequence of milk accumulation) of active secretory alveoli with changes in gene expression that result in impairment and, ultimately, cessation of milk secretion. The emptying of alveoli at milking, following alveolar contraction induced by oxytocin, prevents this process and also allows quiescent alveoli to reactivate. Prolonged engorgement results in apoptosis of the secretory cells and, hence, regression of the mammary gland. Milk yield is linked to alveolar populations, with secretion rates being modulated by nutrition and udder fill effects. The model was used to investigate different management scenarios, and is in agreement with experimental results. The model shows that while milking frequency drives alveolar population, and therefore potential milk production, actual production varies considerably with nutrition. A significant portion of the loss associated with once-daily milking was due to udder fill rather than loss of secretory tissue. The model showed qualitative agreement with experimental data, on the acute and chronic effects of temporary once-daily milking.

An historic and simple experiment has been revitalised through the availability of supercavity mirrors and also through a heightened interest in interferometry as a test of physical theory. We describe our helium-neon ring laser, and present results demonstrating a fractional frequency resolution of 2·1x10-18 (1·0 mHz in 474 THz). The rotation of the earth unlocks the counterrotating beams. A new field of spectroscopy becomes possible, with possible applications to geophysical measurements such as seismic events and earth tides, improved measurements of Fresnel drag, detection of ultraweak nonlinear optical propert~es of matter, and also searches for preferred frame effects in gravitation and for pseudoscalar particles.

In dairy cows, mammary gland involution, and thus a decline in milk production, occurs following peak lactation. To examine the cell signaling pathways regulating involution of the mammary gland, signal transducer and activator of transcription factors (STAT5 and 3), suppressors of cytokine signaling (SOCS1-3 and CIS), insulin-like growth factors (IGF1 and 2), and protein kinase B (Akt) were examined. Mammary involution was induced by termination of milking, and alveolar tissue was collected from 52 nonpregnant, primiparous, mid-lactation Holstein-Friesian cows killed at 0, 6, 12, 18, 24, 36, 72, and 192h postmilking. Qualitative immunohistochemistry showed that activated (phosphorylated) STAT5-P was localized in nuclei of mammary epithelial cells at the early time points, with detection levels decreasing by 24h postmilking. In contrast, STAT3-P was barely detectable at the early time points, with detection levels increasing following longer postmilking periods. This was supported by Western analysis, which showed a decline in STAT5 and STAT5-P protein levels by 24h postmilking, no change in STAT3 levels, and an increase in STAT3-P protein (barely detectable at the early time points) by 72h postmilking. Quantitative real-time reverse transcription PCR analysis showed SOCS1 and SOCS3 mRNA increased by 72h postmilking compared with 6h postmilking. The SOCS2 mRNA remained unchanged across the time series, whereas CIS decreased by 18h postmilking and remained lower compared with that at 6h postmilking until 72h postmilking. The IGF1 mRNA increased by 192h postmilking, whereas IGF2 mRNA decreased by 18h postmilking compared with 6h postmilking. The IGFBP5 mRNA and protein levels of Akt and Akt-P remained unchanged over the time series. These results show that reciprocal activation of STAT5 and STAT3 occurs at the onset of mammary gland involution in the bovine, albeit at a slower rate than in rodents. Mathematical modeling of the pathways indicated that activated STAT3 could block the STAT5 pathway by upregulating SOCS3. The regulation of IGF1-Akt signaling suggests that by 192h postmilking in dairy cows, the involution process is still in the reversible phase, with quiescent mammary epithelial cells not yet in the senescent phase.