Cabbage contains the glucosinolate sinigrin, which is hydrolyzed by myrosinase to allyl isothiocyanate. Isothiocyanates are thought to inhibit the development of cancer cells by a number of mechanisms. The effect of cooking cabbage on isothiocyanate production from glucosinolates during and after their ingestion was examined in human subjects. Each of 12 healthy human volunteers consumed three meals, at 48-h intervals, containing either raw cabbage, cooked cabbage, or mustard according to a cross-over design. At each meal, watercress juice, which is rich in phenethyl isothiocyanate, was also consumed to allow individual and temporal variation in postabsorptive isothiocyanate recovery to be measured. Volunteers recorded the time and volume of each urination for 24 h after each meal. Samples of each urination were analyzed for N-acetyl cysteine conjugates of isothiocyanates as a measure of entry of isothiocyanates into the peripheral circulation. Excretion of isothiocyanates was rapid and substantial after ingestion of mustard, a source of preformed allyl isothiocyanate. After raw cabbage consumption, allyl isothiocyanate was again rapidly excreted, although to a lesser extent than when mustard was consumed. On the cooked cabbage treatment, excretion of allyl isothiocyanate was considerably less than for raw cabbage, and the excretion was delayed. The results indicate that isothiocyanate production is more extensive after consumption of raw vegetables but that isothiocyanates still arise, albeit to a lesser degree, when cooked vegetables are consumed. The lag in excretion on the cooked cabbage treatment suggests that the colon microflora catalyze glucosinolate hydrolysis in this case.

FKBP-like (FKBPL) protein is a novel immunophilin-like protein that plays a role in the cellular stress response. Its three tetratricopeptide repeat motifs are homologous to the heat shock protein 90 interaction sites of other immunophilins that have roles in steroid hormone receptor signaling. In this study, using biomolecular complementation and coimmunoprecipitation techniques, we show that FKBPL also colocalizes and interacts with the components of the heat shock protein 90-glucocorticoid receptor (GR) complex and demonstrate that the PPIase domain of FKBPL is important for the interaction between this complex and the dynein motor protein, dynamitin. Treatment of DU145 cells with the GR ligand, dexamethasone, induced a rapid and coordinated translocation of both GR and FKBPL to the nucleus; this response was perturbed when FKBPL was knocked down with a targeted small interfering RNA. Furthermore, overexpression of FKBPL increased GR protein levels and transactivation of a luciferase reporter gene in response to dexamethasone in DU145 cells. However, these responses were cell line dependent. In summary, these data suggest that FKBPL can be classed as a new member of the FKBP protein family with a role in steroid receptor complexes and signaling.

The objective of this study was to determine the extent to which herbivores are able to use conditioned food aversions and preferences to learn about the nutritional and toxic properties of food plants, when food options are simultaneously available. Conditioned food aversions and preferences have been invoked as important mechanisms by which free-ranging herbivores optimize food selection by learning about the negative and positive consequences of consuming particular plant species through a series of encounters. In most previous tests of this hypothesis, access to individual test foods has been separated in time, giving animals the opportunity to associate particular foods with particular post-ingestive effects. We presented animals with a more complex scenario by offering test feeds simultaneously during the learning phase. Such a test is an important step in assessing the importance of conditioned food responses as mechanisms by which herbivores learn to select an optimal diet. We first assessed the ability of goats to learn about test foods and their post-ingestive effects, when different conifer species were offered on separate days during the learning phase and animals were dosed with compounds eliciting positive, negative, or neutral post-ingestive effects. We then investigated the ability of animals to learn to make appropriate choices when all potential test foods were simultaneously available during the learning phase. The results confirmed that goats can learn to associate particular foods with particular post-ingestive effects and adjust their diet selection accordingly. The success with which animals made such associations was greatly reduced when they were presented with test foods simultaneously during the learning phase. When test foods were simultaneously available, animals tended to select a mixed diet, thereby reducing their opportunity to learn about the post-ingestive effects of particular foods. The results suggest that caution is required in extrapolating results of artificial conditioning experiments to free-ranging herbivores. The results also suggest that reducing the risk of toxicity through selection of mixed diets is an important component of a successful foraging strategy.

The potential use of faecal n-alkanes for estimation of intake and diet composition over periods of 1-2 days was assessed in two experiments. The aim was to determine the accuracy with which intake and diet composition could be estimated by characterizing faecal excretion of n-alkanes following a discrete dose as opposed to steady state kinetics used in previous work.In the first experiment, 16 sheep were fed mixtures of spinach (rich in C $" -alkane) and cabbage (rich in C #* -alkane) in known proportions and amounts for two days. Artificial n-alkanes (C #) -and C $# alkane) were dosed on four occasions during this time. Total intakes were controlled at 0n2, 0n3, 0n4 or 0n5 kg dry matter (DM) per day and nominal amounts of spinach offered (as a proportion of the total diet) were 0n00, 0n15, 0n30 and 0n45. Each sheep received a unique combination of intake and dietary proportions (four intake ratesifour proportions). Sheep were fed fresh grass (timothy, Phleum pratense) before and after feeding spinach and cabbage. Sequential rectal grab samples of faeces were collected at regular intervals and total faecal collections were carried out over 144 h from the start of the spinach\cabbage feeding period to obtain samples for n-alkane analysis. In the second experiment, fresh grass was sprayed with two combinations of artificial n-alkanes (C #% -and C $# -or C #) -and C $' -alkane) and fed to 16 sheep over a 24 h period. Each sheep received one of four intake rates (0n8, 1n0, 1n2 or 1n4 kg DM\day) and, within intake rates, each sheep received one of four different proportions of the herbage sprayed with the combinations of n-alkanes (0n2, 0n4, 0n6 or 0n8), in a similar fashion to the first experiment. In order to estimate intake, C #' -and C $% -alkanes were dosed at the start of the feeding period. Faecal sampling procedures were the same as those in the first experiment.Different parameters of faecal excretion curves of dosed and natural n-alkanes were used to estimate dietary proportions and intake. Parameters tested included area under the excretion curve and curve maximum. Dietary proportions were calculated using an iterative minimization procedure employing faecal and herbage n-alkane concentrations. Intakes were estimated using ratios of dosed : natural faecal n-alkanes.The best estimates of dietary proportions were obtained using faecal concentrations at a single point in time in both experiments ( 80 % variation explained for regressions of estimated v. actual proportions). Intake estimates required the calculation of the area under the excretion curve to obtain acceptable estimates (70-90 % variance explained for regressions of estimated v. actual intakes in Expt 2). The experiments demonstrate that precise estimates of diet composition can be obtained using single faecal samples following consumption of simple herbage mixtures over 24-48 h. Intake may also be estimated using this technique provided that a series of faecal samples are collected over 4-5 days following the period of ingestion.

Oxalic acid is found in high concentrations in some plants consumed by ruminants and may cause renal toxicity. To determine whether exposure to oxalic acid affects the capacity of the rumen of sheep and goats to degrade the compound, 20 animals (10 sheep and 10 goats) were dosed with free oxalic acid by gelatin capsule twice daily for 3 weeks at one of five levels (0·0, 0·3, 0·6, 0·9 and 1·2 mmol/kg live weight (M) per day). Rumen samples were collected by stomach tube in the week prior to the start of dosing and in each week of the 3-week experiment. Oxalic acid degradation capacity was measured by adding uC-labelled oxalic acid to rumen fluid in vitro and capturing evolved 14CO2. Rates of degradation increased with increasing level of administration (2·30, 4·71, 6·74, 9·83 and 13·90 mmol of oxalic acid degraded per I rumen fluid per day for doses 0·0, 0·3, 0·6, 0·9 and 1·2 mmol/kg M per day, respectively; P < 0·001). Rates of degradation increased during the dosing period (P < 0·001) with the largest increases occurring in the 1st week of dosing. Goats showed a greater response than sheep, with a higher mean oxalic acid degradation capacity (9·04 v. 5·95 mmol of oxalic acid degraded per I rumen fluid, P < 0·05). Oxalic acid administration did not influence plasma calcium concentration or cause renal function impairment as measured by plasma creatinine concentrations. The experiment demonstrated adaptation in the rumen to potential toxins in the host diet and suggests that the rumen micro-organisms of goats may have been more adapted to degrading oxalic acid than sheep.