PubMed Health⌕ Search

Biomedical subjects

J France

Publications and source records attributed to J France.

At least 19 recordsLinked to original sources

Modelling mammary metabolism in the dairy cow to predict milk constituent yield, with emphasis on amino acid metabolism and milk protein production: model evaluation.

A model of mammary metabolism has been constructed and parameterized, with milk protein synthesis represented as a function of five essential amino acids (EAA) (Hanigan et al., 2001). Herein the model is evaluated using both the data used to construct the model (reference data) and an independent data set (literature data), and sensitivity to inputs and parameter estimates is assessed. The model predicted metabolite removal well for the reference data with exceptions for glutamate, glucose, and acetate. However, predictions of milk protein synthesis exhibited significant mean positive bias, which apparently was associated with the representation of milk protein synthesis. Adjustment of model parameters removed the mean bias, however, prediction accuracy was still inadequate. Simulation of the single reference experiment containing all critical inputs resulted in predictions of milk protein output that explained 53% of the observed variation, suggesting that the limited accuracy of the model when applied to the entire reference data set was due to assumptions regarding missing inputs. Mammary removal of glutamate, isoleucine, lysine, phenylalanine, tyrosine, valine, glycerol, beta -hydroxybutyrate (BHBA), and acetate were predicted less accurately when simulations of the independent data set were conducted. Twenty-five percent of the observed variation in milk protein yields for the independent data set was explained by the model. Refitting parameters for removal of isoleucine, lysine, phenylalanine, tyrosine, valine, glycerol, BHBA, and acetate raised the variation explained to 43%. Sensitivity analysis indicated that milk protein synthesis was responsive to only the five EAA used in its determination, with sensitivity to any single EAA falling to zero as supply of the EAA exceeded protein synthetic needs. Similarly, milk protein synthesis was readily affected by parameters associated with removal and metabolism of the five EAA. Milk lactose was found to be sensitive to glucose input as well as to similar parameters and inputs as milk protein. It is concluded that representation of the milk protein synthesis process as a function of a single limiting EAA may not be adequate and might be better represented by simultaneous consideration of multiple EAA. Additional work on the description of energy metabolism is also suggested.

Amino Acids↗

A dynamic model of N metabolism in the lactating dairy cow and an assessment of impact of N excretion on the environment.

Improving N utilization in dairy cows and especially reducing N output in excreta is desirable due to global concerns of agricultural contribution of N to environmental pollution, particularly as ammonia. Data from five N balance experiments were used to develop a dynamic model that was evaluated with independent data. Model predictions of feces, urine, and milk outputs were close to observed values. Statistical analysis showed that 96% of mean square prediction error for feces and urine N output predictions was due to random variation. However, the model tends to overpredict milk N output, especially at higher N intake levels. Evaluation of model predictions for independent experimental observations from Agricultural Development Advisory Service at Bridgets (U.K.) showed good agreement between predicted and observed urine N output (95% due to random variation). However, there was a slight underprediction for fecal N output (14% mean square prediction error due to bias) and overprediction of milk N output (22% of mean square prediction error due to bias). The model predictions of N outputs in excreta were sensitive to changes in energy concentration of the diet. Dietary protein degradability had only a small influence on predicted fecal N output. However, the model was sensitive in its predictions of urine N when protein degradability was varied. Application of the model to assess reduction in ammonia emissions from dairy cows showed that increasing the energy concentration could potentially reduce ammonia emissions by up to 25% per cow. Similarly, reducing CP concentration in the diet to about 16% could reduce ammonia production by 20% and lower degradability of CP to match microbial requirement by 19% per cow. The model is a first step toward a mechanistic approach of nutrient modeling, and it is a valuable method for predicting N excretions and estimating N emissions from dairy systems.

Ammonia↗

Modelling mammary metabolism in the dairy cow to predict milk constituent yield, with emphasis on amino acid metabolism and milk protein production: model construction.

Previous efforts to simulate mammary metabolism have focused on energy, mostly considering amino acids (AA) in aggregate. The main objective of this work was to build a model of mammary metabolism, based on data from arterio-venous difference studies, which considered AA in sufficient detail to predict yields of milk solids. The model contains 19 state variables and considers the removal of 37 metabolites from blood, including 22 AA. It is driven by blood flow and arterial concentrations, and outputs include milk protein, milk lactose, and three classes of milk fat (by chain length). The model was parameterized using a balance version of it and the mean observations from four arterio-venous difference experiments, with a limited number of assumptions, and evaluated against these experiments. In assembling the balance model, milk protein output was not predicted satisfactorily, as some essential AA were not present in quantities great enough to support the rates of milk protein synthesis observed experimentally. Tryptophan showed the greatest deficit, followed by tyrosine plus phenylalanine, methionine, and histidine. In addition, significant quantities of pyruvate were needed to synthesize serine, glycine, and alanine. The supply of alpha-ketoglutarate plus glutamate to synthesize proline and glutamine was provided in part by catabolism of arginine; the remainder was derived from catabolism of other AA and energetic substrates.

Algorithms↗

Systemic deficits in transporter for antigen presentation (TAP)-1 or proteasome subunit LMP2 have little or no effect on tumor incidence.

Some tumor cells have deficits in class I MHC antigen processing, suggesting that T cells exert selective pressure on tumor cells. Previous studies have not revealed increased tumor incidence in mice with deficits in T-cell immunity, including mice lacking TAP1 (a subunit of the transporter for antigen presentation) or LMP2 (a regulated subunit of the 20S proteasome). The incidence of spontaneous tumors in these mice, however, is too low to assess differences in host resistance to tumors. To increase tumor incidence and better assess the role of systemic expression of TAP1 and LMP2 in responses to tumors, TAP1-/- and LMP2-/- mice were bred with p53-/- mice to create TAP1-/-p53-/- and LMP2-/-p53-/- double knockout mice. Lymphomas and sarcomas (malignant fibrous histiocytoma and angiosarcoma) occurred with high incidence in all p53-deficient populations. Tumor incidence and death rate were similar in TAP1-/-p53-/- mice and closely matched control TAP1+/+p53-/- mice. Tumor incidence and death rate were slightly accelerated in LMP2-/-p53-/- mice relative to control LMP2+/+p53-/- mice, but the biological significance of this difference was unclear. The relative incidence of lymphomas vs. sarcomas was not significantly altered by variation in TAP1 or LMP2. In conclusion, systemic absence of TAP1 did not alter tumor incidence, while absence of LMP2 was associated with only a slight acceleration of tumor incidence of uncertain significance. These observations are consistent with other evidence that normal T-cell responses do not effectively limit tumorigenesis. Even though T cells can attack some tumor cells, the ability of tumors to alter their immunogenicity and evade T-cell surveillance may render the native immune system ineffective at providing a rate-limiting barrier to tumorigenesis and preventing cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Evaluating sugarcane diets for dairy cows using a digestion model.

To eliminate unnecessary feeding trials, a mechanistic model of sugarcane digestion was used in the search for suitable supplements to improve milk production. Milk production simulated by the model was compared with data observed in four feeding trials published in the tropical literature where crossbred dairy cows were fed sugarcane/urea diets with different types of supplements. The predicted effects of the supplements on the ruminal microbial population, concentrations of ammonia and volatile fatty acids were also compared with the published results in one experiment. The model indicated the nutrient most limiting milk production for the different feeding situations. The addtion of Leucaena to the basal sugarcane/urea improved the availability of amino acids and long-chain fatty acids, with energy becoming the limiting factor. Supplementation with rice bran increased the availability of energy and long-chain fatty acids, but amino acids then became the limiting factor. Supplementation with both Leucaena and rice bran further improved the milk yield, but availability of energy now limited milk production. Supplementation with Leucaena increased milk production more than supplementation with king grass. The main reason for this increase was increased amino acid absorption due to increased microbial outflow. In all feeding situations, the average difference between the predicted milk production and that observed experimentally was 0.57 kg/d (ranging from 0.08 to 1 kg/d).

Animal Feed↗

The effect of energy supplementation on nitrogen utilization in lactating dairy cows fed grass silage diets.

An experiment was conducted to examine the effect that various isoenergetic diets, containing different quantities of soluble carbohydrate and fiber and different types of starch, have on nitrogen (N) balances. Six lactating dairy cows in early to midlactation consuming grass silage diets with not less than 600 g/kg total DMI as forage were used in the experiment. Four concentrates were prepared that had higher amounts of either fiber, soluble sugars, corn (low degradable starch source), or barley (high degradable starch source). Overall N utilization by the cows was poor, rarely exceeding 0.30 g milk N/g of dietary N intake. Fecal N outputs accounted for more than half of total N excreted in all treatments except for diets supplemented with high degradable starch, in which urinary N excretion was significantly higher compared with the other treatments. Milk yield was unaffected by concentrate type, averaging 19.9 kg/d, but milk protein content decreased from 32.9 for starch-based diets to 30.9 and 30.0 g/kg for the soluble sugar- and fiber-based diets, respectively. The efficiency of N utilization improved in the low degradable starch treatment, which had lower N excretion (65%) and higher protein concentration in milk. Furthermore, feeding cows corn-based concentrates reduced urinary N excretion by almost 30% compared with barley-based concentrates; therefore, feeding corn-based diets is recommended for the reduction of nitrogen pollution in lactating dairy cows.

Animal Feed↗

The effect of protein supplementation on nitrogen utilization in lactating dairy cows fed grass silage diets.

The study set out to examine the effects of supplementing grass silage with various levels of protein concentration and degradability on dietary nitrogen (N) excretion in lactating dairy cows consuming at least 60% forage. Six Holstein/Friesian cows in early to midlactation were offered six diets comprising two levels of crude protein (210 and 290 g/kg DM) and three levels of protein degradability in the concentrate achieved using different amounts of untreated or formaldehyde-treated soybean meal. Despite a difference of almost 100 g/d in N intake, apparent fecal and milk N outputs were not significantly affected. Protein degradability also had no effect on N outputs in feces and milk. However, there was a major effect of both level and degradability of CP on urinary N output. Moreover, an interaction between level and degradability of CP was detected, such that the rate at which urinary N increases with increasing CP degradability was higher on the high-CP than on the low-CP diet. A low level of protein (150 g/kg DM in the diet) and medium to low rumen-degradable protein supplements provided a significant reduction in N excretion without compromising lactational performance (mean 24.8 kg/d), in terms of both milk yield and composition. This study also demonstrated that a high efficiency of N utilization could be achieved on low-CP diets (supplying less than 400 g N/d), with feces being the main route of N excretion, whereas an exponential excretion of urinary N was observed as N intake exceeded 400 g N/d.

Animal Feed↗

The effect of season and monensin sodium on the digestive characteristics of autumn and spring pasture fed to sheep.

The effects of season of growth and monensin treatment on ruminal digestion of fresh-cut autumn and spring pasture were measured in a single group of ruminally fistulated castrated male sheep, housed indoors in metabolism crates. Responses were assessed in terms of ruminal volatile fatty acid molar proportions, ammonia concentration, pH, apparent digestibility of the pasture, and nitrogen balance of the animals. Blood plasma concentrations of insulin, glucose, beta-hydroxybutyrate, urea, and NEFA were also evaluated. Autumn pasture contained significantly lower proportions of water-soluble carbohydrate (P < 0.05), cellulose (P < 0.05), and lignin (P < 0.05) and increased pectin (P < 0.05), hemicellulose (P < 0.05), and crude protein (P < 0.10) concentrations when compared with spring pasture. Voluntary DMI by sheep of autumn pasture was lower (P < 0.01) than that of spring pasture and was significantly (P < 0.05) reduced by monensin treatment. Monensin treatment significantly decreased the ruminal molar proportions of acetic acid (P < 0.10) and butyric acid (P < 0.001) and increased the molar proportions of propionic acid (P < 0.001) and minor VFA (P < 0.01). Nitrogen retention of the sheep was significantly (P < 0.05) reduced by monensin treatment. Plasma glucose levels were increased (P < 0.10) by monensin treatment during the fourth 5-d collection period in both seasons. Chemical analysis suggested that the composition of autumn pasture was different from that of spring pasture and that this was manifested in vivo by increased DMI and digestibility of spring vs autumn pasture. Ruminal fermentation of autumn pasture also had an increased acetate-to-propionate ratio compared with spring pasture. Monensin treatment acted consistently across seasons by increasing the proportion of propionate and decreasing the proportion of acetate in ruminal fluid.

Acetates↗

A mechanistic model of whole-tract digestion and methanogenesis in the lactating dairy cow: model development, evaluation, and application.

Dietary intervention to reduce methane emissions from lactating dairy cattle is both environmentally and nutritionally desirable due to the importance of methane as a causative agent in global warming and as a significant loss of feed energy. Reliable prediction systems for methane production over a range of dietary inputs could be used to develop novel dietary regimes for the limitation of feed energy loss to methane. This investigation builds on previous attempts at modeling methanogenesis and involves the development of a dynamic mechanistic model of wholerumen function. The model incorporates modifications to certain ruminal fermentation parameters and the addition of a postruminal digestive element. Regression analysis showed good agreement between observed and predicted results for experimental data taken from the literature (r2 = 0.76, root mean square prediction error = 15.4%). Evaluation of model predictions for experimental observations from five calorimetry studies (67 observations) with lactating dairy cows at the Centre for Dairy Research, in Reading, U.K., shows an underprediction (2.1 MJ/d) of methane production (r2 = 0.46, root mean square prediction error = 12.4%). Application of the model to develop diets for minimizing methanogenesis indicated a need to limit the ratio of lipogenic to glucogenic VFA in the rumen and hindgut. This may be achieved by replacing soluble sugars in the concentrate with starch or substituting corn silage for grass silage. On a herd basis, the model predicted that increasing dietary energy intake per cow can minimize the annual loss of feed energy through methane production. The mechanistic model is a valuable tool for predicting methane emissions from dairy cows.

Animal Feed↗

Estimating the extent of degradation of ruminant feeds from a description of their gas production profiles observed in vitro: comparison of models.

An evaluation of general models that describe gas production profiles is presented. The models are derived from first principles by considering a simple three-pool scheme and permit the extent of ruminal degradation to be calculated, as described in the companion paper. The models evaluated were the generalized Mitscherlich, simple Mitscherlich, generalized Michaelis-Menten, simple Michaelis-Menten, Gompertz, and logistic. Five sets of gas production data consisting of 216 curves, obtained using a wide range of feeds (including straw, hay, silage, grain and various byproducts), were analysed to study the performance of these gas production models. Application of the non-sigmoidal models (simple Mitscherlich and Michaelis-Menten) to the data resulted in convergence problems and these models were found to be inadequate in many cases. Based on results of a pairwise comparison between models (variance ratio test), ranking of residual mean squares, lack-of-fit test, and of analyses of residuals, the generalized Mitscherlich and the generalized Michaelis-Menten models seemed particularly suited because of their flexibility to encompass sigmoidal and non-sigmoidal shapes of gas production profiles, whether symmetrical or not.

Animal Feed↗

Estimating the extent of degradation of ruminant feeds from a description of their gas production profiles observed in vitro: derivation of models and other mathematical considerations.

Equations to describe gas production profiles, obtained using manual or automated systems for in vitro fermentation of ruminant feeds, were derived from first principles by considering a simple three-pool scheme. The pools represented were the potentially degradable and undegradable feed fractions, and accumulated gases. The equations derived and investigated mathematically were the generalized Mitscherlich, generalized Michaelis-Menten, Gompertz, and logistic. They were obtained by allowing the fractional rate of degradation to vary with time. The equations permit the extent of ruminal degradation (hence the supply of microbial protein to the duodenum) to be evaluated, thus linking the gas production technique to animal production.

Animal Feed↗

A rodent model of protein turnover used to design an experiment for measuring the rates of channeling, recycling and protein synthesis.

We described previously a mechanistic model of whole-body protein turnover in rodents. Channeling was defined as the flow of amino acids from the extracellular compartment to aminoacyl tRNA and protein synthesis. Recycling was defined as the flow of amino acids from protein degradation to aminoacyl tRNA (protein synthesis) without mixing with the intracellular pool of amino acids. In this paper, the model is applied to tissues and whole body and is used to develop an experimental protocol for estimating protein fractional synthesis rate, recycling and channeling. Channeling, recycling and protein synthesis must be estimated simultaneously because changes in specific radioactivities over time are highly dependent on the rate of protein synthesis. Injection-specific radioactivities, body weights and experimental variation were used with the model to generate data at different rates of recycling and channeling. The data generated were then used to determine the best time points and experimental method to estimate percentages of recycling, channeling and protein synthesis rate by the iterative Method of Maximum Likelihood. Specific radioactivity at each time point was based on simulated data from three rodents at each of six time points. Predicted protein synthesis rates were within 5%/d of observed rates for all methods. Predicted rates of recycling and channeling were generally within 15% of observed rates except recycling in muscle at high channeling and high recycling. Standard deviations of the predictions of percentages of channeling and recycling were between 0.148 and 44.5% for the pulse dose method, 0.0655 and 197% for the continuous infusion method and 0.351 and 962% for the flooding dose method. The experimental design that yields the best estimates of channeling, recycling and protein synthesis is the pulse dose. Changes in amino acid specific radioactivities in the extracellular, aminoacyl tRNA and protein pools were greatest and should be measured at 2, 6, 10, 40, 70 and 100 min in the pulse method.

Amino Acids↗

A kinetic model of phosphorus metabolism in growing goats.

The effect of increasing phosphorus (P) intake on P utilization was investigated in balance experiments using 12 Saanen goats, 4 to 5 mo of age and weighing 20 to 30 kg. The goats were given similar diets with various concentrations of P, and 32P was injected to trace the movement of P in the body. A P metabolism model with four pools was developed to compute P exchanges in the system. The results showed that P absorption, bone resorption, and excretion of urinary P and endogenous and fecal P all play a part in the homeostatic control of P. Endogenous fecal output was positively correlated to P intake (P < .01). Bone resorption of P was not influenced by intake of P, and P recycling from tissues to the blood pool was lesser for low P intake. Endogenous P loss occurred even in animals fed an inadequate P diet, resulting in a negative P balance. The extrapolated minimum endogenous loss in feces was .067 g of P/d. The minimum P intake for maintenance in Saanen goats was calculated to be .61 g of P/d or .055 g of P/(kg(.75) x d) at 25 kg BW. Model outputs indicate greater P flow from the blood pool to the gut and vice versa as P intake increased. Intake of P did not significantly affect P flow from bone and soft tissue to blood. The kinetic model and regressions could be used to estimate P requirement and the fate of P in goats and could also be extrapolated to both sheep and cattle.

Animal Nutritional Physiological Phenomena↗

A generalized Michaelis-Menten equation for the analysis of growth.

The functional form W = (W0Kc + Wf t(c)) /(Kc + t(c)), where W is body size at age t, W0 and Wf are the zero- and infinite-time values of W, respectively, and K and c are constants, is derived. This new generalized Michaelis-Menten-type equation provides a flexible model for animal growth capable of describing sigmoidal and diminishing returns behavior. The parameters of the nonlinear model are open to biological interpretation and can be used to calculate reliable estimates of growth traits, such as maximum or average postnatal growth rates. To evaluate the new model, the derived equation and standard growth functions such as the Gompertz and Richards were used to fit 83 growth data sets of different animal species (fish, mice, hamsters, rats, guinea pigs, rabbits, cats, dogs, broilers, turkeys, sheep, goats, pigs, horses, and cattle) with a large range in body size. A comparative study was carried out based on mathematical, statistical, and biological characteristics of the models. The statistical goodness-of-fit achieved with the new model was similar to that of Richards, and both were slightly superior to the Gompertz. The new model differed from the others with respect to some of the estimated growth traits, but there were highly significant correlation coefficients between estimates obtained with the different models, and the ranking of animals based on growth parameters computed with the new function agreed with the rankings computed by the other models. Therefore, the new model, with its variable inflection point, was able to adequately describe growth in a wide variety of animals, to fit a range of data showing sigmoidal growth patterns, and to provide satisfactory estimates of traits for quantifying the growth characteristics of each type of animal.

Animals↗

Effects of management practices prior to and during ensiling and concentrate type on nitrogen utilization in dairy cows.

Three experiments with a total of 18 multiparous Holstein-Friesian dairy cows in early to mid lactation were used in incomplete changeover designs with four periods consisting of 4 wk each. The objectives of the experiments were to investigate the effects of 1) grass management practices prior to ensiling and 2) concentrate energy sources on animal performance and N utilization and suggest ways in which the annual N excretion can be reduced. In the first experiment, four silages were prepared as early-cut material from grass that was fertilized with either 75 or 150 kg of N/ha. Two other silages were prepared from the latter but harvested 2 wk later. Within each silage type, both direct cut and wilted silages were produced. In the second experiment, starch-based and fiber-based concentrates were offered with the three wilted silages used in the previous experiment. In the third experiment, barley-based and corn-based concentrates were offered with three silages that had been treated with different additives at the time of ensiling. Neither dry matter intake nor milk yield were significantly affected by either silage or concentrate type. Milk protein content and yield, however, were higher in silages made from medium fertilized grass and also increased with increased starch content of the concentrate. Grass management and diet affected the amount and form of N excreted. Use of nitrogen fertilizer at lower than 75 kg of N/ha and feeding less degradable starch concentrate is recommended for mitigation of N pollution, especially in the form of urine N by dairy cows in intensive farming.

Animals↗

An isotope dilution model for partitioning leucine uptake by the liver of the lactating dairy cow.

An isotope dilution model for partitioning leucine uptake by the liver of the lactating dairy cow is constructed and solved in the steady state. If assumptions ae made, model solution permits calculation of the rate of leucine uptake from portal and hepatic arterial blood supply, leucine export into the hepatic vein, leucine oxidation and transamination, and synthesis and degradation of hepatic constitutive and export proteins. The model requires the measurement of plasma flow rate through the liver in combination with leucine concentrations and plateau isotopic enrichments in arterial, portal and hepatic plasma during a constant infusion of [1-13C]leucine tracer. The model can be applied to other amino acids with similar metabolic fates and will provide a means for assessing the impact of hepatic metabolism on amino acid availability to peripheral tissues. This is of particular importance when considering the dairy cow and the requirements of the mammary gland for milk protein synthesis.

Animals↗