Progress 10/01/09 to 09/30/14
Outputs
Target Audience: Scientists, farm advisors, farm consultants, and producers. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided? These data will be used to update energetic feeding models for bot ruminants and non-ruminants. How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals? We have established a new project CA-D-ASC-2263-AH, (Analyses of the theoretical estimates of the efficiency of protein and energy metabolism) to continue the modeling portion of this research effort.
Impacts
What was accomplished under these goals?
Theoretical estimates of the efficiencies of metabolic and physiological processes impact of the numerical values associated with energy metabolism. In an effort to improve the accuracy of the estimates, new understandings have been applied to various biochemical pathways in ruminants and non-ruminants. Advances in understanding mammalian ATP synthase, membrane transport, electron transport, and oxidative phosphorylation have improved the accuracy of the estimated theoretical efficiencies of energy metabolism. Advances include the identification of the costs of: 1) the malate-aspartate shuttle for transporting protons and electrons into the mitochondria, 2) pyruvate transport into the mitochondria, and 3) counter transport of ATP and guanosine triphosphate (GTP) out of the mitochondria with the concomitant costs of transporting ADP, GDP, and inorganic phosphorous into the mitochondria. The impact of advancing knowledge on the theoretical estimates of the energetic efficiency of physiological processes is demonstrated by showcasing the decreases in that the efficiency of capturing chemical energy as ATP from oxidative processes when recent research findings are applied to the theoretical calculations. We refined the assumptions used in energetics and the impact of the numerical values associated with energy metabolism, focusing on the theoretical biochemical and physiological processes of de novo synthesis, digestion, absorption, storage (both short-term and long-term), and mobilization of glucose in ruminant and non-ruminant animals. At present, it is accepted that electron transport results in 10 and 6 protons pumped from the matrix to the inter-mitochondrial space when the electrons are derived from NADH + H+ and flavin adenine dinucleotide (FADH2), respectively. The recent discovery that bovine heart ATP synthase requires the flow of 8 protons from the inter-mitochondrial membrane space into the mitochondrial matrix through ATP synthase to produce 3 ATP alters previous estimates of energetic efficiency. Recognizing that ATP synthase contains 8 c-proteins and, thus, requires 8 protons to make a complete turn and produce 3 ATP, i.e. it costs 2.67 protons per ATP formed. The newly formed ATP then must be translocated into the cytosol with counter transport of ADP and inorganic phosphorus (Pi) into the mitochondrial matrix with the assistance of a proton, so it actually costs 3.67 protons per ATP formed. Therefore, each proton is worth 0.27 ATP (1/((8/3)+1)). Up to now, many estimates assumed that the mammalian ATP synthase contained 9 c proteins in order to achieve symmetry around the ATP synthase. In other words, 4 protons (3 to spin the ATP synthase and 1 for phosphate translocase) were required in the synthesis of each ATP, and the value of each proton was 0.25 ATP. As a result, coupling electron transport to oxidative phosphorylation indicates that 2.7 ATP are produced from each NADH + H+ formed in the mitochondria, 2.5 ATP from each NADH + H+ formed in the cytosol, and 1.6 ATP from each mitochondrial FADH2. Mitochondrial GTP formed in the TCA cycle is equivalent to 0.7 ATP when GTP is transported out of the mitochondria. Energy available from ATP hydrolysis under mammalian physiological conditions ranges from approximately -32 to -52 kJ/mole of ATP, with an average of -42 kJ/mol. With the use of data, theoretical efficiencies and net ATP production/costs were calculated and compared with those from previous studies. The results demonstrate that the efficiency of capturing chemical energy as ATP from oxidative processes is decreased when recent research findings are applied to the theoretical calculations. Given that the ATPase has 8 c proteins, the ATP produced are 2.7 ATP/ mol NADH + H+ (10 protons/3.67 protons per ATP) and 1.6 ATP/mole FADH2 (6 protons/3.67 protons per ATP). With that realization, one mole of glucose has the potential to produce 32.9 ATP and with the heat of combustion of glucose being 2,820 kJ/mole, then -85.7 kJ/mole ATP (-2820/32.9) are lost as heat for systems that undergo no net metabolic change. The efficiency of glucose metabolism is 48.8% ((32.9 × -41.8)/-2820) for ATP formation with the assumption that under physiological conditions the hydrolysis of ATP to ADP and Pi is approximately -41.8 kJ/mole. We are presently applying these new estimates of energetic efficiency to the metabolic pathways in the dairy cow with a focus on maintenance and milk production. The table below identifies the cost and production of ATP when glucose is aerobically respired to CO2 and H2O in mammalian tissue. Similar analyses are examining the energetic efficiencies of gluconeogenesis in both ruminants and non-ruminants, protein synthesis, milk synthesis, storage of glucose energy as fat, and storage of glucose as glycogen Stoichiometry of glucose oxidation as a function of cofactors with the final column a sum of total ATP produced/consumed. Cofactors Reaction1 ATP NADHc NADHm FADH2 NADPH2 GTP H+ CO2 O2 Total ATP Glc to 2 Pyrc 2 2 0 0 0 0 0 0 0 6.9 NADHc to ATP 2.5 -1 0 0 0 0 0 0 0.5 2.5 Pyrc to Pyrm 0 0 0 0 0 0 -1 0 0 -0.27 Pyrm to ACA 0 0 1 0 0 0 0 1 0 2.7 TCA cycle 0 0 3 1 0 1 0 2 0 10.5 GTP to ATP 0.72 0 0 0 0 -1 0 0 0.5 0.72 NADHm to ATP 2.7 0 -1 0 0 0 0 0 0.5 2.7 FADH2 to ATP 1.6 0 0 -1 0 0 0 0 0.5 1.6 1 Glc = glucose; Pyrc = cytosolic pyruvate; Pyrm = mitochondria pyruvate; NADHc = cytosolic NADH; NADHm = mitochondrial NADH; ACA = Acetyl-CoA; GTP = guanosine triphosphate and FADH2 = flavin adenine dinucleotide.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2014
Citation:
Computer modeling of obesity links theoretical energetic measures with experimental measures of fuel use for lean and obese men.
Rossow HA, Calvert CC.
J Nutr. 2014 Oct;144(10):1650-7. doi: 10.3945/jn.114.192351. Epub 2014 Aug 13.
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Progress 01/01/13 to 09/30/13
Outputs
Target Audience:
Nothing Reported
Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided? One graduate student has been involved in the review and updating the energetic efficiencies of ATP production in Mammalian species. How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals? Complete manuscripts in preparation and revise those that have been returned from review.
Impacts
What was accomplished under these goals?
We have previously embarked on an effort to update the estimates for comparison with animal generated estimates of energetic efficiencies. The manuscript from that effort is currently being revised based on recent reports concerning the efficiency of the bovine heart ATPase.
Publications
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Progress 01/01/12 to 12/31/12
Outputs
OUTPUTS: This project is in year three and has limited outputs. Professor Rossow is working with beef producers collecting the data used to develop computer models that predict carcass quality and carcass characteristics in a specified amount of time on a grass fed management system. Significant effort continues to be expended in outreach to producers and presentations that designed to encourage producers to cooperate with the development of collaborative research efforts. Output is formal discussions with grass-fed beef producers and producers that are interested in moving from a feedlot based feeding system to grass-fed feeding and management systems. An issue with the modeling efforts is that current theoretical estimates of the metabolic and physiological process which can be related to nutritional energetic measurements are outdated. We have embarked on an effort to update the estimates for comparison with animal generated estimates of energetic efficiencies. The theoretical estimates that we develop must also be incorporated into the current models of beef cattle growth, on both feedlot and grass-fed regimes. PARTICIPANTS: Yolo Land and Cattle Company generously provided the beef cattle used in the pasture and feedlot settings. They also provided forage for the feedlot feed animals, with the forage being similar to that of the grass-fed animals. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Current theoretical estimates of the metabolic and physiological process which can be related to nutritional energetic measurements are seriously outdated. We are working to update these estimates and focused on the efficiencies of fat and carbohydrate digestion, absorption and assimilation in ruminants and non-ruminants. There is significant inconsistency in the reported literature as to how these estimates are calculates and the assumptions underlying the calculations. The primary focus of this expanded effort is to reference the basis for the assumptions, quantitate the impact of each assumption on the inference space, and update the actual biochemical value of fat and carbohydrate in terms of ATP production and use.
Impacts
We previously described an experimental effort involving Angus cross cattle of similar genetic that were placed on one of two treatments, a conventional finishing ration at the UC Davis feedlot and a grass finishing regime on irrigated pasture supplemented with grass hay and a free choice supplement. A part of the data has been used to calculate adjustments in the model for grass feeding. Descriptive animal data including body weight, blood profile, age, back fat, rib eye area and marbling score (ultrasound) were measured prior to the finishing phase, were used to adjust the model for each animal, and the same measurements made were made just prior to slaughter. The parameters were measured again and compared to model predictions. These data are being used to challenge our existing beef cattle model. Results are being used to improve model description of the characteristics of beef cattle production in grass fed systems. Blood parameters are presently being measured. Two manuscripts are in revision with a third submitted. The theoretical updates of energetic efficiencies will be used to update the existing model.
Publications
- No publications reported this period
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Progress 01/01/11 to 12/31/11
Outputs
OUTPUTS: This Project is in year two and has limited outputs. Professor Rossow is working with beef producers and developing acceptable protocols for use in collecting the data required in a commercial setting. It has taken a year to get agreement from enough commercial producers to obtain the data required to develop the computer model that will predict carcass quality and carcass characteristics in a specified amount of time on a grass fed management system. Significant effort has been expended in outreach to producers and presentations that designed to encourage producers to cooperate with the development of collaborative research efforts. It has been difficult obtaining permission to work with commercial grass-fed beef operations that have enough numbers in cattle to provide the data required. Small producers are interested but the ability to obtain quality data in the quantity required is very limited with these producers. Output at this time is formal discussions with grass-fed beef producers and producers that are interested in moving from a feedlot based feeding system to grass-fed feeding and management systems. PARTICIPANTS: Yolo Land and Cattle Company generously provided the beef cattle used in the pasture and feedlot settings. They also provided forage for the feedlot feed animals, with the forage being similar to that of the grass-fed animals. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Angus cross cattle of similar genetic backgrounds supplied by a local producer were fed starting at approximately 400 days of age. Treatment 1 was the conventional finishing ration at the UC Davis feedlot, while treatment 2 was grass finished by a cooperating producer on irrigated pasture supplemented with grass hay and a free choice supplement. Data from phase 1 are being used to calculate adjustments in the model for grass feeding. Descriptive animal data including body weight, blood profile, age, back fat, rib eye area and marbling score (ultrasound) were measured prior to the finishing phase and are being used to adjust the model for each animal. Just prior to slaughter these parameters were measured again and compared to model predictions. Subcutaneous fat samples at Shoulder, 12th Rib and Tail head and analyzed for neutral / polar lipids, fatty acids (PUFA), DNA, RNA, protein and muscle samples at Longissimus (Ribeye at 11-12th rib), Semitendinosus (Eye of round) and Psoas Major (Tenderloin) were be collected at the beginning of the finishing phase and at slaughter and analyzed for neutral / polar lipids, fatty acids (PUFA), DNA, RNA, protein, water and vitamins A, D and E to provide an index of growth and lipid composition changes and to compare fat composition and content in feedlot finished to grass finished cattle. Feedlot diet, forage and supplement samples were collected monthly and the resulting analysis is being used to estimate nutrient supply to the animal. At animal harvest, data including the hot carcass weight, viscera weight, quality and yield grade, and carcass composition were collected. These data are currently being used to challenge our existing beef cattle model. Results are being used to improve model description of the characteristics of beef cattle production in grass fed systems. Blood parameters are presently being measured. One manuscript was submitted and is in revision with a second manuscript submitted and a third in preparation.
Publications
- No publications reported this period
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Progress 01/01/10 to 12/31/10
Outputs
OUTPUTS: This Project is in the first year and has limited outputs. Professor Rossow has initiated contact with beef producers and explained the project to those producers. We have indicated to the beef producers that the primary output will be a computer model that computer model that can be used to formulate beef cattle diets, but more importantly, will predict carcass quality and carcass characteristics in a specified amount of time on a grass fed management system. This outreach effort is designed to develop collaborative research efforts with local beef producers interested in increasing their production of grass fed beef cattle. Thus the output at this time is informal discussion with beef producers about the consequences of moving from a feedlot based feeding system to grass-fed feeding and management. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Angus cross cattle of similar genetic backgrounds supplied by a local producer were fed starting at approximately 400 days of age. Treatment 1 was the conventional finishing ration at the UC Davis feedlot, while treatment 2 was grass finished by a cooperating producer on irrigated pasture supplemented with grass hay and a free choice supplement. Data from phase 1 are being used to calculate adjustments in the model for grass feeding. Descriptive animal data including body weight, blood profile, age, back fat, rib eye area and marbling score (ultrasound) were measured prior to the finishing phase and are being used to adjust the model for each animal. Just prior to slaughter these parameters were measured again and compared to model predictions. Subcutaneous fat samples at Shoulder, 12th Rib and Tail head and analyzed for neutral / polar lipids, fatty acids (PUFA), DNA, RNA, protein and muscle samples at Longissimus (Ribeye at 11-12th rib), Semitendinosus (Eye of round) and Psoas Major (Tenderloin) were be collected at the beginning of the finishing phase and at slaughter and analyzed for neutral / polar lipids, fatty acids (PUFA), DNA, RNA, protein, water and vitamins A, D and E to provide an index of growth and lipid composition changes and to compare fat composition and content in feedlot finished to grass finished cattle. Feedlot diet, forage and supplement samples were collected monthly and the resulting analysis is being used to estimate nutrient supply to the animal. At animal harvest, data including the hot carcass weight, viscera weight, quality and yield grade, and carcass composition were collected. These data are currently being used to challenge our existing beef cattle model. Results are being used to improve model description of the characteristics of beef cattle production in grass fed systems. Blood parameters are presently being measured and a manuscript and PhD Dissertation are currently being written.
Publications
- No publications reported this period
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Progress 01/01/09 to 12/31/09
Outputs
OUTPUTS: This is revised project, initiated this year. There are no outputs to report. We are completing the first phase of an effort to improve our model of beef cattle growth. Angus cross cattle of similar genetic backgrounds supplied by a local producer have been fed a conventional finishing ration at the UC Davis feedlot while a second group has been grass finished by a cooperating producer on irrigated pasture supplemented with grass hay and a free choice supplement. All feedlot fed animals have completed the experiment while five grass fed steers remain to be collected in March, 2010. We have collected steer body weight, blood profile, age, back fat, rib eye area and marbling score (ultrasound). We measured these parameters just prior to slaughter. We have collected subcutaneous fat samples at the shoulder, 12th Rib and Tail head for analyses of fatty acids (PUFA), DNA, RNA, protein. We have collected muscle samples from the Longissimus (Ribeye at 11-12th rib), Semitendinosus (Eye of round) and Psoas Major (Tenderloin) for similar analyses as described above. These data are to be used to develop and index of growth and lipid composition changes and to compare fat composition and content in feedlot finished to grass finished cattle. The feedlot diet, forage and supplement samples have been collected monthly for nutrient analyses. The resulting analysis will be used to estimate nutrient supply to the animal. Slaughter data such as hot carcass weight, viscera weight, quality and yield grade, and carcass composition will also be compared to model predictions. The primary outcome from this project will be a computer model that can be used by feedlot consultants and producers to test effects of different feeding strategies, including grass fed management systems, on carcass quality and provide appropriate timing for harvesting. This involves converting the model over to software that will make it easier to use. PARTICIPANTS: Dr. Heidi Rossow is the Co-PI for this project. Dr. Rossow is an Assistant Professor of Population, Health and Reproduction. UCDavis School of Veterinary medicine. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Data collection and sample analyses are currently underway.
Publications
- No publications reported this period
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Progress 01/01/08 to 12/31/08
Outputs
OUTPUTS: A computer program has been made available for teaching, dairy cattle production and research. The model can be down loaded from: http://animalscience.ucdavis.edu/research/molly/Molly.htm PARTICIPANTS: Dr. Heidi Johnson is a key individual in this research project. Heidi A. Johnson, Ph.D. HAJohnson@UCDavis.edu WEBSITE: http://animalscience.ucdavis.edu/research/molly TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
We continue to update Molly and have now begun to expand to model to other species.
Publications
- H. A. Johnson, H. A., J. A. Maas, C. C. Calvert, and R. L. Baldwin. 2008. Use of computer simulation to teach a systems approach to metabolism. J. Anim. Sci. 86:483-499.
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Progress 01/01/07 to 12/31/07
Outputs
OUTPUTS: We have previously described the development and validation of Molly, a dynamic and mechanistic model of dairy cow metabolism. In Molly's diary (Baldwin, 2008), Molly describes herself as the "aggregated version of the 550 kg cow described by Smith (1970) and Baldwin and Smith (1971a). I was developed to simulate overall energy transactions, within-day patterns of nutrient use, longer term day-to-day patterns of nutrient utilization throughout lactation and aid in the identification, design and interpretation of metabolic and energy balance experiments." The value of a mechanistic model is to show where knowledge is lacking by failure in representing the understanding of underlying function in appropriate equation form. With the continued process of model (Molly) development, testing, and critical assessment of whether Molly's behavior simulates observed biology and functions appropriately in different physiological states and conditions, Molly found herself in the
classroom. In Molly's word "They built a nice, user-friendly front end (no pretty horns, but I'm told they don't make you attractive to other species, anyhow) for this purpose. In class, students undertook simulations of experiments in the literature and, when I simulated the reported responses correctly, could request outputs that enabled them to explain the observed responses in their lab reports (Bowers and Baldwin, 1990). This was fun, for me, except when students forgot to feed me or made other errors in required inputs, causing painful exponential overflows. These are now indicated on the screen by a caricature of me, on my back, legs up, to signify my virtual demise. This was introduced by Heidi Johnson, while acting as a TA at the time, to avoid student questions about receiving no outputs." At present Molly reports that she is "ready to receive not only criticism but, more importantly, suggestions in the form of improved equations and parameterization are welcomed. They renew
me and will help ensure my continued relevance." She has issued the invitation to all interested that they can "download a running version of my program from http://animalscience.ucdavis.edu/research/molly/. This site has downloading and running instructions, as well as a listing of my program and a dictionary. At present we are interested in pursuing a specific problem with Molly. There is a cumulative error in Molly that results in excess body fat accretion in the later stages of lactation. Preliminary data analyses indicate that this systematic error is not related to a low metabolic rate and is not associated with nutrient inputs. Quantifying changes in metabolism throughout lactation coupled with existing liver, adipose and mammary models will be used to improve estimates of aggregated metabolic processes represented within Molly. Production data will also help identify the source of excess body fat accretion and determine if it is related to fat metabolism or whole body energy
balance. Energy balance data are available to test these aspects of the model.
PARTICIPANTS: Jim Fadel and Heidi Johnson. Heidi works for the USDA Western Human Nutrition Research Center on campus and is a member of the NC-1040 Regional Research project. Heidi has provided that majority of the actual modeling.
TARGET AUDIENCES: The target audience includes individuals conducting research in ruminant animals, teaching ruminate nutrition and metabolism, or providing advice to producers, especially with regard to feeding strategies.
PROJECT MODIFICATIONS: No Modifications.
Impacts
Future versions of Molly will require accounting for the significant amount of variability in production traits that can be attributed to genetic variation. With the expanding understanding of the genes responsible for production traits, the ability to describe mechanisms that alter genetic variation will improve Molly. Molly provides a management tool for the dairy producer and the dairy industry. Given that Molly is based on mechanism, this management tool has the potential to significantly impact production systems. Molly can be used for teaching, in addition to research.
Publications
- No publications reported this period
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Progress 01/01/06 to 12/31/06
Outputs
We have previously described the development and validation of Molly, a dynamic and mechanistic model of dairy cow metabolism. The value of a mechanistic model is to show where knowledge is lacking by failure in representing the understanding of underlying function in appropriate equation form. While we have continued the process of model development and testing and to critically assess whether model behavior simulates observed biology and functions appropriately in different physiological states and conditions, we have also advanced Molly from a strict research model to a teaching model. Currently we are preparing a manuscript that describes and demonstrates how Molly can be used in the teaching environment. Given that Molly is able to represent carryover effects from changing diets and production responses to changes amino acid and protein supplementation, students of dairy cow metabolism will be able to ask "what if questions" and obtain predictions and simulations
in minutes as compared to collecting data for a complete lactation. We continue to evaluate specific limitations in the model which include how environmental effects, vitamin or mineral metabolism and many disease states affect dairy cow metabolism and production. One specific parameter, the number of udder cells (UCELLS), is used as measure of genetic potential for milk production. Using UCELLS as an index of genetic potential within populations of similar animals, we simulated individual cow lactation curves from a large data set and found that UCELLS accounted for significantly less variance in milk production than the estimated 25 % of within herd variance attributed to genetics. If this term is to serve as a surrogate for genetic potential, it must not only explain more of the variability in phenotypes, we should also be able to insure that estimates of UCELLS for relatives are positively correlated to the degree expected from the theory of quantitative genetics.
Impacts
Future versions of Molly will have to find other terms, along with UCELLS, which can account for the significant amount of variability in production traits that can be attributed to genetic variation. We expect that the expanding understanding of the genes responsible for production traits will add to our ability to describe mechanisms that that alter genetic variation. This future research will require examining the relationship between the UCELLS estimates of genetic relatives. Presently, Molly can be used for teaching, in addition to research. Molly also provides a management tool for the dairy producer, and given that Molly is based on mechanism, this management tool has the potential to significantly impact production systems.
Publications
- No publications reported this period
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Progress 01/01/05 to 12/31/05
Outputs
We have previously described the development and validation of Molly, a dynamic and mechanistic model of dairy cow metabolism. The value of a mechanistic model is to show where knowledge is lacking by failure in representing the understanding of underlying function in appropriate equation form. Central to this process of model development and testing is the use of appropriate statistical tests of comparison and bias for model prediction of observed data. In addition, it is critical to assess whether model behavior simulates observed biology and functions appropriately in different physiological states and conditions. Previous evaluations have shown that Molly is able to represent carryover effects from changing diets, metabolizable energy values for different diets, and production responses to changes amino acid and protein supplementation. Adjusting certain parameters such as number of udder cells (UCELLS), which we use as measure of genetic potential for milk
production, and maximal velocities allows the model to simulate a range of milk volume, milk fat and milk protein levels. However, over long term simulations on some diets and production levels, body fat accumulates in excess of that which is observed. Other model limitations include environmental effects, vitamin or mineral metabolism and many disease states that effect dairy cow metabolism and production. Many of these affect feed intake and, given that feed intake is input to the model, will affect model predictions without any adjustment of model parameters. However, any effects not explicitly represented in the model will be absorbed in the adjustment of parameters such as UCELLS in order to simulate individual cow milk production. In an effort to determine whether UCELLS is an adequate index of genetic potential within populations of similar animals, we simulated individual cow lactation curves from a large data set. UCELLS accounted for significantly less variance in milk
production than the estimated 25 % of within herd variance attributed to genetics. We are in the process of suing UCELLS.
Impacts
Future versions of Molly will have to find other terms, along with UCELLS, which can account for the significant amount of variability in production traits that can be attributed to genetic variation. We expect that the expanding understanding of the genes responsible for production traits will add to our ability to describe mechanisms that that alter genetic variation. This future research will require examining the relationship between the UCELLS estimates of genetic relatives. If this term is to serve as a surrogate for genetic potential, it must not only explain more of the variability in phenotypes, we should also be able to insure that estimates of UCELLS for relatives are positively correlated to the degree expected from the theory of quantitative genetics.
Publications
- No publications reported this period
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Progress 01/01/04 to 12/31/04
Outputs
We have previously described the development and validation of Molly, a dynamic and mechanistic model of dairy cow metabolism. The value of a mechanistic model is to show where knowledge is lacking by failure in representing the understanding of underlying function in appropriate equation form. Central to this process of model development and testing is the use of appropriate statistical tests of comparison and bias for model prediction of observed data. In addition, it is critical to assess whether model behavior simulates observed biology and functions appropriately in different physiological states and conditions. Previous evaluations have shown that Molly is able to represent carryover effects from changing diets, metabolizable energy values for different diets, and production responses to changes amino acid and protein supplementation. Adjusting certain parameters such as number of udder cells (UCELLS), which we use as measure of genetic potential for milk
production, and maximal velocities allows the model to simulate a range of milk volume, milk fat and milk protein levels. However, over long term simulations on some diets and production levels, body fat accumulates in excess of that which is observed. Other model limitations include environmental effects, vitamin or mineral metabolism and many disease states that effect dairy cow metabolism and production. Many of these affect feed intake and, given that feed intake is input to the model, will affect model predictions without any adjustment of model parameters. However, any effects not explicitly represented in the model will be absorbed in the adjustment of parameters such as UCELLS in order to simulate individual cow milk production. In an effort to determine whether UCELLS is an adequate index of genetic potential within populations of similar animals, we simulated individual cow lactation curves from a large data set. UCELLS accounted for significantly less variance in milk
production than the estimated 25 % of within herd variance attributed to genetics. UCELLS can be used to adjust to peak milk production but other parameters such as those governing persistence must be adjusted to adequately simulate within herd genetic variance.
Impacts
Future versions of Molly will have to find other terms, along with UCELLS, which can account for the significant amount of variability in production traits that can be attributed to genetic variation. We expect that the expanding understanding of the genes responsible for production traits will add to our ability to describe mechanisms that that alter genetic variation. This future research will require examining the relationship between the UCELLS estimates of genetic relatives. If this term is to serve as a surrogate for genetic potential, it must not only explain more of the variability in phenotypes, we should also be able to insure that estimates of UCELLS for relatives are positively correlated to the degree expected from the theory of quantitative genetics.
Publications
- No publications reported this period
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Progress 01/01/03 to 12/31/03
Outputs
Rates of fiber hydrolysis and fiber digestiblity continue to limit the effectiveness of th digestive element of our model of lactating cow digestion and metabolism. We are in the process of completing studies directed resolution of problems with representationing effects of pH on fiber digestion and writing final publications from this work. In these we will compare estimates of digestiblities from "in sacco" studies with direct estimates from duodenal cannulae. We completed an analysis of the efficacy of using "ucells" alone to specify the genetic potential of cows in our model and found this was inadequate. Additional parameters including those defining persistency must also be defined to obtain acceptable simulations of reality.
Impacts
Systematic errors in model simulations of digestion and metabolism in lacating cows are being addressed such that predictions relative to experimental data on the lactational performance of cows continue to improve.
Publications
- Baldwin, R.L., Calvert, C.C., Robinson, P.H., Johnson H.A.. 2003. Modeling Amino Acid Metabolism in Ruminants. In: Amino Acids in Animal Nutrition, 2nd Edition, edited by J.P.F. D'Mello. CABI Publishing, Cambridge, MA. Pp. 291-308.
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Progress 01/01/02 to 12/31/02
Outputs
Rates of fiber hydrolysis and fiber digestibility continued to limit the performance of the digestive elements of our current model of the lactating cow. The role of pH relative to digestibility has not been examined in a quantifiable manner. We are in the process of completing studies that address that issue and have some limited initial publications relative to that work. We also examined the impact on estimated rates of protein synthesis when amino acids were separated amino acids between plasma, extracellular and intracellular compartments. This provided further insight on the design of experiments that would help quantify rates of amino acid recycling and channeling upon estimates of protein fractional synthesis rates.
Impacts
Systematic sources of errors in model simulations are being addresses, resulting in more accurate model predictions compared to experimental data. Deficiencies in descriptions of protein metabolism have been identified and experimental protocols identified to extend knowledge relating to protein turnover and amino acid metabolism.
Publications
- Spackman, C., Baldwin, R. L., Sainz, R. D., Sweany, M. L. 2002. Fiber hydrolysis in the rumen: Effects of pH and forage type. Journal of Dairy Science. 85(Supplement 1). 362.
- Spackman, C., Baldwin, R. L., DePeters, E. J., Sweany, M. L. 2001. The effect of rumen pH and forage type on in situ fiber hydrolysis in dairy heifers. Journal of Dairy Science. 84(Supplement 1). 424.
- Johnson, H. A., Baldwin, R. L., Klasing K. C., Calvert, C. C. 2001. Impact of separating amino acids between plasma, extracellular and intracellular compartments on estimating protein synthesis in rodents. Amino Acids 20:389-400.
- McNamara, J. P., Baldwin, R. L. 2000. Estimation of parameters describing lipid metabolism in lactation: Challenge of existing knowledge described in a model of metabolism. Journal of Dairy Science. 83:128-143.
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Progress 01/01/01 to 12/31/01
Outputs
Excessive fat gains simulated by our model of digestion and metabolism in lactating cows when high fat diets were fed was corrected by reducing the lower gut digestion coefficient for Fat and adding a provision for feed intake to alter energy expenditures associated with the Na+ K+ ATPase. Model equations now accept estimates of diet protein and starch degradabilities as inputs. Initial testing indicates the changes introduced resulted in significant improvements. Experimental variance associated with estimates of diet protein and starch passage preclude more rigorous testing. Experimental studies of effects of pH on fiber hydrolysis were completed.
Impacts
Systematic sources of errors in model simulations were addressed resulting in more accurate model predictions as compared to experimental data.
Publications
- Baldwin, R. L. and K. C. Donovan. (2000). Modelling the Lactating Dairy Cow in Feeding Systems and Feed Evaluation Models. Ed. M. K. Theodorou and J. France. CAB International. Wallingford, U.K. and New York pp. 323-342.
- Johnson, H. A., R. L. Baldwin, K. C. Klasing, J. France, and C. C. Calvert. (2000). A Rodent Model of Protein Turnover Used to Design an Experiment for Measuring the Rates of Channeling, Recycling and Protein Systhesis. Journal of Nutrition 130:3097-3102.
- Baldwin, R. L., B. A. Crooker and M. Neil (2001). Discussion: Tissue and Whole Body Metabolism in Energy Metabolism in Animals. Ed. A Chwalibog and K. Jacobsen. Wageningen Pers. Wageningen, Netherlands.
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Progress 01/01/00 to 12/31/00
Outputs
During the past year we addressed three problems identified previously. The first was excessive fat gains simulated when high fat diets were fed. After evaluating a number of possible causes of the model errors, the lower gut digestion coefficient for Fat was reduced to correct the problem. The digestive element of the model tended to predict the passage of diet protein and starch, undigested, from the rumen poorly. Model equations were adjusted to correct accept estimates of diet protein and starch degradabilities as inputs. Initial testing indicates the changes introduced resulted in significant improvements. Experimental variance associated with estimates of diet protein and starch passage preclude more rigorous testing. Experimental studies of effects of pH on fiber hydrolysis were initiated.
Impacts
Systematic sources of errors in model simulations were addressed resulting in more accurate model predictions as compared to experimental data.
Publications
- Baldwin R. L. 2000. History and future of modeling nutrient utilizationin farm animals. In Modelling Nutrient Utilization in Farm Animals. Ed. J. P. McNamara, J. France and D. E. Beever. CAB International. Wallingford, UK and New York. pp.1-9.
- Johnson, H. A., R. L. Baldwin, J. France and C. C. Calvert. 1999. A model of whole Body turnover based on leucine kinetics in rodents. Journal of Nutrition 129:728-739.
- Johnson, H. A., R.L. Baldwin, J. France and C. C. Calvert. 1999. Recycling, channeling, and heterogeneous protein turnover estimation using a model of whole-Body protein turnover based on leucine kinetics in rodents. Journal of Nutrition 129: 740-750.
- McNamara, J. P. and R. L. Baldwin. 2000. Estimation of parameters describing Lipid metabolism in lactation: challenge of existing knowledge described in a model Of metabolism. Journal of Dairy Science 83:128-143.
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Progress 01/01/99 to 12/31/99
Outputs
During the past year we refined the representation of histidine metabolism we reported last year in order to better simulate observed rates of 3-methylhistidine excretion. We also addressed two problems identified previously. The first was the excessive fat gains when experimental data were compared to model simulations. After evaluating a number of alternative causes of the model errors, provisions were added to better accommodate effects of energy inputs upon Na+K+ ATPase activity and effects of high intakes upon weights of visceral organs. Addition of these provisions corrected the problem of excessive fat gains in simulations of actual experimental data. The digestive element of the model tended to predict the passage of diet protein, undigested, from the rumen. Model equations and inputs were adjusted to correct this systematic error of prediction. Initial testing indicated the changes introduced represent an improvement, however, further evaluation is required.
The collection of full lactation data required to further evaluate the model continues.
Impacts
Systematic sources of errors in the model due to underestimates of energy expenditures at high feed intake and diet protein passing from the rumen undigested dietary protein (RUP) were addressed resulting in more accurate model predictions as compared to experimental data.
Publications
- McNamara, J.P. and Baldwin, R.L. (1999) Estimation of parameters describing lipid metabolism in lactation: challenge of existing knowledge described in a model of metabolism. Journal of Dairy Science 83: 128-143.
- Baldwin, R. L. and K. C. Donovan. 1998. Modeling ruminant digestion and metabolism. In Mathematical Modeling in Experimental Nutrition. (A. J. Clifford and H. Muller, editor). Plenum Press, New York, pp. 325-343.
- France, J., J. Dijkstra, M. S. Dhanoa and R. L. Baldwin. 1998. Biomathematical Applications in Ruminant Nutrition. Journal of the Franklin Institute, Vol 335B. Elsevier Science Ltd, UK, pp. 241-258.
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Progress 01/01/98 to 12/31/98
Outputs
The objective of this project is development and refinement of a dynamic, mechanistic research model of lactating cow digestion and metabolism. A specific limitation of the model was that amino acids are represented as a single aggregate pool. As a result, diet limitations in specific amino acids and responses to supplementation with specific amino acids couldn't be simulated. Modifications have been incorporated to enable the model to handle these limitations with confidence. Data obtained from 70 mammary gland arteriovenous studies, previously reported, have been used in behavior and sensitivity analyses. Results from early studies involving supplementation of lactating cows with methionine and lysine were successfully simulated. A further limitation of the model is that effects of ambient pH and forage quality (maturity) on rate constants for hydrolysis of cellulose and hemicellulose cannot be adequately defined using data currently available. Experiments required
defining effects of pH and forage type and quality upon these rate constants have been initiated.
Impacts
(N/A)
Publications
- Baldwin, R.L., and Donovan, K.C. 1997. From the ground up: the development and demonstrated utility of ruminal ecosystem model. In: Mathematical Models in Microbial Ecology. J.A. Robinson & G.A. Milliken (eds.). Chapman & Hall of New York, pp. 209-226.
- France, J., Dijkstra, J., Dhanoa, M.S. and Baldwin, R.L. 1998. Biomathematical applications in ruminant nutrition. Journal of the Franklin Institute, V.335B. Elsevier Science Ltd., UK, pp. 241-258.
- Baldwin, R.L., and Donovan, K.C. 1998. Modeling ruminant digestion and metabolism. In: Mathematical Modeling in Experimental Nutrition. A.J. Clifford & H. Muller (eds.). Plenum Press, New York, pp.
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Progress 01/01/97 to 12/01/97
Outputs
The central objective of this project has long been the development and refinement of a dynamic, mechanistic model of lactating dairy cow digestion and metabolism for use in support of our research and eventual application as an alternative to the largely empirical, static, factorial systems for the feeding management of lactating dairy cows, such as NRC program for calculating the nutrient requirements of dairy cattle. We have documented the advantages of using dynamic, mechanistic models as compared to current systems previously. During the past year, we have shifted our emphasis from research modeling to practical application. We have added provisions to simulate effects of limiting amino acids on animal metabolism. This required major revisions of the model. We have designed a vastly improved user friendly "front end." Before releasing the model for practical use, it must be challenged to predict dairy cow performance better than existing systems. Collection of
full lactation data suitable for this purpose has been progressing well. We hope to collect 15,000-20,000 individual cow records representing a wide range of diets and feeding management strategies to adequately challenge the model.
Impacts
(N/A)
Publications
- BALDWIN, R.L. 1995. Modeling Ruminant Digestion and Metabolism. Chapman & Hall, UK.
- BALDWIN, R.L. and SAINZ, R.D. 1995. Bottlenecks for improvement of future models in animal nutrition science. In: IVth International Workshop on Modelling Nutrient Utilization in Farm Animals. A. Danfaer and P. Lescoat (eds.). National Inst
- BALDWIN, R.L. and SAINZ, R.D. 1995. Energy partitioning and modeling in animal nutrition. In: Annual Review of Nutrition, 15:191-211. Annual Reviews, Inc., Palo Alto, CA.
- BALDWIN, R.L. and DONOVAN, K.C. 1997. From the ground up: The development and demonstrated utility of ruminal ecosystem model. In: Mathematical Models in Microbial Ecology. J.A. Robinson and G.A. Milliken (eds.). Chapman & Hall of New York,
- FRANCE, J., DIJKSTRA, J., DHANOA, M.H. and BALDWIN, R.L. 1998. Biomathematical applications in ruminant nutrition. Journal of the Franklin Institute, V.335B. Elsevier Science, Ltd., UK, pp. 241-258.
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Progress 01/01/96 to 12/30/96
Outputs
Progress Report: The objective of this project is development and refinement of a dynamic, mechanistic research model of lactating cow digestion and metabolism. A specific limitation of the model was that amino acids are represented as a single aggregate pool. As a result, diet limitations in specific amino acids and responses to supplementation with specific amino acids couldn't be simulated. Modifications have been incorporated to enable the model to handle these limitations with confidence. Data obtained from 70 mammary gland arteriovenous studies, previously reported, have been used in behavior and sensitivity analyses. Also, results from early studies involving supplementation of lactating cows with methionine and lysine were successfully simulated.
Impacts
(N/A)
Publications
- Chwalibog, A. and R.L. Baldwin. 1995. Systems to predict the energy and protein requirements of laying fowl. World's Poultry Science Journal 51:187-96.
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Progress 01/01/95 to 12/30/95
Outputs
The central objective of this project over the past five years was development and refinement of dynamic, mechanistic research models of lactating cow digestion and metabolism and move detailed models of adipose tissue, liver and mammary metabolism. This includes the identification of critical experiments identified in the course of integrative (research) modeling analyses followed by utilization of the new data to improve the several models. Experimental research directed to this goal included the conduct of 70 mammary gland arteriovenous studies which were reported in literature cited in interim reports. Results from in vitro radiotracer experiments using liver and mammary gland tissue slices have also been reported. The data obtained in these experiments enabled further development of the mammary tissue and liver metabolism models with particular emphasis on amino acid metabolism (publication identified in interim reports). These data have been used to revise the
lactating cow model to better accommodate the metabolism of critical amino acids (work in progress). Perhaps, the most important research product generated as a result of this project is our book entitled Modeling Ruminant Digestion and Metabolism in which the evolution of this project over the past twenty years is documented along with current models and perspective for the future.
Impacts
(N/A)
Publications
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Progress 01/01/94 to 12/30/94
Outputs
A major thrust of this program continued to be refinement of our dynamic, mechanistic model of ruminant digestion and metabolism and our more detailed models of adipose tissue, liver and mammary gland metabolism. Data from research conducted during this project period include results from 70 mammary gland arteriovenous difference studies were reported in literature cited in interim reports. Results from in vitro radiotracer studies using liver and mammary gland tissue slices have also been reported. Recent progress has been slow but sure as we learn to use iterative parameter estimation software for dynamic models more effectively. In the overall, the data collected have been essential to further model development and our models have progressed very well.
Impacts
(N/A)
Publications
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Progress 01/01/93 to 12/30/93
Outputs
A major thrust of this program has been refinement of our dynamic, mechanistic model of ruminant digestion and metabolism for use in estimating methane emissions by ruminant livestock. Regression analyses of model predictions vs. experimental estimates of metabolizable energy (ME) values and methane emissions for 36 test diets ranging in ME/kg from 6.7 to 13.4 MJ indicated respective r square values of 0.85 and 0.65 with no indications of systematic errors. The 0.85 value is consistent with normal experimental variance in estimates of ME values and, therefore, cannot be improved further. The 0.65 value is considerably better than those estimated using the Blaxter and Clapperton (0.17) and Moe and Tyrell (0.35) equations in current use to estimate methane emissions. Methane emission estimates for livestock in the United States, New Zealand Venezuela, and India were completed. Considerable effort was expended in further development of our model of cow mammary
metabolism. The most important improvements were the addition of explicit representations of the metabolism of six individual amino acids. Behavioral and sensitivity analyses of the model were completed. The carbon/nitrogen/energy balance data for lactating cow udders based upon over 70 arteriovenous difference studies reported for 4901-RR, have been organized in a format consistent with their use to refine estimates of a number of parameter values in the current version of the model.
Impacts
(N/A)
Publications
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Progress 01/01/92 to 12/30/92
Outputs
Our dynamic, deterministic, mechanistic model of dairy cow digestion and metabolism developed previously was revised, and additional analyses and evaluations of the model were undertaken. The model was generalized to enable evaluations of a broader range of animal weights and stages of maturity, including weaned calves, fattening steers, and lactating cows. The model was also revised to evaluate a wider range of diets. The following changes were made to gain these capabilities: initial conditions, such as weight of body (largely muscle and skeleton), viscera, carcass fat, and gut fill were scaled to empty body weight; parameter values for metabolic equations were scaled to metabolic body weight (WO.75); separate equations for hemicellulose and cellulose were added because their fermentation products differ and affect methane emissions; and, separate hydrolytic rate constants for hemicellulose and cellulose from grasses, legumes, and silages were developed. Estimates
of methane emissions from cattle in the U.s. were developed for EPA and CAST. Studies of the role of IGF-1 in the regulations of protein and fat synthesis in mammary secretory cells continued.
Impacts
(N/A)
Publications
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Progress 01/01/91 to 12/30/91
Outputs
Development of equations for the uptake of all major nutrients and amino acids by cow mammary glands and carbon, nitrogen and energy balances which indicate that the net efficiency of milk synthesis in the udder is 89% - very close to theoretical. Completed development & revision of detailed models of liver, adipose and mammary tissue metabolism based on new data. Revised model of ruminant digestion to obtain accurate measurements of ruminant methane emissions. Estimates for U.S. and New Zealand methane emissions completed. Developed reagents and ELISA methods for measurement of all milk proteins and culture methods of MAC-T mammary secretory cell culture which lead to high levels of milk protein secretion.
Impacts
(N/A)
Publications
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Progress 01/01/90 to 12/30/90
Outputs
Studies of live-metabolism in lactating dairy cows were completed. Major findings were that rates of gluconeogenesis from propionate are elevated several-fold when cows are treated with recombinant bovine somatotropin (rBST); the efficiency of propionate -1-14C incorporation into glucose was also significantly enhanced by rBST treatment; and methylmalonyl-CoA and malonyl-CoA inhibit the key enzyme in ketogenesis, carnitine padmitozl-CoA transferase. Data obtained from the liver studies were used in formulation of a model of liver metabolism (Ph.D. thesis) and to introduce provisions for regulation of ketogenesis and ketone body metabolism in our cow model. Our detailed model of cow mammary metabolism was revised using the results of the arteriovenous difference studies on the udder and the mammary metabolism studies previously reported. Also, our detailed model of adipose tissue metabolism was revised to accommodate new data. Considerable effort was directed to
improving and challenging the digestive element of our cow model. A number of systematic errors of prediction of digestibility and products of digestion were corrected and the range of applicability across diets was broadened. For a challenge data set of 35 diets ranging in digestible energy (DE content from 1.8 to 3.5 mcal/kg) regression equations of predicted vs observed data had r2 values of 0.99 for DE, 0.99 for metabolizable energy and 0.96 for methane emissions.
Impacts
(N/A)
Publications
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Progress 01/01/89 to 12/30/89
Outputs
Twenty multiparous cows ranging from 14,000 to 30,000 pounds of milk in previouslactations were used. Ten were treated with bovine somatotrophin (BST) from weeks 10 to 18 of lactation. Mammary arteriovenous difference studies (12 h), D(2)O estimates of body composition and epinephrine challenge studies were conducted on weeks 5, 10 and 18 of lactation. The cows were slaughtered at the end of the eighteenth week of lactation for a body composition study, estimations of organ weights, composition, RNA, DNA and enzyme contents, and in vitro metabolic studies. Results regarding animal performance, body composition and mammary metabolism were reported last year. Results of the arteriovenous difference and liver metabolism studies are now complete. These yielded many fundamental data essential to our modeling studies. Interesting observations were 1) that red blood cells contribute significantly to the uptake of a number of amino acids including methionine, tyrosine
and pheylalanine by the udder 2) a number of interactions among amino acids and other blood nutrients which determine net uptakes and milk production were resolved 3) mammary gland uptakes of acetate and lipids are a linear function of their arterial concentrations while uptake of ketone bodies is a sigmoidal function of arterial concentration.
Impacts
(N/A)
Publications
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Progress 01/01/88 to 12/30/88
Outputs
Twenty multiparous cows ranging from 14,000 to 30,000 pounds of milk in previouslactations were used. Ten were treated with bovine somatotrophin (BST) from weeks 10 to 18 of lactation. Mammar arteriovenous difference studies (12 h), D(subscript 2)O estimates of body composition and epinephrine challenge studies were conducted on eeks 5, 10 and 18 of lactation. The cows were slaughtered at the end of the eighteenth week of lactation for a body composition study, estimations of organ weights, composition, RNA, DNA and enzyme contents, and in vitro metabolic studies. The response in milk production to BST administration was 15%. Milk composition was not altered. Cows treated with BST did not increase feed intake and lost body energy (as fat) to compensate. Milk production was highly correlated with total mammary DNA (R(superscript 2) = 0.8). As milk production increased proportions of glucose uptake used for lactose synthesis and. NADPH(subscript 2 generation via the
pentose cycle while glucose metabolized via the Ebden-Meyerhof pathway and total glucose oxidation decreased. The increase in pentose cycle flux was reflected in increases in the activities of the glucose-6-P and 6-P gluconate dehydrogenases. After covariate adjustments for milk production effects on mammary metabolism, a number of effects BST upon metabolism became evident.
Impacts
(N/A)
Publications
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Progress 01/01/87 to 12/30/87
Outputs
Development of a mechanistic model of growth in a steer suitable for analysis ofeffects of diet, intake, eating patterns and age upon products of digestion, energy expenditures for specific physiological/metabolic functions, rate and composition of gain was completed. Behavior of the model in response to a number of appropriate challenges was quite good. A notable example of the explanatory power of the model is its ability to reconcile the apparent systematic discrepancy between comparative slaughter and indirect calorimetric data. Provisions for water dynamics, monitoring of pH and effects of pH upon digestion in the rumen were added to the general model of ruminant digestion. Kinetic relationships essential to definition of effects of amino acids and peptides upon microbial growth rates and yields in the rumen were characterized.
Impacts
(N/A)
Publications
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Progress 01/01/86 to 12/30/86
Outputs
Major activities have been: Initiation of a major study of physiological/metabolic differences among cows differing in genetic potential for lactation (15-30,000) and of mechanism(s) of growth hormone action (see ASC-4597-CG); Completion of experimental work required for and development of highly mechanistic models of growth in mice and steers suitable for evaluation of concepts and data regarding energetics and partitioning of nutrients (manuscripts submitted-5); Completion of experimental and modelling studies of energy and amino acid and protein metabolism in lactating rats. These provide bases for formulation of equations for amino acid and protein metabolism in lactating cows.
Impacts
(N/A)
Publications
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Progress 01/01/85 to 12/30/85
Outputs
Developed a model of lactating rat metabolism to use in evaluations of energy balance data and to develop and validate equations to represent amino acid and protein metabolism. These can then be used in cow models. Developed a model of steer metabolism to extend interpretations of energy balance data. Developed a model of mouse metabolism for use in evaluations of energy balance data and to examine the quantitative significance of differences between control and high growth mouse strains. Completed studies of kinetic relationships for amino acids and petide effects upon rumen microbial growth rates and yields. Started examination of peptide transport mechanisms in rumen microbes. Revised model of ruminant adipose tissue metabolism.
Impacts
(N/A)
Publications
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Progress 01/01/84 to 12/30/84
Outputs
Completion of our detailed examination of the kinetics of cow mammary metabolism. One manuscript from this work has been published and two are in press. Completion of the experimental phase of the study of relationships among energy transactions and protein-turnover in lactating animals. Data are being utilized to examine dynamic aspects of nutrient partition in lactating animals with emphasis on relationships to protein turnover and metabolism. First phase of effort directed at resolution of quantitative and kinetic aspects of ruminant hepatocyte metabolism were completed. Rate limiting enzymes determinant of rates of gluconeogenesis from alternate substract were identified. A model of digestion and metabolism in lactating cows suitable for evaluation of energy balance and metabolic data and factors influencing partition of nutrients was completed.
Impacts
(N/A)
Publications
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Progress 01/01/83 to 12/30/83
Outputs
Detailed studies of the regulation of gluconeogenesis in isolated ruminant hepatocytes including PG,C-tracer studies examining carbon flow of glucose and fatty acid precursors. Completion of detailed studies of the roles of cAMP and fructose-2,6-diphosphate in regulation of phosphofructokinase in mammary tissue. Examined the role of various tissue nutrient pool turnover to determine which metabolic transactions affect energy balance in lactating animals. This effort utilized a recently developed a model of metabolism in lactating animals suitable for extended analysis of energy balance in lactating animals. Initiation of research examining the effect of dietary levels of protein and energy upon protein turnover in specific tissues during lactation. Initiation of research designed to evaluate the use of chitin as a marker for fungal protein escaping the rumen to the small intestine.
Impacts
(N/A)
Publications
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Progress 01/01/82 to 12/30/82
Outputs
Major progress during the past year has included: Development of a method for isolation of ruminant hepatocytes, completion of preliminary evaluations of ruminant hepatocyte metabolism and initiation of detailed studies of the regulation of gluconeogenesis in isolated hepatocytes. Identification of phosphofructokinase as the critical site of regulation of mammary function by glucocorticoids and (partial) characterization of the roles of cAMP and fructose-2, 6-diphosphate in regulation of this enzyme in mammary tissue. Development and validation of a model of ruminant adipose metabolism suitable for extended interpretation of radioisotope and kinetic data on the metabolism of this tissue. Development and validation of a model of metabolism in lactating animals suitable for extended analyses of energy balance as related to metabolic transactions in lactating animals. Completion of detailed studies of ruminant mammary gland metabolism.
Impacts
(N/A)
Publications
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Progress 01/01/81 to 12/30/81
Outputs
A major study was completed of metabolic changes in calf liver and adipose tissues during development when fed standard diets, a high carbohydrate diet and a high fat diet. Major findings weree adipose lipogenic capacity is responsive to diet and the onset of rumination; liver lipogenic capacity decreases dramatically at birth and does not respond significantly to changes in diet or age thereafter; the major reason for the failures of calves to adapt to high carbohydrate diets is digestive rather than metabolic. Substrate kinetics, enzyme changes and metabolic patterns were also evaluated. A detailed evaluation of effects of 3x milking in high producing dairy cows was completed. Results are being evaluated with regard to total production, persistency, health, nutritional requirements and efficiency. Detailed studies of ruminant liver and mammary metabolisms and regulations continued.
Impacts
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Publications
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Progress 01/01/80 to 12/30/80
Outputs
A major study of effects of high intakes of whole cottonseed and heat extruded whole soybeans on performance of lactating cows, effects on milk composition, and more particularly the fatty acid composition of milk fat, was completed and four papers have been submitted for publication. A modeling analysis of rumination patterns in ruminants was completed. Major findings were that rumination patterns are circadian in nature and that diet composition is a major factor determining amplitude of the cosignor pattern. Continuing modeling analysis of the dynamics of feed protein and nitrogen metabolism in the rumen indicated specific weaknesses in our current conceptual frame. A particular weakness is lack of knowledge regarding factors which determine the rate of hydrolysis of "insoluble protein". Methods for the isolation of ruminant hepatocytes were developed for use in metabolic studies. Ruminant hepatocytes are much more difficult to prepare than are those from
rodents. Because of this, more rigorous cirteria were established for use in evaluating the quality of isolated ruminant hepatocytes. Detailed modeling analyses of ruminant liver and adipose tissue metabolism are progressing well.
Impacts
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Publications
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Progress 01/01/79 to 12/30/79
Outputs
Studies of comparative aspects of nutrition emphasizing the carnivore (domestic cat) continue to be highly productive. Current emphasis is on establishing essential amino acid requirements and the metabolism of ornithine, citrulline and arginine. A separate project for this part of the program is pending. Studies of effects of high fat diets upon metabolism, milk composition and efficiency in dairy cattle continued. A study with whole cottonseed and extruded soybeans was completed. These diets increase efficiency and milk fat content but may reduce casein synthesis. Studies of interactions among nitrogen sources, waste and by-product feeds indicate optimal balances between soluble protein, NPN and insoluble protein maximize microbial growth and fermentation of by-product feeds such as treated straws, almond hulls, apple pomace, etc. A detailed study of the stoichiometry of rumen fermentation and microbial growth was completed. Results were surprising and have
markedly improved the accuracy with which we can predict products of digestion in ruminants.
Impacts
(N/A)
Publications
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Progress 01/01/78 to 12/30/78
Outputs
A series of experiments directed at identification and quantitative evaluation of factors which affect interactions and competitions among rumen microbes was completed. Five prominent rumen microbes were observed to exhibit a complex and complimentary pattern of "catabolite repression" such that each microbe occupies a separate "niche" with regard to carbohydrates fermented and need not compete directly with other microbes. Maintenance requirements, pH tolerances, affinities for substrates and fermentative capacities of rumen microbes were also investigated. These vary greatly among organisms and are major contributors to the diversity of the rumen microbial ecosystem. Computer analyses of these date with regard to rumen ecology are underway. A significant breakthrough in the development of model based analyses of radioisotope tracer data obtained with ruminant tissues (methods used for nonruminants are not valid for ruminants) was made. Also, a number of
detailed analyses of animal metabolic data were completed which indicate that Michaelis-Menton type kinetics can be applied in analyses of factors influencing patterns of nutrient utilization in animals. Experiments with high fat diets (lipid protected from rumen fermentation) fed to lactating dairy cows have been completed.
Impacts
(N/A)
Publications
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Progress 01/01/77 to 12/30/77
Outputs
Modeling studies of ruminant digestive function reported earlier indicated that understanding of interactions among rumen microbes and of nitrogen exchange between the ruminant animal and its digestive tract, is inadequate. A completed experiment led to identification of complementary catabolite repression mechanisms in five prominent rumen microbes. Knowledge of these - not previously observed in anaerobic microbes - led to redefinition of the ecological "niches" occupied by these microbes. Another experiment, still in progress, led to development of improved methods for determination of anaerobic microbe maintenance requirements, affinities for substrates and maximum fermentation and growth rates. Progress was made in experiments defining the nitrogen requirements of rumen microbes. Important problems whose solution is essential to understanding of differences among animals in productive efficiencies include determination of partial efficiencies of use of
different nutrients for maintenance and production and identification of regulatory mechanisms which determine patterns of nutrient utilization. A study of the regulation of ruminant adipose tissue metabolism during lactation indicated that lactation has only minor - other than via effects on energy balance - effects on lipogenesis while elevating lipolytic rates up to three-fold and depressing rates of fatty acid reesterification.
Impacts
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Publications
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Progress 01/01/76 to 12/30/76
Outputs
Significant progress toward development of computer simulation models of animal growth and function was achieved. During periods of growth, lactation, fattening and nutrient restriction, nutrient and maintenance requirements and metabolic capacities of individual tissues can change rapidly. To accommodate and enable full understanding of these variables in terms of animal performance,we continued our experimental studies of ruminant lipid metabolism and energeticefficiencies of growth, fattening and lactation and our computer simulation analyses of ruminant tissue metabolism. In addition, we constructed an interspecific model of animal growth which accounts for the weights and metabolic capacities of nine individual tissues and organ systems. In this model, agreement of simulated growth and experimental data is excellent. Effects of nutrient restrictions on organ sizes, compensatory growth and stunting were also simulated. In order for our models of animal growth
and metabolism to function adequately, a model of ruminant digestion which accurately predicts amounts of the several digestion products available to the animal is required. Excellent progress toward development of a model of ruminant digestion which will fulfill this need was achieved. During model validation, it was found that model outputs agree very well with experimental data on digestibility and products of digestion with the exception that digestibilities of very low quality forages were underestimated.
Impacts
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Publications
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Progress 01/01/75 to 12/30/75
Outputs
Consistent with the objectives of the project a number of computer simulation models of ruminant digestive, metabolic and energetic functions have been constructed. Particular emphasis has been directed towards models of rumen fermentation (e.g., ref. no. 1 and 2) in which the end products of rumen fermentation can be predicted consistent with known metabolic pathways and constrained by the requirement to maintain elemental and electronic balance. A more aggregated model of nitrogen metabolism in the grazing ruminant has been constructed (ref. no. 3). The role of insulin, adrenalectomy and cyclic AMP on rat mammary gland metabolism has been investigated and their hormonal actions ingeneral reviewed (ref. no. 4). A technique for estimating milk production in rats was also developed (ref. no. 5).
Impacts
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Publications
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Progress 01/01/74 to 12/30/74
Outputs
Ruminant (sheep) liver and mammary enzyme levels and metabolic functions are much less affected by adrenalectomy during lactation than is the case for rats. Rat energy requirements for maintenance in kcal metabolizable energy/kg body weight .>1 vary from 45-90 dependent upon food intake (apparent maintenance - 126.1(1+2.0eommDTae,; where x equals food intake in kcal ME/BW(kg).>1). These changes in maintenance requirement are attributable to changes in the relative weights of vital organs including liver, gastrointestinal tract and heart. A similar relationship appears to hold in cattle. In rats, the average efficiencyof body energy conversion is 83% while the net efficiency of food conversion to milk is 80%. In mammary tissue, cyclic AMP appears to inhibit milk synthesis. Insulin acts in an acute fashion to reduce mammary cAMP levels while glucocorticoids acting over a longer term increase mammary cAMP levels. Mixed amino acids increase rumen microbial (Y(ATP))
growth yields in vitro up to two-fold. Our modeling studies are proceeding nicely with major current emphasis being placed on development of methods for statistical estimation of parameters which cannot be measured directly in experiments and analyses of ruminant digestion.
Impacts
(N/A)
Publications
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Progress 01/01/73 to 12/30/73
Outputs
We have made significant progress in all areas of inquiry encompassed by this project. We have developed, updated and are currently validating detailed causal computer simulation models of the metabolisms of ruminant mammary adiposeand liver, of rumen function and ruminant nitrogen metabolism, of a reference ruminant and a lactating dairy cow and of a range production unit. The models incorporate much of our knowledge and concepts of these systems in a quantitative and dynamic format which eanbles evaluations of data and concepts and have been very useful in support of our experimental research activities. Our rumen research has been directed at development of means of determining microbial growth rates and yields. NPN/protein ration, pH, branched chain fattyacid and amino acid concentrations affect microbial growth yields. Several studies of the regulation of ruminant tissue metabolisms were completed including those indicating the role(s) of insulin, adipose
lipolysis and CAMP inthe metabolism(s) of lactating cows and the low milk fat syndrome.
Impacts
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Publications
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Progress 01/01/72 to 12/30/72
Outputs
A study of the lactational efficiency complex in rats resulted in observations that gross efficiency in rats is similar to that of cows; that the maintenance requirement of lactating rats is higher than that of nonlactating rats; and, that the increase in maintenance requirement is due to increases in the relativesizes of high energy expenditure tissues such as liver and to increases in circulating thyroxin in lactating animals. Detailed studies of cow adipose tissue metabolism yielded many relevant observations regarding fluxes through metabolic pathways, epinephrine and insulin actions, and effects of diet and physiological state. These advanced our understanding of ruminant metabolism and enabled further explanation of the low milk fat syndrome. Detailed studies of glucocorticoid actions upon rat mammary metabloism were completed and comparable studies with sheep and rabbits were initiated. The effects of chronic insulin administration upon lactational
performance in rats and cows were evaluated. Key observations increased milk production (up to 20%) in both species and a reversal (by insulin) of milk fat depression in cows induced by low fiber diets.
Impacts
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Publications
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Progress 01/01/71 to 12/30/71
Outputs
A systematic approach to the construction and use of computer simulation modeling techniques in support of studies of animal and tissue metabolism has been developed. Detailed models of ruminant digestion including lower digestivetract function and nitrogen metabolism and ruminant mammary and adipose tissue metabolism and general models of a ruminant of basal and of a lactating cow havebeen constructed and six manuscrips documenting these are in preparation. In their current state these models incorporate and conform to data reported in, literally, several thousand scientific papers and can be used to test and evaluate hypotheses, aid in the selection of critical experiments, compute probable consequences of various treatments, analyze tracer data and retrieve information. Detailed studies of effects of physiological state, diet and hormones in vivo and in vitro upon metabolic rates and patterns in rat and ruminant adipose, liver and mammary tissues. Seven
manuscripts relating these results have been submitted or are in press and an additional four are in preparation.
Impacts
(N/A)
Publications
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Progress 01/01/70 to 12/30/70
Outputs
Modeling: We have completed construction of detailed models of rumen function and ruminant mammary gland metabolism and general, simplified models of ruminantenergy metabolism at basal and of a lactating cow. The models are explicit, anddeterministic, contain 100-400 simultaneous differential equations and are beingwritten up for publication. Experimental: We are completing an extensive studyof patterns and rates of metabolite utilization by cow and rat mammary, adipose and liver tissues to be used in further analyses of relationships between tissuemetabolism and overall animal energy metabolism.
Impacts
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Progress 01/01/69 to 12/30/69
Outputs
This program which is directed at achieving a definitive, quantitative analysis of energy expenditures associated with specific cellular tissue and animal functions under a variety of nutritional and physiological conditions and identification and quantitative evaluation of intracellular, cellular tissue andanimal regulatory mechanisms is in its early stages of development. Methods of representing these various types of biochemical, metabolic, physiological, regulatory and animal energetic functions have been developed and applied in thedevelopment of computer simulation models for analysis of ruminant digestive processes and ruminant mammary gland metabolism. A whole animal energetic modelis currently under development.
Impacts
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Progress 01/01/68 to 12/30/68
Outputs
This project was completely revised in July, 1968 except that the investigator remained the same. There is nothing to report since the last progress report in1968 and the investigator has been on sabbatical leave.
Impacts
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Progress 01/01/67 to 12/30/67
Outputs
Progress during the past year has been restricted to the development of techniques for study of the kinetics of carbohydrate fermentation and turnover in the rumen and carbohydrate passage to the lower digestive tract.
Impacts
(N/A)
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