Progress 07/01/91 to 12/31/06
Outputs
The PI has left the university and we have been unable to obtain a final report.
Impacts
Collectively, these studies are expanding our knowledge of how nutrients are absorbed into the body, how nutrient requirements can be measured using molecular biology techniques, about the role of phytonutrients in protecting human health, and the role of nutrients in modulating signaling cascades involved in human health.
Publications
- No publications reported this period
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Progress 01/02/00 to 12/31/00
Outputs
Research conducted by members of the F21C Nutritional Sciences Cluster this past year has made significant contributions to how nutrition impacts health and disease. Using the yeast Saccharomyces cerevisiae as a model system for understanding these processes in mammals and plants, Dr. David Eide has identified an entire new family of metal transport proteins that are found in humans as well as yeast, plants, animals and bacteria. Using identified yeast genes, this group has now identified the first human zinc uptake transporters, which are likely to be the key transporters for zinc absorption in humans and animals. Dr. Roger Sunde's group has recently extended their approach to studying the selenium requirements in portions of the life-cycle that are less easily evaluated. Using the molecular thermostat approach, they have found that the selenium requirement in rats does not increase during pregnancy and lactation. Dr. Sunde's group has cloned several avian
glutathione peroxidase genes and is developing molecular biology methods to uses these clones to help evaluate the turkey selenium requirement. Dr. David Ledoux in the Department of Animal Sciences has conducted several studies to evaluate the selenium requirement of the turkey when grown with practical rations under conditions similar to the production industry. They have found that the selenium requirement is clearly higher than for other species but that it may not be as high as the current National Research Requirement. Dr. Ruth MacDonald is studying the role of genistein and daidzein, two of the phytonutrients found in soy. These compounds may provide protection against colon cancer. Using estrogen receptor-knock out mice in collaboration with Dr. Dennis Lubahn, they are investigating the effects of genistein on tumor development. Nucleotide receptors (P2 receptors) are present in nearly all cells and tissues where they mediate diverse functions including the regulation of
platelet aggregation, muscle contraction, neurotransmission, insulin secretion, epithelial ion transport, wound healing and cell growth. Dr. Weisman and colleagues isolated the first human P2 receptor gene and expressed it in mammalian cell lines that normally lack this receptor. Current research is directed towards investigating structural features of the receptor that affect its functions. They have cloned or obtained 11 different P2 receptor subtypes belonging to 2 different receptor superfamilies and are investigating the mechanisms of receptor activation, desensitization, and signal transduction in a variety of tissues. Other research is determining the molecular mechanisms whereby activation of P2 receptors can be employed for the treatment of human disease.
Impacts
Collectively, these studies are expanding our knowledge of how nutrients are absorbed into the body, how nutrient requirements can be measured using molecular biology techniques, about the role of phytonutrients in protecting human health, and the role of nutrients in modulating signaling cascades involved in human health.
Publications
- No publications reported this period
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Progress 01/01/99 to 12/31/99
Outputs
Research conducted by members of the F21C Nutritional Sciences Cluster this past year has made significant contributions to how nutrition impacts health and disease. In the Molecular Mineral Nutrition emphasis area, studies to understand zinc homeostasis have identified a human Zinc intake transporter and have begun to use microarray technology to understand the impact of Zinc status on Zinc-regulated genes in yeast. Ongoing studies to establish molecular mechanisms and molecular indicators of Selenium status are focusing on regulation of thioredoxin reductase as well as selenoperoxidases by dietary Selenium and have found that restoration of thioredoxin reductase activity is associated with growth restoration in rats. Continuing studies on the biochemical defect in zinc deficiency have found that stretch-activated calcium channels may be involved in the increased hemolysis in Zinc-deficiency. In the Lipids, Membranes and Signal Transduction emphasis area, studies
investigating the health-promoting benefits of fish oils have found that fish oil impairs IL-12 production in mice when fed at low doses and in the context of a low fat diet. Studies on P2Y2 nucleotide receptor activation by ATP have identified proline-rich regions in the C-terminal domain that mediate activation of the downstream MAP kinase cascade, and have also shown that ERK phosphorylation subsequent to receptor activation may be involved in transactivation of the epidermal growth factor receptor. In addition, eight undergraduate research projects were supervised by Nutritional Sciences researchers to conduct pilot studies in their areas of expertise and to attract the best students to careers in agricultural life sciences.
Impacts
Collectively, these studies are expanding our understanding of the nature of nutrient regulation of gene expression, increase our understanding of the role of nutrients in modulating signaling cascades involved in health and immune function, and are revealing the nature of the molecular processes used to regulate nutrient homeostasis.
Publications
- No publications reported this period
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Progress 01/01/98 to 12/31/98
Outputs
Research conducted by members of the F21C Nutritional Sciences Cluster this past year has made significant contributions to how nutrition impacts health and disease. In the Molecular Mineral Nutrition emphasis area, studies to understand zinc homeostasis have focused on transcriptional regulation of zinc uptake in yeast and characterized a zinc-responsive domain in the transcriptional activator ZAP1 and have identified two potential human metal ion transporters. Ongoing studies to establish molecular mechanisms and molecular indicators of selenium status are focusing on regulation of selenoperoxidases by dietary selenium and have used the GPX1 knockout mouse to show that GPX1 functions as a selenium buffer and that GPX4 is present in erythrocytes. Continuing studies on the biochemical defect in zinc deficiency have found that the decreased feed intake in zinc deficient rats may be caused by decreased response to neuropeptide Y. In the Lipids, Membranes and Signal
Transduction emphasis area, studies investigating the health-promoting benefits of fish oils have found that omega-3 unsaturated fatty acids lower interleukin-12 and interferon-gamma production in listeriosis, studies to better understand the impact of cholesterol on health have found that increased acyl coA:cholesterol acyl transferase expression raises the set-point for neutral lipid concentrations in HepG2 cells. Lastly, studies on use of the P2Y2 receptor activation by ATP, a potential treatment for cystic fibrosis patients, have targeted protein kinase C as a potential mediator of desensitization. In addition, ten undergraduate research projects were supervised by Nutritional Sciences researchers to conduct pilot studies in their areas of expertise and to attract the best students to careers in agricultural life sciences.
Impacts
(N/A)
Publications
- No publications reported this period
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Progress 01/01/97 to 12/31/97
Outputs
Research conducted by members of the F21C Nutritional Sciences Cluster this past year has made significant contributions to how nutrition impacts health and disease. In the Molecular Mineral Nutrition emphasis area, the publication in 1997 of "Handbook of Nutritionally Essential Mineral Elements," edited by Drs. O'Dell and Sunde, shows the national recognition of MU in this area. Ongoing studies on the regulation of selenoperoxidases by dietary selenium initiated studies on the cloning of glutathione peroxidases from turkey liver. Studies on transcriptional regulation of zinc uptake in yeast are finding candidate zinc-responsive genes. Continuing studies on the biochemical defect in zinc deficiency looked at the morphology and IGF receptor expression in small intestine and hypothalamus of rats following short-term zinc depletion. In the Lipids, Membranes and Signal Transduction emphasis area, evidence was obtained that apolipoprotein B100 is made in a diverse sampling
of nonhepatic cell lines. Studies on IGF function revealed that tyrosine phosphorylation of the IGF-1 receptor is affected by fatty acid incubation in cells transfected with an IGF-1 receptor promoter. Mechanisms of P2Y2 nucleotide receptor desensitization were studied to better understand the implication for cystic fibrosis pharmacotherapy. Lastly, nutritional Sciences researchers found that fish oil consumption leads to a 50% reduction in interferon- receptors in murine immune cells.
Impacts
(N/A)
Publications
- SUNDE, R.A. 1997. Selenium. In: Handbook of Nutritionally Essential Mineral Elements (O'Dell, B.L., and Sunde, R.A., eds.), Marcel Dekker, Inc., New York, pp. 493-556.
- O'DELL, B.L. AND SUNDE, R.A. 1997. Introduction to essential mineral elements. In: Handbook of Nutritionally Essential Mineral Elements (O'Dell, B.L., and Sunde, R.A., eds.), Marcel Dekker, Inc., New York,
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Progress 01/01/96 to 12/30/96
Outputs
Research conducted by members of the F21C Nutrition Cluster this past year has made significant contributions to how nutrition impacts health and disease. In the Molecular Mineral Nutrition emphasis area, recombinant constructs of glutathione peroxidase in cultured cells now allows insertion of selenocysteine throughout the middle region of the open reading frame, helping us understand selenium incorporation into proteins. Ongoing studies in turkeys indicate that the selenium requirement is in the 0.17 to 0.3 mg Se/kg diet range, and that phospholipid hydroperoxide glutathione peroxidase is highly regulated in the turkey. Studies investigating the role of zinc found that IGF-1 binding in rat midbrain is unresponsive to zinc or feed intake whereas low feed intake decreases IGF-1 binding in psoas of brain. In the Lipids, Membranes and Signal Transduction area, studies investigating the role of dietary fish oil in the immune response have identified interferon-gamma
receptor down-regulation as a potential mechanism for the observed effects. Use of recombinant mutations of nucleotide receptors has shown that carboxy-terminal truncation lead use of these nucleotides in the treatment of cystic fibrosis. Studies on regulation of cholesterol metabolism via alterations in apolipoprotein B secretion indicate that the impact of unsaturated versus saturated fatty acids on apolipoprotein B secretion may be due to differences in transport.
Impacts
(N/A)
Publications
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Progress 01/01/95 to 12/30/95
Outputs
Research conducted by members of the F21C Nutrition Cluster this past year has made significant contributions to how nutrition impacts health and disease. In the Nutritional Biochemistry of Minerals emphasis area, ongoing studies on the regulation of selenoperoxidases by dietary selenium using recombinant constructs in cultured cells have further defined the mechanism used to regulate glutathione peroxidase mRNA levels, and new studies in avian species indicate that selenoperoxidase regulation may be different as compared to mammalian species. In studies investigating the role of zinc in cell division, the relationship between zinc, IGF-I and cell proliferation is helping to unravel why zinc deficiency leads to altered cell function. In the Lipids, Membranes and Signal Transduction area, a novel nucleotide receptor cDNA was expressed in a null cell line and identified as a uridine nucleotide receptor, and these receptors are being evaluated in efficacy of treatment in
cystic fibrosis treatment. In the area of regulation of cholesterol, a novel drug is being used in studies investigating cholesterol metabolism in liver cells, and studies in control and diabetic pigs are investigating the effect of diabetes on LDL particle size.
Impacts
(N/A)
Publications
- NO PUBLICATIONS REPORTED THIS PERIOD.
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Progress 01/01/94 to 12/30/94
Outputs
Research conducted by members of the Nutrition Cluster this past year has made significant contributions to our understanding of how nutrition impacts health and disease. In the Nutritional Biochemistry of Minerals emphasis area, (superscript 47)Ca was used to evaluate the impact of hormonal profile on bone mineralization in pre-natal and post-natal piglets as a model for neonatal bone mineralization. Research on the essential role of zinc demonstrated that IGF-1 binding and thymidine incorporation were correlated in Zn-deficient cultured cells. Studies with a recently cloned second glutathione peroxidase have shown that selenium status differentially regulates two peroxidases in the same tissues, suggesting distinct roles in protection against peroxidation. In the Lipids, Membranes and Signal Transduction emphasis area, researchers have further elucidated the mechanism whereby dietary fat regulates hepatic cholesterol synthesis and secretion with the demonstration
that unique protease inhibitors alter apoB degradation. In studies with implications on the treatment of cystic fibrosis, ATP receptors from two species have now been cloned, and site-directed mutagenesis is being used to characterize the structure of the receptor. On-going studies on the impact of dietary unsaturated fatty acids on immune response are showing that diets high in polyunsaturated fats, either from fish oil or corn oil, reduce the resistance of mice to bacterial challenge.
Impacts
(N/A)
Publications
- No publications reported this period.
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Progress 01/01/93 to 12/30/93
Outputs
Research conducted by members of the Nutrition Cluster this past year has made significant contributions to our understanding of how nutrition impacts health and disease. In the Nutritional Biochemistry of Minerals emphasis area, studies with neonatal pigs have investigated the role of a newly discovered PTH-like peptide in milk on calcium and phosphorus homeostasis. Research studies on the essential role of zinc have identified impaired calcium transport as a potential primary defect associated with zinc deficiency. Selenium's role in protection against oxidant damage was expanded with the cloning of a full-length second intracellular glutathione peroxidase and with the completion of studies using molecular biology techniques to evaluate dietary selenium requirements. In the Lipids, Membranes and Signal Transduction emphasis area, researchers have cloned the gene for a human ATP receptor that may provide insight into treatment of cystic fibrosis. A better
understanding of cholesterol homeostasis is emerging with novel studies on regulation of apolipoprotein B secretion by nutritional status. Several research groups are studying the interaction of vitamin E status with lipid metabolism and cholesterol oxidation in order to better understand the role of these nutrients in health and disease.
Impacts
(N/A)
Publications
- No publications reported this period.
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