Colonic Cytokinetics and Cell Signaling: Dietary Effects

Summary

Principal Investigator: ROBERT STEPHEN CHAPKIN
Abstract: DESCRIPTION (provided by applicant): There are cogent data indicating a protective effect of n-3 polyunsaturated fatty acids (PUFA) e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on colon cancer. In contrast, dietary lipids rich in n-6 PUFA, e.g., linoleic acid (LA) and arachidonic acid (AA), enhance the development of colon tumors. This is significant because the typical Western diet contains 10 to 20 times more n-6 than n-3 PUFA. Unfortunately, to date, a unifying mechanistic hypothesis addressing why n-3 PUFA selectively suppress colon cancer compared to n-6 PUFA (the major dietary form of PUFA in the U.S. diet) is lacking. In the current funding period, we demonstrated that (i) dietary n-3 PUFA induce perturbations in colonocyte membrane microdomain (caveolae) lipid composition, suppressing oncogenic signaling and Ras protein trafficking;(ii) n-3 PUFA supplant arachidonic acid (AA) in colonocyte membrane phospholipids, with EPA in particular being metabolized into a novel 3-series E-prostaglandin (PGE3), a putative antitumorigenic-cyclooxygenase (COX) metabolite;and (iii) the proapoptotic- chemoprotective effect of n-3 PUFA is enhanced when a highly fermentable fiber, pectin (or its fermentation product-butyrate) is added to the diet. We postulate that the failure to address an interaction between dietary fat and fiber may explain why the chemoprotective effects of fiber are obscured in prospective cohort studies. Therefore, the overall goal of this proposal is to further elucidate how dietary n-3 PUFA and fermentable fiber up-regulate apoptosis effector mechanisms in colonocytes, thereby reducing colon cancer risk. An array of experimental models will be used, including in vivo (azoxymethane-injected oxidatively stressed SOD2+/-, Gpx4+/- knock outs, Gpx4Tg and fat-1 transgenic mouse models) and in vitro (normal and malignant transformed mouse and human colonocyte cell lines) in order to test our primary hypothesis that n-3 PUFA and butyrate work in a coordinated manner to potentiate mitochondrial-mediated apoptosis. As a complementary hypothesis, we propose that DHA and possibly EPA alter colonocyte membrane lipid microdomain composition, thereby favorably modulating eicosanoid metabolism and the relay of extracellular signals from surface receptors to downstream signaling networks. The following specific aims are proposed: Aim #1 will determine the mechanisms by which n-3 PUFA and butyrate interaction modulate intrinsic (mitochondria-mediated) cell death signaling in the colon;Aim #2 will determine the mechanisms by which n-3 PUFA alter the spatio-temporal segregation of Ras-dependent signals;and Aim #3 will characterize the putative chemoprotective properties of a novel EPA-derived cyclooxygenase product, PGE3. The consumption of EPA and DHA may prove an effective adjuvant therapy in colon cancer. Therefore, it is both appropriate and timely to determine precisely how n-3 PUFA modulate cell signaling networks and reduce colon cancer risk.A growing body of literature supports the contention that bioactive food components containing n-3 polyunsaturated fatty acids (PUFA) are important in suppressing colon cancer. Consistent with the objectives and scope of PA-07-100, Prioritizing molecular targets for cancer prevention with nutritional combinations , the overall goal of this proposal is to elucidate how dietary n-3 PUFA and fermentable fiber up-regulate apoptosis effector mechanisms in colonocytes, thereby reducing colon cancer risk.
Funding Period: -----------------199 - ----------------2013
more information: NIH RePORT

Top Publications

  1. ncbi Docosahexaenoic acid selectively inhibits plasma membrane targeting of lipidated proteins
    Jeongmin Seo
    Department of Nutrition and Food Science, Chemistry, and Biochemistry and Biophysics, Texas A and M University, College Station, Texas 77843 2253, USA
    FASEB J 20:770-2. 2006
  2. pmc Inhibitory effects of omega-3 fatty acids on injury-induced epidermal growth factor receptor transactivation contribute to delayed wound healing
    Harmony F Turk
    Program in Integrative Nutrition and Complex Diseases, Texas A and M University, College Station, TX 77843, USA
    Am J Physiol Cell Physiol 304:C905-17. 2013
  3. pmc Alteration of EGFR spatiotemporal dynamics suppresses signal transduction
    Harmony F Turk
    Program in Integrative Nutrition and Complex Diseases, Texas A and M University, College Station, Texas, United States of America
    PLoS ONE 7:e39682. 2012
  4. pmc A chemoprotective fish oil/pectin diet enhances apoptosis via Bcl-2 promoter methylation in rat azoxymethane-induced carcinomas
    Youngmi Cho
    Faculty of Nutrition, Texas A and M University, College Station, TX 77843, USA
    Exp Biol Med (Maywood) 237:1387-93. 2012
  5. pmc fat-1 transgene expression prevents cell culture-induced loss of membrane n-3 fatty acids in activated CD4+ T-cells
    Yang Yi Fan
    Department of Nutrition and Food Science, Texas A and M University, College Station, TX 77843 2253, USA
    Prostaglandins Leukot Essent Fatty Acids 79:209-14. 2008
  6. pmc n-3 polyunsaturated fatty acids suppress the localization and activation of signaling proteins at the immunological synapse in murine CD4+ T cells by affecting lipid raft formation
    Wooki Kim
    Faculty of Nutrition, Texas A and M University, College Station, TX 77843, USA
    J Immunol 181:6236-43. 2008
  7. pmc Upregulation of p21Waf1/Cip1 expression in vivo by butyrate administration can be chemoprotective or chemopromotive depending on the lipid component of the diet
    Kristy Covert Crim
    Faculty of Nutrition, Texas A and M University, College Station, TX 77843 2253, USA
    Carcinogenesis 29:1415-20. 2008
  8. pmc Bioactive dietary long-chain fatty acids: emerging mechanisms of action
    Robert S Chapkin
    Faculty of Nutrition, Texas A and M University, College Station, TX, USA
    Br J Nutr 100:1152-7. 2008
  9. pmc Reduced colitis-associated colon cancer in Fat-1 (n-3 fatty acid desaturase) transgenic mice
    Qian Jia
    Department of Nutrition and Food Science, Intercollegiate Faculty of Nutrition, Texas A and M University, Houston, USA
    Cancer Res 68:3985-91. 2008
  10. pmc Mechanisms by which docosahexaenoic acid and related fatty acids reduce colon cancer risk and inflammatory disorders of the intestine
    Robert S Chapkin
    Center for Environmental and Rural Health, Texas A and M University, College Station, TX 77843 2553, United States
    Chem Phys Lipids 153:14-23. 2008

Scientific Experts

  • ROBERT STEPHEN CHAPKIN
  • Valerian Kagan
  • Priyanka Kachroo
  • David N McMurray
  • Nysia I George
  • Joanne R Lupton
  • Yang Yi Fan
  • Wooki Kim
  • Harmony F Turk
  • Laurie A Davidson
  • Rola Barhoumi
  • Evelyn S Callaway
  • Ivan Ivanov
  • Qian Jia
  • Jennifer M Monk
  • Evelyn Callaway
  • Naisyin Wang
  • Satya Sree N Kolar
  • Manasvi S Shah
  • Chen Zhao
  • Nancy D Turner
  • Lan Zhou
  • Brad R Weeks
  • Roger Smith
  • Brad Weeks
  • Tim Y Hou
  • Meagan A Saldua
  • Youngmi Cho
  • Robert C Alaniz
  • Satya Kolar
  • Shinya Toyokuni
  • Raymond J Carroll
  • Tatiyana V Apanasovich
  • Kristy Covert Crim
  • J Vanamala
  • Jeongmin Seo
  • Gonzalo M Rivera
  • Cory A Olsovsky
  • Yong Q Chen
  • Kristen C Maitland
  • Jeffrey M Peters
  • Weimin He
  • Jennifer E Foreman
  • Jennifer S Goldsby
  • Beiyan Zhou
  • Scott L Schwartz
  • Satya S Kolar
  • Caitlin A Cozby
  • Qitao Ran
  • Chris K Jones
  • Zlatomir Z Zlatev
  • Joshua Wesley
  • Yasumasa Okazaki
  • Naim A Khan
  • Ian A Prior
  • David W L Ma
  • Nancy H Colburn
  • Edward R Dougherty
  • Terryl J Hartman
  • Gerd Bobe
  • Yang Zhan
  • Jennifer Goldsby
  • Harold M Aukema
  • Elaine Lanza
  • Yanan Tian
  • M E Murphy
  • Robert A Newman
  • P Yang
  • Lisa M Sanders
  • N D Turner
  • J R Ford
  • R A Newman
  • David Ruppert
  • L A Braby
  • Jing X Kang
  • Peiying Yang
  • R J Carroll
  • Mee Young Hong
  • Stella S Taddeo
  • J R Lupton
  • A Glagolenko
  • Natasa Popovic
  • Arthur E Johnson

Detail Information

Publications41

  1. ncbi Docosahexaenoic acid selectively inhibits plasma membrane targeting of lipidated proteins
    Jeongmin Seo
    Department of Nutrition and Food Science, Chemistry, and Biochemistry and Biophysics, Texas A and M University, College Station, Texas 77843 2253, USA
    FASEB J 20:770-2. 2006
    ....
  2. pmc Inhibitory effects of omega-3 fatty acids on injury-induced epidermal growth factor receptor transactivation contribute to delayed wound healing
    Harmony F Turk
    Program in Integrative Nutrition and Complex Diseases, Texas A and M University, College Station, TX 77843, USA
    Am J Physiol Cell Physiol 304:C905-17. 2013
    ..This effect is mediated, at least in part, via suppression of EGFR-mediated signaling and downstream cytoskeletal remodeling...
  3. pmc Alteration of EGFR spatiotemporal dynamics suppresses signal transduction
    Harmony F Turk
    Program in Integrative Nutrition and Complex Diseases, Texas A and M University, College Station, Texas, United States of America
    PLoS ONE 7:e39682. 2012
    ....
  4. pmc A chemoprotective fish oil/pectin diet enhances apoptosis via Bcl-2 promoter methylation in rat azoxymethane-induced carcinomas
    Youngmi Cho
    Faculty of Nutrition, Texas A and M University, College Station, TX 77843, USA
    Exp Biol Med (Maywood) 237:1387-93. 2012
    ..These Bcl-2 promoter methylation responses, measured in vivo, contribute to our understanding of the mechanisms involved in chemoprevention of colon cancer by diets containing FO/P...
  5. pmc fat-1 transgene expression prevents cell culture-induced loss of membrane n-3 fatty acids in activated CD4+ T-cells
    Yang Yi Fan
    Department of Nutrition and Food Science, Texas A and M University, College Station, TX 77843 2253, USA
    Prostaglandins Leukot Essent Fatty Acids 79:209-14. 2008
    ..05) number of cell divisions. We conclude that fat-1-containing CD4+ T-cells express a physiologically relevant, n-3 PUFA enriched, membrane fatty acid composition which is resistant to conventional cell culture-induced depletion...
  6. pmc n-3 polyunsaturated fatty acids suppress the localization and activation of signaling proteins at the immunological synapse in murine CD4+ T cells by affecting lipid raft formation
    Wooki Kim
    Faculty of Nutrition, Texas A and M University, College Station, TX 77843, USA
    J Immunol 181:6236-43. 2008
    ..These data imply that lipid rafts may be targets for the development of dietary agents for the treatment of autoimmune and chronic inflammatory diseases...
  7. pmc Upregulation of p21Waf1/Cip1 expression in vivo by butyrate administration can be chemoprotective or chemopromotive depending on the lipid component of the diet
    Kristy Covert Crim
    Faculty of Nutrition, Texas A and M University, College Station, TX 77843 2253, USA
    Carcinogenesis 29:1415-20. 2008
    ....
  8. pmc Bioactive dietary long-chain fatty acids: emerging mechanisms of action
    Robert S Chapkin
    Faculty of Nutrition, Texas A and M University, College Station, TX, USA
    Br J Nutr 100:1152-7. 2008
    ....
  9. pmc Reduced colitis-associated colon cancer in Fat-1 (n-3 fatty acid desaturase) transgenic mice
    Qian Jia
    Department of Nutrition and Food Science, Intercollegiate Faculty of Nutrition, Texas A and M University, Houston, USA
    Cancer Res 68:3985-91. 2008
    ..05) CD3(+), CD4(+) T helper, and macrophage cell numbers per colon as compared with wt mice. These results suggest that the antitumorigenic effect of n-3 PUFA may be mediated, in part, via its anti-inflammatory properties...
  10. pmc Mechanisms by which docosahexaenoic acid and related fatty acids reduce colon cancer risk and inflammatory disorders of the intestine
    Robert S Chapkin
    Center for Environmental and Rural Health, Texas A and M University, College Station, TX 77843 2553, United States
    Chem Phys Lipids 153:14-23. 2008
    ..Ultimately, this may allow organ systems such as the colon to optimally decode, respond, and adapt to the vagaries of an ever-changing extracellular environment...
  11. ncbi Colon cancer, fatty acids and anti-inflammatory compounds
    Robert S Chapkin
    Faculty of Nutrition, Texas A and M University System Health Science Center, College Station, Texas 77843, USA
    Curr Opin Gastroenterol 23:48-54. 2007
    ..To outline recent findings on the efficacy of n-3 polyunsaturated fatty acids in the prevention/treatment of inflammatory bowel disease and colorectal cancer...
  12. ncbi Immunomodulatory effects of (n-3) fatty acids: putative link to inflammation and colon cancer
    Robert S Chapkin
    Faculty of Nutrition, Center for Environmental and Rural Health, Texas A and M University, College Station, TX 77843, USA
    J Nutr 137:200S-204S. 2007
    ..Precisely how the immunomodulatory effects of (n-3) PUFAs influence inflammation-associated colonic tumor development is the subject of an ongoing investigation...
  13. ncbi Docosahexaenoic acid and butyrate synergistically induce colonocyte apoptosis by enhancing mitochondrial Ca2+ accumulation
    Satya Sree N Kolar
    Faculty of Nutrition, Texas A and M University, College Station, Texas 77843 2253, USA
    Cancer Res 67:5561-8. 2007
    ..Collectively, these data show that the combination of DHA and butyrate, compared with butyrate alone, further enhances apoptosis by additionally recruiting a Ca2+ -mediated intrinsic mitochondrial pathway...
  14. ncbi Synergy between docosahexaenoic acid and butyrate elicits p53-independent apoptosis via mitochondrial Ca(2+) accumulation in colonocytes
    Satya Sree N Kolar
    Department of Nutrition and Food Science, Kleberg Biotechnology Center, MS 2253, Texas A and M University, College Station, TX 77843 2253, USA
    Am J Physiol Gastrointest Liver Physiol 293:G935-43. 2007
    ....
  15. pmc Aberrant crypt foci and semiparametric modeling of correlated binary data
    Tatiyana V Apanasovich
    School of Operations Research and Industrial Engineering, Cornell University, Ithaca, New York 14853, USA
    Biometrics 64:490-500. 2008
    ..Finally, we apply the methods to the data from our experiment ACF. We discover an unexpected location for peak formation of ACF...
  16. pmc Dietary fish oil and pectin enhance colonocyte apoptosis in part through suppression of PPARdelta/PGE2 and elevation of PGE3
    J Vanamala
    Faculty of Nutrition, Texas A and M University, College Station, TX 77843, USA
    Carcinogenesis 29:790-6. 2008
    ..These data suggest that the dietary FP combination may be used as a possible countermeasure to colon carcinogenesis, as apoptosis is enhanced even when colonocytes are exposed to radiation and/or an alkylating agent...
  17. pmc Docosahexaenoic acid alters the size and distribution of cell surface microdomains
    Robert S Chapkin
    Center for Environmental and Rural Health, Texas A and M University, College Station, Texas, USA
    Biochim Biophys Acta 1778:466-71. 2008
    ..We speculate that our findings may help define a new paradigm to better understand the complexity of n-3 PUFA modulation of signaling networks...
  18. pmc Integrated microRNA and mRNA expression profiling in a rat colon carcinogenesis model: effect of a chemo-protective diet
    Manasvi S Shah
    Program in Integrative Nutrition and Complex Diseases, Texas A and M University, College Station, TX, USA
    Physiol Genomics 43:640-54. 2011
    ..Complementary gene expression analyses showed that oncogenic PTK2B, PDE4B, and TCF4 were suppressed by the chemoprotective diet at both the mRNA and protein levels...
  19. pmc Dietary fish oil promotes colonic apoptosis and mitochondrial proton leak in oxidatively stressed mice
    Yang Yi Fan
    Program in Integrative Nutrition and Complex Diseases, Texas A and M University, College Station, TX, USA
    Cancer Prev Res (Phila) 4:1267-74. 2011
    ....
  20. pmc Interactive effects of fatty acid and butyrate-induced mitochondrial Ca²⁺ loading and apoptosis in colonocytes
    Satya Kolar
    Program in Integrative Nutrition and Complex Diseases, Texas A and M University, College Station, Texas, USA
    Cancer 117:5294-303. 2011
    ....
  21. pmc n-3 Fatty acids uniquely affect anti-microbial resistance and immune cell plasma membrane organization
    David N McMurray
    Department of Microbial and Molecular Pathogenesis, Texas A and M Health Science Center, College Station, TX 77843 1313, USA
    Chem Phys Lipids 164:626-35. 2011
    ..We conclude that the outcomes of n-3 PUFA-mediated immune cell alterations may be beneficial (e.g., anti-inflammatory) or detrimental (e.g., loss of microbial immunity) depending upon the cell type interrogated...
  22. pmc Immunomodulatory action of dietary fish oil and targeted deletion of intestinal epithelial cell PPARδ in inflammation-induced colon carcinogenesis
    Jennifer M Monk
    Program in Integrative Nutrition and Complex Diseases, Texas A and M University, College Station, Texas 77843 2253, USA
    Am J Physiol Gastrointest Liver Physiol 302:G153-67. 2012
    ..Moreover, we provide new evidence that dietary n-3 PUFAs attenuate intestinal inflammation in an intestinal epithelial cell PPARδ-independent manner...
  23. pmc n-3 polyunsaturated fatty acids suppress phosphatidylinositol 4,5-bisphosphate-dependent actin remodelling during CD4+ T-cell activation
    Tim Y Hou
    Department of Biochemistry and Biophysics, Texas A and M University, College Station, Texas, USA
    Biochem J 443:27-37. 2012
    ..Collectively, these data demonstrate that n-3 PUFA, such as DHA, alter PtdIns(4,5)P2 in CD4+ T-cells, thereby suppressing the recruitment of WASP to the immunological synapse, and impairing actin remodelling in CD4+ T-cells...
  24. pmc Imaging inflammation in mouse colon using a rapid stage-scanning confocal fluorescence microscope
    Meagan A Saldua
    Texas A and M University, Department of Biomedical Engineering, 3120 TAMU, College Station, Texas, 77843 3120, USA
    J Biomed Opt 17:016006. 2012
    ..In contrast to the uniform size, shape, and distribution of colon crypts in confocal images of normal colon, confocal images of chronic bowel inflammation exhibit heterogeneous tissue structure with localized severe crypt distortion...
  25. pmc Membrane lipid raft organization is uniquely modified by n-3 polyunsaturated fatty acids
    Harmony F Turk
    Program in Integrative Nutrition and Complex Diseases and the Center for Environmental and Rural Health, Texas A and M University, College Station, TX 77843, USA
    Prostaglandins Leukot Essent Fatty Acids 88:43-7. 2013
    ..We conclude that these studies provide strong evidence for a predominant mechanism by which n-3 PUFA function in colon cancer prevention...
  26. pmc Classification of diet-modulated gene signatures at the colon cancer initiation and progression stages
    Priyanka Kachroo
    Department of Veterinary Integrative Biosciences, Texas A and M University, College Station, TX 77843 4458, USA
    Dig Dis Sci 56:2595-604. 2011
    ..n-3 PUFAs have received the most attention due to their potential protective role. However, further investigation of the epigenetic perturbations caused by fatty acids in the context of colon cancer development is needed...
  27. ncbi Dietary fish oil and curcumin combine to modulate colonic cytokinetics and gene expression in dextran sodium sulphate-treated mice
    Qian Jia
    Program in Integrative Nutrition and Complex Diseases, Texas A and M University, College Station, TX, USA
    Br J Nutr 106:519-29. 2011
    ..These results suggest that dietary lipids and curcumin interact to regulate mucosal homeostasis and the resolution of chronic inflammation in the colon...
  28. pmc Linoleic acid and butyrate synergize to increase Bcl-2 levels in colonocytes
    Harmony F Turk
    Program in Integrative Nutrition and Complex Diseases, Texas A and M University, College Station, TX, USA
    Int J Cancer 128:63-71. 2011
    ..In comparison, overexpression of bcl-2 blocked the proapoptotic effect of DHA and butyrate. These data provide new mechanistic insights into the regulation of apoptosis by dietary PUFA and fiber...
  29. pmc Noninvasive stool-based detection of infant gastrointestinal development using gene expression profiles from exfoliated epithelial cells
    Robert S Chapkin
    Texas A and M Univ, College Station, TX 77843 2253, USA
    Am J Physiol Gastrointest Liver Physiol 298:G582-9. 2010
    ..As larger data sets become available, this methodology can be extended to validation and, ultimately, identification of the main nutritional components that modulate intestinal maturation and function...
  30. pmc Mitochondria-targeted disruptors and inhibitors of cytochrome c/cardiolipin peroxidase complexes: a new strategy in anti-apoptotic drug discovery
    Valerian E Kagan
    Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA 15219 3130, USA
    Mol Nutr Food Res 53:104-14. 2009
    ..Therefore, mitochondria-targeted disruptors and inhibitors of cyt c/CL peroxidase complexes and suppression of CL peroxidation represent new strategies in anti-apoptotic drug discovery...
  31. pmc Proapoptotic effects of dietary (n-3) fatty acids are enhanced in colonocytes of manganese-dependent superoxide dismutase knockout mice
    Yang Yi Fan
    Program in Integrative Nutrition and Complex Diseases, Center for Environmental and Rural Health, Texas A and M University, College Station, TX 77843, USA
    J Nutr 139:1328-32. 2009
    ..Thus, (n-3) PUFA appear to promote an oxidation-reduction imbalance in the intestine, which may directly or indirectly trigger apoptosis and thereby reduce colon cancer risk...
  32. pmc Noninvasive detection of candidate molecular biomarkers in subjects with a history of insulin resistance and colorectal adenomas
    Chen Zhao
    Department of Electrical Engineering, Texas A and M University, College Station, Texas 77843 2253, USA
    Cancer Prev Res (Phila) 2:590-7. 2009
    ..These results support our premise that gene products (RNA) isolated from stool have diagnostic value in terms of assessing colon cancer risk...
  33. pmc Dietary docosahexaenoic and eicosapentaenoic acid: emerging mediators of inflammation
    Robert S Chapkin
    Department of Nutrition and Food Science, Faculty of Nutrition, Kleberg Biotechnology Center, MS 2253, Texas A and M University, College Station, TX 77843 2253, USA
    Prostaglandins Leukot Essent Fatty Acids 81:187-91. 2009
    ..We propose that lipid rafts may be targets for the development of n-3 PUFA-containing dietary bioactive agents to down-modulate inflammatory and immune responses and for the treatment of autoimmune and chronic inflammatory diseases...
  34. pmc A novel role for nutrition in the alteration of functional microdomains on the cell surface
    Wooki Kim
    Department of Nutritional Sciences, University of Toronto Faculty of Medicine, Toronto, ON, Canada
    Methods Mol Biol 579:261-70. 2009
    ..In addition, methods used to visualize and quantify lipid rafts using a fluorescent probe Laurdan in living cells will also be described...
  35. pmc n-3 Polyunsaturated fatty acids modulate carcinogen-directed non-coding microRNA signatures in rat colon
    Laurie A Davidson
    Program in Integrative Nutrition and Complex Diseases, Texas A and M University, College Station, TX 77843 2253, USA
    Carcinogenesis 30:2077-84. 2009
    ..32-fold) in adenocarcinomas. These results demonstrate for the first time the utility of the rat AOM model and the novel role of fish oil in protecting the colon from carcinogen-induced miRNA dysregulation...
  36. pmc Identification of actively translated mRNA transcripts in a rat model of early-stage colon carcinogenesis
    Laurie A Davidson
    Program in Integrative Nutrition and Complex Diseases, Texas A and M University, College Station, Texas 77843 2253, USA
    Cancer Prev Res (Phila) 2:984-94. 2009
    ..Therefore, during early stage colonic neoplasia, diet and carcinogen seem to predominantly regulate gene expression at multiple levels via unique mechanisms...
  37. pmc Evaluation of fecal mRNA reproducibility via a marginal transformed mixture modeling approach
    Nysia I George
    Department of Statistics, University of Michigan, Ann Arbor, MI 48109 1107, USA
    BMC Bioinformatics 11:13. 2010
    ..We used outcomes from bootstrapped goodness-of-fit tests to determine which approach is less sensitive toward potential violation of distributional assumptions...
  38. pmc Regulatory activity of polyunsaturated fatty acids in T-cell signaling
    Wooki Kim
    Program in Integrative Nutrition and Complex Diseases, Center for Environmental and Rural Health, Texas A and M University, USA
    Prog Lipid Res 49:250-61. 2010
    ..Advantages and limitations of diverse methodologies to study the membrane lipid raft hypothesis, as well as apparent contradictions regarding the effect of n-3 PUFA on lipid rafts will be critically presented...
  39. pmc n-3 polyunsaturated fatty acids--physiological relevance of dose
    Wooki Kim
    Program in Integrative Nutrition and Complex Diseases, Texas A and M University, College Station, TX 77843, USA
    Prostaglandins Leukot Essent Fatty Acids 82:155-8. 2010
    ....
  40. pmc Use of a novel genetic mouse model to investigate the role of folate in colitis-associated colon cancer
    Robert S Chapkin
    Faculty of Nutrition, Texas A and M University, College Station, TX 77843 2253, USA
    J Nutr Biochem 20:649-55. 2009
    ..9+/-0.3) and wild-type control mice (1.1+/-0.1). These data demonstrate that the ablation of two receptor/carrier-mediated pathways for folate transport increases the risk for developing inflammation-associated colon cancer...