Brief Summary of Minutes of Annual Meeting

Copy of Minutes attached

Short Term Outcomes & Activities: This research group has had a highly productive year. First and foremost we were able to compete and secure funding as the W2002 Bioactive research group. This effort included a re-analysis of goals, objectives and strategic partnerships as well as the integration of several new members to enhance the group dynamics and capacity. The University of Arizona (Thomson) was awarded a USDA Bioactive Food Components grant to complete as controlled feeding trial to test the dose-response of vegetable intake in modulating oxidative stress and inflammatory response in overweight post-menopausal women. This study will identify not only changes in biomarkers of vegetable exposure but also assess the association of change in these biomarkers and change in oxidative stress and inflammation. The study is testing doses of 2, 5 and 10 servings of vegetables daily. Discussions with W2002 UConn researchers led to identification of optimal biomarkers to assess oxidative stress and inflammatory response for this research. AZ has also had the opportunity to collaborate with OSU researchers to support efforts to assess dietary exposure estimates to BAFC in cruciferous vegetables for two on-going studies. In addition the Thomson Clinical research group has published several manuscripts to support research in BAFC relevant to the W2002 group. In addition, an abstract presenting the a green tea and weight loss intervention trial among breast cancer survivors was presented at FASEB in 2008 and submitted January 2009 for peer-review. Collaborations are strong between Oregon State University and AZ as well as several other sites where Dr. Ho is advancing our understanding of the role of BAFC in cruciferous vegetables to reduce cancer risk in at-risk people. The classic view of cancer etiology is that genetic alterations damage DNA structure and induce mutations resulting in non-functional proteins that lead to disease progression. More recently, the role of EPIGENETIC alterations during cancer has gained increasing attention. These epigenetic alterations affect gene expression without directly changing DNA sequences, but rather turn on or off gene expression by post-translational modifications. Interestingly, many of these epigenetic modifications can also be modified by dietary factors. For example, pharmacological histone deacetylase (HDAC) inhibitors are currently being tested in human clinical trials and are proposed to have potent anti-cancer activity. The researchers have found that sulforaphane, a chemical found cruciferous vegetables is also an HDAC inhibitor, increases acetylated histone levels and has anti-cancer properties in the prostate. Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables such as broccoli. This anticarcinogen was first identified as a potent inducer of Phase 2 enzymes, but evidence is mounting that SFN acts through other cancer chemopreventive mechanisms. The group recently reported on a novel mechanism of chemoprotection by SFN in human colon cancer cells and prostate epithelial cells, namely the inhibition of histone deacetylase (HDAC). In human subjects, a single dose of 68 g BroccoSprouts® inhibited HDAC activity significantly in peripheral mononuclear cells, 3 and 6 h following consumption. HPLC-mass spec methods have been developed for identifying SFN and its metabolites in plasma and urine. A significant increase in urinary and plasma SFN and metabolites can be found following broccoli sprout consumption 3-6 hours following consumption. We have also found that SFN specifically targets prostate cancer cells. Administration of sulforaphane selectively induces cell death in cancer cells, but not normal prostate epithelial cells. This work suggests that phytochemical may have the ability to alter epigenetic events that lead to disease prevention. Dr. Rich Bruno of U Conn has common research interest with several W2002 investigators related to the role of oxidative stress in chronic disease risk. Specifically he is investigating the role of oxidative stress and excess hepatic lipid accumulation which are strongly implicated in obesity-triggered nonalcoholic fatty liver disease (NAFLD). His research group has evaluated the protective bioactivities of green tea extract (GTE) in mitigating these NAFLD implicated events in genetically obese (ob/ob) mice. 6-Wk dietary supplementation of GTE at 1% (w/w), but not 0.5% reduced (p<0.05) hepatic triglyceride and total lipid whereas both doses reduced the mRNA levels of fatty acid synthase and stearoyl-CoA desaturase suggesting that GTE inhibits de novo lipogenesis. Concurrently, they observed GTE-mediated decreases in serum alanine aminotransferase, hepatic TNF-± and hepatic malondialdehyde. In addition, GTE increased the activities of the CuZn- and Mn-superoxide dismutase, catalase and glutathione peroxidase suggesting that GTE attenuated hepatic injury in association with improved oxidative stress and inflammation. Thiese works have resulted in four publications this year. These publications support the role for tocotrienols and dietary GTE in protecting against NAFLD by regulating hepatic de novo lipogenesis and attenuating inflammatory and oxidative stress responses that contribute to NAFLD. The results provide common research ground for Drs. Bruno and Thomson re: oxidative stress and disease risk as well as the evaluation of the efficacy and mechanisms of green tea in modulating obesity. Dr. Barbara J. Stoecker, Ph.D  Oklahoma as two lines of scientific investigation relevant to the W2002 efforts. The first is related to dietary components and cadmium-induced bone loss in ovariectomized rats Cadmium (Cd) has detrimental effects on bone; however, some dietary components may affect Cd toxicity. Er research group has examined the effects of dietary supplementation of potassium phosphate and/or dried plum (DP) on Cd-induced bone damage. Fifty, 90 day-old ovariectomized Sprague-Dawley rats were assigned to five treatments (n=10): 1) control (3gP/kg diet), 2) 50mg Cd and 3gP/kg, 3) 50mg Cd and 12gP/kg, 4) 200mg Cd and 3gP/kg, and 5) 200 mg Cd and 12gP/kg diet. After 45 days, half the rats in each treatment had 15% DP added to diets for 3 more months. Femoral cortical bone and microarchitecture of L4 vertebra trabecular bone was assessed with microcomputed tomography (µCT). Bone strength was evaluated using finite element analysis. Cortical thickness was decreased by Cd and by high P (p < 0.0001) but increased by DP (p<0.003). L4 bone volume fraction, trabecular separation and connectivity density were impaired synergistically by Cd and high P. With higher dietary Ca/P ratios, DP frequently maintained microarchitecture in Cd-50 rats but not in Cd-200 rats. Force to compress L4 trabecular bone was consistent in showing significant detrimental effects of Cd and high P and beneficial effects of DP in the Cd-0 and Cd-50 groups when high P was not fed. The other area of research interest of the Stroecker laboratory is in regards to the role of green tea polyphenols and bone turnover in rats. The effects of green tea polyphenols (GTP) on bone microarchitecture in middle-aged female rats without (sham, SH) and with ovariectomy (OVX) were evaluated to evaluate GTPs antioxidant capacity. A 16-week study was performed based on a 2 (SH vs. OVX) × 3 (no GTP, 0.1% GTP, and 0.5% GTP in drinking water) factorial design using 14-month-old female rats (n=10/group). An additional 10 rats were euthanized at the beginning of the study to provide baseline parameters. Analysis using dual-energy X-ray absorptiometry, histomorphometric, and micro-computed tomography [microCT in OSUs laboratory] showed that GTP supplementation resulted in (a) increased trabecular volume, thickness, number, and bone formation of proximal tibia, periosteal bone formation rate of tibia shaft, and cortical thickness and area of femur, and (b) decreased trabecular separation and bone erosion of proximal tibia, and endocortical bone eroded surface of tibia shaft. These results suggest that drinking water supplemented with GTP mitigated deterioration of bone microarchitecture in both intact and ovariectomized middle-aged female rats by suppressing bone erosion , enhancing bone formation, and modulating endocortical and cancellous bone compartments, resulting in a larger net bone volume. This line of research supports collaboration with Dr. Bruno (UConn), Dr. Thomson (UAz) and Dr. Weaver (Purdue). In addition, Dr. Stoeker has an active line of research related to nutrient adequacy during pregnancy and childhood in developing countries affording an opportunity for collaborative international research. Obesity is associated with an increased risk of colon cancer and this has been a focus of the research of Dr. Norman Hord. A dearth of nontumorigenic colon epithelial cell model systems are available to address reductionist hypotheses concerning the interaction of endocrine products of adipose tissue and cancer risk. We have used conditionally immortal murine colon epithelial cells with distinct adenomatous polyposis coli (Apc) genotypes (IMCE (Apc Min/+) and YAMC (Apc+/+) to address the roles of leptin, adiponectin and interleukin 6 (IL-6) on cell number homeostasis and to characterize interactions with secreted products of macrophages. We demonstrated that leptin, an adipose-derived hormone, induces cell proliferation in IMCE, but not YAMC, cells by inducing autocrine IL-6 production and trans-IL-6 signaling. Microarray analysis revealed that leptin-induced changes in genes regulating the Wnt/beta-catenin-mediated pathway including Mdm2, Pik3r1, and Rb1. Leptin induced IGF-mediated pathway gene expression changes and their protein products in IMCE cells. In the IMCE cells IGFBP-6, IGF-1, and Crim1 expression was upregulated, while IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-5, and Nov expression was downregulated by leptin treatment. While leptin promoted the proliferation of IMCE cells, we have also shown that it induces the production of chemokines which may activate macrophages and promote macrophage cell chemotaxis. As such, these data provide evidence for leptin-induced cross-talk between IMCE cells and macrophages that model a potential promotional mechanism. Low serum adiponectin, a major secretory product of white adipose tissue, is associated with colon, prostate and breast cancer; serum adiponectin levels decrease as body mass index (and leptin) increase. Under serum-free conditions, adiponectin (1 µg/ml) inhibited leptin-induced autocrine IL-6 production, soluble IL-6 receptor shedding, trans-IL-6 signaling and subsequent STAT3 phosphorylation in IMCE cells. Adiponectin inhibited leptin-induced cell proliferation in the IMCE cells and this inhibition was associated with I kappa B-alpha phosphorylation, I kappa B-alpha degradation and decreased NF-kappaB p65 DNA activation and binding. These data indicate that adiponectin acts on preneoplastic colon epithelial cells to regulate cell growth via 2 distinct pathways inhibiting leptin-induced NF-kappaB-dependent autocrine IL-6 production and trans-IL-6 signaling. Edralin A. Lucas (Oklahoma) I studying Momordica charantia and the modulation of glucose and lipid parameters in mice fed high fat diet. A high fat diet contributes significantly in the development of obesity and diabetes, two major public health concerns in the US and worldwide. Momordica charantia (MC), also known as bitter melon, is a widely consumed vegetable in Asia and reported to have hypoglycemic properties. This study compared the effects of freeze-dried MC with the PPARg agonist- rosiglitazone (rosi), and the known PPARa agonist- fenofibrate (feno), on body weight and clinical parameters using a mouse model of diet-induced obesity. Eight wk old male C57BL/6 mice were randomized to 8 dietary treatment groups (n=20/group): control diet (ad lib), control diet (pair fed), high fat (HF) diet, HF + 1% MC (w/w), HF + 10% MC (w/w), HF+1% MC seeds (w/w), HF + rosi (50mg/kg diet), and HF + feno (500mg/kg diet) for 8 wks. Significant differences in body weights were observed within one week of beginning the experimental diet. The final body weights of mice receiving the 10% MC were similar to the mice receiving the control diet (ad lib). Rosiglitazone and 1% MC were not able to reduce body weight; however, fenofibrate and MC seeds mildly reduced body weight. HF fed mice exhibited the highest percent body fat. Interestingly, 10% MC prevented the increase in adiposity due to high fat diet. A high fat diet containing 10% MC, similar to rosiglitazone, normalized blood glucose after a glucose tolerance test. Triglycerides, total cholesterol, and glucose were all elevated due to high fat diet. The higher dose of MC modulated these clinical parameters similar to fenofibrate and rosiglitazone. Fenofibrate caused an enlargement of liver which was not observed in other treatment groups. The mechanism by which MC modulates glucose and body weight warrants further investigation. Dr. Janos Zempleni (University of Nebraska at Lincoln) has a focused research program in the area of repression of transposable elements by histone biotinylation and its role in cancer prevention. Transposable elements such as long terminal repeats (LTR) constitute about 45% of the human genome; transposition events impair genome stability. Fifty-four promoter-active retrotransposons have been identified in humans. Epigenetic mechanisms are important for transcriptional repression of retrotransposons, preventing transposition events and abnormal regulation of genes. Here, we demonstrate that the covalent binding of the vitamin biotin to lysine-12 in histone H4 (H4K12bio) and lysine-9 in histone H2A (H2AK9bio), mediated by holocarboxylase synthetase (HCS), is an epigenetic mechanism to repress retrotransposon transcription in human and mouse cell lines and in primary cells from a human supplementation study. Abundance of H4K12bio and H2AK9bio at intact retrotransposons and a solitary LTR depended on biotin supply and HCS activity, and was inversely linked with the abundance of LTR transcripts. Knockdown of HCS in Drosophila enhances retrotransposition in the germline. Importantly, his research group has demonstrated that depletion of H4K12bio and H2AK9bio in biotin-deficient cells correlates with increased production of viral particles, transposition events, and ultimately decreases chromosomal stability. Collectively, this study reveals a novel diet-dependent epigenetic mechanism that could affect cancer risk. This work has and will continue to afford opportunities for collaboration with several other W2002 investigators working in cancer prevention research. Dr. Andy Clifford (UCDavis)as completed compelling research in the area of age-related macular degeneration (AMD), the most common cause of irreversible blindness in elderly Americans. There is now evidence that the carotenoids, lutein and zeaxanthin are key to protecting against AMD, by filtering out blue light at a pre-receptoral level, or by quenching free radicals. Lutein and zeaxanthin are dietary xanthophyll carotenoids, that are delivered to the retina via plasma lipoproteins. Mechanisms governing the selective retinal capture and accumulation of lutein and zeaxanthin, over other carotenoids, are unknown except that lipoproteins/apolipoproteins play a key role. Xanthophyll-binding proteins in the retina capture the xanthophyll carotenoids, the Pi isoform of GSTP1 is specific for zeaxanthin but the binding protein for retinal uptake of lutein remains elusive. To explore the beneficial effects of lutein and zeaxanthin for humans one must understand how they are absorbed from the intestine, transported in serum, and taken up by the retina, use of 14C accelerator mass spectrometry (AMS) and kinetic models of datasets to facilitate this task. Dr. Cliffords work has focused on improving high throughput biological/biomedical applications AMS to quantify minute amounts of 14C. The process involves oxidation of carbon (in sample of interest) to CO2 and then reduction of CO2 to graphite-like substances that coat a -400-mesh spherical iron powder (-400MSIP) catalyst. Prior AMS methods often failed to produce robust ion currents that are required for reliable, accurate, precise, and high-throughput AMS for biological/biomedical applications. Therefore, we described our optimized method for reduction of CO2 to high-quality uniform AMS targets (1) and characterized their physical (hardness/color), morphological (Scanning Electron Micrographs), and structural (Fourier Transformed-Infra Red, FTIR; Raman; and X-Ray Defraction, XRD spectra) characteristics that guarantee accurate, precise, and high-throughput AMS measurement (2). In addition the technology was used to determine how ingested 14C-all-trans [10,10',11,11'-14C]-b-carotene is absorbed from the intestine, transported in serum, and metabolized in vivo in humans. The group has demonstrated excentral cleavage of b-carotene in humans for the first time (3). Finally, we discovered that the apparent digestibility of the 14C dose was 50 % (4). The metabolic fecal elimination and AUC0- were 0.05 and 41 %, respectively. The portion of 14C dose eliminated in urine varied 8.2 %. Plasma 14C-b-carotene and 14C- REs accounted for most of the absorbed 14C. Feces was the major excretory path. These data suggested the variable elimination of 14C via urine accounted for the variable plasma/serum responses to ingested b-carotene reported in prior studies. Our data also suggested that plasma levels of ROH plus REs should be considered in estimating vitamin A equivalency of ingested b-carotene. These methodologies have strong potential for application to numerous BAFC and thus offer opportunities to several of the W2002 investigators for collaboration. Barry Shane University of California, Berkeley has continued studies on the metabolic and nutritional effects of common polymorphisms in human folate-related genes that have been shown to influence disease risk. We have continued to evaluate the B12-dependent methionine synthase (MS) and methylene-tetrahydrofolate reductase (MTHFR) genetic mouse models to mimic the effects of these polymorphisms and to evaluate their effects on metabolism and how this is modified by nutritional status. One carbon metabolic fluxes and DNA and histone methylation has been evaluated in these animals and in embryonic fibroblasts. We have investigated the influence of folate and vitamin B12 status in our experimental animals using cDNA array technology and have identified a number of inflammatory response genes that are responsive to vitamin status. We continue to evaluate genetic risk factors for neural tube defects. We are continuing to identify putative modifier genes which influence folate status, homocysteine levels, and methylation potential using a number of mouse strains, and are evaluating the interaction between iron and folate status. We have measured myelination rates in the B12-deficient mouse and have shown that remyelination is impaired. Mathematical models are being developed to better understand regulatory aspects of one carbon metabolism. The impact of this work is significant in that neural tube defects are the most common birth defects in humans and identification of genetic risk factors for this condition will allow screening to identify at risk individuals. Polymorphisms in genes encoding folate-dependent enzymes have been implicated as risk factors for cancer and vascular disease. The studies may indicate whether this risk can be modified by dietary changes and may shed some insight into the etiology of vitamin B12 deficiency symptoms and interactions between folate and iron. Dr. de Mejia from the University of Illinois joined the W2002 investigative team this year as her research focuses on the molecular mechanisms of chemoprevention of bioactive food components, mainly proteins/petides and flavonoids, and their safety. Thus, opportunities for collaborations with several investigators will be abundant. Her research focuses on the study of food components with health benefits; analysis, characterization and mechanism of action of antimutagenic and anticarcinogenic compounds in foods (legumes, oilseeds, and vegetables). Currently the group is working with bioactive proteins in different legumes and investigates the role of processing on the presence, concentration and physicochemical characteristics of proteins/peptides with biological potential against chronic diseases as well as their safety such as allergenic potential. Similar to Bruno (UConn) and Thomson (UAZ) this research group is also studying the health benefits of tea, in particular the molecular mechanisms underlying the biological effects of ethnic teas used in folk medicine to combat several disorders including cancer. This scientific study will introduce new materials to improve human health. In 2007-2008 this research group published over 15 manuscripts indicating involvement of Dr. de Mejia is likely to result in even greater productivity for the W2002 group. Dr. Weaver at Purdue has accomplished instrumental work during this period evaluating bone mass in adolescents. She has found that about 25% of peak bone mass is acquired during the peak rate of bone acquisition in puberty, but factors which influence skeletal calcium accretion are not well understood. We evaluated the role of vitamin D status in calcium absorption and retention in adolescent white and black girls. Her research also evaluated predictors of calcium retention in adolescent boys. Data from controlled feeding studies on a range of calcium intakes were evaluated for factors which are thought to predict calcium utilization in 55 white and 55 black girls and 31 boys. In girls, calcium intake explained about as much of the variation in calcium retention as did race (12.3 vs. 13.7%, respectively). In boys, calcium intake and IGF-1 explained 21.7 and 11.5% of the variation in calcium retention. This shows lifestyle choices can be as important for skeletal growth as genetic determinants. This kind of analysis can only be derived from controlled feeding studies. This work has resulted in the publication of numerous peer-reviewed manuscripts (see publication list). The research of Dr. Winzerlings lab (UAz) is unusual in regards to the W2002 in that they work in mosquitoes as models for iron metabolism. They recently analyzed transferrin 2 from mosquitoes to determine whether this protein is likely to be involved in iron metabolism in this animal. Tf2 showed greatest identity to melanotransferrin from humans. However, like mammalian melanotransferrin, Tf2 in mosquitoes is unresponsive to exposure to iron in a blood meal as well as to iron administrated to mosquito CCL-125 cells in culture. Life stage analysis suggests that Tf2 is most likely involved in development. Ferritin is crucial to iron metabolism in mosquitoes and man. In mosquitoes it is a primary iron transport protein. We evaluated the ability of several chemical inhibitors to block ferritin secretion in mosquito cells. CI-976 a phospholipase inhibitor blocked secretion, whereas Brefeldin A did not, suggesting that ferritin is secreted from mosquito cells by budding of vesicles from the ER membrane. However, when fed to mosquitoes as part of a blood meal, CI-976 (in ethanol) failed to reduce egg numbers or increase mortality. Thus, we are using RNAi to evaluate the effects preventing iron transport from the blood meal to the ovaries and eggs. We also have initiated studies evaluating the ovarian and egg proteome expressed following an artificial blood meal with and without hemoglobin to female mosquitoes. In addition to our mosquito work, we collaborated with a team of scientists in the Czech Republic in work on iron metabolism in ticks that transmit disease. This work determined that Tf2 is not likely involved in iron metabolism. Although CI-976 inhibits ferritin secretion from cells; feeding the compound to animals failed to reduce egg numbers or increase mortality of mosquitoes. Dietary iron is highly mitogenic in mosquitoes and stimulates synthesis of several ovarian and egg proteins. The Medeiros lab is involved in two micronutrient studies. The first one focuses on copper deficiency and cardiac hypertrophy with emphasis on mitochondria and the second on the role of iron in bone. Copper and heart disease studies: During the last year, the group published a paper on the gene program that is up-regulated in mitochondrial biogenesis in hearts from copper deficient rats. We have demonstrated that PGC1-± transcripts and protein are robustly up-regulated in hearts from copper deficient rats. This protein is thought to be the master regulator of mitochondrial biogenesis. Previously we have demonstrated that other proteins and transcription factors involved in mitochondrial biogenesis are up-regulated. However, many of these markers depend on PGC1-±. These results in tandem with other papers we have published prove that all of the markers of mitochondrial biogenesis are upregulated in hearts from copper-deficient rats. This occurs despite the fact that there does not appear to be a shift in substrate utilization. In heart disease, the heart will often shift from fatty acids to glucose as a fuel substrate source to maintain ATP levels. Here we measured rate limiting enzymes in glycolysis and found that medium chain acyl dehydrogenase (rate limiting for beta oxidation of fatty acids), phosphofructose kinase (rate limiting for glycolysis), and Phosphoenolpyruvate carboxykinase (gluconeogenesis enzyme) did not differ by copper status. This suggests that the increase in mitochondria is able to keep up with energy demands of the heart as an adaptive process. Using proteinomics, we were able to determine changes in several proteins, all of which were secondary to heart damage found in the copper deficient heart. Future studies have now focused upon chaperone proteins of cardiac cells as a function of copper deficiency. Iron restriction and bone integrity: The second area deals with iron deficiency and bone integrity. We have published previously that animals fed iron restricted diets, as well as calcium restricted diets either singly or in combination with one another, have reduced bone strength as measured by Instron breakage. Using mico-CT analysis we have been able to demonstrate increased porosity of trabecular of bone from rats fed either calcium or iron restricted diets. These studies were done in collaboration with Dr. Stoecker of Oklahoma State University. A salient additional finding from several of our studies on this topic is an apparent decrease in mineralization of bones from iron restricted animals and also with an in vitro bone cell system using an iron chelator to generate an iron deficiency. The next logical step in this study is to collaborate with others on the multi-state project to assess calcium kinetics as affected by iron restriction, looking at both bone accretion and turnover. A second line of work needed is to determine if the condition is reversible with iron repletion. Finally, human epidemiological studies are needed to confirm the feasibility of iron as a factor in human bone health. Collaborations related to iron and bone health are underway and involve Drs. Medieros, Weaver and Winzerling. Important to all this research is the role of translational research that brings research findings to the consumer. To support the translation of science at this level we have engaged the expertise and experience of Dr. Karen Chapman-Novakofski a well-recognized expert in behavior research and epidemiological study. Various mediating variables influence behavior and identifying those variables continues to be a research interest in epidemiological studies. In addition, we know that knowledge alone is not effective in changing behavior. Grounding in a behavioral theory is required for effective interventions targeting diet and lifestyle change. In addition, in-person education is becoming costly in terms of time and effort for both the educator and learner. In this regards, online interactive education may prove to be an effective alternative to group education settings, or at least augment such efforts. Her research has resulted in several publications during the report period and offers an opportunity for several W2002 investigators to expand collaborations to include epidemiological and/or outcomes-based research. Outputs: As a whole the research group within W2002 has published over 50 peer-reviewed manuscripts in 2007-2008 impacting healthcare, research technology and methodology, consumer knowledge and the food supply. We have met our objectives to expand knowledge of bioavailability of nutrients as well as to assess specific bioactivity of select BAFC in the human diet with a particular emphasis on bioactivity biomarkers/indicators of bone health, cancer risk, cardiovascular disease risk and inflammatory disorders such as obesity. In addition we have explored the role of epigenetics in health and have bridged opportunities between epidemiologists and basic scientists in regard to testing hypotheses across the spectrum of nutrition science research. We have shared methodologies, technologies, expertise and research findings in a meaningful, collaborative and interactive way thus supporting the advancement of scientific knowledge regarding the role of BAFC and nutrients in optimizing human health. Milestones: Successful renewal of the W2002 Multistate project was accomplished. For 2009 we plan to continue to build productive collaborative research projects and joint peer-reviewed manuscripts. In addition we are planning a translational research symposium for the 2010 FASEB meeting. To this end we have engaged 5 different Research Interest groups within FASEB and have submitted our proposal titled, From field to consumer-the science & translation of bioactive food component research. The symposium would be co-directed by Norman Hord and Richard Bruno members of W2002 and all speakers are within our research group.

Abebe Y, Hambidge KM, Teshome A, Stoecker B, Krebs, N, Gibson R. Inadequate feeding practices and impaired growth among children from subsistence farming households in Sidama, Southern Ethiopia. Maternal and Child Nutrition, In Press, 2009. Abebe Y, Bogale A, Hambidge KM, Stoecker BJ, Arbide I, Teshome A, Krebs NF, Westcott JE, Bailey KB, Gibson RS. Inadequate intakes of dietary zinc among pregnant women from subsistence households in Sidama, Southern Ethiopia. Public Health Nutr 11:379-386, 2007. Alwerdt JL, Seigler DS, Gonzalez de Mejia E, Yousef GG, Lila MA. The Influence of Alternative Liquid Chromatography Techniques on Chemical Complexity and Bioactivity of Proanthocyanidin Mixtures. J. Agric. Food Chem. 65 (6): 1896-1906, 2008. Aparicio-Fernández X, Reynoso-Camacho R, Castaño-Tostado E, García-Gasca T, González de Mejia E, Guzmán-Maldonado H, Elizondo-Azuela G, Lila MA, Loarca-Pina G. Antiradical capacity and induction of apoptosis in HeLa cells by a Phaseolus vulgaris extract. Plant Foods Human Nutr., 63(1):35-40, 2008. Ariefdjohan M, Martin B, Lachcik P, Weaver CM. Acute and chronic effects of honey and its carbohydrate constituents on calcium absorption in rats. J. Ag. Food Chem. 56:2649-2654, 2008. Bruno RS, Dugan CE, Smyth JA, DiNatale DA, Koo SI. Green tea extract protects leptin-deficient, spontaneously obese mice from hepatic steatosis and injury. J Nutr. 138(2):323-31, 2008. Bu SY, Lerner M, Stoecker BJ, Boldrin E, Brackett DJ, Lucas EA, Smith BJ. Dried plum polyphenols inhibit osteoclastogenesis by downregulating NFATc1 and inflammatory mediators. Calcif Tissue Int. 82(6):475-88, 2008. Bu SY, Lerner M, Stoecker BJ, Boldrin E, Brackett DJ, Lucas EA, Smith, BJ. Dried plum polyphenols inhibit osteoclastogenesis by downregulating NFATc1 and inflammatory mediators. Calcified Tissue International 82:475-488, 2008. Charoenkiatkul S, Kriengsinyos W, Tutipopipat S, Suthutvoravut U, Weaver CM. Calcium absorption from commonly consumed vegetables in healthy Thai women. J. Food Sci. 73(9):H218-21, 2008. Clarke, JD, Dashwood, RH and Ho E. Multi-targeted prevention of cancer by sulforaphane. Cancer Letters, 269(2):291-304, 2008. Dashwood RH, Ho E. Dietary agents as histone deacetylase inhibitors: sulforaphane and structurally-related isothiocyanates. Nutr Rev, 66 Suppl 1:S36-8, 2008. Devareddy L, Hooshmand S, Collins JK, Lucas EA, Chai SC. Blueberry prevents bone loss in ovariectomized rat model of postmenopausal osteoporosis. J Nutr Biochem. 19(10):694-9, 2008. Dia PV, Torres S, De Lumen BO, Erdman J, Gonzalez de Mejia E. Presence of lunasin in plasma of men after soy protein consumption. Journal of Agricultural and Food Chemistry, In Press 2008. Dia VP, Berhow MA, Gonzalez de Mejia E. Bowman-Birk Inhibitor and genistein among soy compounds that synergistically inhibit nitric oxide and prostaglandin E2 pathways in lipopolysaccharide-induced macrophages. J. Agric. Food Chem., 56 (24), 1170711717, 2008. Dia PV, Wang W, Oh VL, de Lumen BO, Gonzalez de Mejia E. Isolation, purification and characterization of lunasin from defatted soybean flour and in vitro evaluation of its anti-inflammatory activity. Food Chemistry, 113 (5), 2009. doi: 10.1016/j.foodchem.2008.09.023. Droke EA, Hager KA, Lerner MR, Lightfoot SA, Stoecker BJ, Brackett DJ, Smith BJ. Soy isoflavones avert chronic inflammation-induced bone loss and vascular disease. J Inflammation (Lond) 4:17-28, 2007. Fenton JI, Nuñez NP, Yakar S, Susan N, Perkins SN, Hord NG, Hursting SD. Dietary modulation of energy balance alters the serum profile of inflammation in C57BL/6N mice. Diabetes, Obesity and Metabolism. 11(4): 343-354, 2009. Fenton, JI, Birmingham, J, Hursting, SD and Hord, NG Adiponectin blocks leptin induced NFº-B DNA binding, interleukin-6 trans- signaling and cell proliferation in ApcMin colon epithelial cells. International Journal of Cancer. 122(11): 2437-45, 2008. Fenton, JI, Lavigne JA, Perkins, SN, Liu H, Chandramouli, GVR, Shih, JH, Hord, NG, Hursting, SD Microarray analysis reveals that leptin induces autocrine/paracrine cascades to promote survival and proliferation of colon epithelial cells in an Apc genotype dependent fashion. Mol Carcinog. 2008 Jan;47(1):9-21. Frias J. Song Y S, Martínez-Villaluenga C, González de Mejia E, Vidal-Valverde C. Immunoreactivity and Amino Acid Content of Fermented Soybean Products. J. Agric. Food Chem., 56 (1), 99105, 2008. Geiser DL, Shen M-C, Mayo JJ, Winzerling, JJ. Iron Loaded Ferritin Secretion and Inhibition by in Aedes aegypti larval cells. Comparative Biochemistry and Molecular Biology. 2009 Jan 8. [Epub ahead of print], 2009. Geiser DL, Mayo JJ, Shen M-C, Winzerling, JJ. The unique regulation of Aedes aegypti larval cell ferritin by iron. Insect Biochemistry and Molecular Biology, 37(5):418-29, 2007. Gibson RS, Abebe Y, Stabler S, Allen RH, Westcott JE, Stoecker BJ, Krebs NF, Hambidge KM. Zinc, gravida, infection, and iron, but not vitamin B-12 or folate status predict hemoglobin during pregnancy in southern Ethiopia. J Nutrition 138:581-586, 2008. Hajdusek O, Sojka D, Kopacek P, Buresova V, Franta Z, Sauman I, Winzerling, JJ, Grubhoffer L. Knockdown of proteins involved in iron metabolism limits tick reproduction and development. Proceedings National Academy Sciences, USA. 2009 Jan 27;106(4):1033-8. Epub 2009 Jan 26. Heck CI, de Mejia EG. Yerba mate tea (Ilex paraguariensis): a comprehensive review on chemistry, health implications and technological considerations. J. Food Sci., 72 (9), 138-151, 2007. Heck CI, Schmalko M, Gonzalez de Mejia E. Effect of Growing and Drying Conditions on Phenolic Composition of Mate teas (Ilex paraguariensis). J. Agric. Food Chem., 56 (18): 8394-8403, 2008. Herrejon K, Hartke JL, Scherer J, Chapman-Novakofski K. The creation and impact evaluation of Your Guide to Diet and Diabetes, an interactive web-based diabetes tutorial. Accepted to Diabetes Technology and Therapeutics, August, 2008. Hill K, Braun MM, Kern M, Martin BR, Navalta J, Sedlock D, McCabe LD, McCabe GP, Peacock M, Weaver CM. Predictors of calcium retention in adolescent boys. J. Clin. Endocrin. Metab. 93(12):4743-4748, 2008. Ho CC, de Moura F, Kim SH, Clifford AJ. Excentral cleavage of b-carotene in vivo in a healthy man. Am J Clin Nutr, 85:770-7, 2007. Ho CC, de Moura F, Kim SH, Burri BJ, Clifford AJ. b-Carotene absorption and conversion to retinoids in healthy humans assessed with a 14C-b-carotene tracer. J Nutr. (Submitted). Hord NG. Eukaryotic-microbiota cross-talk: potential mechanisms for health benefits of prebiotics and probiotic bacteria. 28:215-31, 2008. Hord NG, Fenton JI. Context is everything: mining the normal and preneoplastic microenvironment for insights into the diet and cancer risk conundrum. Molecular Food and Nutrition Research, 51(1):100-108, 2007. Hubbs-Tait L, Mulugeta A, Bogale A, Kennedy TS, Stoecker BJ. Main and interaction effects of iron, zinc, lead and parenting on children's cognitive outcomes. Developmental Neuropsychology, In Press, 2009. Johnson CD, Lucas EA, Hooshmand S, Campbell S, Akhter MP, Arjmandi BH. Addition of fructooligosaccharides and dried pum to soy-based diets reverses bone loss in the ovariectomized rat. Evid Based Complement Alternat Med. 2008 Jul 30. [Epub ahead of print]. Kennedy TS, Thomas DG, Wogene T, Abebe Y, Hubbs-Tait L, Stoecker BJ, Hambidge KM. Growth and visual information processing in infants in southern Ethiopia. J Applied Develop Psych 29:129-140, 2008. Keylock KT, Lowder T, Leifheit KA, Cook M, Mariani RA, Ross K, Kim K, Chapman-Novakofski K, McAuley E, Woods JA. Higher antibody, but not cell-mediated, responses to vaccination in higher physically fit elderly. J Appl Physiol 102(3): 1090-1098, 2007. Khan N, Nast C, Evans EM, Chapman-Novakofski K. Development of a training program for undergraduate student-assisted teaching. J Nutr Educ Behav, 41(1):xxx 2009. Kim SH, Kelly PB, Clifford AJ. Biological/biomedical accelerator mass spectrometry targets. 1. Optimizing the CO2 reduction step using zinc dust. Anal Chem, 80:7651-60, 2008. Kim SH, Kelly PB, Clifford AJ. Biological/biomedical accelerator mass spectrometry targets. Physical, morphological, and structural characteristics. Anal Chem, 80:7661-9, 2008. MacFarlane AJ, Perry CA, Girnary HH, Gao D, Allen RH, Stabler SS, Shane B, Stover PJ. Mthfd1 is an essential gene in mice and alters biomarkers of impaired one-carbon metabolism. J. Biol. Chem. 284:1533-1539, 2009. Martinez-Villaluenga C, Bringe NA, Berhow MA, Gonzalez de Mejia E. ²-Conglycinin embeds active peptides that inhibit lipid accumulation in 3T3-L1 adipocytes in vitro. J. Agric. Food Chem., 56 (22), 1053310543, 2008. Martinez-Villaluenga C, Dia PV, Berhow M, Bringe NA, Gonzalez de Mejia E. Protein hydrolysates from ²-conglycinin enrich soybean genotypes inhibit lipid accumulation and inflammation in vitro. Molecular Nutrition and Food Research, In Press, 2008. MNF-0473-2008. Martino HSD, Martin BR, Weaver CM, Bressan J, Moreira MA, Costa NMB. Antinutrient factors and bioavailability of calcium of genetically modified soybeans. J. Food Sci. 72:S698-695, 2007. Mederios DM, Jiang Y, Klaahsen D, Lin D. Mitochondrial and sarcoplasmic protein changes in hearts from copper-deficient rats: up-regulation of PGC-1± transcript and protein as a cause for mitochondrial biogenesis in copper deficiency. J. Nutr. Biochem. In press. Medeiros DM. Assessing mitochondria biogenesis. Methods 46: 288-294, 2008. Miller JA, Hakim IA, Thomson CA, et al. Determination of d-Limonene in Adipose Tissue by Gas Chromatography-Mass Spectrometry J Chrom B. 870: 68-73, 2008. Morrow R, Deyhim F, Patil BS, Stoecker BJ. Feeding orange pulp improved bone quality in a rat model of male osteoporosis. Journal of Medicinal Food, In Press, 2009. Mulugeta A, Hagos F, Stoecker B, Kruseman G, Linderhof V, Abraha Z, Yohannes M, Samuel GG. Nutritional status of adolescent girls from rural communities of Tigray, Northern Ethiopia. Ethiopian Journal of Health and Development. In Press, 2009. Mulugeta A, Hagos F, Kruseman G, Linderhof V, Stoecker BJ, Abraha Z, Yohannes M, Samuel GG. Factors contributing to child malnutrition in Tigray, Northern Ethiopia. East African Medical Journal, In Press, 2008. Mustachich DJ, Gohil K, Bruno RS, Yan M, Leonard SW, Ho E, Cross CE, Traber MG. Alpha-tocopherol modulates genes involved in hepatic xenobiotic pathways in mice. J Nutr Biochem, E-pub Sept 10, 2008. Nesaretnam K, Koon TH, Selvaduray KR, Bruno RS, Ho E. Modulation of cell growth and apoptosis response in human prostate cancer cells supplemented with tocotrienols. Eur J Lipid Sci Technol. 110:23-31, 2008. Olvera-Garcia V, Castano-Tostado E, Resendiz-Lopez I, Reynoso-Camacho R, Gonzalez de Mejia E, Elizondo-Azuela G, Loarca-Pina G. Hibiscus sabdariffa L. extracts inhibit the mutagenicity in microsuspension assay and the proliferation of HeLa cells. J. Food Sci. 73 (5): T75T81, 2008. Patade A, Devareddy L, Lucas EA, Korlagunta K, Daggy BP, Arjmandi, BH. Flaxseed reduces total- and LDL-cholesterol concentrations in Native American postmenopausal women. J Womens Health, 7(3):1-12, 2008. Reppert A, Steiner B, Chapman-Novakofski K. Prevalence of metabolic syndrome and associated risk factors in Illinois. Am J Health Promotion 23(2):130-138, 2008. Sprengelmeyer K, Banks D, Camp S, Farner B, Chapman-Novakofski K. From theories of behavior back to knowledge: results of a knowledge-focused diabetes education program. International J Food Science, Technology, & Nutrition 1(2):155-166, 2007. Serrano E, Anderson J, Chapman-Novakofski K. Not lost in translation: Nutrition education as translational science. J Nutrition Educ Behav 39(3): 164-170, 2007. Shane B. Folate and vitamin B12 metabolism: Overview and interaction with riboflavin, vitamin B6, and polymorphisms. In Folate and Vitamin B12 Deficiencies: Proceedings of a WHO Technical Consultation. Food Nutr. Bull. 29:S5-16, 2008. Shen C-L, Yeh JK, Stoecker BJ, Chyu M-C, Wang J-S. Green tea polyphenols mitigate deterioration of bone microarchitecture in middle-aged female rats. Bone Dec 11 (E-pub ahead of print] 2008. Silva-Sánchez C, Barba de la Rosa AP, León-Galván MF, de Lumen BO, de León-Rodríguez A, González de Mejía E. Bioactive peptides in Amaranth (Amaranthus hypochondriacus) Seed. J. Agric. Food Chem. 56 (4): 1233-1240, 2008. Song Y-S, Martinez-Villaluenga C, González de Mejia E. Quantification of human IgE immunoreactive soybean proteins in commercial soy ingredients and products. Submitted, J. Food Sci. 73 (6), T90-T99, 2008. Song Y-S, Frias J, Martinez-Villaluenga C, Vidal-Valdeverde C, Gonzalez de Mejia E. Immunoreactivity reduction of soybean meal by fermentation, effect on amino acid composition and antigenicity of commercial soy products. Food Chem., 108 (2): 571-581, 2008. Stoecker BJ, Abebe Y, Hubbs-Tait L, Kennedy TS, Gibson RS, Arbide I, Teshome A, Krebs NF, Hambidge MK. Zinc status and cognitive function of pregnant women in southern Ethiopia. European Journal of Clinical Nutrition, In Press, 2009. Stoecker BJ. Basis for dietary recommendations for chromium. In: Vincent JB, ed. The Nutritional Biochemistry of Chromium (III). Amsterdam: Elsevier B.V., pp. 43-55, 2007. Taylor AW, Bruno RS, Traber MG. Women and Smokers Have Elevated Urinary F2-Isoprostane Metabolites; Determinations using a Novel Extraction and LC-MS Methodology. Lipids; In Press, 2008. Thomson CA, Stendell-Hollis NR, Rock CL et al. Plasma and Dietary Carotenoids are Associated with Reduced Oxidative Stress in Women Previously Treated for Breast Cancer. CEBP. 16(10): 2008-2015, 2007. Thomson CA, Neuhouser ML, Shikany JM, et al. The Role of Antioxidants and Vitamin A in Ovarian Cancer: Results from the Womens Health Initiative Prospective Cohort. Nutr & Cancer. 60:(6): 710-719, 2008. Thomson CA, Stendell-Hollis NR, West JL, et al. High-Lycopene Tomato Intake Increases Serum Carotenoid Levels but not Biomarker Oxidative Stress and Inflammation in Healthy Adults. The Open Bioactive Compounds Journal. 1: 7-12, 2008. Ulrich CM, Neuhouser M, Liu AY, Boynton A, Gregory JF III, Shane B, James SJ, Reed MC, Nijhout HF. Mathematical modeling of folate metabolism: predicted effects of genetic polymorphisms on mechanisms and biomarkers relevant to carcinogenesis. Can. Epidemiol. Biomark. Prev. 17:1822-1831, 2008. Vaughn N, Rizzo A, Doane D, Beverly JL, Gonzalez de Mejia E. Intracerebroventricular administration of soy protein hydrolysates reduces body weight without affecting food intake in rats. Plant Foods Hum. Nutr., 63(1):41-46, 2008. Villarreal A, Stoecker BJ, Garcia C, Garcia K, Rios R, Gonzales C, Mandadi K, Faraji B, Patil BS, Deyhim F. Cranberry juice improved antioxidant status without affecting bone quality in orchidectomized male rats. Phytomedicine 14:815-20, 2007. Wang W, Dia VP, Vasconez M, Nelson R, Gonzalez de Mejia E. Analysis of soybean protein-derived peptides and the effect of cultivar, environmental conditions, and processing on lunasin concentration in soybean and soy products. In: Special edition of Journal of the Association of Official Analytical Chemists International on Accurate methodology for amino acids and bioactive peptides in functional foods and dietary supplements for assessing protein adequacy and health effects. JAOAC Int. 91 (4): 936-946, 2008. Wang W, Bringe N, Berhow M, Gonzalez de Mejia E. ß-conglycinins among sources of bioactives in hydrolysates of different soybean varieties that inhibit leukemia cells in vitro. J. Agric. Food Chem. 56 (11): 4012-4020, 2008. Wang W, Rupasinghe SG, Schuler MA, Gonzalez de Mejia E. Identification and characterization of topoisomerase II inhibitory peptides from soy protein hydrolysates. J. Agric. Food Chem. 56 (15): 6267-6277, 2008. Wardwell L, Chapman-Novakofski K, Herrel S, Woods J. Nutrient intake and immune function of elderly subjects. J Amer Diet Assoc 108:2005-2012, 2008. Wardwell L, Brewer M, Chapman-Novakofski K. Effects of age, gender and chronic obstructive pulmonary disease on taste acuity. Accepted to the International J Food Sciences and Nutrition, December, 2008. Weaver CM, McCabe LD, McCabe GP, Braun M, Martin BR, DiMeglio LA, Peacock M. Vitamin D status and calcium metabolism in adolescent black and white girls on a range of controlled calcium intakes. J. Clin. Endocrin. Metab. 93:3907-3914, 2008. Wilson S, Martinez-Villaluenga C, Gonzalez de Mejia E. Purification, thermal stability and antigenicity of the immunodominant soybean allergen P34 in soy cultivars, ingredients and products. J. Food Sci. 73 (6), T106-T114, 2008. Zhou G, Kohlhepp P, Geiser DL, Frasquillo C, Vazquez-Moreno L, Winzerling, JJ Fate of blood meal iron in mosquitoes. Journal of Insect Physiology, 53(11):1169-78, 2007. Zhou G, Geiser DL, Velasquez LS, Mayo JJ, Winzerling, JJ. Differential regulation of transferrin 1 and 2 in Aedes aegypti. Insect Biochemistry and Molecular Biology. 2008 Dec. 30. [Epub ahead of print], 2009.