Brief Summary of Minutes of Annual Meeting

Meeting was called to order on May 23 and May 24, 2017 at 8:15 a.m. PST at the Oregon State University Portland Center.

Welcome and Introductions (May 23) – Participants were welcomed by the host (Emily Ho, Oregon State University) and Meeting Chair, Dr. Brian Lindshield, Kansas State University.

Executive session (May 24) – Dr. Jennifer Teske was elected by the members present to be the chair of the next annual meeting. She will coordinate next year’s W3002 meeting in Tucson, Arizona; targeted for some time in February 2017. Yanhong Liu, University of California, Davis, was elected as secretary.

Dr. Lindshield described the meeting objectives, timeline, and responsibilities.

Dr. Paul Cotton, NIFA Program Leader, joined the meeting via Skype and provided an update on the NIFA budget and current and future funding opportunities on May 24.

Each W3002 Investigator attending the meeting provided a brief oral progress report. At the end of each presentation a short discussion took place.

The group focused their attention on discussion and writing for the upcoming renewal this year. Drs. Ho. and Lindshield lead the discussion to first determine research priorities and membership for the upcoming renewal. Then the group assembled three writing teams and each group was modified the grant based on the pre-determined research priorities. Drs. Ho. and Lindshield brought the group together to reflect and clarify sections within the grant to ensure the group was agreed on work performed by each group. The group continued in this manner for the reminder of the meeting. The final group discussion ended with each member tasked with specific writing assignments.

Our new administrative advisor, Dr. Milan Shipka, introduced himself and provided guidance on the project’s renewal.

Included in the agenda was a tour of the Food Innovation Lab.

The meeting adjourned on May 24, 2016 at 4:30 p.m. An informal dinner took place after the meeting.

Members of the W3002 Multistate project have been vastly productive during the past reporting period as evidenced by the dissemination of new products, technologies, and knowledge through peer-review publications, book reviews, presentations at symposia, conferences, and in the media. Project objectives are listed below along with scholarship activities from each of the represented institutions.

1. Determine the bioavailability (absorption, distribution, metabolism, elimination) of nutrients and other food components.
2. Evaluate the bioactivity of nutrients and other food components in order to elucidate their underlying protective mechanisms.

Kansas State University (Brian Lindshield). We completed a 20-week field trial assessing micronutrient and anthropometric outcomes from consuming new extruded micronutrient fortified-blended foods (FBFs), which are commonly used for food aid, in Tanzanian children under 5 years of age. We have also completed a couple of FBF broiler chicken studies and two clinical trials focusing on impact of anti-nutritional factors on iron bioavailability/status. We have completed data collection and analysis, and now are working on drafting a manuscript describing the results. OUTPUTS: We published a protocol manuscript to disseminate what we have learned from observations and experiences in setting up and preparing for the field trial. We have also published a review that concluded that condensed tannins are not the inhibitors of iron bioavailability that tannins might be in general. OUTCOMES: Analyzed evidence suggests that health outcomes are improving in children that are receiving FBFs.

Montana State University (David C. Sands). We have developed rapid selection parameters for potatoes that are lower in glycemic index than the main commodity varieties and 7 cultivars are being tested for agronomic production. A series of high lysine tomato cultivars have been similarly selected and these are in the F2 cross stage however it may be that they have a lysine excreting endophyte. We developed a high throughput screening platform for the oilseed crop, Camelina sativa yielding four lines that are higher, much higher in the omega-3: omega-6 fatty acid ratio than canola, corn, soy, or safflower oils. A food processing company in Illinois is now growing this specialty crop. Proatina a naked oat is being developed for use as a high protein/low glycemic substitute for rice because of its nutritional value compared and high sustainability to produce. A large specialty milling company has contracted to increase production of Proatina. We advanced our research on the plant defense mechanism of plasmid curing, a potentially important approach to reducing plasmid associated antibiotic resistance, a mounting concern for the medical and animal feeding industries. Several animal feeding experiments of an ancient heirloom barley from Ethiopia, have demonstrated efficacy greater than the traditional antibiotic interventions, at much lower cost. OUTCOMES: This was the first year when our improved nutrition cultivars were produced in field scale amounts by processing and marketing concerns aimed at the nutritional food markets. These include high lysine wheats, low glycemic potatoes, a high protein-low glycemic naked oat, and a high omega 3 selection of Camelina sativa. In each case the economic outcome and output based on the nutritional value-added aspect of the new crop had to make up for the trade-off in yield. Nutritional selection reached our milestones of commercial product interest, development and field production. The increased consumer demand for nutritionally improved crops has been prompted by basic research and physiology that defined what was needed in human nutrition and health promoting diets.

The Ohio State University (Richard Bruno). We completed a clinical trial to examine altered metabolism, pharmaocokinetics, and elimination of a novel metabolite of alpha-tocopherol, i.e. alpha-carboxyethyl hydroxychromanol (a-CEHC), in patients with metabolic syndrome compared with healthy adults. The findings of this investigation demonstrate that individuals with metabolic syndrome have lower alpha-tocopherol bioavailability, and their lower bioavailability occurs without upregulating P450-mediated metabolism of alpha-tocopherol to generate a-CEHC. Individuals with metabolic syndrome have substantially less generation of a-CEHC, suggesting insufficient hepatic alpha-tocopherol status. This supports higher dietary alpha-tocopherol requirements for individuals with metabolic syndrome. We also completed preclincial studies in obese mouse models of nonalcoholic steatohepatitis (NASH) to assess the mechanism by which green tea extract (GTE) mitigates NFkB-dependent liver injury.  Studies performed in wild-type mice fed a high-fat diet demonstrate that GTE effectively reduces hepatic NFkB activation to levels no different from controls fed a low-fat diet. The antiinflammatory activity occurred in association with lowering hepatic expression of Toll-like receptor-4 and serum endotoxin levels. This suggests that GTE mediates its antiinflammatory activities through a mechanism involving the gut-liver axis. Subsequent studies in loss-of-function TLR4 mutant mice show that these mice are protected from increased hepatic NFkB activation that otherwise occurs in wild-type controls fed a high-fat diet.  GTE lowered hepatic NFkB activation in wild-type mice to the extent occurring in TLR4 mutant mice. This was accompanied by GTE-mediated decreases in serum endotoxin, and increases in small intestinal tight junction proteins, which occurred regardless of genotype. Thus, GTE likely reduces hepatic NFkB activation in a TLR4-dependent manner at the liver, but independent of intact TLR4 signaling at the level of the intestine.

Oklahoma State University (Edralin Lucas). Consumption of high fat (HF) diets contributes to the increasing rates of overweight and obesity worldwide. One of the underlying pathologies linking HF diet to obesity and its co-morbidities includes changes in gut microbial population (i.e. gut dysbiosis). A HF diet has been shown to induce gut dysbiosis, defined as alterations in the relative proportion of microbial species that leads to changes in their normal balance, function, and products of fermentation. HF diet-induced dysbiosis compromises gut health and increases intestinal permeability to antigens and bacterial products. Furthermore, HF diets result in an imbalance in pro-inflammatory and anti-inflammatory markers, both locally within the gut associated lymphoid tissues and in the systemic circulation. Thus, developing strategies that modulate HF diet-induced gut dysbiosis and inflammation may reduce the incidence of obesity and its co-morbidities. We investigated dietary approaches (i.e. freeze-dried mango pulp, wheat germ and pinto bean supplementation) on the gut microbiota, and its impact on body composition, glucose homeostasis, bone parameters and gut inflammatory markers. We also investigated the effects of freeze-dried mango supplementation on post-prandial responses in healthy men fed HF breakfast meal. Results during this reporting period were presented to both national and local meetings.

Oregon State University (Emily Ho). Recently we have found that zinc status is compromised with age.  Zinc deficiency causes immune cells to be sensitized to inflammation and also occurs in older animals and humans.  We have also examined the impact of zinc deficiency on developmental outcomes, gut microbiota oxidative stress and inflammation induced by arsenic. For these studies we have developed a zebrafish and rodent models to examine the interaction among zinc and arsenic.  Zinc deficiency has an impact on the microbiome in rodents and zebrafish. Developmental zinc deficiency had impact on neurodevelopment behaviors in zebrafish. We have found that sulforaphane, a chemical found in cruciferous vegetables inhibits histone deacetylases, alters DNA methylation and histone methylation, lincRNA expression and has anti-cancer properties in the prostate.  Women diagnosed with ductal carcinoma in situ supplemented with broccoli sprout extracts had decreased Ki67 staining and decreased histone deacetylases. Bioavailability is decreased in supplemental forms of sulforaphane compared to the whole food. Studies in prostate cancer patients and metabolomic profiling studies are ongoing. OUTPUTS:  Identify new risk factors in prostate cancer and offer novel dietary modifications to reduce the incidence of prostate cancer. Establish low cruciferous vegetable intake as a risk factor for the development of prostate cancer by altering histone modifications and cell proliferation pathways. Gain knowledge of the mechanisms behind the health benefits of micronutrients and phytochemicals such as zinc and compounds derived from cruciferous vegetables. Establish low dietary zinc as risk factor for inflammatory processes, DNA damage and cancer risk and identify new biomarkers for human zinc deficiency. Establish function of zinc and changes in zinc metabolism with development and aging.

Oregon State University (Norman Hord). Dietary exposure to nitrates and nitrites is associated with cardiovascular health benefits and improved athletic performance while, in the context of processed meats consumption, increased gastrointestinal cancer risk. Humans concentrate nitrate from dietary or endogenous sources in the salivary glands, which is then reduced to nitrite, swallowed, and absorbed. Circulating nitrite acts as a reservoir for nitric oxide (NO) with its reduction to NO potentiated in acidic or hypoxic areas, such as contracting skeletal muscle. Our project is the first to interrogate the potential effect of dietary nitrate, a component of green, leafy vegetables, on bone loss in an ovariectomized rodent model. The results demonstrate improved muscle performance in zebrafish in response to exercise in a swim test. Using two female rat models we determined that dietary nitrate has no effect on bone growth, bone loss or the community structure of the gut microbiome.  In humans, consumption of supplemental nitrate reduces blood pressure and decreases the oxygen cost of exercise.  Nitrite and nitrate exposure increased tissue nitrite and tissue nitrate; significant increases in blood nitrate and nitrite concentrations were also observed. Nitrate exposure significantly decreased oxygen consumption during exercise in the swim test assay. In contrast, nitrite treatment increased oxygen consumption with exercise and appeared to produce mild gill damage. Metabolomics showed that up to 90% of the tissue nitrite and nitrate can be derived from exogenous, or dietary, sources. Both nitrite and nitrate treatment increased blood concentrations of L-arginine, which is the primary source of endogenous NO production via NO synthase. The data supports existing data that a feedback mechanism inhibits endogenous NO production when high levels of nitrite or nitrate are consumed. These data support a positive effect of dietary nitrate on exercise performance in zebrafish.

Purdue University (Connie Weaver). Higher intakes of potassium and reduced intakes of sodium are associated with reduced blood pressure and serum lipids and are thus cardioprotective.  We are the first to report potassium bioavailability from a food.  We compared bioavailability in a dose response study from potatoes and a salt and found dose, but not source, influenced bioavailability.  Bioavailability was high from both sources.  An ongoing study is evaluating whole body retention and effect of increasing dietary potassium from potatoes and a salt on blood pressure.

Pennsylvania State University (Jairam Vanamala). We showed that dietary supplementation of freeze-dried grape powder (FDGP) decreased the total number of intestinal polyps (early markers of colon cancer) by 55%. This is significant because the aspirin, a drug used for prevention of colon cancer in human, decreased intestinal polyps by 42% in this study. We observed significant weight loss after 10-11 week of age in control APC Min/+ mice due to the colon tumor development. FDGP countered the weight loss significantly compared to the control and aspirin. Indeed, animals on Aspirin had greater weight loss compared to control indicating that aspirin had negative side effects. We showed that FDGP consuming animals had improved neurological functioning and behavior compared to control and aspirin. These results suggest that FDGP not only counters the colon tumorigenesis but ameliorated cancer cachexia and neurological and behavioral problems in mice. This research is significant because it provides evidence for cancer prevention activity of FDGP in vivo similar to that of drug of choice for cancer prevention but without any negative side effects. This work will form the basis for future mechanistic studies using stem cells and clinical trials to develop safe, effective and affordable science-based whole food prevention/therapeutic strategies against colon cancer.

University of Arizona (Frank Duca). As a new hire at the University of Arizona, for the current project period I focused on setting up my laboratory to initiate my research. This included setting up experimental stations to perform pancreatic euglycemic clamps, which are the gold standard for measuring endogenous glucose production/uptake and insulin sensitivity in rodents. These clamps will allow me to start testing the effect of different nutrients and prebiotic/probiotics on the regulation of glucose homeostasis. In addition, I will be attending a 2 week workshop entitled “Strategies and Techniques for Analyzing Microbial Population Structure” which will enable me to better understand how changes in the diet and/or certain xenobiotics interact with the microbes in the gut, and how these interactions impact the development of diabetes and obesity.

University of Arizona (Jennifer Teske). The laboratory focuses on the negative impact of poor sleep and low physical activity to health. We investigate the relationship between sleep curtailment due to environmental noise and metabolism in a rodent model. We expanded these studies to include female rodents to test sex-specific effects and establish a rodent model of sleep deprivation-induced weight gain for females. These studies revealed that noise exposure reduces sleep by reducing the total time spent asleep and sleep quality indicated by an increased number of awakenings. Moreover, sleep loss due to noise exposure caused weight gain and increased feeding. OUTCOMES: Tested whether noise-induced sleep loss exacerbates hedonic feeding behavior and weight gain in male and female rats and performed a methods comparison noise exposure and the gentle handling technique in males and female rats.

University of California, Berkeley (Barry Shane). We have 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 developed a mouse model that mimics the clinical effects of human B12 and folate deficiency, and which will allow us to investigate potential adverse effects of high folate intake. We continue to evaluate genetic risk factors for neural tube defects and to identify putative modifier genes which influence folate status, homocysteine levels, and methylation potential using a number of mouse strains and a cohort of students at Trinity College, Dublin. Changes in tryptophan metabolism through the vitamin B-6–dependent kynurenine pathway have been linked to activation of the immune system. We hypothesized that blood concentrations of tryptophan and its catabolites were associated with biomarkers relevant to inflammatory processes in healthy non-inflamed subjects. Healthy young adults without any known diseases or clinical evidence of inflammation provided blood samples for analysis of serum tryptophan/kynurenine metabolites, neopterin, C-reactive protein (CRP), and plasma pyridoxal 5’-phosphate (PLP). We observed significant positive associations between serum interleukin-10 and serum kynurenine (P, the kynurenine-to-tryptophan ratio (KTR), 3-hydroxykynurenine, and 3-hydroxyanthranilic acid. Serum neopterin was positively associated with kynurenine, the KTR, and anthranilic acid, and was negatively associated with serum tryptophan and PLP. Serum tumor necrosis factor alpha was also negatively associated with tryptophan. In healthy young adults with no apparent inflammatory conditions, serum tryptophan metabolites are significantly associated with key immune system biomarkers.

University of California, Berkeley (Yanhong Liu). Non-nutrients describe a group of dietary compounds which have no nutrient contribution to animals, but have physiological activities beyond provision of bioavailable nutrients. This year, we were focused on two phytonutrients, β-glucan and essential oils. We conducted an animal trial with pigs to evaluate the effects of β-glucan on disease resistance and immunity of weaned pigs that were experimentally infected with a pathogenic E. coli. Results from this experiment indicate that feeding 100 mg/kg β-glucan could enhance disease resistance of pigs as indicated by the reduced frequency of diarrhea. Supplementation of β-glucan also reduced systemic inflammation and improved gut integrity in E. coli challenged pigs. More lab analysis will be performed to decipher the benefits of supplementing β-glucan, including gut morphology and microbiota changes. In addition, we are looking for the antioxidant effects of essential oils. We have conducted several in vitro assays, including chemical-based antioxidant assays, lipid peroxidation assay, and cellular antioxidant assays to evaluate the in vitro antioxidant activities of several essential oils. Results from this project indicate that essential oils extracted from mint have in vitro antioxidant activities. Animal trial will be planned and conducted to investigate the antioxidant efficacy of those essential oils in vivo.

University of Connecticut (Ji-Young Lee; Sung Koo). We previously showed that the organic extract of a blue-green alga, Spirulina platensis (SPE) had potent anti-inflammatory effects in macrophages. We investigated the contribution of the anti-inflammatory effects of SPE in macrophages to adipogenesis/lipogenesis in 3T3-L1 adipocytes. 3T3-L1 preadipocytes were treated with 10% conditioned medium from LPS-stimulated RAW 264.7 macrophages (CMC) or LPS-stimulated but SPE-pretreated macrophages (CMS) at different stages of adipocyte differentiation. The expression of adipocyte differentiation markers were significantly repressed by CMC, while the repression was attenuated by CMS. Oil Red O staining confirmed that adipocyte maturation in CMS-treated cells, but not in CMC-treated cells, was equivalent to that of control cells. In lipid-laden adipocytes, CMC promoted the loss of lipid droplets while CMS had minimal effects. Histone deacetylase 9 mRNA and protein levels were increased during adipocyte maturation, which were decreased by CMC. In conclusion, by cross-talking with adipocytes, the anti-inflammatory effects of SPE in macrophages promoted adipocyte differentiation/maturation, at least in part, by repressing the activation of NF-kB inflammatory pathways, which otherwise can be compromised in inflammatory conditions. Endotoxin tolerance is a phenomenon where exposure of innate immune cells to lipopolysaccharide (LPS) induces a refractory state to subsequent endotoxin exposures, resulting in a lack of pro-inflammatory cytokine and chemokine production.

We evaluated whether SPE induces endotoxin tolerance-like state to exert its anti-inflammatory effect and to determine its effect of macrophage energy phenotype. Splenocytes and resident peritoneal macrophages from mice fed a HF/high sucrose (HF/HS) diet containing SPE displayed significantly less expression of pro-inflammatory genes than those from control mice. We produced endotoxin tolerant (ET) macrophages in vitro by incubating RAW 264.7 macrophages with low-dose of LPS. Compared to naïve macrophages exposed to a high-dose LPS for the first time, ET macrophages showed significantly less pro-inflammatory gene expression after LPS stimulation, which was also observed with SPE treatment. Consistently, nuclear translocation of p65 was markedly reduced in both ET and SPE-treated macrophages upon LPS stimulation. Both SPE-treated and ET macrophages had increased mRNA and nuclear protein levels of p50 and B-cell lymphoma 3-encoded protein, which play a critical role in endotoxin tolerance. Both SPE-treated and ET macrophages had similar energy phenotype in that they relied more on glycolysis than mitochondrial respiration for energy generation compared to naïve cells. In conclusion, the anti-inflammatory effect of SPE is at least partly attributable to the induction of an endotoxin tolerance-like state in macrophages, which shares common characteristics of macrophage endotoxin tolerance.

University of Illinois, Urbana-Champaign (Juan Andrade). Our research focuses on developing technologies or approaches to improve nutrition in vulnerable populations in the US and abroad. Efforts have been focused on: 1) creating valid survey instruments to measure nutrition knowledge, 2) characterization of legume-based protein nanoaggregates to improve stability and delivery of fat soluble bioactives and nutrients; and, 3) characterization of lipid-based nutrition supplement (LNS) to prevent and control severe acute malnutrition. OUTPUTS: Our team validated a nutrition knowledge questionnaire for adults in Uganda. The instrument consisted of 137 items and is useful to measure basic nutrition knowledge in head teachers using five knowledge domains including: expert recommendations (16 items), food groups (70 items), selecting foods (10 items), nutrition and disease (23 items) and food fortification (14 items). A legume-based nanoparticle system can be advantageous for the delivery of fat soluble compounds that can address nutrition gaps due to its enhanced stability and bioavailability. Nanoaggregates containing vitamin D were characterized in terms of stability and bioavailability in animal models. King Saud University in Saudi Arabia is a major partner in this research endeavor. A Lipid-based nutrition supplement (LNS) for children in India was characterized and evaluated. The product follows WHO guidelines for LNS products, is stable under storage conditions, uses flax seed oil for improved essential fatty acid content, and was accepted by populations in India. OUTCOMES: Bioversity International, a CGIAR institution present in Uganda, used the nutrition knowledge questionnaire to measure knowledge of agricultural extension agents. The novel legume-based protein nanoaggregates can disperse vitamin D and enhance its bioavailability and bioefficacy in vivo. Vitamin D dispersed in legume-based protein nanoemulsion was more stable against UV challenge than vitamin D dispersed water or in water containing lecithin. Reduced particle size enhanced vitamin D bioefficacy. The improved LNS will be used to complement foods provided at Anganwadis centers.

University of Maine (Dorothy Klimis-Zacas). Angiogenesis is a normal biological process that occurs in tissue development and is highly linked to wound healing and atherosclerosis. We investigated the effect of anthocyanin (ACNs) and phenolic acid (PA)-rich fractions and their combination, extracted from wild blueberry powder on endothelial cell migration related to angiogenesis. Cytotoxicity assays documented that ACNs at 1000μg/ml was toxic to HUVECs and was not used in further experiments. Analysis of the time-lapse videos documented ACNs inhibited endothelial cell migration speed while PAs induced migration speed. Moreover, combination of both compounds induced migration speed compared to control. ACNs appear to inhibit HUVEC tube formation (meshes) at a specific concentration while PAs and their combination promote this process. Findings from the above studies suggest that endothelial cell migration and angiogenesis are differentially modulated based on the bioactive fraction and are concentration-dependent. ACNs seem to inhibit HUVEC migration and angiogenesis while PAs promote this process. Further investigation is necessary to determine the mechanisms behind this biological phenomenon with possible implications to atherosclerosis. OUTPUTS: Results from the period covered in this report were disseminated at the American College of Nutrition Conference in San Diego, CA, The Berry Health Benefits Symposium, Pismo Bay, CA, The Graduate School Science Conference, University of Maine.  Additionally, several manuscripts are at different stages of development.  Other outputs include presentations at invited lectures and through the media.

University of Massachusetts (Yeonhwa Park). We have continued our efforts to improve bioaccessibility and bioavailability of bioactives using various delivery systems and structural modifications. In addition, we have continued to test bioactives on new activities along with the determination of their mechanisms of action. Compounds of interests were phenolics found in plants: picaetannol, trans-trimethoxyresveratrol, 3,3'-diindolylmethane, nobiletin, chicoric acid, & p-coumaric acid, as well as fat soluble biotactives; n-3 fatty acids, conjugated linoleic acid, & fat-soluble vitamins. We tested these bioactives on inflammation and cancer in cell culture and rodent animal model. Inaddition, we used Caenorhabditis elegans models for aging and obesity studies.

University of Missouri (Ingolf Gruen). Neem (Azadirachta indica) is an evergreen tree cultivated in various parts of the Indian sub-continent. It has been in use over centuries in the Indian folk medicine for its therapeutic value. Extensive research has shown that it may have anti-cancer, anti-diabetic, anti-inflammatory, anti-ulcerogenic, and anti-microbial effects. However, neem is extremely bitter, in large part due to its limonoid content, making it unpalatable and limiting its potential use in dietary supplements or foods alike. The objective of this experiment was to apply two adsorbent based strategies, namely solid phase extraction and Amberlite XAD-16 (AMB) resin, to achieve de-bittering of neem tea and to determine the effects of the de-bittering on the bio-active, color, and volatile properties. The solid phase extraction treatment completely removed the flavonol, quercetin, from neem tea while in Amberlite XAD-16 treated tea (AMB) it was only insignificantly reduced. We also observed decreases in total phenolic content and consequently anti-oxidant activities after de-bittering. A 62% mean reduction of limonoid aglycones indicated diminished levels of bitterness. The loss of phenolics lead to a visually appreciable color change in the treated teas. The de-bittering also leads to a loss of sesquiterpenes, ketones and acids from neem tea. In conclusion, we found that while solid phase extraction cartridges were more efficient in removing bitterness, they caused a greater reduction in bio-active compounds than AMB XAD-16 resins, which may ultimately affect the health properties of neem tea.

University of Nebraska, Lincoln (Janos Zempleni). Virtually every cell produces and secretes exosomes (nanoparticles) loaded with cargos such as various species of RNAs, proteins and lipids. Exosomes play essential roles in cell-to-cell communication. The transfer of exosomes cargos from donor cells to receptor cells alters gene expression and metabolism in receptor cells. We have made the paradigm-shifting discovery that exosomes and their cargos are not only obtained through endogenous synthesis but also from dietary sources such as bovine milk and chicken eggs. Human intestinal cells transport cow’s milk exosomes by endocytosis and secrete milk exosomes and/or microRNA cargos across the basolateral membrane. Glycoproteins on the surface of exosomes and cells are essential for endocytosis. Fluorophore-labeled exosomes in bovine milk accumulate in resident macrophages in liver and spleen in mice, whereas fluorophore labeled RNAs in exosomes are sorted into endogenous exosomes and accumulate in brain and kidneys in mice. The bioavailability of exosomes in bovine milk is less than 100%, and the unabsorbed fraction causes changes in the gut microbiome in mice. Milk (and chicken egg) exosomes are delivered to peripheral tissues and circulating cells, facilitated by endocytosis of exosomes in human vascular endothelial cells. Postprandial concentrations of milk and egg microRNAs are biologically effective in humans and elicit changes in gene expression in circulating lymphocytes. Endogenous synthesis of microRNAs is insufficient to compensate for dietary microRNA depletion. Depletion of milk exosomes and their RNA cargos elicits phenotypes such as impaired fecundity, aberrant purine and protein metabolism, altered immune function, impaired spatial learning and memory, and changes in the gut microbiome. mRNAs in bovine milk exosomes can be translated into proteins in vitro and in human cell cultures. OUTCOMES: Nineteen visiting scientists, postdoctoral fellows, graduate students, undergraduate students, and staff were advised and supervised. Nine papers, five reviews, 15 meeting abstracts and five outreach publications (newspapers, magazines) were published, and 18 presentations were delivered. A public website was created that disseminates information about dietary microRNAs. Our research includes collaborations with one scientist from this W-3002 group and 10 external scientists.

• Abbas, A., J. A. Hall, W. L. Patterson, 3rd, E. Ho, A. Hsu, F. Al-Mulla and P. T. Georgel (2016). "Sulforaphane modulates telomerase activity via epigenetic regulation in prostate cancer cell lines." Biochem Cell Biol 94(1): 71-81.
• Bailey RL, Weaver CM, Murphy S. Using the Dietary Reference Intakes to assess intakes in Research:  Successful Approaches.  Van Horn L, ed.  Academy of Nutrition and Dietetics, Chicago IL, 2017.
• Brannon PM, Weaver CM, Anderson CAM, Donovan SM, Murphy SP, Yaktine AL. Scanning for new evidence to prioritize updates to the Dietary Reference Intakes:  case studies for thiamin and phosphorus.  Am J Clin Nutr  104:1-12, 2016.
• Beaver, L. M., R. Kuintzle, A. Buchanan, M. W. Wiley, S. T. Glasser, C. P. Wong, G. S. Johnson, J. H. Chang, C. V. Lohr, D. E. Williams, R. H. Dashwood, D. A. Hendrix and E. Ho (2017). "Long noncoding RNAs and sulforaphane: a target for chemoprevention and suppression of prostate cancer." J Nutr Biochem 42: 72-83.
• Choi M-K, Weaver, CM. Daily intake of magnesium and its relation to urinary excretion in Korean healthy adults consuming self-selected diets.  Biol Trace Elem Res.  DOI:  1007/s12011-016-0822-0.
• Conley MN, Roberts C, Sharpton TJ, Iwaniec UT, Hord NG. (2017) Increasing dietary nitrate has no effect on cancellous bone loss or fecal microbiome in ovariectomized rats. Mol Nutr Food Res. May;61(5). doi: 10.1002/mnfr.201600372. Epub 2017 Mar 30.
• Conley, M and Hord, NG (2017) Regulation of dietary nitrate and nitrite: balancing essential physiological roles with potential health risks, In: Nitrates and Nitrites in Human Health and Disease, Editors: Joseph Loscalzo, M.D., Ph.D. (Harvard University) and Nathan S. Bryan, PhD (Texas), New York, NY, Springer/Humana Press, 2^nd edition (book chapter).
• Conley MN, Wong CP, Duyck KM, Hord NG, Ho E, Sharpton TJ. (2016) Aging and serum MCP-1 are associated with gut microbiome composition in a murine model. 2016 Mar 31;4:e1854. doi: 10.7717/peerj.1854.
• Dain A, Repossi D, Diaz-Gerevini GT, Vanamala J, Das UN, Eynard AR. 2016. Effect of polyunsaturated fatty acids with and without nordihydroguaiaretic acid (NDGA) on metabolic and inflammatory indices in a rat model of spontaneous type 2 diabetes mellitus. Lipids in Health and Disease.
• Del Bo C, Porrini M, Campolo J, Parolini M, Lanti C, Klimis-Zacas D, Riso P 2016. A single blueberry (Vaccinium corymbosum) portion does not affect markers of antioxidant defense and oxidative stress in healthy volunteers following cigarette smoking, Mutagenesis 31:215-214.
• Bobe G, CobbTJ, Leonard SW, Aponso S, Bahro CB, Koley D, Mah E, Bruno RS, Traber MG (2017). Increased static and decreased capacity oxidation-reduction potentials in plasma are predictive of metabolic syndrome. Redox Biol, 12:121-128.
• Bukenya, R, Ahmed, A, Andrade, JM, Grigsby-Toussaint, DS, Muyonga, J, Andrade, JE. Validity and reliability of general nutrition knowledge questionnaire for adults in Uganda. Nutrients. 9(2): 172. (2017)
• Charepalli V*, Reddivari L, Vadde R*, Walia S, Radhakrishnan S*, Vanamala J. 2016. Eugenia jambolana (Java Plum) fruit extract exhibits anti-cancer activity against early stage human HCT-116 colon cancer cells and colon cancer stem cells. Cancers 8(3):pii E29.
• Coborn JA, Deporter DP, Mavanji, V, Sinton CM, Billington CJ, Kotz CM, Teske, JA. Role of orexin A in the ventrolateral preoptic area on components of total energy expenditure. International Journal of Obesity. Accepted March 27, 2017. (in press) Epub 4/24/17.
• Conley, M. N., C. P. Wong, K. M. Duyck, N. Hord, E. Ho and T. J. Sharpton (2016). "Aging and serum MCP-1 are associated with gut microbiome composition in a murine model." PeerJ 4: e1854.
• Cordonier EL, Jarecke SK, Hollinger FE, Zempleni J. Inhibition of acetyl-CoA carboxylases by soraphen A prevents lipid accumulation and adipocyte differentiation in 3T3-L1 cells. Eur J Pharmacol 780:202-208, 2016Cotten BM, Diamond SD, Banh T, Hsiao Y-H, Cole RM, Li J, Simons CT, Bruno RS, Belury MA, Vodovotz Y. (2017). Raspberry ketone fails to reduce adiposity beyond decreasing food intake in C57BL/6 mice fed a high-fat diet. Food Funct, 8(4):1512-1518
• Deac OM, Mills JL, Gardiner CM, Shane B, Quinn L, Midttun Ø, McCann A, Meyer K, Ueland PM, Fan R, Lu Z, Brody LC, Molloy AM. (2016) Serum immune system biomarkers neopterin and interleukin-10 are strongly related to tryptophan metabolism in healthy young adults. Nutr. doi: 146: 1801-1806.
• Del Bo C, Deon V, Campolo J, Porrini M, Klimis-Zacas D, Riso P. A serving of blueberry (V. corymbosum) reverses endothelial dysfunction in young smokers and non-smokers: a randomized, controlled, crossover study, Food and Function, 2017 (invited paper, submitted)
• Delimont NM, Chanadang S, Joseph MV, Rockler BE, Guo Q, Regier GK, Mulford MR, Kayanda R, Range M, Mziray Z, Ambaksye J, Mugyabuso J, Msuya W, Lilja NK, Procter SB, Chambers IV E, Alavi S, Lindshield BL. The MFFAPP Tanzania efficacy study protocol: newly formulated, extruded fortified-blended foods for food aid. Curr Dev Nutr. 2017: 1(4) doi: https://doi.org/10.3945/cdn.116.000315.
• Delimont NM, Fiorentino NM, Opoku-Acheampong AB, Joseph MV, Guo Q, Alavi S, Lindshield BL. Newly formulated, extruded sorghum, cowpea, corn, and soy containing fortified-blended foods lead to adequate vitamin A, iron outcomes and improved growth compared with CSB+ in rats. J Nutr Sci. 6: e18 doi:10.1017/jns.2017.15.
• Delimont NM, Haub M, Lindshield BL. Does Tannin Consumption Decrease Iron Bioavailability? Curr Dev in Nutr. 2017. 1(2) doi: https://doi.org/10.3945/cdn.116.000042.
• Ellison D, Morris CE, Locatelli B, Sheil D, Cohen J, Murdiyarso D, Gutierrez V, van Noordwijk M, Creed IF, Pokorny J, Gaveau D, Spracklen D, Bargués Tobella A, Ilstedt U, Teuling R, Gebrehiwot SG, Sands DC, Muys B, Verbist B, Springgay E, Sugandi Y, Sullivan C. 2017. Trees, forests and water: cool insights for a hot world. Global Environmental Change (in press)
• Ferira AJ, Laing EM, Hausman DB, Hall DB, McCabe GP, Martin BR, Hill KM, Warden SJ, Weaver CM, Peacock M, Lewis RD. Vitamin D supplementation effects on insulin sensitivity and resistance in early pubertal white and black children.  J Clin Endocrinol Metab, In Press, 2016.
• Fernández-Aparicio M, Bernard A, Falchetto L, Margert P, Chauvel B, Steinberg C, Morris CE, Gibot-Leclerc S, Boari A, Vurro M, Bohan DA, Sands DC, Reboud X. (2017 Investigation of amino acids as herbicides for control of Orobanche minor parasitism in red clover. Frontiers in Plant Science vol. 8, May 22, 2017; article 842.
• Gaur, S, Sloffer, EM, Ojha, A, Patra, F, Shukla, S, Engeseth, NJ, Patel, PR, Andrade, JE. Omega-3 fortified lipid-based nutrient supplement – development, characterization and consumer acceptability. Food and Nutrition Bulletin. (2017). [In press]
• Graef J, Rendina-Ruedy E, Crockett E, Ouyang P, King J, Cichewicz RH, Lucas EA, Smith BJ. Osteoclast differentiation is downregulated by select polyphenolic fractions from dried plum via suppression of MAPKs and Nfatc1. Plos ONE (under review).
• Guo X, Wu L, Wang W, Medeiros DM, Clarke S, Lucas E, Smith BJ, Chowanadisai W, Lin D. Hypothalamic mitochondria in energy homeostasis and obesity. Integ Mol Med. (in press)
• Guo X, Wu L, Lyu Y, Chowanadisai W, Clarke SL, Lucas EA, Smith BJ, He H, Wang W, Medeiros DM, Lin D. Ablation of β,β-carotene-9',10'-oxygenase 2 remodels the hypothalamic metabolome leading to metabolic disorders in mice. J Nutr Biochem. 2017;46:74-82.
• Jacome-Sosa M, Parks EJ, Bruno RS, Tasali E, Lewis GF, Scheenman BO, Rains TM. (2016). Postprandial metabolism of macronutrients and cardiometabolic risk: recent developments, emerging concepts, and future directions. Adv Nutr, 7(2):364-74.
• Jakeman SA, Henry CN, Martin BR, McCabe GP, McCabe LD, Jackson JS, Peacock M, Weaver CM. Soluble corn fiber increases bone retention in postmenopausal women in a dose-dependent manner:  a randomized crossover trial.  Am J Clin Nutr 104:837-843, 2016.Jiang, S, Ding, J, Andrade, JE, Rababah, TM, Almajwal A, Abulmeaty, MM, Feng, H.  Modifying the physicochemical properties of pea protein by pH-shifting and ultrasound combined treatments. Ultrasonics Sonochemistry. [In Press]
• Johnson, G. S., J. Li, L. M. Beaver, W. M. Dashwood, D. Sun, P. Rajendran, D. E. Williams, E. Ho and R. H. Dashwood (2016). "A functional pseudogene, NMRAL2P, is regulated by Nrf2 and serves as a coactivator of NQO1 in sulforaphane-treated colon cancer cells." Mol Nutr Food Res.
• Kim K, Ehrlich A, Perng V, Chase J, Raybould H, Li X, Atwill ER, Whelan R, Sokale A, Liu Y. 2017. Effects of dietary β-glucan on growth performance, diarrhea, and gut permeability of weanling pigs experimentally infected with a pathogenic coli. ASAS-CSAS Annual Meeting & Trade Show.
• Kim K, Perng V, Chase J, Li X, Atwill ER, Whelan R, Sokale A, Liu Y. 2017. Effects of dietary β-glucan on systemic immunity of weanling pigs experimentally infected with a pathogenic  coli. California Animal Nutrition Conference Proceedings. p.282.
• Kopecky SL, Bauer DC, Gulati M, Nieves JW, Singer AJ, Toth PP, Underberg JA, Wallace, TC, Weaver CM. Lack of evidence linking calcium with or without vitamin D supplementation to cardiovascular disease in generally healthy adults: A position statement from The National Osteoporosis Foundation and American Society for Preventive Cardiology  Ann Intern Med  2016  DOI:10.7326/M16-1743.
• Kristo A, Klimis-Zacas D, Sikalidis AK, Protective role of dietary berries in cancer, In Antioxidants (Special Issue, Berries in Health and Disease, guest editor Dorothy Klimis-Zacas), 2016, 5(4), 37; doi:3390/antiox5040037
• Lee J, Yue Y, Park Y, Lee S-H, 3,3'-Diindolylmethane Suppresses Adipogenesis via AMPK-Dependent Mechanism in 3T3-L1 Adipocytes and Caenorhabditis elegans, Med. Food (Accepted)
• Li J, Sapper TN, Mah E, Moller MV, Kim JB, Chitchumroonchokchai C, McDonald JD, Bruno RS. (2017). Green tea extract treatment reduces NFκB activation in mice with diet-induced nonalcoholic steatohepatitis by lowering TNFR1 and TLR4 expression and ligand availability. J Nutr Biochem, 41:34-41.
• Li Y, Bharath LP, Qian Y, Ruan T, Babu PVA, Bruno RS, Symons JD, Jalili T (2016). γ-Carboxyethyl hydroxychroman, a metabolite of γ-tocopherol, preserves nitric oxide bioavailability in endothelial cells challenged with high glucose. Exp Biol Med, 241(18):2056-2062.
• Lipkie T, Ferruzzi M, Weaver C. Low bioaccessibility of vitamin D2 from yeast fortified bread compared to crystalline D2 bread and D3 from fluid milks.  Food & Function 
• Liu Y. 2016. Non-nutrients in swine health and production. J. Anim. Sci. 94 (E-Suppl.5):489.
• Liu Y, Gonzalez-Vega JC, Vazquez-Anon M, Zhao J, Escobar J, Almeida FN, Stein HH. 2016. Effects of phytase on growth performance and metacarpal bone ash in weanling pigs. J. Anim. Sci. 94 (E-Suppl.2):111.
• Kusuma JR, Manca S, Friemel T, Sukreet S, Nguyen C, Zempleni J. Human vascular endothelial cells transport foreign exosomes from cow’s milk by endocytosis. Am J Physiol Cell Physiol 310:C800-C807, 2016
• Pannier A, Kelly A, Plautz S, Zempleni J. Glucocorticoid cell priming enhances transfection outcomes in adult human mesenchymal stem cells. Mol Ther 24:331-341, 2016
• Parrish JB and Teske JA. Acute partial sleep deprivation due to environmental noise increases weight gain by reducing energy expenditure in rodents. 2017. Obesity (Silver Spring) Jan;25(1):141-146. Epub 11/29/16.
• Massey AR*, Reddivari L, Radhakrishnan S*, Karunathilake E*, Vanamala J. 2016. Pro-apoptotic activity against human cancer stem cells differs between different parts of sweet sorghum, a feedstock for biorefining. Journal of Functional Foods. 25: 267–278.
• Macdonald-Clark, CJ, Martin BR, McCabe LD, McCabe GP, Lachcik PJ, Wastney M, Weaver CM. Bioavailability of potassium from potatoes and potassium gluconate:  a randomized dose response trial.  Am J Clin Nutr  104:346-353, 2016.
• Morris CE, Sands DC. 2017. Impacts of microbial aerosols on natural and agro-ecosystems: immigration, invasions and their consequences. IN: Delort A.M., Amato, P. (eds.) Microbiology of Bioaerosols. Wiley, (in press).
• Morris CE, Soubeyrand S, Bigg EK, Creamean JM, Sands DC. 2016. Mapping rainfall feedback to reveal the potential sensitivity of precipitation to biological aerosols. Bull. Amer. Meteorol. Soc. doi.org/10.1175/BAMS-D-15-00293.1
• Nzioki HS, Oyosi F, Morris C, Kaya E, Pilgeram A, Baker C, Sands D.C. 2016, Striga biocontrol on a toothpick: A readily deployable and inexpensive method for smallholder farmers. Frontiers in Plant Sci. 7: Article 1121.
• Ojo B, Simenson AJ, O’Hara C, Wu L, Gou X, Peterson SK, Lin D, Smith BJ, Lucas EA. Wheat germ supplementation alleviates insulin resistance and cardiac mitochondrial dysfunction in an animal model of diet-induced obesity. Br J Nutr (under review)
• Ojo B, Davila El-Rassi G, Payton M, Perkins-Veazie P, Clarke S, Smith BJ, Lucas EA. Mango supplementation prevents gut microbial dysbiosis and modulates short chain fatty acid production independent of body weight reduction in C57BL/6 mice fed a high fat diet. J Nutr. 2016;146(8):1483-91.
• Pinto JT, Zempleni J. Nutrition information brief – riboflavin. Adv Nutr 7:973-975, 2016Pham, TX, Park Y, Bae M, Lee J. The potential role of an endotoxin-like mechanism for the anti-inflammatory effect of Spirulina platensis in macrophages: Insight into energy phenotype. J Med Food 2017; 20: 201-210.
• Pham TX, Park Y-K, Lee J. Anti-inflammatory effects of Spirulina platensis extract via the modulation of histone deacetylases. Nutrients 2016; 8:E381.
• Pham TX, Lee J. Anti-inflammatory effect of Spirulina platensis in macrophages is beneficial for adipocyte differentiation and maturation by inhibiting Nuclear factor-kB pathway in 3T3-L1 adipocytes. J Med Food 2016; 19:535-542.
• Reddivari L, Charepalli V*, Radhakrishnan S*, Vadde R*, Elias R, Lambert J, Vanamala J. 2016. Dietary grape compounds suppress oncogenic stem cells in a mouse model of chemically-induced colon cancer. BMC Complementary and Alternative Medicine. 16:278-290.
• Rendina-Ruedy E, Graef JL, Lightfoot SA, Ritchey JW, Clarke SL, Lucas EA, Smith BJ. Impaired glucose intolerance attenuates bone accrual in young growing skeleton by promoting the maturation of osteoblasts: role of beclin1-mediated autophagy. Bone Reports 2016 5:199-207.
• Sapper TN, Mah E, Ahn-Jarvis J, McDonald JD, Chitchumroonchokchai C, Reverri EJ, Vodovotz Y, Bruno RS. (2016). A green tea-containing starch confection increases plasma catechins without protecting against postprandial impairments in vascular function in normoglycemic adults. Food Funct, 7:3843-3853.
• Shams-White MM, Chung M, Du M, Fu Z, Insogna KL, Karlsen MC, LeBoff MS, Shapses SA, Sackey J, Wallace TC, Weaver CM. Dietary protein and bone health:  a systematic view and meta-analysis from the National Osteoporosis Foundation.  2017  3945/ajcn.116.145110.
• Sharif S, Mustafa G, Munir H, Weaver CM, Jamil Y, Shahid. Proximate composition and micronutrient mineral profile of wild Ganoderma lucidium and four commercial exotic mushrooms by ICP-OES and LIBS.  J Food Nutr Res  4:703-708, 2016.
• Shen P, Yue Y, Kim K-H, ParkY Piceatannol Reduces Fat Accumulation in Caenorhabditis elegans, Med. Food (Accepted)
• Shen P, Yue Y, Sun Q, Kasireddy N, Kim K-H, Park Y Piceatannol Extends the Lifespan of Caenorhabditis elegans Via DAF-16, Biofactors. (Accepted)
• Smith BJ, Crockett EK, Chongwatpol P, Graef JL, Rendina-Ruedy E, Clarke SL, Lucas EA. Tart cherry supplementation demonstrates anabolic properties by increasing bone mineralization in a model of age-related bone loss. J Nutr (under review).
• Song M, Charoensinphon N, Wu X, Zheng J, Gao Z, Xu F, Wang M, Xiao H (2016) Inhibitory effects of metabolites of 5-demethylnobiletin on human nonsmall cell lung cancer cells, J. Ag. Food Chem. 64: 4943-4949.
• Teixeira CD, Cordonier EL, Wijeratne SSK, Huebbe P, Jamin A, Jarecke S, Wiebe M, Zempleni J. A cell death assay for assessing the mitochondrial targeting of proteins (submitted)
• Thorning TK, Bertram HC, Bonjour JP, de Groot L, Dupont D, Feeney E, Ipsen R, Lecerf JM, Mackie A, McKinley MC, Michalski MC, Rémond D, Risérus U, Soedamah-Muthu SS, Tholstrup T, Weaver C, Astrup A, Givens I. Whole dairy matrix or single nutrients in assessment of health effects: current evidence and knowledge gaps.  Am J Clin Nutr  doi: 10.3945/ajcn.116.151548.
• Thomson, C. A., E. Ho and M. B. Strom (2016). "Chemopreventive properties of 3,3'-diindolylmethane in breast cancer: evidence from experimental and human studies." Nutr Rev 74(7): 432-443.
• Traber MG, Mah E, Leonard SW, Bobe G, Bruno RS. (2017). Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial. Amer J Clin Nutr, 105(3):571-579.
• Tsakiroglou P, Ashworth S, Webber J, DelBo C, Klimis-Zacas D, Anthocyanins and Phenolic acids extracted from wild blueberries (V. augustifolium) differentially modulate endothelial cell migration, Food and Function, 2017 (invited paper, submitted).
• Vadde R*, Radhakrishnan S*, Karunathilake E*, Reddivari L, Vanamala, J. 2016. Indian gooseberry (Emblica officinalis Gaertn.) suppresses cell proliferation and induces apoptosis in human colon cancer stem cells independent of p53 status via suppression of c-Myc and cyclin D1. Journal of Functional Foods. 23:601-613.
• Vendrame S, Tsakiroglou P, Kristo A, Schuschke D and Klimis-Zacas D, Wild blueberry consumption attenuates local inflammation in the Perivascular Adipose Tissue of Obese Zucker Rats, Applied Physiology, Nutrition and Metabolism, in press, 1–7 (0000) dx.doi.org/10.1139/apnm-2016-0160
• Vendrame S, Del Bo C, Ciappellano S, Riso P, Klimis-Zacas D, Berry fruit consumption and Metabolic Syndrome, In Antioxidants (Special Issue, Berries in Health and Disease, guest editor Dorothy Klimis-Zacas),2016, 5(4), 34; doi:3390/antiox5040034
• Vogel KA, Martin BR, McCabe LD, Peacock M, Warden SJ, McCabe GP, Weaver Cm. The effect of dairy intake on bone mass and body composition in early pubertal girls and boys:  A randomized controlled trial.  AJCN  105:1214-1229, 2017.
• Wallace TC, Marzorati M, Spence L, Weaver CM, Williamson PS. New frontiers in fibers:  Innovative and emerging research on the gut microbiome and bone health.  J Am Coll Nutr  2017
• Wang, R., Y. Kang, C. V. Lohr, K. A. Fischer, C. S. Bradford, G. Johnson, W. M. Dashwood, D. E. Williams, E. Ho and R. H. Dashwood (2016). "Reciprocal regulation of BMF and BIRC5 (Survivin) linked to Eomes overexpression in colorectal cancer." Cancer Lett 381(2): 341-348.
• Wang W, Yang J, Qi W, Yang H, Wang C, Tan B, Hammock BD, Park Y, Kim D, Zhang G (2017) Lipidomic Profiling of High-Fat Diet-Induced Obesity in Mice: Importance of Cytochrome P450-Derived Fatty Acid Epoxides, Obesity 25: 132-140.
• Watson, G. W., S. Wickramasekara, Y. Fang, C. S. Maier, D. E. Williams, R. H. Dashwood, V. I. Perez and E. Ho (2016). "HDAC6 activity is not required for basal autophagic flux in metastatic prostate cancer cells." Exp Biol Med (Maywood) 241(11): 1177-1185.
• Weaver CM. Ensuring adequate calcium without concern for safety.  Nutr Today  52:90-92, 2017.
• Weaver CM. Miracle berries:  how blueberries can improve bone health.  K Biobank - Research Publishing International  researchfeatures.com pg 64-67, 2016.
• Weaver CM, Hill Gallant KM 44 Osteoporosis:  The Early Years.  In:  Nutrition in the Prevention and Treatment of Disease  2017, 4th Ed.  Coulston, AM, Boushey, CJ, Ferruzzi MG, DeLahanty LM, eds.  Elsevier, Inc.  Pp 969-989.
• Weaver CM, Jakeman S. 14  Prebiotics, calcium absorption, and bone health:  In:  Nutritional Influences of Bone Health.  International Congress Series Proceedings of the 9th International Symposium on Nutrition Aspects of Osteoporosis, Montreal Canada.  Weaver CM, Daly R, Bischoff-Ferrari H,  eds, Springer, pgs 145-152, 2016.
• Weaver CM, Lawlor M, McCabe GP. 16  Predicting calcium requirements in children.  In:  Nutritional Influences of Bone Health.  International Congress Series Proceedings of the 9th International Symposium on Nutrition Aspects of Osteoporosis, Montreal Canada.  Weaver CM, Daly R, Bischoff-Ferrari H,  eds, Springer, pgs 171-178, 2016.
• Weaver CM, Martin, BR, McCabe GP, McCabe LD, Woodward M, Anderson CAM, Appel LJ. Individual variation in urinary sodium excretion among adolescent girls on a fixed intake.  J Hyperten  34:1290-1297, 2016
• Whisner CM, Martin BR, Nakatsu CH, Story JA, Macdonald-Clark CJ, McCabe LD, McCabe GP, Weaver CM. Soluble corn fiber increases calcium absorption associated with shifts in the gut microbiome:  A randomized dose-response trial in free-living pubertal females.  J Nutr  146:1298-1306, 2016.
• Wu L, Guo X, Hartson S, Davis A, He H, Medeiros D, Wang W, Clarke S, Lucas E, B Smith, von Lintig J, Lin D. Lack of β, β-carotene -9’, 10’-oxygenase (BCO2) leads to hepatic mitochondrial dysfunction and intracellular oxidative stress in mice. Mol Nutr Food Res. 2017;61(5). Epub 2017 Feb 9.
• Wu L, Guo X, Wang W, Medeiros DM, Clarke SL, Lucas EA, Smith BJ, Lin D. Molecular aspects of β, β-carotene-9’, 10’-oxygenase 2 in carotenoid metabolism and diseases. Exp Biol Med. (Maywood) 2016; 241(17):1879-1887.
• Yeoh BS, Saha P, Singh V, Xiao X, Ying Y, Vanamala J, Kennett M, Harvatine K, Joe B, and Vijay-Kumar M. Stearoyl CoA Desaturase-1 Aggravates Colitogenic Potential of Adoptively Transferred Effector T cells. American Journal of Physiology - Gastrointestinal and Liver Physiology. Accepted 6 September 2016.
• Yue JT , Abraham MA , Bauer PV , LaPierre MP , Wang P , Duca FA , Filippi BM , Chan O , Lam TK . Inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity. Nat Commun . 2016;7:13501.
• Zempleni J, Aguilar-Lozano A, Sadri M, Manca S, Wu D, Zhou F, Mutai E, Sukreet S. Biological activities of extracellular vesicles and their cargos from bovine and human milk in humans and implications for infants. J Nutr 147:3-10, 2017
• Zempleni J. Milk exosomes: beyond dietary microRNAs. Nutr Genes (in press)
• Zhang, Z., L. L. Atwell, P. E. Farris, E. Ho and J. Shannon (2016). "Associations between cruciferous vegetable intake and selected biomarkers among women scheduled for breast biopsies." Public Health Nutr 19(7): 1288-1295
• Zhong F, Xu M, Bruno RS, Ballard KD, Zhu J. (2017). Targeted high performance liquid chromatography tandem mass spectrometry-based metabolomics differentiates metabolic syndrome from obesity. Exp Biol Med, 242(7):773-780.