Brief Summary of Minutes of Annual Meeting

Meeting Agenda and Minutes

The annual meeting was hosted on the University of California-Davis campus (Walter A Buehler Alumni Center - Founders Room) on Feb 7-8, 2019. 

Feb 7, 2019

8 AM - Meeting called to order 

Opening remarks were provided by Yanhong Liu (Chair) who welcomed the group and highlighted planned scientific activities.  Additional welcoming and administrative-related remarks were provided by Richard Bruno (Secretary) and Milan Shipka (Administrative Advisor). Introductions were then facilitated among meeting participants.

8:30 AM – Scientific Session I

The following investigators provided an annual update on their research progress in relation to W4002 project objectives. Each presentation was approximately 15 minutes in duration followed by 5-10 minutes of questions from participants.  Ingolf Gruen presented “Issues of concurrent analysis of methylxanthines and flavan-3-ols”. Jennifer Teske presented “Sleep and obesity: role of stress”.  David Sands presented “The search for low glycemic potatoes and nutricrops”. Ji-Young Lee was scheduled to present “Sugar kelp: A new agricultural crop for the prevention of obesity associated disease”, but was unable to attend the meeting due to unforeseen circumstances.

10:00 AM – Executive Session with Deirdra Chester – NIFA National Program Leader

Dr Chester joined the W4002 meeting via Skype for a discussion concerning USDA funding opportunities. It was discussed that the federal shutdown resulted in delays to process awarding of USDA projects, and that priority will be given to process awards prior to issuing a new RFA for the next grant cycle. Dr. Chester offered some non-binding commentary on future RFAs, and indicated that she would inform the group when a new RFA becomes available. Dr. Chester opened up the discussion for questions from W4002 participants.

10:45 AM – Scientific Session II

The following investigators provided an annual update on their research progress in relation to W4002 project objectives: Frank Duca (“Role of the small intestinal microbiota in energy regulation”); Richard Bruno (“Gut-level benefits of phytochemicals for alleviating endotoxemia”); Lavanya Reddivari (“Anthocyanin anti-inflammatory properties – Role of gut bacteria”)

12 PM – Break

1 PM – Administrative Discussion led by Milan Shipka (W4002 Administrative Advisor)

Dr. Shipka presented administrative responsible of the group for annual reporting and directed the group to elect a secretary. The current chair (Yanhong Liu) has completed her elected duties and is outgoing following the meeting. Current secretary (Richard Bruno) will be responsible for preparing and submitting the annual report in coordination with Dr. Shipka, and will host/chair the next annual meeting, likely at Ohio State University (Columbus, Ohio) during spring 2020.  Jamie Amengual Terrasa was nominated and unanimously elected to serve as the W4002 secretary to replace the outgoing secretary and to provide assistance with planning of the 2020 meeting.

1:30 PM – Scientific Session III

The following investigators provided an annual update on their research progress in relation to W4002 project objectives, with each 15-minute presentation followed by a Q&A session to stimulate collaborations: Peng Ji (“Risk of iron overload at infancy, a study using neonatal pig model”); Janos Zempleni (“Effects of milk exosomes and their RNA cargos on anti-viral response and postnatal growth”); Yanhong Liu (“Probiotics on intestinal health of weaned pigs”)

2:45 PM - Break

3:00 PM – Scientific Session IV

The following investigators provided an annual update on their research progress in relation to W4002 project objectives, with each 15-minute presentation followed by a Q&A session to stimulate collaborations: Barry Shane (“Genetic modifiers of folate status biomarkers”); Emily Ho (“Dietary bioactive, age-related inflammation and toxicological responses”); Dingbo Lin (“Carotenoid metabolism in mitochondrial biology”); Jaime Amengual (“β-carotene conversion to vitamin A regulates lipid metabolism”); Breitta Oaks (“Fatty acids, cortisol, and lead during pregnancy”)

5:00 PM Day 1 Adjourn

Feb 8, 2019

9 AM - Meeting called to order 

9:15 AM – Business Plan Discussion

Richard Bruno (Secretary) discussed annual reporting requirements.  Participants were provided information to assemble individual reports for the reporting period, which would be utilized for assembling a composite report for subsequent submission to USDA within 60 days of conclusion of the W4002 meeting.  Richard Bruno, in his capacity as incoming chair of W4002, also discussed preparations for the 2020 meeting.  The group agreed to hold the meeting in the Ohio State University campus area (Columbus, Ohio) during spring 2020.  A survey will be distributed electronically in approximately 6-months to identify preferred meeting dates for W4002 participants.

10:00 AM – Collaborative Activities

W4002 participants assembled in groups to discuss potential collaborative activities in relation to presentations delivered.  Participants were provided opportunity to explore and discuss the following federal RFAs as potential collaborative opportunities.

• Age-related Microbiota Changes and their Implications in Chronic Disease Prevention, Treatment and Progression (R01 Clinical Trial Optional; https://grants.nih.gov/grants/guide/pa-files/PA-18-738.html; R21 Clinical Trial Optional; https://grants.nih.gov/grants/guide/pa-files/PA-18-739.html)
• Advancing Mechanistic Probiotic/Prebiotic and Human Microbiome Research (R01 Clinical Trial Not Allowed; https://grants.nih.gov/grants/guide/pa-files/PA-18-876.html; R01 Clinical Trial Optional; https://grants.nih.gov/grants/guide/pa-files/PA-18-902.html)
• Food Specific Molecular Profiles and Biomarkers of Food and Nutrient Intake, and Dietary Exposure (R01 Clinical Trial Optional) (https://grants.nih.gov/grants/guide/pa-files/par-18-727.html)
• The Mechanistic Role of the Microbiome in the Pathobiology of Heart, Lung, Blood, and Sleep Diseases (R01 - Clinical Trial Not Allowed) (https://grants.nih.gov/grants/guide/pa-files/PA-18-784.html)
• Nutrigenetics and Nutrigenomics Approaches for Nutrition Research (R01 Clinical Trial Optional) (https://grants.nih.gov/grants/guide/pa-files/PA-18-034.html)
• Role of Gut Microbiome in Regulating Reproduction and Its Impact on Fertility Status in Women Living with and Without HIV (R01 Clinical Trial Optional) (https://grants.nih.gov/grants/guide/pa-files/PA-18-838.html)
• USDA AFRI - Agriculture and Food Research Initiative - Foundational and Applied Science Program (https://nifa.usda.gov/funding-opportunity/agriculture-and-food-research-initiative-foundational-applied-science-program)

12 PM – Meeting adjourned

Kansas State University (Brian Lindshield). Background: We completed 3 studies focused on micronutrient bioavailability from food aid products. Activities: The first study examined iron outcomes in sorghum-soy versus corn-soy fortified blended foods with whey protein concentrate or more soy to reach equivalent protein levels and different levels of sugar. The second study examined the iron outcomes among rice fortified with different forms of iron. The third study examined iron and zinc outcomes in different Senegalese millet varieties. All 3 studies used rats to assess these outcomes. Outcomes: All fortified blended foods resulted in equal iron outcomes, interestingly in the sorghum-soy fortified blended foods in particular seem to be adequate without the addition of whey protein concentrate. In rice ferric pyrophosphate led to better outcomes that ferric phosphate. However, neither micronizing, nor adding both citric acid and trisodium citrate to, ferric pyrophosphate improved iron outcomes. There were not differences in iron and zinc outcomes found between the different millet varieties.

Ohio State University (Richard Bruno). Background: Green tea extract, which is rich in polyphenolic catechins, alleviates metabolic endotoxemia and NFkB inflammation to protect against obesity and nonalcoholic fatty liver disease. Activities: We conducted studies in obese mice and obese humans to examine the extent to which green tea extract prevents gut-derived endotoxin translocation and systemic TLR4/NFkB inflammatory responses implicated in metabolic disorders. Outcomes: Studies in humans are ongoing.  Studies in mice fed a high-fat diet demonstrate that green tea extract decreased intestinal and adipose TLR4/NFkB inflammation in association with reduced body mass. This was accompanied by decreased circulating endotoxin in association with decreased portal vein endotoxin and greater expression of intestinal tight junction proteins, especially in the distal gut. Functional measures also indicate that green tea extract prevented the absorption of FITC-dextran that was otherwise increased in mice fed a high-fat diet. These data indicate that green tea extract protects against diet-induced obesity consistent with a mechanism involving the gut-adipose axis that limits endotoxin translocation and consequent adipose TLR4/NFκB inflammation by improving gut barrier function. Studies in humans are expected to translate these preclinical findings intro practical dietary recommendations that help to manage the risk of metabolic disorders driven by TLR4/NFkB inflammation.

Oklahoma State University (Dingbo Lin). Background: Carotenoids are a large group of lipophilic pigments. Dietary ingestion is the only source of carotenoids for human nutrition and health. My laboratory focuses on the health benefits of carotenoids and the metabolic enzymes in the prevention of obesity, diabetes, and influenza virus infection. Activities: We used mouse models to determine: 1) astaxanthin alteration of gut microbiome in the wild type and beta-carotene oxygenase 2 (BCO2) knockout mice; 2) BCO2 status in animal energy metabolism and inflammation. Outcomes: We identified the specific profiles of gut microbiome in response to astaxanthin, BCO2 status (with or without BCO2 in mice), and gender. We also characterized that BCO2 expression levels were significantly decreased in the diabetic human liver. Deletion of BCO2 caused low grade inflammation, elevation of blood glucose, and impaired health.  

Oregon State University (David Dallas). Background: Human milk evolved to provide nourishment, immunoprotection and support for the development of a commensal-dominant gut microbiome for term infants. Milk proteins are carriers of encrypted bioactive peptides with antimicrobial, immunomodulatory, anti-hypertensive, calcium delivery and gut barrier enhancement functions. These peptides must be released during infant digestion to be biologically relevant. Preterm infants have poor protein digestion and a structurally and functionally immature digestive system. Little evolutionary adaptation to provide optimal nutrition to significantly preterm infants is likely, as these infants rarely survived prior to advances in modern medical care. Therefore, bioactive peptides that evolved to be released within the term infant may be missing in the preterm infant. Differential or sub-optimal release of these bioactive peptides in early premature infants could conceivably alter health outcomes in multiple ways.  Though evidence has shown that the premature infant gut is structurally immature and protease production is decreased, what remains unknown is how these changes impact the overall breakdown of human milk proteins and release of bioactive peptides in the premature infant. There is, therefore, a critical need to determine how prematurity affects protein digestive function, the release of bioactive peptides in the infant gut, and how that ultimately impacts the infant. Our long-term research goal is to identify the optimal protein nourishment for preterm neonates to improve developmental outcomes. Our overall objective of our several funded projects is to examine the release of peptides in the digestive tract of infants, determine their functions and determine which peptides are missing in the preterm infant gut. These projects have potential for significant impact in that the identification of the degree to which digestion and the release of bioactive peptides is impaired for preterm infants will inform ways in which mother's milk and donor milk could be augmented, for example, with enzymatic supplementation or bioactive peptide supplementation to improve infant gut health. Activities: 1) We have determined the peptides released in the stomach of term and preterm infants; 2) We have determined which milk and gastric proteases are responsible for peptide release; 3) We have identified hundreds of released peptides that are homologous with known functional peptides; 4) We have established a database of known bioactive milk peptides from across literature that is open to all. Outcomes: 3 postdoctoral scholars, 2 graduate students and 6 undergraduates were supervised. Fifteen manuscripts were published and 17 research presentation were given. Our research includes collaborations with many other scientists, including neonatologists in Oregon at Oregon Health & Sciences University and Randall Children’s Hospital.

Oregon State University (Emily Ho). Background: Diet plays an important role in mitigating the development and progression of several cancers, including prostate and breast.   This research demonstrates that nutritional strategies that decrease oxidative stress, inflammation, DNA damage and/or target aberrant epigenetic alterations, such as acetylation and methylation, in prostate and breast cancer have the potential to dramatically reduce the incidence of cancer.    Secondly, declining nutritional status may be a critical determinant of healthy aging and susceptibility to environmental insults.  Activities: We have completed two clinical trials investigating the impact of broccoli sprout supplementation in breast and prostate cancer patients.  We have found that supplement are bioavailable and altered expression of AMCR and novel lncRNA.  Unlike breast cancer patients, supplementation did not change proliferations markers in prostate.  We have also employed zebrafish and rodent models to understand the impact of zinc status on exposure to arsenic.  We have discovered that zinc deficiency sensitizes the microbiome to arsenic induced microbiota changes and oxidative stress.  Finally we have utilized aging mouse models to examine the interrelationship between age-related inflammation and microbiome.  We have found that aged mice have higher susceptibility to zinc losses and chronic inflammation that is reversed with zinc supplementation.  Outcomes:  We have identified new risk factors in prostate and breast cancer and offer novel dietary modifications to reduce the incidence of cancer; Gained knowledge of the mechanisms behind the health benefits of micronutrients and phytochemicals such as zinc and compounds derived from cruciferous vegetables; Established low dietary zinc as risk factor for inflammatory processes, DNA damage and cancer risk and identify new biomarkers for human zinc deficiency;  Established function of zinc and changes in zinc metabolism with toxicological stresses, development and aging.

Oregon State University (Norm Hord). Background: Our laboratory studies the effects of nitrate and nitrite because plant foods rich in these ubiquitous anions lower blood pressure, improve athletic performance and alter behavior in animal models and humans. Activities: We used a zebrafish (Danio rerio) to determine the effect of nitrate (606 mg/liter) and nitrite treatment (19.5 mg/ liter) on exercise performance, as measured by oxygen consumption during a strenuous 2 hour swim test, and behavior as indicated by startle response, shuttle box, free swim, and swim zone assays. After three weeks of nitrate and nitrite exposure, fish were euthanized whole body and brains extracted in 4:1 methanol:water and metabolites  analyzed for untargeted metabolomics. Outcomes: Nitrate treatment of zebrafish improved endurance, as indicated by the decreased the oxygen cost of exercise, as observed in humans, while nitrite exposure increased the oxygen cost of exercise. Nitrate treatment was associated with changes in the relative abundance of metabolic fuels for energy production, both at rest and after exercise, and nitrate-induced difference in net utilization of different fuel sources (such as glycolytic and TCA intermediates, fatty acids, lactate and ketone bodies) may contribute to improvements in exercise performance. While nitrite had similar effects as nitrate on the abundance of metabolites at rest, the data suggest that nitrite treatment lead to net depletion of fatty acids for energy production during exercise. Behavioral assays demonstrate that both nitrate and nitrate treatments altered cognitive function in zebrafish. Brain pathway analysis showed significant differences in more than fifty compounds when comparing the metabolites of control fish with the treatments fish. Overall, we found a very significant depletion in many important metabolites involved in the regulation of neuronal membrane potential. Our metabolomics results correlate well with observed behavioral patterns, anxiety and difficulty to learn in fish exposed to nitrite and nitrate.

Purdue University (Lavanya Reddivari). Background: Gut health is integral to overall health. Recent evidence suggests that gut bacteria are implicated in a variety of chronic diseases including colonic inflammation and related disorders such as colitis. Diet is one of the major factors that influence the gut bacterial profiles. Thus, understanding the interaction between dietary bioactive compounds and gut bacteria in the context of colonic inflammation and oxidative stress will aid in developing evidence-based food products to counter chronic diseases in the US and globally. Activities: To determine the effect of potato bioactive polyphenols on gut inflammation, an animal study has been conducted using DSS induced murine colitis model and IL-10 KO mice model. Mice exposed to DSS in drinking water for seven days showed a significant reduction in colon length, increase in spleen weight (splenomegaly) and liver hypertrophy (increase in liver weight) - typical symptoms of colitis. Outcomes: Intestinal permeability, measured by serum levels of FITC-dextran, was significantly elevated in C57BL/6 wild-type mice on control diet after DSS exposure. Mice supplemented with color-fleshed potatoes at 15 and 25% resisted the DSS-induced reduction in colon length. Purple-fleshed potato supplementation reduced splenomegaly and liver hypertrophy. IL-10KO mice on control diet showed splenomegaly, liver hypertrophy, rectal prolapse and fecal occult blood. IL-10KO mice on purple-fleshed potato diet showed a reduction in splenomegaly and liver hypertrophy compared to IL-10KO mice on the control diet and were similar to wild-type mice. We also completed animal experiments using both conventional and microbiota ablated mice to understand the role of microbiota in the anti-inflammatory potential of color-fleshed potatoes.

Purdue University (Connie Weaver). Background: Blueberries and other fruits with high polyphenolic content have been associated with reducing postmenopausal bone loss.  Activities: We determined the effective dose in an OVX animal model and completed a chronic feeding intervention.  Fecal samples were analyzed for gut microbial communities.  Outcomes: We completed the intervention of a clinical trial in postmenopausal women and are completing sample and data analysis. With collaborators, we are exploring antioxidant and anti-inflammatory mechanisms.

University of Arizona (Frank Duca). Background: My lab is focused on determining how different diets and environmental factors contribute to the development of diabetes and obesity. We are interested in how changes in the gut microbiota and metabolites influence gut-brain axis regulation of glucose and energy homeostasis. Activities: Over the past year, the lab has focused on the role of oligofructose, a prebiotic, in increasing intestinal sensing mechanisms during high-fat feeding. We have found that oligofructose improves the ability of the small intestine to sense nutrients, and that this was dependent on the prebiotic altering the gut microbiota. Outcomes: As such, the lab has demonstrated that oligofructose driven improvements in small intestinal microbiota result in improved energy homeostasis, the first study to ever demonstrate a role of prebiotics in altering small intestinal microbiota to improve metabolism. 

University of Arizona (Jennifer Teske). Background: The laboratory focuses on the impact of insufficient sleep to chronic disease and health outcomes. We investigate how sleep curtailment due to environmental noise exposure worsens metabolic health and how consumption of Westerns diets exacerbates disease risk during sleep disruption in rodent models. We are also interested in addressing sex differences since women are more sensitive to noise, have worse sleep and a higher prevalence of obesity compared to men. These studies revealed that females are more sensitive to the weight-promoting effects of a palatable western diet and that sleep disruption exacerbates the weight-promoting effects of a palatable western diet in both males and females. Finally, consumption of western diets disrupts calorie intake across the estrous cycle and both sleep disruption and consumption of cafeteria diet reduced estradiol levels. Activities: We performed validation studies to determine effects of sleep disruption and cafeteria diet on sex hormones, tested for an interaction between diet and estrous cycle phase on calorie intake and weight gain, tested for sex differences in sensitivity to cafeteria diet and sleep disruption and characterized combined effect of sleep disruption and cafeteria diet feeding on glucose and liver outcomes in male rats. Outcomes: We provided surgery training and determined proficiency for students at all levels, provided hands training on anthropometrics, energy expenditure, energy intake and estrous cycle determination and scientific writing and presentation skills training for both oral and poster presentations for students at all levels.

University of California-Berkeley (Barry Shane). Background: 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 continue to evaluate genetic risk factors for neural tube defects and to identify putative modifier genes which influence folate and vitamin B12 status, homocysteine levels, and methylation potential using a number of mouse strains and a cohort of students at Trinity College, Dublin. Activities: We carried out candidate gene analyses and genome-wide association scans in 2232 young, healthy Irish subjects to evaluate which common genetic polymorphisms influence red cell folate, serum folate and plasma total homocysteine.  Outcomes: The MTHFR 677C->T (rs1801133) variant was the major genetic modifier of all three folate related biomarkers in this Irish population and reached genome-wide significance for red cell folate (p = 1.37 x 10-17), serum folate (p = 2.82 x 10-11) and plasma total homocysteine (p = 1.26 x 10-19) concentrations. A second polymorphism in the MTHFR gene (rs3753584, p = 1.09 x 10-11) was the only additional MTHFR variant to exhibit any significant independent effect on red cell folate.  Other MTHFR variants, including the 1298A->C variant (rs1801131), appeared to reach genome-wide significance, but these variants shared linkage disequilibrium with MTHFR 677C->T and were not significant when analyzed in MTHFR 677CC homozygotes. Two additional genome-wide significant modifiers of plasma homocysteine were found in the region of the DPEP1 gene on chromosome 16 and the TWISTNB gene on chromosome 7.

University of California-Davis (Peng Ji). Background: Our current research aimed to investigate how early life iron excess affect systemic iron homeostasis and neurodevelopment. Activities: During the reporting period of W4002, we conducted two studies using neonatal piglets as translational model to address research objectives. Outcomes: In study 1, neonatal piglets were randomly assigned to treatments that received different iron supplementation (0, 100 mg i.m. injection, 10 mg/kg·d, or 50 mg/kg·d from birth to postnatal day 21). Our major findings are 1) dietary iron excess in early life cause systemic and brain iron overload in nursing piglets; 2) Piglets received high iron supplement showed behavioral phenotypes of diminished social novelty recognition, however, the sociability were normal among all treatment groups; 3) untargeted metabolomics analysis unveil significant enrichment of purine metabolism in hippocampus of iron overloaded piglets compared to those without iron supplementation; 4) Iron excess increased hippocampal lipid peroxidation and decreased expression myelin basic protein, which may explain altered social novelty preference; 5) mRNA expression of iron regulatory proteins/transporters were altered by iron supplement to the direction that is unfavorable to iron uptake. However, protein expression of ferroportin in gut, the primary iron transporter, was not affected by iron overloading. This may attribute to iron overload during early postnatal period. In study 2, we evaluated the risk and benefits of dietary iron excess on growth and iron homeostasis in newborns with low birth weight using piglet model. Neonatal piglets with either normal birth weight or low birth weight were assigned to either high iron or normal oral iron supplement from birth to postnatal day 21. We are currently working on lab analysis of the samples. Results will be reported in next annual meeting.  

University of California-Davis (Yanhong Liu). Background: Recently, a novel concept, non-nutrients, is illuminated to describe a group of dietary compounds which have no nutrients contribution to animal, but have physiological activities beyond provision of bioavailable nutrients. Those dietary compounds include but not limited to phytochemicals, prebiotics, probiotics, etc. Emerging evidence suggested that these non-nutrients provided benefits on animal health and production through different modes of action: regulating nutrient digestibility or absorption, and modulating microbial ecology in the digestive tract and/or immune responses. Activities: We were focusing on several probiotics strains on animal health. We have conducted couple animal trials with pig to evaluate the effects of probiotics (Bacillus subtilis or Bacillus spp.) on disease resistance and immunity of weaned pigs that were experimentally infected with a pathogenic E. coli. Outcomes: We observed very positive benefits of supplementing probiotics in animal feed on weaned pig health and performance. New grant was obtained from National Pork Board to support more research on probiotics in pigs. In one year of W-3002 support, 2 visiting scientists, 4 graduate students, and several undergraduate students were supervised.

University of Connecticut (Ji-young Lee). Project 1 - Treatment of liver fibrosis is very limited as there is currently no effective anti-fibrotic therapy. Spirulina platensis (SP) is a blue-green alga that is widely supplemented in healthy foods. The objective of this study was to determine whether SP supplementation can prevent obesity-induced liver fibrosis in vivo. Male C57BL/6J mice were randomly assigned to a low-fat (LF) or a high-fat/high-sucrose/high-cholesterol (HF) diet, or HF diet supplemented with 2.5% SP (w/w) (HF/SP) for 16 or 20 weeks. There were no significant differences in body weight, activity, energy expenditure, serum lipids, or glucose tolerance between mice on HF and HF/SP diets. However, plasma alanine aminotransferase level was significantly reduced by SP at 16 weeks. Expression of fibrotic markers and trichrome stains showed no differences between HF and HF/SP. Splenocytes isolated from HF/SP-fed mice had lower inflammatory gene expression and cytokine secretion compared to splenocytes from HF-fed mice. SP supplementation did not attenuate HF-induced liver fibrosis. However, the expression and secretion of inflammatory genes in splenocytes were significantly reduced by SP supplementation, demonstrating the anti-inflammatory effects of SP in vivo. Although SP did not show an appreciable effect on the prevention of liver fibrosis in this mouse model, it may be beneficial for other inflammatory conditions. Project 2 - Although the anti-inflammatory effects of astaxanthin (ASTX) have been suggested, the underlying mechanisms have not been fully understood. Particularly, the modulatory action of ASTX in the interplay between nuclear factor E2-related factor 2 (NRF2) and nuclear factor κB (NFκB) to exert its anti-inflammatory effect in macrophages is unknown. The effect of ASTX on mRNA and protein expression of pro-inflammatory and antioxidant genes and/or cellular reactive oxygen species (ROS) accumulation were determined in RAW 264.7 macrophages, bone marrow-derived macrophages (BMDM) from wild-type and Nrf2 deficient mice, and/or splenocytes and peritoneal macrophages of obese mice fed ASTX. The effect of ASTX on M1 and M2 macrophage polarization was evaluated in BMDM. ASTX significantly decreased LPS-induced mRNA expression of interleukin 6 (Il-6) and Il-1β by inhibiting nuclear translocation of NFκB p65; and attenuated LPS-induced ROS with an increase in NRF2 nuclear translocation, concomitantly decreasing NADPH oxidase 2 expression in RAW 264.7 macrophages. In BMDM of WT and Nrf2-deficient mice, ASTX decreased basal and LPS-induced ROS accumulation. The induction of Il-6 mRNA by LPS was repressed by ASTX in both types of BMDM while Il-1β mRNA was decreased only in WT BMDM. Furthermore, ASTX consumption lowered the LPS sensitivity of splenocytes in obese mice. ASTX decreased M1 polarization of BMDM while increasing M2 polarization. ASTX exerts its anti-inflammatory effect by inhibiting the nuclear translocation of NFkB p65 and by preventing ROS accumulation in NRF2-dependent and -independent mechanisms. Thus, ASTX is an agent with anti-inflammatory and antioxidant properties that may be used for the prevention of inflammatory conditions.

University of Hawaii (Kacie Ho). Background: Many agricultural commodities are known to be rich sources of nutrients, vitamins, minerals, and bioactive phytochemicals (e.g., polyphenols, carotenoids), all of which may provide beneficial health effects. However, health impacts and bioactivity of many phytochemicals are limited by their bioaccessibility, i.e., the relative amount of phytochemical that is stable against digestion and available to be absorbed in the small intestines. Our goals are to identify and quantify the major nutrients and phytochemicals (and their potential interactions) in post-harvest commodities across different varieties and to elucidate the effect of food matrix on bioaccessibility. Gaining a better understanding of phytochemical bioaccessibility, namely the effects of plant variety and processing on bioaccessibility, will help to optimally deliver benefits from available crops for the local consumer or to add-value to exported products. Activities:  Bioactive phytochemicals will be extracted from agricultural commodities (e.g. raw fruit vs. processed fruit). Bioaccessibility will be measured by subjecting samples to a simulated digestion to estimate the relative amount that is stable against digestion and available for absorption. Data/results will provide evidence on if certain types of processing or varieties of agricultural products or to provide improved bioaccessibility of bioactive phytochemicals compared to others. This project therefore aims to establish knowledge that can be used to optimize nutrition information/diet so that individuals can more efficiently obtain health-promoting components from their food. This is expected to allow the public to select and process/cook foods in a manner that best optimizes nutrient intakes. This could also help local growers to add-value to special (e.g., nutrient dense or highly bioaccessible) varieties or enable them/industry to make products that can better deliver nutrients. Outcomes: Dr. Kacie Ho is new to the W4002 project (approved Feb. 11, 2019), and outcomes will be reported in future years.

University of Illinois – Urbana-Champaign (Jaume Amengual). Background: Carotenoids are one of the most important bioactive molecules in plants. Among them, β-carotene is particularly important as it is the main precursor of vitamin A in mammals. My laboratory focuses on understanding the role of β-carotene in obesity and atherosclerosis, two diseases deeply related to lipid metabolism. Activities: This past year, my laboratory was focused on elucidating the mechanism(s) by which β-carotene reduces cholesterol and triglyceride plasma levels. Using a mouse model lacking the enzyme involved in conversion of β-carotene to vitamin A, we observed that the bioactive molecule responsible of these effects was retinoic acid, a vitamin A derivative. Mice and hepatic cells exposed to retinoic acid showed a reduced cholesterol and triglyceride secretion rate, which correlated to a reduced apolipoprotein B100 (apoB100) levels, the main component of very-low density lipoproteins (VLDL). The positive effects of β-carotene and retinoic acid on plasma lipid levels were clinically evaluated by using a LDL receptor deficient mice (Ldlr-/- mice). We fed Ldlr-/- mice a diet containing cholesterol and fat for 12 weeks (Control diet) or containing the same components and 50 mg of β-carotene (β-carotene diet) for the same time. We observed that mice fed β-carotene had a lower incidence of atherosclerosis by evaluating the accumulation of macrophages in the aortic root of these mice. Outcomes: This work is currently under preparation, we expect to finish a publication including these data by the end of this year.

University of Maine (Dorothy Klimis-Zacas). Background: Atherosclerosis is a chronic inflammatory, progressive disease of the large arteries that can lead to CVD and stroke. Angiogenesis is the formation of new capillary blood vessels from existing ones and endothelial cell migration and proliferation contribute to the development of angiogenesis; critical in the early stages of atherosclerosis. Wild blueberries (Vaccinium angustifolium) are rich in anthocyanins (ACNs) and phenolic acids (Phen) having an exceptional ranking for antioxidant capacity compared to other berries and fruits. Activities: In one project, we continued to investigate the effect of ACNs and Phen fractions and their combination on endothelial cell migration and angiogenesis and mechanisms thereof, by exploring relevant biomarkers of cell migration and angiogenesis such as RhoA, Rac1 GTPases, AKT, VEGF and eNOS and their gene expression, critical for cell morphology, cytoskeleton integrity, cell permeability, angiogenesis and cell migration. In a second project, targets the role of Red Raspberries (Rubus idaeus) on endothelial function (vasoconstriction and vasodilation) and obesity-induced inflammation by assessing pro-inflammatory markers and their gene expression in hepatic and adipose tissues in an animal model of the Metabolic Syndrome (MetS), the Obese Zucker Rat (OZR). Outputs: For project 1, preliminary results document a differential response of the above bioactive compounds on endothelial cell migration and relevant proteins and their gene expression, based on type of fraction and its concentration. Studies on angiogenesis also document a concentration-depended effect, critical concentrations at which angiogenesis is modulated and differential response based on the different fractions (ACNs or Phen). ACNs seem to inhibit HUVEC migration and angiogenesis while PAs promote this process. In Project 2, preliminary results support the role of Red Raspberries in normalizing the endothelial dysfunction and attenuating inflammation associated with MetS.

University of Missouri (Ingolf Gruen). Background: One of the key elements affecting bioavailability and bioactivity of nutrients is the food matrix that they are in. Thus, the analysis of the concentration of volatile and non-volatile (phyto-) nutrients and the estimation of their release from the food matrix is directly related to their potential bioavailability and bioactivity. Chocolate is made from the fermented, dried, and roasted seeds of the Theobroma cacao tree. It is now understood that cacao, contains a variety of compounds, including well-known flavonoid polyphenols, the consumption of which has positive impacts on human heart health and blood pressure, cancer reduction, LDL cholesterol reduction, and insulin resistance improvements, as numerous in vitro, in vivo, and observational studies have confirmed. A persuasive case has, therefore, been made that cacao is a healthful addition to a balanced diet. However, despite the strong evidence for the healthful qualities of cacao, which has led to an overall increase in consumer purchases of more high-cacao-content chocolate than in previous decades, sales figures still show that there is an unwillingness by many Americans to consume higher-cacao-content chocolate, which tends to be more bitter, a taste modality not readily appreciated by most. Therefore, if the bitterness of cacao could be minimized, higher-cacao-content and lower-sugar chocolate confection sales could capture an even larger segment of the conventional and healthy snack-food market by achieving the elusive combination of being both tasty and healthy. Activities: In the context of this project, we initiated an investigation into the bioactive compounds and the resulting bitterness of cacao and chocolate, specifically our goal is to identify and quantify the complex mixture of important bitter compounds within the three compound classes that are known to be important to cocoa--methylxanthines, flavan-3-ols, and diketopiperazines. After project initiation, cocoa beans were obtained from Ghana, Madagascar, and Peru and have been roasted according to a standard roasting profile by chocolate manufacturer Patric Chocolate, LLC. As an initial preliminary project to show proof-of-concept, we produced three 70% dark chocolates differing only in their roast profile (raw, generic medium roast, generic dark roast), and, in addition to chemical analysis, we had 126 chocolate consumers rate “Overall Liking”, “Perceived Sweetness”, and ”Perceived Bitterness” on 9-point scales. Outcomes: Methods have been developed and validated, and standard curves have been established for the cocoa bitter compounds: Caffeine, Theobromine, Catechin, Epicatechin, and selected Diketopiperazines (DKPs), including cyclo(L-Pro-L-Val), which according to the most recent literature available is considered the most important DKP in regards to cocoa bitterness. Analysis of variance (ANOVA) of our initial cocoa roast showed significant differences (p<0.05) between the chocolates. Significantly lower bitterness and higher liking were seen for both of the roasted chocolates, with the Medium-Roast having the lowest bitterness and highest liking rating. The bitter compounds caffeine, Theobromine, Catechin, and Epicatechin were found in all samples. While we were able to positively identify cyclo(L-Pro-L-Val) in the very dark roasted cocoa using LC-MS-MS, which then allowed us to also detect and quantify this diketopiperazine in other roasts, the concentration of cyclo(L-Pro-L-Val) is apparently considerably lower, i.e. only about 5-10% of that reported in the literature. There are known methods for analysis of bitter flavan-3-ols in plant materials in general, and cacao in particular, but there are also well-defined pitfalls known for such analyses, including the labile and reactive nature of flavan-3-ols, including the monomer of (-)-epicatechin in particular. It is known, for example, that as flavan-3-ols are extracted from the cacao tissue, they begin to oxidize, epimerize, polymerize and otherwise degrade in ways that are quite difficult to characterize. For this reason, we are attempting to circumvent the problem of flavan-3-ol analysis in chocolate by analyzing the compounds directly within the cacao matrix, or by desorbing and analyzing within several brief moments. Our first attempt to use solid-state NMR to analyze the flavan-3-ols in situ did not result in sufficiently intense peaks for the flavan-3-ol compounds within the background of the cacao matrix, even after cocoa butter extraction. We are now pursuing matrix-assisted laser desorption/ionization (MALDI) analysis using solvent-free sample preparation and instrumentation in the Metabolomics center here on the University of Missouri-Columbia campus. Literature suggests that other lipid-rich and waxy samples have lent themselves quite well to analysis using such a technique. We are, therefore, hopeful that this method may also work for analysis of flavan-3-ols in chocolate, though preliminary experiments still must be done.

University of Nebraska – Lincoln (Jiujiu Yu). Background: The NLRP3 inflammasome is a key regulator of innate immune responses, and its aberrant activation is implicated in the pathogenesis of many complex diseases such as gout and atherosclerosis. Targeting NLRP3 inflammasome could hold promise to curb these diseases, but interventions specifically inhibiting NLRP3 inflammasome have not been developed for patient treatment. The current study aimed to identify the food-borne exosome-like nanoparticles (ELNs) that inhibit NLRP3 inflammasome activity. Activities: Nine vegetables or fruits were selected to extract ELNs, which were examined for their inhibitory effects on NLRP3 inflammasome in primary macrophages. Though most of the tested ELNs posed minimal impacts, the ELNs from ginger rhizomes (G-ELNs) strongly inhibited NLRP3 inflammasome activation. The G-ELNs contain lipids, proteins, and RNAs. They were easily taken up by macrophages. G-ELN treatment suppressed the downstream of inflammasome activity including Caspase1 auto-cleavage, IL-1 and IL-18 secretion, and pyroptotic cell death. ASC oligomerization and speck formation assays indicated that G-ELNs blocked assembly of NLRP3 inflammasome. Outcomes: The data suggested that the dietary nanoparticles from ginger represent a new class of NLRP3 inflammasome inhibitor.

University of Nebraska-Lincoln (Janos Zempleni). Background: Virtually every cells 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 do not exclusively originate from endogenous synthesis but may also be obtained from dietary sources such as bovine milk and chicken eggs. Activities: 1) We have assessed the microRNA cargos in chicken egg yolk, the bioavailability of chicken egg exosomes and their microRNA cargos in humans, and the effects of exosomes and cargos in peripheral blood mononuclear cells. 2) We have conducted a comprehensive analysis of the bioavailability and distribution of fluorophore-labeled milk exosomes and microRNAs in mice. 3) We have developed an exosome and cargo tracking (ECT) mouse. 4) We have assessed storage stability and microRNA cargos in human milk, bovine milk and infant formulas by RNA-sequencing analysis and qRT-PCR. 5) We have assessed the role of glycoproteins on the surface of milk exosomes in absorption and distribution of bovine milk exosomes in mice. 6) We have characterized the composition of exosome-defined, AIN-93G-based diets developed in our laboratory. 7) We demonstrated that depletion of milk exosomes and their RNA cargos elicits phenotypes such as impaired fecundity, aberrant purine metabolism, altered immune function, loss of muscle grip strength, impaired spatial learning and memory, loss of antiviral resistance, and changes in microbial communities and their genomes in the gut. We have phenotypes of depletion also include increased severity of inflammatory bowel disease in Mdr1a-/- mice. 8) We have shown that bovine milk exosomes deliver a large load of microbial RNAs to hosts.

University of Rhode Island (Brietta Oaks). Background: Lead exposure is a major public health concern in Rhode Island. There is evidence that omega-3 fatty acid intake may reduce circulating lead concentrations, but research has been limited and has not been explored in pregnant women, whom are at a higher risk for adverse effects of lead exposure. In addition, omega-3 fatty acid intake may reduce circulating cortisol, a stress hormone which has negative effects during pregnancy if at chronically high concentrations. Activities: We have prepared a proposal to research the association between omega-3 fatty acid intake, lead, and cortisol in pregnant women in Providence, RI. We have established collaborations with outside labs to analyze fatty acid status and blood lead concentrations and have recently set up a lab at University of Rhode Island to conduct the lab analysis for cortisol. Outcomes: We anticipate recruitment will start in May 2019 and we should have preliminary results by February 2020.

1. Abelilla JJ, Liu Y, Stein HH. Digestible indispensable amino acid score (DIAAS) and protein digestibility corrected amino acid score (PDCAAS) in oat protein concentrate measured in 20- to 30-kilogram pigs. J Sci Food Agri. 2018, 98:410-414.

2. Aguilar-Lozano A, Baier SR, Grove R, Shu J, Giraud D, Mercer KE, Cui J, Badger TM, Adamec J, Andres A, Zempleni J. Concentrations of purine metabolites are elevated in fluids from adults and infants and in livers from mice fed diets depleted of bovine milk exosomes and their RNA cargos. J Nutr 148:1886-1894, 2018

3. Alvarez B, Gac L, Barrientos T, Teske JA, Perez-Leighton CE. Effects on hedonic feeding and energy expenditure of the non-opioid peptide DYN-A2-17. Neuroscience. 2018, 371(10): 337-345.

4. Amengual J, García-Carrizo FJ, Arreguín A, Mušinović H, Granados N, Palou A, Bonet ML, Ribot J. Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo. Cell Physiol Biochem. 2018;46(1):187-202

5. Amengual J, Guo L, Strong A, Madrigal-Matute J, Wang H, Kaushik S, Brodsky JL, Rader DJ, Cuervo AM, Fisher EA. Autophagy Is Required for Sortilin-Mediated Degradation of Apolipoprotein B100. Circ Res. 2018 Feb 16;122(4):568-582.

6. Ashorn P, Alho L, Allen LH, Ashorn U, Chandrasiri U, Deitchler M, Doyle R, Harjunmaa U,

7. Bailey RK, Weaver Cm, Daly R, Sahni S, Chocano P, Welch A, Bischoff-Ferrari H. Best Practices for Conducting Observational Research to Assess the Relation between Nutrition and Bone: An International Working Group Summary.  Advances  Accepted 
8. 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, 2019.
9. Bauer, PV, Duca FA, Waise TM, Dranse HJ, Rasmussen BA, Puri A, Rasti M, O’Brien CA, Lam TK. Microbiota in the upper small intestine alters ACSL3-dependent fatty acid sensing pathway to influence whole-body glucose homeostasis. Cell Metab 2018, 27 :573-587

10. Beaver LM, Lӧhr CV, Clarke JD, Glasser ST, Watson GW, Wong CP, Zhang Z, Williams DE, Dashwood RH, Shannon J, Thuillier P, Ho E (2017) Broccoli Sprouts Delay Prostate Cancer Formation and Decrease Prostate Cancer Severity with a Concurrent Decrease in HDAC3 Protein Expression in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice. Curr Dev Nutr. 2017 Dec 26;2(3):nzy002. doi: 10.1093/cdn/nzy002

11. Bellanger M, Chalmers D, Sabini G, Weaver CM, Lelievre S. The value of global environmental health for primary prevention research of breast cancer.  Cancer Prev Res  In press.
12. Blumberg JB, Frei B, Fulgoni III, VL, Weaver CM, Zeisel SH. Contribution of dietary supplements to nutritional adequacy by socioeconomic subgroups in adults of the United States.  Nutrients  10:  2018  doi:10.3390/nu10010004

13. Brosnan JT, Mills JL, Ueland PM, Shane B, Fan R, Chiu C-Y, Pangilinan F, Brody LC, Brosnan ME, Pongnopparat T, Molloy AM. Lifestyle, metabolite, and genetic determinants of formate concentrations in a cross-sectional study in young, healthy adults. Am J Clin Nutr. 2018, 107:345-354.

14. Brown KH, Hess SY, Kortekangas E, Lartey A, Maleta K, Oaks BM, Ocansey E, Okronipa H, Ouédraogo JB, Pulakka A, Somé JW, Stewart CP, Stewart RC, Vosti SA, Jimenez EY, Dewey KG. Predictors and pathways of language and motor development in four large prospective cohorts of young children in Ghana, Malawi, and Burkina Faso. J Child Psychol Psychiatry. 2017 Nov;58(11):1264-1275.

15. Camara Teixeira D, 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. J Nutr Biochem 6:48-54, 2018

16. Cao S, Wastney ME, Lachcik PJ, Xiao H-H, Weaver CM, Wong M-S. Both Oleanolic acid and a mixture of oleanolic and ursolic acids mimic the effects of fructus ligustri lucidi on bone properties and circulating 1,25-dihydroxycholecalciferol in ovariectomized rat.  J Nutr  148:1-8, 2018
17. Coborn JE, Lessie RE, Rance NE, Sinton CM, Perez-Leighton CE, Teske JA. Noise-induced sleep disruption increases weight gain and decreases energy metabolism is female rats. Int J Obes. 2018. Epub 2018 Dec. 19.

18. Cristian Del Bo, Valeria Deon, Jonica Campolo, Marisa Porrini, Dorothy Klimis-Zacas and Patrizia Riso. A serving of blueberry (V. corymbosum) reverses endothelial dysfunction in young smokers and non-smokers: a randomized, controlled, crossover study, Food and Function, DOI: 10.1039/c7fo00861a, 2017
19. Cui J. Zempleni J. RNase H2-dependent PCR detects bovine microRNAs in human plasma. [reply: letter to the editor] J Nutr 148:1508, 2018

20. Curran KM, Bracha S, Wong CP, Beaver LM, Stevens JF, Ho E. (2018) Sulforaphane absorption and histone deacetylase activity following single dosing of broccoli sprout supplement in normal dogs. Vet Med Sci. 2018 4(4):357-363. doi: 10.1002/vms3.118. Epub 2018 Aug 17.

21. Dashner-Titus EJ, Hoover J, Li L, Lee JH, Du R, Liu KJ, Traber MG, Ho E, Lewis J, Hudson LG. (2018) Metal exposure and oxidative stress markers in pregnant Navajo Birth Cohort Study participants. Free Radic Biol Med. 2018 Apr 30;124:484-492.

22. Dallas, D. C., Traber, M. (2018) How does breast milk enhance lutein absorption? Journal of Nutrition 148(1): 1-2.

23. Dallas, D. C., German, J. B. (2017) Enzymes in human milk. In: Isolauri E, Sherman P, Walker W, editors. Intestinal Microbiome: Functional Aspects in Health and Disease. Basel, Switzerland: Karger Publishers; p. 129-36.

24. Dallas, D. C., Nielsen, S. D. (2018) Milk peptidomics to identify functional peptides and for quality control of dairy products. In Michael Schrader, Lloyd Fricker (Ed.), Peptidomics--Methods and Protocols (1st ed., vol. 1719). P. 223-240. Methods in Molecular Biology, Springer.

25. Demers-Mathieu, V., Nielsen, S. D., Underwood, M. A., Borghese, R., Dallas, D. C. (2017) Analysis of milk from mothers who delivered prematurely revealed few changes in proteases and protease inhibitors across gestational age at birth and infant postnatal age. Journal of Nutrition 147(6): 1152-1159.

26. Demers-Mathieu, V., Nielsen, S. D., Underwood, M. A., Borghese, R., Dallas, D. C. (2017) Changes in proteases, antiproteases and bioactive proteins from mother's breast milk to the premature infant stomach. Journal of Pediatric Gastroenterology and Nutrition 66(2): 318-324.

27. Demers-Mathieu, V., Qu, Y., Underwood, M. A., Borghese, R., Dallas, D. C. (2018) Premature infants have lower gastric digestion capacity for human milk proteins than term infants. Journal of Pediatric Gastroenterology & Nutrition. 66(5): 816-821.

28. Demers-Mathieu, V., Qu, Y., Underwood, M. A., Dallas, D. C. (2018) The preterm infant stomach actively degrades milk proteins with increasing breakdown across digestion time. Acta Paediatrica. 107(6): 967-974.

29. Demers-Mathieu, V., Underwood, M. A., Beverly, R. L.*, Dallas, D. C. (2018) Survival of Immunoglobulins from Human Milk to Preterm Infant Gastric Samples at 1, 2, and 3 Hours Postprandial. Neonatology. 114: 242-250.

30. Demers-Mathieu, V., Underwood, M. A., Beverly, R. L.*, Drud Nielsen, S., Dallas, D. C. (2018) Comparison of human milk immunoglobulin survival during gastric digestion between preterm and term infants. Nutrients, Special Issue on Breastfeeding and Human Lactation. 10(5): 631.

31. Dewey KG, Oaks BM. U-shaped curve for risk associated with maternal hemoglobin, iron status or iron supplementation. American Journal of Clinical Nutrition. Am J Clin Nutr. 2017 Dec;106(Suppl 6):1694S-1702S.

32. P Dey, E Mah, J Li, T Jalili, JD Symons, RS Bruno. (2018). Improved hepatic γ-tocopherol status limits oxidative and inflammatory stress-mediated liver injury in db/db mice with nonalcoholic steatohepatitis. J Funct Food, 40, 670-678.

33. Doepker C, Franke K, Myers E, Goldberger JJ, Lieberman HR, O’Brien C, Peck J, Tenebein M, Weaver C, Wikoff D. Key findings and implications of a recent systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Nutrients  10:1536, 2018.

34. Drewnowski A, Dwyer J, King JC, Weaver CM. Should Nutrient Density Scores Include Food Groups as Well as Nutrients?  Nutr Rev    In press
35. Duca FA, Bauer, PV, Waise TM, Rasmussen BA, Abraham MA, Dranse HJ, Puri A, O’Brien CA, Lam TK. Metformin alters upper small intestinal microbiota that impact a glucose-SGLT1 sensing glucoregulatory pathway. Cell Metab 2018, 27 :101-117

36. Farruggia C, Kim M-.B, Bae M, Lee Y, Pham TX, Yang Y, Han MJ, Park Y-.K, Lee J-.Y. Astaxanthin exerts anti-inflammatory and antioxidant properties in macrophages in NRF2-dependent and independent manners. J Nutr Biochem. 2018, 62:202-209.

37. Fiorentino NM, Kimmel KA, Suleria HAR, Joseph M, Alavi S, Beyer RS, Lindshield BL. Newly Formulated Fortified Blended Foods Result in Improved Protein Efficiency and Hepatic Iron Levels Compared to CSB+ in Broiler Chickens. Curr Dev Nutr. 2(12): 2018 https://doi.org/10.1093/cdn/nzy073

38. Gaulke CA, Rolshoven J, Wong CP, Hudson LG, Ho E, Sharpton TJ. Marginal Zinc Deficiency and Environmentally Relevant Concentrations of Arsenic Elicit Combined Effects on the Gut Microbiome (2018). mSphere. 5;3(6). pii: e00521-18. doi: 10.1128/mSphere.00521-18

39. M Goodus, A Sauerbeck, PG Popovich, RS Bruno, DM McTigue. (2018). Dietary green tea extract prior to spinal cord injury prevents hepatic iron overload but does not improve chronic hepatic and spinal cord pathology in rats. J Neurotrauma, 35(24):2872-2882.

40. I Hatsu, C Gunther, E Hade, S Vandergriff, N Slesnick, R Williams, R Bruno, J Kennel. (2018). Unaccompanied homeless youth have extremely poor diet quality and nutritional status. Int J Adol Youth, 1-14, doi: https://doi.org/10.1080/02673843.2018.1538885

41. Haufe TC, Ho KKHY, Ferruzzi MG, Neilson AP. Potential Health Effects of Tea. Nutrition Today. 2018, 53(5):213-28.

42. Ho, KKHY, Schroen K, San Martin-Gonzalez MF, Berton-Carabin CC. Synergistic and antagonistic effects of plant and dairy protein blends on physicochemical stability of lycopene-loaded emulsions. Food Hydrocolloids. 2018, 81:180-190

43. Hohman EE, Hodges JK, Wastney ME, Lachcik PJ, Han C-Y, Dwyer D, Peacock M, Kosteniuk PJ, Weaver CM. Serum calcium concentration is maintained when bone resorption is suppressed by osteoprotegerin in young growing male rats.  Bone  116:162-170, 2018.

44. Housley L, Magana AA, Hsu A, Beaver LM, Wong CP, Stevens JF, Choi J, Jiang Y, Bella D, Williams DE, Maier CS, Shannon J, Dashwood RH, and Ho E. (2018) Untargeted Metabolomic Screen Reveals Changes in Human Plasma Metabolite Profiles Following Consumption of Fresh Broccoli Sprouts. Mol Nutr Food Res. 2018 Jan 28. doi: 10.1002/mnfr.201700665.

45. Jun Huang, Yiwei Zhang, Lin Dong, Qinghan Gao, Lei Yin, Hongfeng Quan, Rong Chen, Xueyan Fu, Dingbo Lin. Ethnopharmacology, phytochemistry, and pharmacology of Cornus officinalis Sieb. Et Zucc. J Ethnopharmacol. 2018, 213:280-301.

46. Ji P, Lönnerdal B, Kim K, Jinno CN.Iron Oversupplementation Causes Hippocampal Iron Overloading and Impairs Social Novelty Recognition in Nursing Piglets. J Nutr. 2019, doi: 10.1093/jn/nxy227.
47. Jinno C, He Y, Morash D, McNamara E, Zicari S, King A, Stein H, Liu Y. Enzymatic digestion turns food waste into feed for growing pigs. Anim Feed Sci Technol. 2018, 242:48-58.

48. Jorgensen J, Klein N, Maleta K, Nkhoma M, Oaks BM, Poelman B, Rogerson S, Stewart CP, Zeilani M, Dewey KG. Co-causation of reduced newborn size by maternal undernutrition, infections, and inflammation. Matern Child Nutr. 2018 Jul;14(3):e12585.

49. Kohrt WM, Wherry SJ, Wolfe P, Sherk VD, Wellington T, Swanson CM, Weaver CM, Boxer RS. Maintenance of serum ionized calcium during exercise attenuates parathyroid hormone and bone resorption responses.  JBMR  33:1326-1334, 2018

50. Lawlor MR, Weaver CM, Craig BA, Whiting SJ, Baster-Jones ADG, Vatanparast H, McCabe GP. Ch. 4 Peak BMC growth and calcium requirements for Children.  In:  Nutritional Influences of Bone Health.  International Congress Series Proceedings of the 10th International Symposium on Nutritional Aspects of Osteoporosis, Hong Kong. Weaver CM, Bischoff-Ferrari H, Daly, R, Wong M-S, Eds.  Springer   Pg 37-44, 2018.

51. Lei Wu, Xin Guo, Yi Lyu, Stephen L. Clarke, Edralin A. Lucas, Brenda J. Smith, Deana Hildebrand, Weiqun Wang, Denis M. Medeiros, Xinchun Shen, Dingbo Lin. Targeted metabolomics reveals abnormal hepatic energy metabolism by depletion of β–carotene oxygenase 2 in mice. Scientific Reports 2017 Nov 7;7(1):14624. doi: 10.1038/s41598-017-15222-x.

52. Leiferman A, Shu J, Grove R, Cui J, Adamec J, Zempleni J. A diet defined by its content of bovine milk exosomes and their RNA cargos has moderate effects on gene expression, amino acid profiles and grip strength in skeletal muscle in C57BL/6 mice. J Nutr Biochem 12:123-128, 2018

53. Lewis R, Laing E, Weaver CM.   41 Adolescence and acquisition of peak bone mass.  In:  Vitamin D, Fourth Edition. Feldman  Academic Press  London UK. Pg 731-751, 2018.
54. Leyshon BJ, Ji P, Caputo MP, Matt SM, Johnson RW. Dietary Iron Deficiency Impaired Peripheral Immunity but Did Not Alter Brain Microglia in PRRSV-Infected Neonatal Piglets. Front Immunol. 2019, doi: 10.3389/fimmu.2018.03150.

55. Lillehoj H, Liu Y, Calsamiglia S, Fernandez-Miyakawa ME, Chi F, Cravens RL, Oh S, Gay CG. Phytochemicals as potential antibiotic alternatives to promote growth and enhance host health: a Report from the Second International Symposium on Alternatives to Antibiotics. Vet Res. 2018, 46:76-93.

56. Liu Y, Oliveira MSF, Stein H. Canola meal produced from high-protein or conventional varieties of canola seeds may substitute soybean meal in diets for gestating and lactating sows without compromising sow or litter productivity. J Anim Sci. 2018, 96:5179-5187.

57. Liu Y, Jha R, Stein HH. Nutritional composition, gross energy concentration, and in vitro digestibility of dry matter in 46 sources of bakery meals. J Anim Sci. 2018, 96:4685-4692.
58. Liu Y, Choe J, Lee JJ, Kim J, Campbell JM, Polo J, Crenshaw JD, Pettigrew JE, Song M. Spray-dried plasma attenuates inflammation and lethargic behaviors of pregnant mice caused by lipopolysaccharide. PLoS ONE. 2018, 13(9):e0203427.

59. Liu Y, Espinosa CD, Abelilla JJ, Casas GA, Lagos LV, Lee SA, Kwon WB, Mathai JK, Navarro DMDL, Jaworski NW, Stein HH. Non-antibiotic feed additives in diets for pigs. Anim Nutr. 2018, 4:113-125.

60. Liu Y, Kil DY, Perez-Mendoza VG, Song M, Pettigrew JE. Supplementation of different fat sources affects growth performance and carcass composition of finishing pigs. J Anim Sci Biotech. 2018, 9:56-63

61. Liu Y, Choe J, Kim S, Kim B, Campbell JM, Polo J, Crenshaw JD, Pettigrew JE, Song M. Dietary spray-dried plasma improves intestinal morphology of mated female mice under stress condition. J Anim Sci Technol. 2018, 60:10-15.

62. Lobene AJ, McCabe LD, Stone MS, Kindler JM, Bailey RL, Mosfegh AJ, Rhodes DG, Goldman JD, McCabe GP, Weaver CM. Ch. 6 Dietary minerals, mineral ratios, and bone. In:  Nutritional Influences of Bone Health.  International Congress Series Proceedings of the 10th International Symposium on Nutritional Aspects of Osteoporosis, Hong Kong. Weaver CM, Bischoff-Ferrari H, Daly, R, Wong M-S, Eds.  Springer   Pg 53-67, 2018.

63. Yi Lyu, Lei Wu, Fan Wang, Xinchun Shen, Dingbo Lin. Carotenoid supplementation and retinoic acid in regulation of immunoglobulin A production and gut microbiome dysbiosis. Exp Biol Med (Maywood). 2018, 243(7):613-620.

64. Maiz Rodriguez M. A blueberry-enriched diet may aid in the amelioration of bone loss in ovariectomized rat model.  PhD Thesis  Purdue University, 2019.

65. Manca S, Upadhyaya B, Mutai E, Desaulniers AT, Cederberg RA, White BR, Zempleni J. Milk exosomes are bioavailable and distinct microRNA cargos have unique distribution patterns. Sci Rep 8:11321, 2018

66. JD McDonald, E Mah, C Chitchumroonchokchai, EJ Reverri, J Li, JS Volek, FA Villamena, RS Bruno. (2018). Co-ingestion of whole eggs or egg whites with glucose protects against postprandial hyperglycemia-induced oxidative stress and dysregulated arginine metabolism in association with improved vascular endothelial function in prediabetic men. Br J Nutr, 120(8):901-913.

67. JD McDonald, E Mah, C Chitchumroonchokchai, P Dey, AN Labyk, FA Villamena, JS Volek, RS Bruno (2018). Dairy milk proteins attenuate hyperglycemia-induced impairments in vascular endothelial function in adults with prediabetes by limiting increases in glycemia and oxidative stress that reduce nitric oxide bioavailability. J Nutr Biochem, 63:165-176.

68. JD McDonald, E Mah, P Dey, BD Olmstead, GY Sasaki, FA Villamena, RS Bruno. (2018). Dairy milk, regardless of fat content, protects against postprandial hyperglycemia-mediated impairments in vascular endothelial function in adults with prediabetes by limiting oxidative stress responses that reduce nitric oxide bioavailability. J Nutr Biochem, 63:129-139.

69. JD McDonald, C Chitchumroonchokchai, J Li, E Mah, AN Labyk, EJ Reverri, KD Ballard, JS Volek, RS Bruno. (2018). Replacing carbohydrate during a glucose challenge with the egg white portion or whole eggs protects against postprandial impairments in vascular endothelial function in prediabetic men by limiting increases in glycemia and lipid peroxidation. Br J Nutr, 119(3):259-270.

70. McKenney-Drake M, Moghbel MC, Paydary K, Alloosh M, Houshmand S, Moe S, Salaati A, Sturek JM, Territo PR, Weaver C, Werner TJ, Flemming Hoilund-Carlsen P, Sturek M, Alai A. 18F-NaF and 18F-FDG as molecular probes in the evaluation of atherosclerosis.  Europ J Nucl Med Mol Imaging  45:2190-2200, 2018.

71. Mithen R, Ho, E (2018)  Isothiocyanates for Human Health.  Mol Nutr Food Res. 2018 Sep;62(18):e1870079. doi: 10.1002/mnfr.201870079. PMID:30246304 (Note: Mithen and Ho, Guest Editors for Sept Special Issue “Isothiocyanates” for Mol Nutr Food Res.)

72. Murray, N. M., O'Riordan, D., Jacquier, J.-C., O'Sullivan, M., Holton, T. A., Wynne, K., Robinson, R. C., Barile, D., Nielsen, S. D., Dallas, D. C. (2018) Peptidomic screening of bitter and non-bitter sodium caseinate hydrolysate fractions for bioactive peptides. Journal of Dairy Science. 101(4): 2826-2837.

73. Murray, N. M., O'Riordan, D., Jacquier, J.-C., O'Sullivan, M., Cohen, J., Heymann, H., Barile, D., Dallas, D. C. (2017) Validation of a paper-disk approach to facilitate the sensory evaluation of bitterness in dairy protein hydrolysates from a newly developed food-grade fractionation system. Journal of Sensory Studies 32(3): e12266.

74. Nielsen, S. D., Beverly, R. L.*, Underwood, M. A., Dallas, D. C. (2018) Release of functional peptides from mother’s milk and fortifier proteins in the premature infant stomach. PLOS One. 13(11):e0208204. doi.org/10.1371/journal.pone.0208204

75. Nielsen, S. D., Beverly, R. L.*, Dallas, D. C. (2018) Milk proteins are predigested within the mammary gland. Journal of Mammary Gland Biology and Neoplasia. 22(4): 251-261.

76. Nielsen, S. D., Beverly, R. L., Dallas, D. C. (2017) Peptides released from foremilk and hindmilk proteins by breast milk proteases are highly similar. Frontiers in Nutrition, Nutrition Methodology 4(54).

77. Nielsen, S. D., Beverly, R. L., Qu, Y., Dallas, D. C. (2017) Milk bioactive peptide database: A comprehensive database of milk protein-derived bioactive peptides and novel visualization. Food Chemistry 232: 673-682.

78. Nutritional Influences of Bone Health. International Congress Series Proceedings of the 10th International Symposium on Nutritional Aspects of Osteoporosis, Hong Kong.   Weaver CM, Bischoff-Ferrari H, Daly, R, Wong M-S, Eds.  Springer 

79. Panagiotis Tsakiroglou, Sharon Ashworth, James Webber, Cristian DelBo and Dorothy Klimis-Zacas, Anthocyanins and Phenolic acids extracted from wild blueberries (V. angustifolium) differentially modulate endothelial cell migration through RhoA and RAC1, J. Cell. Biochem., 2018, DOI:10.1002/jcb.28383

80. Penugonda K, Fiorentino N, Alavi S, Lindshield BL. Bioavailable Iron and Vitamin A in Newly Formulated, Extruded Corn, Soybean, Sorghum and Cowpea Fortified-Blended Foods in the In-vitro Digestion/Caco-2 Cell Model. Curr Dev Nutr. 2(7): 2018 https://doi.org/10.1093/cdn/nzy021

81. Picariello, G., Addeo, F., Ferranti, P., Nocerino, R., Paparo, L., Passariello, A., Robinson, R. C., Barile, D., Dallas, D. C., Berni Canani, R. (2016) Antibody-independent identification of bovine milk-derived peptides in breast-milk. Food & Function 7(8): 3402-3409.

82. Rizzoli R, et al. Benefits and safety of dietary protein for bone health.  An experts consensus paper endorse by the European Society for Clinical and Economical Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, and by the International Osteoporosis Foundation.  Osteoporos Intl. 

83. R Pei, DM DiMarco, KK Putt, DA Martin, C Chitchumroonchokchai, RS Bruno, BW Bolling (2018). Pre-meal low-fat yogurt consumption reduces postprandial inflammation and markers of endotoxin exposure in healthy premenopausal women in a randomized controlled trial. J Nutr, 148:1-7.

84. Pham T X, Lee Y, Bae M, Hu S, Kang H, Kim M-.B, Park Y-.K, Lee J-.Y. Spirulina supplementation in a mouse model of liver fibrosis reduced the pro-inflammatory response of splenocytes. Br J Nutr. 2019 (In press).

85. Prado EL, Phuka J, Ocansey E, Maleta K, Ashorn P, Ashorn U, Adu-Afarwuah S, Oaks BM, Lartey A, Dewey KG. A method to develop vocabulary checklists in new languages and their validity to assess early language development. J Health Popul Nutr. 2018 May 11;37(1):13.

86. Prado EL, Ashorn U, Phuka J, Maleta K, Sadalaki J, Oaks BM, Haskell M, Allen LH, Vosti SA, Ashorn P, Dewey KG. Associations of maternal nutrition during pregnancy and post-partum with maternal cognition and caregiving. Matern Child Nutr. 2018 Apr;14(2):e12546.

87. Prado EL, Abbeddou S, Adu-Afarwuah S, Arimond M, Ashorn P, Ashorn U, Bendabenda J, Oaks BM, Stewart CP, Laugero KD, Adu-Afarwuah S, Lartey A, Vosti SA, Ashorn P, Dewey KG. Maternal plasma cholesterol and duration of pregnancy: a prospective cohort study in Ghana. Matern Child Nutr. 2017 Oct;13(4):e12418.

88. Reddivari L, Wang T, Wu B, Li S. Potato: An Anti-inflammatory Food?. Am J Potato Res. Invited Review. 2018. https://doi.org/10.1007/s12230-018-09699-z

89. Reddivari L, Veeramachaneni DNR, Walters WA, Lozupone C, Palmer J, Hewage MKK, Bhatnagar R, Amir A, Kennett MJ, Knight R, Vanamala JKP. Perinatal Bisphenol A Exposure Induces Chronic Inflammation in Rabbit Offspring via Modulation of Gut Bacteria and Their Metabolites. mSystems. 2017 2(5).

90. Schröder A, Corstens MN, Ho KKHY, Schroën K, Berton‐Carabin CC. Pickering Emulsions. Emulsion‐based Systems for Delivery of Food Active Compounds: Formation, Application, Health and Safety. 2018, 3:29-67. (Book chapter)

91. Shams-White MM, Chung M, Fu Z, Insogna KL, Karlsen MC, LeBoff MS, Shapses SA, Sackey J, Shi J, Wallace TC, Weaver CM. Animal versus plant protein and adult bone health: a systematic review and meta-analysis from the National Osteoporosis Foundation.  PLOS One  13:e0192459.

92. Shane B, Pangilinan F, Mills JL, Fan R, Gong T, Cropp CD, Kim Y, Ueland PM, Bailey-Wilson JE, Wilson AF, Brody LC, Molloy AM. The 677C->T variant of MTHFR is the major genetic modifier of biomarkers of folate status in a young healthy Irish population. Am J Clin Nutr. 2018, 108:1334-1341.

93. Stremke E, McCabe L, McCabe G, Martin B, Moe S, Roudebush Veterans Administration Medical Center, Weaver C, Peacock M, Hill Gallant K. Twenty-four-hour urine phosphorus as a biomarker of dietary phosphorus intake and absorption in CKD.  Clin J Am Soc Nephrol.  13:1002-1012, 2018.
94. Swanson B, Zempleni J, Nordgren T, Romberger D, Heires A. Bovine milk-derived exosomes enhance inflammation and promote M1 polarization following agricultural dust exposure in mice. J Nutr Biochem 3:110-120, 2018

95. Taylor K. Bloedon, Rock E. Braithwaite, Imogene A. Carson, Dorothy J. Klimis-Zacas, Impact of whole berry fruit consumption on exercise-induced oxidative stress and inflammation: a systematic review and meta-analysis, Nutrition Reviews, 2019 (accepted)

96. MG Traber, GR Buettner, RS Bruno. (2018). The relationship between vitamin C status, the gut-liver axis, and metabolic syndrome. Redox Biology, 21:101091. https://doi.org/10.1016/j.redox.2018.101091

97. Vanamala JKP, Massey AR, Pinnamaneni SR, Reddivari L, Reardon KF. Grain and sweet sorghum (Sorghum bicolor L. Moench) serves as a novel source of bioactive compounds for human health. Crit Rev Food Sci Nutr. 2017, 1-15.

98. Vorland CJ, Martin BR, Weaver CM, Peacock M, Hill Gallant KM. Phosphorus balance in adolescent girls and the effect of supplemental dietary calcium.  JBRM Plus 2:103-108, 2018.

99. Wallace TC, Bultman S, D'Adamo C, Daniel CR, Debelius J, Ho E, Eliassen H, Lemanne D, Mukherjee P, Seyfried TN, Tian Q, Vahdat LT. (2018) Personalized Nutrition in Disrupting Cancer - Proceedings From the 2017 American College of Nutrition Annual Meeting. J Am Coll Nutr. 4:1-14. doi: 10.1080/07315724.2018.1500499. [Epub ahead of print]

100. Wang L, Sadri M, Giraud D, Zempleni J. RNase H2-dependent PCR and elimination of confounders in sample collection, storage and analysis strengthen evidence that microRNAs in bovine milk are bioavailable in humans. J Nutr 148:153-159, 2018

101. Wang Q, Yu J, Kadungure T, Beyene J, Zhang H, Lu Q. ARMMs as a versatile platform for intracellular delivery of macromolecules. Nat. Commun., 9: 960 (2018).

102. Weaver CM, Bailey R, McCabe L, Moshfegh A, Rhodes D, Goldman J, Lobene A, McCabe G. Mineral Intake Ratios are a Weak but Significant, Factor in Blood Pressure Variability in U.S. Adults.  J Nutr   148:1845-1851, 2018.

103. Weaver CM, Peacock M. Calcium  Adv Nutr:  Int Rev J  In press.

104. Weaver CM. Ensuring adequate calcium with concern for safety.  Nutr Today.  52:90-92, 2017.

105. Weaver CM, Stone M, Lobene AJ, Cladis DP, Hodges JK. What is the evidence base for a potassium requirement? Nutr Today  53:184-195, 2018.

106. Weaver CM. The quest for evidence for calcium requirements for bone during pregnancy and lactation.  Am J Clin Nutr  109:3-4, 2019.

107. Weaver CM, Bischoff-Ferrari H, Daly, R, Wong M-S, Eds. Springer  In Press.  Lewis R, Laing E, Weaver CM.    41 Adolescence and acquisition of peak bone mass.  In:  Vitamin D, Fourth Edition. Feldman  Academic Press  London UK. Pg 731-751, 2018.

108. Wright CS, Laing EM, Pollock NK, Hausman DB, Weaver CM, Martin BR, McCabe GP, Peacock M, Warden SJ, Gallant HK, Lewis RD. Serum 25-hydroxyvitamin D and intact parathyroid hormone influences muscle outcomes in children and adolescents.  J Bone Miner Res  33:1940-1947, 2018.

109. Xia Xiong, Bie Tan, Minho Song, Peng Ji, Kwangwook Kim, Yulong Yin and Yanhong Liu. Nutritional Intervention for the Intestinal Development and Health of Weaned Pigs. Front Vet Sci. 2019, doi: 10.3389/fvets.2019.00046

110. Yali Yu, Lijun Wang, Ying Wang, Dingbo Lin, Jingbo Liu. Hepatoprotective effect of albumin peptides from corn germ meal on chronic alcohol-induced liver injury in mice. J Food Sci. 2017 Dec; 82(12): 2997-3004.

111. F Zhong, M Xu, RS Bruno, KD Ballard, J Zhang, J Zhu. (2018). Comparative metabolomics elucidates postprandial metabolic modifications in plasma of obese individuals with metabolic syndrome. J Proteome Res, 17(8):2850-2860.