Arkansas Childrens Nutrition Center

Arkansas City, AR, United States

Arkansas Childrens Nutrition Center

Arkansas City, AR, United States

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Chiu L.-W.,Cornell University | Zhou X.,Cornell University | Burke S.,Cornell University | Wu X.,Arkansas Childrens Nutrition Center | And 2 more authors.
Plant Physiology | Year: 2010

Anthocyanins are responsible for the color of many flowers, fruits, and vegetables. An interesting and unique Purple (Pr) gene mutation in cauliflower (Brassica oleracea var botrytis) confers an abnormal pattern of anthocyanin accumulation, giving the striking mutant phenotype of intense purple color in curds and a few other tissues. To unravel the nature of the Pr mutation in cauliflower, we isolated the Pr gene via a combination of candidate gene analysis and fine mapping. Pr encoded a R2R3 MYB transcription factor that exhibited tissue-specific expression, consistent with an abnormal anthocyanin accumulation pattern in the mutant. Transgenic Arabidopsis (Arabidopsis thaliana) and cauliflower plants expressing the Pr-D allele recapitulated the mutant phenotype, confirming the isolation of the Pr gene. Up-regulation of Pr specifically activated a basic helix-loop helix transcription factor and a subset of anthocyanin structural genes encoding flavonoid 3'-hydroxylase, dihydroflavonol 4-reductase, and leucoanthocyanidin dioxygenase to confer ectopic accumulation of pigments in the purple cauliflower. Our results indicate that the genetic variation including a Harbinger DNA transposon insertion in the upstream regulatory region of the Pr-D allele is responsible for the up-regulation of the Pr gene in inducing phenotypic change in the plant. The successful isolation of Pr provides important information on the regulatory control of anthocyanin biosynthesis in Brassica vegetables, and offers a genetic resource for development of new varieties with enhanced health-promoting properties and visual appeal. © 2010 American Society of Plant Biologists.


Khanal R.C.,University of Arkansas | Khanal R.C.,Arkansas Childrens Nutrition Center | Howard L.R.,University of Arkansas | Prior R.L.,Arkansas Childrens Nutrition Center | Prior R.L.,U.S. Department of Agriculture
Food Research International | Year: 2010

Fruit by-products are rich sources of procyanidins and anthocyanins known for potential health benefits. Freeze dried blueberry pomace and grape pomace were heated in a forced air oven at 40, 60, 105, and 125°C for 72, 48, 16, and 8. h respectively, to study the stability of procyanidins and total anthocyanins. Heating decreased procyanidin concentrations significantly (p<0.05) in both blueberry and grape pomace, except when heated at 40°C for 72. h. Reduction occurred when heated at 60°C or above with no further reduction when heating temperature increased from 105 to 125°C. Heating also affected total anthocyanin contents in both grape and blueberry pomace with no significant (p>0.05) loss when heated at 40°C. Total anthocyanin loss was highest at 125°C for both blueberry (52%) and grape pomace (70%). Results suggested that while heating at lower temperatures for up to 3. days may not be detrimental, heating at higher temperatures for more than 8. h results in considerable loss of both the compounds. © 2010 Elsevier Ltd.


Nemere I.,Utah State University | Garbi N.,German Cancer Research Center | Hammerling G.J.,German Cancer Research Center | Khanal R.C.,Utah State University | And 2 more authors.
Journal of Biological Chemistry | Year: 2010

We have crossed ERp57flx/flx mice with commercially available mice expressing villin-driven cre-recombinase. Lysates of intestinal epithelial cells were prepared from knock-out (KO) mice and littermates (LM) and used in Western blot analyses with Ab099 against the N terminus of the 1,25D 3-MARRS (membrane-associated, rapid response steroid-binding) receptor: LM mice exhibited one positive band, which was absent in preparations from KO mice. Saturation analyses of cell lysates with [3H]1,25D 3 revealed negligible binding in preparations from either female or male KOs. Lysates from female and male LM mice had similar affinities but different numbers of binding sites. Isolated enterocytes were tested for steroid-stimulated calcium uptake. Treatment of cells from female or male LM mice with 1,25D3 elicited enhanced calcium uptake in females and males within 5 min. Intestinal cells from KO mice exhibited a severely blunted or completely absent response to hormone. Confocal microscopy of intestinal cells revealed the presence of cell surface vitamin D receptors. However, antibodies to the vitamin D receptor failed to block 1,25D3- stimulated calcium uptake. In chick enterocytes we have found that the PKA pathway mediates calcium uptake. The time course for activation of PKA in mouse enterocytes paralleled that for enhanced calcium uptake and for LM females reached 250% of controls within 5 min, and 150% of controls in cells prepared from LM males. Enterocytes from female or male KO mice failed to exhibit steroid hormone-stimulated PKA activity, but did respond to forskolin with enhanced calcium uptake. We conclude that the 1,25D3-MARRS receptor is of central importance to steroid hormone-stimulated calcium uptake in mammalian intestinal cells. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.


Ronis M.J.J.,University of Arkansas for Medical Sciences | Mercer K.,Arkansas Childrens Nutrition Center | Chen J.-R.,University of Arkansas for Medical Sciences
Current Osteoporosis Reports | Year: 2011

It is well established that excessive consumption of high-fat diets results in obesity. However, the consequences of obesity on skeletal development, maturation, and remodeling have been the subject of controversy. New studies suggest that the response of the growing skeleton to mechanical loading is impaired and trabecular bone mass is decreased in obesity and after high-fat feeding. At least in part, this occurs as a direct result of inhibited Wnt signaling and activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) pathways in mesenchymal stem cells by fatty acids. Similar effects on Wnt and PPAR-γ signaling occur after chronic alcohol consumption as the result of oxidative stress and result in inhibited bone formation accompanied by increased bone marrow adiposity. Alcohol-induced oxidative stress as the result of increased NADPH-oxidase activity in bone cells also results in enhanced RANKL-RANK signaling to increase osteoclastogenesis. In contrast, consumption of fruits and legumes such as blueberries and soy increase bone formation. New data suggest that Wnt and bone morphogenetic protein signaling pathways are the molecular targets for bone anabolic factors derived from the diet. © 2011 Springer Science+Business Media, LLC.


Pivik R.T.,Arkansas Childrens Nutrition Center | Pivik R.T.,University of Arkansas for Medical Sciences | Tennal K.B.,Arkansas Childrens Nutrition Center | Chapman S.D.,Arkansas Childrens Nutrition Center | Gu Y.,Arkansas Childrens Nutrition Center
Physiology and Behavior | Year: 2012

To determine the influence of a morning meal on complex mental functions in children (8-11. y), time-frequency analyses were applied to electroencephalographic (EEG) activity recorded while children solved simple addition problems after an overnight fast and again after having either eaten or skipped breakfast. Power of low frequency EEG activity [2. Hertz (Hz) bands in the 2-12. Hz range] was determined from recordings over frontal and parietal brain regions associated with mathematical thinking during mental calculation of correctly answered problems. Analyses were adjusted for background variables known to influence or reflect the development of mathematical skills, i.e., age and measures of math competence and math fluency. Relative to fed children, those who continued to fast showed greater power increases in upper theta (6-8. Hz) and both alpha bands (8-10. Hz; 10-12. Hz) across sites. Increased theta suggests greater demands on working memory. Increased alpha may facilitate task-essential activity by suppressing non-task-essential activity. Fasting children also had greater delta (2-4. Hz) and greater lower-theta (4-6. Hz) power in left frontal recordings-indicating a region-specific emphasis on both working memory for mental calculation (theta) and activation of processes that suppress interfering activity (delta). Fed children also showed a significant increase in correct responses while children who continued to fast did not. Taken together the findings suggest that neural network activity involved in processing numerical information is functionally enhanced and performance is improved in children who have eaten breakfast, whereas greater mental effort is required for this mathematical thinking in children who skip breakfast. © 2012 Elsevier Inc.


Rahal O.M.,Interdisciplinary Biomedical science Program | Rahal O.M.,Arkansas Childrens Nutrition Center | Simmen R.C.M.,Interdisciplinary Biomedical science Program | Simmen R.C.M.,University of Arkansas for Medical Sciences | Simmen R.C.M.,Arkansas Childrens Nutrition Center
Endocrinology | Year: 2011

Mammary stromal adipocytes constitute an active site for the synthesis of the adipokine, adiponectin (APN) that may influence the mammary epithelial microenvironment. The relationship between "local," mammary tissue-derived APN and breast cancer risk is poorly understood. Here, we identify a novel mechanism of APN-mediated signaling that influences mammary epithelial cell proliferation, differentiation, and apoptosis to modify breast cancer risk. We demonstrate that early dietary exposure to soy protein isolate induced mammary tissue APN production without corresponding Effects on systemic APN levels. In estrogen receptor (ER)-negative MCF-10A cells, recombinant APN promoted lobuloalveolar differentiation by inhibiting oncogenic signal transducer and activator of transcription 3 activity. In ER-positive HC11 cells, recombinant APN increased ERβ expression, inhibited cell proliferation, and induced apoptosis. Using the estrogen-responsive 4X-estrogen response element promoter-reporter construct to assess ER transactivation and small interfering RNA targeting of ERα and ERβ, we show that APN synergized with the soy phytoestrogen genistein to promote ERβ signaling in the presence of estrogen (17β- Estradiol) and ERβ-specific agonist 2,3-bis(4-hydroxyphenyl)-propionitrile and to oppose ERα signaling in the presence of the ERα-specific agonist 4,4′,4′-(4-propyl-(1H)- pyrazole-1,3,5-triyl)trisphenol. The enhancement of ERβ signaling with APN + genistein cotreatments was associated with induction of apoptosis, increased expression of proapoptotic/prodifferentiation genes (Bad, p53, and Pten), and decreased antiapoptotic (Bcl2 and survivin) transcript levels. Our results suggest that mammary-derived APN can influence adjacent epithelial function by ER-dependent and ER-independent mechanisms that are consistent with reduction of breast cancer risk and suggest local APN induction by dietary factors as a targeted approach for promotion of breast health. Copyright © 2011 by The Endocrine Society.


Rahal O.M.,University of Arkansas for Medical Sciences | Rahal O.M.,Arkansas Childrens Nutrition Center | Simmen R.C.M.,University of Arkansas for Medical Sciences | Simmen R.C.M.,Arkansas Childrens Nutrition Center
Carcinogenesis | Year: 2010

The tumor suppressors phosphatase and tensin homologue deleted on chromosome ten (PTEN) and p53 are closely related to the pathogenesis of breast cancer, yet pathway-specific mechanisms underlying their participation in mediating the protective actions of dietary bioactive components on breast cancer risk are poorly understood. We recently showed that dietary exposure to the soy isoflavone genistein (GEN) induced PTEN expression in mammary epithelial cells in vivo and in vitro, consistent with the breast cancer preventive effects of soy food consumption. Here, we evaluated PTEN and p53 functional interactions in the nuclear compartment of mammary epithelial cells as a mechanism for mammary tumor protection by GEN. Using the non-tumorigenic human mammary epithelial cells MCF10-A, we demonstrate that GEN increased PTEN expression and nuclear localization. We show that increased nuclear PTEN levels initiated an autoregulatory loop involving PTEN-dependent increases in p53 nuclear localization, PTEN-p53 physical association, PTEN-p53 corecruitment to the PTEN promoter region and p53 transactivation of PTEN promoter activity. The PTEN-p53 cross talk induced by GEN resulted in increased cell cycle arrest; decreased pro-proliferative cyclin D1 and pleiotrophin gene expression and the early formation of mammary acini, indicative of GEN promotion of lobuloalveolar differentiation. Our findings provide support to GEN-induced PTEN as both a target and regulator of p53 action and offer a mechanistic basis for PTEN pathway activation to underlie the antitumor properties of dietary factors, with important implications for reducing breast cancer risk. © The Author 2010. Published by Oxford University Press. All rights reserved.


Simmen F.A.,University of Arkansas for Medical Sciences | Simmen R.C.M.,University of Arkansas for Medical Sciences | Simmen R.C.M.,Arkansas Childrens Nutrition Center
European Journal of Cancer Prevention | Year: 2011

The dramatic rise in worldwide prevalence of obesity has necessitated the search for more efficacious antiobesity strategies to counter the increased cancer risks in overweight and obese individuals. The mechanistic pathways linking obesity status with adult chronic diseases such as cancer remain incompletely understood. A growing body of evidence suggests that novel approaches and interventional agents to disrupt the feed-forward cycle of maternal to offspring obesity transfer that is initiated in utero will be important for stemming both the obesity pandemic and the associated increase in cancer incidence. The convergence of multiple research areas including those encompassing the insulin and insulin-like growth factor systems, epigenetics, and stem cell biology is providing insights into the potential for cancer prevention in adult offspring previously exposed to the intrauterine environment of overweight/obese mothers. Here, we review the current state of this nascent research field, with a focus on three major cancers, namely breast, colorectal, and liver, and suggest some possible future directions to optimize its impact for the health of future generations. © 2011 Wolters Kluwer Health | Lippincott Williams &Wilkins.


Andres A.,Arkansas Childrens Nutrition Center | Gomez-Acevedo H.,Arkansas Childrens Nutrition Center | Badger T.M.,Arkansas Childrens Nutrition Center
Obesity | Year: 2011

Quantitative nuclear magnetic resonance (QMR) is being used in human adults to obtain measures of total body fat mass (FM) with high precision. The current study assessed a device specially designed to accommodate infants and children between 3 and 50kg (EchoMRI-AH). Body composition of 113 infants and children (3.3-49.9kg) was assessed using dual-energy X-ray absorptiometry (DXA), air displacement plethysmography (ADP, PeaPod for infants 8kg and BodPod for children ≥6 years) and QMR. Results were compared with the deuterium oxide dilution technique (D 2O) and a four-compartment model (4-C). The percentages of compliance were: 98% QMR; 75% DXA; 94% BodPod; and 95% PeaPod. Although QMR precision was high (coefficient of variation = 1.42%), it overestimated FM ∼10% compared to the 4-C model and underestimated FM by ∼4% compared to the deuterium method in children ≥6 years. QMR was less concordant with 4-C or D 2O models for infants 8kg. Thus, a piece-wise defined model for mathematically fitting the QMR data to the D 2O data was employed and this adjustment improved the accuracy relative to D 2O and 4-C for infants. Our results suggest that the pediatric QMR with appropriate mathematical adjustment provides a fast and precise method for assessing FM longitudinally in infants and in children weighing up to 50kg. © 2011 The Obesity Society.


Pabona J.M.P.,University of Arkansas for Medical Sciences | Zeng Z.,University of Arkansas for Medical Sciences | Simmen F.A.,University of Arkansas for Medical Sciences | Simmen R.C.M.,University of Arkansas for Medical Sciences | Simmen R.C.M.,Arkansas Childrens Nutrition Center
Endocrinology | Year: 2010

The inability of the uterine epithelium to enter a state of receptivity for the embryo to implant is a significant underlying cause of early pregnancy loss.Wepreviously showed that mice null for the progesterone receptor (PGR)-interacting protein Krüppel-like factor (KLF) 9 are subfertile and exhibit reduced uterine progesterone sensitivity. KLF9 expression is high in predecidual stroma, undetectable in decidua, and enhanced in uteri of mice with conditional ablation of bone morphogenetic protein 2 (BMP2). Given the individual importance of KLF9 and BMP2 for implantation success, we hypothesized that the establishment of uterine receptivity involves KLF9 and BMP2 functional cross-regulation. To address this, we used early pregnant wild-type and Klf9 null mice and KLF9 small interfering RNA-transfected human endometrial stromal cells (HESCs) induced to differentiate under standard conditions. Loss of KLF9 in mice and HESCs enhanced BMP2 expression, whereas recombinant BMP2 treatment of HESCs attenuated KLF9 mRNA levels. IGFBP1 and KLF9-related KLF13 expression were positively associated with BMP2 and inversely associated with KLF9. Prolonged, but not short-term, knockdown of KLF9 in HESCs reduced IGFBP1 expression. Mouse uterine Igfbp1 expression was similarly reduced with Klf9 ablation. PGR-A and PGR-B expression were positively associated with KLF9 in predecidual HESCs but not decidualizing HESCs. KLF13 knockdown attenuated BMP2 and PGR-B and abrogated BMP2-mediated inhibition of KLF9 expression. Results support cross-regulation among BMP2, KLF9, and KLF13 to maintain progesterone sensitivity in stromal cells undergoing differentiation and suggest that loss of this regulatory network compromises establishment of uterine receptivity and implantation success. Copyright © 2010 by The Endocrine Society.

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