bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycan‐dependent Control of Myelopoiesis
Authors: Lowe John , Yao David , Petryniak Bronia , Shim Jeongsup , Stanley Pamela , Zhou Lan
Published: June 2021

Notch1 is modified by O‐fucosylation catalyzed by Protein O‐fucosyltransferase 1 (Pofut1). The Fringe family of glycosyltransferases extend Notch‐borne O‐fucose moieties, and modulate Notch1 signaling by altering the sensitivity of Notch receptors to Notch ligands. To address the physiologic function Notch O‐fucosylation in myelopoiesis, we characterized myelopoiesis in mice carrying a deficiency in fucosylation (the FX(−/−) mouse), or with an inducible deficiency of Pofut1. In either strain, loss of Notch fucosylation yields a myeloid hyperplasia phenotype. Restoration of Notch1 signaling suppresses myeloid hyperplasia. Loss of fucosylation in FX(−/−) mice or in Pofut1‐deficient mice is associated with diminished cell surface expression of Notch family members, loss of binding of Notch ligands to the fucosylation‐deficient cells in the mice, and suppressed activation of Notch target genes. Surface plasmon resonance experiments indicate that Fringe‐mediated elongation of O‐fucosylated Notch modulates binding of Notch ligands to Notch1, corresponding to Fringe‐dependent modulation of Notch1‐dependent signal transduction. These observations indicate that Pofut1‐dependent Notch fucosylation is required for myelopoietic homeostasis via proper (i) cell surface localization of Notch1, (ii) binding of Notch ligands to Notch1, and (iii) Fringe‐dependent modulation of Notch1 signaling.
Three‐Year Incidence of Obesity Among US Children Aged 0–23 Months Living in Low‐Income Families
Authors: Pan Liping , May Ashleigh , Wethington Holly , Dalenius Karen , Grummer‐Strawn Laurence
Published: June 2021

Our objective was to examine the incidence of obesity (BMI‐for‐age ≥ 95th percentile based on CDC growth charts) among young low‐income children. We included 1 million nonobese participants in federally‐funded child health and nutrition programs aged 0–23 months in 2008 and examined their incidence of obesity in 2011. Weight and height were measured; missing, miscoded or biological implausible values were excluded. We used a log‐binomial model to estimate relative risk of obesity adjusting for sex, baseline age, and race/ethnicity. The 3‐year incidence of obesity was: overall, 12.2%; boys, 12.6%; girls, 11.8%; aged<12 months at baseline, 12.9%; aged 12–23 months at baseline, 11.2%; non‐Hispanic(NH) whites, 10.6%; NH blacks, 9.7%; Hispanics, 15.0%; American Indians(AI)/Alaska Natives(AN), 15.4%; and Asians/Pacific Islanders(PI), 9.6%. Compared with boys, girls had 6.2% decreased risk for obesity. Compared with infants, 12–23 month olds had a 13.7% risk reduction. Compared with NH whites, the risk significantly increased by 42.6% among Hispanics and 44.6% among AIs/ANs, and reduced by 7.9% and 9% among NH blacks and Asians/PIs, respectively. The high incidence underscores the importance of early life obesity prevention among low‐income children. The variations within subgroups suggest that Hispanics and AIs/ANs should be prioritized for additional targeted prevention efforts to reduce disparities.
Beverage consumption among young children of different race/ethnic backgrounds from the National Health and Nutrition Examination Survey (NHANES)
Authors: Quann Erin E. , Auestad Nancy , Fulgoni Victor L.
Published: June 2021

Early beverage choices are a predictor of children's later beverage consumption, nutrient intakes and body weight. Beverage intakes and associated calories and nutrients were examined using NHANES 2009–2010 for non‐Hispanic white (NHW), non‐Hispanic black (NHB) and Hispanic American (HA) children <1–5 y (n=1,442) with reliable Day 1 24‐hr recalls. By 1 y of age, 22, 31 and 26% of NHW, NHB and HA, respectively, consume fruit drinks, and 11, 5 and 12% drink soda. Fewer NHB children (67%) drink milk than HA (78%), and those who do consume 12.6 oz./d, about 3–5 oz./d less than HA or NHW (p<0.01). NHB are most likely to consume fruit drinks (40% vs. 28% HA, 29% NHW; p<0.05) with 12.5 oz. consumed daily. HA (23%) are most likely to consume soda, but drink smaller amounts than NHB (6.3 oz./d; p<0.05). More HA (60%) drink 100% fruit juice than NHW (50%; p<0.05). HA who drink fruit juice consume less daily than NHB (8.2 oz. vs. 9.7 oz.; p<0.01). For milk drinkers, milk contributes 63–74% of total daily vitamin D, 43–52% of calcium and 25–35% of potassium intakes, at 15–21% of calories. For those who drink soda and fruit drinks, these beverages supply 26–34 and 32–40% of added sugar intake, respectively. Children from all race/ethnic groups, particularly NHB, can benefit from drinking milk while reducing consumption of nutrient‐poor beverages to help improve their diets. Supported by the Dairy Research Institute/National Dairy Council.
The effect of eating frequency on total energy intake, BMI z‐score and diet quality in children and adolescents
Authors: Evans E. Whitney , Jacques Paul , Dallal Gerard E. , Sacheck Jennifer , Must Aviva
Published: June 2021

To determine if eating frequency is associated with total energy intake, BMI z‐score and diet quality, measured by the Healthy Eating Index 2005 (HEI), in a nationally representative cross‐sectional sample of children and adolescents, we assessed the associations in 9,713 children, ages 2–18, studied in the National Health and Nutrition Examination Survey, 2005–2010. Eating frequency was determined using one in‐person 24‐hour recall. Multiple linear regression models were stratified by pediatric life stage group given statistically significant effect modification. Eating frequency was significantly and positively associated with total energy intake in each group without adjustment and after controlling for sex, race/ethnicity, poverty to income ratio and physical activity. Each additional eating occasion was associated with a 5.2% increase in total energy intake for preschool‐age children, a 6.5% increase in elementary school‐age children, and a 12% increase in adolescents (all p<.0001). The relationship between eating frequency and BMI z‐score was inverse and seen only in adolescents (β=−.10; p<.0001). Similarly, total HEI scores were related to eating frequency only in adolescents (β=0.74; p=.0002). Findings suggest that eating frequency is positively associated with energy intake and diet quality and inversely associated with BMI z‐score in adolescents, but not in young children.
An Italian Obesity Prevention Intervention Study in Teenagers: the EAT project. Effectiveness of a School‐Based Program on measures of fatness and behaviour over 2 school years
Authors: ROMANELLI MASSIMILIANO MARCO CORSI , Malavazos Alexis Elias , Briganti Silvia , Ermetici Federica , Zelaschi Roberta , Oggioni Clio , Goggi Silvia , Ignaccolo Daniela , Kapeoldasi Mirtò , Romeo Gloria , Vazzoler Sara , Dozio Elena , Morricone Lelio , Pelissero Gabriele
Published: June 2021

A controlled study including classroom nutrition lessons, incentives to increase physical activity and environmental school changes was performed in 870 adolescents (aged 11–14 years) over 2 school years.

Body height and weight, waist circumference and dietary and physical activity habits data were measured at the beginning and at the end of each school year.

At the end of the second school year of our program, we observed a significant increase in the prevalence of normal‐weight adolescents (+10.3%, p<0.01), and a reduction in the prevalence of overweight and obese adolescents (−7.9%, p<0.05 and −2.4%, p=ns, respectively), as well as a significant reduction in mean waist circumference (−2 cm, p<0.05), in the intervention group. Moreover, we observed an increase in the frequencies of consumption of vegetables and fruits and a reduction in the consumption of sugar‐sweetened beverages, as well as a significant enhancement in daily walking. No significant changes in measures of fatness and in dietary or physical activity‐related habits were observed in the control group.

We conclude that the EAT project resulted in beneficial effects on measures of fatness and behavior in an adolescents population. SANOFI
Acculturation and food label use among Korean immigrants in New York City
Authors: Shim Hyun Jung , Doak Colleen , Jasti Sunitha
Published: June 2021

Objective

This study explores the level of acculturation of Korean immigrants living in New York City in relation to food label use, food label comprehension and whether label information influences the decision to purchase the food.

Method

A cross‐sectional survey of 355 church going Korean immigrants in Queens, New York City.

Results

In this sample, mean age was 42.3±14.5 y, 58% were women, 60% married, 67% had at least some college education, 52% lived in the U.S more than 12 y, and 22% were overweight or obese. While 59% used food labels at least sometimes, 44% scored ≥5 out of 6 in comprehension. Food label information reportedly changed purchasing decision for 46%. Mean acculturation was low at 2.06±0.69 (scale 1 – 5). Higher acculturation (score >;2) was associated with food label use, comprehension and whether the food label influenced the decision to purchase. Acculturation was associated with food label use (OR=3.13; CI=1.8, 5.42) and its influence on purchasing decision (OR=2.28; CI=1.29, 4.01) after adjusting for age, education and marital status. The associations were much stronger in men as compared to women (data not shown).

Conclusions

These results show that acculturation is an important determinant, particularly for men, both in relation to using food labels as well as the importance of food labels in purchasing decisions.
Infant iodine supplementation and motor and cognitive development: a randomized controlled trial
Authors: Bouhouch Raschida R. , Bouhouch Sabir , Stinca Sara , Cherkaoui Mohamed , Aboussad Abdelmounaim , Andersson Maria , Zimmermann Michael
Published: June 2021

The efficacy of two strategies to correct iodine deficiency in infants was tested in a double‐blind, randomized controlled intervention trial using oral iodized oil in a moderate‐to‐severely iodine deficient area in Morocco. Breastfeeding mother‐infant pairs (n=240) enrolled at <1 mo after birth received: 1) 400 mg iodine to the mother and placebo to the infant or; 2) placebo to the mother and 100 mg iodine to the infant. Iodine and thyroid status were measured at baseline, 3, 6, 9 mo and motor and cognitive development were measured at 12 and 18 mo (Bayley Scales of infant development II). Both interventions improved urinary iodine concentrations and thyroid function in infants (p<0.05). Iodine supplementation to the mother improved the median breast milk iodine concentration (P<0.05). At 12 mo the median Psychomotor Development Index (PDI) and Mental Development Index (MDI) in group 1 and 2 were 97 to 95 (PMI) (p = 0.46) and 101 to 105 (MDI) (p = 0.76), respectively. The data at 18 mo are currently being analyzed. Direct and indirect iodine supplementation appears equally effective in improving the iodine status, thyroid status and motor/cognitive development in breastfed infants. This study was funded by the Laboratory of Human Nutrition, ETH Zurich, Switzerland.
Plasma vitamin D, hormonal contraceptive use, and biomarkers of cardiometabolic disease
Authors: Garcia‐Bailo Bibiana , Badawi Alaa , El‐Sohemy Ahmed
Published: June 2021

The relationship between vitamin D and cardiometabolic disease is unclear. Hormonal contraceptive (HC) use among women is associated with elevated plasma 25‐hydroxyvitamin D [25(OH)D]. HC use is also associated with cardiometabolic disease risk. The objective was to examine whether the association between 25(OH)D and biomarkers of cardiometabolic disease differs between healthy young women HC non‐users (n=677), women HC users (n=280), and men (n=427) aged 20 – 29 years. Participants provided overnight fasting blood samples for measurement of 25(OH)D, glucose, insulin, and blood lipids. HC use was determined by questionnaire. In models adjusted for age, waist circumference, physical activity, ethnicity, and season of blood collection, vitamin D deficiency was associated with higher insulin, HOMA‐IR, and HOMA‐Beta among men and women HC non‐users, and with higher triglycerides among men only. No biomarkers were associated with 25(OH)D among women HC users. Circulating 25(OH)D concentrations are inversely associated with biomarkers of glycemic dysregulation in young adults; however, HC use among women attenuates this association. Given the widespread use of HC by women throughout the world, a better understanding of the extent to which these medications modify the relationship between vitamin D and disease‐related processes is warranted. Research support from the Advanced Foods and Materials Network.

Grant Funding Source: Advanced Foods and Materials Network
Vitamin K modulates lipopolysaccharide‐induced expression of Interleukin (IL)‐6 through inactivation of NF‐κB
Authors: Fu Xueyan , Wu Dayong , Meydani Simin N , Booth Sarah L
Published: June 2021

Vitamin K (VK) status is inversely associated with circulating proinflammatory markers but the mechanism is not known. In this current study, we performed an in vitro study to determine if VK suppress LPS‐induced inflammatory cytokines in mice peritoneal macrophage (Mø). Male (3, 21 and 33 mo, n=9–12 per group) and female C57BL6 mice (3 mo, n=12) were injected with 2.98% thioglycollate into peritoneum to elicit Mø. Harvested Mø were incubated with phylloquinone (VK1) or menaquinone‐4 (MK‐4) at different doses for 24h, and then stimulated with 0.1μg/ml lipopolysaccharide (LPS) for 24 h. IL‐6 and TNF‐α concentration in medium were measured. To determine if VK inhibits translocation of NF‐κB into nucleus, RAW Mø were incubated with 10μM VK1 or MK‐4 for 24h, and then stimulated by LPS at 1μg/ml for 0, 15, 30 and 60 min. NF‐κB /p65, IκB‐α and IKK‐β protein levels were measured.VK1and MK‐4 suppressed LPS‐induced expression of IL‐6, but not TNF‐α, in a dose‐dependent manner. Warfarin, a VK antagonist, had no effects, suggesting that VK suppress IL‐6 expression via a mechanism unrelated to its role as enzyme‐cofactor. The p‐IKK and p‐NF‐κB /p65 protein levels were significantly lower in both VK1 and MK‐4 treatments. The inhibitory effect of VK on proinflammatory cytokine production maybe mediated through the NF‐κB pathway.
Diet composition but not rat source affects bone quantity and strength in rats with subclinical inflammation
Authors: Miotto Paula Michelle , Castelli Laura M , Bruce W Robert , Ward Wendy E
Published: June 2021

Previous studies have shown differences in sensitivity to colon carcinogens among similar strains of rats from different suppliers, suggesting differences in colonic inflammation and epithelial cell proliferation. It is unclear if these differences may affect bone health differently. We determined if rats from different suppliers fed either control or experimental diet would have different bone mineral content (BMC), bone mineral density (BMD), and bone strength. Male Wistar rats (supplier was Harlan or Charles River, n = 12/group) were randomized to control diet (AIN‐76A, carbohydrate as glucose) or an experimental diet (AIN‐76A, carbohydrate as fructose as well as high iron, low calcium). Left femur (LF) and lumbar vertebrae (LV) were collected after 11 weeks of feeding. BMC and BMD of LF and LV were measured using DEXA. Peak load (PL), the maximum force a bone can withstand before fracture, was measured by 3‐point bending (LF) and compression (LF neck, LV3). The experimental diet resulted in lower (P <0.001) BMC and BMD of LF and LV, and lower (P <0.001) PL at all three sites, regardless of rat source. There was an interaction of rat source and diet in which Harlan rats fed control diet had higher (P < 0.05) PL at the LF neck than Charles River rats fed control diet. These results suggest that rat source and differences in subclinical inflammation are lesser determinants of bone quantity and strength than diet composition.
Effect of tart cherry versus PPAR agonist pioglitazone on stroke‐related phenotypes and inflammation
Authors: Seymour E Mitchell , Wolforth Janet , Bosak Kristen , Kondoleon Michael , Mehta Vivek , Brickner Paula , Bolling Steven F
Published: June 2021

Epidemiology data show that anthocyanin intake reduces stroke mortality. Anthocyanins can activate PPAR isoforms, but PPAR agonist drugs can increase stroke risk. Tart cherries are a rich source of anthocyanins, so we compared the effect of tart cherry (1% w:w) and PPAR agonist drug pioglitazone (Actos®) in the stroke‐prone spontaneously hypertensive rat. Over 5 months, we serially measured locomotion, balance, coordination, and systolic blood pressure. Compared to control, cherry intake affected morbidity but not mortality and reduced systolic blood pressure beyond Week 8. Tart cherry intake significantly improved balance (tapered beam, unassisted rearing) and coordination (ladder climb). Tart cherry reduced serum TNF‐α, reduced brain NF‐κB‐and PPAR‐associated mRNA, and reduced brain TNF‐α expression. Compared to cherry, Actos worsened tapered beam and ladder climb performance and increased brain PPAR‐related mRNA and brain TNF‐α. In summary, intake of a physiologically‐relevant amount of anthocyanins from tart cherry significantly reduced stroke‐related phenotypes, was safer than Actos, and may be a good preclinical model to explore the stroke‐protective effects of an anthocyanin‐rich diet. Supported by private gift (to SF Bolling).
Cranberry juice cocktail consumers have healthier cardio‐metabolic profiles
Authors: Duffey Kiyah , Sutherland Lisa A , Khoo Christina
Published: June 2021

We examined the association between cranberry juice cocktail (CJC) consumption with cardio‐metabolic outcomes in the U.S. Data for adolescents (12–18 y) and adults (≥19 y) were drawn from the NHANES 2005–2008 survey (n=13,897). A CJC consumer (n=477) was defined as anyone consuming CJC over two nonconsecutive 24‐hour dietary recalls. We use multivariate linear and logistic regression models to examine differences in anthropometric and cardiometabolic outcomes comparing CJC consumers to non‐consumers. Consumers drank an average 406 ml (14 fl oz) of CJC over two days. In fully adjusted models, adolescent CJC consumers had significantly lower weight (p=0.011), waist circumferences (WC, p=0.021), and fasting glucose (p<0.041) and significantly lower odds of high total cholesterol (C) (OR [95% Confidence Interval]: 0.10 [0.02, 0.61]) and high LDL‐C (0.04 [0.01, 0.39]) compared to non‐consumers. Adult consumers had significantly lower triglyceride (p=0.085) and CRP levels (p=0.018) and lower odds of high WC (0.78 [0.65, 0.95]) and elevated CRP levels (0.60 [0.42, 0.86]) and higher odds of being normal weight (1.28 [1.00, 1.64]). CJC consumers are healthier on many cardiometabolic measures compared to nonconsumers, perhaps due to high polyphenol intake.
Understanding low‐income parents’ decisions to participate in a subsidized fruit and vegetable buying program in four urban childcare centers
Authors: Agrawal Tara , Devine Carol , Hoffman Jessica , Wirth Catherine , Castaneda‐Sceppa Carmen
Published: June 2021

The Institute of Medicine recognizes increasing fruit and vegetable (F+V) access among low‐income children and their families is an important strategy to prevent childhood obesity. The aim of this qualitative study was to understand factors shaping low‐income, urban parents’ decisions to participate in Farm to Family (F2F), a subsidized fresh F+V buying program. F2F aims to increase fresh F+V consumption among young children by addressing cost and access barriers to F+V purchasing among low‐income parents in Boston, MA. Semi‐structured interviews were conducted with F2F participant (n=13) and non‐participant (n=9) parents at four of five participating Head Start programs. Analysis using the constant comparative method revealed emergent themes related to factors facilitating and inhibiting parents’ participation. Facilitating factors included perceived social, emotional, financial, and health benefits, food provisioning self‐efficacy, proximal social distance to the Head Start program, and program compatibility with personal identity and values. Inhibiting factors included parental feelings of time scarcity, limited agency in home food provisioning, and institutional communication challenges. Findings suggest strategies to engage vulnerable families in food access interventions. Funding by Boston Children's Hospital, Northeastern University, and the Gerber Pediatric Scholarship.
The Effect of Menu Labels, Displaying Minutes of Brisk Walking Needed to Burn Food Calories, on Calories Ordered and Consumed in Young Adults
Authors: James Ashlei , Adams‐Huet Beverley , Crisp Kelli , Mitchell Joel , Dart Lyn , Turner Marcel , Kasper Mike , Bowman Jessica , Joeckel Sarah , Toomey Nicole , Heefner Heather , Blasco Eric , Shah Meena
Published: June 2021

The effect of menu labels displaying amount of exercise needed to burn the food calories on foods ordered and consumed is unknown. Three hundred (18–30 y) men and women were randomly assigned to a menu without calorie labels (NCL) (n=99), a menu with calorie labels (CL) (n=99), or a menu with labels on the minutes of brisk walking needed to burn the food calories (EL) (n=102). All menus contained the same food/beverage options. Subjects were blinded to study purpose. Analysis of covariance, adjusted for pre‐meal hunger levels and sex, was used to examine the effect of the study menu condition on the outcome variables. There was a menu main effect for calories ordered (p=0.008) and consumed (p=0.04). Fewer calories were ordered (adjusted mean (CI): 763 (703, 824) vs. 902 (840, 963) kcal, respectively; p=0.002) and consumed (673 (620, 725) vs. 770 (717, 823) kcal respectively; p=0.01) by the EL compared to NCL group. There was no difference between the CL and NCL groups in food calories ordered (827 (766, 888) vs. 902 (840, 963) kcal, respectively; p=0.09) and consumed (722 (669, 776) vs. 770 (717, 823) kcal, respectively; p=0.21). Calories ordered (p=0.15) and consumed (p=0.19) were not different between the CL and EL groups. There was no difference in post lunch calorie intake by menu condition (p=0.39). In conclusion, EL menu led to fewer calories ordered and consumed compared to the NCL menu condition. Study was supported by TCU.
Creating Student Alliances in Nutrition Medicine Education
Authors: Hernandez Alejandra Mandisa , Schoettler Cynthia , Feldman Stephanie , Peace Kaitlin , Smith‐Lin Carolyn , Campbell Jeffrey , Johnson Connor , Redshaw James , Stamm Andrew , Oldfield Justin , Mildenhall Nicholas , Ireland Kathy , Lenders Carine , Lo Clifford , Saltzman Edward
Published: June 2021

Objective

To increase medical students’ knowledge, attitudes and skills in nutrition medicine through the creation of a student partnership and inter‐professional activities across universities.

Methods

The Boston Medical Student Committee on Nutrition (BMSCoN) is a partnership between nutrition student leaders of 3 Boston medical schools. Its mission is to increase student awareness of nutrition's impact on health and of the roles all health care professionals play in promoting healthy lifestyles. Each school's student nutrition group elects a representative to the BMSCoN committee. The group is led by a chair elected by school representatives and members.

Results

BMSCoN created a yearly lecture series highlighting nutrition topics in medicine with open attendance to all students. Themes included “Eating by Example – Empowering Future Doctors to be Healthy Role Models” and “Socioeconomic Issues in Nutrition”. Participation in nutrition interest groups is rising from 78 (2011) to 86 (2012). Lecture attendance increased from 28 (Jan 2012) to 38 (Oct 2012). An average of 35 students from all 3 schools attend each lecture.

Conclusion

Student interest in nutrition medicine is increasing. By forming an intercollegiate alliance of students, a network to further enhance nutrition medicine education now exists. We will continue our lecture series and create more opportunities for student nutrition involvement.
Assessing the Utility of a Network‐Based Curriculum Search Application (KnowledgeMap) for Evaluating Nutrition Content in a Medical School's Pre‐Clinical Curriculum
Authors: Seres David Stuart , Bogart Jane S , Richards Boyd F , Goglia Alexander G , Peever Steven M. J. , Marr Joshua R
Published: June 2021

Methods

Nutrition Master's students manually reviewed the slides from every lecture in the 18 month pre‐clinical medical curriculum at Columbia University College of Physicians & Surgeons (P&S) to identify content related to teaching of objectives defined in the Nutrition Curriculum Guide for Training Physicians (NCGTP), a former NIH‐funded program to improve medical nutrition education. An analogous curriculum review for ten representative NCGTP objectives was then performed using KnowledgeMap. Satisfactory KnowledgeMap search parameters unique to each objective were defined empirically.

Results

The manual review identified an average of 4.00 unique lectures with content relevant to each of the representative NCGTP objectives. KnowledgeMap identified an average of 6.10 unique lectures per representative NCGTP objective, an average of 4.38 of which were relevant. An average 45.8% of the presentations identified by KnowledgeMap and relevant to the objectives were not identified by the manual search.

Conclusions

Preliminary results indicate that KnowledgeMap is an effective means of searching the P&S curriculum for nutrition‐related content on an ad libitum basis, may be more sensitive than hand searching, and may serve as a useful tool for further medical curriculum content evaluation.
Energy‐density and macronutrient profiles of samples of infant formula provided by low‐income mothers of formula‐feeding infants at ~2 and ~4 months of age
Authors: Kavanagh Katherine F , Nicklas Jennifer C , Burney Janie L , Greer Betty P
Published: June 2021

The objective was to analyze samples of prepared infant formula, collected from formula‐feeding mothers, and to evaluate the energy‐density and macronutrient profiles in relation to infant weight variables. Subjects were low‐income mothers of formulafed infants < 3 months of age at recruitment. Mothers collected 1‐ounce samples of bottle contents for 24 hours, at two time points. Infants were weighed within 3 days of sample collection. Data were also collected on maternal use of infant cereal in the bottle. Samples were analyzed for moisture, protein, fat, and ash content. Carbohydrate content was determined by difference. Fifty‐four mothers provided ~7 samples per time point. Preliminary results indicate the percent calorie contribution from macronutrients was similar at both time points: protein ‐ 9.4% and 10.1%; fat ‐ 44.5% and 44.4%; and carbohydrate ‐ 46.1% and 45.6%, at ~2 and ~4 months, respectively. Assuming formula‐only content, energy‐density was 21.2 and 21.0 kcals/ounce at ~2 and ~4 months, respectively. However, dichotomization into cereal‐users and nonusers indicated that cereal‐users provided bottle contents with significantly greater energy‐density (23.4 and 22.1 kcal/ounce) than non‐users (19.9 and 19.6 kcal/ounce), at ~2 (p=0.001) and ~4 (p=0.039), respectively. Results relating energy‐density and macronutrient profile to infant weigh variables are pending and will be discussed.
Glutamine‐mediated Dual Regulation of Heat Shock Transcription Factor‐1 Activation and Expression
Authors: Xue Hongyu , Slavov Dobromir , Wischmeyer Paul
Published: June 2021

Heat shock factor‐1 (HSF1) is the master regulator for cytoprotective heat shock protein (Hsp) expression. It is widely thought that HSF1 expression is non‐inducible and thus the key control point of HSP expression is regulation of HSF1's transactivation activity. How HSF1 expression is regulated remains unknown. Herein, we demonstrate that glutamine (Gln) enhanced Hsp expression both in rat colonic epithelium in vivo and in cultured non‐transformed colonic YAMC cells. This was associated with upregulated HSF1's transactivation activity via increased HSF1 trimerization, nuclear localization and DNA binding. Intriguingly, Gln enhanced HSF1 protein and mRNA expression and Hsf1 gene promoter activity. Within the −281/−200 region of the Hsf1 promoter, deletion of the putative CCAAT enhancer binding protein (C/EBP) binding site abolished Gln's HSF1 response. Gln availability strikingly altered the ratio of C/EBPβ inhibitory and active isoforms, i.e., liver‐enriched inhibitory protein (LIP) and liver‐enriched activating protein (LAP). LIP and LAP were further shown to be independent repressor and activator respectively for Hsf1 gene transcription and the relative abundance of these two C/EBPβ isoforms was demonstrated to determine Hsf1 transcription. We show for the first time that Gln not only enhances HSF1's transactivation, but also induces Hsf1 gene transcription in a C/EBPβ‐dependent manner.
Dynamic regulation of hepatic vitamin E secretion by the α‐ tocopherol transfer protein
Authors: Chung Stacey , Thakur Varsha , Atkinson Jeffrey , Parker Robert , Manor Danny
Published: June 2021

Vitamin E, a plant‐derived neutral lipid, is an essential nutrient for all vertebrates that scavenges free radicals in biological membranes, thereby preventing oxidative stress. Of the eight naturally‐occurring forms of vitamin E, α‐tocopherol is the most biologically active. This discrimination is achieved by the selective retention of α‐tocopherol by the hepatic α‐tocopherol transfer protein (α‐TTP), and by the selective degradation of all other vitamin E isoforms by CYP4F2. In cultured hepatocytes, α‐TTP facilitates the secretion of α‐tocopherol to the circulation for uptake by extrahepatic target tissues. We aim to understand how the actions of α‐TTP are regulated in vivo. Specifically, we study how α‐tocopherol status affects the intracellular localization of α‐TTP, and whether phosphorylation of tyrosines in α‐TTP affects it activity. Using live‐cell fluorescence imaging, we found that localization of α‐TTP in hepatocytes is dynamic: in the absence of α‐tocopherol, the protein is found in a punctate perinuclear pattern, but upon addition of vitamin E, the protein redistributes to a diffuse cytosolic pattern. In addition, we found that tyrosine residue(s) of α‐TTP are phosphorylated, and that this modification is necessary for α‐TTP's activity. These findings suggest that trans‐localization and tyrosine phosphorylation of α‐TTP are regulated under physiological conditions. Thus, dynamic and homeostatic mechanisms regulate the body‐wide distribution of α‐tocopherol.

Research support: NIH 5T32DK007319–33 and NIH RO1DK067494.
The P2Y2 receptor mediates uptake of matrix‐retained and aggregated low‐density lipoprotein in primary smooth muscle cells
Authors: Dissmore Tixieanna , Mamedova Laman , Medeiros Denis , Weisman Gary A
Published: June 2021

The internalization of matrix retained and aggregated low‐density lipoprotein (agLDL) may involve the actin cytoskeleton in a manner that distinguishes this process from the endocytosis of soluble LDL. We have previously shown that UTP‐induced phosphorylation of filamin A (FLN‐A) is associated with actin polymerization in 1321N1 cells expressing the hemagglutinin (HA)‐tagged P2Y2 receptor (P2Y2R). Aortic smooth muscle cells (SMCs) were isolated from wild type (WT) and P2Y2R−/− mice to investigate the role of P2Y2R/FLN‐A interaction in the uptake of matrix‐bound agLDL. Cells were transiently transfected with cDNA encoding HA‐tagged WT P2Y2R or a mutant P2Y2R that does not bind FLN‐A, then treated with 10 μM UTP and plated on top of the matrix. We produced the SMC‐derived matrix by extracting the lipids with 3:2 hexane:propanol (v/v). DiI‐LDL was aggregated by incubation with 50‐milliunits/ml bacterial sphingomyelinase (SMase) in the presence of 5mM MgCl2 for 4 h at 37°C under argon. In preparation for LDL‐matrix binding 1 μg of lipoprotein lipase was added to the lipid‐extracted matrix for 1 h followed by 100 μl Smase‐treated DiI‐LDL. Confocal microscopy results showed no uptake of agLDL in P2Y2R−/− cells transfected with mutant P2Y2R. However, there was agLDL uptake in P2Y2R −/− cells transfected with the WT P2Y2R, indicating that an intact P2Y2R is necessary for agLDL uptake in mouse vascular SMCs.

Grant Funding Source: NHLBI Ruth L Kirschstein pre‐doctoral NRSA
Maresin 1 a Novel Macrophage n‐3 Derived Mediator is a Potent Tissue Regenerative Immunoresolvent
Authors: Dalli Jesmond , Karamnov Sergey , Zhu Min , Petasis Nicos , Serhan Charles N
Published: June 2021

Maresins are a novel family of pro‐resolving mediators recently described in self‐resolving inflammatory exudates that are biosynthesized by macrophages (Mϕ). The complete stereochemistry of Maresin 1 (MaR1), the first member of this family to be identified, remained of interest. Here we demonstrate that MaR1 produced by human Mϕ from endogenous DHA matched material obtained by total organic synthesis with stereochemistry 7R,14S‐dihydroxydocosa‐4Z,8E,10E,12Z,16Z,19Z‐hexaenoic acid. We next confirmed the defining potent anti‐inflammatory and pro‐resolving actions of MaR1 with synthetic, demonstrating that MaR1 effectively reduced polymorphonuclear neutrophil infiltration in murine peritonitis and enhanced human Mϕ efferocytosis. At concentrations as low as 10nM, MaR1 accelerated tissue regeneration in surgically injured planaria (Dugesia tigrina). Upon injury planaria were found to biosynthesize MaR1 from deuterium labeled DHA, a process that was inhibited by lipoxygenase inhibitor. These findings demonstrate that MaR1 is a potent immunoresolvent exerting anti‐inflammatory, pro‐resolving and tissue regenerative actions. Moreover, they offer new pathways for assessing macrophage functions and novel mediators in regulating local tissue homeostasis and regeneration.

This work was supported by NIH (Grants GM095467 and DE019938)
Increased carotenoid bioavailability from a unique, cislycopene containing tangerine‐type tomato
Authors: Cooperstone Jessica L , Ralston Robin A , Riedl Ken M , Francis David M , Lesinski Gregory B , Clinton Steven K , Schwartz Steven J
Published: June 2021

Red tomatoes accumulate lycopene (LYC) in the trans configuration while orange‐colored tangerine tomatoes accumulate LYC in cis forms. Previous work suggests cis‐LYC may be more bioavailable compared to all‐trans. We hypothesized that LYC will be more bioavailable from tangerine tomato juice compared to dose‐matched red juice. A human clinical trial (n=12) was performed with a randomized, cross‐over design to identify post‐prandial carotenoids in triglyceride rich lipoprotein (TRL) fraction of plasma. Following a two week low LYC diet, healthy subjects consumed tangerine or red tomato juice, followed by blood collection for 12 hours. Both juices provided 10 mg of total LYC; the tangerine juice had 94% cis‐LYC while the red juice had 10% cis‐LYC. We identified and quantified LYC, phytoene, phytofluene, ζ‐carotene and neurosporene from TRLs using high performance liquid chromatography‐tandem mass spectrometry. Increased area under the curve LYC was observed in subjects consuming tangerine compared to red tomato juice. These findings confirm enhanced bioavailability of cis‐LYC from tomatoes and provide rationale to explore tangerine tomatoes to deliver LYC in future studies of biological impact.
The relative vitamin A value of 9‐cis and 13‐cis β‐Carotene as compared to all‐trans β‐Carotene in Mongolian gerbils
Authors: Bresnahan Kara , Davis Chris , Tanumihardjo Sherry
Published: June 2021

Provitamin A biofortification of staple crops may ameliorate vitamin A (VA) status in countries where deficiency is prevalent. To assess the VA impact of these crops, the unique bioefficacies of cis‐isomers (formed during cooking) as compared to all‐trans (at) β‐carotene must be determined. We evaluated the VA efficacy of 9‐cis (9c) and 13‐cis (13c) isomers as compared with at β‐carotene and VA‐positive and negative control groups in VA‐depleted Mongolian gerbils in two studies (Study 1, n = 56; Study 2, n = 57). Gerbils were fed a VA‐deficient diet throughout the studies. A 4‐wk depletion was followed by 3‐wk (Study 1) or 4‐wk (Study 2) treatment with 9c, 13c, or at β‐carotene in cottonseed oil (Study 1, 8.06 μg/day; Study 2, 16.1 μg/day). In Study 1, no treatment group maintained baseline liver stores (0.70 ± 0.21 μmol/liver). at Liver stores (0.54 ± 0.15 μmol/liver) did not differ from the VA group (0.56 ± 0.10 μmol/liver) when fed 2:1, but did differ significantly from 13c (0.41 ± 0.14 μmol/liver) and 9c (0.44 ± 0.18 μmol/liver). As baseline liver reserves were not maintained in Study 1, the study was repeated at a higher dose and for an extended experimental period. HPLC analysis of carotenoid and retinol concentrations in liver, serum, kidney, spleen, testes, and lung samples from Study 2 is underway. Funded by a College of Agricultural and Life Sciences Honors Scholarship, Standard Process, Inc., and HarvestPlus 8907.
Impaired intracellular Ca2+ signaling alters the activity of growth promoting signaling molecules in Ryr2ADA/ADA mice
Authors: Zou Min‐Xu , Huang Taiqin , Pasek Daniel A , Meissner Gerhard
Published: June 2021

Substitution of three amino acid residues in the calmodulin (CaM) binding domain of the cardiac ryanodine receptor ion channel (W3587A, L3591D, F3603A, RyR2ADA) impairs CaM inhibition of RyR2, alters intracellular Ca2+ handling and leads to rapid increase in heart size and death of Ryr2ADA/ADA mice within about 2 weeks of birth (Yamaguchi et al., J Clin Invest 117: 1344–1353, 2007). To elucidate mechanisms by which cardiac heart size is increased, we determined the protein and phosphorylation levels of signaling molecules in hearts of 1‐day and 10‐day old Ryr2ADA/ADA and wild type mice. Immunoblots showed a significant increase in phosphorylation levels of mTOR at Ser2448, p70 S6 kinase at Thr389, S6 ribosomal protein at Ser235/236 and 240/244 and eukaryotic translation initiation factor 4B (eIF4B) at Ser422 with no major changes in protein expression levels. Phosphorylation of AMP‐activated protein kinase (AMPK) at Thr172 was decreased, whereas phosphorylation of insulin receptor substrate 1 (IRS1) at Ser612, p38 mitogen‐activated protein kinase (p38MAPK) at Thr180/Tyr182, phosphoinositide kinase 1 (PDK1) at Ser241 and p90 ribosomal S6 kinases (p90RSKs) at Ser380 and Thr 359/Ser 363 were all increased at postnatal day 10 in Ryr2ADA/ADA mice. The results indicate that impaired CaM regulation of RyR2 alters the activity of multiple signaling pathways regulating cardiac metabolism and growth. Supported by NIH.
Phenylephrine‐induced cardiomyocyte hypertrophy and calcification are regulated by CD73‐TNAP interaction and inhibited by adenosine receptor activation
Authors: Gan Tracey X , Taniai Seiichi , Zhao Ganjian , Huang Cathy , Velenosi Thomas J , Urquhart Bradley L , Karmazyn Morris
Published: June 2021

CD73 has 5′ exonucleotidase activity converting AMP to adenosine (Ado) and inorganic phosphate (Pi). Ado supresses the activity of intracellular Tissue Nonspecific Alkaline Phosphatase (TNAP) resulting in decreased conversion of pyrophosphate (PPi) to Pi thus inhibiting intracellular calcification via increased PPi formation. We studied potential interplay between these systems in cultured rat ventricular myocytes treated for 24 h with 10 μM of the hypertrophic agent phenylephrine (PE). PE produced myocyte hypertrophy which was associated with a time‐dependent reduction in protein levels of CD73 (P<0.05) concomitant with marked increases in TNAP levels (P<0.05). The upregulation of TNAP was supressed by the non‐specific Ado analogue 2 chloro‐Ado whereas the downregulation of CD73 was only partially reduced. Inhibition of CD73 with α,β‐methylene ADP significantly reduced myocyte‐derived Ado levels by >;50%, produced a direct hypertrophic effect and sensitized cardiomyocytes to the pro‐hypertrophic effects of PE. The TNAP inhibitor tetramisole also reduced the hypertrophy and completely abrogated PE‐induced cardiomyocyte calcification, effects mimicked by 2 chloro‐Ado. Our results show that CD73 downregulation coupled with TNAP upregulation contribute to cardiomyocyte hypertrophy and injury which can be attenuated by exogenous Ado. Supported by the Heart and Stroke Foundation of Ontario.
Disparate β‐Catenin Activation Following Iron Overload is Responsible for Hepatocyte Proliferation in Male Mice
Authors: Logan Gregory John , Misse Amalea , Monga Satdarshan P.S.
Published: June 2021

Iron overload in diseases such as hemochromatosis is associated with development of hepatocellular cancer (HCC). Since β‐catenin signaling is a key molecular mechanism in HCC, we investigated the impact of high iron diet on mice with normal or absent β‐ catenin in hepatocytes. Male and female β‐catenin conditional knockouts (KO) or littermate controls (Con) were fed high iron diet for 3 months. Male and female Con and female KO tolerated the regimen, while male KO showed signs of morbidity. The liver weight to body weight ratio of KO males was 50% of controls. Serum biochemistry showed a mild elevation of serum bilirubin in KO. Histological analysis showed increased apoptotic hepatocytes and increase in CD45 cells in KO. There was no change in fibrosis. KO male mice show 1.6‐fold more liver iron (p=0.012), lower serum iron, and similar hepcidin and Id1. There was about 64‐fold increase in Saa‐1 (p=0.05) coinciding with inflammation. All controls & KO females showed an increase in cell proliferation and number of cyclin‐D1‐positive hepatocytes, while KO males did not show cell proliferation and cyclin‐D1. Compared to mice that did not receive iron diet, Con males showed increased levels of cyclin‐ D1; however, other β‐catenin mediated transcripts—cmyc and glutamine synthetase—decreased. Thus high iron diet appears to be affecting the activity of β‐catenin, resulting in association with different transcription factors.
Region‐specific alterations in adipose tissue function: cardiometabolic risk goes belly‐up
Authors: Tchernof Andre , Lessard Julie
Published: June 2021

Human body fat distribution patterns are heterogeneous and result from extrinsic influences (e.g. hormonal effects) and regional differences in intrinsic properties of adipose cells. The capacity of preadipocytes to differentiate and then store or mobilize lipids in each fat compartment is a major determinant of body fat distribution patterns. It also reflects the metabolic role of the cells of each region and directly relates to the high cardiometabolic risk closely associated with abdominal, visceral obesity. Visceral adipocytes (e.g. omental cells) are efficient for hypertrophy through lipid storage and show high lipolytic responsiveness, whereas subcutaneous cells have a high capacity for hyperplasia. We examined the potential of omental and subcutaneous adipose tissues as stem cell sources using the ceiling culture approach of adipocyte dedifferentiation. This cellular process generates multipotent mesenchymal stem cells through rapid downregulation of lipogenic/adipogenic transcripts and activation of matrix remodelling programs. Dedifferentiation is slightly more effective in subcutaneous than omental cells. Thus, adipose cell characteristics and origin closely relate to metabolic status and stem cell properties.
The Effects of Image on Learning and Vice Versa
Authors: Wilson Timothy D.
Published: June 2021

Technology's impact on education is undeniable. Advanced image representation is almost a requirement by many institutions and governing bodies in medicine, dentistry, and allied health sciences. Endorsement to use technologies for demonstrative, training, and simulation purposes is almost ubiquitous. Often, efficacy and principles surrounding the use or development of complex visualisation tools is sparse for broad applications, and/or narrow for specific scenarios. This presentation will highlight methods that inform a “learner‐centred” approach to using images. The author will attempt to widen the understanding of complex images on learner behaviour and the underlying physiology of “what” and “how” learners achieve goals. We know learners are different, thus, this presentation will utilize learner spatial ability as the context. Learner differences can be described both by behaviour (extrinsic characteristics) and physiological consequence (intrinsic characteristics) supporting individual learning strategies. Pairing intrinsic and extrinsic information about the learner, pedagogical approaches incorporating complex visualisation can be developed, studied, and incorporated from an informed position. Educators, educational technologists, and industry will be in better position to develop meaningful and directed visualisation environments.

Grant Funding Source: N/A
Operant conditioning of spinal reflexes to improve function recovery after CNS damage
Authors: Thompson Aiko Kido
Published: June 2021

The elicitation of spinal reflexes, which has traditionally been used to monitor basic motor and sensory functions, is now finding uses for modifying CNS pathways and thereby restoring more effective function after spinal cord injuries and in other disorders. Reflex conditioning protocols can changes the simple pathways that are responsible for these reflexes. These changes reflect multi‐site anatomical and physiological plasticity. Because these simple pathways are also important for complex motor skills such as locomotion, modifications in them also affect important skills. Reflex conditioning protocols can be designed to target each person's particular deficits and can thereby supplement traditional rehabilitation methods.
Lactoferrin (Lf) modulates microbe‐associated molecular pattern (MAMP)‐ and cytokine‐induced inflammation in human fetal intestinal epithelial cells
Authors: Nonnecke Eric B. , Winters Sarah G. , Lönnerdal Bo L.
Published: June 2021

Immune dysregulation of postnatal enteropathies includes aberrant exposure to microbe‐associated molecular patterns (MAMP) that potentiate an exaggerated inflammatory cytokine profile. The antimicrobial protein lactoferrin (Lf) associates with its cognate receptor (LfR) on intestinal epithelial cells (IEC) of breast‐fed infants where it may exert immunomodulatory activity. Lf binds lipopolysaccharide (LPS) with high affinity possibly mitigating overt pattern‐recognition receptor signaling; however, little is know regarding the capacity of Lf to interrupt alternative MAMPs and their downstream cytokine profiles. Using a human fetal intestinal epithelial cell line (FHs74), we investigated effects of commercial bovine Lf (C‐bLf) on MAMP‐ (LPS: 1 μg/ml; DNA: 10 μg/ml, and flagellin: 1 μg/ml) and cytokine‐ (IL1β, TNFα, and IFNγ) induced inflammation. Analysis of protein expression showed that C‐bLf attenuates IL1β‐ and TNFα‐mediated up‐regulation of IL6 across time. Compared to unstimulated cells, LfR protein expression was up‐regulated in IL1β‐ (10 ng/ml) and TNFα‐ (50 ng/ml) stimulated cells. C‐bLf (400 μg/ml) inhibited MAMP‐induced IL6 and IL8 gene expression in unstimulated and cytokine‐stimulated cells at 4, 12, and 24 h. These findings suggest that Lf modulates cytokine‐ and MAMP‐induced inflammation in IECs suggesting a role for Lf in limiting the pathogenesis of postnatal enteropathies.

Grant Funding Source: N/A