bluuebunny/crossref_metadata_2025 huggingface dataset:
Entamoeba histolytica evades innate immunity by triggering the degradation of macrophage cytoskeletal‐associated proteins (152.4)
Authors: St‐Pierre Joelle , Moreau France , Chadee Kris
Published: June 2021

Entamoeba histolytica (Eh) is the causative agent of amebiasis, a disease responsible for ~100 000 deaths/year. In most cases, Eh colonizes the mucus layer of the colon without causing symptoms, however in some individuals Eh invades the colonic mucosa causing amebic colitis. The first response of the host at sites of Eh invasion is a robust acute inflammatory response mediated by macrophages. Eh‐macrophage interaction is thus a critical first step in determining how the innate immune response will be shaped, yet the mechanisms that regulate this interaction remain largely unknown. In this study, we investigated the early cellular events triggered in macrophages in response to Eh and the putative virulent factors involved. Through biochemical and microscopy techniques, we have unravelled that only live Eh in direct contact with human naïve macrophages triggered an instantaneous degradation of the cytoskeletal‐associated proteins Pyk2 and paxillin. This event was critically dependent on the major surface virulent factor, cysteine proteinase 5 (EhCP5) as revealed using EhCP5‐deficient Eh and protease inhibitors. As macrophage cytosketal proteins are critically involved in cell adhesion, migration and inflammation, we surmise that Eh has evolved mechanisms to “stun” macrophages during infection to dampen the innate immune response. Taken together, our findings advance a unique mechanism by which Eh modulates immune cells by interfering with the cell cytoskeleton, which may favour parasite colonization and/or altering pro‐inflammatory responses in Eh pathogenesis.

Grant Funding Source: Supported by the Natural Sciences and Engineering Research Council of Canada (NSERC)
The differential spread of prion strains into the brain (153.1)
Authors: Sigurdson Christina , Bett Cyrus , Kurt Tim , Kong Qingzhong , Nilsson K. Peter , Masliah Eliezer , Oldstone Michael
Published: June 2021

Prions are the only protein aggregates that naturally transmit as infectious agents, and recently human to human transmission has occurred through transfusion of prion‐contaminated blood. Most cases of natural transmission start with a peripheral exposure followed by prion spread to the CNS. Yet certain prions do not invade the CNS, despite prion accumulation in non‐neural organs, such as spleen or heart. Intriguingly, all of these poorly neuroinvasive prions form fibrils, which are uncommon structures in prion disease. We are investigating the molecular basis for the remarkable differences between the spread of nonfibrillar and fibrillar prions to the brain using in vivo models. We have found that the fibrillar prions were more resistant to enzyme digestion and were extraordinarily stable when exposed to protein denaturing conditions, in mice and in humans. Taken together, these results provide evidence for a striking separation in the biochemical of fibrillar and nonfibrillar prions that underlie their differences in neuroinvasion.

Grant Funding Source: NIH NS069566 and NS076896
Genome‐wide organization of chromatin and the transcription machinery (225.1)
Authors: Pugh Frank
Published: June 2021

With the advent of high throughput and high‐resolution genome‐wide protein‐DNA detection assays, the inter‐relationships between chromatin and the transcription machinery are now becoming clearer. We recently developed ChIP‐exo as a genome‐wide ultra‐high resolution assay to identify where specific proteins bind across any genome at near single base resolution. ChIP‐exo reduces false positives and false negatives, thereby providing a largely unambiguous view. From this, in the context of crystallographic data, structural and mechanistic insights into genome‐wide binding events can be attained. This will be demonstrated for sequence‐specific DNA binding proteins, chromatin regulators, and the general transcription machinery. Remarkably, several unifying themes emerge such as the presence of the same core promoter elements and mechanisms of transcription initiation occurring at most genes, from yeast to humans, from TATA‐containing to TATA‐less, and from coding to noncoding genes.
The function of PINK1 and parkin in mitochondrial quality control (234.2)
Authors: Fon Edward
Published: June 2021

Parkinson’s disease (PD) is a common, devastating neurodegenerative disorder. Both genetic and environmental models strongly implicate mitochondrial dysfunction in PD. In particular, PINK1 and Parkin, two recessive PD genes, function in a common pathway regulating mitochondrial quality‐control. In healthy mitochondria, PINK1, a mitochondrial kinase, is rapidly degraded in a process involving both mitochondrial proteases and the cytosolic proteasome. This process is highly dependent upon the membrane potential across the mitochondrial inner membrane (ΔΨm), which drives PINK1 import into mitochondria. Indeed, mitochondrial damage that dissipates ΔΨm blocks PINK1 import and leads to its accumulation on the surface of mitochondria. PINK1 accumulation triggers the translocation of parkin, an E3 ubiquitin ligase, from the cytosol to mitochondria, where it mediates the elimination of dysfunctional mitochondria by autophagy (mitophagy). From these studies, a concept of PD pathogenesis is emerging whereby defects in PINK1 or parkin function reduce the efficiency with which damaged mitochondria, a major source of toxic reactive oxygen species, are eliminated. We will present recent work, based on the crystal structure of parkin and on genetic screens to identify regulators of parkin function, exploring how parkin is activated upon its recruitment to damaged mitochondria.
Influence of weight loss on insulin sensitivity in the mature horse (246.4)
Authors: Zambito Jennie , Spooner Holly , Hoffman Rhonda , Barnes Kimberly
Published: June 2021

The obese horse has impairments in insulin sensitivity and glucose homeostasis similar to other species. Weight loss as a result of caloric restriction is thought to be beneficial in counteracting obesity related metabolic dysfunction. We hypothesized that 8 light‐type horses would display improvements in morphometric measurements, circulating metabolic markers, and minimal model estimates of glucose tolerance and insulin sensitivity during weight loss from an obese (7 to 8) to moderate (5) body condition score (BCS). Horses displayed significant decreases in all morphometric measurements (p蠄0.04) except for abdominal circumference (p=0.08). A decrease in rump fat thickness from 11.5 ±1.2 to 6.1 ± 1.1 mm reflected decreasing body fat mass (p<0.0001). Weight loss had no effect on circulating concentrations of glucose or insulin measured every other week. Insulin sensitivity increased from 1.078 ± 0.270 to 4.319 ± 1.592 x10‐4 L*mU‐1*min‐1 with both reduction in BCS and weight loss (p蠄0.04), yet glucose effectiveness and acute insulin response to glucose were not affected. The disposition index as an assessment of β‐cell function tended to increase with percent weight loss (p=0.09) but not lower BCS. Lack of changes in circulating markers along with only small changes in minimal model parameters suggest that while horses were obese, metabolic function was conserved.
Curcumin antagonizes the effects of EPA and DHA supplementation on oxidative stress in dogs (246.7)
Authors: Martineau Anne‐Sophie , Breniaux Marion , Leray Véronique , Nguyen Patrick
Published: June 2021

In obese dogs, some beneficial effects of PUFAs have been reported. They affect oxidative status as they stimulate endogenous antioxidant system, and are prone to be oxidized. The addition of a polyphenol antioxidant to an EPA+DHA supplement could be useful to better understand their mechanism of action.

Our aim was to check the effects of EPA and DHA w/wo curcumin on hepatic gene expression in obese dogs.

Animals were given a hyperenergetic diet with EPA+DHA (970 mg EPA/d and 780 mg DHA/d) for 6 wks, then EPA+DHA+curcumin for 6 wks. Liver biopsies were taken before (T0) and at the end of each period. The mRNA levels of antioxidant enzymes (SOD1, PON1, GPx, catalase, NQO1), of nuclear factor Nrf2 and hypoxia marker HIF1 α were assayed by RT‐PCR.

At the end of the EPA+DHA supplementation, the mRNA levels of SOD1, Nrf2, PON1, GPx, catalase, NQO1 and Nrf2 were higher than at T0, whereas at the end of the EPA+DHA+curcumin supplementation, the expression was not modified. The expression of HIF1 α was lower at the end of the EPA+DHA supplementation, and unchanged at the end of the EPA+DHA+curcumin supplementation.

Our results suggest that the PUFAs effects could be inhibited when curcumin was added. Nevertheless, these results do not permit to conclude if the higher expression of genes involved in antioxidant system reflects a defense against oxidized products, which generation could be avoided by the antioxidant curcumin.
Do aggressive feeding guidelines eliminate first week nutrition deficits in very low birth weight infants fed exclusively mother’s own milk? (247.2)
Authors: Ng Dawn , Brennan‐Donnan Joan , Unger Sharon , Bando Nicole , Gibbins Sharyn , Nash Andrea , O'Connor Deborah
Published: June 2021

Background: Hospitalized VLBW infants fed human milk are reported to have lower growth rates compared to those fed nutrient‐enriched formulas. Aggressive parenteral nutrition guidelines for VLBW infants have been adopted in many neonatal intensive care units (NICUs) in response to data confirming short‐term safety of this approach and potential long‐term neurocognitive benefits. However, actual intakes during the first week of life have not been extensively evaluated since adoption of these guidelines.

Objective: To describe the parenteral and enteral energy and macronutrient intakes in human milk‐fed VLBW infants from NICUs with aggressive nutrition guidelines.

Design: Daily parenteral and enteral intakes were prospectively collected for 96 VLBW infants fed only MOM enterally during the first week. Feeding goals included provision of protein (>2.0) and lipids (1.0 g/kg/day) on the day of birth, advancing to 3.5 (protein) and 3.0 (lipid) g/kg/day within the first few days.

Results: We found that 34% and 70% of infants did not meet protein and energy goals (of 3.5 g/kg/day and 90‐100 kcal/kg/day), respectively, at the end of the first week.

Conclusions: Despite the adoption of more aggressive nutrition guidelines, most MOM‐fed VLBW infants remain undernourished at the end of the first week of life. Strategies to address these deficits may significantly impact the health outcomes of this vulnerable population.

Grant Funding Source: Supported by CIHR (MOP#210093).
Watermelon supplementation reduces aortic hemodynamic responses to cold exposure in obese hypertensive adults (249.4)
Authors: Figueroa Arturo , Wong Alexei , Hooshmand Shirin , Kalfon Roy
Published: June 2021

Cold‐induced increase in aortic blood pressure (BP) may cause cardiac complications in adults with hypertension by increasing wave reflection and left ventricular afterload (augmentation pressure [AP] and index [AIx]). The purpose of the study was to examine the effects of L‐citrulline‐rich watermelon supplementation on aortic hemodynamic responses to cold pressor test (CPT) in hypertensive adults. Brachial (bSBP) and aortic systolic BP (aSBP), AP, AIx, AIx adjusted to 75 beats/min (AIx@75), and systolic tension time index (STI, myocardial oxygen demand) at baseline, during CPT, and magnitude of the response from baseline‐to‐CPT were evaluated in 13 adults with hypertension (10 women; age 57 ± 1 yr, bSBP 151 ± 5 mmHg). Participants were randomized to a 6‐week placebo or watermelon supplementation in a crossover design. Watermelon reduced (P< 0.05) bSBP and aSBP at baseline and during CPT, but did not affect the increases from baseline‐to‐CPT. Watermelon did not affect AP, AIx, AIx@75, and STI at baseline, but decreased (P< 0.05) AP and STI during CPT and the increases in AP (~5 mmHg) and AIx@75 (~7.3%) from baseline‐to‐CPT. Our findings indicate that watermelon supplementation reduces aortic SBP, pressure wave reflection, and myocardial oxygen demand during CPT in obese hypertensive adults. Watermelon supplementation may provide cardioprotection by attenuating cold‐induced aortic hemodynamic responses.

Grant Funding Source: National Watermelon Promotional Board
Effect of a food aid program on BMI/A of Mexican children, mediated by diet (251.3)
Authors: Gamboa Delgado Edna , González de Cossío Teresita , Colchero Aragonés Arantxa , Pelletier David , Quezada Amado David , Rodríguez Ramírez Sonia
Published: June 2021

Objective: To evaluate the effect of a Mexican Food Aid Program (Programa de Apoyo Alimentario, PAL) on Body Mass Index for Age (BMI/A) and the role of diet of < 5 y. Design: Secondary analysis of a program impact evaluation using a cluster randomized control effectiveness trial design. Setting: Poor and rural households in southern Mexico. Subjects: We analyzed a sample of 2,100 beneficiary children < 5 y from 206 communities that were randomly assigned to receive monthly transfers of either a food basket, with (FBE) or without (FB) an education (E) component, or cash with E (~14 USD/month) vs. a control group. Results: PAL did not contribute to an unhealthy weight of beneficiary children < 5 y as expressed as BMI/A z‐scores. Children in the FBE group had lower BMI/A z‐scores than those children in the control group (p=0.027). This effect is explained by a higher fruit and vegetables consumption and by a smaller sweet consumption in children belonging to the FBE group.
Location influences snacking patterns of U.S. toddler and preschoolers: results from the Feeding Infants and Toddlers Study, 2008 (252.4)
Authors: Deming Denise , Reidy Kathleen
Published: June 2021

Snacking patterns according to location were assessed among children from FITS, 2008. Dietary intake interviews (24‐hr recalls) were conducted by telephone with parents or primary caregivers of toddlers 12‐23 months (n=925), and preschoolers 24‐47 months (n=1,461). Parents or caregivers self‐defined snacks and location of snacking occasions. More children consumed snacks at home (AtH) than away from home (AwH) (toddlers, 73% vs 27%; preschoolers, 67% vs 33%). Mean intake of calories from snacks consumed AwH was higher than that consumed AtH differing by ~50 calories between the two locations for toddlers (346 vs 298 kcal/d, p<0.05) and for preschoolers (371 vs 326 kcal/d, p<0.05). While the contribution of snacks to TEI was not different between the two locations among toddlers (26.6% vs 27.6%), snacks consumed AwH contributed more to TEI (28.2%) than those consumed AtH (25.0%) among preschoolers (p<0.05). Snack choices were similar for toddlers and preschoolers (milk and milk products, fruit/juice, grains and sweets), but differed in frequency of consumption by location. Among toddlers, milk and milk products were the most frequently consumed snacks AtH (66%), while sweets were the top snacks consumed AwH (69%). Among preschoolers, sweets were the top snacks consumed both AtH (60%) and AwH (83%). FITS data show that location is an important factor influencing snacking patterns of young children.

Grant Funding Source: Funded by Nestle
Preference and acceptability of alternative delivery vehicles for prenatal calcium supplementation among pregnant women in urban Bangladesh (256.2)
Authors: Baxter Jo‐Anna , Roth Daniel , Mahmud Abdullah , Islam Munirul , Ahmed Tahmeed , Zlotkin Stanley
Published: June 2021

Prenatal calcium supplementation is recommended by the WHO to decrease the risk of preeclampsia when dietary calcium intake is low; yet, this recommendation has not been successfully implemented to date. We aimed to evaluate preference and acceptability of alternate delivery vehicles for prenatal calcium supplementation (conventional tablets, chewable tablets, unflavored powder, and flavored powder) among pregnant women in urban Bangladesh. In a modified discrete‐choice experiment, pregnant women (n = 132) completed a 4‐day ‘run‐in period’ in which each option was sampled once, followed by a 21‐day ‘selection period’ during which participants freely selected a single option per day. Preference was objectively based on the probability of selection of each option; acceptability was assessed using questionnaires. Conventional tablets demonstrated the highest probability of selection (62%); the probability of selection of chewable tablets (19%), flavored powder (12%), and unflavored powder (5%) were all significantly lower than for conventional tablets (P < 0.001). Conventional tablets were also more acceptable based on subjective reports. Observation of actual use and expressed perceptions showed that a conventional tablet is likely to be the most successful prenatal calcium supplement for scale‐up of the WHO recommendation in Bangladesh.

Grant Funding Source: Supported by the Hospital for Sick Children and Sprinkles Global Health Initiative
Evidence for a functional intestinal‐renal axis for arginine synthesis in the neonatal pig (258.2)
Authors: Marini Juan , Premkumar Murali , Didelija Inka , Stoll Barbara , Burrin Doug
Published: June 2021

Endogenous arginine (Arg) synthesis is a complex multiorgan process, in which citrulline (Cit) made in the gut is converted into Arg in the kidney, by what is known as the intestinal‐renal axis. In neonates, since the enzymes required to convert Cit into Arg are present in the gut, the prevailing dogma is that this axis is not functional and that Arg, but not Cit, is exported by the gut. Paradoxically, plasma Cit is also used as a marker for gut health and development in the neonate. We have determined Cit and Arg interorgan transactions (µmol•kg‐1•h‐1) in multi‐catheterized, anesthetized neonatal pigs (6‐10 d) using tracers and enzyme localization by immunohistochemistry. The gut released Cit (48±12) and Arg (41±12). Only a small fraction (4±1) of Arg was synthesized from circulating Cit. Because there was no direct utilization of ornithine for Arg synthesis, it is likely that the rest was from proteolysis. Due to enteral Arg uptake (27 ±12) the net Arg balance across the gut was not different from zero. The kidney took up Cit (37±4) and released Arg (28±3). Approximately 50% of the Arg released by the kidney originated from circulating Cit (13±3). The uptake of Arg by kidney (19±7) reduced the net output of renal Arg. Our results in neonatal pigs demonstrate a substantial Cit flux that can be explained by the lack of co‐localization of the enzymes for Cit and Arg synthesis in the gut, and the conversion of plasma Cit into Arg by the kidney.

Grant Funding Source: Supported by USDA/ARS Cooperative Agreement No 58‐6250‐6‐001
L‐[2,3,3,4,5,5,5,6,6,6‐2H10]leucine improves accuracy of muscle protein synthesis determinations when using blood amino acid enrichment as the precursor pool (258.8)
Authors: Tran Lee , Masters Haley , Katsanos Christos
Published: June 2021

The amino acid enrichment in blood (Eb) is often used in clinically relevant stable isotope studies to calculate muscle protein fractional synthesis rates (FSR), but it underestimates the FSR compared to methods using intracellular enrichment in muscle (Ei). We compared the FSR calculated with intravenous infusion of the novel tracer L‐[2,3,3,4,5,5,5,6,6,6‐2H10]leucine ([2H10]leu) to infusion of the traditional tracer L‐[13C6]phenylalanine ([13C6]phe) using Eb and Ei. Because [2H10]leu is intracellularly metabolized to [2H9]leu prior to reentry into the blood, we hypothesize that using [2H10]leu will minimize the discrepancy between FSR values calculated using Eb or Ei compared to [13C6]phe‐calculated FSR values using the corresponding Eb or Ei. To test our hypothesis, six healthy subjects received simultaneous infusions of the two stable‐isotope tracers following standard protocols. The [2H9]leu‐calculated FSR (%h‐1) was 0.08±0.01 based on Eb and 0.18±0.01 based on Ei. The corresponding [13C6]phe‐calculated FSR values were 0.06±0.01 and 0.25±0.02, respectively. Moreover, the difference in the [2H9]leu‐calculated FSR values using Ei vs Eb was significantly less (P<0.01; 0.10±0.01) compared to the difference in the corresponding [13C6]phe‐calculated FSR values (0.19±0.02). We conclude that, compared to [13C6]phe, the [2H10]leu tracer offers a more accurate approach to calculating FSR when Eb is sought as an alternative to the Ei.

Grant Funding Source: Supported by NIH/NIDDK Grant# R01 DK094062; NCATS Grant# UL1 TR000135
Manuka honey with cycloPower™ ő a novel bioactive complex of manuka honey and α‐cyclodextrin (259.4)
Authors: Chepulis Lynne , Harre Vikke , Truter Elsie , Suddes Mandy , Hockey Hans
Published: June 2021

Manuka honey is recognised for its health‐promoting properties and its use in medicine is well documented. However, the actions of Manuka honey are limited by rapid digestion and the inactivation of bioactive components such as methylglyoxal (MG). Cyclodextrins are naturally‐occurring glucose rings that improve stability and bioactivity of products. This study investigates the tolerability and bioactivity of α‐cyclodextrin‐complexed Manuka honey called Manuka Honey with CycloPower™ (MH‐CP).

Product tolerability was evaluated in a randomized, double‐blind, ascending dose study. Healthy participants (n=64) consumed 400‐4800mg or placebo for two weeks. MH‐CP was well tolerated. The most common events were headache and temporary mild/ moderate gastrointestinal disturbances (diarrhea, nausea). The rate of adverse events (AEs) was not dose‐related and most AEs resolved within 48 hours. A further study assessed the glycemic index (GI) of MH‐CP and revealed that the GI was significantly reduced (GI=18 vs 55) compared with uncomplexed Manuka honey. In addition, a suite of in vitro analyses indicated that MH‐CP has enhanced antimicrobial efficacy against a range of common gut organisms compared with Manuka honey. This demonstrates that Manuka honey with CycloPower™ is a well‐tolerated product with enhanced bioactive properties.
Hypoglycaemic and hypolipidemic effects of crude saponins extracted from Vernonia colorata in normoglycaemic albino rats (259.6)
Authors: Ijeh Ifeoma , Inyang Ekomobong , Egedigwe Agatha , Ahaiwe Udochukwu
Published: June 2021

The effect of oral administration of Crude saponin extract (CSE) from leaves of Vernonia colorata (Vc) on blood glucose concentration (BGC) and blood lipid profile in Wistar rats was investigated. Twelve male albino rats aged between 8 and 10 weeks were housed in stainless steel cages under humid tropical conditions. They were exposed to 12hr light and dark cycles and fed normal rat chow. Animals were divided into 3 groups of 4 animals each . A low dose (50mkg/kg body weight) and a high dose (100mg/kg body weight) of the CSE were administered to each test group while the control group received an equivalent volume of physiological saline on alternate days over a period of 28 days. Standard laboratory methods were used for the determination of the rats’ BGC and lipid profile. A significant decrease in BGC (mg/dl) was observed in the high (86.00 ± 4.69) and low (88.00 ± 8.33) dose groups relative to the control group (114.50 ± 8.58) after the first week of CSE administration. After the 2nd and 3rd weeks of CSE administration BGC (mg/dl) continued along the week 1 trend and at week 4 decreased further to 109.50 ± 5.00 (control), 64.33 ± 6.64 (low dose), and 65.33 ± 8.39 (high dose). Serum cholesterol (Chol) and triacylglycerol (TAG) concentrations (mg/dl) decreased significantly in a dose‐ and time‐dependent manner relative to the control (Chol: control, 130.83 ± 4.99a; low dose, 98.91 ± 2.96 and high dose, 83.84 ± 4.33 ; TAG: control, 126.50±4.03; low dose,94.80 ± 1.89; and high dose, 85.75 ± 2.39). The low dose did not significantly alter the HDL‐Cholesterol concentration in the test rats, but the high dose was found to significantly reduce HDL cholesterol (control, 56.28 ± 4.08; low dose, 52.22 ± 7.36; high dose, 38.24 ± 3.93). The CSE was found to significantly reduce LDL‐cholesterol concentration in the test rats at both high and low doses (control, 49.27 ± 3.02; low dose, 31.63 ± 2.56; high dose, 28.45 ± 1.32). CSE from Vernonia colorata may be useful in the management glycemic and lipidemic disorders.
γ‐Tocopherol supplementation attenuates arterial dysfunction in db/db mice (260.8)
Authors: Li Youyou , Quan Ying , Panneerseelan Leena , Mah Eunice , Guo Yi , Hawkins Makenzie , Jalili Thunder , Bruno Richard , Symons J David
Published: June 2021

γ‐Tocopherol (γ‐T) prevents endothelial dysfunction evoked by acute hyperglycemia. We hypothesized that γ‐T supplementation would attenuate arterial dysfunction induced by chronic hyperglycemia. Wild‐type (WT) mice were fed a diet with no γ‐T and db/db mice were fed 0 or 500 mg/kg γ‐T for 8 wk. Db/db mice had higher (p<0.05) plasma glucose and liver malondialdehyde (MDA) vs. WT animals. Compared to db/db controls, db/db mice fed γ‐T had higher (p<0.05) plasma γ‐T and hepatic levels of its metabolite γ‐carboxyethyl‐hydroxychroman (γ‐CEHC), and reduced (p<0.05) hepatic MDA, while plasma glucose was similar between groups. Relaxation to acetylcholine in precontracted femoral arteries was impaired in db/db controls vs. WT animals, and γ‐T reduced the severity of impairment in db/db mice. Arterial responses to sodium nitroprusside were similar among groups. p‐eNOSS1177 / total eNOS was lower (p<0.05) in arteries from db/db controls vs. WT and db/db mice fed γ‐T. In human aortic endothelial cells exposed (24 h) to 25 mM glucose, 3 µM γ‐CEHC prevented (p<0.05) glucose‐induced increases in reactive oxygen species, and decreases in p‐eNOSS1177 / total eNOS and nitrates + nitrites. These data suggest that γ‐T, either directly and/or indirectly through γ‐CEHC, protects against arterial dysfunction evoked by chronic hyperglycemia, potentially by lowering oxidative stress and improving NO bioavailability.

Grant Funding Source: UU‐VPR‐0981
1,25 Dihydroxyvitamin D regulation of glucose metabolism via pyruvate carboxylase in MCF10A‐ras human breast epithelial cells (261.7)
Authors: Zheng Wei , Koser Stephanie , Donkin Shawn , Teegarden Dorothy
Published: June 2021

Previous studies from our laboratory, employing Harvey‐ras oncogene transfected MCF10A (ras) cells, a model of early breast cancer progression, show that 1,25 dihydroxyvitamin D (1,25D) regulates glucose metabolism with reduced glycolysis and lactate production, and reduced flux to the TCA cycle in ras cells. Further, 1,25D reduced cell “glucose addiction”, a characteristic of cells in progression to cancer. In the current study, glucose restriction from 5 mM to 1 mM increased G1 cell cycle arrest (flow cytometry) in ras cells (62% vs. 71%, respectively). shRNA knockdown of pyruvate carboxylase (PC), a key enzyme for the anaplerosis of the TCA cycle, prevented the increase in G1 cell cycle arrest at 1 mM glucose in ras cells, which was a similar effect to 1,25D. However, 1,25D treatment in addition to PC knockdown had no effect in preventing the increase in G1 cell cycle arrest at 1 mM glucose, suggesting PC may mediate the effect of 1,25D. 1,25D inhibited PC mRNA (45%) and protein (65%) expression starting at 24 and 48 hours, respectively. Consistent with potential transcriptional regulation of the PC gene by 1,25D, six consensus sequences to the negative vitamin D responsive element (nVDRE) were found on PC gene promoter. Therefore, negative regulation of the PC gene is part of the mechanism by which 1,25D regulates glucose metabolism and prevents early breast cancer progression.

Grant Funding Source: Supported by NIH R25CA128770 and NCI CCSG CA23168
Exercise‐related effects of p53 on cancer preventative pathways (261.8)
Authors: King Brenee , Standard Joseph , Ewert Emily , Su Xiaoyu , Wang Weiqun
Published: June 2021

The American Cancer Society estimates over 1 million new cancer cases to be diagnosed in 2013. Thus, efforts to understand the mechanisms of cancer prevention are vital. Physical activity is a modifiable lifestyle choice with the potential to reduce the risk of certain cancers. As such, research into the molecular mechanisms of how physical activity results in cancer prevention is imperative. Changes to the insulin‐like growth factor‐1(IGF‐1) pathway are important to cancer preventative mechanisms. Recently, the p53 protein was linked to IGF‐1 pathways under specific dietary conditions. Currently, there is a gap in knowledge surrounding p53 and the molecular mechanism of its involvement in IGF‐1 signaling pathways following exercise. The objective of this study was to first investigate the molecular mechanisms regulating exercise‐induced activation of p53. Female mice underwent a moderate exercise regime five days a week for ten weeks. Dorsal skin tissue was collected and prepared for down‐stream analysis. Using western blotting and immunohistochemistry techniques, we observed a significant increase in p53 nuclear protein in exercised mice which may result from changes with its interaction with MDM2. Planned experiments, including immunoprecipitations, aim to investigate the interaction between p53 and its regulatory proteins. Furthermore, future experiments will focus on p53 and its effects on the IGF‐1 signaling pathway following exercise. Completion of these experiments will provide new information regarding p53‐related pathways in the cancer preventative effects of exercise.

Grant Funding Source: Supported by: NIH CA167678
iCook4H: dyad model (youth/adult pair) used in recruiting for a multistate study (262.5)
Authors: Olfert Melissa , White Jade , Wells Amy , Franzen‐Castle Lisa , Colby Sarah , Kattlemann Kendra , Matthews Douglas , White Adrienne
Published: June 2021

Recruitment of a unique approach using a dyad model, defined as youth/adult pair, (9‐10 year old youth and the main preparer of meals adult) incurred challenges in five states. With the goal of 500 dyads the end result was 223 pairs (ME=63, NE=58, TN=34, SD=22, WV=46) over a five‐month recruitment period (April‐August) to include two intense recruiting blitzes. Various approaches used by states: getting into schools before summer break and immediately when school resumed for fall; summer camps such as sports, Girl & Boy Scouts, YMCA; flyers in kid friendly venues, on cars, food bank boxes/bags/backpack program; involved Extension/4H partners; targeted EFNEP eligible participants, hiring a local community recruiter, etc. Barriers identified by states: parent not ready to commit to schedule in summer months; difficult to find venues where child/adult both were; flyer was vague; flyer was inclusive of both control and treatment; conflict with other functions such as sports; not with afterschool programs; access to parents (decision makers) limited; children out of age range or siblings wanting to participate; no internet access; no child care for other children during treatment sessions. Conclusions, using the dyad model the decision maker, scheduler/attendee is the adult even with a child’s enthusiasm and desire to enroll in a study focusing on culinary and nutrition skills, family mealtime and physical activity.

Grant Funding Source: USDA AFRI Integrated Childhood Obesity Multi‐state Grant No. UM‐S881
A longitudinal analysis of sugar‐sweetened beverage intake during infancy and obesity at six years of age (267.2)
Authors: Pan Liping , Li Ruowei , Park Sohyun , Galuska Deborah , Sherry Bettylou , Freedman David
Published: June 2021

Sugar sweetened beverage (SSB) consumption may contribute to obesity through excess calorie intake. We examined whether SSB intake during infancy predicts obesity at 6 years. We included 1189 US children who participated in the Infant Feeding Practices Study II in 2005‐2007 and were followed up at 6 years in 2012.

Children’s weight and height were measured by mothers. Obesity was defined as BMI‐for‐age and sex 蠅 95th percentile on the CDC growth chart. We used multivariable logistic regression to estimate the associations of SSB consumption in infancy and obesity at 6 years controlling for child’s birth weight, maternal prepregnancy weight status, and maternal and child demographic and dietary characteristics. The obesity prevalence at 6 years among children who consumed SSBs during infancy was twice as high as that among non‐SSB consumers (17.0% vs 8.6%). The adjusted odds of obesity at 6 years was 71% higher for any SSB intake and 92% higher for SSB introduction before 6 months compared with no SSB intake during infancy. Children who consumed SSBs 蠅3 times/week during 10‐12 months had twice the odds of obesity compared with those who consumed no SSBs in this period. However, among children who consumed SSBs, the odds of obesity at 6 years did not differ by age at SSB introduction during infancy or mean weekly SSB intake during 10‐12 months. Our study findings suggest that SSB consumption during infancy may be a risk factor for obesity in early childhood.

Whether unmeasured behaviors contributed to the association is unclear.
Diet quality of adult cancer survivors in NHANES 1999‐2010 (267.8)
Authors: Liu Shanshan , Must Aviva , Folta Sara , Nelson Miriam , Roberts Susan , Parsons Susan , Saltzman Edward , Zhang Fang Fang
Published: June 2021

Introduction: Cancer diagnosis can act as a ‘cue to action,’ motivating survivors to make positive changes in health behaviors, including dietary habits. However, it remains unclear whether cancer survivors have better diet quality than individuals without cancer, and how their diet quality is associated with their age, gender, weight status and length of survivorship.

Method: We assessed the Healthy Eating Index (HEI) 2010 in 1,988 adult cancer survivors in the National Health and Nutrition Examination Survey (NHANES) 1999‐2010 and 3,976 noncancer controls matched by age and gender. HEI 2010 was calculated based on dietary data assessed by 24‐hour diet recall. Logistic regression models were used to compare HEI 2010 total score and its components between cancer survivors and controls after adjustment for age, sex, education, alcohol consumption, cigarette smoking and body mass index. Sampling weights were included in all analyses.

Result: The mean total HEI 2010 score in cancer survivors was 50.3 (SD=0.5) (range:0‐100), similar to that in noncancer controls (mean=50.5, SD=0.4, p=0.63).Cancer survivors had a significantly lower score for total vegetables (OR=0.81, 95% CI: 0.71‐0.93) and empty calories (calories from solid fats, alcohol and added sugars) (OR=0.86, 95% CI: 0.75‐0.99) than those without cancer. The low adherence to total vegetable was more profound in long‐term survivors (years since diagnosis 蠅10 years) (OR=0.72, 95% CI: 0.60‐0.86) than recent survivors (years since diagnosis <10 years) (p for interaction <0.05).

Conclusion: In a large national survey, cancer survivors did not have better diet quality than individuals without cancer. Rather, cancer survivors scored worse in following the recommendation for total vegetables and empty calories, based on the 2010 Dietary Guidelines for Americans. Dietary intervention is needed to increase vegetable intake and reduce solid fat, alcohol and sugar intake in cancer survivors to improve their long‐term health outcomes.
Household food insecurity and its determinants in the Kalalé district of Benin (268.1)
Authors: Alaofè Halimatou , Taren Douglas , Burney Jennifer
Published: June 2021

Despite making significant economic progress, food insecurity and malnutrition present key policy challenges in Benin. We analyzed the determinants of food insecurity in northern Benin, based on primary data that we collected from 368 randomly selected households from 4 villages of Kalalé district in 2007. Food insecurity was defined as how often in the year they are unable to fully provide for family's food needs. Logistic regression analyses were used to investigate the association of demographic and socio‐economic factors on food insecurity. Food insecurity was prevalent in the district surveyed (96%) categorized as moderately or severely food insecure. Using bivariate analysis, key livelihood assets indicators associated household food insecurity were identified as: number of illiterate in households (OR, 1.76; 95% CI, 1.14‐2.70; P=0.01), family size (OR, 1.29; 95% CI, 0.99‐2.69; P=0.04), self‐reported satisfaction with health status (OR, 4.63; 95% CI, 2.61‐8.20; P<0.001), housing material (OR, 0.09; 95% CI, 0.01‐0.60; P=0.01), participation in agricultural organization (OR, 3.25; 95% CI, 1.82‐5.81; P<0.01) and access to credit (OR, 3.25; 95% CI, 1.82‐5.81; P<0.001). Access to credit and housing material were the strongest predictors of food insecurity in multivariate modeling (P<0.05). Food insecurity is a timely and relevant issue, as it affects a significant number of households in the district surveyed. Targeted policy interventions aimed at increasing money available in households are needed. Furthermore, making health, family planning, education and agricultural organization which bond women together, targets of food security programs should help significantly to reduce the incidence of food insecurity.

Grant Funding Source: SELF
Effect of dietary (‐)‐epigallocatechin‐3‐gallate (EGCG) pretreatment on the hepatotoxicity of acute high dose EGCG (270.3)
Authors: James Karma , Forester Sarah , Lambert Joshua
Published: June 2021

Green tea based dietary supplements containing high levels of (‐)‐epigallocatechin‐3‐gallate (EGCG) have become popular for weight loss. Case‐studies have reported hepatotoxicity associated with consumption of green tea‐based supplements and laboratory studies have demonstrated the potential hepatotoxicity of EGCG. We examined the effect of pretreatment with dietary EGCG on the bioavailability and hepatotoxicity of high oral bolus EGCG in CF‐1 mice. EGCG (750 mg/kg, i.g., once daily) for 3 d increased plasma alanine aminotransferase by 80‐fold compared to controls. High dose EGCG also decreased hepatic levels of reduced (59% decrease) and total glutathione (33% decrease), and increased hepatic phosphorylation of histone 2AX compared to vehicle‐treated control mice. Pretreatment with dietary EGCG (3.2 mg/g) for 2 wk blunted these changes. EGCG pretreatment also raised the levels of several oxidative stress‐related genes. Analysis of plasma and liver levels of EGCG showed that pretreatment with dietary EGCG reduced the peak plasma (38% reduction) and hepatic (57% reduction) EGCG concentrations following oral bolus dosing. In conclusion, EGCG appears to modulate its own bioavailability and chronic exposure to dietary EGCG may reduce the hepatotoxic potential of high oral bolus EGCG. These data may help explain the variation in sensitivity of human subjects to green tea‐containing supplements.

Grant Funding Source: NIH AT004678
Metabolomic phenotyping of cancer metabolism (350.2)
Authors: Fiehn Oliver , Wikoff Bill
Published: June 2021

The NIH Common Fund has created three regional resource cores to increase the capacity for metabolomic research for NIH‐funded projects. At UC Davis, the West Coast Metabolomics Center integrates more than 30 mass spectrometers and 5 NMR instruments in eight laboratories, focusing on glycomics, complex lipids, eicosanoids and lipid mediators, imaging, primary metabolism and identification of unknowns. In addition, integration with genomic data including pathway mapping and statistics is part of research advancements and fee‐based services. In its first year, the West Coast Metabolomics Center has hosted three symposia on cancer metabolism, microbial metabolism and a hands‐on workshop for training the next generation of scientists.

We will show how metabolomic data from blood screening from patient cohorts at‐risk can provide biomarkers of lung cancer even more than 6 months prior to clinical diagnosis, potentially giving more time for treatment for these individuals. We further detail differences in cancer metabolism in the lungs of adenocarcinoma patients and provide details for exogenous compounds found in such human lung tissues.
Validation of the Remote Food Photography Method to quantify intake of infant formula (36.1)
Authors: Duhé Abby , Lammi‐Keefe Carol , Martin Corby , Redman Leanne
Published: June 2021

Background: Accurate methods of assessing food intake in infants are needed to assess the relationship between infant feeding practices and the risk of childhood obesity. Current methods are either subjective or have limited ability for widespread use beyond clinical research settings due to cost and high burden.

Objective: To assess the accuracy of the Remote Food Photography Method (RFPM), a novel food intake assessment method, to estimate infant formula as compared to the gold standard, the directly weighed foods method.

Design: Fifty‐three adults were recruited to prepare infant formula bottles and use the RFPM to capture photographs of infant formula at different stages of bottle preparation (dry powdered formula, liquid prepared formula, and liquid waste). Gram weights were measured by the RFPM and the directly weighed foods method with the aim of the RFPM to estimate food intake within 10% of the directly wegihed foods method. The effects of trial number and caregiver status on the preparation of dry powdered formula and liquid prepared formula were also examined.
Results: The RFPM estimated liquid formula intake within 10% of the directly weighed foods method in 2 fluid ounce, 4 fluid ounce, and 6 fluid ounce bottles by ‐4.1 ± 14.4% (P<0.0001), 2.8 ± 16.3% (P=0.1550), and 7.0 ± 12.4% (P<0.0001), respectively. The RFPM estimated liquid formula intake by 14.0 ± 10.3% (P<0.0001) in 8 fluid ounce bottles. There were no significant differences for the effects of trial number and caregiver status on infant formula preparation except for a significant main effect of caregiver status on the preparation of dry powdered formula of 2 fluid ounce bottles (P=0.05).

Conclusion: Accuracy of the RFPM is comparable to other objective methods without excess cost or burden. The RFPM is therefore a viable method for measuring infant formula intake in infants with potential for widespread use in research and clinical practice.
Performance of Food Frequency Questionnaire, 4‐d food record and 24‐h dietary recall to measure total sugars (TS) against the urinary TS biomarker in postmenopausal women (36.4)
Authors: Tasevska Natasha , Midthune Douglas , Tinker Lesley , Neuhouser Marian , Beasley Jeannette , Van Horn Linda , Lampe Johanna , Potischman Nancy , Prentice Ross , Kipnis Victor
Published: June 2021

Measurement error (ME) in self‐reported sugars may be obscuring the true association of sugars with disease risk in epidemiologic studies. We aimed to assess performance of 3 self‐report methods to measure TS relative to 24‐h urinary sucrose and fructose, previously reported as predictive biomarker of TS intake. The Nutrition and Physical Activity Assessment Study (NPAAS) is a biomarker study within Women’s Health Initiative Observational Study including 450 post‐menopausal women aged 60‐91 during NPAAS. FFQ, 4DFR and three 24HDRs, along with urinary TS biomarker were collected. The biomarker, calibrated based on ME parameters previously estimated, was used as a measure of TS intake. Performance (% variation explained) of the 3 self‐report methods to measure TS was assessed by regressing calibrated biomarker on FFQ‐, 4DFR‐ or 24HDR‐based TS, adjusting for participants’ characteristics. Across all methods, self‐reported intake explained only small fraction of variation in biomarker‐predicted TS (Table 1). Age, BMI, smoking, education and physical activity somewhat improved predictability of the model, yet left majority (73‐88%) of variation unexplained. Based on the biomarker, none of self‐reports provided good estimate of intake. Measuring a sugars biomarker in a subset in epidemiologic studies may be necessary to yield more reliable intake, hence disease risk estimates for sugars.

Table 1. Adjusted R2 for regression of log calibrated biomarker on log self‐reported sugars with and without additional covariates in the regression model

Dietary intake
Regression model
Adjusted* R2

FFQ
4DFR
Average of 3 24HDR

Total sugars intake (g/day)
Self‐reported intake only
0.04
0.05
0.04

Multipleâ€
0.13
0.13
0.12

Total sugars density(g/1000 kcal)
Self‐reported intake only
0.08
0.06
0.12

Multipleâ€¡
0.24
0.22
0.27

* R2 and multiple R2 are adjusted for within‐subject error in the biomarker.â€ Included log self‐reported intake, log age, log BMI, square root physical activity (METs/week), smoking status (current, former/never) and education (< HS graduate, HS graduate, some college, college graduate).â€¡ Included log self‐reported intake, log age, log BMI, smoking status (current, former/never) and education (< HS graduate, HS graduate, some college, college graduate).

Grant Funding Source: Supported by the Intramural Research Program of the NCI, NIH, U.S. DHHS
The Sedentary Time and Activity Reporting Questionnaire: reliability and validity against doubly labeled water and seven‐day activity diaries (36.8)
Authors: Csizmadi Ilona , Neilson Heather , Kopciuk Karen , Khandwala Farah , Liu Andrew , Friedenreich Christine , Yasui Yutaka , Rabasa‐Lhoret Remi , Bryant Heather , Lau David , Robson Paula
Published: June 2021

We determined the measurement properties of the Sedentary Time and Activity Reporting Questionnaire (STAR‐Q) designed to estimate past‐month activity energy expenditure (AEE). STAR‐Q validity and reliability were assessed in 102 men and women in Alberta, Canada (2009‐2011), who completed 14‐day doubly‐labeled water protocols, 7‐day activity diaries beginning on Day 15 and the STAR‐Q on Day 14 and again at three and six months. Reliability of the STAR‐Q over the first three months was substantial (ICC = 0.84 and 0.73) for total energy expenditure (TEE) and AEE, respectively. STAR‐Q‐derived TEE and AEE were moderately correlated with DLW estimates (Spearman rhos =0.53 and 0.40 respectively; p<0.001). Body mass index, age, gender and season adjusted‐concordance correlation coefficients (CCCadj) were 0.24 (95% CI: 0.07, 0.36) and 0.21 (95% CI: 0.11, 0.32) for STAR‐Q versus DLW‐derived TEE and AEE, respectively. Agreement between the diaries and STAR‐Q in MET‐hours/day was strongest for occupational sedentary time (CCCadj=0.76 (95% CI: 0.64, 0.85)) and for strenuous activity (CCCadj=0.64 (95% CI: 0.49, 0.76)). The STAR‐Q demonstrates substantial reliability and reasonable validity for ranking individuals by AEE, occupational sedentary time, and strenuous activity and can be used in epidemiologic studies investigating the health effects of overall energy expenditure and its sub‐dimension components.

Grant Funding Source: Supported by the Canadian Institutes of Health Research and the Alberta Cancer Research Institute
Vitamin D receptor polymorphisms predict greater decrease in calcium absorption (373.1)
Authors: Chang Brian , Sukumar Deeptha , Schlussel Yvette , Gordon Derek , Shapses Sue
Published: June 2021

Genetic variation may account for more than 70% of the variance in Ca absorption, and several studies suggest that vitamin D receptor (VDR) gene polymorphisms influence absorption. Estrogen is also known to affect Ca absorption, yet only one study has examined the influence of estrogen‐α (ESR1) gene polymorphisms. Ca absorption is attenuated during caloric restriction (CR) and is increased by vitamin D supplementation (VitD). We therefore studied whether the ESR1 and VDR polymorphisms influence the Ca absorption response 6 weeks after either CR or VitD supplementation. True fractional calcium absorption (TFCA) was measured in 180 pre‐ and post‐menopausal women. Genotypes for the VDR (BsmI, ApaI, TaqI, and FokI) and the ESR1 (XbaI, PvuII) polymorphisms were determined through PCR‐RFLP analysis and the haplotypes were reconstructed using PHASE v2.1.1. Multiple linear regression and two‐way ANOVA analyses using dietary interventions and the dominant/recessive models as predictors showed that in the absence and presence of a dietary intervention, the BB genotype and the 2 copies of BAt allele predicted a greater decrease in TFCA. We found no association with the ESR1 polymorphisms. Our findings suggest that the VDR polymorphism improves the ability to predict Ca absorption under a variety of conditions and may influence dietary Ca requirements.

Grant Funding Source: NIH‐AG12161