bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Access in Food Deserts: A Case Study in an Urban Midwestern Neighborhood
Authors: Gibson Cheryl A , Endicott Diana , Pritchard Corie C
Published: June 2021

Food deserts are a persistent challenge in urban districts. Because of lack of access to full line grocery stores most dietary choices that are readily available are highly processed items with elevated saturated fat and/or sugar and low nutrient density. As a result, community members in areas designated as food deserts are at an increased risk for obesity, diabetes, heart disease and hypertension. One solution for increasing access to fresh fruits and vegetables is partnering with a faith based organization and creating a farmer's market in a church. Through partnership with the church, local farmers and community members, this market has increased access to fresh fruits, vegetables, lean meats and dairy for residents of this neighborhood. Access has been increased not only by providing a market within a food desert, but also by implementing EBT match for visitors to the market. In addition to increasing access to fresh foods, education on nutrition, physical activity and chronic disease has also been implemented. Through surveys administered to customers and members of the church, we have tracked dietary intake, chronic disease and purchasing habits over the past year in an effort to evaluate what impact the church has had on the most vulnerable in the community, particularly the very young and the elderly. Funded by the W.K. Kellogg Foundation
Do front‐of‐pack nutrition rating systems and symbols (FOPS) direct consumers to the healthiest products in an unregulated environment?
Authors: Emrich Teri , L'Abbe Mary
Published: June 2021

Concern has been raised that unregulated FOPS may mislead consumers into believing that a single food is ‘healthier’ than foods not bearing the FOPS. The nutritional criteria of a non‐profit (Health Check™) and a manufacturer (Sensible Solutions™) FOPS were applied to a national database of packaged food products. The proportion of foods qualifying for a given FOPS was compared to the proportion carrying the FOPS using exact binomial test. 7503 and 3010 of the 10,487 foods in the database could be assigned a Health Check™ or Sensible Solutions™ food category, respectively. 3360 (44.8%) of the foods assigned a Health Check™ category qualified for a Health Check™ symbol and 560 (7.5%) foods carried the symbol. Up to 2380 (79.1%) of the foods assigned a Sensible Solutions™’ category qualified for a Sensible Solutions™ symbol and 122 (4.1%) foods carried the symbol. The discord between products qualifying for and carrying these FOPS persisted at the food category and subcategory level. More than 75% of the products in many of the subcategories of either FOPS qualified for their respective symbols. These results suggest that FOPS are not always a useful guide to identifying the healthiest food products as more products qualify for these systems than are identified by the systems’ symbols.

Grant Funding Source: Earle W. Mc Henry Research Chair Award (M.L.), CIHR Frederick Banting and Charles Best Canada Graduate Scholarship, Cancer Care Ontario/CIHR Training Grant in Population Intervention for Chronic Disease Prevention: A Pan‐ Canadian Program (#53893), and CIHR Strategic Training Program in Public Health Policy (T.E.)
Gene‐dietary fat interaction and bone mineral density in Children: a twin study in China
Authors: Huang Tao , Zhao Wei , Liu Huijuan , Wang Youfa
Published: June 2021

Aims

Dietary fat correlates with bone mineral density (BMD). However, it is unknown if gene‐diet interaction modulates the relationship. We tested the association between dietary fat and BMD, and test if dietary fat modifies the degree of genetic influence on BMD and bone speed of sound (SOS) in Chinese child twins.

Methods

We included 622 twins aged 7–15 y (n=311 pairs, 162 monozygotic (MZ), 149 dizygotic (DZ)) from South China. Data on anthropometry, dietary intake, BMD, and SOS were collected. Quantitative genetic analyses of structural equation models were fit using the Mx statistical package.

Results

The within‐pair intra‐class correlations (ICC) for BMD and SOD were higher for MZ than for DZ twins. The ICC for BMD in DZ twins were nearly half of that for MZ twins (ICC=0. 39vs0. 70). The heritability of BMD and SOS were 71% and 79%. Phenotypic correlation between fat intake and SOS was significant (r=−0.185, p=0.035). SOS was negatively correlated with fat intake in boys (r=0.111, p=0.048), but not in girls. Full Cholesky decomposition models show SOS has a strong genetic correlation with fat intake (rA =−0.88, 95% CI=−0.94, 0.01); the environmental correlation between fat intake and SOS was weak (rE =−0.04, 95% CI=−0.20, 0.13). Fat intake modified the additive genetic effects on BMD.

Conclusions

Genetic factors explain 71% and 79% of individual variance in BMD and SOS, respectively. Low fat intake counteract genetic predisposition to low BMD.

Grant Funding Source: NIH/NIDDK (P60 DK0079637) and NIH/NICHD (U54 HD070725‐01)
Dietary supplementation of ginseng prevents obese and metabolic syndromes in high fat diet‐fed mice
Authors: Li Xiaoxiao , Luo Jing , Velayuthan Anandh Pon , McMillan Ryan , Hulver Mattew , Zhen Wei , Alkhalidy Hana , Liu Dongmin
Published: June 2021

Obesity and diabetes are growing health problems world‐wide. In this study, we found that dietary provision of Chinese ginseng (0.5 g/kg diet) greatly prevented body weight gain in high fat diet‐fed mice. Gensing‐fed mice had lower body fat mass, while lean mass was only moderately modulated. In addition, treatment with ginseng improved fasting blood glucose, glucose tolerance, peripheral insulin sensitivity, and blood pressue in obese mice. Body temperature was higher in mice fed gensing‐supplemented diet but energy expenditure and cage activity were not altered. Dietary intake of ginseng increased fatty acid oxidation in the liver but not in skeletal muscle. These data suggest that Chinese ginseng can potently prevent the development of metabolic syndrome in high fat diet‐fed mice.

Grant Funding Source: This work was supported by grants from National Center for Complementary and Alternative Medicine of National Institute of Health (1R01AT007077–01 to DL) and the American Diabetes Association research award (7–11‐BS‐84 to DL)
Quercetin and Green Tea Extract Supplementation in High‐ Fat Diet‐Induced Inflammation and Glucose Intolerance in Mice
Authors: Cialdella‐Kam Lynn , Ghosh Sujoy , Meaney Mary Pat , Knab Amy M. , Shanely R. Andrew , Nieman David C.
Published: June 2021

Quercetin (Q) and green tea extract (GTE) modulate glucose homeostasis and have anti‐inflammatory influences. The purpose was to determine if Q and GTE would synergistically counter glucose intolerance and inflammation induced by a high fat diet (HFD; saturated fat=60% kcal) in mice. Male C57BL/6J mice were put on a HFD for 12‐wk and then randomly assigned to either: HFD + Q (n=10; 25 mg Q/kg); HFD + GTE (n=10; 3 mg GTE/kg); HFD + Q + GTE (Q‐GTE; n=10; 25 mg Q/kg, 3 mg GTE/kg); or HFD only (CON, n=10) treatment for 4‐wk. At 16‐wk, glucose tolerance was measured over 120 min, and area under curve (AUC) was determined using the trapezoidal method. Plasma was collected for Q and cytokines (IFN‐γ, IL‐10, IL1‐β, IL‐6, KC/GRO, and TNF‐α) analyses. Comparisons were made using ANOVA and multiple linear regression (α=0.05). In Q and Q‐GTE, plasma Q was 525% and 225% higher respectively vs. CON and GTE. The average 16‐wk weight gain was 30.74g across all groups. The glucose AUC was 14% lower in Q vs. GTE (p=0.0311) and trended 11% lower in Q vs. CON (p=0.0809). No differences in cytokines were found among groups (p>;0.05). In conclusion, Q supplementation in HFD fed mice had no effect on inflammation and mildly improved glucose tolerance; this was not altered by Q‐GTE or GTE alone.

Funded by Quercegen Pharma.
Effects of Egg Ingestion on Endothelial Function in Adults with Coronary Artery Disease: A Randomized, Controlled, Crossover Trial
Authors: Katz David Lawrence , Ma Yingying , Kavak Yasemin , Njike Valentine
Published: June 2021

Objective

To determine effects of daily egg consumption on endothelial function, biomarkers, and anthropometric measures in individuals with coronary disease (CHD).

Methods

This was a randomized, controlled, single‐blind, crossover trial. Thirty‐two participants (mean age 67 years; 6 women and 26 men) with CHD were randomly assigned to one of 6 possible sequence permutations of 3 different treatments (breakfast with 2 eggs, ½ cup Egg Beaters, or a high‐carbohydrate breakfast as part of an ad libitum diet) for 6 weeks. The primary outcome measure was endothelial function measured as flow mediated dilatation (FMD).

Results

As compared to the control breakfast, daily consumption of eggs showed no adverse effects on FMD (7.2 ± 2.9% vs. 7.5 ± 2.9%; p=0.33), lipids (total cholesterol: 158.3 ± 28.6 mg/dL vs. 156.2 ± 27.4mg/dL; p=0.49), blood pressure (systolic BP: 132.8 ± 14.1 mmHg or vs. 135.5 ± 14.9mmHg; p=0.52, diastolic BP: 77.2 ± 6.1 mmHg vs. 76.7 ± 6.9 mmHg; p=0.86) or body weight (90.8 ± 17.5 kg vs. 91.8 ± 17.1 kg; p= 0.92). Outcomes did not differ between eggs and Egg Beaters.

Conclusions

Our findings, and the overall weight of evidence, argue against the exclusion of eggs from heart‐healthy diets, even among those with actual coronary disease.

The source of research support:

the Egg Nutrition Center/America Egg Board and Centers for Disease Control and Prevention.
Changing prevalence of overweight, obesity and metabolic syndrome criteria among college students
Authors: Morrell Jesse Stabile , Reilly Ruth A , Carey Gale B
Published: June 2021

Overweight and obesity prevalence is high among young adults in the U.S. The purpose of the study was to determine if the prevalence of overweight/obesity, as well as metabolic syndrome (MetS) criteria, has changed since 2005–2007. Initiated in the fall of 2005, the College Health and Nutrition Assessment Survey (CHANAS) at the University of New Hampshire is an on‐going cross‐sectional survey of the health of young (18–24 yrs) adults; participants represent all majors at the university. Participants from 2005–07 (n=1,599; 71.5% female) and 2010–12 (n=1,384; 73.2% female) were included in the analyses. The prevalence of overweight/obesity was 32.9%/7.4% in 2005–07 and 25.1%/4.5% in 2010–12 (both p<0.01). Although no difference in MetS prevalence was observed (2.9 vs. 4.1%, p=0.1), reductions in hypertension (32.6 vs. 26.1%, p<0.01), abdominal obesity (4.3 vs. 2.8%, p<0.05), and elevated glucose (6.6 vs. 4.1%, p<0.01) were observed. Conversely, prevalence of low HDL‐C increased (24.6 vs. 31.1%, p<0.01). These observations suggest the improving rates of overweight and obesity among young, college adults may be associated with modest improvements in many MetS criteria. Supported by NHAES grant NH00541.

Grant Funding Source: New Hampshire Agricultural Experiment Station
Skin total carotenoids predict plasma carotenoid levels during a 28‐week experimental feeding study with varying levels of vegetables and fruit
Authors: Jahns Lisa , Whigham Leah , Johnson LuAnn , Mayne Susan T , Cartmel Brenda , Ermakov Igor , Gellermann Werner
Published: June 2021

Objective biomarkers are needed to assess adherence to vegetable and fruit intervention trials. This study compared plasma carotenoid concentrations to non‐invasive skin carotenoid assessments. Thirty participants consumed a low‐carotenoid diet (6 wk, Phases 1 & 3), a provided diet containing 6 c/day vegetables and fruit (8 wk, Phase 2) and their usual diet (final 8 wks, Phase 4). Skin was measured 5x/wk during Phase 2 and at least 2x/wk for the duration. Plasma carotenoids were measured at baseline and mid and end of each phase.

Skin and plasma carotenoid levels decreased (p<0.01) by a third from baseline to end of phase 1, then increased (p<0.01) over 300% at end of phase 2. Plasma carotenoids returned to baseline concentrations at the end of phase 3 and skin carotenoid levels by end of phase 4.

At baseline, skin and plasma total carotenoid values were significantly correlated (p <0.01). Skin carotenoid status significantly predicted plasma values using a mixed linear model including all 9 time points (p < 0.001), indicating that changes in skin carotenoid status closely follow changes in plasma across a broad range of intakes. At the individual level, skin carotenoids predicted plasma values as strongly (p < 0.001).

This study supports the use of skin carotenoid status as an objective indicator for interventions involving carotenoids or fruit/vegetable intake. Support: USDA‐ARS
Perceptions surrounding food preferences and avoidances in pregnant and lactating women in the Western Highlands of Guatemala
Authors: del Rosario García María , Vossenaar Marieke , Bonorden Melissa JL , Solomons Noel W
Published: June 2021

Background

The health and nutrition of the mother are the most directly accessible element of the 1000‐days window‐of‐opportunity. Determining patterns of food avoidances and preferences should allow efficient interventions specifically targeting maternal nutrition.

Objective

To conduct formative research on dietary selection in pregnancy (P) and lactation (L) using qualitative methods.

Methods

Six focus‐groups were conducted with attendance of 5–12 women, 3 with P and 3 with L women. They were conducted with a reflective dialogues‐focus. Sessions were recorded, transcribed verbatim and analyzed using HyperResearch®.

Results

The perception was that dietary specificity (both selections and omissions) was more important during L than in P, with the caveats that foods considered to provoke nausea were avoided, but cravings were viewed as not to be resisted. Diet during L was seen as supporting both the quantity and quality of milk, with thin gruels (atoles) judged superior. “Hot” and “Cold” concepts guided dietary choices during both L and P. Noxious elements in both the external and internal maternal milieu were considered transmissible through milk.

Conclusion

Sensitivity to community perceptions of best eating practices in L and P is essential to guiding dietary intervention in this setting.

Funded by Hormel Foods Corporation
Closing the energy gap through passive energy expenditure
Authors: Roemmich James N.
Published: June 2021

Development of obesity is a gradual process occurring when daily energy intake persistently exceeds energy expenditure (EE). Typical daily weight gain is attributed to an energy gap or excess of stored energy of 15 to 50 kcal/day. Sedentary jobs likely promote weight gain. Standing may be a passive means of increasing EE throughout the workday. The purpose of this study was to determine the EE and liking of performing clerical work while sitting and standing. EE was measured in 11 men and women while word processing for 15 min in standardized postures of sitting in a supportive office chair and while standing. Adults scored their liking of each posture and how long they would be willing to perform clerical work in each posture on a daily basis. EE was 8.8 kcal/h greater (p < 0.05) while performing clerical work while standing than while sitting in an office chair. Subjects liked sitting in an office chair more than standing (p < 0.05), but were willing to perform clerical while standing for 193+36 min/day. Given that EE while standing was 8.8 kcal/hr greater than while sitting, the median 15 to 50 kcal/day of excessive energy stored/day could be countered with ~2to 6 hours of standing clerical work. In conclusion, standing rather than sitting in an office chair while performing clerical work increases passive energy expenditure and may help to prevent weight gain.
Hemoglobin at age 6 weeks and subsequent mortality among HIV‐exposed infants
Authors: Carter R. Colin , Kupka Roland , Manji Karim , Aboud Said , Okuma James , Kisenge Rodrick , Fawzi Wafaie , Duggan Christopher
Published: June 2021

OBJECTIVE

To examine the relation between hemoglobin (Hb) at age 6 weeks and all‐cause mortality among infants born to HIV‐infected mothers.

METHODS

Among 2266 infants with HIV exposure enrolled in a randomized trial of micronutrient supplementation, maternal demographics, birth characteristics, Hb, HIV status, breastfeeding, and mortality were assessed through age 24 months. Cox proportional hazard models were used to examine the relation between 6 wk Hb and all‐cause mortality.

RESULTS

239 (10.5%) children died and 339 (15.0%) children became infected with HIV over the follow up period. A linear relationship was seen between lower 6 wk Hb and mortality among children who became HIV‐infected (p = .0114 for trend) but not among those who did not. This relation held after adjusting for prematurity, exclusive breastfeeding, and maternal WHO HIV stage (p = .0072) but not when adjusting for low birthweight (< 2500 g).

CONCLUSIONS

Lower Hb at age 6 wks was related to increased risk of all‐cause mortality, perhaps as a marker for children with HIV infection and/or low birthweight. This simple, low‐cost test may help to identify HIV‐exposed infants at higher risk for mortality.
Maternal high fat feeding results in higher fat mass and bone mineral content in weanling but not 3 month old female offspring
Authors: Castelli Laura M , Miotto Paula M , MacPherson Rebecca EK , Johnston Bryan D , LeBlanc Paul J , Peters Sandra J , Roy Brian D , Ward Wendy E
Published: June 2021

Using rodent models, maternal exposure to an obesogenic diet ‐ high in fat and sucrose ‐ can have adverse effects on offspring health and may set them on a trajectory for unfavorable body composition. The objective of this study was to determine whether maternal exposure to a high fat diet results in higher fat mass and lower lean and bone mineral content (BMC) and density (BMD) in female offspring at weaning (19 days) and young adulthood (3 months). Female rats (28 days old) were fed control (C, AIN93G with 7% soybean oil by weight) or high fat diet (HF, modified AIN93G with 20% lard by weight) for 10 weeks at which time they were bred and continued on the same diet throughout gestation and lactation. Body composition in female offspring at 19 days and at 3 months of age was measured using dual energy X‐ray absorptiometry. There was no significant effect of HF diet on body weight or absolute BMC, BMD, lean and fat mass at 19 days and 3 months of age. When corrected for body weight, fat mass and BMC was higher (P<0.05) while lean mass was lower (P<0.05) in 19 day old but not 3 month old offspring of mothers fed HF compared to C diet. These findings demonstrated that effects on offspring at time of weaning are not sustained when offspring consume a “healthy” diet post‐weaning. Moreover, understanding whether the higher quantity of bone mineral at PND 19 is accompanied by improved bone structure and strength requires further investigation.
Results from the self‐administered gerocognitive examination (SAGE) are not associated with misreporters of energy intake among multiethnic older adults
Authors: Ettienne‐Gittens Reynolette , Boushey Carol Jo , Steffen Alana , Murphy Suzanne , Wilkens Lynne R
Published: June 2021

Examine association between misreporting on 24‐hr dietary recalls (24HDR) and SAGE, a screening tool to identify mild to severe cognitive impairment (MSCI). Adults (n=265) from a substudy of the Multiethnic Cohort (MEC) completed 3 telephone 24HDR. The sample represented the 5 ethnic groups in MEC (African American (AA), Hawaiian, Japanese, Latino, non‐Hispanic white (NHW)). SAGE scores defined likely to be normal (17–22) or MSCI (¡Ü16). Estimated Energy Requirement (EER) was computed using low activity. The ratio of reported energy intake (rEI) to EER identified under (<0.75), acceptable (0.75–1.25), or overreporters (>;1.25). The primary outcome of reporting status (under or acceptable/over) was examined using logistic regression adjusted for confounders.

The sample included 131 men and 134 women, ages 55–80y. The majority (80%) were characterized as unimpaired. The proportion of underreporters in the sample was 35%. Adjusted for sex, ethnicity, and age, there was no significant association between cognitive status and misreporting. Independent of cognitive status, AA were more likely (p=.046) and Japanese were less likely (p=.023) to underreport compared to NHW.

In this sample of older adults, no association between cognitive impairment and misreporting of rEI based on dietary recalls was found.

Support for this work was made possible by the National Cancer Institute NIH/NCI 4R37 CA 54281.
Intakes, sources and blood levels of folate in Canadian pregnant women in the post‐fortification era
Authors: Masih Shannon , Plumptre Lesley , Ly Anna , Berger Howard , Lausman Andrea Y. , Croxford Ruth , O'Connor Deborah L. , Kim Young‐in
Published: June 2021

Canadian pregnant women are exposed to high levels of folate due to periconceptional folic acid (FA) supplementation and mandatory FA fortification, both aimed at reducing the risk of neural tube defects (NTDs). Although there has been a marked decrease in NTD rates, concerns have been raised regarding potential adverse effects of high folate intake during pregnancy on maternal and fetal heath outcomes. At present, there is paucity of data concerning folate intakes and blood levels in Canadian pregnant women in the post‐fortification era. We determined intake levels and sources of folate using a food frequency questionnaire and RBC folate concentrations in 368 pregnant women at 11–16 wks gestation. 85% reported FA supplemental intakes of ≥ 1 mg of which 86% reported daily use. Mean intakes of folate were 320 ± 146 μg/d from natural sources and 162 ± 100 μg/d from fortified foods. The median RBC folate was 2438 nmol/L (1096–4750 nmol/L) with 60% above the previously reported 97th percentile of RBC folate (2299 nmol/L) in Canadian women of childbearing age. Our data indicates dietary folate intakes in the majority of Canadian pregnant women in the post‐fortification era exceeds the UL for FA. Furthermore, RBC folate levels are in a supraphysiologic range. Future studies are warranted to investigate the impact of high intake and blood folate levels during pregnancy on maternal and fetal health outcomes.

Grant Funding Source: CIHR (MOP# 106446)
Increased Alveolar Surface Area in Neonatal Pups with Acute Lung Injury
Authors: Mezu‐Ndubuisi Olachi J , Reddy Narsa M , Reddy Sekhar P
Published: June 2021

Objective

Premature infants exposed to hyperoxia have acute lung injury with impaired gas exchange. The total area occupied by alveoli or total alveoli volume are closely related to total lung volume and pulmonary function. Using a newborn mouse model of Acute Lung Injury, we have quantified alveolar surface area.

Methods

An acute lung injury was induced by exposing one week old C57BL/6J mice to 77% oxygen for 5 days before returning to room air. On post‐natal day 17, lungs were inflated and slides stained with H & E. An automated software was used to quantify alveolar surface area as a ratio of total lung surface area.

Results

Lung histology in OIR mice showed more vascular congestion, increased cellularity and loss of regular alveolar architecture with patchy areas of atelectasis and overdistension, compared to controls. The ratio of alveolar surface area was 92% of total lung area in controls (N=3) while OIR mice (N=5) showed increase in alveolar volume of 95% of total lung surface area, (p=<0.004).

Conclusions

Despite varied histological features, hyperoxia exposure increases alveolar surface area from over‐distension. Thus affecting pulmonary function in acute lung injury. Automated quantification of pathological changes in lung surface area and alveolar ratio is less subject to bias, and useful for monitoring lung injury and repair.

Source of Research Support: R01 HL66109
Evidence for epigenetic regulation of UGT1A1 protein expression and activity in healthy human livers
Authors: Yasar Umit , Greenblatt David J , Guillemette Chantal , Court Michael H.
Published: June 2021

Interindividual variability in UDP‐glucuronosyltransferase 1A1 (UGT1A1) is only partially explained by genetic polymorphisms and enzyme inducers. Here we determined whether cytosine methylation explains an additional proportion of this variability in human liver. UGT1A1 phenotypes, including UGT1A1 protein and bilirubin glucuronidation, and UGT1A1*28 were determined using a human liver bank (n=46). Methylation levels were quantified at 5 CpG sites associated with known transcription factor response elements in the UGT1A1 promoter and distal enhancer, as well as a CpG‐rich island 1.5 kb further upstream. Individual CpG sites showed considerable methylation variability ranging from 10‐ to 29‐fold difference with average methylation levels from 25 to 41%. Multivariate regression analysis identified *28/*28 genotype, −4 CpG site methylation, and alcohol history as significant predictors of UGT1A1 protein content, accounting for 12%, 11%, and 9% of the variability (R2=0.32, p=0.003). Similarly, −4 CpG methylation and alcohol history accounted for 13% and 12% of the variability in bilirubin glucuronidation (R2=0.25, p=0.005). These results suggest that differential methylation of the −4 CpG site located within a known USF response element may explain a proportion of variability in hepatic glucuronidation by UGT1A1. Funded by NIH‐R01‐GM061834 (to MHC) and NIH‐N01‐DK‐7–0004/ HHSN267200700004C.
Nondestructive microCT imaging of soft tissues using phosphotungstic acid‐hematoxylin, intravascular contrast agent, and perfluorochemical
Authors: Barbe Mary F , Phillips Steve J , Ruggieri Michael R , Miller Larry S , Wolfson Marla R
Published: June 2021

Nondestructive imaging of soft tissues can be an important tool experimentally. However, the low X‐ray attenuation of most soft tissues renders them nearly invisible in radiographs. Whole tissue staining with phosphotungstic acid‐hematoxylin (PTAH) in conjunction with micro‐CT will be discussed for visualizing cartilaginous structures in animal fetuses. Combining PTAH with microCT will be discussed for examining the anatomic orientation and mean cross‐sectional thickness of muscle components of the gastro esophageal junction components in human organ donor specimens (50 mm3 in size), findings confirmed in patients with endoscopic ultrasonography. Whole lung staining with PTAH in combination with Microfil (an intravascular contrast agent) and then microCT will be presented for segmenting lung parenchyma from microvasculature in rodents for quantitative morphometry. Also, the use of perfluorochemical (PFC) to fill lung airways combined with Microfil and then microCT will be presented. Since PFC is radiopaque, its concentration can be adjusted to different Houndsfield units than Microfil to assay bronchial/alveolar volumes separately from microvasculature and lung parenchyma volumes.
Cerebral Cavernous Malformations and the Neurovascular Unit
Authors: Louvi Angeliki
Published: June 2021

Communication between neural cells and the vasculature is integral to the proper development and later function of the central nervous system. A mechanistic understanding of the interactions between components of the neurovascular unit has implications for various disorders, including cerebral cavernous malformations in which focal vascular lesions form throughout the CNS. Loss of function mutations in three genes with demonstrated endothelial cell‐autonomous roles, CCM1/KRIT1, CCM2 and PDCD10/CCM3, cause familial CCM. In addition to the arterial endothelial cells, the CCM genes are expressed in cortical pyramidal neurons and astrocytes. We have uncovered a dual role of CCM3 in astrocytes: cell autonomous involvement in proliferation, activation and survival, and cell non‐autonomous regulation of neural/vascular interactions within the neurovascular unit. Extending this work, we will examine the role of Ccm3 in neurovascular development and disease with particular emphasis in the neural‐specific functions of the protein demonstrating an essential role of CCM3 in brain development.
Mis‐translation as a potential, new mechanism of adaption and stress response
Authors: Pan Tao , Jones Thomas , Weisberg Chloe , Wiltrout Elizabeth , Schwartz Michael
Published: June 2021

A central tenet of biology is the accurate flow of information from nucleic acids to proteins through the genetic code. It is commonly believed that translation deviating from the genetic code is to be avoided at all times in cells. We have discovered that in contrary, mammalian cells can deliberately reprogram the genetic code with the amino acid methionine upon innate immune activation and chemically triggered oxidative stress. Reprogramming the genetic code with methionine occurs through aminoacylation of non‐methionyl‐tRNAs with methionine in unstressed cells, and is further inducible upon regulated production of the reactive oxygen species (ROS) in the cell. We also found that tRNA misacylation with methionine occurs in all three kingdoms of life, and is highly regulated under cell growth conditions. We propose that mis‐translation via regulated tRNA misacylation is a common mechanism for environmental adaption and for stress response in cells. We are exploring and testing hypotheses on the regulatory mechanism, the biological effects and function of mis‐translation with methionine. The results and conceptual understanding obtained here shall help establish mis‐translation as a new mechanism of stress response in biology.

Supported by NIH Director's Pioneer Award (DP1GM105386).
Sensing of DNA breaks by the ATM and ATR checkpoint kinases
Authors: Zou Lee
Published: June 2021

DNA breaks are commonly induced during genome engineering and are recognized as DNA damage. Understanding how cells recognize and respond to DNA breaks is critically important for developing and improving strategies for genome engineering. In human cells, ATM and ATR are the two master checkpoint kinases that recognize and respond to double‐stranded DNA breaks (DSBs). While both ATM and ATR are activated by DSBs, their DNA damage specificities are distinct and their functions are not redundant. How ATM and ATR are activate by DSBs and how they execute their distinct functions are yet to be fully understood.

To understand how ATM and ATR are activated by DSBs, we developed an in vitro biochemical assay in which both ATM and ATR can be activated in a DNA structure‐regulated manner. Using this assay, we found that ATM and ATR are activated by distinct types of DSBs. While ATM is activated by DSBs with blunt ends or short single‐stranded DNA (ssDNA) overhangs, ATR is activated by DSBs carrying long ssDNA overhangs. Our findings suggest that ATM and ATR are sequentially activated during the cellular response to DSBs. When DSBs with blunt ends or short ssDNA overhangs are generated in cells, they will primarily activate ATM. If DNA breaks are engaged in homologous recombination and long ssDNA is generated by nucleolytic processing of DNA ends, ATR will become the primary sensor of these processed DSBs. Using this biochemical assay, we have also characterized which DNA damage sensors are required for the activation of ATM and ATR by DSBs. Surprisingly, the Nijmegen breakage syndrome protein 1 (Nbs1), a known regulator of ATM, is also important for ATR activation. Our results suggest that Nbs1 is a multi‐functional sensor of DSBs that is able to detect different types of DSBs and regulate the activation of both ATM and ATR.
Endocytic membrane traffic and cell signaling
Authors: von Zastrow Mark , Temkin Paul , Henry Anastasia , Irannejad Roshanak
Published: June 2021

Receptor endocytosis plays important roles in mediating physiological adaptation of many signaling systems, and in determining the longer‐term signaling responsiveness of cells under conditions of prolonged or repeated activation by drugs. We have been engaged in elucidating the mechanistic basis for this regulation, focusing on how receptors are sorted between divergent downstream membrane trafficking fates after endocytosis, and on identifying physiological consequences of this trafficking in the mammalian central nervous system. We have identified a conserved machinery mediating the sorting of internalized G protein‐coupled receptors (GPCRs) into the plasma membrane recycling pathway, and converse regulation of the endocytic machinery by activated signaling receptors. We will discuss these findings and recent progress in developing methods to probe the signaling status of receptors in defined subcellular membrane domains.
Radicals: Your life is in their hands
Authors: Stubbe JoAnne
Published: June 2021

It will come as a surprise to many scientists, that Nature uses free radical chemistry in essential metabolic pathways. She has figured out how to harness the considerable reactivity of these species to carry out very difficult chemical transformations with exquisite specificity. I will discuss the role of “good” radicals in biology using ribonucleotide reductases (RNRs) as a paradigm, a problem that my lab has investigated for 30 years. Specifically the use of unnatural tyrosine analogs to study oxidation of a cysteine to a thiyl radical in the active site of the enzyme in one subunit, by a tyrosyl radical (tyrosyl radical analog) in the second subunit over a distance of 35 angstroms will be discussed. Time resolved biophysical methods to elucidate the mechanism of this unprecedented reaction will be described.
Effect of gender on long‐term effects of catch‐up growth in neonatal rats
Authors: Ebanks Erica , Lonnerdal Bo , Griffin Ian J.
Published: June 2021

Poor early growth in preterm infants leads to impaired neurodevelopment but may reduce the risk of metabolic syndrome. Although elevated leptin levels in young animals may increase the risk of later leptin resistance, hepatic steatosis and metabolic syndrome, it is required for normal neurocognitive development. We therefore examined the effect of differences in early growth rates on serum leptin, triglycerides (TG) and cognition. Newborn rat pups were randomized into normal (N, n=10) or reduced growth (R, n=16) litters. On d11, R pups were re‐randomized into litters creating catch‐up (R‐6, n=6), normal (R‐10, n=10) or reduced growth (R‐16, n=10). Serum leptin, serum TG and hepatic TG were measured at d 10, 22, and 60; cognition in a T‐maze on d35. Leptin was higher in N pups than R on d10 (p<0.0001), and N animals scored highest on the T‐maze. In females, leptin on d22 and T‐maze score were significantly lower in the R‐16 group than other R groups. On d10, serum TG was significantly higher in N than R pups (p=0.001). In females, hepatic TG was significantly greater in R‐6 and N animals than in R‐10 or R‐16. We conclude that early growth restriction leads to lower serum leptin, serum TG, and impaired long‐term cognitive development. Subsequent catch‐up growth improves cognition, but worsens hepatic steatosis, in female rats. This model may contribute to our understanding of poor developmental outcomes in preterm infants.

Grant Funding Source: UC Davis Department of Pediatrics
The effect of non‐marine vs. marine sources of the omega‐3 fatty acids, DHA and EPA, on serum lipoproteins
Authors: Rodavich Mary C , Ketz John S , Barnes Kimberly M
Published: June 2021

Fish oil (FO) is a marine source of omega‐3 fatty acids, eicosapentaenoic acid (EPA) and docosahexanaenoic acid (DHA), and has been shown to improve heart health. Our objective was to determine the cardiovascular effects of non‐marine sources, algae oil (AO) and yeast oil (YO), as compared to fish oil (FO). Male ICR mice (8‐wk, n=100) were randomly assigned to dietary groups: soy oil (SO) (no DHA or EPA), FO (DHA + EPA), AO (DHA), YO (EPA), or AO+YO (DHA + EPA) for 2 or 4 wk. Serum triglycerides (TG), total cholesterol (TC), and HDL‐cholesterol were measured and non‐HDL cholesterol (NHDLC) was calculated. Liver DHA and EPA concentration were determined. The FO diet lowered all fractions of plasma lipids and was the only diet to reduce TG (p<0.05). YO, alone and in combination with AO, reduced TC and NHDLC at 4 wks. At 2 wk, AO reduced TC and NHDLC (p<0.05). The AO and AO+YO‐fed mice incorporated less DHA into liver lipids compared to the FO‐fed mice at 2 wk (p<0.05). There were no differences in the incorporation of EPA. Therefore, non‐marine sources do not appear to be as effective as FO at reducing serum lipids.
Race/ethnicity and Overweight/obesity as Contributors to Serum Vitamin D Insufficiency in Urban Schoolchildren
Authors: Van Rompay Lammi Maria I. , Eliasziw Misha , Economos Christina D. , Sacheck Jennifer M.
Published: June 2021

Vitamin D insufficiency [vitDinsuff; serum 25(OH)D < 20 ng/ml] is prevalent among racial/ethnic minorities and overweight/obese individuals, but these relationships are still not well understood. Using data from 4th–8th grade schoolchildren enrolled in the Daily D Health Study from the Boston area, we used multivariable logistic regressions to assess the associations between vitDinsuff and race/ethnicity and overweight/obesity, adjusting for age and sex. Among 311 children, mean (sd) age was 11.9 (1.5) years, 52.4% were female, 25(OH)D was 18.4 (6.8) ng/ml, 60.1% were vitDinsuff, and 45.3% overweight/obese. Racially, 38.3% were white, 15.1% black, 16.7% Hispanic, 11.9% Asian, and 18.0% multiracial/other. The adjusted odds of vitDinsuff was 2.2 times higher among racial/ethnic minority children relative to white children (CI:1.4–3.6, p=0.001). An interaction was observed between race/ethnicity and overweight/obesity (p=0.08). The association between vitDinsuff and overweight/obesity was positive among Hispanics (adjOR=2.7, CI:0.8–9.2, p=0.10), inverse among multiracial/other children (adjOR=0.24, CI:0.07–0.81, p=0.02), and near neutral among whites, blacks, and Asians (adjOR=0.81, 1.07, and 0.87, respectively). The reason for the differential association between vitDinsuff and overweight/obesity between different racial/ethnic groups of children warrants further investigation.

Grant Funding Source: NIH/ODS #3R01HL106160
Self efficacy and quality of life in a worksite weight loss intervention.
Authors: Batra Payal J , Roberts Susan , Salinardi Taylor , Robinson Lisa , Saltzman Edward , Scott Tammy , Pittas Anastassios , Das Sai
Published: June 2021

We examined changes in weight self efficacy (WSE) and quality of life (QOL) in relation to weight loss in a 6‐month study in employees participating in a study randomizing worksites to a behavioral weight loss intervention or to a wait‐listed intervention. Outcome assessments included non‐fasting body weight, blood lipids, fasting blood glucose, blood pressure, WSE (Weight Efficacy Lifestyle questionnaire) and QOL (WHO‐BREF), and were obtained from 74 participants at the intervention sites and 21 participants at the control sites. Significant improvements in both, overall scores and in all 5 dimensions of WSE (p<0.001) and all 4 domains of QOL (p<0.05) were observed in the intervention group compared to the control group. Within the intervention group, increases in overall WSE (adj R2=0.35, p=<0.007) and all 5 dimensions of WSE were significantly correlated with weight change after controlling for baseline weight, age, gender and worksite (adj R2=0.36; p<0.05). Change in the overall perception of health related quality of life was significantly correlated with weight change (adj R2=0.35, p=<0.005). Change in QOL was not correlated with change in blood lipids, blood glucose or blood pressure. In conclusion, our worksite weight loss intervention resulted in significant improvements in WSE and QOL; improvements in WSE were correlated with greater weight loss.
1,25(OH)2‐vitamin D3 increases leucine and insulin‐dependent activation of protein synthesis in C2C12 myotubes
Authors: Salles Jerome , Chanet Audrey , Giraudet Christophe , Patrac Veronique , Jourdan Marion , Luiking Yvette , Verlaan Sjors , Boirie Yves , Walrand Stephane
Published: June 2021

A growing body of evidence suggests that vitamin D may affect muscle mass and function, especially in older people. The aim was to investigate the effect of 1,25(OH)2‐vitamin D3 (1,25OHD) combined or not with anabolic factors, insulin and leucine (Leu), on protein fractional synthesis rate (FSR) and its intracellular regulating pathways in mouse C2C12 myotubes. After differentiation, myotubes were cultured in 1,25OHD solutions at 0 or 10nM for 72h. Cells were then treated for 30min by L‐[1‐13C]valine in presence or not of Leu (5mM) and insulin (100nM), and FSR was determined by measuring tracer enrichments in free amino acids and proteins. Protein expression and phosphorylation of Akt/mTOR‐dependent pathway were measured by western blot. mRNA level of insulin receptor (IR) and vitamin D receptor (VDR) was determined by qPCR. ANOVA was used for statistical analysis. 1,25OHD alone stimulates protein FSR (p<0.05). When combined with 1,25OHD, the stimulation of protein FSR by Leu and insulin was further increased by 14% (p<0.05). Akt/mTOR‐dependent pathway was activated by Leu and insulin and this was further increased by 1,25OHD (p<0.05). IR and VDR mRNA and protein expression were also increased by 1,25OHD (p<0.05). To conclude, 1,25OHD sensitizes the Akt/mTOR‐dependent pathway to the stimulating effect of insulin and Leu resulting in a further activation of protein synthesis in C2C12 myotubes.
System Science Models and National Data Projected Future Trends and Racial/Ethnic Disparities in Childhood Obesity in the US
Authors: Xue Hong , Chen Hsin‐Jen , Wang Youfa
Published: June 2021

Background

Although the obesity prevalence seems to level off in young children in the US recently, the racial/ethnic disparities remain substantial. The non‐linear dynamic complexity in the increase of childhood obesity rates over time is not well studied.

Objectives

To forecast future trends and disparities in childhood obesity in US till 2030.

Methods

We fit system dynamics models to simulate changes in obesity rates in children (aged 2–19 y) using the 1999–2010 National Health and Nutrition Examination Survey (NHANES) data and forecasted the trends till 2030.

Results

Our models reproduced the leveling off in the past decade. Incorporating the projection of demographic composition changes in US population, our simulations suggest that by 2030 27% of boys and 23% of girls will be obese. The disparities gap will increase, and by 2030, 38%, 32%, and 18% of Mexican‐American, Non‐Hispanic black, and non‐Hispanic white boys will be obese, respectively. In girls, the figures are 26%, 40% and 17%, respectively.

Conclusions

Our simulations demonstrate the recent plateau is temporary, and current efforts are not sufficient to stop the increase. Specially more effort need to target minorities.

Grant Funding Source: NIH/NICHD (U54 HD070725‐01,1R01HD064685–01A1) and NIDDK (R01DK81335–01A1)
Arterial Compliance in Response to a Single Meal Rich in Long‐Chain Omega‐3 Fatty Acids
Authors: McKenzie Jane Marie , Banks Cerian , Gow Iain
Published: June 2021

Consumption of long‐chain omega‐3 fatty acids (LC n‐3 PUFA) lowers the risk of cardiovascular disease, however little is known about the immediate effects of meals rich in LC n‐3 PUFA on arterial compliance, an indicator of cardiovascular function. Seven healthy females were fed high energy meals, varying only in their LC n‐3 PUFA content (Test meal – 1000kcal, 9.7g LC n‐3 PUFA; control meal 998kcal, 0.2g LC n‐3 PUFA). Habitual LC n‐3 PUFA intake was determined by a validated food frequency questionnaire. Arterial compliance was assessed by measuring pulse wave velocity (PWV) and augmentation index (AIx). PWV, AIx and blood pressure were measured at fasting baseline and at 30, 60, 90, 120 and 180 minutes post‐prandially. There was no significant difference in PWV from baseline or between meals. AIx decreased significantly from baseline following consumption of the test meal (p<0.05), although this effect was only evident in those habitually consuming less than the UK recommendation of 0.45g LC n‐3 PUFA per day (n=3). Within this small cohort, the difference diminished when AIx was corrected for heart rate (AIx@75). Post‐prandial responses to LC n‐3 PUFA may be influenced by habitual intake.
Distinct pathological and lipidomic signature of guinea pigs with cholesterol‐induced non‐alcoholic fatty liver disease (NAFLD)
Authors: Deogburn Ryan C , Aguilar David , Smyth Joan A , Bibus Doug , Volek Jeff , Fernandez Maria Luz
Published: June 2021

The first aim of this study was to evaluate the extent of pathological changes in guinea pig liver following six weeks of dietary cholesterol (Chol) challenge. Livers from guinea pigs fed either low (L‐Chol, 0.04%) or high (H‐Chol, 0.25%) (n =10 per group) were examined for histological evidence of NAFLD and quantified for fatty acids (FA) in liver triglycerides (TG) and phospholipids (PL). H‐Chol caused moderate hepatic steatosis and mild inflammation and coincided with marked depletion of total PUFA (p =0.03) and n6 PUFA content in PL (p =0.03), specifically arachidonic acid (p =0.001). A second aim was to investigate whether animals randomized to diets either low (LCD) (n =9) or high in carbohydrate (HCD) (n =10) following the H‐Chol phase could improve liver pathology induced by H‐Chol. Unexpectedly, despite less steatosis both groups displayed deterioration of liver pathology with evidence of hepatocyte ballooning, fibrosis, and biliary hyperplasia. Total PL PUFA (p =0.001) and n6 PUFA (p =0.001) were reduced compared to H‐Chol and were inversely correlated with liver enzymes. Hepatic free cholesterol was increased in LCD and HCD livers with the most severe liver damage. These data identify a relationship between Chol‐induced liver injury and PL composition; additionally, excess cholesterol has profound effects on hepatic morphology, which appears unresponsive to dietary intervention.
Maternal BMI, weight gain during pregnancy, gestational age and Filipino ethnicity are important predictors of birth weight in a multiethnic population in Hawaii
Authors: Novotny Rachel , Oshiro Caryn Etsuko Shima
Published: June 2021

Birth weight remains an important indicator of future health. Mother‐infant pairs (n=334) were studied, using electronic medical record data from Kaiser Permanente Hawaii, to examine determinants of birth weight in an understudied population. Maternal education, maternal age, tobacco use during pregnancy, and gestational diabetes diagnosis did not predict infant birth weight. Maternal BMI and pregnancy weight gain predicted infant birth weight in multiple regression analysis, explaining 5% of the variability in birth weight. Adding gestational age and ethnic group (Native Hawaiian, Asian, Filipino, Pacific Islander, Hawaiian‐Asian, Other Mixed ethnicity, Other ethnicity, with White reference group) to maternal BMI and pregnancy weight gain yielded a model where 48% of the variability in birth weight was explained. Birth weight of Filipinos was 231g lower than Whites, controlling for gestational age, maternal weight gain during pregnancy and pre‐pregnant BMI. These findings confirm findings of earlier studies done in other ethnic populations that show that key predictors of infant birth weight are maternal BMI and weight gain during pregnancy. After controlling for key variables, this study reveals lower birth weight among Filipinos as compared to Whites in Hawaii. USDA AFRI/NIFA Grant #2007–04557