bluuebunny/crossref_metadata_2025 huggingface dataset:
Transferring an innovation in food and lifestyle education: adaptation of a French obesity prevention methodology in Australia (262.2)
Authors: Hartwick Carol Anne , Coveney John , Cox David , Meyer Samantha , Sue Roger
Published: June 2021

Property of the UNESCO Patrimony of Humanity, the French food model (FFM) is founded upon taste, social conviviality and structure. EPODE, a community‐based obesity prevention program promoting the FFM in France, was developed in 2003 and has been disseminated globally, including to Australian communities. There is no literature informing on the conditions for such cross‐cultural methodology transfers.

The objective of this study is to examine French and Australian cultural contexts (food habits, environments, etc.), how the EPODE and OPAL programs function within them, and to understand the conditions for transfer.

Qualitative, case study approaches used focus groups, semi‐structured interviews, and observations in EPODE and OPAL communities in France and Australia with program coordinators, implementers, children and families.

The findings show that, although the holistic food principles behind EPODE gave ground for its importation, they did not transfer to OPAL. French study participants hold unquestioned assumptions toward their own cultural particularities and therefore the French food principals were not included in the formalized EPODE methodology. OPAL used Australian, nutrition‐focused principals without question, in line with Australian evidence. Unexamined assumptions of one’s own culture may be a barrier to cross‐cultural methodology transfers and thus cultural principals should be examined, defined and taken into account.

Grant Funding Source: Supported by Flinders University, the Commonwealth Scientific and Industrial Research Organisation
Effects of high oleic canola oil‐rich feeding on in vitro LDL proteoglycan binding affinity in individuals with at least two criteria for metabolic syndrome (269.5)
Authors: Jones Peter , Rudel Lawrence , Sawyer Janet , Hantgan Roy , Rempel Julia , Pu Shuaihua , Kris‐Etherton Penny , Liu Xiaoran , West Sheila , Couture Patrick , Lamarche Benoît , Jenkins David
Published: June 2021

Dietary n‐9 monounsaturated fatty acids (FA) decrease metabolic syndrome (MetS) risk factors; however, whether consumption of novel vegetable oils high in MUFA affect LDL binding characteristics has not been determined. We utilized the Canola Oil Multi‐Centre Intervention Trial (COMIT), a human intervention study consisting of five dietary treatments differing in qualitative fat content, each treatment fed for 29 days and separated by a 4 week washout period. We evaluated the efficacy of three vegetable oil treatments from COMIT including corn/safflower oil (control), high oleic canola oil, and high oleic canola oil with DHA on plasma FA profiles, LDL cholesterol ester FA composition and in vitro LDL proteoglycan binding affinity. A multi‐centre, double blind, randomized, 3‐period crossover, controlled feeding study was conducted where subjects with MetS criteria (n=50) were fed isocaloric diets (50% CHO, 15% PRO, 35% FAT) containing three of the five treatments, each for 29 days. Plasma FA profiles at day 29 reflected the FA composition of each diet, suggesting high compliance to diet. Similarly, LDL cholesterol ester FA distribution mirrored the FA composition of the dietary fat at day 29, but not day 1, on each treatment. However, proteoglycan binding affinity values of LDL particles did not differ significantly across day 1 to day 29 for corn/safflower (‐2.46+3.63%) (mean+SEM), high oleic canola (‐6.47+1.95%) or oleic canola oil with DHA (‐0.52+2.85%). No difference was observed in binding affinity assessed at day 29 as a function of diet treatment. These data suggest that, despite the demonstration of diet induced shifts in LDL cholesterol ester FA patterns, n‐9 FA rich canola oil diets does not induce any change in LDL binding affinity compared with a n‐6 FA rich diet.

Grant Funding Source: Supported by Canola Council of Canada/Agr Agr Food Canada and Canada Research Chairs program
Maternal adiposity in the absence of excessive gestational weight gain is associated with distinct changes in DNA methylation patterns in umbilical cords of infants (271.1)
Authors: Thakali Keshari , Saben Jessica , Faske Jennifer , Lindsey Forrest , Gomez‐Acevedo Horacio , Badger Thomas , Andres Aline , Shankar Kartik
Published: June 2021

Maternal obesity has been hypothesized to lead to developmental programming of excessive weight and adiposity in offspring. In addition, excessive gestational weight gain (GWG) is also a demonstrated determinant of later‐life adiposity. We examined genome‐wide DNA methylation (Infinium® HumanMethylation450K BeadChip) in umbilical cords (UC) from lean (Ln, BMI<25) and overweight/obese women (OB, BMI蠅25) who gained weight within Institute of Medicine guidelines to specifically identify the epigenetic influence of maternal obesity. Offspring birth weight and infant adiposity at 2‐wk did not differ between groups. Multivariable linear regression analysis of CpG methylation against maternal fat mass at 12 wk while controlling for maternal age, mode of delivery, infant birth‐weight and sex identified 1,269 CpG sites whose methylation status was associated with maternal adiposity (p<0.05). Of these, 54% sites were located in 5’‐UTR and proximal promoter (‐1500 bp) regions. Gene ontology analysis identified processes related to fat cell differentiation to be hypomethylated and processes related to RNA stability to be hypermethylated in OB compared to Ln UCs. Our data suggest that maternal adiposity in the absence of excessive GWG is associated with epigenetic modifications of fetal tissue that may contribute to the development of obesity in offspring. Funding USDA ARS‐CRIS 6251‐51000‐007‐04S.

Grant Funding Source: Supported by USDA ARS‐CRIS 6251‐51000‐007‐04S
Innovating nutrition education: the promotion of food appreciation and basic nutrition for school‐aged children at an international sporting event (273.1)
Authors: Hartwick Carol Anne , Moreno Luis , Fisberg Mauro , Hart Kathryn , Fielding Barbara , Boyle L. , Ferris R. , Lenham‐New Susan , Richards Zoe
Published: June 2021

The Danone Nations Cup (DNC) is an international soccer tournament. It comprises 32 national final competitions and one world final event annually, involving more than 2.5 million school‐aged children from up to 40 countries.

The Danone Institute International, a non‐for‐profit organization promoting human health, has designed an innovative approach to nutrition education for the multi‐cultural environment of the DNC. The objective of the program is to promote food appreciation and basic nutrition through interventions around taste, conviviality, food origins and basic nutrition.

Qualitative thematic analyses of program pilot data (DNC World Final 2011, Spain), collected through focus groups and observations, suggest the program’s acceptability and feasibility. Children spent more time at the table and reported discovering new foods. They recalled key messages and expressed a desire to make changes to their food behavior at home. Children enjoyed sharing meals and activity experiences and many described the habits of children from other countries.

A long‐term study (FitFood) has been designed and data were collected at the 2013 DNC World Final in London to further evaluate the program and to investigate children’s nutritional knowledge, social interactions around food, usual dietary intake, body composition and n‐3 fatty acid status in relation to dietary intakes. Analysis is underway using mixed methods in collaboration with the University of Surrey (UK).

Grant Funding Source: Supported by the Danone Institute International
Pericyte dysfunction in blood brain barrier impairment caused by HIV infection (278.1)
Authors: Persidsky Yuri , Rom Slava , Dykstra Holly , Reichenbach Nancy , Winfield Malika , Ramirez Servio
Published: June 2021

Studies performed over the last decade indicated that functional alterations of brain endothelium is the main factor in blood brain barrier (BBB) injury during HIV infection. However, other cells constituting the BBB (like pericytes) received almost no attention. We propose that pericyte dysfunction present in HIV infection can contribute to BBB compromise and progression of HIV‐associated neurocognitive disorders (HAND). We used co‐cultures of primary human brain pericytes (BP) and human primary brain micsovascular endothelial cells (BMVEC) and human brain tissues of HIV infected patients to study alterations of pericyte function in chronic neuroinflammation driven by HIV infection. We found partial pericyte loss and down‐regulation of key receptors on these cells in brain tissue of HIV infected patients (even without detectable HIV in the brain) and in HIV infected ‘humanized’ mice that paralleled BBB compromise and neuroinflammation. BP treated with IL‐1β or TNFα demonstrated decreased secretion of angiopoetin 1 and transforming growth factor‐β1, diminished expression of platelet derived growth factor‐B receptor β1 and connexin 43 (critical for pericyte recruitment to BBB and gap junctions between BP and BMVEC). BP exposed to IL‐1β/TNFα showed enhanced expression of numerous pro‐inflammatory factors (relevant to HIV neuropathogenesis) and adhesion molecules paralleling increased adhesion of monocytes to pericyte monolayers. Using BBB models (composed of BMVEC‐BP), we showed increased monocyte migration across BBB constructs in response to the relevant chemokine, CCL2. IL‐1β/TNFα treatment of pericytes altered their ability to spread or migrate providing a potential mechanism for their decrease in brain tissue of HIV‐infected patients. These data point to a major decrease in barrier‐supporting function and enhanced inflammatory responses in brain pericytes after exposure to relevant cytokines and in brain tissues of HAND patients.

Grant Funding Source: supported by NIH grants MH65151, AA015913
Genetic variation in aldo‐keto reductase 1D1 (AKR1D1) affects expression and activity of multiple cytochrome P450s (292.1)
Authors: Chaudhry Amarjit , Thirumaran Ranjit , Yasuda Kazuto , Yang Xia , Fan Yiping , Strom Stephen , Schuetz Erin
Published: June 2021

Human liver gene regulatory network analysis identified a cytochrome P450 subnetwork with AKR1D1 as its key regulatory driver. This study assessed the biologic importance of AKR1D1 [key enzyme in synthesis of bile acids, ligand activators of FXR, PXR and CAR, known P450 regulators] to hepatic P450 expression. Overexpression of AKR1D1 in primary human hepatocytes led to increased expression of CYP3A4, 2C8, 2C9, 2C19, and 2B6. Conversely, AKR1D1 knockdown decreased expression of these P450s. Resequencing AKR1D1 from donor livers identified a 3'‐UTR (rs1872930) SNP that was significantly associated with higher AKR1D1 mRNA. AKR1D1 3'‐UTR‐luciferase reporter studies showed that variant allele resulted in higher luciferase activity, suggesting that the SNP increases AKR1D1 mRNA stability and/or translation efficiency. AKR1D1 3'‐UTR SNP was significantly associated with increased hepatic mRNA of multiple P450s (CYP3A4, 2C8, 2C9, 2C19, and 2B6) and CYP3A4, 2C8, 2C19, and 2B6 activities. After adjusting for multiple testing, association remained significant for AKR1D1, CYP2C9, and CYP2C8 mRNA and CYP2C8 activity. These results provide new insights into the variation in expression and activity of P450s that can account for interindividual differences in drug metabolism/efficacy. In conclusion, we provide the first experimental evidence supporting a role for AKR1D1 as a key genetic regulator of P450 network.
Conjugated linoleic acid promotes endurance capacity via SIRT1 and AMPK mediated mechanisms (37.3)
Authors: Kim Yoo , Park Yeonhwa
Published: June 2021

Previously it was reported that conjugated linoleic acid (CLA) and exercise training improves endurance capacity potentially via peroxisome proliferator‐activated receptor δ (PPARδ)‐mediated mechanism in mice. Based on these results, the current study was designed to determine the role of exercise and/or CLA in improved endurance capacity and upstream regulator(s) for PPARδ. Male 129Sv/J mice were fed either control or CLA (0.5%) containing diet for 4 weeks and further divided into sedentary or training regime (25 min three times per week). Consistent with previous observations, CLA feeding significantly reduced body weight and fat mass independent of excise during the experimental period. Endurance capacity was significantly improved by CLA treatment, while there was no significant effect of training alone. Similarly, CLA treatment significantly increased expression of peroxisome proliferator‐activated receptor gamma coactivator 1‐α (PGC1α), an upstream regulator of PPARδ, in both sedentary and trained animals, 58% and 28%, respectively. It was further determined that CLA influences silent information regulation 2 homolog‐1 (SIRT1) and AMP‐activated protein kinase (AMPK) regardless of activity levels, which are upstream regulators of PGC1α. These results suggest that CLA improves exercise outcome independent of activity levels via SIRT1 and AMPK mediated mechanisms.
Dietary energy intakes in children with mental health conditions treated with second‐generation antipsychotics (371.8)
Authors: Barker Mikaela , Panagiotopoulos Constadina , Devlin Angela
Published: June 2021

Second generation antipsychotics (SGA) are used to treat mental health conditions (eg ADHD, psychosis) in children. In some children, SGA‐treatment is associated with rapid weight gain and cardiometabolic dysfunction. The objective of this study is to determine if greater dietary energy intakes are associated with adiposity and cardiometabolic dysfunction in a cross‐sectional study of SGA‐treated (n=15) and SGA‐naïve (n=9) children. Children (6‐19 yrs) with mental illness were recruited through BC Children’s Hospital. Demographics, medical history, and anthropometrics were obtained. As all variables are normally distributed, means ± SD are reported. SGA‐treated children had higher zBMI (1.31 ± 0.79 vs 0.25 ± 0.86, P = 0.005) and waist circumference (cm; 79.83 ± 11.61 vs 64.90 ± 9.37, P = 0.004) compared to SGA‐naïve children, respectively. Three 24‐hour dietary recalls were conducted and analyzed to calculate energy intakes. A caloric ratio for each participant was calculated based on their mean 3‐day total energy intake (kcal) and their estimated energy requirement using the Dietary Reference Intakes equation. The mean caloric ratio of 0.92 ± 0.24 for SGA‐treated children and 1.11 ± 0.28 for SGA‐naïve children is not statistically significant. These findings suggest that differences in dietary energy intakes do not account for SGA‐related side effects in children.

Grant Funding Source: Supported by BC Mental Health and Addiction Services
Mammary cells synthesize appetite hormones that may contribute to breastmilk (38.8)
Authors: Hassiotou Foteini , Savigni Donna , Hartmann Peter , Geddes Donna
Published: June 2021

Breastmilk contains appetite hormones, which may participate in both short‐term appetite control in breastfed infants and developmental programming protecting against adult obesity. Breastmilk appetite hormones have been thought to originate from the maternal bloodstream. It is unknown whether they are also synthesized endogenously by mammary cells. In this study, we accessed mammary cells from the human lactating breast via freshly expressed breastmilk and examined expression of appetite genes at the mRNA and protein levels using RT‐PCR and FACS. Sections from rare specimens of human resting and lactating breast were stained for expression of these hormones, which included leptin and its receptor, ghrelin, adiponectin, and resistin. Transcript for these hormones was detected in breastmilk cells at varying levels among women. FACS analysis of breastmilk cells showed that leptin was expressed in mature cells, such as lactocytes and myoepithelial cells, as well as in stem cells. This was confirmed in the breast specimens examined, with heterogeneity in expression not only between the two epithelial layers, but also amongst different lobules for all appetite hormones, which were more strongly expressed in the lactating than the resting breast. These findings provide comprehensive evidence of the synthesis of appetite hormones in the female breast, with a marked upregulation during lactation.
Serum folate concentrations and cancer risk in older U.S. adults in the post‐folic acid fortification period (384.5)
Authors: Ganji Vijay , Baldauff Regine , Zhang Xu
Published: June 2021

Studies have reported an increase in total serum folate since the implementation of folic acid fortification on January 1, 1998. However, the literature published during the post‐folic acid fortification period is controversial with regards to the safety and potential risk for cancer in non‐target population. The association between serum folate and cancer in older US adults was investigated. Data from NHANES 1999‐2008 were used to form the study population. Among 7981 subjects who were aged >60y and had a measured serum folate from 1999‐2008, 1459 reported having cancer. Among 4007 women who were aged 60+ and had serum folate measured between 1999 and 2008, 288 reported a history of breast cancer. The study population was categorized into four equal‐size groups using the serum folate quartiles as cutoff values and odds ratio of having cancer was calculated between these four groups. Those over the age of 60y with the highest concentration (fourth quartile) of serum folate were 1.6 times more likely to have cancer than participants with lowest serum folate (first quartile) (P<0.001). Women over the age of 60y with the highest concentration of serum folate (fourth quartile) were 1.5 times more likely to have breast cancer compared to women with lowest serum folate (first quartile) (P=0.004). The presence of high total serum folate was related to an increased prevalence of cancer. Because of cross‐sectional nature of the data, the cause and effect relationship should not be inferred. Further research is warranted to investigate the cause and effect relationship between serum folate and cancer.

Grant Funding Source: Department of Nutrition, Georgia State University
Lipid‐based nutrient supplementation during pregnancy decreases maternal cortisol in younger women (389.6)
Authors: Oaks Brietta , Adu‐Afarwuah Seth , Lartey Anna , Stewart Christine , Ashorn Per , Vosti Steve , Dewey Kathryn
Published: June 2021

Background: High maternal cortisol during pregnancy is associated with negative birth outcomes. It is unknown whether nutritional supplementation during pregnancy might reduce maternal cortisol. Objective: To determine if cortisol at 36 wk gestation is lower in pregnant women receiving a lipid‐based nutrient (LNS) supplement vs. two other supplements. Methods: A randomized controlled trial of 1,320 pregnant Ghanaian women 蠄 20 wk gestation assigned to receive daily throughout pregnancy either: 1) 60 mg iron + 400 µg folic acid (IFA); 2) multiple micronutrients (MMN); or 3) 20 g LNS (containing 118 kcal, 22 micronutrients & protein), designed for pregnant and lactating women (LNS‐P&L). Morning salivary cortisol was measured at baseline and 36 wk gestation. Results: 691 women had a cortisol measurement at 36 wk gestation. There was no difference in final mean (±SE) cortisol among groups (LNS‐P&L= 7.14 ± 0.02, MMN = 7.35 ± 0.02, IFA = 7.44 ± 0.02 nmol/L, p > 0.05), adjusting for time since waking, baseline cortisol, BMI, and education. However, there was an interaction between supplementation group and women’s age (p=0.01), with significantly different mean (±SE) cortisol among groups in women 蠄 25 y (LNS‐P&L= 6.60 ± 0.03, MMN = 7.81 ± 0.03, IFA = 7.60 ± 0.03 nmol/L; p = 0.02 for LNS‐P&L vs. MMN) but not in older women. Conclusion: LNS during pregnancy may be an effective method to reduce cortisol at 36 wk gestation in women < 25 y.

Grant Funding Source: Funded by a grant to the University of California, Davis from the Bill & Melinda Gates Foundation.
Types of liquids in Mexican infants’ diets: results from three National Health and Nutrition Surveys (393.1)
Authors: Gonzalez de Cosio Teresita , Escobar Zaragoza Leticia , González Castell Luz Dinorah , Rodríguez Ramírez Sonia
Published: June 2021

Types of liquids in Mexican infants’ diets: Results from three National Health and Nutrition Surveys González de Cosío T, Escobar‐Zaragoza L, González‐Castell D, Rodríguez‐Ramírez S.

Studies on infant dietary intake do not focus generally on the types of liquids consumed, which deter exclusive breastfeeding and relate to future obesity.

Our objective was to describe the types of liquids present in Mexican <1y infants’ diets, by age and breastfeeding status (BFS).

Methodology: We used 3 National Health & Nutrition Surveys (1999, 2006, 2012) and analyzed information on infant feeding practices for <1y‐olds by status quo.

We calculated median age of consumption (MAC) of: plain water, formula, nutritive liquids (NL; thinned cereal‐based gruel with water or milk, coffee with milk, fruit juices) and non‐nutritive liquids (NonNL; sugared water, water‐based drinks, tea, beans or chicken broth, coffee, sugar‐sweetened soft drinks); and confidence intervals with boot‐strap method with 1,000 reps.

Results: MAC for all liquid types was shorter than the recommendation by WHO (>6 mo); generally liquids tended to be consumed earlier in non‐breastfed (BF) than BF infants, differences not statistically significant. Water MAC was 3mo; 5 mo for NonNL, and between 5‐>11mo for NL. MAC differences between BFS among surveys were heterogeneous. Conclusions: Non‐breastmilk liquids are present undesirably early in Mexican infants’ diets; NonNL are consumed earlier than NL, highlighting that negative dietary practices in Mexican children set off early in life.
Altered CD4+ T cell subset balance in lymphoid organs of mouse model of colorectal cancer (397.2)
Authors: Tanner Scott , Hill Stephanie , Martin Colin , Lorenz Robin
Published: June 2021

The adenomatous polyposis coli (APC) gene is a known tumor suppressor gene, and mutations resulting in APC inactivation leads to the formation of multiple intestinal neoplasms (Min) within mutant mice (APCMin/+). Thus, the APCMin/+ mouse is used as a model of human colorectal cancer (CRC). The intestinal compartment is especially susceptible to tumor formation due the high turnover rate of epithelial cells. Also, the presence of the intestinal microbiota makes the intestines a very immunologically active site. Reports show that tumor associated CD4+ T cell derived IL‐17 promotes intestinal tumor development in APCMin/+ mice. To further investigate the role of the APCMin/+ mutation on CD4+ T cell function, we performed flow cytometric, histochemical, and immunofluorescent studies on both wild type (APC+/+) and APCMin/+ mice. We identified increased levels of IFN‐+ CD4+ and IL‐17A+ CD4+ cells, and decreased levels of IFN‐+IL‐17+ double positive CD4+ cells in the mesenteric lymph nodes and Peyer’s patches of APCMin/+mice. Culture of naïve CD4+ T cells from the spleens of APCMin/+mice lead to increased regulatory T cell development and lower IL‐17A expression. These results suggest an altered T cell balance in APCMin/+ mice. This intrinsic imbalance in CD4+ T cell subsets may disrupt the intestinal immune environment, inhibiting intestinal tumor destruction in the APCMin/+mouse.

Grant Funding Source: UAB Comprehensive Cancer Center
Synthetic glycopeptide antigens for HIV vaccine design (469.1)
Authors: Wang Lai‐Xi
Published: June 2021

Heavy glycosylation of the HIV‐1 outer envelope glycoprotein gp120 forms a dense glycan shield that constitutes a strong defense mechanism for viral immune evasion. Nevertheless, the recent discovery of a new class of glycan‐dependent broadly neutralizing antibodies (bNAbs) from HIV‐infected individuals, including PG9, PG16, PGT121, PGT128 and PGT135, suggests that the viral defensive carbohydrates can also serve as targets of vaccine. Epitope mapping indicates that these bNAbs target glycopeptide structures at the variable (V1V2 or V3) regions of gp120. However, further characterization of the fine epitopes is complicated by the glycosylation heterogeneity of gp120. We have launched a project aiming to characterize and reconstitute the minimal antigenic glycopeptide structures through synthetic chemistry. A series of homogeneous glycopeptides corresponding to the V1/V2 and V3 domains were synthesized by a chemoenzymatic method, in which defined N‐glycans were installed selectively at the conserved glycosylation sites (N156, N160, N301, and N332). This study permits a detailed assessment of the glycan specificity at the respective glycosylation sites for recognition by antibodies PG9, PG16, PGT121, and PGT128. The ability to reconstitute the minimal neutralizing epitopes using well‐defined synthetic glycopeptides provides a useful template for HIV vaccine design.
Long‐term weight loss with a novel minimally‐invasive, restrictive bariatric medical device, the Onciomed Gastric Vest System (47.3)
Authors: Stein Paul , Nihalani Raj
Published: June 2021

To demonstrate the applicability of novel implantable medical devices for bariatric use, long‐term large animal studies are necessary. METHODS: Seven female ketamine‐diazepam anesthetized Yorkshire pigs had a three‐port laparoscopic system placed. The greater curvature of the stomach was isolated. A 34‐French Bougie was inserted down the esophagus resting along the lesser curvature. The greater curvature was tucked in along the Bougie and the stomach plicated. An Onciomed Gastric Vest System (GVS) was snugly placed around the stomach and sutured to itself. Three pigs served as controls. At three months, two control and four GVS animals were terminated and a necropsy performed. The remaining were followed for nine months. No post‐surgical complications arose and all animals remained healthy. Animal weights were taken. RESULTS: Different from controls, interest in food was noted to markedly decrease in the GVS animals.

GROUP
WEIGHT (kg)

Day 0
Month 1
Month 2
Month 3
TOTAL WEIGHT GAIN (+) OR LOSS (‐)

CONTROL*
Mean
36.3
42.3
45.0
49.0
+36%

SD
5.5
1.5
2.8
3.6
12

GVS**
Mean
37.5
34.7
31.4
29.6
‐21%

SD
2.0
2.0
1.1
0.7
5

Trend ANOVA: *P<0.05; **P<0.0001. At nine months, the control animal weighed 59 kg, gaining 97% from 30.0 kg on Day 0, while the three GVS animals weighed 24.7±2.5 kg (P<0.0001), losing 31±10% from 36.2±2.3 kg on Day 0. At necropsy, all animals had normally appearing abdominal organs. The internal surface of the stomachs of all animals also appeared normal. CONCLUSIONS: The Onciomed GVS is highly effective at promoting long‐term weight loss with no apparent adverse effects.
Meal timing during alternate day fasting: effects on body weight and coronary heart disease risk in obese adults (47.5)
Authors: Hoddy Kristin , Kroeger Cynthia , Trepanowski John , Bhutani Surabhi , Barnosky Adrienne , Varady Krista
Published: June 2021

Alternate day fasting (ADF), consisting of a feed day (24‐h ad libitum food intake) alternated with a fast day (25% energy intake at lunchtime), results in moderate weight loss (3‐4 kg) in 8 weeks. It has been speculated that moving the fast day meal to dinnertime, or dividing the meal into smaller meals, may improve adherence and weight loss. Accordingly, this study compared the effects of three ADF protocols with different fast day meal times on body weight and coronary heart disease (CHD) risk. Obese subjects (n = 45) were randomized to 1 of 3 groups for 8 weeks: 1) ADF‐L: fast day meal as lunch, 2) ADF‐D: fast day meal as dinner, or 3) ADF‐SM: fast day meal as small meals throughout the day. Body weight decreased (P < 0.05) to a greater extent in the ADF‐D (4.6 ± 0.6 kg) and ADF‐SM (4.9 ± 0.6 kg) groups, compared to the ADF‐L (3.3 ± 0.6 kg) group. Fat mass and visceral fat mass also decreased (P < 0.05) to a greater extent by ADF‐D (3.1 ± 0.3 kg; 0.2 ± 0 kg) and ADF‐SM (3.3 ± 0.4 kg; 0.2 ± 0 kg), versus ADF‐L (1.8 ± 0.4 kg; 0.1 ± 0 kg). Systolic blood pressure decreased (P < 0.05) only in the ADF‐SM group (19 ± 10 mm Hg), while diastolic blood pressure and heart rate remained unchanged. These findings suggest that allowing individuals to consume the fast day meal at dinner or as small meals throughout the day may increase weight loss with ADF. The effect of these regimens on CHD risk warrants further investigation.
Programming of mitochondrial fuel metabolism in the control of seizure responses (474.2)
Authors: Danial Nika
Published: June 2021

The capacity of mitochondria to process alternate energy substrates such as carbohydrates and ketone bodies can influence neuronal excitability. For example, the ketogenic diet (KD), which reduces glucose metabolism and promotes the breakdown of fatty acids to generate ketone bodies, is effective in pharmacoresistant epilepsy. However, the molecular underpinnings of the link between mitochondrial fuel utilization and neuronal activity are not fully understood. We have found that BAD, a protein with dual functions in apoptosis and glucose metabolism, imparts reciprocal effects on metabolism of glucose and ketone bodies in brain cells. These effects involve phospho‐regulation of BAD and are independent of its apoptotic function. BAD modifications that reduce glucose metabolism produce a marked increase in the activity of metabolically sensitive KATP channels in neurons, as well as resistance to behavioral and electrographic seizures. Seizure resistance is reversed by genetic ablation of the KATP channel, implicating the BAD‐KATP axis in metabolic control of neuronal excitation and seizure responses.
Modulating glycerolipid synthesis and its effects on signaling and metabolism (476.2)
Authors: Finck Brian
Published: June 2021

Lipin 1 is a bifunctional intracellular protein that regulates intermediary metabolism. In the nucleus, lipin 1 regulates gene transcription by interacting with DNA‐bound transcription factors to control metabolic gene expression. Interestingly, lipin 1 also dephosphorylates phosphatidic acid to form diacylglycerol [phosphatidic acid phosphohydrolase (PAP) activity], a key step in triglyceride synthesis and a bifurcation point in phospholipid metabolism. PAP activity is not required for direct transcriptional regulatory effects of lipin 1. Thus, lipin 1 regulates lipid metabolism at two distinct regulatory levels. Mice constitutively‐deficient in lipin 1 are lipodystrophic, insulin‐resistant, and exhibit neonatal hepatic steatosis. In contrast, mutations in the human gene encoding lipin 1 are associated with severe, recurrent rhabdomyolysis in children. It is not clear whether defects in lipin 1‐mediated transcriptional regulatory function or PAP activity provide a mechanistic basis for phenotypic abnormalities in mice or humans with loss of lipin 1. Recent development of mice with tissue‐specific expression of a lipin 1 allele with selective loss of PAP activity and molecular analysis of rhabdomyolysis‐associated single amino acid substitutions in lipin 1 provide evidence that defects in PAP activity lead to muscle injury and defects in adipocyte differentiation.
Recruiting undergraduate biology majors to attend experimental biology EB2015 Boston (531.3)
Authors: Halpin Patricia
Published: June 2021

The goal of this study is to increase undergraduate participation in EB2015 Boston. Prior to EB2013 Boston, the meeting was announced to undergraduate biology majors. Four methods were used; 1) in‐class announcements to Principles of Biology, Genetics and Animal Physiology classes, 2) Blackboard (Bb) announcements, 3) Facebook post and 4) posters were put up on campus. Seven students attended the EB2013 meeting. After the meeting was held, the classes were given a ten question in‐class survey. Of the 86 students surveyed 61 stated they knew about the meeting. The most effective way to inform the students was having the professor announce it in‐class (n=49). The most common reasons why they did not attend were they had to work (n=19), were unaware it was free (n=9), and were afraid to go to Boston alone (7). When asked what would increase the likelihood of students attending EB2015, the responses were to: notify students in January 2015 (n=42), notify via in‐class announcements (n=68), remind often (n=34) and provide group transportation (n=31). Announcements (in‐class and via Bb) will be made in January 2015 and students will be reminded throughout the semester. Group transportation from campus to the Boston Convention Center will be investigated. Based on this strategy it is anticipated that a larger group of students will attend and benefit from EB2015.
Quality of MCQ‐based exams: why functioning distractors matter (533.4)
Authors: Ali Syed Haris
Published: June 2021

BACKGROUND: Item difficulties on Free‐response (FR) and MCQ versions of an exam were compared over four study cohorts in this experimental study. The purpose was to investigate factors underlying differential performance on these two versions and the resultant threat to validity of obtained scores.

METHODS: The two versions (FR and MCQ) of a Neurohistology practice exam comprising 23 items were randomly distributed among Year 1 medical students in four study cohorts. An index of expected MCQ difficulty was calculated via expected inflation in each item’s ease due to provision of options, and was then compared with the actually observed MCQ difficulty. No significant difference between expected and observed MCQ difficulty indices was hypothesized.

RESULTS: A significant difference between FR and observed MCQ difficulty indices (p < 0.05), and not between FR and expected MCQ difficulty indices, was found in all cohorts. Moreover, a consistently low mean number of functioning distractors (0.95, 0.95, 0.86, 0.87), and a significant correlation (p < 0.01) between number of functioning distractors and MCQ difficulty were also noted.

CONCLUSION: Low number of functioning distractors threatens the validity of scores obtained on MCQ‐based exams. To assess true knowledge, careful evaluation of plausibility of every provided MCQ option or a mix of MCQs and alternate assessment tools is recommended.
The anatomy of public health: integrating population health in the anatomy lab (536.14)
Authors: Chock Megan , Lachman Nirusha , Havyer Rachel , Pawlina Wojciech
Published: June 2021

For several years, medical schools in the United States have been urged to integrate public health and population science into their curricula. The first‐year Gross Anatomy course at Mayo Clinic serves as a teaching platform for many non‐technical skills that include professionalism, patient communication and near‐peer teaching that aim to meet core ACGME requirements. As part of the standard Gross Anatomy curriculum, students are assessed on a laboratory based learning activity referred to as a “bedside presentation,” where each small group is assigned a clinical condition and asked to present a hypothetical case as it relates to the anatomy and radiology on their cadaver. The objective of this study is to assess whether first‐year medical students’ knowledge of global health disparities and national population health improved after a longitudinal curriculum revision that combined public health concepts with the bedside presentation. Students first learned to examine a major cause of morbidity and/or mortality on a global/population level following which each team was asked to present a hypothetical patient (relating to their assigned cadaver) with an acute condition associated with the disease or behavior that they had researched earlier. Teams focused on associated anatomic and radiographic findings and used full‐body CT scans and corresponding anatomic parts to illustrate the effects of the disease. Pre‐course data indicate that students have a 50% understanding of population health trends. We anticipate that first‐year medical students will have an improved awareness of public health problems globally and in the United States after completing this activity in Gross Anatomy.
Effect of addition of high fiber ingredients on protein quality of casein and gluten diets assessed by bioassays in growing rats (540.8)
Authors: Falcón María
Published: June 2021

The food industry has responded to consumer demand for foods with higher fiber content, developing products with high‐fiber ingredients. These ingredients have unique properties that raise the level of fiber. Excessive consumption of high‐fiber products can have an impact on the digestibility and protein quality. The aim of this study was to evaluate the effect of three commercial products used to increase fiber content of food on the protein quality of diets based on casein and gluten bioassays, employing Sprague Dawley rat as an experimental model. Six synthetic diets were prepared, three of casein, and three of gluten with three different ingredients high in fiber: insoluble fiber from wheat bran, soluble fiber with resistant maltodextrins and fiber obtained from orange pulp formed by similar amounts of fiber soluble and insoluble. Biological indicators were determined, Net Protein Ratio (NPR) and % Apparent and true digestibility of nitrogen (ADN, VDN). Results were analyzed by a statistical program with 95% significance. ADN and VDN of casein diets with high fiber ingredients ranged from 83.7 to 86.2% and from 86.6 to 89.1% respectively. In gluten diets with different fiber ADN and VDN ranged from 88.0 to 90.5% and from 91.1 to 94.8% respectively and NPR results ranged from 1.44 to 1.77. The results showed that commercial fibers showed significant differences in digestibility and RNP gluten diets.
Association between serum dehydroepiandrosterone sulfate and cardiac autonomic modulation in individuals with different ages (545.7)
Authors: Lemos Marina , Miranda Munique , Melo Poliana , Fernandes Cristhiene , Motal Gustavo , Junior Moacir , Neto Octavio
Published: June 2021

The aim of present study was to evaluate the correlation between serum DHEA‐S and the cardiac autonomic modulation through heart rate variability (HRV) analysis in individuals in different ages. Twenty one volunteers were assigned in 3 groups: G1 (20‐39 years, n=7); G2 (40‐59 years, n=8); G3 (蠅60 years, n=6). The HRV evaluate was realized by electrocardiographic record, for subsequent linear analysis in the time and frequency domain. Following, the volunteers were underwent to antecubital vein puncture to collect blood samples to determine DHEA‐S concentration, that was measured by chemiluminescense. In the results, we found smaller variance in G2 (1014.30 ± 265.21 ms2) and G3 (897.33 ± 274.18 ms2) compared to G1 (2235.16 ± 457.84 ms2; p<0.05). In HRV, the high frequency band was lower in G3 (172.80 ± 37.91 ms2) and in G2 (244.26 ± 76.86 ms2) when compared with G1 (996.09 ± 279.83 ms2; p<0.05). About hormonal analysis, G1 presented higher DHEA‐S levels (240.02 ± 47.08 ug/dL) compared to G2 (91.22 ± 19.67 ug/dL) and G3 (54.21 ± 17.76 ug/dL; p<0.005). We evidenced that there are a strong and positive correlation between low serum DHEA‐S and an impaired HRV associated with aging (r=0.768; p<0.001). We concluded that with aging there are an association between low serum DHEA‐S and impairment of the HRV, which can be related to the cardiovascular events occurrence.
Moderately high fructose (6%) ingestion reduces the vascular reactivity to vasoconstrictors and vasodilators in rats (546.1)
Authors: Fonseca da Silva Rita de Cássia , de Souza Priscila , Marques Maria Consuelo , da Silva Santos José Eduardo
Published: June 2021

It has been shown that very high amounts of fructose in the diet may induce vascular dysfunction in rats. We hypothesized that significantly small amounts of fructose ingested in early life stages is enough to impair the vascular function. Wistar rats were fed with a moderately high (6%) fructose diet (6% F group) for six weeks from weaning (control group received regular chow). Endothelium‐intact (E+) aortic rings and perfused mesenteric arteries from 6% F rats presented reduced responses to phenylephrine (PE, 1 μM: 0.59 ± 0.05 g against 1.26 ± 0.22 g in control), and vasopressin (30 nM: 0.26 ± 0.07 g against 0.61 ± 0.11 g in control). PE‐induced constriction was reestablished in endothelium‐denuded (E‐) rings and after incubation with L‐NAME (100 μM) or ODQ (10 μM). However, PE‐contracted aortic rings (E+) displayed reduced relaxation (~ 60%) induced by acetylcholine (ACh, 1 μM), but not by sodium nitroprusside. E‐ aortic rings from 6% F group maintained in Ca2+‐free solution presented enhanced contractile responses to caffeine (100 mM), but not to PE. This study shows that the ingestion of moderately high fructose in early life stages is enough to impair the vascular reactivity of rats.

Grant Funding Source: Supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES, Brazil; Conselho Na
Coupling between alternative polyadenylation and alternative splicing is limited to terminal introns (560.2)
Authors: Movassat Maliheh , Crabb Tara , Busch Anke , Shi Yongsheng , Hertel Klemens
Published: June 2021

Alternative polyadenylation (APA) has been implicated as an important regulator of gene expression. In some cases APA is known to couple with alternative splicing to influence last intron removal, however it is unknown whether APA events influence alternative splicing decisions at upstream exons. A genome‐wide approach was used to examine the correlation between APA and upstream alternative splicing. CstF64 knockdown in HeLa cells coupled with Pas‐Seq was used to trigger and identify APA events. APA genes were then evaluated for changes in alternative splicing using RNA‐seq analyses of the same knockdown samples. Although a significant number of alternative splicing events were identified, no general correlation between APA and upstream alternative splicing events were observed. These results suggest that the coupling and diversification achieved between APA and alternative splicing in general is fixed to defining the last exon. iClip‐Seq experiments identified CstF64 binding to be predominantly in intronic regions. Interestingly, the genome‐wide binding analysis also showed that CstF64 density is elevated upstream of skipped exons indicating a potential role for CstF64 in alternative splicing. We conclude that while the influence of APA on alternative splicing is generally limited to terminal introns, CstF64 binding to nascent pre‐mRNA may contribute to the modulation of splicing patterns.

Grant Funding Source: NIH
Somatic spliceosomal factor mutations in bone marrow neoplasms ő downstream effects and mechanistic insights (560.3)
Authors: Padgett Richard , Dietrich Rosemary , Singh Jarnail , Przychodzen Bartlomiej , Makishima Hideki , Maciejewski Jaroslaw
Published: June 2021

Somatic mutations of spliceosomal proteins such as U2AF1, SF3B1, SRSF2 and PRPF8 have been identified in myeloid malignancies. These mutations are usually single heterozygous missense mutations at highly recurrent sites. While all of these mutations affect proteins in the common splicing pathway, their downstream consequences may be diverse and involve distinct oncogenic pathways. To identify affected genes and gain mechanistic insight into the effects of these mutations, we have analyzed the tumor transcriptomes of multiple AML patients with and without spliceosomal factor mutations. For U2AF1, we analyzed 6 tumors with U2AF1 mutations and 14 tumors that had no known splicing factor mutations. Focusing on cases of alternative exon inclusion, we identified 35 exons in 35 genes whose inclusion was altered using stringent statistical cutoffs. Of these, 8 exons were more included while 27 were more excluded in the U2AF1 mutant tumors. We examined the splice site signals flanking the alternative exons and noted a highly unusual sequence pattern adjacent to the 3’ AG dinucleotide, which is the recognition site of U2AF1. The sequence at this position showed a mutually exclusive pattern upon comparing the excluded to the included exons and this pattern also differed from the consensus 3’ splice site sequence. Biochemical analysis of the RNA binding specificities of purified mutant and wild type U2AF1/U2AF2 heterodimers showed alterations that correlated with the splicing alterations observed in vivo. Engineered cell lines expressing the mutant U2AF1 protein recapitulated the splicing alterations observed in vivo. These results suggest that the mutations in U2AF1 lead to altered splice site recognition and aberrant splicing of a subset of genes that contribute to the neoplastic state. Similar analyses of the splicing effects of mutations in other spliceosomal factors showed that there is little overlap in the most affected genes.

Grant Funding Source: Supported by NIH grant HL118281
The 26S proteasome in transcription elongation (561.2)
Authors: Maganti Nagini , Moody Tomika , Greer Susanna
Published: June 2021

Accumulating evidence shows the 26S proteasome is involved in the regulation of gene expression. We and others have demonstrated that proteasome components bind to sites of gene transcription, regulate covalent modifications to histones, and are involved in the assembly of activator complexes in mammalian cells. The mechanisms by which the proteasome influences transcription remain unclear. Here, we define novel roles for each of the three 19S proteasome heterodimers, represented by the ATPases Sug1, S7, and S6a, in mammalian gene expression using the inflammatory gene CIITApIV. These ATPases are recruited to induced CIITApIV promoter and also associate with the coding regions. Additionally, these ATPases interact with elongation factor PTEFb complex members CDK9, Hexim and with Ser5 phosphorylated RNA Pol II. Both the generation of CIITA transcripts and efficient recruitment of RNA Pol II to CIITApIV are negatively impacted by siRNA mediated knockdown of these ATPases. Further, the histone H3 accumulation at CIITApIV promoter in the absence of ATPases, indicates failure in activation induced nucleosome eviction. It remains to be determined how these ATPases are utilized to drive requisite conformational changes in histones, transcription factors to regulate their interactions with CIITA gene. Together, these results define novel roles for 19S ATPases in promoting mammalian gene expression.
Use of genetic markers to determine change in population structure of deer ticks in Wisconsin (570.2)
Authors: Much Cody , Caporale Diane , Swiatnicki Mathew
Published: June 2021

During the early 2000’s, tick infection rates in the endemic Northwest and nonendemic Central areas of WI were 36% and 4%, respectively, for Borrelia burgdorferi, the Lyme disease pathogen. In 2004, Borrelia populations and deer ticks populations were both found distinct among Northwest WI, Central WI, and Northeast WI, with very little gene flow among them. However, in 2013, Borrelia abundance has increased with 44% infection rate in Central WI. Possible cause for increased prevalence may be due to increased tick abundance and increased gene flow from high to low endemic regions in the state. The use of 16S mtDNA sequences was used to assess the current population structure of deer ticks in Northern Wisconsin. In 2013, tick 16S haplotypes were identified from Northwest WI, Central WI, and Northeast WI and the distribution of haplotypes among the study sites were determined. Several unique haplotypes found only in Northwest WI from 1999 are now found in Central WI. Phi statistical estimates may reveal ticks as being one population between the Northeast and Central WI, due to an increase in gene flow. This may be the possible cause of increased incidences of tick‐borne disease in Wisconsin. The study may also be informative for medical professionals in Wisconsin.

Grant Funding Source: Supported by UWSP College of Letters and Science