bluuebunny/crossref_metadata_2025 huggingface dataset:
Goji berry improves colitis in IL10‐/‐ mice through modulating gut microbiota
Authors: Kang Yifei , Du Min , Yang Guan , Zhu Meijun
Published: June 2021

Inflammatory bowel diseases (IBD) are chronic gut disorders with complex and obscured etiologies. Accumulating evidences implicate gut microbiota as a pivotal factor in the IBD pathogenesis. Goji berry, a tonic food in China, is known for its immune‐modulating properties. The objective of this study was to examine beneficial effects of Goji on experimental colitis in IL10‐ deficient (IL10 ‐/‐) mice and further explore underlying mechanisms. IL10‐/‐ mice that develop enterocolitis spontaneously were assigned to a standard rodent diet (CON) or a diet supplemented with Goji (1% of dry feed weight) for 10 weeks, when the colonic tissues and fecal contents were collected. Goji supplementation has no effect on body weight gain and feed intake in IL10‐/‐ mice. Histologically, Goji supplementation improved pathobiological scores in IL10‐/‐ mice. Pyrosequencing revealed that Goji supplementation dramatically increased Actinobacateria in gut microbiota with no change in other phyla. At family level, Goji supplementation increased Bifidobacteriaceae and Lachnospiraceae‐Ruminococcaceae, while decreased Peptostreptococcaceae abundance. At genus level, Goji supplementation was associated with increased Bifidobacterium, Clostridium XVIII, Pseudoflavonifractor, Sporobacter, Anaerotruncus and Butyriccicoccus, but has no effect on Bacteriodes, Akkemansia, Mucispirillum and Desulfovirio genus. qRT‐PCR further confirmed a drastic increase in the abundance of Bifidobacterium as well as Fecalibacterium prazusnitzii and Clostridium leptum and Roseburia spp. In conclusion, Goji supplementation ameliorates chronic colitis likely through promoting beneficial gut microbiota.
Change in Knowledge of and Adherence to Dietary Sodium Restrictions in Heart Failure Patients after Education by a Registered Dietitian
Authors: Tan Candice , Holland Sarah , Tangney Christy , Betz Melanie , Mozer Marisa , Sarcinella Kali , Rasmussen Heather
Published: June 2021

A low‐sodium diet (< 2000 mg) is often recommended for heart failure (HF) patients to help control symptoms. Often HF patients lack both knowledge of and adherence to the sodium guidelines, which may contribute to hospital readmissions. It is unclear whether a visit with a Registered Dietitian (RD) will improve dietary sodium knowledge and adherence of HF patients. Therefore, 57 HF patients completed two questionnaires in which sodium knowledge and intake before and after RD education was assessed. The sample was middle‐aged (56 ± 14 years), 58% male, and 63% African American. The mean ± SD time in between the first and follow‐up visit was 5.1 ± 3.4 months. Wilcoxon signed‐rank, paired t, and McNemar tests were used to assess the change in median knowledge score, mean sodium intake, and components of Parkland Questionnaire, respectively. A p‐value of < 0.05 was considered statistically significant. Following RD education, 25 patients (44%) had increased knowledge (increase in median score from 7 to 8, maximum score of 10, p = 0.002), and 33 (58%) had decreased sodium intake, with a reduction from 2,493 ± 1346 mg to 2,093± 1218 mg (p = 0.01). Patients were more likely to sort all 12 food containers by sodium content correctly after the education (54% vs. 72%, respectively; p = 0.03). The year before education, 49% of patients were admitted to the hospital with HF symptoms, but only 21% were readmitted within one year after education; 28% of patients who were admitted the year before education were not admitted after education. Education by an RD improved both knowledge of and adherence to the low‐sodium diet, which may lead to decreased hospitalizations. Therefore, an RD is an essential part of the HF team.
A Randomized Controlled Trial Evaluating Online to In‐Person Education to Improve Breakfast Behaviors, Beliefs and Knowledge in WIC Participants
Authors: Au Lauren , Whaley Shannon , Rosen Nila , Meza Martha , Ritchie Lorrene
Published: June 2021

The purpose of this randomized‐controlled trial was to compare the impact of online to in‐person group nutrition education on changes in knowledge, beliefs, and behaviors related to breakfast eating. The content of the lesson focused on ways to reduce breakfast skipping and promoted healthy options at breakfast for parents and their 1‐5 year‐old children on WIC. Questionnaires were administered before and after‐education, and at a 2‐4‐month follow‐up to 604 California WIC participants. T‐tests and x2 tests were used to compare changes within and between in‐person versus online groups. ANOVA and GEE analysis were used to assess differences in change between groups over time. Increases in the frequency of eating breakfast were greater for both parents (P=0.001) and children (P=0.003) in the online group compared to the in‐person group. Both groups reported reductions in barriers to eating breakfast due to time constraints, not having enough foods, and hunger. Positive changes in knowledge were similar, but decreasing 100% fruit juice consumption was only seen in the in‐person compared to the online group for both parents (P=0.005) and children (P=0.01). Satisfaction with the class was high in both groups, but significantly higher in the online group (P=0.0001). Overall, this study supports online nutrition education as a viable supplement to traditional education to promote healthy breakfast behaviors; however in‐person education may be better for sustained behavior change in WIC participants.
An Exploratory Study of High School Students' Intrinsic Motivation and Perceived Competence to Cook: Development of a Culinary Skills Curriculum and Survey Instrument
Authors: Miketinas Derek , Cater Melissa , Zawodniak Brittany , Roy Heli , Bailey Ariana , Tuuri Georgianna
Published: June 2021

Adolescents' lack of motivation and competence to cook may hinder consumption of a healthy diet; however, tools to estimate these behaviors are lacking. A survey to determine adolescents' intrinsic motivation (IM) and perceived competence (PC) to prepare healthy foods was developed based on the Self Determination Theory (SDT). Adolescents responded to statements pertaining to IM or PC using a 5‐point Likert Scale ranging from 1 “Disagree a lot” to 5 “Agree a lot.” Exploratory Factor Analysis using Principal Axis Factoring with a Promax (oblique) rotation returned 2 factors. Factor 1 statements described IM (45.2% of variance) and Factor 2 statements described PC (15.4% of variance). Chronbach's alpha for Factor 1 = 0.889 and Factor 2 = 0.889. The survey was tested with the Nutritional Health component of a 6‐week high school wellness pilot program offered to 20 public school students in southeast Louisiana. The curriculum included 6 lessons and taught culinary skills, nutrition education, and food safety. 13 students completed surveys before and after participating in the program. Wilcoxon signed ranks test indicated a significant increase in IM from baseline (Mdn = 24) to completion (Mdn = 26), T = 6, p = 0.027, r = ‐0.434 and an increase in PC from baseline (Mdn = 18) to completion (Mdn = 22) T = 10.5, p = 0.044, r = ‐0.394. This survey was able to detect measurable change in these SDT constructs when used to evaluate a school‐based nutrition education pilot program for high school students. Funded by the Expanded Food and Nutrition Education Program and Hatch Project 94127
Nutrition and Physical Activity Education among SNAP‐Ed Eligible Middle School Students Reveals Disconnect between Knowledge and Behavior
Authors: LeGros Theresa , Misner Scottie , Farrell Vanessa , Hartz Vern , Jacobs Laurel , Armstrong Florian Traci
Published: June 2021

Schools eligible for Supplemental Nutrition Assistance Program Education (SNAP‐Ed) can offer programs to address overweight and obesity among low income youth. This study assessed changes in knowledge and behavior among middle school students in SNAP‐Ed eligible schools after nutrition and physical activity education.

Students in SNAP‐Ed eligible schools across five AZ counties received nutrition and nutrition‐integrated physical activity education during the school year. A randomized cohort of 6th‐ 8th grade classrooms (N=40, mean fall class size=25) was surveyed in fall and spring. The anonymous survey asked about behavior the previous day and knowledge of national nutrition and physical activity guidelines. Paired t‐tests assessed change in weighted classroom averages.

Significant knowledge gains were found in two of five national guidelines, recommended vegetable consumption (p<0.05) and physical activity (p<0.01). Self‐reported behaviors had a significant increase in whole grain consumption (p<0.05) and a significant decrease in water intake (p<0.05). There was no change in vegetable consumption or in any physical activity category except active travel home from school (p<0.05).

These data suggest that behavior change may occur independent of knowledge change. This disconnect underscores the importance of addressing factors other than knowledge (e.g. self‐efficacy and environment) when delivering programs to address overweight and obesity prevalence among low income youth.
A Dietary Prebiotic Blend of Polydextrose and Galactooligosaccharides with Bioactive Whey Protein Fractions Affects Piglet Intestinal Function and Brain Microstructure
Authors: Alexander Lindsey , Mudd Austin , Berding Kirsten , Waworuntu Rosaline , Berg Brian , Donovan Sharon , Dilger Ryan
Published: June 2021

Identifying nutritional strategies to optimize early‐life development is a relevant and important focus of pediatric nutrition research. The piglet has been accepted as the best pre‐clinical model of infant development. Beginning at 2 d of age, 24 male pigs received either a control formula (CONT) or test formula containing a prebiotic blend of polydextrose and galactooligosaccharides with bioactive whey protein fractions (TEST) for 30 days. Neuroimaging was used to quantify brain composition and structure while intestinal histomorphology, vasoactive intestinal peptide (VIP) expression, and disaccharidase activity were measured as markers of gut development and function. Pigs fed TEST had greater (P < 0.05) jejunal lactase activity, increased (P < 0.05) ileal VIP expression and small intestine morphology comparable to CONT. Analysis of brain microstructure by diffusion tensor imaging indicated lower (P < 0.05) mean and radial diffusivities values in the internal capsule (IC) of TEST‐fed pigs, suggesting advanced white matter development in TEST‐fed pigs. Since the IC is one of the first subcortical structures to myelinate, these data may indicate advanced brain maturation in the TEST‐fed pigs. In conclusion, a combination of nutritional technologies elicited changes in gut functions and brain microstructure that may translate into functional benefits. However, future research is warranted to explore how these changes may impact other aspects of piglet development. Supported by Mead Johnson Nutrition.
A Ganoderma lucidum extract derived from Mexican genetic resources and its effect on lipid metabolism gene expression and liver fatty acid composition
Authors: Meneses‐Alvarez Maria , Martinez‐Carrera Daniel , Morales Porfirio , Sobal Mercedes , Bernabé Teodoro , Granados‐Portillo Omar , Torres Nimbe , Tovar Armando
Published: June 2021

The medicinal mushroom Ganoderma lucidum (Gl) provides diverse health benefits, however, strains from Mexican origin have not yet been studied. The aim of the present work was to study the effect of the consumption of a standardized Gl extract in mice fed a high colesterol diet on the expression of genes involved in fatty acid and colesterol metabolism in the liver, as well as the impact on liver lipid concentration and fatty acid composition. Mice were fed 20% casein (AIN93G) diet, with and without cholesterol (0.5%) and supplemented with a low and high dose of Gl extract. Mice fed with high dose of Gl extract in the diet gained less body weight than mice fed control diet or low dose Gl extract and high colesterol diet. Consumption of Gl extract significantly reduced hepatic and serum cholesterol and triglycerides concentration compared to high cholesterol group. These effects were associated with a significant reduction of expression of lipogenic genes (SREBP1, FAS, ACC) as well genes involved in reverse cholesterol transport (ABCG5, ABCG8) in the liver. The consumption of Gl extract modified the fatty acid composition in liver. Mice fed with Gl extract showed a decrease of SFA, while an increase of MUFA and PUFA, as compared to mice fed with high cholesterol diet. Our data showed that the Gl extract effectively regulates lipid metabolism through the presence of bioactive compounds helping to prevent the accumulation of hepatic lipids.

This work was supported by CONACYT
Hypolipidaemic effects of Methanol Extract of Vernonia amygdalina Del in male Wistar albino rats fed High fat diet
Authors: Ijeh Ifeoma , Egedigwe Agatha
Published: June 2021

Obesity and its primary co‐morbidities are emerging as a serious health problem among urban dwellers in developing countries such as Nigeria, with class I obesity being the most common pattern and hypertension being the most common primary co‐morbidity. The study was aimed at assessing the effects of high‐fat diets and concomitant administration of methanol extracts of Vernonia amygdalina (Va) on body weight changes and lipid profile in male Wistar rats. Thirty male albino rats aged 4‐6 weeks old were placed in five groups of six animals each. Group 1 served as the control (Non high fat diet), Groups 2 and 3 received methanol extracts of Va at 50mg/kg and 100 mg/kg body weight respectively. Group 4 served as the positive control received orlistat (drug control). Group 5 received high fat diets only. After 12 weeks of feeding, Serum total cholesterol, Triacylglycerol, HDL‐cholesterol and LDL‐cholesterol concentrations were determined using standard biochemical methods. Daily body weight changes were also recorded.Results: There were significant (p<0.05) decreases in total cholesterol, triacylglycerol and LDL cholesterol concentrations in experimental rats who received extracts at 50mg/kg and 100mg/kg body weight relative to the obesity control fed on high fat diets. HDL‐cholesterol concentrations showed an insignificant (p>0.05) increase compared to the obesity control group fed high fat diets. These findings provide a preliminary scientific support for the use of extracts of Va in ethnomedicine as slimming bitters and in treatment of hypertension. Its inclusion in diet could serve as a dietary regimen in management of obesity and other disorders associated with hyperlipidaemia.
Dietary Cocoa Improves Hepatic Mitochondrial Function in Obese Mice
Authors: Sun Mingyao , Tao Ling , Gu Yeyi , Lambert Joshua
Published: June 2021

Nonalcoholic fatty liver disease (NAFLD) is an important co‐morbidity of obesity. Previously, we found that dietary cocoa (Theobroma cacao) supplementation reduced hepatic lipid content and inflammation in obese mice. Here, we investigated the effect of dietary cocoa on hepatic mitochondrial biogenesis, oxidative stress, and antioxidant response. Male C57BL/6J were fed HF (60 % kcal from fat) diet for 8 wks, and then randomized to continue HF diet or to consume HF diet supplemented with 80 mg/g cocoa powder (HF‐HFC) for an additional 10 wks. We found cocoa treatment increases hepatic mitochondrial DNA copy number by 48.6% compared to HF‐fed mice, suggesting increased mitochondrial biogenesis. Using real‐time PCR, we found that mRNA levels of sirtuin (sirt)1, peroxisome proliferator‐activated receptor gamma coactivator 1a, and nuclear respiratory factor 1 were significantly increased in HF‐HFC compared with HF‐fed mice. These genes have been reported to promote mitochondrial biogenesis. We found that cocoa supplementation decreased hepatic lipid peroxidation by 57% compared to HF‐fed controls indicating reduced oxidative stress. Cocoa supplementation also increased the expression of Sirt3, an important mitochondrial redox regulator, as well as manganese superoxide dismutase and glutathione peroxidase (Gpx)1 was increased in cocoa supplemented mice HF‐HFC compared to HF‐fed controls. Cocoa also increased hepatic Gpx activity by 43% compared to HF‐fed controls. In summary, our results demonstrate that the beneficial effects of cocoa supplementation on NAFLD may be mediated by increases in mitochondrial biogenesis and related antioxidant response signaling.
From Shelf to Health: Product Reformulations in Cookies Impacts the Public Health Consumption Estimates of Saturated Fat and Sugar Intakes
Authors: Hooker Neil , Spees Colleen , Watowicz Rose , Taylor Christopher
Published: June 2021

Policies that limited trans fat forced the food industry to provide foods that mirrored pre‐legislation properties with new formulations; thus, many manufactures altered the saturated fat and sugar composition of cookies to address policy requirements and hedonic properties demanded by consumers. These phenomena present a challenge for national surveillance activities to accurately assess dietary patterns using a food composition database that represents point estimates of nutrient composition of the food supply. The purpose of this study was to overlay the nutritional data of industry innovation in 3,308 cookies from the 2005‐12 Global New Products Database (GNPD) to national cookie consumption from 2005‐12 NHANES to estimate the population consumption trends that may exist from such innovation. GNPD product data were cleaned and matched to the 115 cookies in the FNDDS. Aggregated minimum, maximum, mean and median estimates from each cookie type were appended to individual intake data to estimate the FNDDS and GNPD variability for total nutrient intakes for cookies per person per day (n=6,566). National estimates from FNDDS closely mirrored the GNPD mean and median product profiles; however, FNDDS had higher sodium and lower saturated fat estimates than the central tendencies of GNPD estimates. Cookie intakes predicted from minimum and maximum GNPD products had a considerable impact on estimating the saturated fat and sugars to offset the removal of trans fat. Product innovation can influence national consumption estimates when these products comprise a critical mass of the US food supply.
Impact of School Lunch Period Length on Meal Consumption
Authors: Cohen Juliana , Jahn Jaquelyn , Richardson Scott , Parker Ellen , Rimm Eric
Published: June 2021

The objective of this study was to examine the impact of school lunch period length on meal consumption among children (n=3481) attending four elementary/middle schools in a low‐income, urban school district. Schools had lunch period lengths that varied from 20‐30 minutes, with some students arriving early or late. Children's selection and consumption of foods were assessed using plate waste study methods and the time that children left the lunch line (the time to eat) was recorded on six non‐consecutive days. Food selection was analyzed using logistic regression, and consumption was analyzed using mixed‐model analysis of variance, accounting for the correlations associated with repeated measures of students nested within schools. Models were adjusted for gender, grade category (elementary or middle school), race/ethnicity, and the lunch period time of day (e.g. early morning, afternoon). Overall, the amount of time to eat ranged from 10‐33 minutes. Compared with students who had at least 25 minutes to eat their meal, students with fewer than 20 minutes to eat were significantly less likely to select a fruit (44% vs. 57%; p=0.0001). There were no significant differences in entrée, milk, or vegetable selection. Among those who selected a meal component, students with fewer than 20 minutes to eat consumed 12% less of their entrée (p<0.0001), 10% less of their milk (p<0.0001), and 11% less of their vegetable (p=0.0002) compared with students with at least 25 minutes to eat. These results suggest that policies that encourage lunch periods that enable at least 25 minutes of seated time in the cafeteria will improve the quality of students' diets.
THE EFFECT OF A LOW GLYCEMIC INDEX DIET ON DIABETIC NEPHROPATHY
Authors: Srichaikul Korbua , Hertzog Valerie , Dutton Heidi , Kendall Cyril , Sievenpiper John , Jenkins David
Published: June 2021

Background

Microvascular complications, including renal disease, have been strongly associated with poor glycemic control. We have therefore assessed the effect of improved glycemic control after consumption of a low glycemic index diet on the degree of microalbuminuria.

Methods

155 type 2 diabetic subjects treated with antihyperglycemic agents were randomized and completed either 6 months of high fiber or low glycemic index dietary advice in a parallel design. In 150 completers, 24 hour urine collections were obtained pre‐treatment and at the end of the 6 month study period.

Results

A total of 107 subjects had detectable albumin in their baseline 24 hour urine collections with 14 subjects having microalbuminuria (urinary albumin >30 mg/24 hours). The treatment difference in the change in microalbuminuria was not significant. However, with improved glycemic control on the low glycemic index diet microalbuminuria decreased by 63±24 mg/d (n=7, p=0.039) compared to a reduction of 15±13mg/d (n=7, p=0.308) on the high fiber diet. No between treatment difference was seen in serum creatinine or creatinine clearance.

Conclusion

These preliminary data suggest a possible benefit of low glycemic index diets on microalbuminuria in type 2 diabetes.

Funding the Canadian Institutes of Health Research, Canada Research Chair Endowment of the Federal Government of Canada, and Barilla (Italy).
Effects of Gluten on the Plasma Proteome in Humans
Authors: Jamnik Joseph , Garcia‐Bailo Bibiana , Borchers Christoph , El‐Sohemy Ahmed
Published: June 2021

Gluten‐free foods have increased in popularity over the past decade and are now being consumed by individuals without celiac disease; however, the physiological effects of gluten intake in individuals without celiac disease remain unknown. High‐abundance plasma proteins involved in inflammation, endothelial function and other physiological pathways may represent potential biomarkers of biological effects of gluten intake. The objective was to examine the association between gluten intake and plasma proteomic biomarkers in a population of young adults without celiac disease (n=1,095). Dietary gluten intake was estimated using a one month 196‐item semi‐quantitative food frequency questionnaire. The concentrations of 54 plasma proteins were measured using a multiple reaction monitoring HPLC‐MS/MS assay. The association between gluten intake and each proteomic biomarker was examined using general linear models. Increased gluten intake was associated with increased concentrations of plasma α2‐macroglobulin (p=0.01), a marker of inflammation and cytokine release. The association remained after adjusting for age, sex, BMI, ethnicity, physical activity, energy intake, fiber intake, and hormonal contraceptive use among women. This relationship was not modified by human leukocyte antigen (HLA)‐DQ2 or ‐DQ8 risk variants required for the development of celiac disease. These results suggest that gluten consumption may have effects on inflammation independent of celiac disease. Research support from the Advanced Foods and Materials Network.
Diet‐induced Weight Loss Changes in Gene Regulatory Networks in the Rectum: Network Analysis as a Compliment to Traditional Gene Expression Analysis
Authors: Vargas Ashley , Quackenbush John , Glass Kimberly
Published: June 2021

Objective

To determine if there are different transcription factor‐gene relationships in rectal mucosa tissue after ~10% body weight loss.

Methods

10 obese women underwent clinically supervised weight loss via a very low calorie diet. Rectal mucosal biopsies were obtained before and after the ~ 46.5 day intervention, and mRNA expression was measured. An earlier study used a traditional analysis approach (Gene Set Enrichment Analysis; GSEA) to examine changes in expression. However, we hypothesize that building a network that includes known transcription factors‐gene relationships provides more detail on how regulatory pathways are changed. A network of transcription factor‐gene interactions was constructed for baseline and for end‐of‐study samples using Passing Attributes between Networks for Data Assimilation (PANDA). The baseline network was then compared to the end‐of‐study network to look for regulatory and pathways changes.

Results

The transcription factors NFκB1, INSM1 and MAX are all changing their targets between baseline and end‐of‐study samples. Further, changes in glucose transport from baseline to end‐of‐study were observed.

Conclusions

Complementing traditional GSEA analyses, this network approach identified changes in glucose transport. These changes are supported by circulating biomarkers of glucose tolerance and suggest that NFκB1, INSM1 and MAX are the key mediators of the effect of weight loss in rectal mucosa.
The role of antenatal anemia and lead exposure in determining early child temperament: evidence from the Avon Longitudinal Study of Parents and Children (ALSPAC).
Authors: Kordas Katarzyna , Taylor Caroline , Golding Jean
Published: June 2021

Elevated blood lead levels (BLL) and anemia are related to poor developmental outcomes in young children, but it is unclear how they relate to temperament. We examined the association of maternal BLL and anemia in early pregnancy to child temperament in ALSPAC. Pregnant women were enrolled Dec 1990‐Apr 1992. BLLs were measured in whole blood in 4,134 mothers, hemoglobin (Hb) was abstracted from antenatal records (both median 11 wks ga). Mothers reported on temperament at 4wks (crying score [n=2875] and child states—happy/cuddly and fretful/demanding [n=3407]), 6 mo, and 24 mo (Activity, Rhythmicity, Approach, Adaptability, Intensity, Mood, Persistence, Distractibility, Threshold scores from Carey Infant and Toddler Temperament Scales; higher scores indicate problematic temperament, [n=3160‐3330]). Sample was 51.8% boys. Mean±SD BLL and Hb were 3.7±1.5 µg/dL and 12.3±0.9 g/dL; 5.7% had anemia (Hb<11.0 and <10.5 in 1st and 2nd trimester). Independent effects of maternal BLL, anemia, and their interaction were tested on temperament outcomes in multivariate models. Maternal BLL was associated with lower 4wk crying scores if maternal anemia was also present (β±SE: ‐0.6±0.2 p<0.01 vs. ‐0.03±0.05, ns). At 6 mo, higher BLL was associated with lower approach (‐0.3±0.1 p=0.01) and adaptability (‐0.2±0.1 p=0.04) scores; anemia was related to higher adaptability scores (1.1±0.6 p=0.05). At 24 mo, BLL was associated with lower rthythmicity (‐0.8±0.4, p=0.06 vs. 0.02±0.09, ns.) but higher intensity (0.7±0.4 p=0.07 vs. 0.05±0.07, ns) scores when anemia was present. BLL was also linked with distractibility (0.2±0.1 p=0.03). Maternal BLL and anemia had mixed effects on temperament.
Loss of Cortactin is Associated with Intestinal Epithelial Barrier Dysfunction and Development of Colitis
Authors: Citalán‐Madrid Alí , García Alexander , Vargas Hilda , Betanzos Abigail , Nava Porfirio , Rottner Klemens , Menningen Rudolf , Schnoor Michael
Published: June 2021

A stable intestinal epithelium is the basis for healthy intestines. Its dysfunction causes increased intestinal permeability and bacterial translocation that may eventually cause an aberrant immune response leading to chronic inflammatory diseases of the intestines such as inflammatory bowel disease (IBD). The actin cytoskeleton regulates epithelial barrier integrity but the role of actin regulators such as cortactin (CTTN) is not well understood. Analyzing CTTN‐KO mice, we found increased basal intestinal permeability similar to what has been shown in the vasculature. Using a CTTN‐depleted Caco‐2 cell line, we confirmed epithelial dysfunction by reduced transepithelial resistance (TER), a weaker cortical actin ring, internalization of occludin and ZO‐1 and accelerated transmigration of neutrophils. Calcium‐switch assays revealed a strong delay in barrier formation without CTTN. While CTTN depletion did not cause increased apoptosis, we observed increased proliferation. Importantly, CTTN localized at cell contacts in colon biopsies of healthy individuals, whereas in IBD patients we observed strong translocation of CTTN into the cytosol and loss of colocalization with actin and ZO‐1. Our data imply that CTTN controls intestinal barrier integrity under basal conditions and that loss of CTTN triggers epithelial dysfunction as seen in IBD.
miR‐186 Inhibition Alters Cell Proliferation and Colony Formation in Prostate Cancer
Authors: Jones Dominique , Hobbing Katharine , Schmidt M. , Clark Geoffrey , Kidd LaCreis
Published: June 2021

Numerous published reports show microRNAs (miRs) influence PCA development and disease progression. However, there are no published reports on the role of miR‐186 in relation to PCA. Previously, we observed miR‐186 expression was significantly up‐regulated in the serum of PCA patients (n = 15) diagnosed with stage III and IV disease compared to controls (n = 5). We also observed miR‐186 expression was significantly up‐regulated in metastatic PCA cells (PC3) after normalization with control cell line (RWPE1) and endogenous miR (U6). Mir‐186 overexpression is associated with the down‐regulation of pro‐apoptotic and tumor suppression‐related genes in various cancers. We hypothesized that miR‐186 inhibition will reduce the aggressive PCA phenotype.

To test this hypothesis, PC3 cells were transiently transfected with miR‐186 inhibitor and scramble control for 24hrs. Cell viability and colony formation of transfected cells were evaluated via ATPlite and soft agar assays, respectively.

MiR‐186 inhibition significantly decreased both cell viability by 48‐58% at 72‐96hrs and colony formation by 30% after 21 days. These findings suggest miR‐186 inhibition represses cell proliferation and anchorage independence. Additional studies are needed to: (1) discern whether stable miR‐186 inhibition will reduce cell migration, invasion and metastasis using in vitro assays and murine models; (2) identify and validate miR‐186 targets using gene/protein analyses. Such efforts will lead to the identification of a biomarker to help improve current PCA detection, prognostic and clinical management strategies.
Differential Responses to Hormone Therapy Among ER+/PR+/HER2‐ Breast Cancers That Differentially Express the Estrogen Response Signature
Authors: Sandhu Rupninder , Parker Joel , Anders Carey , Coleman William
Published: June 2021

ER+/PR+/HER2‐ breast cancers are frequently associated with good outcomes, but some patients experience disease progression/recurrence. We examined responses to hormone therapy (HT) in 182 ER+/PR+/HER2‐ breast cancers (with known molecular subtype) that differentially express a 583‐gene estrogen response signature (ERS). Overall, 13/33 (39%) patients treated with HT relapsed versus 77/149 (52%) untreated patients. 142 ER+/PR+/HER2‐ breast cancers are ERS+ (27% relapse with HT, 48% untreated relapse), and 40 ER+/PR+/HER2‐ breast cancers are ERS‐ (100% relapse with HT, 62% untreated relapse). Kaplan‐Meier analysis revealed a significant improvement in relapse‐free survival among ERS+ ER+/PR+/HER2‐ breast cancers that received HT versus untreated (P=0.0489). ERS+ ER+/PR+/HER2‐ Luminal A breast cancers benefit from HT – 5/19 (26%) treated relapsed versus 36/75 (48%) untreated relapsed. ERS+ ER+/PR+/HER2‐ Luminal B (LumB) breast cancers show less benefit from HT – 1/3 (33%) treated relapse versus 12/29 (41%) untreated relapse. Any HT benefit observed is lost among ERS‐ ER+/PR+/HER2‐ LumB breast cancers – 5/5 (100%) treated relapse versus 10/17 (59%) untreated relapse. ER+/PR+/HER2‐ HER2‐enriched breast cancers do not benefit from HT – Over 50% relapse irrespective of ERS or HT status. Despite small numbers, ERS+ ER+/PR+/HER2‐ Basal‐like and Claudin‐low breast cancers appear to show benefit from HT – 0/3 (0%) treated relapse versus 4/6 (67%) untreated relapse. Most molecular subtypes of ERS+ ER+/PR+/HER2‐ breast cancer benefit from HT.
Atp6v1c1 Facilitates Breast Cancer Growth and Bone Metastasis through the mTORC1 Pathway
Authors: McConnell Matthew , Feng Shengmei , Chen Wei , Zhu Guochun , Deng Lianfu , Li Yi‐Ping
Published: June 2021

The mTORC1 kinase promotes growth in response to growth factors, energy levels, and amino acids, and its activity is often deregulated in cancers, including breast cancer. Recent studies have shown that mTORC1 senses lysosomal amino acids through an inside‐out mechanism that requires vacuolar H+‐ATPase activity. However, the mechanism underlying how V‐ATPases activate the mTORC1 pathway in cancer growth and metastasis remains largely unclear. Atp6v1c1, an assembly regulator of the V0 and V1 domains of the V‐ATPase complex, is highly expressed in metastatic cancer cells. Our data revealed that silencing Atp6v1c1 in metastatic 4T1 mouse breast cancer cells (4T1) severely impairs 4T1 cell growth, migration, and metastasis, as well as inhibiting mTORC1 pathway activation stimulated by amino acids. Notably, Atp6v1c1 knockdown also inhibited the proliferation of MCF‐7, MDA‐MB‐231, and MDA‐MB‐435s human breast cancer cells and blocked their mTORC1 pathway activation stimulated by amino acids. Surprisingly, Atp6v1c1 knockdown in normal cells C3H10T1/2 has no effect on its proliferation and mTORC1 pathway activation stimulated by amino acids. Our study demonstrates, for the first time, a potential mechanism by which Atp6v1c1 facilitates cancer cell growth and metastasis through its function in mTOR pathway activation and may provide a novel therapeutic approach for breast cancer metastasis.
Iron Metabolism and Prostate Cancer Aggressiveness: A Meta‐Analysis of Gene Expression Microarray Datasets
Authors: Kajdacsy‐Balla Andre , Ali Waleed , Shah Jarna , Macias Virgilia , Hall Andrew , Walden William , Dai Yang
Published: June 2021

Changes in iron metabolism in prostate cancer are not understood. We address the hypothesis that more aggressive prostate cancers exhibit markers of higher acquisition and intracellular retention of iron.

Analysis of Oncomine, a public microarray database demonstrated elevation in mRNA gene expression in high grade tumors (Gleason scores 8‐10) when compared to low grade tumors (scores 4‐6) for several genes involved in iron metabolism, including Transferrin Receptor 1 (TfR1; 7 out of 11 databases), Ferritin Light Chain (FTL; 6 of 6) and Ferritin Heavy Chain (FTH; 6 of 8). The differences were statistically significant (p<0.05) in 4/7, 3/6, and 1/8 databases respectively (Welch t‐test or Wilcoxon rank‐sum test). Meta‐analysis by Z‐transform test showed significant global p‐values for TfR1 and FTL, but not for FTH.

TfR1 over expression in more aggressive tumors was confirmed by immunohistochemistry by comparing prostatectomy samples in a 400 cases outocomes‐based tissue microarray (TMA) built by the Cooperative Prostate Cancer Tissue Resource. The recurrence group had higher TfR1 intensity levels (p<=0.04).

In a previous publication we showed that iron levels were decreased in areas surrounding tumors that had poorer prognosis. Others have shown that within the tumor itself, iron levels are increased and high Gleason grade tumors have the highest levels. Overall our data suggest that 1) iron is less available to prostate cancer cells with worse prognosis, and 2) TfR1 and FTL overexpression in more aggressive tumors may contribute to the ability to accumulate iron.
Critical Roles for the IQ‐Motif and Actin‐Bnding Domain of Endothelial Cell IQGAP1 During Leukocyte Transendothelial Migration
Authors: Sullivan David , Dalal Prarthana , Muller William
Published: June 2021

In order to mount an appropriate inflammatory response, leukocytes must cross the endothelium to gain access to the target tissue and carry out their essential roles. This process is referred to as transendothelial migration (TEM) and requires a novel endothelial cell membrane compartment, the Lateral Border Recycling Compartment (LBRC), which is delivered to the migrating leukocyte to supply it with several requisite membrane proteins. IQGAP1, a large soluble scaffolding protein, is associated with the LBRC and is required for its function during TEM. In a variety of other processes, IQGAP1 integrates signals from diverse pathways to regulate cytoskeletal remodeling, Rho family GTPase activity, and other downstream readouts, however its role in TEM remains unclear. Here we show that genetic ablation of endothelial IQGAP1 expression arrests leukocytes during TEM by preventing the targeted delivery of the LBRC. Expression of a full length GFP‐tagged IQGAP1 construct completely restores this defect and also shows that endothelial IQGAP1 is enriched around the leukocyte during TEM. Furthermore, using fluorescently tagged IQGAP1 truncation constructs, we show that the actin‐binding domain of IQGAP1 is required for its localization to the junction in resting endothelial cells and its recruitment and function during TEM. Interestingly, the IQ motif of IQGAP1, which facilitates its interaction with calmodulin, is not required for localization to the junction or recruitment during TEM, but is necessary for IQGAP1′s function during TEM. Together these data suggest that IQGAP1 integrates signals from various sources to facilitate the function and recruitment of the LBRC during TEM. Supported by R01 HL046849 and R37 HL064774.
Patterns of Fetal Growth based on Ultrasound Measurement and its Relationship to Small‐for‐Gestational Age at birth in Vietnam
Authors: Nguyen Phuong , Addo O Yaw , Gonzalez‐Casanova Ines , Pham Hoa , Truong Truong , Nguyen Son , Nguyen Hieu , Martorell Reynaldo , Ramakrishnan Usha
Published: June 2021

Small‐for‐gestational age (SGA) is a global public health concern with important short‐ and long‐ term consequences. Identifying the timing of growth faltering is critical for the prevention of SGA. This study aims to examine patterns of fetal growth and the use of ultrasound measurements in predicting SGA at birth. We used ultrasound and birth data (n=1,412) that were collected in a randomized controlled trial evaluating pre‐conception micronutrient supplements on maternal and child health outcomes in Vietnam (PRECONCEPT). Biparietal diameter (BPD), head (HC) and abdominal circumference (AC) and femur length (FL) were compared with the INTERGROWTH 21st fetal growth standards. SGA was defined as birthweight <10th percentile. Growth faltering began around mid‐pregnancy and continued through delivery. The timing varied by measurement and began earlier for BDP and AC (at 20 w) compared to HC and FL (later than 30 w). Infants born SGA had lower Z‐score in all measures as early as 14 weeks. Ultrasound measures <10 percentile were predictive of increased odds of SGA at birth: AC had the largest effects (OR: 5.5, 95% CI: 3.6, 8.5), followed by FL (OR: 3.7, 95% CI: 2.6, 5.2), BP (OR: 3.5, 95% CI: 2.3, 5.5), and HC (OR: 3.4, 95% CI: 2.3, 5.1). In conclusions, among infants born small fetal growth faltering begins in early gestation. Prenatal growth retardation is a key predictor of SGA at birth. Early detection of growth faltering is important for implementing interventions to prevent SGA and its consequences. Supported by the Mathile Institute and the Micronutrient Initiative.
A Role for BCO1 Beyond Carotenoid Metabolism: Effects on Androgen Status and Prostatic Homeostasis
Authors: Smith Joshua , Ford Nikki , Austin Kathryn , Clinton Steven , Erdman John
Published: June 2021

In human studies, higher serum lycopene (Lyc) levels are inversely associated with risk of prostate cancer, which is driven by androgens. Genomic alterations in carotene‐15,15′‐monooxygenase (BCO1) have been shown to alter Lyc metabolism. However, potential functions of BCO1 beyond carotenoid cleavage are unknown. We hypothesized that Bco1 genotype would interact with dietary Lyc or tomato powder (TP) to alter murine androgen and prostatic biology. We conducted three separate studies in which 9‐ to 14‐week‐old male wild‐type (WT) and Bco1‐/‐ mice were fed AIN‐93G control or diets containing 10% TP or matched levels of Lyc for four days. Across all three studies, we found that Bco1 gene loss significantly (p<0.05) and consistently depressed androgen status and disrupted prostatic homeostasis – independently of Lyc or TP feeding. Loss of Bco1 decreased testicular mRNA expression of 17β‐hydroxysteroid dehydrogenase 3 ‐ a key enzyme in testosterone (T) synthesis ‐ by 29% and reduced serum T levels by 79%. Regardless of diet, the weight of the prostate was reduced by 14‐19% in Bco1‐/‐ mice compared to WT. In agreement with this, Bco1‐/‐ mice demonstrated reduced androgen signaling in the prostate (Msmb mRNA expression, ‐30%, Igfbp3 mRNA expression, +20%) as well as decreased mRNA expression of markers of cellular proliferation (Pcna, ‐12%; Ki67, ‐44%) and cell cycle entry into mitosis (Aurkb, ‐54%; Ccnb2, ‐51%). In summary, BCO1 seems to play a significant role in androgen and prostate physiology independent of its function in carotenoid metabolism.
Wide and Deep Preparation for any Residency? Really?
Authors: Topp Kimberly
Published: June 2021

Standard 7 of the LCME Standards for Accreditation of Medical Education Programs states that, “The faculty of a medical school ensure that the medical curriculum provides content of sufficient breadth and depth to prepare medical students for entry into any residency program and for the subsequent contemporary practice of medicine”. Is it possible to deliver enough curricular content to achieve this standard? Can students achieve competency in knowledge of gross anatomy, histology and embryology, given the small number of hours in integrated curricula common to our present‐day medical schools? Yes, and yes! Previous standards required us to “include” basic science content (ED‐7, ED‐11) and “include” laboratory opportunities (ED‐12). Students struggled to learn all that we were “including”, as we tried to consolidate our course content. The new standard asks us to “support medical students' mastery of contemporary scientific knowledge and concepts” (7.1), and to provide “opportunities for medical students to acquire skills of critical judgment based on evidence and experience” and “use those principles and skills effectively in solving problems of health and disease” (7.4). We will present approaches to help our schools meet Standard 7, the 2015 accreditation standard for curriculum content. We will discuss opportunities for inquiry‐based anatomy education, longitudinal curricula, and clinical skills training designed to advance knowledge of functional anatomy. There are opportunities for interprofessional education, as well as for faculty development, as we assist clinical colleagues recalling details of basic science and provide clinical context for basic science faculty. Furthermore, we must teach with outcomes in mind, and ask the students to learn and demonstrate mastery of anatomical principles in diverse application venues spread throughout the pre‐clinical and clinical years. Success will depend on significant effort toward content coordination in integrated curricula, documentation of educational activities, and student and faculty self‐reflection and growth. Anatomy faculty will need to ensure that anatomy principles are included in contemporary entrustable professional activities.
Developmental context and the genotype‐phenotype map
Authors: Richtsmeier Joan
Published: June 2021

Much of what we know about phenotypic variation comes from the study of mutations and disease phenotypes that arise as genetic and environmental influences interact within a developmental program. These studies routinely analyze disease traits as isolated phenomena. Though of clinical significance, such analyses ignore the importance of developmental context in the production of these traits. Variation in human disease traits is often attributed to genetic background and environmental influences, but when environment and genotype are experimentally controlled in animal models, quantitative analysis of disease phenotypes can reveal persistent variation. Variation is produced at least in part by developmental context, loosely defined as the combination of genetic background and the individual growth trajectory, with growth trajectory driven in part by epigenetic factors that are not under strict genetic control (e.g., rates of cell‐cell and tissue‐tissue interactions). Focusing on a specific disease trait, premature cranial vault suture closure, we use an experimental mouse model system to demonstrate why analysis of the disease phenotype (suture patency) cannot explain the variation observed. In our experience, differences in developmental timing and the interaction of developing tissues contribute to the mechanisms by which phenotypic variation is realized.
From Genotype to Phenotype in the Drosophila Wing
Authors: Houle David
Published: June 2021

The central goal of phenomics is to expand our ability to measure phenotypes. A wider range of phenotypic data is critical to understanding the genotype‐phenotype map, the total set of processes through which genomes shape phenotypes. The evolutionary fate of a DNA variant will depend on its effects on all phenotypes, not just the one we happen to have measured. The causation of key biological phenomena such as natural selection and disease takes place in a continuous phenotype space whose relationship to genomes is only dimly grasped. I describe a systematic approach to the study of the genotype‐phenotype map using phenomic data for one well‐studied model system, the wing of Drosophila melanogaster. We are constructing a Dictionary of Genetic effects by systematically and quantitatively manipulating gene expression, then measuring the resulting effect on the wing phenotype. We demonstrate that the structure of genetic variation from the Dictionary is similar to variation among species, in standing genetic variation, and at the mutational level. This suggests that the map itself is conservative and perhaps the product of natural selection.
Morphological and Population Genomic Analysis Demonstrates that Natural Selection and Neutral Evolutionary Processes Contributed to the Evolution of the Human Skeleton
Authors: Roseman Charles
Published: June 2021

The advent of the post‐genomic era and the concomitant availability of large genome‐wide polymorphism data has opened a new set of perspectives on old problems in the evolution of human phenotypic variation. Matching phenotypic and genomic data at the population level allows for an unprecedented opportunity to separate the effects of natural selection from those of random genetic drift and gene flow on morphological variation. Using this approach, I compare the goodness of fit of a series of models of human phenotypic evolution for both cranial and post cranial characteristics. None of the models traditionally used in the study of human phenotypic evolution are well supported. Models that include both terms reflecting natural selection and the neutral evolutionary processes that arise through human population history are typically the best fit. The complex and multi‐causal nature of human phenotypic evolution means that the study of human adaption needs to take forces of evolution other than natural selection into account through a synthesis uniting genome and phenome.