bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gamma‐tocotrienol antagonizes adipogenesis through activation of AMPK/autophagy axis in primary human adipocytes
Authors: Zhao Lu , Ha Jung‐Heun , Kang Inhae , Okla Meshail , Chung* Soonkyu 
Published: June 2021

Tocotrienols are a subclass of vitamin E, exerting stronger biological activity than tocopherols. In particular, gamma tocotrienol (γT3) possesses potent anti‐inflammatory and anticancer properties by modifying multiple signaling pathways. However, little is known about the effects of T3 on adipogenesis. The aim of this study was to investigate the anti‐adipogenic effects of γT3 in primary human adipose‐derived stem cells (hASCs). Here, we showed that γT3 specifically inhibits early stage adipocyte differentiation by acting on downstream of C/EBPβ, but upstream of C/EBPα Inhibition of adipogenesis by γT3 was confirmed by dramatic decreases in adipogenic gene, protein and TG accumulation. Interestingly, γT3 reduced anabolic signaling of Akt/mTOR, but activated catabolic signaling of AMPK. Inhibition of AMPK via adenoviral delivery of the mutant form of AMPK partly restored the adipogenic gene and adipocyte morphology. Unexpectedly, γT3 promoted an abnormal increase in LC3II formation, suggesting that AMPK activation may subsequently induce autophagy. Continuous exposure of γT3 eventually led to an apoptotic cell death by increasing PARP cleavage and caspase‐3 activation. Collectively, our work demonstrated that γT3 antagonizes adipogenesis in hASCs by triggering multiple signaling pathways of growth inhibition, including activated AMPK/autophagy axis and apoptosis.Grant Funding Source: NIH NCRR
Associations among body mass index, waist circumference, dietary factors and cardiometabolic risks in 10th grade students: The NEXT Generation Health Study
Authors: Pratt Charlotte A , Iannotti Ronald J , Li Kaigang , D'Elio MaryAnn , Olson Sarah , Lipsky Leah , Simons‐Morton Bruce , Fan Ruzong 
Published: June 2021

ObjectiveTo identify associations among body mass index (BMI), waist circumference (WC), dietary factors and cardiometabolic indicators in US adolescents.ApproachA random sample of overweight (N=282) and normal‐weight (N=278) 10th‐grade students at baseline of the NEXT Generation Health Study.ResultsLow density lipoprotein cholesterol (LDL‐C), high density lipoprotein cholesterol (HDL‐C), triglycerides (TG), total cholesterol (TC), diastolic blood pressure (DBP), mean arterial pressure (MAP), WC, hemoglobin A1C, C‐reactive protein (CRP), uric acid and serum fructose were significantly higher in overweight 10th graders than in normal weight. Overweight youth had 2.4 unit higher DBP than normal weight. Controlling for covariates, BMI percentile was significantly associated with WC (B=0.03, p<.001), DBP (= 0.06, p<.01), MAP (B=0.06, p<.001), TC(B = 0.01, p<.01), LDL‐C (B = 0.01, p<.01), HDL‐C (B=− 0.002, p<.001), CRP (B=0.02, p<.01), and uric acid (B=0.01, p<.01). Tenth graders with WC ≥90th percentile had significantly higher metabolic indicators. SBP was associated with intake of added sugar (B=0.09, p<.03) but not with sodium or solid fats.ConclusionThese findings underscore the role of obesity in increasing cardiovascular disease (CVD) risk factors and a need for interventions that target high school students to prevent further CVD risks.Grant Funding Source: This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Developmentand the National Heart, Lung, and Blood Institute (Contract #HHSN2672008000009c).
The developmental basis for jaw size variation in evolution and disease
Authors: Fish Jennifer L , Sklar Rachel S , Woronowicz Katherine C , Schneider Richard A 
Published: June 2021

Variation in jaw size was critical for the adaptive evolution of vertebrates, yet variation during development is often associated with disease. To test the hypothesis that NC progenitor number and proliferation rates contribute to variation in jaw size, we compared NC development in two birds with distinct jaw size, duck and quail. At stage HH10, duck and quail embryos have substantial differences in brain shape and expression of the brain regionalization genes, Pax6, Otx2, Fgf8, and Krox20. There is no significant difference in Pax7‐postive NC precursors in HH8 duck and quail embryos. But by HH13, duck embryos have nearly twice as many Dlx2‐positive NC in their jaw primordia as do quail, a ratio which is maintained in HH20 embryos. At HH20, quail NC divide 1.4 times faster than duck NC, however, quail embryos also develop 1.6 times faster during this developmental window. After reduction of NC precursors, post‐migratory NC compensate within the jaw primordia to produce a symmetric and relatively normally sized jaw. Importantly, while chick undergo complete compensation, ablated duck embryos form slightly smaller than normal jaws. Our results suggest that modification of multiple aspects of NC cell biology was important to the evolution of large jaw size. Further, our finding of compensatory mechanisms opens avenues for treatment of disease associated with NC progenitors loss.Grant Funding Source: none
Biochemical and metabolomic effects of perinatal choline deficiency in the piglet
Authors: Getty Caitlyn M , Dilger Ryan N 
Published: June 2021

Choline plays an essential role in tissue development during gestation and early postnatal life, and the piglet (Sus scrofa) may serve as a translational animal model to study perinatal effects of choline deficiency. Our objective was to determine developmental changes in piglets exposed to differing levels of choline both prenatally and postnatally. A factorial arrangement of choline sufficient (CS; 50% above requirement) and choline deficient (CD; 50% below requirement) diets were provided during the prenatal (last 65 d of gestation) and postnatal (48 h after birth through 28 d of age) periods. An interactive effect of choline level and perinatal period was observed for body weight gain (P < 0.001), and prenatal CD piglets had smaller (P = 0.014) brains than prenatal CS piglets. Blood chemistry panels revealed generalized impairments in liver function in postnatal CD piglets. Overall, metabolomic analysis identified 276 biochemicals and revealed that choline deficiency in the pre‐ and postnatal periods altered plasma levels of metabolites related to choline biosynthesis, glycolysis, and lipid metabolism. Additionally, interactive effects were noted for glycolytic intermediates, carnitine‐related metabolites, and many choline‐containing lysolipids. We conclude that the piglet is a sensitive animal model for studying developmental aspects of perinatal choline deficiency.U.S. Department of Agriculture Hatch Project ILLU‐538–319
Influence of a polyphenol‐enriched protein powder on exerciseinduced inflammation and oxidative stress in athletes: a metabolomics approach
Authors: Nieman David Christopher , Knab Amy , Shanely R. Andrew , Cialdella‐Kam Lynn , Gillitt Nicholas , Pappan Kirk , Lila Mary Ann 
Published: June 2021

Polyphenol intake was tested as a countermeasure to inflammation and oxidative stress induced by 3‐d intensified training. A soy protein isolate matrix was sorbed with polyphenols (SPMP) from blueberry and green tea extracts (2,136 mg/d gallic acid equivalents). Runners (N=31) were randomized to 40 g/d SPMP or placebo for 17 d using double‐blinded methods, with 3 d running inserted at day 14 (2.5 h/d, 70% VO2max). Blood samples were collected pre‐ and post‐14 d supplementation, and immediately and 14 h after the third day of running, and analyzed at Metabolon (Durham, NC) using GC‐MS and LC‐MS. Metabolites characteristic of gut bacteria metabolism of phenolics were increased with SPMP (e.g., hippurate, catechol sulfate, 4‐methylcatechol sulfate,1.8‐, 1.7‐, 2.5‐fold, respectively, P<0.05), an effect which persisted for 14‐h recovery. Fatty acid oxidation and ketogenesis were induced by exercise in both groups, with more ketones at 14‐h recovery in SPMP (3‐hydroxybutyrate, 1.8‐fold, P<0.05). Traditional biomarkers for inflammation (CRP, cytokines) and oxidative stress (protein carbonyls) did not differ between groups. In conclusion, 17‐d SPMP enhanced ketogenesis and fat oxidation in runners during recovery from 3‐d heavy exertion, and was linked to a gut‐derived phenolic signature that may exert anti‐oxidative and anti‐inflammatory effects not captured by typical biomarkers.Funded by Dole Foods
The association between seafood consumption and blood mercury levels in adults age 20 years and up, 2007–2010
Authors: Nielsen Samara Joy , Kit Brian K. , Ogden Cynthia L. 
Published: June 2021

BackgroundSeafood is a dietary source of mercury, a neurotoxin with adverse health consequences. No previous studies have examined associations between seafood consumption and blood mercury in the entire US adult population.ObjectiveTo determine the association between seafood consumption and blood mercury levels in US adults, using the most recent national data.DesignAdults, ages 20 years and older, who participated in the 2007–2010 National Health and Nutrition Examination Survey. Frequency of fish and/or shellfish (seafood) consumption was determined using a limited food frequency questionnaire over the past thirty days. Geometric mean blood mercury levels for quartiles of seafood consumption were calculated overall and by sex. Trends in mean mercury levels by quartile of seafood consumption were tested using linear trend tests.ResultsThere was a positive linear trend in blood mercury as seafood consumption increased (p<.001 for all trends). Geometric mean blood mercury was 0.5 ug/L among the lowest consumers of seafood compared to 2.1 ug/L among the highest consumers. Trends for men and women separately were also significant (p<.001).ConclusionIn the US adult population blood mercury levels are highest among those who consume the largest amounts of seafood.
Association of serum 25OHD with race/ethnicity and quantitative measures of skin color in urban schoolchildren
Authors: Au Lauren Elizabeth , Harris Susan S , Dwyer Johanna T , Jacques Paul F , Sacheck Jennifer M 
Published: June 2021

To determine the extent to which differences in skin color explain racial/ethnic differences in serum 25OHD levels in urban schoolchildren. Multivariate regression was used to determine associations of serum 25OHD, race/ethnicity and skin color, measured by reflectance colorimeter [Individual Typology Angle (ITA°, higher value corresponds to lighter skin)], in 307 schoolchildren aged 9–15 from the Boston area during winter. Nearly 60% of all children had inadequate 25OHD (<20 ng/mL) and only 5% achieved optimal 25OHD status (≥30 ng/ml). Prevalence of inadequate 25OHD differed by race/ethnicity (P<0.001): white (47%), black (74%), Hispanic (65%), Asian (89%), multi‐racial/other (53%). Mean (SD) ITA° skin color also varied by race/ethnicity (P<0.001): white 50.1° (10.1), black −10.7° (25.2), Hispanic 34.1° (10.7), Asian 28.7° (14.6), multi‐racial/other 31.3° (14.9). Serum 25OHD increased 0.6 ng/mL per 10° increase in ITA° value (P<0.001). However, addition of skin color to models that included race/ethnicity did not increase explanatory value of the model (R2 for models with and without skin color were 0.19). Most urban schoolchildren had inadequate 25OHD, but prevalence of inadequate status was higher in racial/ethnic minorities. Objective measures of skin color did not explain additional variability in 25OHD beyond that explained by parent‐reported race/ethnicity. Supported by NIH/ODS #3R01HL106160.Grant Funding Source: NIH/ODS #3R01HL106160
Bone loss during hematopoietic cell transplantation (HCT) in children
Authors: Bechard Lori J. , Feldman Henry A. , Gura Kathleen , Venick Robert , Guinan Eva C. , Gordon Catherine , Duggan Christopher 
Published: June 2021

HCT may be deleterious to bone health and vitamin D status in children, but longitudinal studies are few. We conducted a multicenter, prospective cohort study to define time related changes in bone health markers during the first 100 days following allogeneic HCT in 26 children. Bone mineral density (BMD), bone mineral content (BMC), bone‐specific alkaline phosphatase (BSAP) and serum 25‐hydroxyvitamin D (25‐OHD) concentrations were measured at baseline, 30 days, and 100 days after HCT. Mean BMD and BMC Z‐scores (mean ± SD, −0.48 ± 1.09 and −0.59 ± 1.36, respectively) were normal at baseline. Repeated‐measures analysis revealed a 0.5 decline in BMD Z‐score (p<.0001) over the 100 day study period, when adjusted for age, sex, Tanner stage, lean mass, fat mass, resting energy expenditure, total energy intake, insulin sensitivity, and serum phosphorus. BMC and BSAP concentrations also declined significantly. Adjusted mean (SE) serum 25‐OHD concentrations declined from 30.1 ± 2.9 ng/ml at baseline, to 18.9 ± 2.0 ng/ml at 100 days after HCT. At 100 days after HSCT, 50% of patients were vitamin D deficient (serum 25‐ OHD <20 ng/ml). Significant bone loss and vitamin D deficiency occur in children in the first 100 days following allogeneic HCT. Strategies to attenuate acute bone loss in this setting are needed.Grant Funding Source: This project was supported by the Massachusetts Vitamin Litigation Grant and NIH grants M01‐ RR02172, UL1 RR025758–01, M01‐RR00865, M01‐RR00188, and K24 HD 058795.
Rotation and reorganization of dissection groups promotes professionalism and enhances cadaver based learning
Authors: Mork Amy Lovejoy , Klement Brenda , Paulsen Douglas F. , Wineski Lawrence E. 
Published: June 2021

In order to promote both professionalism and exposure to human anatomical variation, the integrated first year medical curriculum at Morehouse School of Medicine has developed a program combining periodic dissection group rotation and reorganization with regular group quizzes. Reorganization involves changing the membership of each dissection team; rotation involves moving teams to new cadavers. Group quizzes are shared scoring demonstrations of each team's dissections. Group restructuring ensures each dissecting team is composed of academically and demographically diverse individuals, repeatedly introducing students to new learning cohorts. Unlike traditional static group assignments, dissection team reorganization advances professionalism by tightly linking individual and group responsibility and accountability, emphasizing cooperative work habits within shifting environments, and underscoring the need for ongoing development of interpersonal communication and tolerance. Dissection of multiple cadavers throughout the course highlights human anatomical variation, one of the major educational benefits of cadaver based gross anatomy. Group quizzes serve to further promote cooperative engagement in active learning and support among group members. Student buy‐in to this methodology has been very positive, and we regard this dissection system as highly successful.Grant Funding Source: Supported in part by NIH PO3 1B04017 and G12‐RR 03034
Nutrition in Medicine: Effectiveness of a web‐based curriculum for obstetrics and gynecology residents
Authors: Kaplan Barrie Suskin , Karkowsky Chavi Eve , Kohlmeier Martin , Dayal Ashlesha , Chazotte Cynthia , Landsberger Ellen 
Published: June 2021

OBJECTIVESTo assess the effectiveness and feasibility of a web‐based nutrition education curriculum on improvement of clinical practice skills of Obstetrics and Gynecology (OBGYN) residents.STUDY DESIGNPre & post‐intervention surveys compared practices and confidence level of OBGYN residents for nutritional issues before and after an interactive web‐based nutrition curriculum*. The intervention consisted of 3 modules from the Nutrition in Medicine/Nutrition Education for Practicing Physicians program. Data was analyzed using paired T tests & chi‐square tests for non‐paired categorical variables. P value <0.05 was considered significant.RESULTS36/44 of the residents participated. After completing the modules, residents reported they were more likely to complete many of the discussed skills. Provider confidence in counseling regarding nutritional issues improved in all areas. More residents were willing to refer patients to bariatric surgery. 35/36 found the modules informative and most (86.1%) believed their clinical skills improved.CONCLUSIONThe web‐based nutritional curriculum improved the clinical skills of OBGYN residents. This is a feasible and acceptable method of learning for practicing physicians.
The Metabolic Fingerprints of Prostate Cancer
Authors: Priolo Carmen , Pyne Saumyadipta , McDunn Jonathan , Rose Joshua , Ravasz Erzsebet , Zadra Giorgia , Photopoulos Cornelia , Scaglia Natalia , DeMarzo Angelo , Loda Massimo 
Published: June 2021

Cancer cells undergo profound metabolic changes as a result of either abnormal signaling pathways or mutations occurring in genes encoding metabolic enzymes. A fundamental unanswered question is whether all oncogenic drivers harness a similar metabolic response or whether each oncogenic event results in its own specific metabolic program.Mass spectrometry‐based metabolomics was performed on immortalized human prostate epithelial cells transformed by the MYC and Akt oncogenes, transgenic mice driven by the same oncogenes under the control of a prostate‐specific promoter and human prostate tumors that were characterized for the expression and activation of these proteins, respectively. Genomic and gene expression analyses of the prostate tumors were also carried out. Through metabolite profiling and metabolite set enrichment analysis ran across the three datasets (human prostate cells, transgenic mice and human prostate tumors), we found that Akt1 drives primarily aerobic glycolysis while MYC does not elicit a Warburg‐like effect and significantly enhances glycerophospholipid synthesis instead. This regulation is Gleason grade‐ and pathological stage‐independent.Our data provides evidence that prostate tumors exhibit metabolic fingerprints of their molecular phenotypes, which may have significant impact on both diagnostics and targeted therapeutics.Funding: NIH/NCI R01 CA131945
Evidence of autophagy activity in stage V seminiferous epithelium
Authors: Young J'Nelle (Ellie) , Saber Nelly , Vogl A. Wayne 
Published: June 2021

Autophagy involves the breakdown of cytosolic components in conjunction with lysosomes. In this study, we test the prediction that tubulobulbar complexes (TBCs) formed by Sertoli cells in rat testes are associated with autophagy. TBCs are cytoskeleton‐related structures that are formed in association with intercellular junctions in the seminiferous epithelium (SE). TBCs are most defined at apical junctions between Sertoli cells and spermatids, although they also are found at basal junctions between adjacent Sertoli cells. TBCs contain a tubular region surrounded by a cuff of actin and a distal region that is associated with cisternae of endoplasmic reticulum. Mounting evidence suggests that Sertoli cells internalize junction proteins via the budding off of double‐membrane vesicles from TBCs followed by fusion with lysosomes resulting in degradation or recycling of junction proteins to newly forming junctions. We used immunological probes to explore the potential of autophagy activity in the SE. Immunostaining of the epithelium suggests that autophagy marker LC3A is not present at apical TBCs in rat testes as predicted but rather, is present elsewhere in the cells, particularly during Stage V of spermatogenesis. Our results indicate that autophagy is not associated apical junction disassembly in Sertoli cells.Grant Funding Source: NSERC
The role of APOE genotype on neuropathological changes in human's olfactory bulb
Authors: Aboud Orwa , Griffin Sue T , Biedermann JoAnn , Mrak Robert E 
Published: June 2021

Changes in olfaction often precede clinical signs and symptoms of Alzheimer's disease (AD) and other neurodegenerative disorders. We have shown self‐propagating cycles in which proinflamatory cytokines IL‐1 and S100B induce each other in glia and induce excess expression of the precursors of Aβ plaques and neurofibrillary tangles.Anatomical and pathological features were determined in frozen and paraffin‐embedded tissue sections of olfactory bulbs resected from autopsy tissue of 15 patients (5 APOE ε3,3 neurologically normal, 5 APOE ε3,3 and 5 APOE ε4,4 AD patients) with an age range from 68 to 85 yrs.Microscopical assessment of the olfactory bulb showed that there were fewer glomeruli and the glomerular layer was thinner in AD patients than in controls. Olfactory bulbs of all APOE ε4,4 AD patients had many Aβ plaques, and most of them were “senile” type, mature dense core neuritic plaques compared to the diffuse non‐neuritic plaques present in some APOE ε3,3 AD patients. Neurologically normal controls had fewer plaques than AD, and those plaques were of the diffuse, non‐neuritic type, and there were fewer activated GFAP immunoreactive glia overexpressing S100B than were present in either of the AD patient groups.Our findings suggest that olfaction should be tested and noted for assessing the disease progression, especially in those with APOE ε4,4 genotype.Grant Funding Source: NIA‐AG12411 and the Windgate Foundation
A potential role for LIM protein Ajuba in repression of DNA damage response in human cells
Authors: Kalan Sampada , Matveyenko Anastasiya , Loayza Diego 
Published: June 2021

Mammalian telomeres are specialized DNA‐protein structures located at each end of chromosomes. Telomeric DNA is bound by a six‐protein complex called shelterin, which prevents DNA damage response activation at the ends.In addition to shelterin, several accessory proteins associate with telomeres and assist in proper functioning of the complex. Our laboratory has discovered interaction between shelterin and LIM domain proteins. Of those, TRIP6 and LPP participate in the repression of the DNA damage response at telomeres.Here, using immunoprecipitation, we show that another LIM protein, Ajuba, associates with POT1 in tumor cells. Ajuba was detected at telomeres by chromatin immunoprecipitation. We also discovered that depletion of Ajuba by siRNA caused decrease in cell proliferation and increase in DNA damage response. An overall increase in p53‐BP1 damage foci was observed in nuclei of Ajuba‐depleted cells. By using FACS analysis, we observed an accumulation of cells in S phase. An activation of p53 with concomitant hyperphosphorylation of Rb was observed. Our results point to a vital role of Ajuba in the repression of endogenous DNA damage response in tumor cells, and could provide insights in understanding of senescence or immortalization of human cells.This research was funded by National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH).