bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of Instruments to Assess Home Food Environment of Pre‐adolescents: A Pilot Study
Authors: Nepper Martha , Ludemann McKena , Chai Weiwen 
Published: June 2021

ObjectiveTo validate a Home Food Assessment tool (HFA) to evaluate the availability, visibility and accessibility of actual home foods and a 30‐day Home Food Environment Survey (HFES) to assess the foods regularly present in the homes of pre‐adolescents.MethodsThirteen pairs of parents and their children (9 to 12 years) participated in the study. The HFA was completed by the research staff and parents independently for criterion validity. Kappa statistics was used to compare parent and staff reports. Parents also completed HFES during the home visit and one week after for test/retest reliability. Cronbach's alpha was used to test the internal consistency of the instruments.ResultsOf the 23 healthy and unhealthy items from HFA, moderate to outstanding agreement (0.41 – 1.00) between research staff and parents was observed on 21, 14, and 18 items for availability, visibility, and accessibility, respectively. Agreement levels for items of fresh fruits and vegetables ranged from moderate to outstanding (0.41‐1.00), with the exception of four items. Internal consistency for 12 healthy food, 11 unhealthy food, 18 fresh fruit, and 14 fresh vegetable items were 0.94, 0.91, 0.90, and 0.87, respectively. For HFES, test and retest scores were significantly correlated except for two reduced‐fat items. The total scores of the available healthy (r=0.87, P =0.0001) or unhealthy items (r=0.85, P=0.0005) from the HFA were positively correlated to those from HFES.ConclusionOur results demonstrated that HFA and HFES are participant‐friendly, reliable and valid instruments to assess the home food environment of pre‐adolescents. These two instruments complement each other and are useful for future research in exploring the relationship between home food environment and weight status of pre‐adolescents.
The Home Food Environment and a Young Child's Weight Status
Authors: Emond Jennifer , Gilbert‐Diamond Diane , Ma Yu , Grewal Dhrev , Ailawadi Kusum 
Published: June 2021

The majority of a young child's diet is from foods available in the home. We investigated how a home's nutritional profile associates with a young child's weight. Data were from a national household panel completed 2006‐2008. Participants scanned all foods and beverages purchased for the home with a handheld UPC‐barcode scanner and data were linked to a nutritional database. Households completed a survey including demographics, weight and height for all household members. Analyses were limited to families with young children 2‐12 years old with a year of purchase data and complete anthropometric data (N=4,276). A series of adjusted logistic regression models fit the odds of a young child in the home being overweight (蠅85th age and sex adjusted BMI percentile) on the nutritional profile of the home. Households purchased 985 calories in packaged foods per capita daily. Total calories purchased increased with head of household weight status. Thirty‐nine percent of homes had at least one young child who was overweight. In a logistic regression model adjusted for household size, dual vs. single head of household, head of household weight status and total protein and total calories in the home, total levels of fat in the home was statistically, positively associated with a child being overweight. Results were similar when further adjusting for total levels of sodium in the home and sodium was statistically, positively associated with a child being overweight: aOR 4th vs. 1st quartile 1.73 (p=0.001). In conclusion, a greater availability of foods high in fat and sodium in the home may be obesogenic for young children.Funded by Norris Cotton Cancer Center.
A High Throughput Image‐based Screening Reveals Novel Autophagy Inducers For Treating Drug‐Induced Liver Injury
Authors: Li Yuan , McGreal Steven , Zhao Jean , Huang Ruili , Xia Menghang , Ding Wen‐Xing 
Published: June 2021

ObjectiveTo identify novel autophagy modulators using a high throughput image‐based screening and to explore their mechanisms of regulation and the application for drug‐induced liver injury.MethodsThe library of pharmacologically active compounds (LOPAC) was screened in mouse embryonic fibroblasts (MEFs) stably expressing GFP‐LC3. Compounds were tested at different concentrations with or without lysosome inhibitor chloroquine (CQ), and GFP‐LC3 puncta were quantified to measure the autophagic flux. Mechanisms of autophagy induction of several selective positive compounds and the protection against acetaminophen (APAP)‐induced liver injury in mice were determined.ResultsThe primary screening revealed 173 compounds with sufficient hit efficacy. The confirmation study indicated several novel autophagy inducers, inhibitors, and compounds showing dual‐effect at different concentrations. Indatraline hydrochloride (IND), chlorpromazine hydrochloride (CPZ) and fluphenazine dihydrochloride (FPZ) were able to increase autophagy in a dose‐ and time‐dependent manner in MEF and other cancer cells. Mechanistically all three compounds inhibited mTOR, a key regulator of autophagy. Moreover, CPZ significantly suppressed APAP‐induced liver injury either co‐treated with or given 2 hours post APAP administration.ConclusionWe identified known and novel autophagy inducers through the high throughput image‐based screening. CPZ significantly suppressed APAP‐induced liver injury by inducing autophagy.[R01 AA020518, R01 DK 102142, P20 RR021940 (COBRE)]
Picking the PADlock: Chemical Probes to Study the Protein Arginine Deiminases
Authors: Thompson Paul 
Published: June 2021

The Protein Arginine Deiminases (PADs) are a small family of human enzymes that catalyze the post‐translational hydrolysis of arginine residues to generate citrulline. These enzymes are important regulators of gene transcription and their activity is upregulated in multiple inflammatory diseases, including rheumatoid arthritis, ulcerative colitis, and cancer.Herein, I will discuss our efforts to develop chemical probes targeting the PADs and protein citrullination, focusing on our success in validating the PADs as therapeutic targets, as well as our more recent efforts to develop phenylglyoxal based reagents that can be used to readily visualize protein citrullination and identify disease biomarkers. Additionally, I will describe our efforts, both crystallographic and enzymological, to understand how calcium regulates the activity and nuclear localization of PAD2.
Positive Feedback Regulation in Histone Demethylases
Authors: Fujimori Danica 
Published: June 2021

Histone demethylases are chromatin‐modifying enzymes that antagonize lysine methylation. Despite their crucial roles in regulating transcription in physiology and disease, the mechanisms by which demethylases are regulated on chromatin are largely unknown. This is particularly the case for the jumonji subfamily of demethylases, the most recently discovered family of epigenetic enzymes. The need to mechanistically dissect the function of these enzymes rests on evidence that jumonji demethylases are important regulators of transcription in development and differentiation, and that several of these enzymes act as oncogenes.By investigating the regulation of catalysis in demethylase KDM5A, we have uncovered a novel allosteric mechanism that regulates the activity of this enzyme. Specifically, we demonstrated that binding of the product of demethylation catalysis to one of three PHD reader domains in KDM5A strongly stimulates the catalytic activity of this enzyme. Our findings expand the function of reader domains in jumonji demethylases beyond their canonical function in the recruitment. The unprecedented functional coupling between a PHD domain liganded with the demethylation product and a catalytic domain reveals positive feedback regulation and provides a mechanism by which demethylation could spread on chromatin.
Structure and Function of the Protein Arginine Kinase McsB
Authors: Clausen Tim , Broch Trentini Débora , Suskiewicz Marcin 
Published: June 2021

Across evolution, cells adapt their proteome in response to internal and external signals. A simple model of such a process is provided by the heat‐shock response in Gram‐positive bacteria. Importantly, the temperature‐induced adaptation at the transcriptional level is preceded and indeed caused by post‐transcriptional modifications of the existing protein pool. The central player here is the protein kinase McsB that is known to phosphorylate and regulate certain heat‐shock transcription factors.McsB is of great interest for at least two reasons. First, McsB is the only protein kinase shown to phosphorylate arginine residues and, consistently, displays no homology to classic protein kinases. Second, owing to its importance for the virulence of notorious Gram‐positive pathogens such as Staphylococcus aureus and given its unique protein kinase mechanism, McsB represents a promising pharmacological target.In order to investigate the function of McsB, we determined a series of X‐ray structures revealing the molecular mechanism of protein arginine phosphorylation in great detail. This mechanism is not only strikingly different from that of canonical protein kinases, but also is under control of an allosteric coupling between the two protomers of the McsB dimer, as phosphoryl‐transfer at one subunit triggers the product release at the other. Accompanying in vitro and in vivo functional studies of McsB shed further light on its mechanism and elucidate its biological role in coordinating the bacterial heat‐shock response.
Weird Ion…Weird Ion Channels Mediating Resistance to Fluoride Toxicity
Authors: Miller Christopher , Turman Daniel 
Published: June 2021

F‐ specific ion channels of the newly discovered “Fluc” family act as F‐ exporters protect many microorganisms from the toxic effects of this environmentally pervasive halide. The channel is constructed as an four‐TM helix dual‐topology homodimer, in which the two subunits adopt antiparallel orientation within the membrane. We previously used fibronectin domain‐based “monobodies” selected by phage display methods to establish this unusual membrane architecture, showing that these small proteins block single Fluc channels from either side of the membrane. We now ask whether the two blocking sites on opposite sides of the membrane can both be occupied simultaneously by monobodies. Our analysis examines the dependence of single‐channel block‐times as a function of monobody concentration varied symmetrically on the two sides of the channel. If both sides can be blocked symmetrically, a linear blocking scheme should be followed: Open ‐‐‐‐ Block(1) ‐‐‐‐Block(2),Where both blocked states are nonconducting. This scheme makes quantitative predictions for the increase in block‐times with monobody concentration that provide information about any cooperativity, negative or positive, that may operate between the two sites.
MCAT 2015 and the Academy: Undergraduate, Graduate and Health Professional Ramifications
Authors: Brenner Charles 
Published: June 2021

MCAT is a significant driver of undergraduate education because so many students start college with premedical inclinations. Annually, ~500k US students take general chemistry, 165k take organic chemistry, 45k apply to medical schools, 19k matriculate to medical schools, and 18k receive the MD. Because the vast majority of students who begin in the premedical track do something else besides medicine, care should be taken to develop coursework and curricula that effectively educate students in the molecular sciences and keep their options open. The MCAT was last revised in 1991 when it was possible for a skilled molecular biologist to determine human genotypes at 4 genetic loci. Today, a company offers genotyping for 1.2 million SNPs for @99 direct to consumers. In addition, the epidemics of obesity and type 2 diabetes have the potential to drastically alter health care as we know it. These changes in medicine demand a more educated first year medical student, who will need at least a semester of undergraduate biochemistry. In 2012, Dagmar Ringe and I developed the ASBMB premedical curriculum recommendations, which call for molecular genetics inside of the biology requirement, data analysis inside of the laboratory course requirement, a new course in life‐oriented organic chemistry, and 1‐2 semesters of biochemistry. Now armed by data from over 24,000 students who took MCAT 2015 practice questions, we are able to update the Experimental Biology community on student performance vis a vis foundational concepts in biochemistry. We describe changes in undergraduate, graduate, medical and health professional education that are driving substantive changes in biochemistry teaching across the academy.Brenner, C & Ringe, D ASBMB Today 12, n. 3, p. 12, 2012Brenner, C BAMBED 41, p. 1, 2013Brenner, C J Chem Ed 90, p. 907, 2013
Acculturation, Dietary Behaviors, and Body Mass Index among Vietnamese American Adults
Authors: Lam Carolyn , Jasti Sunitha 
Published: June 2021

ObjectiveTo examine the association of acculturation level with dietary behaviors and body mass index (BMI) in adult Vietnamese Americans.MethodsA cross‐sectional online survey assessed acculturation level using the Suinn‐Lew Asian Self Identity Acculturation Scale (SL‐ASIA), dietary behaviors, and the BMI of 257 adult Vietnamese Americans across America.ResultsMean (SD) age was 24(8.45) years, BMI 22.9(4.46) and acculturation 3.08(0.46) on a scale of 1‐5. Vietnamese Americans with lower acculturation scores (<3.1, median) were more likely to report higher consumption of non‐starchy vegetables (p<0.005) and green‐leafy vegetables (p<0.035) than more acculturated Vietnamese Americans. Female gender and being married were also associated with healthier dietary behaviors.ConclusionPublic health campaigns promoting increased consumption of fruits and vegetables targeted to male, unmarried and more acculturated Vietnamese Americans may be beneficial to this population.
Whole Wheat‐supplemented Diet Prevents Risk Biomarkers of Cardiovascular Diseases in Obese Diabetic Mice
Authors: Mohanty Indira , yuan Jialing , Noratto Giuliana , Balemba Onesmo , Morris Craig 
Published: June 2021

Cardiovascular disease (CVD) is the number one cause of death around the world.Our objective was to investigate if whole wheat consumption can delay or prevent the onset of CVD.Obese diabetic (db/db) mice were fed with standard or whole‐wheat supplemented diets ad libitum for eight weeks. The lean counterpart controls were fed standard diet. At the end of the study blood and heart tissues were analyzed for protein expression of risk markers for CVD using standard biochemical and molecular biology procedures.Results show that whole wheat consumption decreased biomarkers of oxidative damage in blood including reactive oxygen species levels in blood erythrocytes and protein carbonyls in plasma. This was accompanied by lower plasma levels of proinflammatory cytokine interleukin‐6 which contribute to endothelial dysfunction in obesity. Accordingly, the nuclear factor‐κB (NF‐κB) pro‐inflammatory transcription factor and NF‐κB‐target TNF‐α were downregulated in heart tissues. The downregulation of inflammatory markers in heart tissues might be correlated with decreased abdominal, subcutaneous, and heart adipose tissues and adipokine resistin, which plays a key role in the alteration of immune and inflammatory processes that favor metabolic disorders and atherosclerosis development. Overall, these results strongly support that whole wheat consumption mitigates the obesity‐induced inflammation and metabolic disorders that promote the onset of CVD.
Relations to Cognitive Change with Age of Micronutrients Found in Green Leafy Vegetables
Authors: Morris Martha Clare , Booth Sarah , Dawson‐Hughes Bess , Barnes Lisa , Bennett David , Wang' Yamin 
Published: June 2021

Consumption of green leafy vegetables has been reported to reduce cognitive decline in older adults. We investigated the relations to cognitive decline of various micronutrients for which green leafy vegetables are a rich dietary source, including phylloquinone (vitamin K), folate and carotenoids (lutein, lycopene, beta‐cryptoxanthin, alph carotene, beta carotene), in a cohort study of 954 participants of the Memory and Aging Project, mean age 81 years, 75% female. Diet was assessed by a 144‐item semi‐quantitative food frequency questionnaire. Energy‐adjusted nutrients were modeled in quintiles. Cognition was assessed annually by a battery of 19 tests. Nutrient intakes were related to change in cognitive function over a mean 4.5 years using linear‐mixed models adjusted for age, sex, education, and participation in cognitive activities. Higher green leafy vegetable consumption was associated with slower cognitive decline (β=0.033, SE=0.010, p=0.001). In analyses of micronutrients, we observed slower rates of cognitive decline for food folate (Q5 vs Q1 β=0.044, p=0.004), phylloquinone (Q5 vs Q1 β=0.040, p=0.001), lutein (Q5 vs Q1 β=0.039, p=0.001), and total beta carotene (Q5 vs Q1 β=0.029, p=0.01). No associations were observed for lycopene, alpha carotene, or beta‐cryptoxanthin. Cognitive decline in older adults may be slowed through the consumption of green leafy vegetables rich in folate, phylloquinone, lutein and beta carotene.Supported by grants R01 AG031553 and R01 AG17917
Serum Micronutrient Status during Pulmonary Exacerbation and Following Recovery in Adults with Cystic Fibrosis
Authors: Lee Moon Jeong , Smith Ellen , Ziegler Thomas , Alvarez Jessica , Tangpricha Vin 
Published: June 2021

ObjectivePatients with cystic fibrosis (CF) may be at risk for micronutrient depletion, particularly during periods of acute illness and infection. The purpose of this study was to investigate serum micronutrient status over time in adults with cystic fibrosis hospitalized with a pulmonary exacerbation.MethodsThis was an ancillary study of a multi‐center trial investigating the role of high‐dose vitamin D supplementation in adults with CF. We measured serum micronutrient concentrations in subjects during a pulmonary exacerbation (baseline) and again three months later. Serum calcium (Ca), copper (Cu), iron (Fe), potassium (K), magnesium (Mg) and sulfur (S) concentrations were measured using inductively‐coupled plasma‐atomic emission spectrometry. Statistical analyses included paired t‐tests.ResultsSubjects were 24 hospitalized adults with CF (mean age 28.4 ± 7.4 yr). At baseline, CF subjects exhibited significantly lower mean serum concentrations of Ca (9.8 ± 0.8 vs. 10.8 ± 2.0 mg/dL, p<0.05), Cu (1.5 ± 0.6 vs. 1.6 ± 0.6 μg/mL, p<0.05), and Fe (0.8 ± 0.3 vs. 1.3 ± 1.1 μg/mL, p<0.05) compared to levels obtained 3 months following the pulmonary exacerbation. Serum concentrations of K, Mg, and S did not change over time. (K: baseline, 4.9 ± 0.3 vs. three months, 5.1 ± 0.5 mEq/L; Mg: 1.8 ± 0.2 vs. 2.0 ± 0.3 mg/dL; S: 1288.6 ± 343 vs. 1309.9 ± 290 μg/mL; p>0.05 for all).ConclusionsSerum concentrations of calcium, copper and iron increased significantly several months following recovery from acute pulmonary exacerbation in adults with CF. This may reflect decreased inflammation, improved food intake and/or increased absorption following recovery.Supported By: CF Foundation and National Institutes of Health
Co‐administration of a Grape Seed Procyanidin Extract and the Bile Acid Sequestrant, Cholestyramine, Results in Beneficial Metabolic Alterations, Including Decreased Triglyceride Levels
Authors: Heidker Rebecca , Caiozzi Gianella , Ricketts Marie‐Louise 
Published: June 2021

Bile acid (BA) sequestrants, used to lower cholesterol levels, may be taken alone or in combination with cholesterol‐lowering medication. We previously showed that grape seed procyanidin extract (GSPE) reduces enterohepatic BA recirculation as a new mechanism to reduce serum triglyceride (TG) levels. This study aimed to determine the effects of co‐administering an acute dose of GSPE with the BA‐binding resin cholestyramine (CHY) on TG levels and BA homeostatic gene expression. Eight‐week old C57BL/6 mice were treated for 4 weeks with a control diet, or a 2% CHY‐supplemented diet, after which, they were administered vehicle or GSPE (250mg/kg) for 14 hours. Tissues were harvested and gene expression levels were analyzed via qPCR. Biochemical analysis was performed to assess serum BA and TG levels. Data were analyzed using one‐way ANOVA. Results show that CHY‐GSPE co‐administration reduces intestinal IBABP (61%, p<0.0001) and FGF15 (99.5%, p<0.0001) expression, relative to control. In addition serum BA levels were decreased 74% (p<0.0001), while hepatic CYP7A1 expression was increased 13‐fold (p<0.0001), indicative of increased BA synthesis. SREBP1c expression was reduced 42% and serum TG levels were decreased 34% in the CHY‐GSPE group, compared to control. We present novel evidence showing that GSPE works synergistically with CHY to lower serum TG levels, which is achieved via enhanced de novo BA biosynthesis.
Discrete Functions Of GSK3α And GSK3β Isoforms In Prostate Tumor Growth And Micrometastasis
Authors: Gao Fei , Al‐Azayzih Ahmad , Shenoy Somanath P.R. 
Published: June 2021

ObjectiveRole of glycogen synthase kinase‐3 (GSK3) in cancer is controversial and the isoform specific function of GSK3 in cancer is not well defined. The present study aims to explore the discrete functions of GSK3α and GSK3β in prostate cancer growth and metastasis. Methods and ResultsWe report that silencing the expression of GSK3α or GSK3β isoforms inhibit overall growth and proliferation of the metastatic prostate cancer cells with a predominant role of GSK3α isoform in the process. Deficiency of GSK3α, but not GSK3β inhibited colony formation by the PC3 and DU145 metastatic prostate cancer cells, and the growth of PC3 tumor xenografts in athymic nude mice. Despite the modest effect of GSK3β knockdown on the cell proliferation in vitro, knockdown of GSK3α, but not GSK3β resulted in reduced proliferation and enhanced apoptosis in tumor xenografts in vivo. ShRNA‐mediated knockdown of GSK3α and GSK3β equally inhibited the ability of PC3 cells to migrate and invade the endothelial‐barrier in vitro, and micrometastasis in vivo. Mechanistically, whereas silencing GSK3α resulted in increased expression of pro‐apoptotic markers cleaved caspase‐3 and cleaved caspase‐9 in both PC3 and DU145 cells, silencing GSK3β resulted in the inhibition of cell scattering, establishment of cell‐cell contacts, increased expression and membrane localization of β‐catenin, and reduced expression of epithelial to mesenchymal transition (EMT) markers such as Snail and MMP‐9 indicating specific role for GSK3β in EMT, and acquisition of motility and invasive potential. ConclusionsThe isoform specific role of GSK3α and GSK3β in prostate cancer cells in vitro, and tumor growth and micrometastasis in vivo, via distinct molecular and cellular mechanisms.