bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship Between Breast Feeding and Eating Patterns in a Rural, Mexican‐origin Population during a Nutrition Intervention
Authors: Cabrera Roxana , Aguilera Alberto Leopoldo , de la Torre Adela , Kaiser Lucia Lynn 
Published: June 2021

Breastfeeding has demonstrated a promising effect on health outcomes later in life. European cohort studies have found a positive relationship between exclusive breastfeeding and increased fruit and vegetable (F/V) intake in children. The purpose of this study was to observe the relationship between retrospectively parent‐reported breastfeeding practices and eating patterns in young Mexican‐origin children. The Niños Sanos, Familia Sana (Healthy Children, Healthy Family) study is a multi‐year intervention aimed at reducing obesity and increasing F/V consumption among Mexican‐origin children. Participants included 172 mother and child dyads (ages 3–8 years) from a rural community in California. Spanish‐speaking interviewers asked mothers to recall breastfeeding practices during the first year of life. Breastfeeding practices were defined as: “Not breastfed” if child never breastfed and/or formula fed only; “Combined feeding” if formula fed and breastfed < 6 months; and “Exclusively breastfed” if breastfed for ≥ 6 months and child not formula fed until after age of 6 months or older. Eating patterns were assessed using a 26‐item food frequency questionnaire. An analysis of variance examined changes in vegetable intake over a 2‐year period by intervention group and breastfeeding practices. Preliminary results show a significant positive independent effect of exclusive breastfeeding on more frequent vegetable intake (F= 3.64, p=0.014). These results need to be confirmed by biomarkers or other measures of vegetable intake.Support or Funding InformationFunded by USDA‐NIFA Fund number: 82705
Improvement in Long‐term Household Food Security among Indiana Households with Children did not Differ between Rural and Urban Counties after a Supplemental Nutrition Assistance Program‐Education Intervention
Authors: Rivera Rebecca L , Maulding Melissa K , Abbott Angela R , Wang Qi , Eicher‐Miller Heather A 
Published: June 2021

ObjectiveTo determine the relationship of rural and urban county household status to long‐term food security among households with children in Indiana after a Supplemental Nutrition Assistance Program‐Education (SNAP‐Ed) intervention.MethodsA randomized, controlled parallel nutrition education intervention study using SNAP‐Ed as the intervention was implemented across 38 Indiana counties from August 2013 to March 2015. Study participants (n=575) were low‐income SNAP‐Ed eligible adults ≥ 18 years with ≥ 1 child living in the household. SNAP‐Ed paraprofessionals recruited and randomized participants to either the control or intervention treatment group. Intervention group participants received at least the first 4 SNAP‐Ed lessons over an intervention period of 4–10 weeks. All participants completed a baseline, post‐intervention, and 1 year follow‐up assessment. Food security score was assigned using the 18‐item United States Household Food Security Survey Module. Urban or rural county status was assigned using the classifications provided by the United States Office of Management and Budget. A linear mixed regression model adjusted for household characteristics and urban or rural county status was included as an independent variable to compare study treatment group and urban or rural county status effects over time on food security.ResultsRural or urban county status was not significantly associated with improvement in household food security score from baseline to 1 year follow‐up assessment (p=0.6).ConclusionSNAP‐Ed was consistently effective at improving long‐term food security between rural and urban county Indiana households with children.Support or Funding InformationFunding: This project was supported with a grant from the University of Kentucky Center for Poverty Research through funding by the U.S. Department of Agriculture, Food and Nutrition Service, contract number AG‐3198‐S‐12‐0044.
Obesogenic diets enriched in oleic acid vs saturated fatty acids differentially modify polyunsaturated fatty acid composition in liver and visceral adipose
Authors: Picklo Matthew , Murphy Eric 
Published: June 2021

Emerging evidence indicates that the fatty acid composition of obesogenic diets impacts physiologic outcomes. Much attention is focused on the biologic effects of consuming monounsaturated fatty acids (MUFA) vs saturated fatty acids (SFA). We investigated the extent to which an obesogenic diet high in MUFA vs SFA modified lipid composition in liver and visceral adipose tissue with a focus upon polyunsaturated fatty acids (PUFA).Adult male mice were fed (8 wks) (1) a control 16% fat energy (en) diet with 6% en MUFA as oleic acid (18:1n‐9) and 4 % en SFA, (2) a 50% fat en high MUFA diet with 33% en MUFA and 10% en SFA, or (3) 50% a high SFA diet with 9% en MUFA and 33% en SFA. Intake of linoleic acid (LA; 18:2n‐6) and alpha‐linolenic acid (ALA;18:3n‐3) were kept constant at 3% en and 2% en, respectively. By the end of the study, mice on the high MUFA diet were heavier with a higher total fat content and liver mass than the control mice.Total hepatic fatty acid content was elevated (78%) in the high MUFA group only, mostly as a result of oleic acid (18:1n‐9) in the neutral lipid fraction. ALA content was lower (30%) in the high MUFA group than the low fat and high‐SFA‐fed mice. However, both high fat diets elevated hepatic content of arachidonic acid (ARA; 20:4n‐6) by 10% and docosahexaenoic acid (DHA; 22:6n‐3) by 48% (MUFA group) and 22% (SFA group).Epididymal adipose tissue mass was 45% higher in both high fat groups than the control group. When evaluated as amount/gram tissue, the content of LA, ALA, ARA, and DHA was reduced by both high fat diets. However, the high MUFA diet caused a greater reduction in ALA and LA than the SFA diet. Normalizing PUFA content to the entire adipose depot mass removed the reductions in ARA and DHA in both groups. While normalization yielded similar levels of ALA and LA in the SFA group compared to the controls, ALA and LA contents were still lower in the entire epididymal adipose pool in the MUFA group.These data indicate that dietary MUFA and SFA in high‐fat diets impact hepatic and adipose PUFA metabolism. These data indicate that these obesogenic diets, at least in the short term, increase long chain PUFA content in liver. Moreover, these data show that MUFA has selective effects upon PUFA distribution in adipose tissue.Support or Funding InformationUSDA/ARS funding
Javamide‐I found in coffee is a potent p38 MAP kinase inhibitor suppressing MCP‐1 expression significantly in LPS‐stimulated monocytic THP‐1 cells
Authors: Park Jae , Wang Thomas 
Published: June 2021

Monocyte chemotactic protein‐1 (MCP‐1) is an inflammatory cytokine, profoundly implicated in pathogeneses of several chronic diseases such as rheumatoid arthritis, atherosclerosis, CVD and CKD. Coffee is one of most consumed drinks worldwide with potential health effects. Javamide‐I (N‐coumaroyltryptophan) is a phenolic amides found in coffee, which is believed to contain some important biological activities including anti‐inflammatory activity. However, its anti‐inflammatory actions have not been fully investigated related to MCP‐1. Interestingly, p38 MAP kinase plays a crucial role in regulating the production of several pro‐inflammatory cytokines including MCP‐1. Therefore, blocking p38 kinase may offer an effective therapy for treating many inflammatory diseases. Therefore, in this study, potential effects of javamide‐I on p38 MAP kinase and the production of MCP‐1expression were investigated in LPS‐stimulated monocytic THP‐1 cells. Javamide‐I was able to inhibit p38 MAP kinase, and also showed noncompetitive inhibition of p38 MAP kinase against ATP. In supporting the inhibition, a docking simulation showed stronger binding pose of javamide‐I to p38 MAP kinase than SB‐203580. Additionally, javamide‐I decreased ATF‐2 phosphorylation in LPS‐stimulated monocytic THP cells. Consequently, the treatment of javamide‐I (1–20 μM) showed significant decrease not only in the expression of MCP‐1 mRNA but also the production of MCP‐1 protein in the stimulated cells (P < 0.05). In addition, in this study, potential effects of javamide‐I on NF‐kB and other MAP kinases will be also discussed related to MCP‐1 expression.Support or Funding InformationUSDA
The Role of NADPH Oxidase Isoform 1 (NOX1) in L‐NAME‐Induced Leukocyte‐Endothelial Interactions in Rat Mesenteric Postcapillary Venules
Authors: Zabrecky Alita , Pham Hung , Koon Amber , Rueter Brian , Barsotti Robert , Young Lindon , Chen Qian 
Published: June 2021

Vascular endothelial dysfunction and subsequent inflammation underlie many pathological diseases such as cardiovascular disease, diabetes, and hypertension. Both events are principally initiated by reduced endothelial‐derived nitric oxide (NO) bioavailability and/or activation of vascular/leukocyte NADPH oxidase. NADPH oxidase has 7 isoforms (NOX1‐5 and Duox1‐2). We currently have limited knowledge regarding the roles of individual NOX isoforms in diseases, particularly NOX1, which is a major NADPH oxidase isoform in the vasculature but not in leukocytes. In this study, we evaluated the roles of NOX1 in vascular endothelial dysfunction‐induced inflammation by recording leukocyte rolling, adherence, and transmigration in a postcapillary venule of rat mesenteric tissue in real time via intravital microscopy. We superfused the mesenteric tissue with Krebs’ buffer, and Krebs’ buffer with a non‐selective NO synthase inhibitor, NG‐nitro‐L‐arginine‐methyl‐ester (L‐NAME, 50 μM) with/without a selective NOX1 inhibitor, ML171. We found that at 2 hrs of superfusion, leukocyte rolling (21±8 cells/min), adherence (3±2 cells/100 μm), and transmigration (2±1 cells/200 μm2) was minimal in Krebs’ control (n=8). By contrast, L‐NAME (n=6) significantly increased leukocyte rolling (74±12), adhesion (19±6), and transmigration (18±4) (all P<0.05 compared to Krebs’ control). Whereas, ML171 (1 μM, n=7) prevented the L‐NAME‐induced effect on leukocyte rolling (25±5), adhesion (5±2), and transmigration (5±1). These findings suggest that NOX‐1 activation participates in L‐NAME induced inflammatory responses; whereas inhibition of NOX1 can mitigate inflammation following vascular endothelial dysfunction.Support or Funding InformationThis study was supported by Division of Research, the Center for Chronic Disorders of Aging, and Department of Bio‐Medical Sciences at Philadelphia College of Osteopathic Medicine.
Chronic and Acute Hypoxia Markedly Alter Ca2+ Signaling in Adult and Fetal Pulmonary Arterial Myocytes
Authors: Cothran Kyle , Sandy Scott , Romero Monica , Dobyns Abby , Paez Ricardo , Francis Michael , Taylor Mark S , Longo Lawrence D , Wilson Christopher G , Wilson Sean M 
Published: June 2021

Ca2+ signaling is well regarded as being vital to hypoxic induced pulmonary arterial (PA) vasoconstriction and chronic high altitude living can exacerbate this process. To test the hypothesis that chronic hypoxia will increase Ca2+ wave activity due to acute hypoxia in pulmonary arterial myocytes (PAM) of both fetal and adult sheep and better understand the Ca2+ signals, we exposed pregnant and non‐pregnant ewes to 3800m for >110 days to induce chronic hypoxia. We then performed confocal imaging of PAM in Fluo‐4 loaded intact arteries using an en face preparation. Images were recorded in an atmospheric chamber at ~37°C adjusted to either normoxic conditions, at ~300m, or acute hypoxic conditions, simulated by exposing PAs to ~4% O2 for 30 min. Ca2+ signal characteristics in regions of interest (ROIs) were examined with automated analysis procedures. Chronic hypoxia increased Ca2+ wave size in adults, rate of cytosolic Ca2+ removal in fetuses, and ROI recruitment in adults, albeit most ROIs occured in the same cell. Acute hypoxia decreased Ca2+ wave size in chronically hypoxic adults and decreased ROI recruitment in normoxic but not chronically hypoxic adults. It also reduced Ca2+ wave size in normoxic fetuses and obliterated Ca2+ signaling in chronically hypoxic fetuses. Maturation increased Ca2+ wave size as well as recruited more ROIs across the artery wall. These results indicate that chronic hypoxia modifies the influence of acute hypoxia on Ca2+ signaling in fetal and adult PAM in marked ways that may be important to pulmonary vascular dysfunction in those who live and are born at high altitude.Support or Funding InformationSupport from NIH, NSF, and the Walter E. Macpherson Society
AFP anti‐sense transcripts in mouse liver and their potential role in gene regulation
Authors: Dixon Maria S. , Qiu Guofang , Spear Brett T. , Peterson Martha L. 
Published: June 2021

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, ranking the sixth most common cancer and third most common cause of cancer mortality worldwide. We have been studying mouse liver gene regulation to better understand mechanisms by which changes in gene expression contribute to liver development, homeostasis and disease. We identified Zinc Fingers and Homeoboxes 2 (Zhx2) as a regulator of alpha‐fetoprotein (AFP), a plasma protein that is highly expressed in the fetal liver but is shut off after birth. AFP expression is elevated in regenerating adult liver and hepatocellular carcinoma (HCC) and has been used extensively as a diagnostic marker of liver cancer. Interestingly, all genes that are misregulated in the absence of Zhx2 are also misregulated in HCC. Thus, to better understand gene regulation during HCC, we have been studying of the mechanism by which Zhx2 regulates gene expression. While studying AFP mRNA regulation by Zhx2, we identified previously unannotated antisense transcripts (asAFP) that partially overlap the 3′ half of the mouse AFP gene. asAFP RNAs are ~5kb alternatively spliced, mainly cytoplasmic, transcripts containing 2–4 exons that are likely to be non‐coding RNAs. These antisense transcripts were also detected in mouse liver RNA‐seq data. The abundance of asAFP RNA inversely correlates with AFP mRNA levels during postnatal development. Normally, asAFP RNA levels are high and AFP mRNA levels are low in the adult mouse liver. However, in the absence of Zhx2, AFP mRNA levels are higher and asAFP RNA levels are reduced. When portions of the asAFP RNA are over‐expressed in a liver cell line, endogenous AFP mRNA was reduced, suggesting asAFP transcripts repress AFP mRNA expression in trans. We will also knock‐down asAFP RNA and predict that AFP mRNA levels will increase. My central hypothesis is that asAFP RNA contributes to the post‐transcriptional regulation of AFP mRNA through an RNA‐RNA interaction. We are designing experiments to test this hypothesis and to determine at what level the regulation may occur.Support or Funding InformationMCB‐1158234 from the National Science Foundation, R01‐DK59866 from the National Institutes of Health
Zhx2 and the Regulation of AFP Anti‐sense RNAs in Mouse Liver
Authors: Qiu Guofang , Dixon Maria , Spear Brett , Peterson Martha 
Published: June 2021

Although the genomes of eukaryotes are mostly transcribed, only a very small percentage of the transcripts code for proteins. The majority of the transcripts do not have known functions. In recent years, growing evidence has suggested that these non‐coding transcripts may play important roles in gene regulation. In the past two years, our lab has identified and characterized long non‐coding RNAs that are transcribed from the anti‐sense strand of, and partially overlap with, the alpha‐fetoprotein (AFP) gene. AFP is highly expressed in fetal liver, but its expression decreases to a very low level after birth. In adult liver, AFP expression increases during regeneration due to liver damage or during the onset of hepatocellular carcinoma. Our study has shown that anti‐sense AFP (asAFP) transcripts are alternatively spliced and their abundance is inversely correlated with AFP mRNA during liver development. While these asAFP RNAs had not been annotated, RNA‐seq data from mouse liver confirmed and extended our characterization and ENCODE data for histone modifications and DNase I hypersensitivity show signals near the asAFP exons we have identified. Expression levels of AFP mRNA and asAFP RNA also are inversely correlated in the presence or absence of the Zinc fingers and homeoboxes 2 (Zhx2) gene. Zhx2, a putative transcription factor, was shown previously to contribute to the developmental repression of AFP; in the absence of Zhx2, AFP mRNA is high while asAFP RNA is low, compared to wild‐type. Transiently transfecting asAFP into a liver cell line causes a decrease in endogenous AFP, showing asAFP contributes to AFP regulation in trans. We have shown that the asAFP transcripts localize mainly in the poly(A)+ fraction of cytoplasmic RNA, but this does not identify where the asAFP RNA functions. To determine whether the asAFP RNA represses AFP mRNA in the nucleus or cytoplasm, we have been analyzing the abundance of these two RNAs in nuclear and cytoplasmic RNA from liver of Zhx2 wild‐type or knock‐out animals. To better understand the role of Zhx2 in modulating AFP and asAFP RNA expression, future studies will use chromatin IP to determine whether Zhx2 interacts directly with these genes. To identify which of the genes that are mis‐regulated in the absence of Zhx2 are direct targets, we plan to do Zhx2 ChIP‐seq experiments.Support or Funding InformationMCB‐1158234 from the National Science Foundation, R01‐DK59866 from the National Institute of Health
Temporal Shifts in Differential Changes and Regulatory Relations among Multi‐Omic Assays in Social Defeat Mouse Model of Post‐Traumatic Stress Disorder
Authors: Muhie Seid , Gautam Aarti , Chakraborty Nabarun , Hammamieh Rasha , Meyerhoff James , Jett Marti 
Published: June 2021

We collected hemi‐brain, hippocampus, amygdala, medial prefrontal cortex and ventral striatum from mice exposed to modified social‐stress for 1 to 12 days. We performed transcriptome, DNA‐methylome, miRNAome, and genome‐wide Creb1 transcription binding assays. Temporal and integrative analyses of the multi‐omics datasets were carried out using time‐dependent features extraction, and combinatorial algorithms. Our analyses showed unexpected shifts in relational time coordinates among the different omics datasets. Specifically, for a given gene or probe with significantly changed multi‐omics data points, we observed a temporal shift in its expression changes, methylation of its promoter, modulation of its transcript by upstream miRNAs, and binding of its promoter by transcription regulator. For many significantly changed features, the methylation changes occurred, unexpectedly, at earlier stress days while gene expression changes occurred at later time points. Many of the miRNA changes occurred at eight and later stress days. Our findings showed importance of temporal assays to capture time‐dependent multi‐omics changes as reliable signatures for a given condition. Integrative analyses of multi‐omics measurements based on a single time point may be deficient in many aspects, and may also be misleading if missed observations are interpreted as absence of changes.Disclaimers: Research was conducted in compliance with the Animal Welfare Act, and all other Federal requirements. The views expressed are those of the author(s) and do not constitute endorsement by the U.S. Army.Support or Funding InformationFunding: USAMRMC grant number 09284002
Simultaneously Revealing All Lysine Acylations in an Organism to Elucidate Substrate Metabolism
Authors: Nguyen Hong Hanh T. , Loo Joseph A. , Ogorzalek Loo Rachel R. 
Published: June 2021

Within the past 8 years, lysine acetylation knowledge has extended greatly beyond one modification important for chromatin maintenance and transcription regulation to the whole family of reversible conserved short‐chain acylations emerging as an important regulatory mechanism coordinating metabolism in response to changes in nutrient availability. Inspired by these lysine acylation discoveries, we devise a mass spectrometry (MS) method to simultaneously reveal and evaluate all lysine acylations in an organism. Hypothesizing that an organism's pool of acyl‐CoA esters could suggest potential acyl‐lysine modifications hidden within MS/MS datasets, we chose two syntrophic bacteria, Syntrophomonas wolfei and Syntrophus aciditrophicus, for the study. They activate fatty acid and/or aromatic substrates with coenzyme A and stepwise convert acyl‐CoAs down to acetyl‐CoA for ATP production, thus containing a variety of acyl‐CoA intermediates. Different from the current approach of immuno‐enriching acylated peptide prior to MS, our shotgun non‐enrichment MS approach allows a quick, non immuno‐bias, economical and quantitative one‐step assessment of all lysine acylations within an organism, and the modification stoichiometries and their relative levels. We also showed characteristic ions are reliable to detect and confirm lysine acylations, establishing seven lysine acylations first seen in any organism and doubling the number of known short‐chain acylations. Our lysine acylation studies suggest a metabolism regulation mechanism in these syntrophs living at the thermodynamic limit of feasibility. This proteomic approach can be applied to any organism having a complex profile of acyl‐CoAs, especially anaerobic bacteria degrading fatty acids and aromatic compounds and gut bacteria producing butyrate.Support or Funding InformationThis work is funded by the US Department of Energy (UCLA Institute of Genomics and Proteomics, DE‐FC03‐02ER63421 to J. Loo) and the National Institutes of Health (R01GM085402 to J. Loo and R. Ogorzalek Loo).
Kinetics and Binding Studies Reveal that His‐40 is Essential for Catalysis in F420‐Dependent Glucose‐6‐Phosphate Dehydrogenase from Mycobacterium tuberculosis
Authors: Oyugi Mercy , Mayfield Joshua , Bashiri Ghader , Baker Edward , Zhang Yan , Johnson‐Winters Kayunta 
Published: June 2021

Tuberculosis disease (TB) is a deadly infectious disease that is caused by Mycobacterium tuberculosis (Mtb). Our study focuses on F420‐dependent glucose‐6‐phosphate dehydrogenase (FGD), the enzyme that catalyzes the first committed step of the pentose phosphate pathway within Mtb. FGD uses the oxidized F420 cofactor to convert glucose‐6‐phosphate (G6P) to 6‐phosphogluconolactone, yielding reduced cofactor F420H2. F420H2 has been linked to the activation of a promising TB pro‐drug (PA‐824) and it also protects Mtb from nitrosative damages caused by the host's macrophage system. The FGD crystal structure revealed an active site His‐40 residue that has been proposed to be the active site base for the FGD reaction. We aim to probe the functionality of this His‐40 residue using site‐directed mutagenesis, crystallography, binding assays, circular dichroism, and steady state kinetic methods. Here, we present the results of the characterization of wild‐type FGD (wtFGD) and one FGD His‐40 mutant (FGD H40A). The circular dichroism data showed similar spectra for the FGD H40A and wtFGD, suggesting that the H40A mutation did not cause any structural changes within the enzyme. The steady state kinetics yielded kcat values of 1.40 ± 0.03 s−1 for wtFGD and 0.0016 ± 0.00 s−1 for FGD H40A, thus resulting in over 1000‐fold decrease in catalytic efficiency for the FGD H40A mutant. From the binding assays, we were able to conclude that His‐40 is not involved in G6P binding, but it helps in anchoring the F420 cofactor into the active site. The drastic loss in catalytic efficiency for the FGD H40A mutant led to crystallography experiments aimed at solving an FGD crystal structure with both F420 and G6P in the active site. FGD H40A crystals grew in 0.1 M ammonium citrate dibasic (pH 5.0) with 19% PEG 3350 as the precipitant, and diffracted to 2.9 Å to reveal the basis of substrate binding. In conclusion, the results presented here support the previously proposed mechanism which suggested that His‐40 is the active site base for the FGD reaction.Support or Funding InformationThis research was supported by NSF Grants 1120837