bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary Depletion of Bovine Milk Exosomes Elicits Changes in Amino Acid Metabolism in C57BL/6 Mice
Authors: Leiferman Amy L. , Aguilar Ana , Mutai Ezra , Adamec Jiri , Zempleni Janos 
Published: June 2021

BackgroundExosomes are small, cargo‐containing vesicles that are secreted by donor cells to elicit changes in gene expression and metabolism in recipient cells. We have discovered that dietary exosomes from bovine milk can be absorbed by non‐bovine species; studies in murine C2C12 myotube cell cultures suggest that bovine exosomes promote the growth of myofibers.HypothesisThe dietary intake of bovine milk exosomes alters amino acid metabolism, and possibly muscle protein accretion, in non‐bovine species.SignificanceThe dietary intake of exosomes might promote muscle protein accretion in patients with sarcopenia and low‐birth‐weight babies.MethodsC57BL/6 mice, age 3 weeks, were fed an exosome‐depleted (Exo−) AIN93G‐based diet for four weeks; controls were fed an exosome‐sufficient (Exo+) diet. Livers were harvested. The hepatic metabolome was assessed by non‐targeted LC/MS‐MS and by peak intensity analysis; the hepatic transcriptome was assessed by RNAseq using an Illumina HiSeq2500 platform. A second cohort of mice was fed Exo− or Exo+ diets for 4–6 weeks for subsequent analysis of grip strength, respiratory exchange ratio (RER), feeding and activity patterns; skeletal muscle samples are currently analyzed by RNAseq. Statistical significance was assessed using unpaired, two‐tailed t‐test.ResultsHepatic concentrations of several amino acids were significantly higher (up to 18 times) in mice fed the Exo− diet than in Exo+ controls (Fig. 1). The mRNA expression of branched chain amino acid (BCAA) transporters 1 (cytoplasm) and 2 (mitochondria) was greater in mice fed Exo− compared to Exo+ (n.s. for BCAT2; Fig. 2). The RER was not affected by feeding, whereas grip strength was a moderate 5% higher in Exo+ vs. Exo− females after only 4 weeks of feeding (n.s.; not shown). The trend toward a greater grip strength was not caused by differences in food and water consumption or physical activity, which were not significantly different between treatment groups in females.Conclusion & future plansDiets defined by their bovine milk exosome content alter amino acid metabolism in mice. Future studies will investigate protein metabolism by using stable isotopes, and assess muscle protein accretion in response to stimuli such as muscle wasting.Support or Funding InformationNIFA 2015‐67017‐23181, NIFA 2016‐67001‐25301/NIH DK107264, NIH 1P20GM104320, the Gerber Foundation, and USDA Hatch Act and W3002.
Curcumin and piperine inhibit mTORC1 signaling in intestinal epithelial cells
Authors: Moreau Regis , Kaur Harleen 
Published: June 2021

Persistent mTORC1 activation is not only linked to metabolic disorders but also cancer and inflammation by inducing transcription and translation of pro‐inflammatory cytokines. Gastrointestinal cancers are frequently associated with chronic inflammation and excessive secretion of IL‐6 family cytokines, which promote tumorigenesis through persistent activation of PI3K/mTORC1 pathway. Curcumin is the major natural phenol in turmeric, Curcuma longa. Curcumin inhibits a number of different molecules that play a role in inflammation such as TNFα, cyclooxygenase‐2, inducible nitric oxide synthase. Curcumin like many other dietary phenolic compounds has poor bioavailability in part due to extensive metabolism in the intestinal mucosa. Piperine, one of the major components of black pepper, has been shown to increase the bioavailability of dietary phenolics including curcumin. The long‐term objective of the study is to determine whether curcumin and piperine have individual and combined effects in the prevention of gut inflammation via inhibition of mTORC1 in Caco‐2 and HT‐29 cells. Results show that curcumin inhibited mTORC1 activity (phosphorylation state of its downstream targets, ribosomal protein S6 kinase β‐1 and ribosomal protein S6) in a dose dependent manner (ribosomal protein S6 phosphorylation: −52% at 2.5 μM, −84% at 20 μM, P<0.05). Piperine inhibited mTORC1 activity in its own right (ribosomal protein S6 kinase β‐1 phosphorylation: −84% at 2.5 μM, −91% at 20 μM, P<0.05). The combination of curcumin + piperine further inhibited the mTORC1 signaling. mTORC1 activity was markedly elevated (+2600%) in undifferentiated vs. differentiated Caco‐2 cells. Since epithelium dedifferentiation precedes the release of pro‐inflammatory cytokines and the neoplastic process, we are investigating the link between mTORC1 and the pro‐inflammatory cascade in these cells, and how curcumin +/− piperine mitigate these events. We conclude that widely available dietary phenolics, curcumin and piperine, have the potential to regulate the mTOR pathway in the intestine. While curcumin and piperine inhibit mTORC1 signaling independently of each other by mechanisms yet to be characterized, piperine may also indirectly potentiate curcumin activity through enhancement of its bioavailability.Support or Funding InformationSupported by USDA‐NIFA.
Test‐retest reliability of questions assessing physical activity levels among low‐income women
Authors: Li Cheng , Palmer‐Keenan Debra 
Published: June 2021

Self‐reported surveys are used to assess dietary and physical activity (PA) behavior changes among low‐income Expanded Food and Nutrition Education Program (EFNEP) adult participants. A multi‐state research project (NC2169) has been established to create a new EFNEP survey that is consistent with America's most recent dietary and physical activity guidelines. The aim of this portion of the project's work was to examine the test‐retest reliability for the survey's PA questions, for which face validity had previously been verified via cognitive interviews. Due to pragmatic concerns (i.e. literacy levels, participant burden and time constraints), questions used for EFNEP evaluation need to be relatively quick and easy to complete. Thus, a single item was used to address each of three PA concepts: Item 1: moderate to vigorous aerobic PA; Item 2: muscle strengthening/resistance training; and Item 3: bodily exertion to intentionally develop and maintain fitness via everyday activities (e.g., taking the stairs instead of the elevator, parking far from a destination to walk more, etc.). Items 1 and 2 were measured on a 7‐point scale, (“0” to “7” days); Item 3 was assessed using a 5‐point Likert‐type scale (“Never” to “Always”). Sixty‐eight low‐income women from Colorado, New Jersey, and Nevada were asked to respond to the questions on two separate occasions, 7–10 days apart. Care was taken to administer questions during periods for which consistent weather patterns had been predicted, as inconsistent weather has been correlated with changes in individuals' activity patterns. Spearman's correlation coefficient, intra‐class correlation coefficient (ICC) and paired t‐test were used to examine test‐retest reliability using SAS (version 9.3). Demographic information was also collected, and analyzed using descriptive statistics (frequencies, means and standard deviations). Of the 68 participant recruited, 64 completed both the test and retest; most were Black (56.3%), had a high school degree or lower (51.5%), and received SNAP benefit (68.0%). Neither test nor retest responses differed significantly by age, race or education levels. Spearman correlation coefficients ranged from 0.60 (Item 3) to 0.88 (Item 2), suggesting a “strong” (0.60–0.79) to “very strong” (0.80–1.00) correlation between the test and retest responses. ICC for Items 1–3 were 0.71, 0.77, 0.64, respectively, which also indicated “good” reliability (ICC= 0.61 to 0.80). Paired t‐tests showed no significant differences between test and retest responses, which, in the absence of external influences, reflected their reliability. In conclusion, these PA questions demonstrated satisfactory test‐retest reliability for assessing low‐income women's physical activity levels. Research to examine the questions' validity remains necessary.Support or Funding InformationFunding resource: United States Department of Agriculture, New Jersey Agricultural Experiment Station Grant Number: NJ 14211; (Multi‐State Project NC‐2169)
The Impact of a Western Diet on Ossabaw Pig Tissue Transcriptome and Intestinal Microbiome Composition
Authors: Solano‐Aguilar Gloria I , Lakshman Sukla , Molokin Aleksey , Jang Saebyeol , Beshah Ethiopia , Xie Yue , Urban Joseph F , Vinyard Bryan , Escalante Mariana , Walker Maura , Goldbaum Audrey , Meng Huicui , Lamon‐Fava Stefania , Lichtenstein Alice , Matthan Nirupa 
Published: June 2021

To determine the impact of dietary patterns on cardiovascular risk factors, tissue transcriptome and intestinal microbiome, we designed a study to compare the effect of feeding Ossabaw pigs two isocaloric diets with 38% energy from fat designed to represent a 1) “Western diet” rich in saturated fatty acids, refined carbohydrates, low fiber and high cholesterol versus 2) a “Heart Healthy Diet” rich in monounsaturated and polyunsaturated fatty acids, unrefined carbohydrates, fruits/vegetables and fiber with low cholesterol content. Half of the pigs fed each diet were also given atorvastatin (Lipitor®) starting at three months of age. Thirty two pigs were randomly allocated in a 2 × 2 factorial design (n=8/group) and fed for six months a 1) Western diet [WD]; 2) Western Diet+ atorvastatin [WD+ S]; 3) Heart‐Healthy Diet [HHD] and a 4) Heart‐Healthy Diet+ atorvastatin [HHD+S]. Compared to HHD, pigs on the WD had higher plasma total cholesterol (C), LDL‐C, non‐HDL‐C, HDL‐C and triglyceride concentrations(p<0.05), and developed early stage atherosclerotic lesions in the aorta and coronary arteries, with reduced damage in WD groups in the presence of Atorvastatin therapy (p<0.1). No significant differences were observed in inflammatory biomarker tumor necrosis factor (TNFα), liver enzymes, DEXA‐body fat distribution and visceral adipocyte morphometry. Liver transcriptome analysis indicated a reduction in the cholesterol and sterol molecular pathways in liver and a small increase in LDLR gene expression in pigsfed HHD independent of statin intervention, and no change in adipose tissue derived stromal cell transcriptome compared to WD. Analysis of fecal microbiota composition by Illumina16S RNA sequencing indicated a significant five to six‐fold reduction of bacterial taxa abundance within Firmicutes phylum including Lachnospiraceae, Lactobacillaceae, and Ruminococcaceae with a five‐fold increase in taxa within Actinobacteria, and two‐fold within Tenericutes and Proteobacteria in WD‐fed pigs compared to baseline levels. Pigs fed the HHD showed a two‐ to four‐fold reduction in Lachnospiraceae, Lactobacillaceae and Ruminococcaceae with a two‐ to three‐fold increase in Bacteroidales, Aeromonadales and Deferribacterales (P<0.05). Statin treatment only induced a two‐fold increase in Deferribacteraceae in pigs fed HHD+S. This study demonstrated that a Heart Healthy Diet combined with statin therapy may prophylactically reduce clinical expression of diet‐induced cardiovascular disease.Support or Funding InformationHNRCA Research Cluster Initiative and the U.S. Department of Agriculture, under agreement No. 58‐1950‐4‐401 and USDA‐appropriated CRIS 8040‐51530‐056‐00D
Identification of activation of tryptophan‐NAD+ pathway as a central metabolic response to chemical stress from feeding thermally‐oxidized soybean oil in mouse through metabolomics‐based biochemical analysis
Authors: Wang Lei , Yao Dan , Urriola Pedro , Saqui‐Salces Milena , Shurson Gerald , Chen Chi 
Published: June 2021

Consumption of thermally‐oxidized lipids is associated with metabolic disorders and cardiovascular disease. However, the specific metabolic events induced by thermally‐oxidized lipids and their underlying mechanisms are not well defined. In this study, the metabolic responses to consuming thermally‐oxidized vegetable oil were examined through metabolomics‐guided biochemical analysis. The control diet containing 7% (w/w) fresh soybean oil diet (CSO) and the treatment diet containing 7% (w/w) heated soybean oil (HSO) were fed to two groups of C57BL/6 mice for 4 weeks, respectively. Liquid chromatography‐mass spectrometry (LC‐MS)‐based metabolomic analysis indicated that HSO greatly altered the composition of metabolomes in serum, urine, and liver samples. A group of hydroxylalkenoic acids in urine were identified as newly formed metabolites from HSO treatment. HSO altered the lipidome, which was indicated by the increases of phospholipids containing saturated fatty acids and the decrease of phospholipids containing polyunsaturated fatty acids in the liver and serum. In the liver, HSO‐induced disruption of redox balance was reflected by the decrease of glutathione (GSH) and ascorbic acid and the upregulation of detoxifying gene expression. Moreover, the levels of several microbial metabolites in urine were affected by HSO, suggesting the changes in microflora. Above all, the most prominent metabolic changes induced by HSO occurred in the tryptophan‐NAD+ pathway since multiple metabolites in this pathway were affected, including the decrease of serum tryptophan, the increases of NAD+ and adenosine metabolites in the liver, and the increases of kynurenic acid, nicotinamide, and nicotinamide N‐oxide in urine. The activation of tryptophan‐NAD+ pathway was confirmed by observing the upregulation of tryptophan 2,3‐dioxygenase, kynureninase, and quinolinate phosphoribosyl transferase expression in this pathway, likely contributed by the activation of peroxisome proliferator‐activated receptor α (PPARα), as suggested by the upregulation of PPARα target genes in the liver and the decreases of triacylglycerols in both serum and liver. Since NAD+ and its metabolites are the indispensable cofactors or substrates of major metabolic events induced by HSO, including the detoxification of reactive aldehydes through aldehyde dehydrogenase, sustaining redox balance and DNA repair activities, and PPARα–mediated metabolic reactions, such as fatty acid β‐oxidation, the activation of tryptophan‐NAD+ pathway is deemed to be a central metabolic event induced by thermally‐oxidized lipids.Support or Funding InformationNIFA project MIN‐18‐092
The Ratio of HDL to LDL in Serum Is Related to Macular Pigment Density and Cognitive Function in Older Adults: Potential Insights into Lutein Transport to Neural Tissue
Authors: Mohn Emily S , Scott Tammy M , Johnson Elizabeth J 
Published: June 2021

The dietary carotenoid, lutein, is selectively taken up into neural tissue. Neural lutein is related to better cognition. However, serum lutein concentrations may not accurately reflect neural levels. Lutein is mainly transported on high‐density lipoprotein (HDL) followed by low‐density lipoprotein (LDL). HDL may play a significant role in delivery of lipophilic nutrients to neural tissue. Therefore, lutein content on HDL may better reflect neural levels. However, this has yet to be investigated in humans. The relative amounts of HDL and LDL (HDL/LDL) is an indicator of the distribution of lutein in the circulation. The aim of this study was to determine the relationship between changes in lipoprotein profiles, neural lutein concentration (measured by macular pigment density, MPD), and cognitive performance in older adults (n=31) using a previously conducted study in which participants were followed for 6 months. Serum collection, MPD (using heterochromatic flicker photometry), and cognitive testing (computerized cognitive assessment battery, CANTAB) were performed at baseline, 3 months, and 6 months. Serum lipoproteins and carotenoids were determined using an enzymatic colorimetric method and HPLC, respectively. There was a group of individuals who had MPD increases >0.10 optical density (OD) over the study period (n=17). These subjects were classified as “MPD responders”. In these subjects, adjusting for age, change in HDL/LDL was positively associated with change in MPD (r=0.66, p=0.006) and the strength of this association was greater in a subset of MPD responders who also had increases in serum lutein (n=10, r=0.77, p=0.01). The association between change in HDL/LDL and MPD was not significant in MPD responders without increases in serum lutein. In all MPD responders, change in both HDL/LDL and MPD were positively associated with change in spatial working memory and increased spatial planning, while change in serum lutein was positively related to spatial planning only (adjusted for age and education, P<0.05). Associations between HDL/LDL and cognition were stronger in the subset of MPD responders who also had increases in serum lutein (P<0.05). In MPD non‐responders (ΔMPD ≤0.05 OD), HDL/LDL was not related to MPD, but was associated with spatial planning. Collectively, these findings lend support to the hypothesis that lutein carried on HDL is targeted to neural tissue and may be important for cognition.Support or Funding InformationThis work was supported by the Hass Avocado Board and USDA (1950‐51000‐087)
Chemical discovery in the microbial world
Authors: Balskus Emily P. 
Published: June 2021

Microorganisms like bacteria, archaea, and fungi have amazing chemical capabilities, performing challenging transformations and producing complex, biologically active molecules not easily accessed via any other means. However, we do not yet have an understanding of the enzymatic chemistry responsible for the full diversity of reactions performed by these organisms. Recent advances in DNA sequencing technologies have delivered a wealth of microbial genomes, providing an unprecedented opportunity to discover enzymes that have the potential to change the way chemists make molecules. My lab is identifying new enzymatic transformations by studying the biosynthesis of secondary metabolites with atypical structures or chemical functionality. This talk will discuss our recent progress deciphering the enzymatic chemistry that mediates unusual C–C and C–Cl bond‐forming reactions in several biosynthetic pathways. Functional and mechanistic characterization of these biosynthetic enzymes is revealing new reactivity with potential applications in biocatalysis and metabolic engineering.Support or Funding InformationThis work is supported by the NSF (CAREER Award # 1454007), the Searle Scholars Program, and the Cottrell Scholar Award.
Using the Wilder Collaboration Factors Inventory to Assess SNAP‐Ed Coalitions in Arizona: Results from Four Counties
Authors: McCullough Lauren , Jacobs Laurel , Orzech Kathryn , Farrell Vanessa , McDonald Dan , Florian Traci Armstrong , Zilliox Patricia , Martinez Cathy , Misner Scottie 
Published: June 2021

BackgroundIn 2014, the Supplemental Nutrition Assistance Program ‐ Education (SNAP‐Ed) incorporated Policy, Systems and Environmental (PSE) approaches to reinforce obesity prevention efforts. This expansion included engagement in multi‐sectoral coalitions which provide community‐level supports for healthy eating and active living. Coalition success depends on creating well‐defined collaborations that share authority, accountability, resources, and achievements. Arizona's SNAP‐Ed utilized the Wilder Collaboration Factors Inventory (WCFI) to evaluate coalitions' effectiveness in supporting food systems and active living PSE goals at the community level.MethodsThe University of Arizona Nutrition Network (UANN), part of the SNAP‐Ed program in Arizona, used the WCFI to assess six coalitions in four counties (Maricopa, Mohave, Pima, and Pinal).The WCFI uses a 40‐question Likert scale (1.0–5.0) questionnaire to evaluate collaborations on 20 success factors. The WCFI identifies areas of collaboration strength (4.0–5.0) and weakness (1.0–3.9). Coalition members were invited to complete the WCFI online or in‐person. Of the 117 surveys distributed, 64 were returned, and 61 provided complete responses. The results (N=61) were aggregated to identify similar factor scores across coalitions.ResultsFour out of six coalitions (66%) scored highly in the same success factor: members see collaboration in their self‐interest (average score: 4.5). Half of the coalitions identified unique purpose as a stronger success factor within their collaboration (average score: 4.2).All coalitions identified the same weaker success factor: lack of sufficient funds, staff, materials, and time (average score: 2.8). Three coalitions had the development of clear roles and policy guidelines as a weak success factor within their coalition (average score: 3.0).ConclusionThe WCFI results suggest that community coalitions in which SNAP‐Ed staff participate in Arizona reflect an invested membership and a unique purpose in their communities, yet sufficient resources and clear goals are areas that should be strengthened. By providing timely and actionable WCFI data and recommendations to these active living and food systems coalitions in Arizona, capacity can be strengthened to achieve the goals of the collaborations in which SNAP‐Ed participates. The coalitions that use the WCFI results to encourage the strengthening of their coalition's capacity will be more likely to succeed in achieving PSE changes in their communities.Support or Funding InformationUSDA HI050073
Identification of p‐cresol sulfate and secondary bile salts in human urine as sensitive biomarkers of fecal microbiota transplantation in R‐CDI patients
Authors: Bi Zheting , Lu Yuwei , Weigarden Alexa R , Yao Dan , Wang Lei , Khoruts Alexander , Sadowsky Michael J , Chen Chi 
Published: June 2021

Fecal microbiota transplantation (FMT) has become an effective therapy for recurrent Clostridium difficile infection (R‐CDI). Besides reestablishing a normal intestinal microbiome that offers better resistance to R‐CDI, the introduction of microflora from healthy donors through FMT is also expected to change the metabolomes in the intestine and the whole body due to diverse metabolic activities of transplanted microbiota. Therefore, monitoring the metabolic changes in biofluids and excretes provides the opportunities for identifying noninvasive biomarkers of microbial recolonization and understanding the metabolic influences of FMT on host and microflora. In this study, FMT‐induced metabolic changes were examined by the metabolomic comparison of pre‐FMT and post‐FMT urine samples from 18 R‐CDI patients who had symptoms rapidly resolved after receiving FMT from two donors. After the liquid chromatography‐mass spectrometry (LC‐MS) analysis of urine samples from the patients and the donors, the LC‐MS data were processed by partial‐least squares‐discriminant analysis (PLS‐DA), leading to the establishment of a multivariate model revealing the separation between pre‐ and post‐FMT urine samples as well as the similarity between post‐FMT and donor samples. Among a group of urinary metabolites affected by the FMT, the most prominent biomarkers are p‐cresol sulfate and secondary bile acid conjugates, which were absent in most pre‐FMT samples, but dramatically increased in the post‐FMT samples. The presence of p‐cresol sulfate and secondary bile acid conjugates in urine after FMT reflected the recovery of microfloral metabolism on tyrosine and primary bile acids in R‐CDI patients. Their levels in urine may function as effective and sensitive therapeutic indicators of the readiness of CDI patient for FMT as well as the recolonization of healthy microfloral colonies after FMT.Support or Funding InformationNIAID grant R21 AI114722 and NIFA project MIN‐18‐092