bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbiome Impact from a Nutrition Intervention in Young Adults: FRUVEDomics Pilot Study
Authors: Famodu Oluremi A , Infante A M , Cuff Chris C , Holaskova Ida , Olfert I Mark , Downes Marianne T , Murray Pamela J , McFadden Joseph W , Colby Sarah E , Morrell Jesse , Olfert Melissa Diann 
Published: June 2021

BackgroundIndividuals have long since co‐existed with their gut microbiota and it is now being accepted as indispensable in healthy living. Researchers have linked an imbalanced gut microbiome with obesity, atherosclerosis and inflammation, with momentum gaining at how diet can impact the gut bacteria.ObjectiveThe purpose of this study was to examine the effects of a healthy dietary intervention on the microbiome of young adults attending West Virginia University.MethodsSubjects (n=36) followed a free‐living diet intervention for 8‐weeks centered on the 2010 Dietary Guidelines for Americans and the Choose MyPlate recommendations. Anthropometrics, surveys, venous blood samples, stool samples, and body composition were collected at baseline and post intervention. Participants underwent individual weekly consultations with a Registered Dietitian Nutritionist, using food logs, food pictures and receipt management to evaluate adherence. Alterations in the fecal microbiome were assessed using high throughput sequencing of the V3–V4 regions of the 16S rRNA gene (Illumina MiSeq). Paired t–testing with inverse beta binomal distribution was used to assess changes in microbiome from baseline to post and linear regression was used to calculate relationships between bacteria and certain diet components.ResultsA significant decrease in empty calories (p<0.0001) and increases in fiber (p<0.001) and cups of fruit and vegetables (p<0.0001) were seen after 8 weeks demonstrating improvements in waist circumference, systolic blood pressure, and insulin sensitivity (p<0.01, p<0.05, p<0.05 respectively). Significant increases were seen in the phyla Cyanobacteria (fold change=3.68, adj p=0.005), the order of Clostridiales (fold change=3.14, adj p=0.003) and the families of Barnesiellaceae (fold change=15.89, adj p<0.0001), and Paraprevotellaceae (fold change=15.89, adj p<0.0001). A significant decrease was seen in S‐24 7 (fold change=−15.89, adj p<0.0001) a family in the phylum of Bacteroidetes. At baseline, alcohol was significantly related to Cyanobacteria (F=30.1, p<0.001) and Clostridiales (F=5.80, p=0.02). Following the intervention, significant relationships were seen in Bacteroidaceae and Firmicutes with grams of protein (F=10.27, p=0.004 and F=7.82, p=0.01 respectively). Additionally, Rikenellaceae was significantly related to total sugar (F=10.53, p=0.003) following the intervention.ConclusionOur major findings indicate that a short‐term, healthy, diet changed the microbiota of young adults and specific dietary components are linked to certain bacteria. It will be important to determine if these changes to the microbiota are linked to lower incidence of disease.Support or Funding InformationUSDA/AFRI #2014‐67001‐21851; WV Clinical and Translational Science Institute (NIH/MIGMS AwardNumber U54GM104942); WVU Mountains of Excellence Pilot Grant Program
Construction of Comprehensive Flavonoid Analysis Tool by Using UV‐vis Spectra Library, In‐house Database, and Chemometrics
Authors: Zhang Mengliang , Sun Jianghao , Harnly James , Betz Joseph M. , Chen Pei 
Published: June 2021

Liquid Chromatography and mass spectrometry methods, especially ultra‐high performance liquid chromatography coupled with high resolution accurate mass‐mass spectrometry (UHPLC‐HRAM‐MS), have become the best methods for flavonoid identification and quantification. However, processing acquired UHPLC‐HRAM‐MS data for flavonoid analysis is very challenging and highly expertise‐dependent because of the complexity of the physical and chemical properties of the flavonoids. An expert data analysis program, FlavonQ, has been developed to facilitate this process. The program first categorizes the flavonoids using a chemometric model based on the UV‐Vis spectra library compiled for 146 flavonoid reference standards. A novel stepwise classification strategy is used that provides data representation in each step as optimized by a projected distance resolution (PDR) method. The stepwise classification strategy significantly improves the performance of the classifiers which results in more accurate and reliable classification results. An in‐house flavonoid database which contains 5686 previously reported flavonoids is used for identification of flavonoids. FlavonQ was validated by analyzing data from samples with spiked flavonoid mixed standards and plant samples including blueberry, mizuna, purple mustard, red cabbage, and red mustard green extract. Accuracies for identification for all samples were above 88%. FlavonQ greatly facilitates the identification and quantitation of flavonoids from UHPLC‐HRAM‐MS data. The process is automated, saving tremendous resources, and allowing less‐experienced people to perform data analysis on flavonoids with reasonable results.Support or Funding InformationThis research is supported by the Agricultural Research Service of the U.S. Department of Agriculture, an Interagency Agreement with the Office of Dietary Supplements at the National Institutes of Health (Y01 OD001298‐01). The John A. Milner Fellowship program by USDA Beltsville Human Nutrition Research Center and the NIH Office of Dietary Supplements is acknowledged for the support to Dr. Mengliang Zhang. We thank to Dr. Peter de B. Harrington for providing his codes on chemometric models.
Gene Expression Profile During the Repair Process in a Rat Calvarial Bone Critical Size Defect
Authors: Clifford John L , Yang Ruoting , Bowman Phillip D , Bynum James A , Wenke Joseph C , Hammamieh Rasha 
Published: June 2021

Bone is a complex tissue, providing support and protection while also adapting to the body's mechanical needs. In response to injury or fracture, bone has a significant capability for self‐repair and regeneration that requires the regulated expression of diverse families of genes that coordinate complex interactions among various cell types. Studies on bone non‐union have led to the critical size defect (CSD) theory, which states that as bone defects increase in size, a point will be reached where bone union will not occur and the bone will not heal spontaneously during the lifetime of the animal. CSDs fail to heal and regenerate bone, while noncritical defects produce an acceptable repair after bone loss. To improve outcome following significant bone loss we sought to identify genes differentially expressed between an 8 mm (CSD) and 4 mm (non‐CSD) size defects in a rat calvarial bone defect model. Rat whole genome microarrays were used to measure gene expression over the course of bone healing, and analysis of differentially expressed genes (DEGs) with Cytoscape® software revealed multiple temporal patterns of fold differences for DEGs. The patterns indicated that greatest number of differences occur at the earliest time point post‐injury (day 1), and starting at day 7 and continuing through day 21. Gene ontology and functional classification of genes altered in expression between the CSD and non‐CSD was conducted using Ingenuity Pathway Analysis software®. During the earliest (day 1,3) and later (day 14,21) times post injury, multiple DEGs and gene networks related to cell death and survival, cancer, connective tissue development and function, DNA Replication/recombination/repair, skeletal and muscular system development and function, and others, were identified. At the early time points TGF‐β1 and VEGFα signaling pathways are down modulated in CSD relative to non‐CSD include. Pathways that regulate movement of lymphocytes and activation of antigen presenting cells, as well as NFk‐B signaling, are upregulated at later times post‐ injury in CSD compared to non‐CSD. We conclude that genes and signaling pathways that promote healing and tissue homeostasis are suppressed in the CSD, in favor of activation of pro‐inflammatory signaling.Disclaimer: Research was conducted in compliance with the Animal Welfare Act, and all other Federal requirements. The views expressed are those of the authors and do not constitute endorsement by the U.S. Army.Support or Funding InformationThis work was supported by funding from the United States Army Medical Research and Material Command Combat Casualty Care and Clinical and Rehabilitative Medicine Research Programs
Modulations of calcium in adipose tissue by TRPC1: a key player in obesity
Authors: Schaar Anne , Krout Danielle , Roemmich James N , Claycombe‐Larson Kate J , Singh Brij B 
Published: June 2021

The disruption of metabolic homeostasis, the regulation of energy the body extracts, stores and uses, leads to excess adipose tissue accumulation and the onset of obesity. White adipose tissue (WAT) is a metabolically dynamic endocrine organ responsible for maintaining metabolic homeostasis through mitochondrion function and the secretion of cytokines. A key modulator of glucose and lipid metabolism is the WAT secreted cytokine adiponectin, however, the regulation of it is not fully known. Transient Receptor Potential Canonical (TRPC) channels are a major class of Ca2+ permeable channels found in key metabolic tissues (hypothalamus, adipocytes, and skeletal muscle). Fluctuations in intracellular Ca2+ are due to the release of Ca2+ stores from the endoplasmic reticulum (ER) that initiates store‐operated Ca2+ entry (SOCE) mechanism, or by direct Ca2+ entry from the extracellular space upon membrane depolarization. Within our work, we provide evidence that Ca2+ entry into the cell, especially upon store‐depletion, plays an important role in WAT functionality and subsequently metabolic regulation. It was found that mice deficient in the Ca2+ channel TRPC1−/− have significantly increased adipose deposition without an increase in overall weight as compared to control. When investigating WAT, the reduced Ca2+ influx due to a loss of TRPC1 results in a decline in mitochondria function. Further, TRPC1−/− mice were found to have reduced serum adiponectin levels along with a reduction in the downstream enzymes adiponectin regulates necessary for lipid metabolism. Combined, these results indicate that TRPC1 may have an important role in the regulation of metabolic homeostasis and the onset of obesity through the regulation of WAT.Support or Funding InformationThis work was supported by the National Institutes of Health awarded to B.B.S (DE017102; DE024300; GM113123), by ND EPSCoR through National Science Foundation (IIA‐1355466) awarded to A.S., and from the USDA Agricultural Research Service Project #3062‐51000‐052‐00D awarded to K.C.
Nuclear Blebbing Solely as a Function of Chromatin Compaction State
Authors: Liu Patrick Z. , Stephens Andrew D. , Banigan Edward J. , Almassalha Luay , Backman Vadim , Adams Stephen A. , Goldman Robert D. , Marko John F. 
Published: June 2021

The nucleus houses the genome and is critical for regulating its functional organization. Classically, in mammalian nuclei, the compact, transcriptionally silent heterochromatin is docked to the lamina network at the periphery, thereby providing mechanical support to the nucleus. In many human diseases, such as progeria, cancers, and muscular dystrophies, nuclear morphology becomes severely altered and demonstrates blebbing as a result of impaired nuclear rigidity stemming from disruptions to chromatin compaction and lamina content. To elucidate chromatin's individual role in contributing to the formation of pathologically misshapen nuclei, we show that decompacting chromatin via histone deacetylase inhibitor (HDACi) treatment alone is sufficient to induce nuclear blebbing. Through immunofluorescence imaging via confocal microscopy, we demonstrate that treating mouse embryonic fibroblasts with HDACi decompacts chromatin, relocates euchromatin to the periphery, and causes blebbing independent of disruptions to the lamina or actin network. Moreover, the divalent ion magnesium is known to compact chromatin. In accordance with this, we found that increasing extracellular magnesium chloride concentrations rescues nuclear blebbing in a dose‐dependent manner, restores heterochromatin signal at the periphery, and significantly increases the heterochromatin signal histone H3 lysine 27 tri‐methyl. Moreover, nuclear morphology in HeLa cells expressing progerin, a mutated form of lamin A present in progeria that causes severe nuclear deformities, was also rescued via magnesium chloride treatment. Thus, nuclear blebbing can both be induced and suppressed through solely altering chromatin compaction states. Similarly, a pathological phenotype that stems from a lamina mutation can be rescued through the same chromatin mechanism, thereby suggesting a significant role of chromatin in disease and providing a potential therapeutic target.Support or Funding InformationJ. F. M. is supported by NSF Grants DMR‐1206868 and MCB‐1022117 and by NIH Grants GM105847 and CA193419.
Longitudinal study of the human gastrointestinal microbiota following fecal microbiota transplant (FMT) for Clostridium difficile infections
Authors: Joseph Oluyemisi D , Thompson Sharon V , Bogner Anna , Martin Daniel , Farrell John J , Swanson Kelly S , Holscher Hannah D 
Published: June 2021

BackgroundClostridium difficile infection (CDI) is a nosocomial infection known to be the most crucial antecedent of healthcare‐associated diarrhea. Fecal microbiota transplant (FMT) has emerged as a successful treatment method when standard antibiotic therapy is ineffective for refractory CDI. However, our understanding is limited regarding the longitudinal differences in the gastrointestinal (GI) microbiota between patients with a successful or failed FMT.ObjectiveWe aimed to investigate the microbial structure and predictive metagenome functional content of FMT patients over a 90‐day period, and to determine if these outcomes differed in patients with a successful or failed procedure over time.MethodsPatient microbiome samples were assessed prior to FMT (n=8), and at 30 (n=4) and 90 days (n=4) post treatment. Treatment failure was defined as ≥3 episodes of diarrhea/day or, within 30 days, retreatment with antibiotics or FMT. Metagenome functional potential was predicted using PICRUSt (v. 1.0.0). PICRUSt data and relative abundances of microbial taxa were then analyzed using LEFSe (v. 1.0), a Linear Discriminant Analysis model which evaluated discriminant features using a Kruskall‐Wallis test for FMT status (success/fail) followed by Wilcoxon test for pairwise comparisons between timepoints (baseline/30‐d/90‐d).ResultsAcross timepoints, relative abundance of Fusobacteriaceae was significantly higher among patients with a failed FMT (p=0.015), and Enterococcaceae (p=0.020) and an unclassified family of Lactobacillales (p=0.023) were significantly greater in patients with a successful FMT. At the genus level, relative abundance of Lactococcus (p=0.027) and Fusobacterium (p=0.007) were higher in patients with failed FMT over time. Metagenome functional potential analyses revealed that enzymes related to steroid hormone and glycosphingolipid synthesis and glycosaminoglycan degradation were significantly higher in participants with a failed FMT over time.ConclusionsThe use of innovative bioinformatic tools in the present study permits identification of key differences in microbial community structures and functional gene potential between participants with a successful or failed FMT procedure across a 90‐day period. Differences in steroid hormone synthesis, glucocorticoid in particular, has been linked to increased mortality of CDI patients. An increase in the synthesis and metabolism of glycoconjugates have also been associated with an increase in the pathogenicity of microbes such as C. difficile. More research is required to determine if the gut microbial structure of patients with CDI can be used to predict if FMT is the best route for treatment.Support or Funding InformationPartial funding for this study was provided by the USDA National Institute of Food and Agriculture, Hatch project ILLU 538 384.
Assessment of Dietary Intervention Compliance of Subjects Participating in an Ongoing Randomized Controlled Trial
Authors: Dietrich Jessica R , Kaczmarek Jennifer L , Reeser Ginger E , Khan Naiman A , Holscher Hannah D 
Published: June 2021

BackgroundWhen conducting human subject research, outcomes vitally depend upon how well participants follow instructions provided by the research team. Assessing compliance to interventions enables participant classification as per protocol or intention to treat for outcome assessments. It also provides insight into participant characteristics that may be related to study compliance, with relevance to future dietary intervention studies.ObjectiveHerein we aimed to determine overall self‐reported compliance of study participants to a dietary intervention during an ongoing randomized, controlled trial. Our secondary objectives were to determine whether factors such as age, sex, income, or education are related to study compliance.MethodsAll study participants were counseled to consume the entire study meal daily throughout a 12‐week intervention. Daily compliance records were provided throughout the study. Participants were instructed to indicate the percentage of the meal consumed each day. Consumption was computed on a per‐week basis for each participant. Statistical analyses was performed in SAS 9.4, accepting a p‐value of 0.05 as statistically significant. A general linear mixed model was created for each demographic variable using compliance as the outcome measure and including week of the study as a repeated measure predictor. Week was included in order to examine not only what variables were associated with compliance, but also how compliance changed over the duration of the study.ResultsThe average overall consumption of the control group (n=31) was 87%, and the average overall consumption of the intervention group (n=27) was 90%. The average meal consumption for females was 86% (n=36) and 92% (n=22) for males. The analysis of the entire participant pool (n=58) showed no significant relationships between meal compliance and group, age, sex, income, or education level.ConclusionThese results reveal that overall study compliance is high with no differences between groups or over time. Even when other variables such as age, sex, income, and education were considered, there still were no significant associations with compliance, nor did compliance decrease significantly over the course of the study.Support or Funding InformationPartial funding for this study was provided by the Hass Avocado Board and the USDA National Institute of Food and Agriculture, Hatch project ILLU 538 384.
Self‐reported diabetes status moderates the association between food insecurity and body mass index
Authors: Liu Yibin , Remley Daniel T. , Zhang Yumin , Eicher‐Miller Heather A. 
Published: June 2021

Food insecurity is associated with reduced consumption of fruits, vegetables, dairy, and lower levels of micronutrients. These dietary patterns are linked to the development of chronic diseases. Few studies have explored disease factors that impact the relationship of food insecurity with obesity. The purpose of this study was to investigate the role of self‐reported diabetes status in moderating the association between food insecurity and body mass index (BMI) among Indiana food pantry users aged 21 – 80 y (n = 285). Food pantry users that speak and read English were recruited from eight rural and low income counties in Indiana. Participants were interviewed for individual and household characteristics, household food security status (US Household Food Security Survey Module), and measured for height and weight to determine BMI. Results from adjusted multiple linear regression model showed that marginal food‐secure adults had an estimated 8.2 kg/m2 higher BMI (P = 0.03), low food‐secure adults had an estimated 9.3 kg/m2 higher BMI (P = 0.008), and very low food‐secure adults had an estimated 6.6 kg/m2 higher BMI (P = 0.06), compared with high food‐secure adult BMI. There was a significant interaction between food security status and self‐reported diabetes status. Among adults with self‐reported diabetes, BMI was significantly higher in marginal and low food‐secure groups (P = 0.03, P = 0.007), compared with the high food‐secure group. Among adults without diabetes, BMI in marginal, low, and very low food‐secure groups was not significantly different from the high food‐secure group (P = 0.59, P = 0.55, P = 0.42). Results of this study suggest that overweight and obesity are more prevalent among diabetic food pantry clients in marginal and low food‐secure groups. Food pantries may serve diabetic clients in marginal and low food secure groups by supporting provision of appropriate foods for these clients and allowing client choice along with offering nutrition education to improve self‐sufficiency and enable healthy, high‐quality, and appropriate food selection.Support or Funding InformationThis project is supported by the Agriculture and Food Research Initiative competitive grant no. 2013‐69004‐20401 of the USDA National Institute of Food and Agriculture.
Not all silver nanoparticles are equal: Effect of functionalization on K homeostasis in human red blood cells
Authors: Alla Praveen Kumar , Lauf Peter K , Sizemore Ioana , Paluri Arathi S.L , Yaklic Jerome , Adragna Norma C 
Published: June 2021

Although silver nanoparticles (AgNPs) are one of the most frequently used nanomaterials (NMs) in industrial and biomedical applications, their toxicity and interaction with blood components, such as erythrocytes, has been insufficiently investigated. Here, we report on the effect of AgNPs at the level of cellular function, and particularly on ion transport in human red blood cells (HRBCs). These AgNPs were size‐selected, concentrated and purified by tangential flow filtration before HRBC exposure. Two methods of synthesis were used for the functionalization of AgNPs, Creighton and Lee‐Meisel. HRBCs were obtained from adult donors at a blood bank, expired or fresh or further stored refrigerated in the laboratory for variable lengths of time, and from fresh or stored refrigerated cord blood. Rubidium, used as a K congener to measure K influx, and the K concentration were determined in the presence and absence of several concentrations (0–150 μg/mL) of negatively charged, spherical 10 nm AgNPs at different time points (0–60 min). Our findings indicate that Creighton AgNPs, independently of the source and in a time‐ and dose‐dependent manner, inhibited Rb influx by ~ 80 % (p < 0.001, n=7) and depleted the cells of K by more than 90 % (p < 0.0001, n = 7), although interindividual differences were observed. In comparison to the Creighton, Lee‐Meisel AgNPs caused a maximum Rb inhibition of ~ 50 % and K loss of ~ 15 % with larger interindividual variability than Creighton AgNPs, albeit in a small sample. The loss of K from HRBCs was entirely accounted for by an increase in K concentration in the extracellular medium. These findings indicate that functionalization of AgNPs has a significant effect on HRBC K homeostasis. Further studies are required to identify the mechanisms underlying the observed changes in HRBC ionic composition.Support or Funding InformationFunded by NSF