bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between Promoter CpG Methylation and mRNA Levels of Genes Regulated by Fatty Acids in Muscle Cells and Adipocytes
Authors: Alam Md Masudul , Cheng Elliott , Li Yi 
Published: June 2021

In obesity and type 2 diabetes, adipose and muscle tissues are significantly affected. It has been demonstrated that many of the changes are associated with gene expression. We tried to study the involvement of epigenetic modifications in mediating gene expression induced by hyperlipidemia. L6 Muscle cells and differentiated 3T3L1 adipocytes were treated with saturated and polyunsaturated fatty acids to mimic hyperlipidemia condition. After treatments, methylation sequencing was done to identify the methylated regions of the genomic DNA samples from the cells. In combination with validated DNA microarray data, we have found an inverse correlation between DNA CpG methylation in the promoter region and the mRNA level of a number of genes including FADS3, PPARγ, RASA2, MEF2C. At present we are individually validating the methylation status of the genes and studying the signaling pathways mediating in methylation of these genes.Support or Funding InformationThis research is supported by grant SC3GM116737 from the NIGMS of the NIH to Y. Li.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Responses of Muscle Satellite Cells to Lemon Myrtle Supplementation Combined with Electrical Stimulation in Disuse‐induced Skeletal Muscle Atrophy
Authors: Takuwa Miho , Matsumoto Tomohiro , Hirabayashi Takumi , Ikeji Takuya , Ono Kohei , Honda Shinichi , Yamamoto Ayumi , Kondo Hiroyo , Fujino Hidemi 
Published: June 2021

Disuse condition leads to decrease fiber cross‐sectional area and satellite cell activity in skeletal muscle. Transcutaneous electrical stimulation (ES) can suppress unloading‐induced muscle atrophy, but not prevent. Lemon myrtle (LM), one of herbs, could activate muscle satellite cells in our previous study. Therefore, the preventive effects of the lemon myrtle supplementation on muscle atrophy were investigated. In addition, we determined the activation in muscle satellite cells, the number of myonuclei, and the prevention of disuse‐induced muscle atrophy by the combination of LM supplementation and ES. Wistar rats were divided into 5 groups; control (CON), hindlimb unloading (HU), HU + LM, HU + ES and HU + LM + ES groups. The experiment period was 14 days. Unloading condition resulted in a decrease in the fiber cross‐sectional area (FCSA). The FCSA was significantly increased in HU + LM + ES group than in the other three groups (HU, HU + LM and HU + ES). In addition, the expression levels of Pax 7, MyoD and myogenin were higher in HU + LM + ES group compared with the other three groups (HU, HU + LM and HU + ES). Furthermore, the number of myonuclei were significantly decreased in HU, HU + LM and HU + ES groups than in CON group although there was no significant difference between in HU + LM + ES group and CON group. These results suggest that the combination of lemon myrtle supplementation and electrical stimulation suppressed the reduction of the fiber cross‐sectional area compared with lemon myrtle supplementation or electrical stimulation alone, and these alterations were accompanied with an increase in the number of myonuclei associated with the activation of muscle satellite cells.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Age‐Related Changes in Resting State Connectivity of Brain Areas Related to Appetite, Mood and Food Homeostasis in Response to Glucose Ingestion
Authors: Peters Riccarda , White David , Pipingas Andrew , Scholey Andrew 
Published: June 2021

ObjectiveAging is associated with decreases in appetite and energy intake. Appetite regulation is a complex system and age‐related changes in the brain response to food is not completely understood.The aim of this study was to investigate the influence of a glucose load on resting state functional connectivity of brain regions involved in the regulation of appetite, motivation and reward processes as well as energy homeostasis in aging. We further investigated the relationship of changes in functional connectivity to changes in subjective mood and appetite as well as to measures of cerebral metabolic rate of oxygen consumption (CMRO2).MethodIn a randomized, double‐blind, crossover trial, 32 adults (16 young and 16 elderly) completed two counterbalanced testing sessions. Participants received a 25g glucose load in one session and a matched placebo in the other. Participants underwent resting state fMRI, blood glucose levels were monitored and mood and appetite were taken via self‐report at several time points. Seed‐based connectivity analyses were performed to assess resting state connectivity to the whole brain from seeds in the striatum (caudate, putamen, amygdala, thalamus) and the hypothalamus.ResultsSignificant treatment by age‐group interactions were found between putamen and inferior frontal gyrus, and from thalamus to parietal operculum and middle temporal gyrus. Elderly participants exhibited increased functional connectivity to these clusters. Changes in resting state connectivity from thalamus were correlated with changes in perceived hunger after glucose ingestion in the elderly group.Further, increased connectivity between hypothalamus and posterior cingulate and medial frontal cortex, core regions in the default mode network, were observed in the elderly group, which were correlated with changes in CMRO2.ConclusionThese findings suggest that a glucose load modulates brain connectivity related to appetite, mood and food homeostasis differently in younger and older healthy adults. Our findings have implications for the understanding of how the brain's response to energy intake changes in aging.Support or Funding InformationThis study was funded by an Australian Research Council (ARC) Grant.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of 8 Months of E‐cigarette Exposure on Cytokine expression in Mice
Authors: Pitzer Christopher , Breit Matthew , Hoskinson Hannah , Aboaziza Eiman , Mashall Kent , Burrage Emily , Chantler Paul , Bryner Randall , Olfert I. Mark 
Published: June 2021

IntroductionElectronic cigarettes (E‐cigs) are gaining popularity in the United States and worldwide. Little is currently known about the effects of chronic E‐cigarette exposure on cytokine expression throughout the body.MethodsC57BL/6 female mice were randomly assigned to cappuccino flavored E‐vapor (18 mg/ml nicotine, N=12) or filtered air (N=13) exposed groups. Animals were exposed 4 hours per day, 5 days per week for 8 months. After exposure major organs including lung, serum, and gastrocnemius were removed and flash frozen for cytokine analysis. Lung and skeletal muscle (i.e. gastrocnemius muscle) were homogenized with Tris‐HCL‐ buffer. Total protein from homogenates and serum were analyzed with the Bradford method and equal concentrations of total protein were analyzed using a Meso Scale Discovery U‐Plex kit according to manufacturer's instructions. Cytokines analyzed included: vascular endothelial growth factor (VEGF), Interleukin (IL)‐6, IL‐5, IL‐4, tumor necrosis factor‐ alpha (TNF‐α), IL‐1β, IL‐15, IL‐ 10, interferon gamma (IFN‐γ) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF).ResultsThe lungs of E‐cig exposed mice had 54% less VEGF compared to air exposed controls. IL‐6 was reduced by 57% in serum, but IL‐6 increased 994% in the skeletal muscle of E‐cig exposed mice compared to air exposed controls. IL‐10 was reduced by 87% in the gastrocnemius muscle of E‐cig exposed mice compared to air exposed control mice. No significant differences in the remaining factors (i.e. IL‐5, IL‐4, TNF‐α, IL‐1β, IL‐15, IFNγ, GM‐CSF) were identified between E‐cig and air groups in any of the other organs/tissues tested.DiscussionThe results of this study have implications for immune system response time and muscle growth/regeneration. IL‐6 is important for initiating immune system responses, decreases in its expression may lead to increased frequency or duration of infections by viruses or bacteria. IL‐10 in muscle has been shown to influence macrophages to increase anabolic capability of the muscle. Decreases in VEGF may indicate altered angiogenic potential, changes in muscle permeability and/or increased potential of apoptosis in the lung. Long‐term exposure to E‐cig vapor results in changes in cytokines and growth factors that may negatively influence immune and angiogenic potential.Support or Funding InformationNIH P20GM103434 (West Virginia IDeA Network for Biomedical Research Excellence) and Marshall‐WVU Health Cooperative AwardThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Metformin Restores Doxorubicin Induced Reduction in Complex II Respiration in C2C12 Skeletal Muscle Myotubes
Authors: Harley Jackson S , Mackay Amy D , Hancock Chad R 
Published: June 2021

Doxorubicin (DOX) is a widely used chemotherapeutic drug that blocks cell proliferation, but is limited because of its cardio‐toxic effects. Current research is directed towards finding treatments that reduce the cardio‐toxic effects without compromising the chemotherapeutic properties of DOX. Recent studies have shown that the negative effects of doxorubicin could be due to a disruption of mitochondrial energy metabolism, causing an increase in harmful free radicals. Metformin (MET), a highly prescribed drug for insulin resistance, has been shown to suppress the negative side effects associated with DOX, possibly by decreasing free radical damage. In this study, mitochondrial respiratory function was evaluated in order to further understand the effects of DOX treatment with or without the addition of MET. Given that MET is known to inhibit complex I of the electron transport chain, we wanted to examine the combined effects of DOX and MET on mitochondrial respiration. C2C12 mouse skeletal muscle myotubes were pretreated with 0.5 uM DOX and/or 0.5 mM MET for 16 hours. Consistent with the known inhibitory effect of MET on complex I, there was a 27% (p< .05) higher complex I mediated respiration rate in cells treated with DOX compared to DOX + MET. Interestingly DOX showed a 21% (p<.05) decrease in complex II respiration when compared to DOX + MET. Furthermore when comparing the difference between complex I respiration and complex II respiration, DOX treatment was 42% (p<.01) lower than the DOX + MET treatment. Even in the light of the direct inhibition of complex I by MET, there was an improvement in complex II mediated respiration in cells treated with MET. These results suggest that MET limits the damage caused by DOX treatment in tissues.Support or Funding InformationMentoring Environment Grant, Brigham Young UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Nucleolar Matrix Metalloproteinase‐2 Regulates rRNA Transcription
Authors: Garcia‐Vilas Javier , Ali Mohammad , Ilarraza Ramses , Hendzel Michael , Schulz Richard 
Published: June 2021

Gene expression in eukaryotic cells is a tightly regulated process, from pre‐transcriptional through post‐transcriptional stages. A major control point in gene expression is ribosome synthesis, since it executes mRNA translation and also regulates their stability. Genes encoding ribosomal proteins and ribosomal RNA (rRNA) are physically located and transcribed in specialized structures within the nucleus known as nucleoli. We previously reported that the protease matrix metalloproteinase‐2 (MMP‐2) was located inside the nucleus but its role there remains elusive.Confocal microscopy studies in our lab showed an accumulation of MMP‐2 in nucleoli in U‐2OS human osteosarcoma cells, suggesting a role in rRNA transcription. We found that MMP‐2 co‐localizes with nucleoli markers fibrillarin and nucleophosmin, and is located in active rRNA transcription sites within nucleoli of U‐2OS cells pulsed with 5‐fluorouridine (5‐FU).Chromatin immunoprecipitation (ChIP) assays showed an enrichment of MMP‐2 in the rRNA gene promoter region. We also found evidence of MMP‐2‐mediated proteolysis of purified histones (H1, H2A, H2B, H3 and H4), in a concentration‐dependent manner. Interestingly, we identified histone H3 to be the most susceptible to MMP‐2 activity and found at least one MMP‐ 2 cleavage site in the N‐terminal tail of histone H3.The N‐terminal tail of histone H3 is the location of a large number of known post‐translational modifications that are involved in the regulation of DNA relaxation and transcription, RNA splicing and DNA repair. Emerging evidence indicates that one of the mechanisms behind this is the proteolytic removal of the N‐terminal tail of histone H3 by a yet uncharacterized protease. Therefore, we sought to elucidate if nucleolar MMP‐2 has proteolytic activity on recombinant histone H3. We incubated MMP‐2 immunoprecipitated from isolated nucleoli with recombinant histone H3, in presence or absence of the MMP‐2 preferring inhibitor ARP‐100. Our data revealed that nucleolar MMP‐2 has proteolytic activity on histone H3 and is sensitive to ARP‐ 100.The involvement of MMP‐2 in rRNA gene expression in the nucleolus is a major novel mechanism by which intracellular may MMP‐2 regulate cell function via histone proteolysis.Support or Funding InformationCanadian Institutes of Health Research (CIHR) grants FDN‐143299 (to RS) and MOP‐119515 (to MH)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Behavioral Assessment of Mice with Mitochondrial CaMKII Inhibition
Authors: de la Rosa‐González Nicole , Joiner Mei‐ling 
Published: June 2021

Oxidative stress is thought to be the common underlying mechanism that leads to cellular dysfunction and demise in Parkinson's disease. Recent studies indicate that mitochondrial CaMKII (mtCamKII) activation is responsible for excess Ca2+ uptake under stress conditions, which ultimately leads to increased levels of cell death due to over‐production of reactive oxygen species. Inhibition of mtCaMKII, by CaMKIIN, has been established to decrease cell death under stress conditions in tissues such as the heart. It remains unidentified if inhibition of mtCaMKII in the Substantia nigra can counteract the loss of dopaminergic neurons, a hallmark of Parkinson's disease. To start addressing this interrogant, we utilized the 6‐OHDA unilateral lesion of the Substantia nigra model in mice expressing CaMKIIN, the inhibitor of mtCaMKII. Assessment of cell viability, using the Trypan blue exclusion test of cell viability, as well as confocal imaging of mitochondrial shape of SH‐SY5Y cell line, was performed to validate functionality of 6‐ OHDA. After 2 weeks, training motor impairment assays including rotarod, pole descent, inverted grid and footprint analysis were performed. Preliminary results validated the detrimental effects of 6‐OHDA on SH‐SY5Y cells and showed that mtCaMKIIN‐expressing mice were slower in the pole descent test. Thus, the 6‐OHDA unilateral lesion of the Substantia nigra model in mice shows great promise to assess level of motor impairment in mice expressing mtCaMKIIN, that way, assessing if inhibition of mtCaMKII is protective against cell death.Support or Funding InformationSpecial thanks to the lab's of Dr.'s Amy Lee, Ryan Boudreau and Nandakumar Narayanan, the Interdisciplinary Summer Undergraduate Research Program (ISURP), the PRISE program and the CCOM Office of Cultural Affairs and Diversity Initiatives. This project was supported by NIH (AL: NS084190, DC009433) and a Carver MRIG (MAJ).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Expression of myogenic regulatory factors is not different between whole muscle and isolated human muscle satellite cells following eccentric contractions
Authors: Fortino Stephen A , Nederveen Joshua P , Joanisse Sophie , Baker Jeff M , Snijders Tim , McGlory Christopher , McKay Bryon R , Kumbhare Dinesh , Parise Gianni 
Published: June 2021

Skeletal muscle satellite cells (SC) play an important role in muscle repair following injury. The regulation of SC activity is governed by myogenic regulatory factors (MRF), including MyoD, Myf5, myogenin and MRF4. The mRNA expression of these MRF in humans following muscle damage has been predominately measured in whole muscle homogenate. Whether the temporal expression of MRF in whole muscle homogenate accurately reflects SC specific expression of MRF remains largely unknown. Fourteen young men (21±0.5 yrs) performed 300 unilateral eccentric contractions (180 deg·s−1) of the knee extensors on a Biodex dynamometer. Percutaneous muscle biopsies from the vastus lateralis were taken prior to (Pre) and 48h post‐exercise. Fluorescence‐activated cell sorting (FACS) analysis was utilized to purify a population of NCAM+ muscle SC from the whole muscle homogenate. 48h post‐eccentric exercise, MyoD mRNA expression increased in whole muscle homogenate (~2.0‐fold, p<0.05) and in isolated SC (~2.2‐fold, p<0.05). Myf5 mRNA expression increased in whole muscle homogenate (~3.0‐fold, p<0.05) and in isolated SC (~3.2‐fold, p<0.05). Myogenin mRNA expression increased in whole muscle homogenate (~1.9‐fold, p<0.05) and in isolated SC (~12.0‐fold, p<0.05). MRF4 mRNA expression was not increased in 48h post‐exercise whole muscle homogenate or in isolated SC (p>0.05). These results suggest that the temporal mRNA expression of MRF in a population of isolated muscle SC accurately reflects the expression observed in whole muscle homogenate. Whole muscle homogenate represents a reliable proxy for the temporal expression of MRF in human muscle satellite cells.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
HIGH RESISTANCE OF CHICKEN EMBRYO RED BLOOD CELLS TO ACID ACTION
Authors: Mischenko Alexander , Lebedeva Elena , Golovko Vladimir 
Published: June 2021

In this paper, the results of the comparative studies of the resistance of Gallus gallus chicken embryo and human erythrocytes are presented to acid action.MethodsRed blood cells from decapitated 10–12 day‐old chicken embryos (5±0.6 g) and human donor blood were used in the experiments. The cells were isolated by centrifugation and washed three times with 145 μmol/l NaCl solution. The hemolysis was performed using: a) Mcllvein buffer solution (MBS) (0.31 g/l Na2HPO4 and 1.87 g/l citric acid, pH = 2.5); b) 0.1 N HCl. The optical density (D) was registered by using photocolorimeter at λ=540 nm. The part of the experiments was made by using isotonic 145 μmol/l choline chloride solution. The experiments were carried out at 18–20°C; the reliability of the differences was evaluated with the Van der Waerden test.ResultsThe hemolytic resistance of the chick embryo erythrocytes was higher than of human erythrocytes. The lag phase value, the time to 50% hemolysis (t50) and the time to complete hemolysis increased twice (p<0.05). The D value remained high after the completion of hemolysis. We believe that the effect of acid on the erythrocyte nucleus led to the decondensation and swelling of chromatin, causing an increase in optical density. The replacement of NaCl with choline chloride did not affect the resistance of human erythrocytes and led to an increase in the chick embryo resistance (p<0.05). In particular, the hemolytic start time (t0) and the end time (tend) were increased by 16% (p <0.05) and 21% (p <0.05) respectively. The results of these experiments showed that Na+/H+ exchange couldn't lead to an increase in the acid resistance of chick embryo erythrocytes. The calculations indicated that at the anion exchanger density of 2760 copies/μm2 and 8,300 copies/μm2 in chicken and human erythrocytes, respectively. The amount of anion exchangers was 1.2 × 106 copies per human erythrocyte and 6.3 × 105 copies per chick embryo erythrocyte. This is a in good agreement with the 2‐fold increased resistance of the chicken embryo erythrocytes compared to the human erythrocytes.Thus, the high resistance of chicken erythrocytes in comparison with human erythrocytes can be associated with a lower density of anion exchangers in the chicken red blood cells membrane.Support or Funding InformationThe study was supported by project № AAAA‐A17‐117012310152‐2This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Prior Menopausal Hormone Treatments And Association of Peripheral Markers of Neurovascular Unit Integrity And β‐amyloid in The Brains of Menopausal Women
Authors: Jayachandran Muthuvel , Lahr Brian D , Bailey Kent R , Lowe Val J , Kantarci Kejal , Miller Virginia M 
Published: June 2021

BackgroundBreak down of the blood brain barrier and activation of brain cells are implicated in progression of deposition of β‐amyloid that is associated with the pathophysiology of Alzheimer's disease. A previous study from our group indicated that deposition of β‐amyloid may be reduced in the brains of menopausal women treated with transdermal 17β‐estradiol. This study aimed to determine the association of peripheral microvesicles carrying markers of cells of the neurovascular unit with β‐amyloid in the brains of menopausal women and if the association was affected by prior menopausal hormone treatments (MHT).MethodsMenopausal women previously enrolled in the Kronos Early Estrogen Prevention Study at Mayo Clinic underwent β‐amyloid positron emission tomography (PET) imaging of their brains 3 years following treatment with either placebo (PL, n=29), transdermal 17β‐estradiol (tE2; n=21), or oral conjugated equine estrogen (oCEE; n=17) for 4 years. Microvesicles (MV) were isolated from peripheral venous blood by differential centrifugation and analyzed by flow cytometry using fluorophore conjugated antibodies directed toward total tau, β‐amyloid 1‐42 (Ab1‐42), neuron specific class III β‐tubulin (Tuj1), microglia ionized calcium adaptor molecule 1(Iab‐1), glial fibrillar acid protein (GFAP), and low density lipoprotein receptor‐related protein 1. Principal components analysis was used to reduce the dimensionality of the 6 brain markers to 2 principal components (PCs). Proportional odds ordinal logistic regression analysis was used to regress deposition of β‐amyloid on the 2 PCs with and without adjustment for MHT group.ResultsNumber of blood MV positive for Ab1‐42 differed significantly among MHT groups (median [IQR]: 6.06 [2.11, 12.55] in the PL; 2.49 [0.73, 3.59] in the tE2 and 4.96 [0.83, 10.31] in the oCEE; P=0.036). The first 2 PCs explain 58% of the variance of the 6 markers. PC#1 represented a contrast between MV‐Iab‐1 and the MV‐GFAP and MV‐Tuj1. In multivariable models, brain β‐amyloid load positively associated with the first PC after adjustment for MHT (P= 0.006).ConclusionMV derived from cells of the neurovascular unit can be detected in peripheral blood, and, when combined into summary scores, showed an association with deposition of β‐amyloid in the brain that is independent of MHT.Support or Funding InformationSupported by grants from NIH P50 AG044170 and the Mayo FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.