bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of the Gut Microbiome‐Derived Metabolite Trimethylamine N‐oxide Prevents Western Diet‐Induced Arterial Dysfunction
Authors: Brunt Vienna E. , Sapinsley Zachary J. , Gioscia‐Ryan Rachel A. , Richey James J. , Zigler Melanie C. , Seals Douglas R. 
Published: June 2021

Consumption of a Western‐style diet (WD; high fat, high sugar) is associated with impaired arterial function and increased risk of cardiovascular diseases (CVD). One possible link between WD and impaired arterial function may be the gut microbiome. WD induces adverse changes to the gut microbiome, and consequently, increased production of the gut‐derived metabolite trimethylamine N‐oxide (TMAO). TMAO is causally atherogenic in mice and predicts incident risk of major CV events in humans, but it is unknown whether TMAO mediates arterial dysfunction that precedes clinical CVD.PURPOSETo determine if inhibition of TMAO with 3,3‐dimethyl‐1‐butanol (DMB; inhibitor of microbial TMA lyase) prevents WD‐induced large elastic artery stiffening and endothelial dysfunction.METHODSTwenty‐four young (3 mo) male C57BL/6 mice were fed WD (40% fat, 25% sugar) for 5 months and were supplemented without (WD‐Control, WD‐C; N=11) or with 1% DMB (N=13) in drinking water for the last 8 weeks. Arterial stiffness was assessed as aortic pulse wave velocity (aPWV) following 3 mo of WD (intervention baseline, BL) and following 4 and 8 weeks on the intervention. Endothelial function and its suppression by oxidative stress were evaluated ex vivo as carotid artery endothelium‐dependent dilation (EDD) to increasing doses of acetylcholine (10−9 to 10−4M) alone and following pre‐incubation with the superoxide dismutase mimetic TEMPOL. Total whole‐cell superoxide production was assessed in aortic rings via electron paramagnetic resonance spectroscopy. The same assessments were made in a reference group of age‐matched C57BL/6 male mice fed standard rodent chow (Normal Chow, NC; N=10). Data are mean±S.E.RESULTSWD induced progressive increases in aPWV (BL: 346±15, 4wks: 363±14, 8wks: 420±23 cm/sec, p=0.01), which were prevented by DMB (BL: 347±10, 4wks: 349±20, 8wks: 355±16cm/sec, p=0.98; DMB vs. WD‐C at 8wks: p=0.02). WD impaired EDD (peak dilation: 83.0±1.1% vs. NC: 92.5±2.0%, p<0.01), which was prevented by DMB (93.4±1.5%, p<0.0001 vs. WD‐C, p=0.71 vs. NC). Group differences in EDD were no longer significant after inhibition of oxidative stress with TEMPOL (peak EDD: p=0.22). Aortic superoxide production tended to be lower in DMB (2.2±0.3 AU) vs. WD‐C mice (3.9±1.1 AU, p=0.12) and was not different from NC (2.5±0.6 AU, p=0.52).CONCLUSIONSDMB supplementation prevented WD‐induced arterial stiffening and endothelial dysfunction, possibly through attenuation of oxidative stress. These data establish a role of the gut microbiome and TMAO in mediating WD‐induced arterial dysfunction and provide initial evidence of a novel strategy for preventing arterial dysfunction and reducing CVD risk.Support or Funding InformationSupported by R01 HL134887 & T32 HL007822This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Analysis of mutations in Muscle LIM Protein associated with human heart failure
Authors: Boateng Samuel , Atkins Jennifer , Hawanatu Sesay , Sorensen Thomas , McGuffin Liam 
Published: June 2021

Heart failure is defined as a progressive condition in which the heart is unable to pump enough blood to meet the body's needs for oxygen and nutrients. A common cause of heart failure is due to genetic mutations in cytoskeletal proteins required for contractile activity and/or mechanosensing. These include proteins such as CSRP3 or muscle LIM protein (MLP) and a number of these mutations result in cardiomyopathy, heart failure and sudden death.MLP is a small protein comprised of 194 amino acids and is found in the Z‐disk of the myofilaments in cardiac myocytes. MLP functions as a signalling molecule linking mechanosensing with cellular growth and adaptation. MLP can also interact with numerous proteins in the cytoplasm and nucleus. There are 5 key mutations in the MLP gene that can lead to cardiomyopathies. We investigated the L44P, S54R‐E55G, C58G, K69R and G72R mutations.The aim of this investigation was to determine how these mutations elicit their effects by examining protein structural changes and effects on binding partners. The analysis was performed using bioinformatics tools and online servers.The full length wildtype MLP sequence was submitted to a variety of servers along with the mutations. The results showed that L44P and C58G to have the most deleterious effect on the protein structure and function. G72R results in a stabilisation within the site directed mutator server, while K69R shows little effect. However, the G72R is likely to affect the nuclear localisation signal function thereby impairing its nuclear activity. We have previously shown that nuclear translocation of MLP is required for stretch dependent cellular adaptation in cardiac myocytes.Radius of gyration and root‐mean‐square deviation of atomic positions plots indicate a more compact and less flexible protein with the L44P mutation compared with the wildtype. This would change the protein's sensitivity to mechanical stress thereby affecting downstream signalling and subsequent cellular remodelling.Finally we examined the effect of the mutations on protein‐protein interactions with binding partners. All the mutations inhibited interactions with alpha actinin‐2 and cofilin while L44P, S54R‐E55G, C58G and G72R all prevented interaction with NRAP and TCAP. These interactions are essential for mechanosensing within the myofilaments or downstream signalling required to elicit an effective cellular response. This analysis gives a better understanding of the molecular function of MLP and how these mutations result in maladaptation and heart failure in man.Support or Funding InformationDiamond Light Source Ltd and the University of ReadingThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Nuclear‐mitochondrial crosstalk in the heart during diabetes mellitus – the impact on RNA in mitochondrial subpopulations
Authors: Hathaway Quincy Alexander , Shepherd Danielle Lee , Durr Andrya Jean , Hollander John Michael 
Published: June 2021

The cellular milieu of diabetes mellitus, with changing substrate utilization, ROS, inflammation, and other factors, influences the function of the mitochondrion, which plays a vital role in bioenergetics. How the mitochondrion functions is affected both by the import of nuclear‐encoded mitochondrial proteins and by regulation of RNA transcripts within the mitochondrion. We have previously shown during diabetes mellitus, that pathways involving protein (HSPA9) and small RNA (PNPase) import are directly impacted. The implications of epigenetic control of the genome, which is shown to be globally altered in the diabetic heart, is relatively unexplored in regards to mitochondrial health and function. Type 2 Diabetic and non‐diabetic human right atrial tissue and db/db mouse whole heart were used for evaluation of epigenetic modifications to nuclear‐encoded mitochondrial proteins involved in protein and RNA import into the mitochondrion, HSPA9 and PNPT1, respectively. Also, analysis of human atrial mitochondrial RNA was examined. The promoter region of HSPA9 and PNPT1 were processed for histone activation/repression (H3K4me3 and H3K27me3, respectively) and DNA methylation. Chromatin‐immunoprecipitation qPCR evaluated differentially bound regions of H3K4me3 and H3K27me3. Bisulfite treatment, methylation PCR, and cloning were used to measure methylation status of CpG islands. Small RNAs were sequenced through NextGen sequencing for mitochondrial subpopulations, subsarcolemmal (SSM) and interfibrillar (IFM). During the diabetic pathology, HSPA9 was shown to have increased H3K27me3 association in human and mouse (P ≤ 0.05), while PNPT1 exhibited significantly lower H3K27me3 (P ≤ 0.05) and higher H3K4me3 (P ≤ 0.05) association in human and mouse. Neither gene had differential methylation patterns during type 2 diabetes mellitus. In type 2 diabetes mellitus, all human mitochondrial transcribed RNA transcripts had a significant decrease in expression in the SSM (Padj ≤ 0.05), while no changes in the IFM were observed. Our results suggest that during type 2 diabetes mellitus, nuclear‐encoded proteins that comprise the mitochondrial proteome and are involved in protein and RNA import can be epigenetically altered. Mitochondrial subpopulations also differentially express RNA during diabetic insult, with the SSM being more detrimentally impacted. Epigenetic alterations, and changes in RNA, reveal how environmental changes to the nuclear genome could shape mitochondrial structure and function.Support or Funding Information(Support: NIH R01 HL128485; AHA 17PRE33660333)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
MODULATION WAY CLASSICAL AND ALTERNATIVES OF RENIN ANGIOTENSIN SYSTEM (RAS) IN MESANGIAL CELLS AFTER EXPOSURE TO FRUCTOSE.
Authors: Yokota Rodrigo , Jara Zaira Palomino , Matsumoto Larissa Emi , Aragao Danielle Sanchez , Casarini Dulce Elena 
Published: June 2021

BackgroundOur group demonstrated previously that rats subjected to a high fructose diet showed increased activity of kidney ACE. In order to understand the effect of fructose in the forming process of angiotensin II (Ang II) and angiotensin 1–7 (Ang1–7) affecting the levels of these effectors, the aim of this study was to evaluate the activities of the RAS enzymes responsible for the formation of Ang1–7 and Ang II of immortalized human mesangial cells (IMCH)exposed to low and high concentration of fructose.MethodsIMCH were divided into control (low glucose medium), Fructose 5 mM(medium + 5 mM Fructose) and Fructose 30mM(medium + 30 mM Fructose) groups. The enzymatic activity of ACE, chymase, cathepsin D, Neutral Endopeptidase (NEP) and ACE2 were evaluated using Z‐Phe‐His‐Leu, Abz‐AIKFFSAQ‐EDDnp, Abz‐AIAFFSRQ‐EDDnp, Abz(d)‐Arg‐Gly‐Leu, Mca‐APK (DNP) as substrates, respectively. Data were analyzed using ANOVA one way.ResultsAmong the AngII forming enzymes, fructose decreased ACE activity (CG:0,044±0,01 vs.F5:0,016±0,004* vs. F30:0,008±0,002* mU/mg protein) in cell lysate. Both fructose concentrations increased chymase (CG:0,85±0,03 vs. F5:1,07±0,07* vs. F30:0,99±0,05* nM/min/mL) in the culture medium. No effect was observed on the activity of cathepsin D. When evaluating the activities of peptidases forming Ang‐1–7, NEP activity was decreased in lysate cells in F30 group and decreased in F5 group in culture medium. We did not detect differences in ACE2 activity.ConclusionThe results suggest fructose modulates renal and systemic RAS in IMCH acting in the classical and alternative pathways of Ang II formation. Additionally, this sugar was able to decrease NEP activity, forming Ang‐1–7. Quantitation of angiotensin remains necessary to better understand how the end effector is available in IMCH and to evaluate possible effects on glomerular physiology.Support or Funding InformationCapesThis 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 Yoga based cardiac rehabilitation on Vascular and Endothelial function in patients post myocardial infarction – A randomized controlled trial
Authors: Christa S. Edmin , Jaryal Ashok Kumar , Yadav Raj Kumar , Roy Ambuj , Chandran Dinu S. , Deepak Kishore Kumar 
Published: June 2021

BackgroundVascular and Endothelial dysfunction is an independent predictor of cardiovascular and all cause mortality. We tested the effect of 12‐week Yoga‐based cardiac rehabilitation program on Vascular and Endothelial function in patients following acute myocardial InfarctionMethodsIn this study, 80 patients (50.06 ± 9.43 years) were randomly assigned to either Yoga based cardiac rehabilitation group (YG) or Standard care group (CG) post acute‐myocardial infarction (MI). The YG received a structured yoga based cardiac rehabilitation program in addition to usual care. CG participants received three brief educational sessions. Baseline (at 3 weeks post MI) and post intervention assessments included carotid‐femoral pulse wave velocity (cf‐PWV), augmentation index (AIX@HR75) normalized to heart rate and flow mediated dilation (FMD). All recordings were done in the Autonomic & Vascular function lab, Department of Physiology at AIIMS, New Delhi (CTRI/2017/09/009925).ResultsValues are expressed as mean change score. After 12 weeks, no significant changes were found between groups in cf‐PWV(−0.29±2.18 vs. −0.18±1.70, p=0.82). AIX@HR75 decreased (0.35±5.08 vs. 3.88±8, p=0.02) and FMD increased (2.72±5.49 vs. −0.14±4.81, p=0.01) significantly in YG than the control group. Per‐protocol analysis (n=52) also provided similar results. There was no significant changes were found between groups in cf‐PWV(−0.84±2.90 vs. −0.12±1.89, p=0.40). AIX@HR75 decreased (−0.85±4.29 vs. 2.13±7.13, p=0.05) and FMD increased (3.36±6.38 vs. −0.28±5.22, p=0.02) significantly in YG than the control group.ConclusionsYoga based cardiac rehabilitation improved endothelial function and functional measure of arterial stiffness significantly. There was no significant change in structural measure of arterial stiffness. This signifies that short term yoga based rehabilitation could improve only the functional measures and may be insufficient to elucidate structural changes over 12 weeks.Support or Funding InformationAIIMS, New Delhi, IndiaICMR, New Delhi, IndiaMRC, UKThis 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 Resistance Training on Antioxidant Expression in Type I Muscle from Doxorubicin Treated Rats
Authors: Ahn WonMo , Hydock David Scott , Twaddle Mackenzie , Tigner Allison , Wagner Meghan , Bredahl Eric 
Published: June 2021

The purpose of this study was to determine the effects of resistance training prior to and during doxorubicin (DOX) treatment on antioxidant enzyme expression in the primarily type I soleus muscle. Thirty‐six male, Sprague‐Dawley rats were randomly assigned to one of four groups: sedentary+saline (SSS), sedentary+DOX (SSD), resistance training+saline (RRS), and resistance training+DOX (RRD). The resistance training protocol incorporated a raised cage model where food and water were elevated progressively which provided hindlimb loading 10 weeks prior to DOX injection and during the course of DOX treatment. Animals receiving DOX received 3 mg/kg DOX administered i.p. weekly for 4 weeks (12 mg/kg cumulative). Five days following the final DOX injection, solei were excised and Western blotting was performed to quantify superoxide dismutase (SOD)1 and SOD2 expression. No significant main activity or drug effects were observed with SOD1 or SOD2 expression, but a significant activity × drug interaction was observed for SOD1 expression with RRD expressing significantly higher SOD1 than SSD. This interaction, however, was not observed for SOD2. In conclusion, resistance training prior to and during weekly DOX administration promoted an increase in SOD1 expression (the cytosolic form of SOD) suggesting that resistance training may play a role in combatting DOX myotoxicity by enhancing cytosolic antioxidant defenses.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Body weight influences genes related to energy metabolism in human skeletal muscle
Authors: Wu Hexirui , Dridi Sami , Ferrando Arny A. , Kim Il‐Young , Wolfe Robert R. , Baum Jamie I. 
Published: June 2021

Over one third of adults in the United States are obese. Skeletal muscle is a major site of metabolic activity and the most abundant tissue in the human body. For skeletal muscle to function at optimal levels, the efficient activation of processes that regulate muscle development, growth, regeneration and metabolism is required. Mitochondria play a key role in ensuring adequate levels of ATP needed for skeletal muscle contraction. In addition, the capacity of skeletal muscle to contribute to whole‐body energy expenditure is related to the fact that muscle makes up ~40% of total body mass and accounts for 20–30% of total resting oxygen uptake. This indicates that mitochondrial functional capacity is likely to directly affect muscle metabolic function and have a significant impact on whole‐body metabolism. Mitochondria are also important for ensuring muscle is able to modulate substrate oxidation (e.g. lipid and carbohydrate oxidation) following a meal. The objective of this study was to determine if there was an effect of body weight on genes related to mitochondrial function in skeletal muscle from normal weight (NW) and obese/overweight (OW) participants. Muscle biopsies were taken from OW (n=31, ages 48±19) and NW (n=12, ages 43±18) adults. Gene expression was measured using real‐time PCR. There was an increase (p<0.05) in the expression of both PGC1α and PPARγ, which are regulators of mitochondrial biogenesis, in OW vs NW participants. Expression of UCP2, a key regulator involved in ATP synthesis, was higher (p<0.05) in OW participants. In addition, genes related to mitochondrial respiration, mitochondrial DNA replication and transcription, NRF1 and Tfam, had higher (p<0.05) expression in OW. Cpt1a, a gene encoding carnitine palmitoyltransferase 1A, which is necessary for fatty acid oxidation, had lower (p<0.05) expression in OW compared with NW. Conclusively, these data provide a preliminary view of differences in energy metabolism gene expression in obese/overweight versus normal weight individuals.Support or Funding InformationArkansas Biosciences InstituteThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterizing Heat Stress and Strain in Electric Utility Workers by Means of a Questionnaire
Authors: Kenny Glen P. , Flouris Andreas D. , Brosseau Lucie , Dervis Sheila , Notley Sean R. 
Published: June 2021

In recent field work we showed that the high physical demands combined with restrictions to heat loss due to protective work uniforms caused some electric utility workers to experience dangerous levels of hyperthermia (J Occup Environ Hyg. 2015;12:708). These findings indicate that heat stress in the electric utility industry may be detrimental to worker health and safety. In the present study, 414 workers in the power generation and delivery industry across 15 US states completed a two‐part on‐line questionnaire anonymously. Part 1 comprised 15 general questions on the worker's age, sex, role in the organization, general duties, workplace location, work shift duration, years of experience, level of physical activity, frequency of heat exposure, other. The second part consisted of a validated questionnaire for the assessment of heat stress at the workplace – the ‘Heat Strain Score Index (HSSI)’ (Int J Prev Med 2013; 4:631). It was composed of 18 questions which included key factors in heat stress evaluation (environmental parameters, work intensity, level of heat exposure, clothing insulation and permeability, etc.) and indicators of heat strain (sweat rate, fatigue, thirst, symptoms of heat‐related illness, etc.) with cut‐off scores as follows: ≤13.5, green zone or safe level; 13.6 to 18.0, yellow zone or alarm level; >18.0, red zone or danger level. The average (±SD) age of the respondents was 46(10) years and they reported being in their present position for 11(10) years. They typically performed 5(1) consecutive days of work lasting 10(6) hours each day. For all job types (all workers), 79% of respondents reported heat stress was a problem. This number was greater (93%) in those performing physically demanding jobs (e.g. linesman). Further, 30% and 67% of all workers indicated they were exposed to heat stress occasionally and daily, respectively. In contrast, 81% of linesman reported being exposed to heat stress on a daily basis with only 19% experiencing occasional exposure. Based on the HSSI, 43% of all workers and 68% of linesman were categorized in the red zone (danger level) and therefore at an elevated risk of a heat‐related injury (both p<0.01). Our findings demonstrate that electric utility workers are likely to experience excessive heat strain and research must be conducted to explore methods to effectively and efficiently manage heat stress and strain in these workers.Support or Funding InformationHuman and Environmental Physiology Research Unit (G.P. Kenny).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exercise effects on Thermoregulation in Obese Mexican Young Women
Authors: Garcia‐Pelagio Karla , Ambrosio Natalia , Espinoza Beda , Galicia Eugenio , Mejia Jorge , Navarro Luz 
Published: June 2021

Obesity has become a serious global health problem affecting both adults and children that remains unclear. Mexico is one of the countries with the highest rate of obesity worldwide. As a disease, obesity has deleterious effects on metabolic homeostasis associated with increased heat production; however, subcutaneous adipose tissue provides an insulating layer that impedes heat loss. To maintain normothermia, obese individuals must increase heat dissipation. We explore the potential role of external and core temperature in energy balance, and develop the hypothesis that basal temperature and changes in the temperature response in various situations to the enhanced metabolic efficiency of the obese state. 45 participants divided in Normal (N), overweight (OW) and obese (O) young women out of the ovulatory state performed bicycle exercise for 15 min in a climatic chamber at 38°C previous acclimatization period. Skin and core temperature, cardiac frequency, arterial pressure and oxygen consumption were measured every 2 minutes before, during and after the exercise reaching the initial temperature value. Our results indicate an important increase in core temperature for OW and O population compared to N women. External temperature was higher in N women compared to OW and O. Notably; N women reach its initial temperature 3‐fold times quicker than O and OW women. Our data suggest a compelling evidence for a thermogenic handicap in the obese Mexican population.Support or Funding InformationSupported partially by UNAM (PAPIIT IA207818) to KPGPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.