bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential Role of Structural Variants of Circulating Lipopolysaccharide in Exercise‐Induced Heat Illness
Authors: Wright Skylar , Hosokawa Yuri , Dadzie Ekow C , Lopez Virgilio , Colburn Abigail T , Bivona Joseph J , Thorton Staci N , Adams William M , Brown Cyrus , Katch Rachel K , Huggins Robert A , Stearns Rebecca L , Jardine John F , Davis Robert J , Casa Douglas J , Lee Elaine C 
Published: June 2021

Previous investigations at the Falmouth Road Race (FRR; Falmouth, MA) indicated that combined exercise, heat, and dehydration stress increased gastrointestinal tract permeability. This subsequently exposed the circulatory system to components of the microbiome usually found only in the gut. Lipopolysaccharide (LPS), a component of Gram‐negative bacterial membranes, is one such element released into circulation, especially post‐exercise. LPS in circulation activates host immune cell signaling cascades that can lead to inflammatory responses (e.g. cell pyroptosis, exertional heat stroke, and sepsis) and upregulated proinflammtory gene expression (e.g. TNF‐α and IL‐1β). While subjects of the 2015 FRR (N=30) had elevated core temperature post race compared to pre (pre 36.87°C vs. post 39.87°C, p<0.05), there is unexplained variation in the relationship among the level of circulating LPS (2.90EU/ml pre vs. 3.48EU/ml post, p<0.05; Hycult Biotech, ELISA), core temperature, and subsequent heat stroke presentation. Since some strains of bacteria induce a strong immune response while others do not, it is of interest to determine if structural variations in LPS contribute to varying immune system activation during exercise‐heat stress. Diet influences the composition of the microbiome and different microbiome species have varying LPS structures. Because of this, even short‐term alterations in macronutrient consumption can alter the composition and gene expression of the microbiome. Ongoing research will utilize extraction of LPS from pre‐race and post‐race plasma and HPLC/MS to characterize structural variations in LPS in individuals of the 2015, 2016, and 2017 FRR.Support or Funding InformationNew investigator start‐up, McNair Scholar Program, FRRThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Translational Control and the Integrated Stress Response Regulate the Fate of UVB‐Irradiated Human Keratinocytes
Authors: Wek Ronald C , Collier Ann E , Spandau Dan F 
Published: June 2021

Upon exposure to sublethal UVB irradiation, human keratinocytes transiently inhibit progression of the cell cycle to allow time for DNA repair and determination of cell fate. These processes are critical for evading the initiation of carcinogenesis in skin. Central to these adaptive processes is the Integrated stress response (ISR) that features repression of the initiation phase of protein synthesis by induced GCN2 phosphorylation of eIF2 (eIF2‐P). Phosphorylation of eIF2 prevents delivery of initiator tRNA to the ribosome machinery. Coincident with the reduction in global mRNA translation, eIF2‐P selectively enhances translation of mRNAs that participate in stress adaptation. In this study, we determined a cytoprotective mechanism for eIF2‐P in response to UVB in human keratinocytes. In response to UVB, genetically engineered loss of induced eIF2‐P lowered G1 arrest, DNA repair, and cellular senescence, coincident with enhanced apoptosis. Using polysome profiling and RNA‐seq analyses, we carried out genome‐wide measurements of translation in human keratinocytes. A collection of gene transcripts showed enhanced association with large polysomes in response to UVB, suggestive of enhanced translation efficiency. Network analysis of the preferentially translated genes indicated eIF2‐P regulation of the cell cycle, cell communication, stress responses, metabolism, and inflammation. One of the identified preferentially translated genes was CDKN1A (WAF1, CIP1) encoding p21 protein, that functions to block the progression from G1 to S phase of the cell cycle and to initiate cellular senescence. While enhanced levels of CDKN1A mRNA occurred in response to UVB independent of induced eIF2‐P, enhanced synthesis of p21 protein required the ISR. Two splicing variants of CDKN1A mRNA, V1 and V4, are expressed in keratinocytes, with V4 being preferentially translated following UVB induced eIF2‐P by a mechanism mediated in part by upstream ORFs situated in the 5′‐leader of CDKN1A mRNA. These results show that eIF2‐P is cytoprotective in response to UVB by a mechanism featuring translation of a specific splice variant of CDKN1A that facilitates G1 arrest and subsequent DNA repair.Support or Funding InformationNIH grants R01 GM049164 (RCW), F31 ES026517 (AEC), and R01 ES20866 (DFS)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sympathetic Neuro‐Hemodynamic Transduction at Rest in Subjects with Low and High Tolerance to Simulated Blood Loss
Authors: van Helmond Noud , Baker Sarah E , Bukartyk Jan , Miller Andrew D , Convertino Victor A , Joyner Michael J 
Published: June 2021

BackgroundCentral hypovolemia elicited by hemorrhage triggers sympathetically‐mediated baroreflex responses to maintain organ perfusion through peripheral vasoconstriction; humans with low tolerance (LT) to central hypovolemia have a diminished vasoconstrictor response during progressive reductions in central volume. Using the lower body negative pressure (LBNP) hemorrhage model, we tested the hypothesis that humans with LT to central hypovolemia would display attenuated resting beat‐to‐beat neuro‐hemodynamic transduction of muscle sympathetic nerve activity (MSNA) compared to those with high tolerance (HT).MethodsMSNA (microneurography, peroneal nerve) and diastolic arterial pressure (DAP; finger photoplethysmography) were recorded in 33 human subjects (23 men, 10 women, age: 31 ± 9 years, BMI: 26 ± 4 kg/m2) who subsequently underwent LBNP to tolerance (onset of pre‐syncopal symptoms) – Figure 1. Consistent with previous studies, subjects were classified as LT if they experienced pre‐syncopal symptoms prior to completing LBNP of −60 mm Hg, or as HT if they experienced pre‐syncopal symptoms after completing LBNP of −60 mm Hg. We performed linear regression analysis on data of binned MSNA burst areas against DAP; the slope of this regression represents transduction.ResultsOf the 33 subjects, 8 exhibited LT (time to pre‐syncope for LT: 17 ± 2 min and HT: 27 ± 5 min) Contrary to our hypothesis, resting beat‐to‐beat neuro‐hemodynamic transduction was not different between LT and HT subjects (median 0.09 IQR 0.03 – 0.16 mmHg (%s) −1 vs. median 0.12 IQR 0.06 – 0.16 mmHg (%s) −1, respectively, p = 0.44) and was not related to time to pre‐syncope (p = 0.70).ConclusionTolerance to simulated blood loss is not related to resting sympathetic neuro‐hemodynamic transduction.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Are Improvements in Skeletal Muscle Oxidative Capacity Possible in the Elderly?
Authors: Chung Susie , Rosenberry Ryan , Bhella Paul S , Park Suwon , Dombrowsky Thomas , Ogidan Felicia A , Haykowsky Mark J , Nelson Michael D 
Published: June 2021

Loss of skeletal muscle function is a key factor contributing to the reduced quality of life and mobility in aging individuals. While several mechanisms have been implicated, reduced skeletal muscle oxidative capacity is thought to play a major role. Exercise training is known to improve skeletal muscle oxidative capacity in young healthy populations. Whether exercise training can improve skeletal muscle oxidative capacity in elderly individuals, with associated cardiovascular risk factors, remains unclear. To address this question, we recruited 8 elderly participants from the local Dallas‐Fort Worth community (73 ± 7 yrs; m/f: 2/6; BMI: 25.9 ± 3.1 kg). Subjects completed two baseline visits to establish our day‐to‐day reproducibility, followed by 4‐weeks of handgrip exercise training at 30% of maximal voluntary contraction (MVC, non‐dominant arm), five (5) days a week. MVC was reassessed each week, and the total number of contractions was gradually increased, for a total of 600, 900, 1200, and 1500 grips per day, respectively. Skeletal muscle oxidative capacity was assessed using a well‐established near‐infrared spectroscopy (NIRS) protocol, expressed as the post‐exercise muscle oxygen consumption recovery time constant (i.e. tau, in seconds). To date, we have completed data collection on 5 of 8 participants. All five participants increased their MVC with exercise training (pre‐training MVC: 23.1 ± 17.2 kg; post‐training MVC: 26.8 ± 16.1 kg, or 16.0% increase). Despite measurable increases in muscle strength however, skeletal muscle oxidative capacity was unchanged from baseline (pre‐training tau: 45.9 ± 16.5 s; post‐training tau: 49.6 ± 13.5 s, or 8.1% increase). These data are in contrast to at least two prior reports showing an improvement in skeletal muscle oxidative capacity in young, healthy subjects, and elderly participants at least 10 years younger than those studied here. We interpret these data to reflect an upper limit to the training adaptation previously reported.Support or Funding InformationThis work was supported by a UT Arlington Interdisciplinary Research Program 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.
Glycocalyx degradation impairs endothelial function in cultured cells and a mouse model of type 2 diabetes
Authors: Ghiarone Thaysa , Foote Christopher A. , Padilla Jaume , Martinez‐Lemus Luis A. 
Published: June 2021

IntroductionThe endothelial glycocalyx is a critical component of the vascular intima putatively essential for the mechanotransduction of shear stress and arterial flow‐mediated dilation (FMD). Neuraminidase degrades the glycocalyx and is elevated in the plasma of patients with type 2 diabetes (T2D) and a mouse model of insulin resistance. Therefore, we hypothesized that exposure of cultured endothelial cells and isolated arteries to neuraminidase would degrade the glycocalyx and impair FMD, while neuraminidase inhibition in vivo would improve arterial FMD in a mouse model of T2D.MethodsHuman umbilical vein endothelial cells (HUVECs) in culture were treated with neuraminidase (125 mU) for 1h and subsequently assessed for glycocalyx content by immunocytochemistry. Isolated mouse mesenteric arteries were also treated with neuraminidase and evaluated for FMD. In addition, T2D db/db mice were treated with the neuraminidase inhibitor, Zanamivir (10mg/day) for 5 days and their femoral arteries isolated and tested for FMD and acetylcholine‐induced vasodilation.ResultsNeuraminidase reduced Syndecan‐1 staining by 43% and presence of glycosaminoglycans by 28% in HUVECs, indicating a significant (P<0.05) reduction in glycocalyx content. Mesenteric arteries exposed to neuraminidase displayed a significant (P<0.05) reduction in FMD. In addition, treatment of db/db mice with Zanamivir significantly improved FMD and acetylcholine‐induced vasodilation in isolated femoral arteries, while reducing serum neuraminidase activity in plasma.ConclusionOur results demonstrate that neuraminidase reduces glycocalyx content in endothelial cells and impairs FMD in isolated arteries. Furthermore, neuraminidase inhibition improved overall endothelial function suggesting that targeting neuraminidase may be a viable treatment for endothelial dysfunction in the setting of T2D.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Implications‐Enzymatic Degradation of the Endothelial Glycocalyx on the Microvascular Hemodynamics and the Arteriolar Red Cell Free Layer of the Rat Cremaster Muscle
Authors: Jani Vivek P , Yalcin Ozlem , Johnson Paul C , Cabrales Pedro 
Published: June 2021

BackgroundThe endothelial glycocalyx is a complex network of glycoproteins, proteoglycans, and glycosaminoglycans; it lines the vascular endothelial cells facing the lumen of blood vessels forming the endothelial glycocalyx layer (EGL).ObjectiveThis study aims to investigate the microvascular hemodynamics implication of the EGL by quantifying changes in blood flow hydrodynamics post enzymatic degradation of the glycocalyx layer.MethodsHigh‐speed intravital microscopy videos of small arteries (around 35 μm) of the rat cremaster muscle were recorded at various time points after enzymatic degradation of the EGL. The thickness of the cell free layer (CFL), blood flow velocity profiles, and volumetric flow rates were quantified. Hydrodynamic effects of the presence of the EGL were observed in the differences between the thickness of CFL in microvessels with an intact EGL and glass tubes of similar diameters.ResultsMaximal changes in the thickness of CFL were observed 40 min post enzymatic degradation of the EGL. Analysis of the frequency distribution of the thickness of CFL allows for estimation of the thickness of the endothelial surface layer (ESL), the plasma layer, and the glycocalyx. Peak flow, maximum velocity, and mean velocity were found to statistically increase by 24%, 27%, and 25%, respectively, after enzymatic degradation of the glycocalyx. The change in peak‐to‐peak maximum velocity and mean velocity were found to statistically increase by 39% and 32%, respectively, after 40 min post enzymatic degradation of the EGL. The bluntness of blood flow velocity profiles was found to be reduced post degradation of the EGL, as the exclusion volume occupied by the EGL increased the effective volume impermeable to RBCs in microvessels.ConclusionThis study presents the effects of the EGL on microvascular hemodynamics. Enzymatic degradation of the EGL resulted in a decrease in the thickness of CFL, an increase in blood velocity, blood flow, and decrease of the bluntness of the blood flow velocity profile in small arterioles. In summary, the EGL functions as a molecular sieve to solute transport and as a lubrication layer to protect the endothelium from red blood cell (RBC) motion near the vessel wall, determining wall shear stress.Support or Funding InformationThis work was supported by NIH grants from the Heart Lung and Blood Institute, P01‐HL11090, R01HL126945, and R01‐ HL138116.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Increased Intracellular Lipid Accumulation in Cholesterol Loaded VSMCs upon MRTFA Overexpression
Authors: Alajbegovic Azra , Holmberg Johan , Ekman Mari , Albinsson Sebastian 
Published: June 2021

Accumulation of lipids in in the arterial wall is a key feature of atherosclerosis. In atherosclerotic plaque from human and mouse origin it has recently become appreciated that more than 50% of total foam cells are derived from vascular smooth muscle cells (VSMCs) suggesting a much larger role for VSMCs in foam cell formation then previously assumed. The molecular mechanism behind this process and clinical significance remains yet to be elucidated. Myocardin Related Transcription Factor –A (MRTFA) is a transcriptional co‐activator that has been demonstrated to play a key role in pathological vascular remodelling including progression of atherosclerotic lesions. Here we aim to investigate the functional role of MRTFA on cholesterol loading of VSMCs.To address this, human coronary artery smooth muscle cells (HCASMCs) were loaded with cholesterol‐cyclodextrin complexes for 96 hours. Foam cell formation was evident by accumulation of intracellular Oil red O‐stained lipids. Notably, overexpression of MRTFA increased lipid accumulation with considerable build‐up of lipid droplets in the cytoplasm. Small molecule N‐cyclopropyl‐5‐(thiophen‐2‐yl)‐isoxazole‐3‐carboxamide (ISX), an activator of MRTFA‐driven transcription, further potentiated this effect. Although expression of macrophage markers by mouse SMCs following cholesterol loading has been demonstrated, we did not observe any consistent change in the expression of macrophage or SMCs markers in lipid loaded cells of human origin.These preliminary findings suggest that MRTFA in VSMCs plays a significant role in foam cell formation following cholesterol loading. A better understanding of the mechanisms for cholesterol handling may enable us to come up with better therapeutic strategies for prevention of cholesterol accumulation in the arterial walls and its clinical outcomes.Support or Funding InformationThis work was supported by the Swedish Research Council; the Swedish Heart and Lung Foundation, the Novo Nordisk Foundation, the Crafoord Foundation; the Royal Physiographic Society and the Magnus Bergvall Foundation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Pre‐eclampsia and future cardiovascular disease: role of circulating micro‐RNAs
Authors: Delles Christian , Schlosser Kenny , Dayan Natalie , Kaur Amanpreet , Stewart Duncan J , Pilote Louise 
Published: June 2021

BackgroundWomen with a history of pre‐eclampsia (PE) are at increased risk of cardiovascular events later in life. The mechanisms underlying this association are incompletely understood but likely include changes in vascular function and structure. microRNAs (miRs) may play a role in vascular health and disease; therefore, we assessed profiles of circulating miRs in women who had PE, with or without subsequent cardiovascular disease.MethodsWe performed comprehensive profiling of circulating miRs by RNA sequencing (Qiagen, Hilden, Germany) of plasma samples from two independent cohorts: a cohort of women who presented with premature acute coronary syndrome (ACS; cohort 1: n=18 with and n=17 without history of PE) and a cohort of women without overt cardiovascular disease (cohort 2: n=20 with and n=20 without history of PE). miR profiles associated with history of PE and ACS were established based on fold change ≥ ±1.5 and P < 0.05. Targetscan 7.0 was used to predict miR targets and KEGG pathway enrichment was determined with Partek Pathway and Genomics Suite.ResultsWomen in the two cohorts were on average 48 years of age and had prior pregnancy over 20 years before. A total of 183 and 107 miRs were found to be differentially expressed between cases and controls in cohorts 1 and 2, respectively. Five miRs (hsa‐miRs 3131, 346, 4305, 4670‐3p and 5698) were concordantly increased or decreased in both cohorts. There were 39 and 29 KEGG pathways significantly (FDR <0.05) enriched in cohorts 1 and 2, respectively, of which 23 pathways overlapped between the cohorts. Further analysis identified 13 KEGG pathways that were common between all comparisons of PE vs control in cohorts 1 and 2, and ACS vs non‐ACS across the cohorts, including cancer, Wnt signalling, TGF‐beta and focal adhesion pathways (Figure 1).ConclusionsBy analysing circulating miR profiles, we identified pathways that are common between women with ACS and women with history of PE. Of particular importance, pathways involved in cell growth and adhesion may provide explanations for the link between PE and future cardiovascular diseases.Support or Funding InformationFunded by grants from the Canadian Vascular Network and the British Heart Foundation (Centre of Research Excellence award RE/13/5/30177)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of vascular ferrochelatase deregulation in the progression of monocrotaline‐induced pulmonary arterial hypertension in rats
Authors: Alhawaj Raed O , Ghadhanfar Elham , Cherian Susan 
Published: June 2021

Ferrochelatase is a redox sensitive mitochondrial enzyme that is prone to deregulation under many conditions, giving way to a number of diseases. These diseases may involve the altered/decreased production of heme or the overproduction of Zinc Protoporphyrin IX (ZnPPIX), which is a competitive inhibitor of both heme oxygenase‐1 (HO‐1) and soluble guanylate cyclase (sGC). In this study, we aim to characterize the role of ferrochelatase deregulation in pulmonary arterial hypertension (PAH). In order to evaluate ZnPPIX as a possible contributor to PAH, we employed HPLC analysis of isolated small pulmonary arteries from monocrotaline (MCT)‐induced PAH rats, in which we quantified the ZnPPIX content. Our data suggests a decrease in ZnPPIX, which is reflective of a decrease of ferrochelatase activity and/or expression which overrides a possible iron deficiency mechanism as a principle contributor to PAH. Our study may provide some insight into the progression of PAH, highlighting possible future therapeutic targets.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Functional cardiac differences in young adults born premature, assessed by MRI
Authors: Centanni Ryan , Haraldsdottir Kristin , Beshish Arij , Goss Kara , Palta Mari , Eldridge Marlowe 
Published: June 2021

PurposePremature birth, defined as birth prior to 37 weeks of gestation, affects 1 in 10 births in the United States. Young adults born preterm have been shown to have impaired gas exchange and diminished aerobic capacity, but little is known about the functional cardiac differences at rest and in exercise. The intent of this study is to quantify the cardiac differences between preterm‐born young adults and term‐born young adults through measurements of heart rate (HR), stroke volume (SV), cardiac output (Q), end diastolic volume (EDV), end systolic volume (ESV), and ejection fraction (EF).MethodsFive young adults born preterm (PT) (age 25–28, birthweight <1500g, gestational age <32 weeks) and 5 age‐matched young adults born full term (CT) (gestational age 38–40 weeks) completed supine steady state exercise on an exercise stepper while in a magnetic resonance imaging (MRI) machine with continuous measurement of cardiac variables. Q and SV were indexed to body surface area (BSA (m2), Qi and SVi). Statistical analysis was done using multiple t‐tests.ResultsAt rest, there was no difference in PT compared to CT in SV (91.2 ± 5.8 v 99.0 ± 20.7, p=0.44), SVi (53.8 ± 5.2 v 52.0 ± 7.5 ml, p=0.67), EDV (143.6 ± 17.0 v 172.8 ± 30.5, p=0.1), ESV (52.5 ± 12.7 v 73.7 ± 20.1, p=0.08), and EF (63.9 ± 4.6 v 57.5 ± 7.4, p=0.14). Compared to CT, PT had significantly higher Q (7.2 ± 0.46 v 5.9 ± 0.82, p=0.02), Qi (4.2 ± 0.37 v 3.1 ± 0.17, p=0.0003), and HR (78.8 ± 6.6 v 60.8 ± 8.5, p=0.006) at rest. Exercise data yet to be analyzed.ConclusionYoung adults born preterm exhibit lower maximal aerobic capacity than age‐matched controls. Despite difficulty with exercise, PTs have higher Qi at rest, suggesting a decreased ability to augment Q in response to increasing metabolic demand, which may reduce their ability to exercise at higher intensities. This inability to adequately increase Q appears to be driven by a higher HR at rest. Both SV and HR increase during exercise, but HR of PTs reaches max at an earlier time point, which restricts further increase of Q.Support or Funding InformationNIH/NHLBI R01 HL115061This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.