bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelin‐1 Receptor Responses in Overweight Women
Authors: Nathaniel Sangeetha , Kuczmarski Andrew V. , Haigh Katherine , Wenner Megan M. 
Published: June 2021

Increased adiposity is associated with endothelial dysfunction, and contributes to an increased risk of cardiovascular disease. Endothelin‐1 (ET‐1), a potent vasoconstrictor, has been associated with the reduction in endothelium‐dependent vasodilation in overweight and obese adults via the ETA receptor. However, ETB receptors can elicit vasodilation, and have been shown to be important for maintaining vascular health in women. Therefore, the purpose of this study was to test the hypothesis that impaired endothelial function is mediated in part by loss of ETB receptor mediated dilation in overweight women compared with women of normal weight. We tested 8 young normal weight women (22±2 years, BMI 21±1 kg/m2) and 6 young overweight women (21±1 years, BMI 27±1 kg/m2). We measured the vasodilatory responses in the cutaneous circulation using laser Doppler flowmetry during microdialysis perfusions of lactated Ringer's (Control), ETB receptor antagonist (BQ‐788, 300nM), and ETA receptor antagonist (BQ‐123, 500 nM). We utilized local skin heating (42°C) to induce vasodilation, followed by increase in heat (43°C) and perfusion of sodium nitroprusside (28mM) to elicit maximal dilation. Overweight women had impaired vasodilation compared to normal weight women (94±2 vs. 87±3 %max CVC; P=0.05). ETB receptor blockade tended to reduce vasodilation in normal weight women (Control: 94±2 vs. BQ‐788: 89±3 %max CVC; P=0.06) but not in overweight women (Control: 87±3 vs. BQ‐788: 87±3 %max CVC). ETA receptor blockade did not alter blood flow responses in either normal (BQ‐123: 91±2) or overweight young women (BQ‐123: 87±2). These preliminary results suggest that young overweight women have impaired vasodilatory function, possibly related to altered ETB mediated dilation.Support or Funding InformationNIH Grant P20 GM 103446, U54 GM 104941, P20 GM 113125 and University of Delaware Research 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.
Role of viral RNA in virion stability and disassembly
Authors: Anand Ganesh , Lim Xin Xiang , Ramesh Ranita , Raghuvamsi Palur Venkata 
Published: June 2021

Viruses are metastable macromolecular entities that are assembled into compact particles. Entry into a target host cell initiates quaternary conformational changes in response to distinct host‐specific environmental changes including temperature, pH, osmolality, divalent cation concentrations, which promote disassembly and release of the virion's genome into the host cell. This host stimulus‐triggered disassembly is critical for initiating the infectious phase of the particle. How viruses use their quaternary coat protein structures as thermodynamic sensors for detecting entry into a conducive host cell environment is largely unknown. The process of viral disassembly is largely impervious to static structural methods as these only capture end‐state conformations. Amide Hydrogen Deuterium Exchange Mass Spectrometry (HDXMS) can be used to monitor whole viral particle dynamics in solution. The disassembling virion represents the virus at its most vulnerable state and is consequently a transient dynamic intermediate. A map of the quaternary structural changes in this state offers critical insights into cryptic epitopes as novel vaccine targets. Our research has pioneered structural mass spectrometry characterization of temperature and divalent cation‐dependent conformational changes on Dengue virus and Turnip Crinkle Virus (TCV) and mapped the specific disassembly processes in these two model virus systems. We have extended these studies to deconstruct the whole viral particle‐antibody (DENV2‐2D22) complex. Our results reveal the high intrinsic dynamics of the RNA packing capsid C‐protein which underpins viral transition from compact to expanded states in the process of disassembly. We have also uncovered new disassembly intermediates triggered by varying monovalent and divalent cation concentrations. Viral disassembly processes in TCV and Dengue reveal conformations of disassembly intermediates which represent powerful new targets for therapeutic antibody design as well as offer fundamental insights into strategically timed viral disassembly processes which can be extended to all viruses.Support or Funding InformationSingapore Ministry of Education Tier 3 grantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cerebral autoregulation during exposure to artificial gravity
Authors: Sanjana Faria , Knox Allan , Falvo Michael , Evans Joyce , Knapp Charles , Serrador Jorge 
Published: June 2021

Our work has previously shown that exposure to artificial gravity (AG) can improve orthostatic tolerance. The purpose of this work is to examine whether cerebral autoregulation is improved with AG in twelve hypovolemic men and women. The protocol consisted of an initial ~45 minutes of a “step up” tolerance period, used to determine participants' presyncopal limit, followed by ~45 minutes training period at GZ below participants presyncopal limit. Beat‐by‐beat blood pressure (Portapres), heart rate (ECG), middle cerebral artery blood flow velocity (Transcranial Doppler) and end‐tidal carbon dioxide (capnography) were collected on participants during short arm centrifugation. Cerebral autoregulation was assessed using transfer function analysis between mean arterial pressure (MAP) and mean cerebral blood flow velocity (MCBFV) in 3‐min intervals during the training period. Exposure to AG resulted in a significant positive correlation between GZ and MAP, MAP variability and MCBFV variability in the low frequency (LF) range (0.07–0.15 Hz). In addition, coherence between MAP and MCBFV in the LF range was positively correlated. There was no change in gain and phase between MAP and MCBFV in the same frequency range. With higher GZ, there was a significant positive correlation in coherence and significant negative correlation in gain between MAP and MCBFV in the very low frequency range (0.03–0.07 Hz). These data suggest that increasing GZ exposure is correlated to increasing MAP variability. However, despite this increased MAP variability gain values demonstrated a negative correlation with GZ, suggesting that cerebral autoregulation tended to improve with increasing GZ exposure. We expect increased coherence was a result of the increased MAP variability associated with higher GZ. These data may suggest that exposure to AG may be helpful to improve cerebral autoregulation. Therefore, one could speculate that AG may be a useful tool to consider as a countermeasure for post‐flight astronauts to improve their orthostatic tolerance as well as cerebral autoregulation and improve re‐adaptation to a gravity environment.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inhibition of Medial Preoptic Area Improves Physical Performance in Trained Rats
Authors: Müller‐Ribeiro Flávia Camargos , Wanner Samuel Penna , Drummond Lucas , Campos Helton Oliveira , Coimbra Candido Celso 
Published: June 2021

The medial preoptic area (MPO) plays a key role in the regulation of autonomic thermoeffectors and this area seems to be more activated after physical training, as evidenced by greater number of exercise‐induced c‐Fos immunoreactive neurons in trained rats. This observation raised the question as to whether inhibition of MPO can affect physical performance and thermoregulatory responses in trained rats. Following 2 weeks of high‐intensity interval training (HIIT), Wistar rats were submitted to an incremental‐speed exercise on a motor‐driven treadmill until fatigue after bilateral microinjection of muscimol (80 pmol/100 nl) to evaluate their aerobic capacity and thermoregulatory responses. The core body temperature (Tc) and the maximal oxygen uptake (VO2 max) were recorded continuously during exercise. Physical training increased the time to fatigue (43 ± 2 min vs. 64 ± 2 min; p=0.0009; n=6); the maximum speed attained during the incremental exercise (24 ± 1 m/min vs. 31 ± 1 m/min; p=0.0013), the distance traveled (675 ± 36 m vs. 1261 ± 68 m; p=0.0008); and resulted in a higher oxygen uptake (38 ± 1 ml/min/kg vs. 42 ± 1 ml/min/kg; p=0.01). Interestingly, at fatigue, no difference in the absolute Tc was found between the groups (38.28 ± 0.2 °C vs. 38.78 ± 0.1 °C; p=0.1). Bilateral blockade of MPO using muscimol improved physical performance, as observed by the increased time to fatigue (71 ± 6 min muscimol vs. 58 ± 2 min ‐ control, p=0.004; n=3); distance traveled (1528 ± 188 m muscimol vs. 1094 ± 84 m control; p=0.05); and maximum oxygen uptake (49 ± 1 ml/min/kg muscimol vs. 44 ± 2 ml/min/kg control; p=0.04). Regarding the thermoregulatory adjustments, MPO inhibition tended to increase Tc at fatigue (40.37 ± 0.5 °C muscimol vs. 39.35 ± 0.2 °C ‐ control; p=0.08). There was an increase in the Tc of the control animals during exercise but this temperature remained lower than that of the muscimol group (p<0.001). Our findings show that neurons in the MPO are involved in the control of the aerobic capacity of trained rats, however, the improved physical performance of these animals caused by MPO inhibition did not result from changes in thermoregulatory adjustments.Support or Funding InformationConselho Nacional de Desenvolvimento Científico e Tecnlógico ‐ CNPq; grant 434646/2016‐4This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Microvascular Dysfunction, Inflammation and Tissue Injury in Polymicrobial Sepsis
Authors: Kowalewska Paulina M , Ellis Christopher G 
Published: June 2021

Sepsis is an overwhelming systemic inflammatory response to infection that may lead to multiple organ failure and shock. One of the characteristics of sepsis is early microvascular dysfunction. In our rat model of polymicrobial sepsis, microvascular dysfunction is detected as early as 3 hours after infection (Bateman et al., Am J Physiol Heart Circ Physiol, 2001). The objective of this study was to examine the timing of microvascular dysfunction in the context of tissue injury and inflammation. Sepsis was induced in male Sprague‐Dawley rats with an intraperitoneal injection of a fecal slurry. Control animals were injected with normal saline. The septic and control animals were then prepared for intravital video microscopy (IVVM) of the right extensor digitorum longus (EDL) muscle. The microvasculature was examined for changes in hemodynamics and erythrocyte oxygen saturation using dual wavelength IVVM for a period of 4 or 6 hours after the injection of the fecal slurry. The data were set aside for future analysis and comparisons were made to our existing hemodynamic data in order to further characterize our sepsis model. Completion of IVVM observations was followed by perfusion fixation and organ collection. Hematoxylin and eosin‐stained sections were graded for pathological and inflammatory changes normalized to tissues collected from naïve control animals. Livers from septic and control animals were both marked by mild leukocyte infiltration in the 4‐hour and 6‐ hour groups, while erythrocyte trapping within the microvasculature did not rise above naïve levels and parenchymal cell architecture was not altered. The EDL muscles from septic animals did not exhibit increased inflammatory cell infiltration. Immunohistochemical labelling of brain sections for rat MHC class II did not show signs of inflammatory microglial activation in coronal slices spanning the entire brain in the septic animals from the 4‐hour and 6‐hour groups. Intravenous injection of Evans Blue prior to perfusion fixation also indicated that the blood‐brain barrier was not broken. On the other hand, septic rats had evidence of increased dye leakage in the liver and kidneys, which was not observed in the saline‐injected animals. Evans Blue leakage was not observed in the intact EDL muscles of either group. The findings of this study suggest that microvascular dysfunction occurs before detectable organ injury in our rat fecal‐induced peritonitis model of sepsis.Support or Funding InformationCollaborative Health Research Projects ( CHRP )This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
xCDxCDx‐PHD, a distinct type of PHD‐finger
Authors: Basu Shraddha , Boamah Daniel , Poppinga Franchesca AnneMarie , Lin Tao , Chakravarty Suvobrata 
Published: June 2021

Plant homeodomain (PHD) scaffolds are conserved protein modules in eukaryotes that typically recognize unstructured histone tails, and thus, play a critical role in chromatin signaling. Being a zinc‐finger, the sequences of PHD‐fingers, since their origin, have diverged. However, certain sequence signature features in PHD‐finger sequences suggest that there could be different subtypes among PHD‐fingers. One such subtype is the PHD‐finger featuring the xCDxCDx motif in the treble clef. Even though PHD‐finger binding‐site is rich in negatively charged residues for interacting with positively charged histone proteins, we note that a number of nonpolar amino acids are enriched at the binding site of xCDxCDx‐PHD subtype. These nonpolar residues have likely coevolved with the xCDxCDx motif. In general, coevolving residues contribute to: (a) folding of a scaffold, and/or (b) function (e.g., substrate binding). Here, we probed the coevolving residues of xCDxCDx‐PHD to find which of the two contributions (a or b or both) do they make. We have learned that the coevolving residue of xCDxCDx‐PHD are necessary for peptide binding and contribute little toward folding of xCDxCDx‐PHD scaffold.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cerebral Autoregulation and Cerebrovascular Reactivity is Similar in African American And Caucasian Males Despite Different Blood Pressures and Anterior Cerebral Artery Flow Velocities
Authors: Knox Allan , Favre Michelle , Haber Yaa , Falvo Michael , Serrador Jorge 
Published: June 2021

Cerebral autoregulation maintains adequate cerebral perfusion over varying systemic blood pressures, with any dysfunction giving opportunity for cerebral insult. African American (AA) males experience higher prevalences of hypertension and cerebrovascular abnormalities than their Caucasian (CAUC) counterparts. Potential racial differences in cerebral autoregulation may contribute to the high incidences of cerebrovascular events suffered by AA males. Therefore, the purpose of this investigation was to determine cerebral autoregulation and flow velocities of the cerebral circulation in AA and CAUC males. Cross‐sectional data of beat‐by‐beat blood pressure (BP), end‐tidal CO2 (ETCO2) middle cerebral artery (MCA) and anterior cerebral artery (ACA) velocities, cerebrovascular reactivity (CVR), and cerebral autoregulation was determined at the very low frequency (VLF: 0.03–0.07 Hz) and low frequency (LF: 0.07–0.15 Hz) domains in sample of AA (n=30, 44.91 ± 12.04 years) and CAUC (n=51, 44.48 ± 12.71 years, p=0.879) males. Mean BP was higher in AAs (96.25 ± 14.34 mmHg) than CAUCs (88.39 ± 11.93 mmHg, p=0.015). Systolic BP was elevated in AAs (137.64 ± 20.39 mmHg) compared to CAUCs (128.52 ± 16.65, p=0.037), with the same trend seen with diastolic BP (AA: 77.53 ± 12.81 mmHg; CAUC: 70.49 ± 11.31 mmHg, p=0.021). ETCO2 and CVR was comparable between groups (p=0.351 and p=0.290, respectively). Cerebral autoregulation was similar between groups in the MCA at the VLF (Coherence: p=0.184, Gain: p= 0.748, Phase: p=0.841) and LF (Coherence: p=0.683, Gain: p=0.800, Phase: p=0.178) domains. Cerebral autoregulation was also proportionate in the ACA at the VLF (Coherence: p=0.360, Gain: p=0.266, Phase: p=0.231) and LF (Coherence: p=0.293, Gain: p=0.530, Phase: p=0.360) domain. Autoregulation index at the MCA and ACA was comparable between groups (p=0.358 and p=0.620, respectively). MCA mean flow velocity was similar between groups (p=0.814), although ACA mean flow velocity was higher in AAs (52.17 ± 8.89 ml/cm/s) compared to CAUCs (44.02 ± 11.19 ml/cm/s, p=0.013). The current data demonstrate comparable levels of cerebral autoregulation in AA and CAUC males, despite differing systemic BP and ACA velocities. This proposes that cerebral autoregulation is intact within AA males and may not contribute to the increased prevalence of cerebrovascular insults shown in current epidemiological data. Future studies are warranted to include larger sample sizes in addition to absolute cerebral blood flow measures to confirm these findings.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The effects of localized heating on insulin‐stimulated leg blood flow
Authors: Walsh Lauren , Manrique‐Acevedo Camila , Martinez‐Lemus Luis , Padilla Jaume 
Published: June 2021

Vasodilator actions of insulin contribute to glucose disposal in skeletal muscle. Previous studies have shown that increased physical activity, or even a single bout of leg exercise, improves insulin‐stimulated leg blood flow; however, the mechanisms by which exercise mediates this apparent improvement in vascular insulin sensitivity remain largely unknown. Herein we tested the hypothesis that increased limb blood flow‐induced shear stress primes the vasculature to become more insulin‐sensitive. Eleven young healthy subjects (eight men, three women) underwent one‐hour of single‐leg heating (limb immersion in a 40–42°C water bath) to increase blood flow, while the contralateral leg remained outside of the water bath serving as a non‐heated internal control. The heating was followed by a 60‐minute cooldown. Thereafter, bilateral measures of popliteal artery blood flow (via Doppler ultrasound) were performed at baseline and at 45 and 60 minutes during systemic infusion of insulin to mimic postprandial levels. Dextrose was co‐infused at varying rates to maintain euglycemia. As expected, 60 minutes of leg heating increased popliteal artery blood flow by ~3‐fold, relative to the non‐heated control leg. Leg blood flow returned to basal levels following cooldown. Consistent with the hypothesis, popliteal artery blood flow was significantly elevated after 45 minutes, but not 60 minutes, of insulin infusion in the previously heated leg; whereas no significant changes were noted in the control leg throughout. These preliminary results indicate that one‐hour of single‐leg heating improves insulin‐stimulated popliteal artery blood flow, supporting the notion that increased blood flow‐induced shear stress sensitizes the vasculature to the actions of insulin. Additional experiments are underway to confirm these findings.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Myocardial Impairments Rather Than Rhythm Status Contributes to Exercise Intolerance in Patients with Atrial Fibrillation
Authors: Elliott Adrian , Verdicchio Christian , Gallagher Celine , Linz Dominik , Mahajan Rajiv , Sanders Prashanthan 
Published: June 2021

BackgroundExercise intolerance is commonly reported in patients with atrial fibrillation (AF) despite preserved ejection fraction. However, the contribution of rhythm, echocardiographic parameters and cardiovascular risk factors to exercise intolerance is poorly understood. Furthermore, recent data shows a high prevalence of heart failure with preserved ejection fraction amongst AF patients, which may contribute to exercise intolerance. Our aim was to evaluate the prevalence of exercise intolerance and its potential contributors amongst a cohort of AF patients undergoing cardiopulmonary exercise testing (CPET).MethodsWe assessed 151 AF patients (34% female) referred for CPET. All patients underwent routine clinical assessment, including detailed evaluation of cardiovascular risk factors, transthoracic echocardiography and a maximal CPET using a modified Balke treadmill protocol. To investigate the contribute of cardiac rhythm to exercise tolerance, CPET was reported in a select cohort of patients with persistent AF, 21 days following electrical cardioversion to sinus rhythm (SR).ResultsThe mean age was 67±8 years with a BMI of 29.4±4.4 Kg/m2. 59% of the cohort were in sinus rhythm (SR) at the time of testing. 41% of patients reached a peak VO2 <85% of age and gender predicted values. There was no significant difference in peak VO2 between patients in AF versus SR (p=0.22). After adjustment for age and gender, only chronotropic response (p=0.017) and echocardiographic indices of left ventricular (LV) filling pressures (E/E′, p=0.014) were significant predictors of peak VO2. In 20 patients who underwent subsequent cardioversion from AF to SR, peak VO2 improved significantly from 19.7±7.0 to 21.4±6.1 ml/kg/min (p=0.003).ConclusionOur main findings are that (i) the main predictors of peak VO2 are chronotropic response to exercise and indices of LV filling pressure, (ii) peak VO2 can be significantly improved in patients with persistent AF by restoration of SR. These findings highlight potential targets alongside rhythm control, for the improvement of exercise tolerance in AF patients.Support or Funding InformationNational Heart Foundation of Australia Postdoctoral FellowshipThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The promoting role of hnRNPK‐DDX3 interaction in the apoptosis upon DNA damage
Authors: Chen Chiao‐Che , Yang Jen‐Hao , Lin Chao‐Hsiung 
Published: June 2021

Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an RNA/DNA binding protein that participates in multiple cell functions due to its functional domains. In addition, some of its post‐translational modifications (PTMs) are critical for functions of hnRNPK. Importance of hnRNPK in cancers has been implied by its strong correlation with cancer transformation, progression and migration, but the mechanism how hnRNPK promotes cancer remains ambiguous. Our previous study reported that arginine methylation of hnRNPK negatively regulates U2OS cell apoptosis upon DNA damage. Recently, we showed that DDX3 helicase is a molecular partner of hnRNPK and may be involved in the hnRNPK‐mediated apoptosis upon DNA damage. In this study, we further investigated the role of DDX3 activity in the apoptosis regulation of U2OS cells using a DDX3 inhibitor. Interestingly, this inhibitor not only increased hnRNPK‐mediated apoptosis upon DNA damage but also elevated hnRNPK‐DDX3 interaction during early DNA damage. These results suggests that hnRNK‐DDX3 interaction is important for apoptosis induction by DNA damage. On the other hand, DDX3 has been shown to enhance p53 stabilization during DNA damage. We thus measured the protein level of p53 during treatment of DDX3 inhibitor but found that such treatment decreased both p53 and p21, implying that hnRNK‐DDX3 interaction promotes DNA damage‐induced apoptosis in a p53‐independent manner. In summary, our results suggests that the hnRNPK‐DDX3 interaction is critical for apoptotic regulation upon DNA damage.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.