bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of temperature on athletic performance in the pelagic Mahi‐mahi (Coryphaena hippurus)
Authors: Heuer Rachael M , Stieglitz John D , Enochs Ian C , Pasparakis Christina M , Benetti Daniel D , Grosell Martin 
Published: June 2021

Temperature is an environmental factor that can have profound impacts on physiological processes, behavior, and performance in poikilotherms. Temperatures that deviate too far from thermal tolerance are thought to reduce organismal performance by constraining aerobic scope. The objective of the present study was to examine how temperature influences metabolic rate, aerobic scope, and swimming performance in the circum‐global pelagic teleost Mahi‐mahi (Coryphaena hippurus). Mahi were acclimated to a range of temperatures experienced in their natural habitat (20, 24, 28, and 32°C) for 1–2 weeks and then aerobic performance was assessed using swim tunnel respirometry. Using this technique, maximal sustained swimming speed (Ucrit), maximal and minimal metabolic rate, and aerobic scope were measured. Mahi exposed to the lowest (20°C) and highest temperatures (32°C) experienced a reduction in aerobic scope compared to intermediate temperature treatments. A reduction in maximal metabolic rate accounted for the reduction in cold‐acclimated animals, while an increase in minimal metabolic rate led to the reduction in warm‐acclimated animals. Maximal sustained swimming speed showed similar but, non‐significant trends. These results indicate that performance is impaired in mahi at temperatures at the extreme ends of their natural range. These results are particularly relevant in the context of future climate change predictions for mahi residing in areas like the Gulf of Mexico, where 32°C is the mean temperature expected during summer months throughout surface waters by year 2100. Pairing data from the present study to environmental parameters may help assess habitat utilization by many pelagic species as oceans continue to warm.Support or Funding InformationThis research was made possible in part by a grant from The Gulf of Mexico Research Initiative. Data are/will be publicly available through the Gulf of Mexico Research Initiative Information & Data Cooperative (GRIIDC) at https://data.gulfresearchinitiative.orgThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Simvastatin Inhibits Allergen‐induced IL‐33 Secretion in Human Bronchial Epithelial Cells by Blocking ATP Release and Ca2+ Uptake
Authors: Srisomboon Yotsawee , Maniak Peter , Squillace Diane , Kita Hirohito , O'Grady Scott 
Published: June 2021

Previous studies have demonstrated that simvastatin possesses immunomodulatory effects in airways, but the precise mechanisms and therapeutic potential are poorly understood. The objective of the present study was to investigate the inhibitory effects of simvastatin and b‐methyl‐cyclodextrin (β‐MCD) on the innate immune response of the airway epithelium induced by Alternaria alternata (100 μg/ml) and house dust mite (200 μg/ml, HDM) allergens. Experiments were performed with cultured human bronchial epithelial cells transfected with the human IL‐33 gene to produce a robust and reproducible cell model for the study of IL‐33 secretion. Cells were pretreated with varying concentrations of simvastatin ranging from 0.1 to 10 μM for 24 hours prior to allergen exposure. IL‐33 release was quantified by ELISA (Quantikine®) following the procedure provided by the manufacturer. Simvastatin produced a concentration‐dependent inhibition of IL‐33 release that was nearly abolished at 10 μM (IC50; 1.0 μM). In contrast, simvastatin was ineffective at blocking the effects of HDM on IL‐33 release (IC50; >10 μM). Similarly, pretreatment with β‐MCD (5 mM) for 30 minutes also inhibited the Alternaria response, suggesting that depletion of cholesterol from the plasma membrane was responsible for the effects of simvastatin and β‐MCD. Subsequent experiments explored the effects of simvastatin and β‐MCD on Alternaria‐evoked Ca2+ uptake, which is necessary for activating IL‐33 release. Simvastatin (10 μM, 24 hrs) and β‐MCD (5 mM; 30 minutes) both abolished the increase in [Ca2+]i induced by Alternaria. We next examined the possibility that abolition of Ca2+ uptake resulted from inhibition of ATP release, since ATP activates P2X7 receptors that mediate Ca2+ influx in response to Alternaria exposure. ATP release was measured in real time using a luciferin/luciferase‐based photon counting assay. Both simvastatin and β‐MCD blocked ATP release. Moreover, addition of 100 μM cholesterol to the extracellular media rescued the effects of simvastatin. These results demonstrated that inhibition of IL‐33 secretion by simvastatin and β‐MCD following Alternaria exposure involved suppression of ATP release that was dependent on membrane cholesterol content. Thus, membrane cholesterol likely plays a pivotal role in innate immune function of airway epithelial cells.Support or Funding InformationThis study was supported by NIH R01 AI128729 to HK and SMO.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of Estrogen on Alveolar Macrophage Polarization in Response to Particulate Matter Exposure
Authors: Fuentes Nathalie , Pesantez Jonathan , Nicoleau Marvin , Wal Randy Vander , Chroneos Zissis , Silveyra Patricia 
Published: June 2021

BackgroundLung diseases affect more than 500 million people worldwide. Exposure to air pollutants such as particulate matter (PM) contributes significantly to lung disease, especially in women, indicating an intersection of air pollution and sex hormones in lung disease outcomes. Studies have been performed on the effects of estrogens on lung immunity, particularly in alveolar macrophages (AM). AMs provide one of the first lines of defense in the airways and are important mediators of inflammation. However, the mechanisms by which estrogens control the immune response to PM exposure remain unclear. Here, we hypothesized that PM exposure triggers AM polarization to the pro‐inflammatory (M1) macrophage phenotype in a sex‐dependent matter, and that this process is mediated by estrogens in female cells.MethodsWe tested this hypothesis by exposing male (RAW264.7, BALB/c) and female mouse AMs (J774A.1, BALB/c) to a synthetic PM preparation in the presence or absence of estrogen agonists/antagonists. Cell viability and cytotoxicity were measured at 8h to determine PM dose‐responses. Cells were then stimulated with LPS or IL‐4, which have been described as mediators of AM polarization. The polarization phenotype, determined by expression of specific markers (iNOS, Arg1), was evaluated by quantitative real‐time PCR.ResultsOur results demonstrate that estrogen treatment decreases iNOS expression and increases Arg1 expression, impairing the LPS‐induced pro‐inflammatory phase and triggering resolution of inflammation in RAW 264.7 cells. In addition, induction of AM polarization towards different phenotypes not only was altered by PM and estrogen treatment, but also depended on the sex of the cell. Interestingly, PM treatment led to decreased expression of estrogen receptors when compared to the non‐PM treated cells.ConclusionsWe conclude that estrogens regulate the immune response to PM in a sex‐dependent manner. These findings may be relevant to elucidate the transcriptional mechanisms involved in the sex‐specific inflammatory response and particularly for the identification of novel hormone receptor modulators efficacious in the prevention or mitigation of chronic inflammation in men and women.Support or Funding InformationThis research was supported by funding from NIH K01HL133520, the Center for Research on Women and Newborn Health and the American Physiological Society Porter Physiology Development Program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cloning, purification, and enzymatic activity of the quorum sensing signal synthase RhlI
Authors: Wetherald Noah , Ricciardi Meghan , Ulrich Scott Michael 
Published: June 2021

Quorum sensing is a bacterial cell‐cell communication system that functions through the synthesis, secretion, and detection of signaling molecules called autoinducers. Quorum sensing enables bacteria to assess their cell density and coordinate group behaviors that are advantageous at high cell density. Many bacteria that cause acute and chronic infections in humans use quorum sensing to control expression of virulence factors and formation of biofilms, so inhibitors of quorum sensing hold significant promise as novel antibacterial agents. By targeting bacterial virulence as opposed to growth and survival, quorum sensing inhibitors avoid the selective pressure for drug resistance that is inherent to traditional antibiotics.The main quorum sensing system in Gram‐negative bacteria is based on the synthesis and detection of acyl homoserine lactone (AHL) autoinducers. Efforts to inhibit AHL‐mediated quorum sensing have focused on developing synthetic AHL analogs that act as antagonists of AHL receptors. These compounds have been shown to block virulence controlled by quorum sensing, validating quorum sensing as an antibacterial drug target.The overall goal of the project is to develop inhibitors of AHL synthase enzymes, an alternative quorum sensing drug target that remains under‐explored. Towards this goal, we have cloned and purified RhlI from Pseudomonas aeruginosa and established its enzymatic activity as an assay platform for candidate synthetic inhibitors.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Crossing Blood‐Brain Barrier with Carbon Quantum Dots
Authors: Seven Elif S. , Zhou Yiqun , Seven Yasin B. , Mitchell Gordon S. , Leblanc Roger M. 
Published: June 2021

The blood‐brain barrier (BBB) is a semi‐permeable structure, which is essential for the protection of the central nervous system (CNS). BBB selectively allows the passage of the necessary small molecules/nutrients from the blood to the brain while blocking pathogens or toxins. However, BBB becomes a major obstacle during disease since it significantly hinders the drug delivery to the CNS. Therefore, developing a drug delivery system to cross BBB is highly desired. Recently, nanoparticles (NPs) have become emergent tools to assist drugs to cross BBB. Since most NPs cannot cross BBB by themselves, the nanoparticle‐mediated drug delivery heavily depends on conjugating the NPs to the ligands such as transferrin to pass through the BBB via receptor‐mediated endocytosis.Here, we designed Carbon quantum dots (CDs) that can cross BBB without the need of a ligand. We hypothesized that the saccharide‐based CDs will have an amphiphilic structure with surface groups that resemble the saccharide precursor. Therefore, these CDs will be able to cross BBB either with the aid of glucose transporter proteins or by passive diffusion.CDs were prepared via a bottom‐up approach using hydrothermal carbonization of saccharides and characterized using various spectroscopic, microscopic and surface chemistry methods such as UV/vis, fluorescence, FTIR/ATR, TEM, AFM and Langmuir monolayers. To test our hypothesis, CDs were injected into the heart of wild‐type zebrafish, Danio rerio. The confocal images showed the accumulation of CDs in the CNS of zebrafish confirming the ability to cross BBB. CDs were also shown to pass through rat BBB 45 min after intravenous tail injection (2.5 mg/kg). Following transcardial perfusion, rat spinal cord is post‐fixed in paraformaldehyde overnight and cryoprotected in sucrose. Presence of CDs in the CNS was confirmed in 40 μm tissue sections via epifluorescence microscopy. These proof‐of‐principle studies suggest that saccharide‐based CDs can cross BBB in different vertebrate species. Further studies should address if the amount of BBB penetration is sufficient to cause a biologically meaningful effect in the CNS.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Engineered High‐Specificity Affinity Reagents for the Detection of Glycan Sialylation
Authors: Woods Robert J. , Wu Shengcheng , Meng Lu , Gerner‐Smidt Christian , Sanders Matthew J. , Ben‐Ayre Shani Leviatan , Padler‐Karavani Vered , Yang Loretta 
Published: June 2021

As alternatives to established carbohydrate‐detection reagents (antibodies and lectins), Lectenz® Bio is developing lectin‐like, enzyme‐derived proteins (known as Lectenz®), that target glycan sequences for which existing reagents either do not exist or are sub‐optimal. Lectenz® are engineered from catalytically inactivated glycan‐processing enzymes that have been optimized for high affinity towards specific glycan sequences. The conversion of such enzymes into affinity reagents is facilitated by computationally‐guided directed evolution. Lectenz® are being developed for a variety of glycan detection and enrichment applications including affinity chromatography, Western blot, and immunohistochemistry. Here we demonstrate the performance and specificity of two novel sialic acid recognizing Lectenz® engineered from a sialidase enzyme.Support or Funding InformationNIH R44 GM113351, R44 OD024964This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Polyphenols and other Phytochemicals in Cancer Prevention and Management
Authors: Asuzu Peace C , Besong Samuel Ayuk , Aryee Alberta NA 
Published: June 2021

Phenolic compounds and other phytochemicals are significant resources for drug discovery and development. Plant‐derived natural products have contributed in preventing and managing oxidative stress, and in cancer therapeutics. Recent reports indicate that 83% of new anti‐cancer agents are of natural product origin. The aim of this study was to assess the content and properties of bioactive phytochemicals in water, ethanol, methanol, acetone, and dichloromethane extracts of Prunus africana, Pausinystalia yohimbe, Moringa oleifera, Momordica charantia and Orthero spp, and test their therapeutic effect on a wide range of diseases. In the first part of the study, the content of total polyphenols (TPC), flavonoids (TFC), carotenoid, anthocyanin, and antioxidant properties of the extracts of the different plant parts of these five plants were measured using the Folin‐Ciocalteu, 2,2‐diphenyl‐1‐picrylhydrazyl radical scavenging activity (DPPH), ferric reducing antioxidant power (FRAP), and 2,2′‐Azino‐bis(3‐ ethylbenzthiazoline‐6‐sulfonic acid) radical scavenging (ABTS) assays. For most samples, extraction yields were highest when either ethanol or methanol were used as extraction solvent. The FRAP values were in the range of 6.04 – 112.00 μM Fe2+/g, while the highest TPC and TFC were seen in the methanol extract of P. africana bark from Cameroon (1397.33 mg GAE/g) and acetone extract of M. charantia leaf (217.33 mg RU/g), respectively. The concentration required to obtain a 50% antioxidant effect (EC50) for the acetone and methanol extracts of P. africana bark (Cameroon), methanol and ethanol extracts of P. yohimbe leaf and the methanol extract of P. yohimbe root were comparable to that of ascorbic acid. Seven phenolic acids were identified in the extracts of P. africana and P. yohimbe using high performance liquid chromatography (HPLC). The most abundant phenolic acids were; vanillic acid (116.41 mg/g dry extract in P. yohimbe leaf methanol extract) and trans‐sinapic acid (102.22 mg/g dry extract in P. africana bark water extract). This study shows that these plants parts are valuable sources of natural polyphenols and antioxidants and their individual and/ synergistic effect may modulate cellular and signaling events involved in growth and invasion of cancer cells.Support or Funding InformationUSDA‐NIFADelaware State UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterizing the Insulin Staining of LEW.1WR1 and LEW/SsNHsd Rats in Response to Polyinosinic‐Cytidylic Acid
Authors: Wade Amber , Wimalarathne Madushika , Cantrell Kayleigh , Gibson Helen , Love‐Rutledge Sharifa 
Published: June 2021

The experimental model LEW.1WR1(1WR1) rats show increased type 1 diabetes (T1D) onset with the administration polyinosinic‐polycytidylic acid (PIC). The susceptibility window of inducible T1D in the LEW rat occurs between 21–35 days (3–5 weeks) of life, which is a similar life stage of the onset of human T1D (peak age of onset is 14 years old). The susceptibility of this model is related to FAT10 overexpression, a ubiquitin‐like protein that plays an unclear role in the regulation of lipid metabolism. The objective of this study was to compare the size and number of insulin stained pancreatic islets in 1WR1 rats treated with PIC with control rats during disease induction. Using immunohistochemistry we were able to visualize pancreatic islet infiltration by CD3+ and CD68+ stained cells. We observed increased immune cells in the PIC treated pancreata. There were also no significant differences in blood insulin level which appeared to be trending up. Using blinded trained scorers we observed islet size varied as well as intensity of staining. We believe that the beta cells may be responding to the inflammatory stimulus which could play a role in increasing the susceptibility to T1D.Support or Funding InformationThe University of Alabama in HuntsvilleThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effect of Different Antihypertensive Classes on the Complexity of Heart Rate and Blood Pressure Variability
Authors: Salgado Hélio Cesar , Silva Luiz Eduardo Virgilio , Silva Carlos Alberto Aguiar , Nobre Fernando , Fazan Rubens 
Published: June 2021

Hypertension is associated with several physiological dysfunctions, including changes in the neurohumoral control of heart and vessels. Different classes of antihypertensive drugs may have distinct effects on the autonomic system and body homeostasis, but their individual effects on the complexity of cardiovascular regulation are still not established. We investigated the effect of five different classes of antihypertensive on the complexity of pulse interval (PI) and arterial pressure (AP) variability in an experimental model of renal hypertension (2 kidney 1 clip, 2K1C) in the rat. Hypertensive rats were treated (by gavage) during 15 days with: water (N=12), ramipril (2 mg/kg/day; N=7), losartan (10 mg/kg/day; N=8), atenolol (90 mg/kg/day; N=9), amlodipine (10 mg/kg/day; N=7) or hydrochlorothiazide (20 mg/kg/day; N=8). A normotensive (sham‐operated) control group (N=10) received water for the same period. After the treatment, rats had their raw AP recorded and beat‐by‐beat series of systolic AP and PI were created. The complexity of AP and PI was assessed by multiscale entropy (MSE) and detrended fluctuation analysis (DFA). For PI series, hypertensive rats treated with water showed decreased MSE and increased DFA in the middle range of scales. For AP series, hypertensive rats untreated or treated with amlodipine have lower MSE at short and middle time scales. Hypertensive rats treated with amlodipine also showed altered DFA in comparison to the other groups. All antihypertensive drugs were efficient to restore AP to normal levels. Moreover, 2K1C untreated (water) rats presented the lowest cardiovascular complexity and all antihypertensive drugs, except for amlodipine, were capable to restore the cardiovascular complexity to normal levels. Therefore, amlodipine seems to have a deleterious effect on the cardiovascular integrative control, probably due to the increased sympathetic activity induced by amlodipine.Support or Funding InformationThis study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ‐ Brasil (CAPES) ‐ Finance Code 001, São Paulo Research Foundation (FAPESP, Proc. 2013/20549‐7) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Proc. 402076/2016‐8).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Peripherally Administered Proinflammatory Cytokines Increase Afferent Renal Nerve Activity in Rat
Authors: Cao Yiling , Yu Yang , Bell Balyssa , Felder Robert B. , Wei Shun‐Guang 
Published: June 2021

Inflammation plays an important role in sympathetic activation in cardiovascular diseases. Systemic administration of the proinflammatory cytokines (PICs) tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) increases mean blood pressure (MBP), heart rate (HR) and efferent renal sympathetic nerve activity. However, the renal nerve contains both afferent and efferent fibers. The afferent renal nerve is composed of chemoreceptor and mechanoreceptor fibers, and delivers peripheral signals to the brain that have been reported to increase sympathetic outflow in hypertension and heart failure. The effect of circulating PICs on afferent renal nerve activity (ARNA) has not previously been investigated. The present study sought to determine whether peripherally administered PICs TNF‐α and IL‐1β increase ARNA. Urethane anesthetized male Sprague Dawley rats (300–350 g) underwent an intravenous (IV) or a renal artery injection of TNF‐α or IL‐1β. MBP (mmHg), HR (beats/min) and ARNA (% change from baseline) were continuously recorded for 4–5 hours. IV injection of TNF‐α (500 ng/kg) or IL‐1β (500 ng/kg) significantly (* p<0.01 vs. baseline) increased MBP (20.1 ± 2.2* and 23.4 ± 2.1*, respectively), HR (51.5 ± 6.7* and 58.8 ± 7.1*, respectively) and ARNA (37.2 ± 3.5* and 42.1 ± 3.5*, respectively) with peak responses 20–30 mins after injection. Similarly, renal artery injection of the same doses of TNF‐α or IL‐1β induced increases (*p<0.01 vs. baseline) in MBP (17.0 ± 2.1* and 19.9 ± 2.2*, respectively), HR (45.5 ± 5.6* and 49.3 ± 4.6*, respectively) and ARNA (30.7 ± 3.5* and 38.4 ± 4.5*, respectively) that began within 5–10 mins and peaked at 20–30 mins after the injection. Quantitative real‐time PCR showed high mRNA levels of TNF‐α receptor 1 and IL‐1β receptor in renal cortex and medulla. These data indicate that circulating TNF‐α and IL‐1β can act at the kidney to augment afferent renal nerve activity, suggesting that circulating PICs may activate ARN fibers to elicit a sympathetically mediated pressor response. PIC activation of renal afferent nerves may be an important mechanism contributing to inflammation‐driven sympathetic activation in heart failure and hypertension. These findings provide support for the potential therapeutic benefit of renal afferent denervation.Support or Funding InformationSupported by NIH grant R01 HL139521 (S.G. Wei)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.