bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of GPR40/120 omega‐3 fatty acid receptors on barrier function of airway epithelial cells
Authors: Wattanaphichet Panisara , Moonwiriyakit Aekkacha , Muanprasat Chatchai 
Published: June 2021

The airway epithelium serves as a physical barrier, whose integrity is maintained by tight junctions. Disruption of epithelial barrier function leads to increased permeability of harmful particles and pathogens, causing the development of various airway diseases. G protein‐coupled receptor 40 (GPR40) and G protein‐coupled receptor 120 (GPR120) have been discovered as receptors of omega‐3 fatty acids, and activation of these receptors induces AMP‐activated protein kinase (AMPK) activation, which is known to promote tight junction assembly. This study aimed to investigate the effect of omega‐3 fatty acid receptors, namely GPR40 and GPR120, on tight junction integrity of airway epithelial cells (Calu‐3 cells). Cell junctional assembly was measured by calcium switch assays and transepithelial electrical resistance (TER) analyses. We found that GW9508, an agonist of GPR40/120, promoted tight junction assembly of airway epithelial cells. This effect was abolished by specific antagonists of GPR40 and GPR120. In addition, the enhancement of airway barrier function by GPR40/120 agonist was mediated via a phospholipase C‐ calcium/calmodulin‐dependent protein kinase kinase (CaMKK)‐AMPK pathway. Taken together, these results indicate that activation of GPR40/120 has a beneficial effect in promoting airway epithelial barrier integrity and may be of therapeutic potential in airway diseases resulting from airway epithelial disruption including chronic obstructive pulmonary disease.Support or Funding InformationThis work was supported by Thailand Research Fund and Mahidol University (Grant BRG5980008), Faculty of Science, Mahidol University, and Faculty of Medicine Ramathibodi Hospital, Mahidol University (Tonkla Ramathibodi Project).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Novel cholesterol‐dependent regulation of cardioprotective KATP subunit expression in HL‐1 cardiomyocytes
Authors: Geiger Robert , Fatima Naheed , Flagg Thomas 
Published: June 2021

Hypercholesterolemia is associated with poor cardiovascular health. In a recent study, we discovered that histone deacetylase inhibitors (HDIs) cause a significant depletion of cholesterol in HL‐1 cardiomyocytes that is associated with increased expression of the sulfonylurea receptor subunit (SUR2/ABCC9) of the ATP‐sensitive potassium (KATP) channel. This implies that cellular cholesterol levels modulate the number of KATP, which play a key role in protecting the heart from damage during stress. The mechanism by which cholesterol modulates SUR2 expression is unknown. Analysis of the sequence upstream of the SUR2 gene revealed binding sites for the cholesterol‐sensitive transcription factor, SREBP (Sterol Response Element Binding Protein), in the SUR2 promoter. Therefore, we tested the hypothesis that HDI‐dependent cholesterol depletion increases SUR2 by activating SREBP. As expected, treatment of HL‐1 cardiomyocytes with canonical HDI, trichostatin A (TSA; 30 ng/mL) for 72 hours caused a marked increase (20‐fold) of SUR2 mRNA expression compared to control. In addition, we observe increased activation of SREBP and marked increases in expression of selected SREBP‐target genes, including SCAP, IDOL, and PCSK9. Finally, in luciferase promoter assays, SREBP markedly increases reporter gene expression driven by the upstream SUR2 promoter (−510/−40) sequence, which contains a putative SREBP binding site. Taken together, our findings demonstrate a cholesterol‐dependent mechanism regulating expression of the cardioprotective KATP channel and suggest a novel mechanism by which hypercholesterolemia may promote poor cardiovascular health.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dysfunction of Acid‐Sensing Ion Channel 5 (ASIC5) in Unipolar Brush Cells of the Vestibulocerebellum Causes Ataxia
Authors: Boiko Nina , Kucher Volodymyr , Stockand James D. 
Published: June 2021

Acid‐sensing ion channels (ASICs) are ligand‐gated ion channels in the Degenerin/Epithelial Na+ channel (Deg/ENaC) family. ASIC proteins are richly expressed in mammalian neurons. Mammals express five ASIC genes: ASIC1‐5. The gene product of ASIC5 is an orphan member of the family about which little is known. To assess the function of ASIC5, we created ASIC5 reporter and knockout mice. We find that ASIC5 is chiefly expressed in the brain in the cerebellum, specifically in the ventral uvula and nodulus of the vestibulocerebellum. Here, ASIC5 is restrictively expressed in a subset of interneurons in the granular layer. The locale, distinctive shape and immunohistochemical properties of these ASIC5‐expressing interneurons identify them as unipolar brush cells (UBC). ASIC5 is richly expressed in a subset of UBCs that also express the metabotropic glutamate receptor 1α (mGluR1α). Such observations are consistent with ASIC5 playing a key role in the physiology of UBCs and in the function of the vestibulocerebellum, which is essential for normal balance and movement. Consistent with this, knockout of ASIC5 results in ataxia and uncoordinated bodily movements.Support or Funding InformationThis work was funded by a CPRIT IIRG grant (RP150408) and a NIH/NCI R21 grant (CA194138)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mechanistic Study of Four Co‐Morbid Hyperlipidemia‐Related Pathologies Reveals NFκB and STAT3‐Mediated miR‐155 and miR‐221 Potentially Serve as Master Regulators, and Elucidates Metabolically Healthy Obese Model
Authors: Johnson Candice , Drummer Charles , Virtue Anthony , Gao Tracy , Hernandez Miguel , Singh Lexy , Wang Hong , Yang Xiao‐Feng 
Published: June 2021

Hyperlipidemia afflicts more than 70 million Americans and is commonly linked with atherosclerosis, obesity, non‐alcoholic fatty liver disease (NAFLD) and type II diabetes. In recent years, microRNAs (miRNAs) have been firmly established as important regulators in these hyperlipidemia‐related pathologies. However, much remains to be understood regarding miRNAs' overlap and function within these hyperlipidemia‐related pathologies. Our recent JBC paper (PMID: 27856635) has shown that miRNA‐155 is significantly increased in atherosclerosis but reduced in high‐fat diet‐induced obesity. We published the findings that global miR‐155 deficiency in an atherosclerotic mouse background yielded a novel metabolically healthy obese mouse model, which exhibits improved atherosclerosis but resulted in obesity, NAFLD, and hyperinsulinemia without insulin resistance. Such a finding implied 1) a potent role of a single miRNA to differentially affect hyperlipidemia‐related diseases such that miRNAs achieve master gene candidacy status; and 2) a differential expression of downstream targets of miRNA in different cell types. In our current study, we sought to expand our understanding of the various miRNAs in these hyperlipidemia‐related conditions, specifically in regards to their expression direction, regulation and function. We hypothesized that miRNAs function as a potent master regulator that directs pathogenesis of hyperlipidemia‐related diseases where only a few miRNAs are shared between two or more hyperlipidemia‐related conditions (e.g., atherosclerosis, obesity, insulin resistance/type II diabetes and NAFLD). Using microarray and other experimentally verified‐based datamining approaches, we found that, among nearly 150 miRNAs, miR‐155 and miR‐221 are significantly modulated in all four hyperlipidemia‐related diseases. Our results also show a significant role for NFκB and STAT3 as upstream regulators for these and other miRNAs. Our datamining results identified mRNA targets that could contribute to the disease manifestations. Additionally, we identified groups of miRNAs that are unique to one hyperlipidemia‐related disease type as well as miRNAs that were modulated in comorbidities, which may be useful as future disease biomarkers in differentiation, diagnosis and prognosis. Taken together, we are first to show that NFκB‐ and STAT3‐mediated miR‐155 and miR‐221 potentially serve as master regulators for four co‐morbid hyperlipidemia‐related diseases.Support or Funding InformationNIH‐NHLBIThis 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 Short Chain Fatty Acid Mixtures on Colonic Motility
Authors: Kendig Derek M. , Hurst Norman , Favreau Alexander 
Published: June 2021

The effects of nutrients on a variety of colonic function has been well studied. Recent evidence has suggested that sensing of many different intraluminal nutrients (glucose, amino acids) is accomplished through plasma membrane receptors within the intestinal epithelium. These membrane receptors are often linked to hormone release from enteroendocrine cells. While many digested nutrients are present at higher intraluminal concentrations within the small intestine before they are absorbed, short chain fatty acids (SCFAs) in particular are generated by bacterial metabolism of nutrients within the colon. Based on previous studies, the most prominent individual SCFAs (butyrate, acetate, and propionate) have differential effects on cellular signaling and motility within the colon. However, the overall effects of mixtures of these SCFAs, which are more similar to intraluminal conditions, have not been elucidated. In this study, we measured colonic motility of both the proximal and distal colon in response to SCFA mixtures. Motility in the proximal colon of guinea pigs was measured as full‐propagating, shortpropagating, or non‐propagating contractions through video capture and subsequent generation of spatiotemporal maps. Motility in guinea pig distal colon was measured by velocity of fecal pellet propulsion. An 30mM SCFA mixture with a molar ratio of 3:2:1 (acetate: butyrate: propionate) increased velocity of fecal pellet propulsion. This increase in distal colonic motility was inhibited by GR113808, an antagonist of 5‐HT4 receptors, suggesting that mediation of motility effects was through serotonin. Statistical comparisons of pellet velocity were made by one‐way repeated measures ANOVA. In the proximal colon, the same SCFA mixture reduced the presence of short‐propagating contractions (<50% of the tissue length) while not affecting full‐propagating contractions. These results suggest that SCFA mixtures have differential effects on propulsive motility in the proximal and distal colon of guinea pigs. Future work will elucidate the presence of the FFAR2 and FFAR3 receptors in relation to enteroendocrine cells containing serotonin and other endocrine mediators of colonic function (peptide YY, neurotensin).Support or Funding InformationThis work was supported by a summer research grant to DMK from Loyola University Maryland and a small grant by the VCU postdoctoral association. DMK was also partially supported by an NIGMS IRACDA grant GM093857 to VCU.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Creatine Supplementation and Doxorubicin Treatment on Diaphragm Myogenic Regulatory Factor Expression
Authors: Jones Megan , Busekrus Raquel , Torok Zoltan , Hydock David 
Published: June 2021

The purpose of this study was to explore the effects of creatine monohydrate (Cr) supplementation and the chemotherapy drug doxorubicin (DOX) on myogenic regulatory factor (MRF) expression in the diaphragm. Male Sprague‐Dawley rats were fed either a diet supplemented with 3% Cr or a standard control (CON) diet for two weeks. Animals were then randomly assigned to receive 15 mg/kg of DOX or saline (SAL) as a placebo. After five days, animals were anesthetized, diaphragms were removed, and expression of the primary MRFs MyoD and Myf5 were quantified using Western blotting. When compared to CON+SAL diaphragm, MyoD expression was 24% and 31% lower in diaphragms from CON+DOX and Cr+DOX, respectively. Myf5 expression was 15% and 41% higher in diaphragm from CON+DOX and Cr+DOX, respectively, when compared to CON+SAL diaphragm. A trend toward DOX decreasing MyoD and increasing Myf5 expression in diaphragm was observed, and the trend toward Cr increasing Myf5 expression with DOX treatment warrants further investigation.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 natural products from a medicinal plant (Cinnamosma fragrans) on contractions of a visceral muscle in the Zika vector Aedes aegypti
Authors: DeLaat Andrew , Rakotondraibe Harinantenaina Liva , Piermarini Peter 
Published: June 2021

Mosquito‐borne diseases such as malaria, dengue fever, and Zika, are a constantly evolving problem with newly emerging and reemerging pathogens threatening the health of millions of individuals worldwide. Prevention of these diseases relies on the effective control of mosquito populations with insecticides. Our group is developing new insecticides derived from natural products of the Madagascan medicinal plant Cinnamosma fragrans by understanding the interactions of these compounds with mosquitoes on a molecular and physiological level and how they exert their toxic effects. The goal of this study is to determine the effects of natural drimane sesquiterpene compounds isolated from the medicinal plant C. fragrans on the visceral muscle contractions of the ventral diverticulum (crop) in adult female yellow fever mosquitoes (Aedes aegypti), an important vector of Zika virus. Using an established bioassay, we evaluated the acute effects of several drimane sesquiterpenes on contraction rates of isolated crops in Ringer solution. Our results demonstrate that at least two insecticidal drimane sesquiterpenes significantly inhibit the spontaneous and serotonin‐stimulated contractions of the crop. The potency of their inhibition correlates with their potency as insecticides, suggesting that visceral muscle inhibition may be responsible for the toxic effects of the compounds on mosquitoes. Moreover, parallel experiments in the crop with a calcium ionophore (A23187) duplicate the effects of the natural compounds, suggesting that they may elicit muscle inhibition by modulating calcium permeability of the crop muscle cells. Future research will investigate the presence and roles of calcium channels within the crop, attempting to better understand their interaction with C. fragrans natural compounds.Support or Funding InformationSupported by NIH grant R21AI129951.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
LRRC8A/C Voltage‐Dependent Anion Channels Are Required for NADPH Oxidase 1 Activation in Response to TNFα
Authors: Choi Hyehun , Nguyen Hong N. , Dikalova Anna , Lamb Fred S. 
Published: June 2021

Tumor necrosis factor‐α (TNFα), a pro‐inflammatory cytokine, is linked to cardiovascular risk. TNFα‐induced superoxide (O2−•) production by NADPH oxidase 1 (Nox1) is required for inflammatory signaling in vascular smooth muscle cells (VSMC). Leucine Rich Repeat Containing 8 (LRRC8) family proteins (LRRC8A, B, C, D and E) comprise volume‐regulated anion channels (VRACs) which are activated by TNFα. VRAC inhibitors suppress the inflammatory response to TNFα, however, the specific subtype of VRAC that is required for this remains to be determined. We hypothesized that a specific type of VRAC is required for Nox1 activation in TNFα signaling. Based upon PCR screening, VSMCs express all five LRRC8 subtypes. However, only knockdown (siRNA) of LRRC8A and C inhibited NF‐κB activation by TNFα (siLRRC8A 49 % decrease, siLRRC8C 31 % decrease). LRRC8D siRNA increased TNFα‐mediated NF‐κB activation (47 % increase). Heterologously expressed LRRC8A and C co‐localized at both the plasma membrane and in intracellular vesicles. LRRC8C knockdown reduced extracellular superoxide production (CAT1H spin trap; siControl+TNFα 1151±25, siLRRC8C+TNFα 774±27 pmol/mg of protein) in response to TNFα as well as TNFα receptor endocytosis (54.5% decrease), subsequent intra‐endosomal superoxide production (CAT1H; siControl+TNFα 201±8.2, siLRRC8C+TNFα 164±9.0 pmol/mg of protein) and proliferation (PCNA protein expression; 31.4 % decrease). These results demonstrate that LRRC8A/C VRACs supports TNFα‐induced Nox1 activity in VSMC. Selective LRRC8A/C inhibition may provide a novel and selective strategy for inhibition of TNFα signaling.Support or Funding InformationAmerican Heart Association, Scientist Development Grant, 16SDG30610002This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Development of a Self‐assessment Tool to Help Students Develop Metacognitive and Critical Reasoning Skills During High‐fidelity Medical Physiology Simulations
Authors: Kibble Jonathan D. , Harris David D. , Fiore Stephen D. , Garbayo Luciana D. 
Published: June 2021

The UCF College of Medicine M.D. curriculum includes a 16‐week Structure and Function module in the first year in which students learn basic medical physiology. The module includes five high‐fidelity simulations that require students to apply physiological knowledge to develop treatment plans in acute care situations. Students work collaboratively in teams of six in a 15 min period to complete a simulation exercise, each of which is followed by debriefs on physiological reasoning and the effectiveness of team process. Past experience has shown that student teams often struggle to identify and organize information and to reach a group consensus about treatment. In this study we developed a survey tool for students to use during a simulation that provides a framework to organize thinking to decision making. The instrument was deployed on an iPad and required each student to first identify sources of information, to list problems requiring attention, to prioritize the problem list and to make a note of physiological rationale. Students could then discuss as group before proceeding to treatment decisions. Each item was followed by a self‐rating of confidence on a 7‐point Likert scale. Eighty out of 120 students gave informed consent for their data to be included in this IRB‐approved study. The most common errors were omission of key information, misconceptions of physiology and over‐treatment of the patient. Despite the prevalence of error students showed high levels of confidence, demonstrating an over‐confidence bias in their decision making. In conclusion the tool shows promise as a way to identify misconceptions in physiology and to reflect on errors in critical reasoning and decision making.Support or Funding InformationUCF College of Medicine, Medical Education GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Breaking Out From Tradition: Redesign of Large Physiology Lecture Increases Engagement, Inclusion, and Student Outcomes
Authors: Dickey Jordyn , Kimball Kristen , Redden John M. 
Published: June 2021

Mounting evidence suggests that traditional lecturing is less effective, less engaging, and less inclusive than active learning. However, transitioning to active learning, particularly in a large science course, presents unique administrative and pedagogical challenges. In this study, we present the results of our recent effort to redesign and restructure our large human anatomy and physiology course at the University of Connecticut.In place of a traditional lecture, we developed an active instructional model that subdivided hundreds of students into “break out” groups of no more than five students. Breakout groups met concurrently in multiple classrooms during the scheduled lecture time to work through modules in the renal and digestive systems with an undergraduate peer facilitator. Modules were designed with input from undergraduate facilitators, with attention to scientific teaching techniques (active learning, inclusive teaching, assessment). Students concept mapped the molecular basis of urine formation in nephrons and the regulation of acid secretion in the gastric pit; worked through an interrupted case study on ulcer formation and modified think‐pair‐share question sets on renal and gastric pharmacology; and practiced critical reflection on the clinical and socioeconomic factors influencing the incidence and treatment of disease.At the end of the semester, students registered in the redesigned course were compared to peers registered in another section, taught by the same instructors, that followed a traditional large lecture format. This assessment involved an analysis of student performance on paired exam questions of varied difficulty, a modified SALG (Student Assessment of Learning Gains), and solicited and unsolicited student feedback. Our results indicate that, on average, students in the redesigned course performed better on exam questions related to the renal and digestive systems. Furthermore, many of these questions were found to be less “discriminating”, indicating less disparity between higher performing and lower performing students. The vast majority (95%) of students gave positive feedback on the redesigned classes, and nearly 90% reported learning gains related to the major concepts from the digestive and renal system. Summarily, our study describes and evaluates a new instructional model for large, undergraduate anatomy and physiology courses that has been developed and implemented using undergraduate students. Most importantly, we offer preliminary evidence supporting the conclusion that this model is more inclusive, more effective, and better liked than traditional lecturing.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.