bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Notch Act Through mTOR to Regulate Protein Synthesis?
Authors: Huot Joshua , Thompson Brian , McMullen Charlotte , Arthur Susan 
Published: June 2021

PURPOSENotch signaling is thought to be crucial in regulating skeletal muscle regeneration, however, the impact Notch signaling has on other skeletal muscle processes (e.g. protein synthesis) remains unclear. The purpose of this project was to determine the effects of Notch inhibition on protein synthesis in C2C12 cells.METHODSC2C12s were seeded, proliferated to ~ 90% confluence and then differentiated for four days. At the onset of differentiation, C2C12s were treated every 12 hours (from 0hr–96hr) with one of the following conditions: 4 μmoL of gamma secretase inhibitor (GSI: Notch inhibitor), 100 nmoL of Rapamycin (mechanistic target of rapamycin (mTOR) inhibitor), both, or control. Four days post‐differentiation C2C12s were fixed for immunofluorescence to quantify myotube formation, or were collected and analyzed for components of Notch, anabolic signaling, and protein synthesis (via puromycin incorporation).RESULTSGSI treatment increased fusion index compared to the other three treatments (fusing nuclei/total nuclei) (p <0.0001). Rapamycin abrogated fusion index relative to control (p <0.0001). GSI + Rapamycin‐treated CC12s also had reduced fusion index compared to control (p<0.0001). GSI‐treated C2C12s displayed elevated protein synthesis compared to all other groups (p < 0.05). Rapamycin reduced protein synthesis compared to control (p < 0.05). GSI+Rapamycin‐treated C2C12s did not differ in protein synthesis compared to control or Rapamycin.CONCLUSIONSOur data suggests that Notch may regulate protein synthesis through mTOR.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Phytoecdysteroids Enhance Skeletal Muscle Function Recovery Following In Vivo Eccentric Contraction‐Induced Injury in Old Mice
Authors: Hodgman Charles F. , Godwin Joshua S. , Zwetsloot Kevin A. , Shanely R. Andrew 
Published: June 2021

Phytoecdysteroids are natural plant steroids synthesized by a variety of hardy plants. Previous work by our group has shown that administration of phytoecdysteroids, such as 20‐hydroxyecdysone (20E), in old mice results in an increase in protein synthesis signaling and skeletal muscle fiber size. The effect of phytoecdysteroids on recovery from eccentric contraction‐induced skeletal muscle damage is unknown. Therefore, the purpose of this study was to investigate the degree to which 7 days of 20E supplementation, in old male mice, improves recovery of isometric skeletal muscle function following injurious eccentric muscle contractions (EC), compared to placebo (PLA). Old male mice (mean age 27.5 ± 0.5 months) were assigned to either EC+20E or EC+PLA treatment groups. Mice were anesthetized with isoflurane and then in vivo isometric contractions (Aurora Scientific, 1300A) were performed to obtain optimal electrode placement for stimulation of the anterior crural muscle group. Following electrode placement, the isometric torque‐frequency relationship was established (PRE). Then, 150 EC were performed to induce injury in the anterior crural muscle group. Upon completion, the torque‐frequency relationship was re‐measured to confirm damage (POST). Following recovery from anesthesia, the mice received either 20E (50 mg•kg−1 BW) in liquid diet (BioServ, AIN‐76) or PLA (liquid diet only) by oral gavage. Mice were gavaged daily for 6 days. On day 7, mice were anesthetized with isoflurane and the torque‐frequency relationship was re‐assessed (7‐day). Repeated measures ANOVA revealed that EC in EC+PLA led to a depression in the torque‐frequency relationship, as measured at 7‐day (p<0.01). Conversely, 7 days of 20E supplementation led to recovery of the torque‐frequency relationship to PRE levels (p=0.461). Additionally, maximal (250 Hz) and submaximal (40 Hz) isometric torques remained depressed in EC+PLA (p=0.014 and p=0.004, respectively), while EC+20E showed no change (p=0.559, p=0.632, respectively) from PRE to 7‐day. In conclusion, these findings suggest that 20E exerts anabolic or ergogenic effects in old male mice that aid in recovery of isometric skeletal muscle function following EC‐induced injury.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Regulation of Intracellular Calcium in Uterine Leiomyomas
Authors: Ravix Jovanka L. , Purdy Mackenzie D. , Thompson Michael D. , Wicher Sarah A. , Roesler Anne A. , Manlove Logan , Britt Rodney D. , Wheeler Lydia D. , Parikh Pavan , Stewart Elizabeth , Pabelick Christina , Prakash Y.S. 
Published: June 2021

BackgroundUterine leiomyomas (fibroids) are benign smooth muscle cell tumors of the uterus that affect a large percentage of reproductive aged women, contribute to infertility, excessive menstrual bleeding, and represent the leading cause of hysterectomy (~70%). Despite their importance, the mechanisms that promote fibroid growth are still not well‐understood. Fibroids are comprised of smooth muscle cells (SMCs) and fibroblasts and their growth is modulated by hormones including estrogen and progesterone. Intracellular calcium [Ca2+]i signaling is a key aspect of SMC physiology in promoting contractility, cell proliferation, and fibrosis: aspects relevant to fibroid biology. While [Ca2+]i regulation in normal myometrium is well characterized, this has not been explored in fibroids. The goal of this study was to explore [Ca2+]i regulation in fibroid SMCs and the effect of sex steroids towards obtaining insights into tumor progression.MethodsCells were enzymatically isolated from normal myometrium and select fibroids of different sizes from patients undergoing myomectomy at Mayo Clinic, Rochester, MN (IRB approved). [Ca2+]i was measured using fura‐2/AM and real‐time fluorescence microscopy. The contribution of Ca2+ influx vs. intracellular pathways in the responses to 1uM oxytocin were assessed using pharmacological inhibitors/activators. Cells were pretreated with vehicle, 1nM estrogen, or 1nM progesterone to assess the effect of sex steroids.ResultsFibroid‐derived cells showed a greater contribution of Ca2+ influx pathways in their responses to oxytocin than normal myometrium. Here, the Ca2+‐activated chloride channel TMEM16A (Ano1) was found to be contributory, with Western analysis showing higher levels of Ano1 in fibroids. Exposure to estrogen resulted in significantly higher [Ca2+]i responses compared to cells treated with vehicle or progesterone, although progesterone did enhance [Ca2+]i responses as well. Estrogen increased Ano1 expression. Cell proliferation was also increased in fibroid cells.ConclusionsExposure to estrogen and progesterone enhances oxytocin induced [Ca2+]i responses of fibroid‐derived cells, potentially via increased TMEM16A (Ano1). Such increases may further contribute to the observed hormone‐induced enhancement of fibroid cell proliferation. Menstrual cycle fluctuations in reproductive aged women may thus contribute to the progression of fibroids. Greater understanding of calcium signaling pathways such as Ano1 in fibroid tissue may allow for novel therapeutic targets in uterine leiomyomas.Support or Funding InformationSupported by NIH grants R25 GMO75148 (JLR), R01 HL088029 (YSP), and R01 HL56470 (YSP).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Secondhand smoke exposure impairs vascular reactivity in mesenteric arteries
Authors: Nieves‐Cintron Madeline , Syed Arsalan , Pan Shiyue , Karey Emma , Sun Junqing , Navedo Manuel , Chen Chao‐Yin 
Published: June 2021

Secondhand smoke (SHS) has significant detrimental vascular effects, including enhanced vasoconstriction and hypertension. Yet, the mechanisms linking SHS exposure to these complications are unclear. Although the multifactorial nature of these changes is well appreciated (e.g. endothelial dysfunction, aberrant central control regulation), impaired vascular smooth muscle (VSM) function may also be a key, yet poorly explored, contributing factor. In this study, we tested the hypothesis that vascular reactivity of small diameter mesenteric arteries is altered in mice exposed to SHS. Mice were randomized into control (filter air, FA) and experimental (SHS) groups and exposed to either FA or SHS (Total Suspended Particle, TSP = 3 ± 1 mg/m3; 6 hrs/day, 5 days/week) for a 12 weeks period. After 12 weeks, mesenteric arteries from mice exposed to SHS showed higher (P < 0.05) myogenic tone compared to arteries from the FA group (15.7 ± 2 vs. 23.2 ± 2 FA vs. SHS, respectively). Moreover, we found reduced ACh‐induced vasodilation in SHS arteries (p < 0.05). Consistent with elevated myogenic tone, the resting membrane potential (Vm) of VSM cells isolated from mesenteric arteries of mice exposed to SHS was more depolarized (p < 0.05) than in cells from arteries from the FA group (−42.3 ± 3 vs. −35 ± 2, FA vs. SHS, respectively). Our next series of experiments will examine mechanisms mediating changes in Vm in VSM from SHS versus FA. Our results suggest that SHS have deleterious effects on the vasculature that may involve changes in VSM function.Support or Funding InformationThis work was supported by NIH R01ES025229, R01HL098200, R01HL121059, and NIH‐T32 HL086350.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of metabolic syndrome and aging on coronary artery disease severity and Ca2+ dysregulation in coronary smooth muscle in Ossabaw miniature swine
Authors: Badin Jill K. , Bruning Rebecca S. , Sturek Michael 
Published: June 2021

BackgroundMetabolic syndrome (MetS) and aging are prevalent risk factors for coronary artery disease (CAD) that play a role in the etiology of CAD, including dysregulation of Ca2+ transporter function in coronary smooth muscle (CSM). The current study examined Ca2+ dysfunction in MetS‐ compared to aging‐induced CAD.MethodsYoung (2.5 ± 0.2 years) and old (8.8 ± 1.2 years) swine were fed an atherogenic diet for 11 months to induce MetS and were compared to lean age‐matched controls. The metabolic profile was confirmed by body weight, cholesterol, triglycerides, and intravenous glucose tolerance test. CAD was measured with intravascular ultrasound (IVUS) and histology. Intracellular Ca2+ ([Ca2+]i) was assessed with fura‐2.ResultsCAD severity was similar between MetS young and lean old swine, with MetS old swine exhibiting the most severe disease. Fura‐2 imaging of [Ca2+]i in CSM revealed that both MetS young and lean old swine had increased sarcoplasmic reticulum Ca2+ store release, and MetS young swine exhibited increased Ca2+ influx through voltage‐gated Ca2+ channels. Lean old swine exhibited attenuated sarco‐endoplasmic reticulum Ca2+ ATPase activity. MetS old and MetS young swine had similar Ca2+ dysregulation.ConclusionsCa2+ dysregulation in CSM is more pronounced in lean old compared to both MetS groups, which is indicative of mild, proliferative CAD. MetS old and MetS young swine exhibit Ca2+ dysfunction that is typical of late, severe disease. The more advanced, complex plaques in MetS old swine suggest that the “aging milieu” potentiates effects of Ca2+ handling dysfunction in CAD.Support or Funding InformationThis research was supported by HL125385, P30 DK097512, T32 HL079995, Indiana University School of Medicine Center of Excellence in Cardiovascular Research, and the Fortune‐Fry Ultrasound Research Fund.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Synergistic effects of Dantrolene and Nimodipine on the Phenylephrine‐induced Contraction and ACh‐induced Relaxation in Aortic Rings from Diabetic Rats
Authors: Roman Marie , Ramirez Jose , Torres Ricardo , Morales Myrna , Torres Hector , Crespo Maria J. 
Published: June 2021

Diabetics have a higher risk of developing cerebral vasospasms (CVSP) than non‐diabetics. The addition of the ryanodine receptor (RyR) blocker dantrolene to standard therapies reduces vasospasms in non‐diabetics. Whether diabetics with CVSP also benefit from this drug, however, is unknown. We evaluated the effects of a 30‐min incubation with dantrolene (50 μM), nimodipine (50 nM), and both drugs in combination, on phenylephrine (PHE)‐induced contraction, and on acetylcholine (ACh)–induced relaxation in aortic rings from streptozotocin (STZ) diabetic rats. Age‐matched, non‐diabetic rats served as controls. The oxidative‐stress markers malondialdehyde (MDA) and 4‐hydroxyalkenal (4‐HAE) were also evaluated in the presence and absence of dantrolene and nimodipine. The combination of these two drugs acted synergistically to reduce the PHE‐induced contraction by 80% in both diabetics and controls. In contrast, it increased the Emax value for ACh‐induced relaxation (from 56.46 ± 5.14% to 96.21 ± 7.50 %; n=6, P < 0.05), and it decreased MDA +4‐HAE values in diabetic rats only. These results suggest that the combination of dantrolene and nimodipine benefits both diabetics and non‐diabetics by decreasing arterial tone synergistically.Support or Funding InformationSupported by NIH (MBRS‐RISE Grant R25GM061838), and NIMHD‐RCMI (Grant G12‐MD007600).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Glucose and NADPH Oxidase Dependent Trans‐plasma Membrane Electron Transport
Authors: Kelly Shannon C. , Patel Neej N. , Fisher Jonathan S. 
Published: June 2021

Trans‐plasma membrane electron transport (tPMET), a process common to multiple cell types, transfers electrons from the cytosol to the extracellular space. The objective of this study was to determine the mechanism of tPMET in muscle cells. C2C12 myotubes and water‐soluble tetrazolium salt‐1 (WST‐1), a cell impermeable electron acceptor, were utilized along with metabolic inhibitors to elucidate the mechanism of tPMET. Upon addition of superoxide dismutase to extracellular media, WST‐1 reduction by myotubes was decreased by ~70%, indicating that the release of extracellular superoxide is the main mechanism of tPMET in C2C12 myotubes. The addition of GKT137831, a NADPH oxidase (NOX) 1 and 4 inhibitor, suppressed WST‐1 reduction while the addition of GSK2795039, a NOX2 inhibitor, did not decrease WST‐1 reduction. Preliminary western blot analysis showed the presence of NOX1 and NOX2 protein but not NOX4 protein. In the absence of glucose, tPMET was significantly decreased, thus indicating that tPMET is a glucose dependent process. The addition of the hexokinase inhibitor, 2‐deoxy‐D‐glucose, also suppressed tPMET as did the addition of glucose‐6‐phosphate dehydrogenase inhibitor, dehydroepiandrosterone. In contrast, glycolytic inhibitors including the 6‐phosphofructo‐2‐kinase inhibitor, 3PO, and enolase inhibitor, sodium fluoride, did not affect WST‐1 reduction. This indicates that the process of tPMET is dependent upon the pentose phosphate pathway and not glycolysis. In conclusion, these data suggest a glucose‐sensing model of tPMET in which presence of extracellular glucose provides substrate for NADPH production and subsequent NOX1‐dependent release of superoxide.Support or Funding InformationThis work was supported by the United States Public Health Service award R15DK102122 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Two Case Studies Comparing Flipped Teaching and Online Teaching with the Traditional Lecture‐based Teaching
Authors: Fentem Andrea , Beard Rachael , Gopalan Chaya 
Published: June 2021

Flipped teaching has expanded into many classrooms over the recent years due to its student‐centered focus. Similarly, online teaching has also gained popularity due to the flexibility it offers to students. In the first case study, we compared scores on exams from the traditional lecture‐based teaching method with that of a flipped teaching style in a graduate level Advanced Human Physiology (NURS514) course for the Nurse Anesthesia (CRNA) students. In the second case study, we compared scores on exams between a traditional and an online NURS514 course from the Nurse Practitioner (NP) program between two semesters. Since the exam averages were consistently high in every exam whether it was lecture‐based or flipped teaching, there was no significant difference between the two methods of teaching among the CRNA classes. However, over 80% of the CRNA students reported that they would recommend flipped teaching in the future. The NP class, on the other hand, performed significantly better in their exams in the online course compared to the face‐to‐face class (p < 0.05). The success with online student performance is partly due to the flexibility students have in pacing their learning through lecture videos instead of the continuous four‐hour weekly lectures in the face‐to‐face setting. Newer teaching methods such as flipped teaching and online class could successfully replace traditional lecture‐based courses.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
How do astrophysicists organize a party? Their wives planet: Gender differences in student perceptions of instructor humor in college science courses
Authors: Cooper Katelyn , Hendrix Taija , Cala Jacquie , Brownell Sara 
Published: June 2021

Instructor's use of humor in college classrooms is generally viewed positively by students and has been correlated with positive student learning, motivation, perceptions of instructor immediacy, and classroom environment. However, the majority of studies on instructor humor used in college classrooms have explored student perception of funny humor and not of unfunny or offensive humor. Female students, who are more likely to report feeling unwelcome in college science courses, may be particularly affected by instructor use of unfunny or offensive humor. However, few studies have explored how male and female students perceive instructor humor and more specifically, whether male and female students perceive different subjects as offensive. Further, no humor study has been conducted in the context of college science courses.This study was conducted as a course‐based undergraduate research experience (CURE) in biology education with 12 undergraduate and 4 graduate students. Students in the CURE engaged in the process of selecting a research question, iteratively developing a survey tool, collecting data, and analyzing data. We surveyed 1637 undergraduate students across 25 different college science courses at one institution and found that 97% of students appreciate when instructors use humor in college science classes. Using a combination of grounded theory and content analysis, we identified 12 distinct reasons for why students appreciate instructor use of humor in science classes, including that it enhances student learning, makes students more excited to attend class, and makes the instructor more approachable. We found that instructor use of funny humor positively impacted student sense‐of‐belonging to the science classroom, instructor relatability, and student attention to course content. We also found that while instructor use of unfunny humor appeared to neither have a positive nor a negative effect on students, instructor use of offensive humor negatively impacted student sense‐of‐belonging to the science classroom and instructor relatability. There was no difference in the extent to which instructor use of humor positively or negatively affected male and female students. Lastly, we identified a suite of subjects that students broadly perceive as funny, yet less than 5% of students perceive as offensive. We also identified a suite of subjects that some students perceive as funny, yet more than 50% of students perceive as offensive. Specifically, female students were more likely to be offended by humor used by instructors. We hope that these findings will aid in the development of more inclusive classrooms by encouraging instructors to use humor that is most likely to benefit all students.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Comparison of medical students' performance in multiple choice questions and integrated short answer essay questions in end unit examination at PBL School
Authors: Hasan Zuheir A. , Almarabheh2 Amer J. , Abdul Razzak Rima L. , kamal Amer H. 
Published: June 2021

The Arabian Gulf University (AGU) is a regional university serving the Gulf Cooperation Council Countries. One of the most distinguished features of the MD program at AGU is problem based learning curriculum where teaching and learning of basic medical sciences are delivered through nine integrated organ system based units. At the end of each unit, medical students are required to pass a comprehensive end unit exam, where multiple formats of assessment are currently used This retrospective study compared the performance of year II medical students in multiple choice (MCQ) and short answer integrated questions (SAQ) of the end unit I examination The grades of three cohorts (471 students) were analyzed. The average score was 69.8(±SD 12.) in the MCQ component and 65.5 (± SD 13.7) in the SAQ component. Regression analysis showed a significant correlation (r=0.819, P< 0.000) between MCQ and SAQ.. when students performance was grouped by final end unit grade, a significant correlation existed between MCQ and SAQ score for 40 students who failed the end unit exam, 234 students who received a passing or a good score and for 132 students who received a very good score A positive but none significant correlation existed between the MCQ score and the SAQ score for students who received an excellent grade in the end unit exam. Finally two ANOVA revealed that MCQ scores were higher than (P < 0.01) SAQ scores for all groups. The results of this study showed that for most students, there is strong correlation between MCQ and SAQ scores, indicating that student performance was independent of testing format.Support or Funding InformationArabain Gulf UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.