bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical use of audience response system provides opportunity to formatively assess teaching and improve learning outcomes
Authors: Hopper Mari K , Wright Serena M , Carroll Megan , Bauer Erich , Carlos W. Graham 
Published: June 2021

PURPOSEAlthough audience response systems (ARS) are frequently used to formatively assess student learning, this technology is rarely employed to formatively assess teaching. Aim of study was implementation of novel approach using ARS to assess teaching methods in order to enact rapid improvement.METHODSSecond‐year students of large multi‐center medical school participated anonymously. Study involved nine sequential, three‐hour pulmonary class sessions delivered live on one campus and livestreamed to others. Following each session, ARS delivered three Likert scale and one open‐ended question: 1)What degree have you utilized higher order skills; 2)Rate your level of engagement; 3)Estimate percentage of time focused; and 4)What went well/suggestions for improvement. Following each session, course leaders considered student input and adjustments made before delivery of next session. Faculty also quantified parameters including number of cases, key concepts, videos, and slides per session and “Bloomed” embedded questions.RESULTSApproximately 60% of students responded to ARS questions. Results indicated consistent improvement from session one to nine in all parameters: number of students perceiving very high use of higher order skills increased from 10% to 30%, students rating the session as highly engaging rose from 55% initially to 80% for final session, and ability to remain focused for more than 70% of the class time rose from 55% of students to over 75%. Comparison of student perceptions to objective measures is underway.CONCLUSIONInnovative ARS use allowed faculty to immediately gather feedback from diverse students at distributed locations. Feedback guided change leading to improved student engagement, focus, and utilization of higher order skills. Students were also highly appreciative of opportunity to impact change in the class while participating.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Improving Cardiac Function and Body Composition through Incentive‐Based Smartphone Application in Sedentary Overweight Adults
Authors: Choi Myung Dong , Standridge Austin , Landis‐Piwowar Kristin 
Published: June 2021

Smartphones evolved from simple calling, texting to streaming video and tracking your daily physical activity. Previous studies support the use of financial incentives in increasing daily physical activity, leading to an increase in human health and lifestyle behavior modification can reduce the risk of cardiovascular disease. However, there is a lack of evidence that smartphone apps which provide incentives, are associated with health promotion.PurposeThe aim of this study is to determine the effects of an incentive based smartphone app to promote physical activity and improve cardiopulmonary health and body composition in sedentary overweight individuals.MethodsTwenty sedentary overweight adults (body mass index≥25) were randomly assigned to a control group (20.4±1.3 yrs, n=10) or an intervention group (27.5±12.7 yrs, n=10). The intervention group downloaded an incentive‐based step counter app (Carrot wellness app) on their smartphone. If the daily step goal was met in the intervention group, they were rewarded with a coin that could potentially be traded in for gift cards. The control group downloaded a step counter app (Google Fit app), which does not provide any incentives. Data was collected twice: pre‐ and post‐ten weeks Carrot wellness app usage. Pre and post‐testing evaluations included blood lipid profile, body mass index (BMI), body fat percentage (% body fat), maximal oxygen consumption (VO2max) and cardiac output at 50% of a subject's VO2max. A one‐way ANCOVA was used to determine differences in variables between the groups.ResultsThere were significant differences in BMI (P=0.017), body weight (P=0.045), cardiac output (P=0.002) and stroke volume (p=0.002) between the control and the intervention group. However, there were no significant differences in blood lipid profile (e.g. high density lipoprotein, low density lipoprotein, and total cholesterol) or VO2max.ConclusionsTen weeks of incentive‐based step counter app usage may be beneficial to improve body composition and submaximal cardiac function in sedentary overweight adults. These findings may support that providing incentives to sedentary adults for exercising may contribute to further health improvements. However, there is no significant improvement on blood lipids and maximal cardiovascular fitness. Overall, our study may indicate that incentive‐based health promoting smartphone apps can be especially helpful for those sedentary adults having difficulty self‐motivating themselves to exercise.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
No changes observed in Circulating Tumor Necrosis Factor‐alpha or receptors following Prolonged Exercise in a Cold Environment
Authors: Jajtner Adam R , Arroyo Eliott , Followay Brittany N , Vaughan Jeremiah A , Laudato Joseph A , Gibson Brandon M , Glickman Ellen L 
Published: June 2021

Tumor Necrosis Factor‐alpha (TNF‐α) is a pro‐inflammatory cytokine that is known to increase during exercise in the heat, however, has not been examined in a cold environment.OBJECTIVEThe purpose of this study was to examine the circulating concentration of TNF‐α and the corresponding expression of TNF‐receptor 1 and 2 (TNFr1 and TNFr2) on classical monocytes following aerobic exercise in a cold environment.METHODSSeven recreationally active men (25.0 ± 3.2 yrs; 1.82 ± 0.06 m; 85.3 ± 7.6 kg; 4.04 ± 0.40 L·min−1) completed three experimental visits: a VO2max test, and cycling in 5°C (LT) and 23°C (MT) in a counterbalanced fashion. Cycling consisted of 60 minutes at 60% of their previously determined VO2max (TC60), and a time to exhaustion trial at 90% of their VO2max (TTE). Rectal core temperature was monitored and recorded continuously, while blood samples were taken prior to exercise (PRE), at TC60, TTE and after one hour of recovery (REC). Samples were analyzed for circulating TNF‐α via ELISA, while a subset of participants (n=4) were assessed for TNFr1 and TNFr2 expression on classical monocytes (CD14++/CD16−) via flow cytometry. Non‐normally distributed data were LN transformed, and area under the curve (AUC) was calculated via the trapezoidal method. Data were analyzed using a within‐subjects repeated measures ANOVA, and a paired samples t‐test. Data are presented as mean ± SD.RESULTSNo significant interaction (F = 0.811, p = 0.504, η2p = 0.119) nor main effects of time (F = 0.670, p = 0.581, η2p = 0.100) or trial (F = 4.093, p = 0.090, η2p = 0.406) were observed for circulating TNF‐α concentration. Additionally, no significant difference was observed between trials for TNF‐α AUC (p = 0.083). No significant interaction (F = 0.811, p = 0.519, η2p = 0.213), nor main effects of time (F = 1.144, p = 0.383, η2p = 0.276) or trial (F = 0.303, p = 0.621, η2p = 0.092) were observed for TNFr1. No significant difference was observed between trials for TNFr1 AUC (p = 0.117). No significant interaction (F = 0.196, p = 0.896, η2p = 0.061), nor main effects of time (F = 0.974, p = 0.447, η2p = 0.245) or trial (F = 0.320, p = 0.611, η2p = 0.096) were observed for TNFr2. Additionally, no differences were observed between trials for TNFr2 AUC (p= 0.236).CONCLUSIONSNeither 60 minutes of moderate intensity exercise, nor exercise to exhaustion at a high intensity were sufficient to induce a response in circulating TNF‐α, nor classical monocyte expression of TNFr1 or TNFr2. Furthermore, exercise in the cold does not appear to modify this response.Support or Funding InformationThis study was partially funded by the Kent State University Research Council.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Empagliflozin effects on ischemic contracture and I/R injury in isolated mouse hearts perfused with or without insulin
Authors: Uthman Laween , Nederlof Rianne , Eerbeek Otto , Baartscheer Antionius , Buchholtz Ninée , Coronel Ruben , Hollmann Markus W. , Weber Nina C. , Zuurbier Coert J. 
Published: June 2021

IntroductionThe kidney‐targeted Empagliflozin (EMPA) has shown large unexpected cardiovascular benefits, which cannot be explained by general cardiovascular risk factors. We recently reported that EMPA has sodium hydrogen exchanger (NHE) inhibition properties in isolated cardiomyocytes. Classic NHE inhibitors such as Cariporide (CARI) delay ischemic contracture onset and reduce ischemia reperfusion (I/R) injury in the heart. Here we examined whether EMPA delays contracture onset and reduces I/R injury. Both normal‐ and low‐glycogen hearts were used, because the rate of glycogen depletion during ischemia affects contracture onset and IR injury.Methods/ResultsIsolated mouse hearts were perfused with and without 50 mU/L insulin, to create normal‐ and low‐glycogen hearts respectively, and subjected to 25 min I and 120 min R. 1μM EMPA, 10μM cariporide (CARI; positive control) or vehicle was administered prior to ischemia until 10 minutes post‐reperfusion. In normal‐glycogen hearts, EMPA and CARI did not change ischemic contracture (in seconds, vehicle 1056±56, EMPA 900±44, CARI 880±84) and IR injury (infarct size (%): vehicle 59±6, Empa 62±10, Cari 68±4), however in low‐glycogen hearts, both EMPA and CARI delayed ischemic contracture onset (vehicle 459±25, EMPA 559±22, CARI 588±31). Higher EMPA concentration further delayed contracture onset. Only CARI reduced I/R injury (from 51±6 to 34±5). The presence of insulin (same concentration used) did not alter NHE activity, nor the ability of CARI or EMPA to inhibit NHE, in isolated cardiomyocytes. The increased IR injury in normal‐glycogen hearts was associated with increased end‐ischemic lactate and glucose‐6‐phosphate accumulation, and consequently decreased mitochondrial hexokinase ll.ConclusionEMPA does not protect against I/R injury in isolated hearts, yet EMPA delayed ischemic contracture onset in low‐glycogen hearts, suggesting a direct cardiac, ATP preserving, effect of EMPA during ischemia. Cardiac glycogen content interferes with the effects of NHE inhibitors on I/R injury in isolated hearts. These data indicate that empagliflozin and cariporide may inhibit NHE in different manners.Support or Funding InformationNone.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
PVN Orexin Receptor 1 Knockdown Effect on Metabolism and Fluid Homeostasis
Authors: Bigalke Jeremy Andrew , Jiang Enshe Jasen , Hahka Taija Marie , Chen Qing Hui , Shan Zhiying Jenny 
Published: June 2021

Previous research has shown the importance of orexin, a neuropeptide, in the regulation of appetite, sleep, and arousal. However, limited research has been done on the impact of orexin in the hypothalamic paraventricular nucleus (PVN) on the control of metabolism and body fluid homeostasis. In this study, we investigated the role of PVN orexin signaling on metabolism through chronic knockdown of orexin 1 receptor (OX1R) using AAV1‐OX1R‐shRNA. Seven‐week‐old male Dahl Salt sensitive rats were divided into two groups and were microinjected with either AAV2‐scembled‐shRNA (n=6) or AAV2‐OX1R‐shRNA (n=5) into the PVN. After one week recovery from the surgery, all rat baseline body weights were measured. There was no significant difference found between the groups. The rats were then fed with a high salt diet (HS, 4% NaCl) for 5 consecutive weeks, after which body weights were once again measured and the rats were then transferred into individual metabolic cages. Rats were given 24 hours to get accustomed to the new environment and their food intake, water intake, urine excretion, and fecal output were measured for 24 hours. The results showed that PVN OX1R knockdown rats had a lower body weight when compared to control rats after the 5 weeks of high salt intake (Control: 336.6±9.10, vs. OX1R‐shRNA: 299.8±14.62 g P<0.05). In addition, chronic knockdown of PVN OX1R showed a significant decrease in water intake (Control: 43.67±3.72, vs. OX1R‐shRNA: 24.96±5.16 mL P<0.05), urine output (Control: 27.0±3.32, vs. OX1R‐shRNA: 14.04±2.75 mL P<0.05), and food intake (Control: 20.85±2.16, vs. OX1R‐shRNA: 13.68±1.84 g P≤0.05), but there was no fecal output alteration observed between PVN OX1R knockdown rats and control rats. At the end of this protocol, rats were euthanized and their brains were removed and subjected to either real time PCR or immunostaining to test mRNA or protein expression of the genes of interest in the PVN. Real time PCR showed that AAV2‐OX1R‐shRNA injection decreased OX1R mRNA level by 41%, and melanocortin‐4 receptor (MC4R) mRNA by 68% compared to control vector injection group. Immunostaining showed that both vasopressin immunoreactivity and positive vasopressin expressing cells are dramatically decreased in the PVN of AAV2‐OX1R‐shRNA rats as well. These observations coupled with the importance of MC4R in controlling satiety, and vasopressin in controlling urine water excretion, suggest that orexin plays a large and complex regulatory role in fluid homeostasis within the body as well as in appetite, through direct mediation by the PVN.Support or Funding InformationNIHR15 HL129213 (Shan) and Michigan Tech and Portage Health Foundation Research Excellent Fund (Shan).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Reciprocal Interaction between Hypothalamic Orexin‐A and Corticotropin‐releasing Factor under Stressed Condition
Authors: Sinen Osman , Bülbül Mehmet 
Published: June 2021

In response to stressful stimuli, expression of orexin‐A (OXA) is increased within central nervous system. The orexinergic cells reside in lateral hypothalamic area (LHA) have dense projections on hypothalamic paraventricular nucleus (PVN), furthermore, corticotropin‐releasing factor (CRF) receptors are expressed in orexin‐producing neurons within LHA. However, the interaction between these neuropeptides is understood incompletely. Using acute restraint stress (ARS) model in rats, the purpose of the present study was designed to investigate (i) the interaction between hypothalamic OXA and CRF, and (ii) the contribution hypothalamic OXA in CRF‐mediated glucocorticoid release. Adult male Wistar rats underwent stereotaxic cannulation for intracerebroventricular (icv) drug injection and microdialysis 7 days prior to the experiments. Under basal and stressed conditions, microdialysis samples were collected from LHA and PVN to monitor the alterations in OXA and CRF, respectively, whereas, their antagonists were administered centrally prior to the stress loading. The immunoreactivities for both neuropeptides were detected in hypothalamic sections by immunohistochemistry. The corticosterone (CORT) concentrations in plasma samples were assayed using enzyme immunoassay. Compared to their basal levels, OXA and CRF concentrations in microdialysates were increased in ARS‐loaded rats, while they were attenuated significantly by the receptor antagonists. ARS increased the immunoreactivities for OXA and CRF in hypothalamus remarkably, while increasing the plasma CORT. Central preadministration of the antagonists reduced the ARS‐induced increased hypothalamic immunoreactivites and plasma CORT. Under stressed condition, OXA and CRF seem to play in a synergistic signaling pathway through their specific receptors. The endogenous hypothalamic OXA appears to contribute to the CRF‐mediated neuroendocrine stress response. The interaction between OXA and CRF may lead to better understanding of the etiopathogenesis of stress‐related disorders.Support or Funding InformationThe present study was supported by the Research Foundation of Akdeniz University (Project number: TSA‐2017‐2418)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 the Nuclear PKA Holoenzyme
Authors: Clister Terri , Sample Vedangi , Zhang Jin 
Published: June 2021

cAMP and PKA activity is regulated in time and space to ensure proper cellular responses. Recently a novel pool of activatable PKA holoenzyme was discovered to reside in the nucleus, expanding the traditional model of PKA signaling. Based on live‐cell imaging we hypothesize that the regulation of the nuclear PKA holoenzyme is dependent on phosphodiesterases (PDEs) anchored to A‐kinase Anchoring Proteins (AKAPs) which create a local microdomain with a lower concentration of cAMP, thus controlling the activation of anchored nuclear PKA. Using superresolution (pcSOFI) and FRAP techniques we've characterized AKAP95 in the nucleus. Co‐IP experiments using nuclear extracts revealed that both the RIIα subunit of the PKA holoenzyme, and multiple PDE4D isoforms interact with AKAP95, supporting our hypothesis and providing specific candidates to further explore this regulation. Our ICUE3 cAMP biosensor was localized to AKAP95 to measure the levels of cAMP directly around AKAP95 in response to differently localized sources of cAMP. We are able to generate cAMP in different cellular compartments in a dose‐dependent manner by targeting genetically encoded soluble adenylyl cyclase (sAC) and stimulating transfected cells with sodium bicarbonate. When a low concentration of cAMP is generated, only cAMP produced in the nucleus can be detected in the vicinity of AKAP95, whereas cAMP produced at the plasma membrane was not detected within this microdomain. These results support the hypothesis that AKAP95 and PDE4Ds create a microdomain that prevents the activation of scaffolded nuclear PKA holoenzyme except by local cAMP signals. We are still exploring the endogenous source of nuclear PKA activation, but hypothesize that cAMP generated by internalized GPCR signaling at the endosome could activate AKAP95‐tethered PKA.Support or Funding InformationThis work was funded by R01 DK073368.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mitochondrial Driving Forces and Metabolic Resilience
Authors: Muoio Deborah Marie 
Published: June 2021

Evidence supporting a causal link between mitochondrial performance and disease risk has been bolstered by the advent and application of state‐of‐the‐art multi‐omics molecular profiling technologies, such as genomics, proteomics and metabolomics. Although these are powerful tools that can produce provocative molecular signatures of disease, they still do not tell us how well (or not) mitochondria resident in specific tissues are able to maintain the free energy of ATP hydrolysis (ΔGATP, i.e. ATP:ADP ratio)–the energetic currency that powers normal cell and organ function. Thus, we came to recognize that progress toward deciphering the precise role of mitochondria in the disease process requires sophisticated approaches that can assess changes in carbon flux and bioenergetics in intact mitochondria working to regenerate ATP, and maintain ΔGATP, in the context of physiologically relevant energy demands and thermodynamic constraints (i.e. backpressure). To this end, we developed a new multiplexed assay platform for interrogating respiratory kinetics and thermodynamics under multiple substrate and energetic conditions. Unlike conventional respirometry methods, the new platform permits comprehensive assessment of respiratory fluxes (JO2) and energy transduction, which refers to the transfer of energy in carbon fuels–to electron potential energy (NAD(P)H/NAD+ redox)–to membrane potential–to ΔGATP. Importantly, these assays are performed in the context of dynamic extramitochondrial ATP:ADP concentrations (i.e. ΔGATP) that are precisely controlled within a (near) physiologic range. In simple terms, our diagnostic assays mimic an exercise “stress test” by evaluating how well a given population of mitochondria, fueled by specific mixtures of carbon substrates, responds to a graded energetic challenge. We have been combining this platform with mass spectrometry‐based metabolomics and proteomics to evaluate mitochondrial remodeling, and corresponding changes in respiratory power and efficiency, in response to a variety of nutritional and genetic maneuvers. This seminar will discuss new insights pertaining to the interplay between mitochondrial driving forces and metabolic resilience.Support or Funding InformationSupported by grants from NIDDK and NHLBI.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The actin‐binding protein cortactin controls transendothelial migration and organ infiltration of acute lymphoblastic leukemia T‐cells
Authors: Castellanos Ramón , Vadillo Eduardo , Schnoor Michael 
Published: June 2021

T‐cell acute lymphoblastic leukemia (T‐ALL) is an aggressive neoplasm due to high rates of organ infiltration and relapse, which are major obstacles for curing the disease. Infiltration of T‐ALL cells requires extravasation, a migratory process highly dependent on actin cytoskeleton dynamics. Cortactin is an actin‐binding protein that regulates actin remodeling and thus cell migration. High expression of cortactin is associated with invasiveness in several types of solid tumors, and recently, expression of cortactin in adult B‐cell chronic lymphocytic leukemia was correlated with negative prognostic factors. However, it is unknown whether cortactin plays a role in T‐ALL biology. Here, we analyzed cortactin expression in the murine and human T‐ALL cell lines 6645/4 and Jurkat, and cortactin functions using different in vitro and in vivo methods such as transendothelial migration, bone marrow (BM) colonization and xenotransplantation assays. Compared to normal T cells, leukemic T cells expressed significantly higher levels not only of cortactin but also of the integrin VLA‐4 and CXCR4, the receptor for the T cell chemokine CXCL12, which are both required for T cell extravasation. Leukemic T cells transmigrated significantly more, and cortactin levels were significantly higher in cells capable of transmigrating across endothelial monolayers towards CXCL12. Of note, only leukemic T cells with highest cortactin levels were capable of invading BM‐like organoids. Preliminary in vivo assays showed that leukemic T cells had different levels of cortactin depending on the infiltrated organ. Surprisingly, once leukemic T cells completed infiltration they diminished cortactin expression suggesting that cortactin is needed for initial organ invasion, but not for subsequent functions. Taken together, our results highlight an important role of cortactin in T‐ALL infiltration; and contribute to a better understanding of T‐ALL aggressiveness. Thus, cortactin may be a potential pharmacological target to prevent T‐ALL organ infiltration.Support or Funding InformationCONACyTThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.