bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kv7 channel isoforms contribute to H2O2-mediated vasodilation in the ischemic heart after exercise training
Authors: Self Trevor , Heaps Cristine 
Published: May 2023

Ischemic heart disease is a multifaceted pathological manifestation that continues to impose a significant burden on individuals and the healthcare system. As a potential therapeutic modality, exercise training has been reported to induce vascular adaptations that improve coronary perfusion in the compromised myocardium distal to coronary occlusion. Coronary arteriolar hydrogen peroxide (H2O2) production is enhanced after exercise training and contributes to improved vasodilation of arterioles supplying ischemic myocardium. Voltage-gated potassium (Kv) channels have been identified as significant contributors to resting membrane potential and enhanced vasodilation in ischemic models, yet specific isoforms remain elusive. Many Kv isoforms exhibit redox-sensitivity with Kv1-4 families being implicated in H2O2-mediated vasodilation in rodents and human. Based on these previous findings, we tested the hypothesis that redox-sensitive Kv isoforms contribute to exercise training-enhanced H­2O2-mediated dilation in arterioles of the ischemic heart. Yucatan miniature swine were surgically instrumented with an ameroid occluder around the left circumflex coronary artery, gradually inducing complete occlusion and creating a collateral-dependent vascular bed. Arterioles fed by the left anterior descending artery served as nonoccluded control vessels. Pigs were separated into two groups, one of which underwent a progressive exercise training regimen (treadmill run; 5 days/week for 14 weeks) and another that remained sedentary, limited to normal pen activity. Candidate Kv channel isoforms were pharmacologically targeted in tension myography studies of isolated coronary arterioles (~125 μm internal diameter) and whole-cell voltage clamp studies of arteriolar smooth muscle cells. Our findings revealed a significant role for the Kv7 family, specifically implicating Kv7.4 and Kv7.5, in H2O2-mediated vasodilation of the coronary microcirculation. We show that the contribution of Kv7 channel isoforms to vascular relaxation was eliminated by ischemia or exercise training in tension myography, although together, ischemia and exercise training restored a significant role for Kv7 channel isoforms. Interestingly, whole-cell voltage clamp recordings of isolated vascular smooth muscle cells revealed unaltered Kv7 channel currents among all treatment groups. With no observed changes in whole cell Kv7 currents after ischemia and/or exercise training, our data suggest that adaptations in a second messenger signaling pathway are driving the changes in channel contribution to H2O2-mediated vasodilation. NIH RO1 HL139903 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Spinal Afferent Innervation of the Rat Heart: Anterograde Tracing
Authors: Ma Jichao , Bizanti Ariege , Kwiat Andrew , Madas Jazune , Chen Jin , Cheng Zixi 
Published: May 2023

Spinal afferent innervation of the heart regulates cardiac function. Understanding the precise distribution and morphology of spinal afferent nerves in the heart is crucial as remodeling of cardiac sensory innervation results in cardiovascular diseases. To specifically study the spinal afferent innervation of the heart, we injected tracer dextran biotin (DB) into the left DRG (C8-T3; 1.5 μl/each ganglion). Rats were allowed to recover for 14 days, then perfused through the left ventricle with 40°C PBS (1M phosphate-buffered saline, pH = 7.4). Tissues were then fixed by perfusion with 4% paraformaldehyde in 0.1M PBS (4°C, pH 7.4). After the perfusion, hearts were harvested, and the atria and ventricles were separated. Then, a cut was introduced along the interatrial septum to separate the left and right atrium, and DAB staining was performed. DB-labeled single spinal afferent axons in the flat-mounts of the left and right atria were traced using the Neurolucida system. We summarized our findings based on morphology, innervation area, and target of individual spinal afferent axons. 1) Morphological characteristics of single spinal afferent axons: DB-labeled single axons entered the atria and bifurcated into many branches with or without varicosities. Varicose branches which arose from a single axon traveled through the atria either in the same direction or a non-preferential direction. 2) Distinct regions received single spinal afferent axons include left and right auricles, the sinoatrial node, the atrioventricular node, left precaval vein, pulmonary veins, and the junction between the left atrium and pulmonary veins. Axons with different terminal structures could be found in all these regions. 3) Single afferent axons were identified on different targets: such as cardiac and smooth muscles, fat tissue, blood vessels, and intrinsic cardiac ganglia. Our work will provide a foundation for specific labeling of spinal afferent innervation of the heart. This study was supported by NIH HEAL/SPARC U01 NS113867-01, NIH R15 R15HL137143-01A1, and UCF dissertation completion Fellowship. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Open-book, open-web versus closed-book, closed-web examinations in anatomy and physiology classes
Authors: Milam Lauren , Jimenez Xavier , Shaw Donald 
Published: May 2023

Due to COVID and distance learning, a possible evaluation is open-book examinations. We tested the hypothesis that students taking open-book, open-web exams spend less time studying anatomy and physiology and would performed more poorly on critical thinking exam questions compared to students taking closed-book, closed-web exams. We tested the exam performance using different types of exam questions according to Bloom's taxonomy. As well, students that participated in the research submitted study journals that accounted for the time they spent studying for each exam. Data has been collected for both open-book, open-web and closed-book, closed-web sections over Exams #1, #2, #3, and Final. Data from Exams #1 and #2 for both sections has already been completely analyzed. Data from the open-book section had shown that students' exam performance over five different types of questions were descending as the level of difficult became more challenging in both Exams #1 and #2. Data from the closed-book section showed that as the level of difficult became more challenging, there was not a decline in performance on Exam #1 and there was a less steep decline in performance on Exam #2 than the open-book section. For both exams, there was a statistical significance between the study times of the sections as the average study times of the closed-book section was significantly greater than of that of the open-book section. These results suggest that students in the open-book section deal with challenging questions more poorly than the closed-book section while also studying significantly less than the closed-book, closed-web section. Moreover, the data for Exams #1 through Final of both sections has been collected and will be analyzed and included for further comparison. This research was supported and funded by the Department of Biological Sciences at the University of Tennessee at Martin. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Impact of cannabidiol and lamotrigine on parameters of action potentials in sciatic nerves of frogs
Authors: Milam Lauren , Jimenez Xavier , Shaw Donald 
Published: May 2023

Cannabidiol causes inhibitory effects on sodium channels, but its action on nerve impulses is not understood. Lamotrigine blocks the nerve impulses, however, it is not known if this action is of extracellular or intracellular origin. With the use of nerve chambers, we are hoping to elucidate this unknown mechanism. We hypothesize that these two chemicals may modify components of action potentials of nerve fibers in frogs. Action potential recording was made possible by the IWorx Data Quest system and a nerve chamber. Action potential data was analyzed by looking at two different components—the peaks of depolarization and the difference between the peak of depolarization and the nadir of repolarization. For every 50 minutes of recording, the data was divided into three clusters—before chemicals, after 10 minutes of treatment, and 30 minutes after treatment. In frogs, we found the high dosage (1.0 milligram/milliliter (mg/mL)) of cannabidiol had no effect on the maximum amplitude of depolarization among the three data clusters—saline, 10 minutes after cannabidiol, and 30 minutes after cannabidiol. The high dosage of cannabidiol also had no effect on the repolarization of action potentials when compared among the above three data clusters. In addition, in frogs we found the low dosage (0.1 mg/mL) of cannabidiol showed a significant difference in the maximum amplitude of depolarization when the saline data cluster was compared to the 10-minute cluster after cannabidiol cluster. Likewise, there was a significant difference on the repolarization of action potentials when the saline data cluster was compared to the 10-minute cluster after cannabidiol cluster and when the 10-minute cluster was compared to the 30-minute cluster after cannabidiol cluster. High dosage of lamotrigine showed a significant difference on the maximum amplitude of depolarization when the saline cluster was compared to the 10-minute cluster after lamotrigine on action potentials. Low dosage of lamotrigine data is currently being collected to be analyzed and presented cumulatively with all the data. This research is being supported and funded by the Department of the Biological Sciences at the University of Tennessee at Martin. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Identifying the role of HSP70 co-chaperones in modulating sarcomeric proteostasis
Authors: Branscom Graham , Wagner Marcus , Day Sharlene 
Published: May 2023

Background: Hypertrophic cardiomyopathy (HCM) is the most common genetically inherited cardiovascular disease that affects one in 500 people. Variants in MYBPC3 result in premature termination codons, ultimately causing haploinsufficiency in MyBP-C protein–a hallmark of familial HCM pathophysiology. Recent GWAS reports identify risk alleles for HCM that are concordant with left ventricular (LV) functional traits of decreased left ventricular chamber volumes and increased ejection fraction, and in contrast are protective alleles for dilated cardiomyopathy. Several of the top HCM risk alleles encode for co-chaperones of HSP70. However, how these co-chaperones directly modulate sarcomeric protein turnover and HCM pathophysiology is unknown. Hypothesis: We hypothesize that HSP70 co-chaperones identified by recent GWAS regulate contractility by affecting sarcomeric and Z-disc steady state expression. Methods and Results: Human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) were transduced with GFP-tagged adenovirus (AdV) expressing shRNA targeted against BAG3, DNAJC18, HSPB7, or scrambled shRNA (control) and transduction efficiency was assessed by flow cytometry for GFP expression. A >70% transduction efficiency was achieved with each viral construct (p<0.0001). Viral transduction and knockdown of HSP70 co-chaperone did not induce cellular toxicity. BAG3, DNAJC18, and HSPB7 were reduced by ≥50% at both the transcript and protein levels as measured via RT-qPCR and western blot. BAG3 KD reduced MyBP-C protein levels (p<0.0001) by 53%, along with most other profiled sarcomeric and Z-disk proteins (p<0.05). DNAJC18 had no significant effect on MyBP-C protein levels, but caused a decrease in tropomyosin (p<0.0001) and myosin light chain 3 (p<0.0001). HSPB7 KD increased MyBP-C protein levels (p<0.01) by 46%. Myosin (p<0.01), tropomyosin (p<0.05), and myosin light chain 2 (p<0.05) also showed increased expression upon HSPB7 knockdown. Conclusion: GWAS-identified HSP70 co-chaperones BAG3, DNAJC18, and HSPB7 regulate the steady state expression of sarcomeric and Z-disc proteins. Further studies will be needed to elucidate whether regulation is occurring at the transcription, translational, or posttranslational level, and whether therapeutic modulation of these co-chaperones can be leveraged to stabilize MyBP-C and other sarcomeric and Z-disc proteins in patients with familial HCM. Institutional/internal grants This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Transcriptional regulation of gastrointestinal solute transporters by growth hormone and cortisol in Atlantic salmon
Authors: Runiewicz Ellie , Richardson Sierra , Bradley Serena , Hall Daniel , McCormick Stephen , Breves Jason 
Published: May 2023

To maintain hydromineral balance in marine habitats, teleost fishes drink ambient seawater to replace water that is passively lost to the external environment. Initially, the esophagus desalinates imbibed seawater to produce a fluid closer to the osmolality of plasma. This desalination enables the intestine to partake in fluid uptake through solute-linked transport processes. In parallel with gastrointestinal processes that support water balance, branchial ionocytes promote ion balance by actively extruding Na+ and Cl-. Despite growth hormone (Gh) and cortisol being firmly established as “seawater-adapting hormones” in euryhaline teleosts, it remains largely unknown how they regulate gastrointestinal processes. We therefore examined the responses of Atlantic salmon ( Salmo salar) parr implanted with ovine Gh (5 μg/g body weight), cortisol (10 μg/g body weight), or the combination of both hormones. We first determined that our implants were sufficient to elicit physiological responses by confirming that cortisol stimulated branchial Na+/K+-ATPase (NKA) activity. Cortisol also stimulated branchial Na+/K+/2Cl- cotransporter 1 ( nkcc1) and cystic fibrosis transmembrane regulator 1 gene expression, whereas the combination of Gh and cortisol stimulated nka-α1b expression. Of the two Na+/H+ exchangers (Nhes) proposed to underlie the removal of Na+ from the lumen of the esophagus, nhe2, but not nhe3 expression, was stimulated by cortisol. In the current model of how solute-linked water absorption occurs in teleost intestine, Na+ and Cl- enter into enterocytes via apical Nkcc2 prior to their basolateral exit via NKA and Clc-family Cl- channels. Water is absorbed from luminal fluid by enterocytes in a transcellular fashion via aquaporins (Aqps). The combination of cortisol and Gh stimulated the expression of intestinal nkcc2, nka-α1b, and nka-β1b in the anterior intestine whereas there were no effects on aqp1a, -1b, -8ab, or -10. Collectively, our data indicate that cortisol and Gh coordinate the expression of solute transporters in salmon esophagus and intestine in a fashion that supports hydromineral balance in marine habitats. Supported by the National Science Foundation (IOS-1755131 to J.P.B.). National Science Foundation [IOS-1755131] This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Assessing conversational oral communication in an undergraduate anatomy and physiology course
Authors: Brundage Cord 
Published: May 2023

Effective oral communication is an important competency for scholars and health professionals. This is more traditionally assessed through orations and class presentation. Practically, graduates may be tasked with more instances of interpersonal and conversational oral communication. It is also difficult to assess student recall knowledge in prepared speeches and presentations. The Cal Poly Pomona institutional rubric for oral communication was adapted to be used in group discussions and one-on-one conversations. Evaluation criteria included central message, organization, language and delivery. Each criterion was evaluated on a 4-tier (0-3) mastery scale. The specific evaluation criteria area needing the most development was also noted. Undergraduate upper-division, anatomy and physiology students (n = 48) participated in five topic discussions in randomly assigned groups of 12 throughout the laboratory section of the course. The facilitator evaluated student oral communication skills using the adapted rubric throughout each discussion. At the end of the semester the same rubric was used to score responses to 5-prompts during a one-on-one oral examination with the instructor. This modified rubric was able to be used in real-time. Overall students demonstrated modestly higher scores in the discussions 1.952 +/- 0.36 than in the oral examinations 1.717 +/- 0.23. In both assessments the area of greatest need of development was language (56.6% - 68% of statements) followed by delivery (28% -37.6% of statements). During oral examinations the rubric was used while concurrently evaluating student content knowledge. Some students were consistent, while others scored at a range of levels. It remains to be determined whether student peak achievement or average performance are better indicators of competency. In either case this project highlighted the need to support student use of anatomy and physiology language to improve their conversational oral communication skills in that content area. Cal Poly Pomona Office of Academic Programs This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Intact endothelial cell autophagy mitigates outcomes of acute ischemic stroke
Authors: Mookherjee Sohom , Light Milo , Tandar Megan , Hill Nathan , Begaye Lori , Chaix Amandine , Denorme Frederik , Campbell Robert A. , Symons John David 
Published: May 2023

Acute ischemic stroke (AIS) deprives cerebral artery endothelial cells (ECs) of nutrients which decreases mechanistic target of rapamycin complex 1 (mTORC1) activity to initiate autophagic flux. We tested the hypothesis that depletion of EC autophagy worsens tissue injury, and neurobehavioral and motor outcomes of AIS. First, using a gain of function approach, adult male C57Bl6 mice consumed standard diet that was not (control) or was supplemented with the mTORC1 inhibitor rapamycin (14 milligrams / kilogram chow). After 3-weeks, phosphorylated ribosomal S6 / total S6 was greater (p<0.05) in liver segments of rapamycin vs. control fed mice, indicating mTORC1 repression. All mice were challenged with transient middle cerebral artery occlusion (tMCAO, 60-minutes;) followed by reperfusion (R, 23 hours). AIS -induced infarct volume, neurobehavioral deficits, and motor dysfunction was less severe (p<0.05) in mice fed rapamycin-supplemented vs. control chow. Next, using a loss of function procedure, adult male C57Bl6 mice with intact EC autophagy-related protein 3 ( Atg3WT ) or inducible depletion of EC ATG3 ( Atg3EC-/- ) completed the AIS protocol. AIS increased (p<0.05) ATG3 colocalization with the EC marker VE-Cdh5 after 23 h R in ipsilesional (ischemic) vs. contralesional (non-ischemic) hemispheres of Atg3WT but not Atg3EC-/- mice. Neutrophil infiltration (flow cytometry), cell death (TUNEL), microglia (IBA-1) and astrocyte (GFAP) activation, and neurodegeneration (NeuN) were greater (p<0.05) in ischemic hemispheres of Atg3EC-/- vs. Atg3WT mice. Further, infarct volume was greater, and motor function (grip test, rotarod) and neurobehavioral performance (Y-maze, Bederson score, modified neurological severity score) were worse (p<0.05), in Atg3EC-/- vs. Atg3WT mice. These findings suggest that outcomes of AIS are: (i) better in response to mTORC1 inhibition but are (ii) exacerbated in response to EC autophagy depletion. To test whether intact EC autophagy is necessary for protection afforded by mTORC1 inhibition in the context of AIS, Atg3WT and Atg3EC-/- mice consumed rapamycin-supplemented chow for 3-weeks. In preliminary studies, AIS-induced infarct volume was less severe after rapamycin feeding in Atg3WT vs. Atg3EC-/- mice, underscoring the importance of EC autophagy. Initiating EC autophagic flux might be protective in the context of AIS by enabling: (i) recycling of damaged proteins; (ii) nutrient generation from degraded substrates; and / or (iii) arterial vasodilation for nutrient delivery. Supported by R01HL141540 to JDS This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Targeting LRP1 in a rodent cervical injury model to promote functional recovery
Authors: Sunshine Michael , Taylor Chase , Devine Caroline , Alilain Warren 
Published: May 2023

Impairments following spinal cord injuries (SCI) are due to the primary trauma and secondary complications. Secondary complications include 1) degeneration of white matter tracts and 2) persistent neuroinflammation. Here we test a novel compound, NOVO-118 that is designed to mitigate these secondary complications in a rodent model of SCI. NOVO-118 is an antagonist of the low-density lipoprotein receptor regulated protein 1 (LRP1) which is expressed in all cell types in the central nervous system. Antagonism of LRP1 in neurons is implicated in promoting axon regeneration by reducing RhoA activation. Further, antagonism of LRP1 within microglia may reduce myelin uptake and mitigate the transition to their pro-inflammatory state. We hypothesize that LRP1, we can promote regeneration and mitigate neuroinflammation leading to functional recovery following cervical contusion SCI. As LRP1 is broadly expressed throughout many organ systems, we delivered NOVO-118 (or vehicle) to the intrathecal space above the lesion over a 30-day period after injury to mitigate off target effects. We measured the effect of NOVO-118 on ventilation and locomotor function using whole body plethysmography and open-field activity chambers. Behavioral assessments were performed pre-injury, 3, 7-, 14-, 21-, and 28-days post injury. Minute ventilation under normoxia was reduced in both groups at days 3 and 7 post injury which recovered towards pre-injury levels by day 14. The vehicle treated animals also had reduced minute ventilation during hypoxic challenge at days 3 and 14 post injury. However, the NOVO-118 treated rats were able to maintain pre-injury minute ventilation under hypoxic challenge at all time points. This suggests LRP1 as a new therapeutic target to promote recovery after SCI. Ongoing work is investigating the possible mechanisms through which NOVO-118 led to these functional improvements. Novoron Bioscience (WJA, MDS), NIH NINDS R01NS101105 (WJA) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.