bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the effects of thermoneutral housing on skeletal muscle SERCA efficiency in mice fed a high-fat diet with and without exercise training
Authors: Braun Jessica , Raun Steffen , Karavaeva Iuliia , Ali Mona , Møller Lisbeth , Gerhart-Hines Zachary , Fajardo Val , Richter Erik , Sylow Lykke
Published: May 2023

Thermoneutral (TN) housing of mice is an important factor to better mimic human metabolism and optimize translational research. The sarco(endo)plasmic reticulum (SR) Ca2+ ATPase (SERCA) pump actively transports Ca2+ from the cytosol into the SR, making it a regulator of muscle relaxation and energy metabolism. In response to cold or caloric excess, SERCA inefficiency generates heat and drives the combustion of metabolic substrates in muscle; however, whether TN housing affects SERCA efficiency is unknown. Here, we determined SERCA pump efficiency in skeletal muscles of mice housed at room temperature (RT, 22°C) or TN (30°C) with and without 60%E high-fat diet (HFD) and exercise training (ET) interventions. We hypothesize that TN would increase SERCA efficiency compared to RT on a chow diet, and that HFD and HFD + ET would reduce SERCA efficiency at both housing temperatures. Mice housed at RT or TN were fed a chow or 60%E HFD for 16 weeks. Eight weeks into the diet, half of the mice on HFD were randomly assigned to either ET or remained sedentary (SED) for the remaining 8 weeks. HFD + ET increased SERCA’s affinity for Ca2+ and maximal SERCA activity trended reduced by ET compared to HFD + SED mice. Investigating SERCA efficiency at low physiological [Ca2+]free shows that TN reduced Ca2+ uptake by ~60% in HFD mice and reduced SERCA activity by ~60% in SED mice. This increased SERCA efficiency 4-fold in chow-fed mice housed at TN compared to RT and reduced SERCA efficiency in HFD mice at TN to ~80% of that of chow-fed mice at TN. Similarly, at high physiological [Ca2+]free, TN reduced Ca2+ uptake by ~40% in HFD mice and reduced SERCA activity by ~35% in SED mice, but had no effect on SERCA efficiency. Together, TN housing appears to influence SERCA efficiency especially under chow and HFD conditions at a low [Ca2+]free. In conclusion, housing mice at TN should be considered when investigating non-shivering thermogenic mechanisms and skeletal muscle Ca2+ handling.

Jessica L. Braun and Steffen H. Raun contributed equally. Erik A. Richter and Lykke Sylow are co-corresponding authors. Disclosure of funding: JLB. is supported by a Canadian Institute for Health Research Doctoral grant and a Michael Smith Foreign Study Supplement. SHR is supported by the Lundbeck Foundation and the Independent Research Fund Denmark. LS is supported by the Novo Nordisk Foundation and Independent Research Fund Denmark.

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.
Neonatal hyperoxia does not exacerbate hypertension in adult obese offspring from obese mothers
Authors: da Silva Alexandre , Dai Xuemei , Larson Kaylie , Aitken Nikaela , Frierson Timia , Walker Xavier , Oppedal Kari , Omoto Ana , Wang Zhen , Li Xuan , Mouton Alan , Hall John , do Carmo Jussara
Published: May 2023

Maternal obesity increases the risk of preterm delivery which may result in rapid transition of their offspring from a relatively hypoxemic environment to normal or elevated oxygen environment, especially if the baby receives oxygen therapy. This exposure of premature infants to increased oxygen levels could induce oxidative stress and detrimental effects on organ development and maturation. Previous studies have shown that early-life exposure to high oxygen levels (hyperoxia) induces cardiovascular disease later in life. In the present study, we tested the hypothesis that neonatal exposure to hyperoxia (HO) leads to elevated blood pressure (BP) at adulthood in offspring from lean mothers and exacerbates the adverse impact of maternal obesity on offspring BP regulation. Male (n=5-7) and female (n=5-7) offspring from lean and high fat diet-fed obese mothers were exposed to room air (21% O2) or hyperoxia (80% O2) between postnatal (P) days P3-P10, and then returned to room air. The rats were provided food and water ad libitum and followed until 12-13 weeks of age when telemetry probes were implanted to measure BP and heart rate (HR) 24-hrs/day. After 10 days of recovery from surgery, BP and HR were measured for 5 consecutive days. Contrary to our hypothesis, neonatal HO was associated with lower BP compared to control offspring from lean mothers (males: 111±1 vs. 105±1 mmHg and females: 108±0.4 vs. 102±0.4 mmHg). Neonatal HO exposure was also associated with similar reductions in BP in hypertensive obese offspring from obese mothers (males: 123±1 vs. 117±1 mmHg and females: 116±1 vs. 113±1 mmHg). Offspring exposed to neonatal HO showed a tendency for reduced HR compared to lean and obese offspring not submitted to HO with significant reduction observed in obese female offspring from obese mothers (393±3 vs. 379±2 bpm). These results suggest that exposure to hyperoxia in early postnatal life is not associated with elevated BP in adulthood and it does not exacerbate the hypertensive effects of maternal obesity on offspring BP regulation.

NIDDK 1R01121411, NIGMS P20GM104357 and NIGMS U54GM115428

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.
Role of potassium ion diffusion from neurons to capillaries in neurovascular coupling: effects of astrocytic endfeet geometry
Authors: Djurich Sara , Secomb Timothy
Published: May 2023

Neurovascular coupling (NVC) refers to a local increase in cerebral blood flow (CBF) in response to increased neuronal activity. Diffusion of K+ released by neurons through the extracellular space (ECS) to capillaries may contribute to NVC. Increased perivascular K+ levels can initiate a conducted response that travels to arterioles, triggering vasodilation and increased CBF. Astrocytic endfeet almost completely cover cerebral capillaries, and K+ must diffuse through narrow clefts between endfeet to reach the capillaries. It has therefore been assumed that astrocytes form a barrier to diffusion of K+ in the ECS. The goal of this study is to determine the effects of astrocytic endfeet on the diffusion of K+ from neurons to blood vessels. Two simplified 2D geometries of the ECS, endfeet, and perivascular space (PVS) are used. The first geometry represents diffusion of K+ from a source 1 μm away from a capillary of diameter 5 μm. The second geometry represents K+ diffusion from a neuron 15 μm from the capillary, the average distance between a neuronal soma and the nearest blood vessel. A baseline [K+] of 3 mM is assumed throughout the region. K+ release from neurons is modeled as a prescribed concentration of 12 mM along the outer boundary of the ECS. The time-dependent diffusion equation is used to describe K+ diffusion through the region. Effective diffusivity of K+ is 937.5 μm2/s. Standard conditions are a PVS width of 100 nm and an astrocytic endfeet cleft width of 20 nm, with 2.5 clefts per vessel circumference such that the total width of the clefts represents 0.31% of the capillary’s circumference. In the first geometry, [K+] in the PVS approaches 12 mM within 0.05 s. Decreasing the astrocytic endfeet cleft width to 6.67 nm slows the rise in [K+] to 10 mM at 0.05 s. Increasing PVS width also slows the rise in [K+]. In the second geometry, the rise in [K+] is slower due to the greater diffusion distance and PVS [K+] approaches 12 mM within 0.5 s. Decreasing cleft width or increasing PVS width in the second geometry slightly slows the rise in [K+]. The predicted rise in [K+] at the blood vessel occurs well within the time that increased CBF is observed in NVC, 1-2 seconds. The predicted PVS [K+] levels are sufficient to cause the vasodilation seen in NVC. The present results suggest that direct diffusion of K+ through the ECS is a possible NVC signaling mechanism.

Supported by NIH Grant U01 HL133362.

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.
Sex differences in proximal tubule metabolism influence hemodynamics and salt reabsorption to mediate dimorphic susceptibility to kidney diseases
Authors: Xiong Lingyun (Ivy) , MacLean Adam , McMahon Andrew
Published: May 2023

Evidence suggests that decline in renal function is more severe in males than in age-matched females, manifesting in increased susceptibility to both chronic and acute kidney diseases among males. Our previous single-cell studies on renal transcriptomes in human and mouse demonstrated that sex differences are the most prominent in proximal tubules (PTs), where over 70% of salt reabsorption happens. However, it remains elusive how these molecular differences affect renal physiology and pathophysiology. Widely known as an indicator of renal function, glomerular filtration rate (GFR) is tightly regulated by tubuloglomerular feedback (TGF) within the nephron to optimize ultrafiltration of plasma and reabsorption of essential molecules. Importantly, GFR shows a sustained oscillatory pattern over time with a period of 30-45 seconds in rodents, and loss of GFR oscillations is associated with cessation of reabsorption activities and ischemia-reperfusion injuries in the kidney, as well as systemic hypertension. To study the relationship between intracellular events and renal function, we developed a mathematical model of TGF linking metabolic regulation within PT cells to fluid handling and salt reabsorption in the nephron, using real-time transdermal GFR readings in conscious, free-moving mice of both sexes. Bifurcation analysis on model parameters revealed that due to heightened oxidative profile to supply energy for reabsorption, male PTs operate near the critical boundary of losing oscillatory behavior in the system, hence they are prone to damage upon metabolic stress. In contrast, female PTs situate further away in the parameter space and are more resilient to failure because of biases towards an anti-oxidation state. Feminized male nephrons showed an intermediate phenotype, and inhibition of peroxisome activities improved recovery post injury. Combining single-cell genomics, physiological measurement and computational modeling of renal function, this study provides a multiscale explanation for sexual dimorphism in kidney diseases.

NIDDK funding: DK126925

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.
Contrasting the production and molecular composition of venom from varying species of Belostomatidae
Authors: Preveza Natalie , Preveza Natalie
Published: May 2023

True bugs, also known by their scientific name- Hemipterans, are an order of insects that use piercing and sucking mouthparts to consume prey. Belostomatidae is one family within hempitera currently containing eight described genera. The genus Belostoma is smaller in size, and tends to feed on smaller invertebrate prey, while a second more distantly related genus, Lethocerus, is much larger in body size and known to feed on small fish, reptiles, and amphibians. We wished to know if this diversification in prey selection also represents a diversification in the venom used to hunt different animal types. To test this we extracted and analyzed the venom from multiple Belostomatid species representing an evolutionary diversity of the family: Lethocerus americanus, Lethocerus medius, Abedus herberti, and Belostoma fluminium. We then compared the relative protein size composition and functional performance of each species’ venom to determine if venoms are similar or different among genuses. We predicted that if venom composition and functionality is similar among species, larger volumes of venom will be associated with larger species.Venom was collected over 10 weeks from 2 L. americanus, 1 L. medius, 5 A. herberti, and 22 B. fluminium. We also extracted from 4 B. flumineum that were collected and raised in a different region of N. America, which were kept separate from the locally occurring B. fluminium to test for regional differences that may be indicative of speciation events. B. fluminium produced a mean mass of 0.65mg of venom per individual insect, whereas the remote B. fluminium had a mean mass of 1.08mg per individual. While the mean venom collected from the remote B. fluminium individuals was greater than local specimens, the total mass for all B. fluminium was generally smaller than that of the larger species. The mean mass of venom extracted per individual from the remaining species were as follows: A. herberti, 1.44mg, L. medius, 1.30 mg, and L. americanus, 1.47mg. From this data, we conclude that larger sized Belostomatids produce larger volumes of venom. To compare the general protein composition and functional performance of the toxins, extracted venoms were pooled, frozen, and lyophilized to stabilize protein components. An SDS PAGE gel was then run with samples to test for different size protein compositions among species. Additionally, a functional dilution analysis was performed using monocultures of chicken embryonic cells followed by a cell viability assay to compare the relative toxicity of each species’ venom.

Funding for this project was provided by Union College Undergraduate Research 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.
Mirabegron-mediated vasodilation in resistance-sized arteries
Authors: Bulley Simon , Choi Young , Reinert Angela
Published: May 2023

β3-adrenergic receptors (β3-ARs) are the most recently established member of the beta-adrenergic sub-family of receptors, however, it’s apparent that β3-ARs contribute to the regulation of the cardiovascular system, including metabolism, vasodilation, and cardiac contractility. β3-ARs have been identified in the cardiac tissue of multiple species, including canine, rodent, and human, where observations suggest that its expression is upregulated in pathological conditions, such as heart failure. Less is understood about the function of β3-ARs in resistance-sized arteries, with most studies utilizing first-generation β3-AR agonists BRL37344, CL316243, and SR58611, which between them have been shown to cause vasodilation in coronary microarteries and thoracic arteries in rodents and dogs. Preliminary Simple Western and immunofluorescence data indicate that β3-ARs are expressed in resistance-sized mesenteric artery endothelial and vascular smooth muscle cells. Mirabegron, an agonist of the more recently established β3-AR subtype, and recently FDA-approved for the treatment of overactive bladder (OAB), causes vasodilation of mesenteric arteries through a cGMP-mediated β3-AR-dependent mechanism at low concentrations, and a β3-AR-independent mechanism at higher concentrations. These data suggest that β3-AR regulates arterial tone in systemic resistance-sized arteries and that Mirabegron causes vasodilation through additional, unknown mechanisms at higher concentrations.

American Heart Association

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.
An Innovative Liver-Specific GalNAc-RNAi Suppression of UGT1A1 in Obese Mice Improves Metabolic-Associated Fatty Liver Disease (MAFLD)
Authors: Bates Evelyn , Kipp Zachary , Badmus Olufunto , Xu Mei , Mitchell Zachary , Stec David , Hinds, Jr Terry
Published: May 2023

Several population studies have found lower serum bilirubin levels to be associated with the pathology of metabolic-associated fatty liver disease (MAFLD). Yet, treatments to target this metabolic trend have not been explored. In our study, we hypothesized that inhibition of hepatic UGT1A1 would increase serum bilirubin levels and improve conditions like MAFLD and hepatic insulin resistance. Therefore, we designed an RNAi targeting murine Ugt1a1 expression in the liver. The RNAi molecule was constructed by conjugating it with an amino sugar derivative of galactose, N-Acetylgalactosamine (GalNAc) [GalNAc-UGT1A1-RNAi]. GalNAc covalently linked to the siRNA enables delivery through the asialoglycoprotein receptor (ASGPR)-mediated targeting to hepatocytes in vivo. Hence, the treatment of the GalNAc-UGT1A1-RNAi primarily targets the liver. In this study, male C57BL/6J mice were fed a high-fat diet (HFD, 60%) for 30 weeks for diet-induced obesity (DIO) and were treated subcutaneously with GalNAc-UGT1A1-RNAi (3mg/kg, n=7) or sham control (n=6) once weekly the final 4 weeks while on the HFD. The results show that GalNAc-UGT1A1-RNAi treatment significantly raised serum bilirubin levels compared to sham control-treated (0.38±0.01 vs. 1.36±0.08 mg/dL, Sham vs. GalNAc-UGT1A1-RNAi, p<0.05), decreased hepatic fat content (26 ± 1.4 vs. 18 ± 1 %, p<0.05) and hepatic triglycerides (17±1.5 vs. 11.5±1 nM, p<0.05), and improved fasting blood glucose (261±11 vs. 201±8 mg/dL, p<0.05) and insulin (9.9±0.1 vs. 3.5±0.3 ng/ml, p<0.05) levels. We performed extensive kinase activity analyses using PamGene PamStation technology and found a significant increase in insulin receptor downstream mediators such as SRC, AKT, and ERK kinase families with the GalNAc-UGT1A1-RNAi treatment, indicating improved hepatic insulin sensitivity. These results show that GalNAc-UGT1A1-RNAi improves MAFLD, increases serum bilirubin, reduces its catabolized produce urobilin in the plasma, and reduces hyperglycemia and hyperinsulinemia. These indicate that UGT1A1 antagonism might serve as a treatment for MAFLD and hepatic insulin resistance, which could improve obesity-associated comorbidities.

This work was supported by the National Institutes of Health 1R01DK121797-01A1 (T.D.H.) and 1R01DK126884-01 (D.E.S.), the National Heart, Lung and Blood Institute K01HL-125445 (T.D.H.) and P01 HL05197-11 (D.E.S.), and the National Institute of General Medical Sciences P20GM104357-02 (D.E.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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.
Altered autonomic control or coronary artery blood flow by the aortic body chemoreceptors in conscious normotensive and hypertensive sheep
Authors: Shanks Julia , Pen Dylan , Abukar Yonis , Ramchandra Rohit
Published: May 2023

Peripheral arterial chemoreceptors monitor the chemical composition of the blood. While, the carotid bodies located at the bifurcation of the common carotid arteries have been extensively studied. The physiological role of the aortic bodies located in the walls of the aortic arch remains relatively under-studied, and its role in hypertension is unexplored.We hypothesized that activation of the aortic bodies would increase coronary blood flow in the normotensive state and that the parasympathetic nerves to the heart would mediate this.Experiments were conducted in conscious and anesthetized ewes instrumented to record arterial pressure, coronary blood flow, and cardiac output. Two groups of animals were studied, one made hypertensive using a 2 kidney one-clip model (HTN. n=6) and a sham-clipped normotensive group (Con. n=6). Unilateral renal clipping increased resting mean arterial pressure (Con: 84±5 vs HTN 115±6 mmHg). The aortic body chemoreceptors were stimulated by a bolus infusion of potassium cyanide (KCN; 10-30 μg/kg) into the left ventricle.Activation of the aortic bodies in the normotensive and hypertensive animals resulted in a significant increase in coronary blood flow ( P<0.05, 2-way ANOVA, interaction effect), which was not different between groups. In normotensive sheep, the aortic body chemoreflex-mediated coronary vasodilation was attenuated by atropine infusion. Interestingly, the coronary vasodilation in hypertensive animals was not altered by the blockade of muscarinic receptors but was attenuated after propranolol infusion ( P<0.05, interaction effect). Bilateral vagotomy is not possible in conscious animals; under anesthesia, the coronary blood flow response to aortic body stimulation was significantly attenuated in normotensive sheep. Neither atropine nor propranolol affected the aortic body chemoreflex meditated changes in either group's blood pressure, heart rate, or cardiac output. This data suggests that the aortic bodies play an important role in modulating coronary blood flow and that their effector mechanism is altered in hypertension. Many patients with hypertension are on beta-blockers. Our finding indicates that the aortic bodies modulate coronary blood flow via a beta-adrenergic mechanism in hypertension, which may have important implications for regulating coronary blood flow during exertion in hypertensive patients.

Work is supported by the Health Research Council (HRC) of New Zealand.

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.
Circulating hepatokine ANGPTL8, but not ANGPTL3, is increased in low-capacity runner (LCR) rats
Authors: Trauner Erica , Wilson Emily , Costa Tiago , Fonte Milene , Nielson Andrew , Bailey Anne , Koch Lauren , Webb R. Clinton , Wenceslau Camilla , McCarthy Cameron
Published: May 2023

Metabolic syndrome, including hypertension, hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and visceral adiposity, increases your risk of heart disease, stroke, and type 2 diabetes. Unfortunately, there is an increase in prevalence of metabolic syndrome among women. While lifestyle interventions (e.g., diet and exercise), are desirable for preventing morbidity and mortality, the genetic predisposition of some people to these conditions means that therapeutic interventions are also necessary. Hepatokines are liver-derived hormones which convey energy status and assist in controlling the availability of endogenous nutrients to a variety of peripheral tissues. Hepatokines, therefore, are important signaling molecules that allow the liver to communicate with other organs throughout the body. Angiopoietin-like Protein (ANGPTL3) is a secreted glycoprotein and hepatokine. ANGPTL3 directly inhibits lipoprotein lipase, an enzyme responsible for hydrolyzing circulating triglycerides. Therefore, it promotes an increase in circulating triglyceride levels without altering phospholipid secretion or uptake. Moreover, ANGPTL3 inhibition has been unequivocally associated with reduced hypercholesterolemia and atherosclerosis. Therefore, we hypothesized that circulating ANGPTL3 expression would be increased in low-capacity runner (LCR) rats. LCR is an animal model metabolic syndrome and presents vascular dysfunction. On the other hand, rats selectively bred for high intrinsic capacity (HCR), presents a healthy state and reduced inflammatory markers. Plasma was extracted from the blood of female LCR (28-week-old), as well as HCR, and control [high-response trainer (HRT)]. Western blot for ANGPTL3 expression was performed. Opposite our hypothesis, we did not observe any difference in circulating ANGPTL3 in LCR relative to HCR (arbitrary units, LCR: 7.5±1.1 vs. HCR: 7.2±0.9, p>0.05) or HRT (arbitrary units, LCR: 7.5±1.1 vs. HRT: 8.2±1.5, p>0.05). However, it has been established that ANGPTL8 promotes the ability of ANGPTL3 to bind and inhibit lipoprotein lipase. Therefore, we performed another Western blot for ANGPTL8 expression. We observed that ANGPTL8 is significantly increased in LCR relative to HCR (arbitrary units, LCR: 12.2±0.6 vs. HCR: 9.7±1.1, p<0.05) and HRT (arbitrary units, LCR: 12.2±0.6 vs. HRT: 9.2±0.4, p<0.05). Overall, these data suggest that the hepatokine ANGPTL8 may be a more physiologically relevant target for the treatment of metabolic syndrome associated with low-intrinsic exercise capacity.

NHLBI (R00HL151889), NIGMS (1P20GM103641 - Pilot Project), UofSC SOM (Startup funds).

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.
Offering Flipped Teaching Training to Faculty at Rural Nursing Programs
Authors: Gopalan Chaya , Daughrity Sheyenne , Hackman Elizabeth , Rowbotham Melodie , Whittington Kelli
Published: May 2023

Flipped teaching is a practical instructional method where the lecture is shifted out of the classroom, thus allowing time for rehearsing and mastering the content through in-class activities and formative assessments. Innovative Flipped Learning Instructional Project or IFLIP is a pilot study involving faculty and their students of rural nursing programs to develop clinical judgment and critical thinking skills essential to enter the healthcare workforce to serve their communities. Most students in these rural programs are marginalized, under-resourced, and come from underserved high schools. Rural nursing programs may also need more resources to provide faculty training in innovative student-centered teaching methods to develop classroom activities and promote clinical judgment. The instructional approach of the faculty before and after the proposed faculty development training was assessed using surveys and course design data. Through rigorous mixed-methods research, the study measured the impact of the nursing faculty transition from the traditional lecture method to the flipped teaching format by capturing the design, implementation, and refinement of their courses. It was found that the flipped teaching training significantly enhanced knowledge among all participants. More specifically, the faculty felt confident creating instructional videos, designing assessments of pre-class work, and assessing student learning. Thus, the flipped teaching training helped faculty be prepared to engage students in their classrooms.

Illinois Innovation Network

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.
An Inclusive Approach Toward Success in Undergraduate Anatomy and Physiology
Authors: Tamarkin Dawn , Deryugina Elena , Aleshire David , Jasemian Yousef
Published: May 2023

With a diverse group of students taking undergraduate Anatomy and Physiology (A&P), it is imperative to find methods that enable every student to be more successful. At National University, we have been applying a new approach in our online and onsite classes that includes more learners: offering multiple attempt homework assessments. The A&P homework is scaffolded to be done with either unlimited attempts or limited to 10 attempts, depending on the specific section. The homework is given online, while subsequent assessments are either given onsite or online. The homework assignments precede more traditional, single-attempt quizzes and/or exams. Some students only complete a homework assessment once, while other students complete the homework assessment multiple times (occasionally over 50 times) in order to achieve their desired grade. The number of attempts per student is specific to each student and not to the specific topic of the homework; some students routinely carry out multiple attempts while others do not. Although making multiple attempts available may seem to allow for grade inflation, our results show that is not the case. Analysis of the number of homework attempts in relation to homework assessment grade had no correlation. Further, the number of homework attempts has no correlation with the grade students earned on quizzes or the entire course. However, a positive correlation has been established between the achieved homework grade in relation to quizzes, exams, and course grade. This positive correlation exists in both online and onsite classes. Our results indicate that enabling students to work through homework assignments according to their needs until they master each topic increases their opportunities for success in the A&P course. Our approach of offering multiple homework attempts is inclusive because it provides any learner with an opportunity to succeed.

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.
H19X-encoded non-coding RNAs are associated with loss of muscle and old age in human: A quantitative histological study using the Genotype-Tissue Expression (GTEx) database
Authors: Zou Joy , Ji Xuan , Yuan Fei , Zhang Yingtao , Liu Yu
Published: May 2023

Loss of skeletal muscle mass and function is commonly seen in individuals with chronic illness, older age, and altered hormonal and/or endocrine functions. Whole-genome survey of human muscle biopsies has identified several miRNAs which are associated with chronic diseases and thus named “atromiRs.” Using murine models, we have showed that H10X-encoded atromiRs miR-424/miR-503 downregulates muscle mass by directly targeting protein translation initiation factors. We hypothesized that H19X-encoded non-coding RNAs (ncRNAs) are involved in the pathogenesis of muscle atrophy/wasting in humans, and the levels of the ncRNAs are correlated with the loss of skeletal muscle mass in old age. A total of 803 samples from the GTEx project, which contains both skeletal muscle RNA expression information and skeletal muscle biopsy images, were included in the study. The samples were further classified into eight groups based on the levels of miR-503HG (host gene of miR-424/miR-503) reported in the database. Quantification of histopathology in HE-stained muscle sections were manually performed in group 1 (n=89) and 8 (n=100), which had the lowest levels or highest levels of miR-424/miR-503, respectively. The degree of muscle atrophy, fibrosis, and interfascicular/perifascicular fat accumulation were assessed with a grading scale of 0-3. The total muscle histology score was also calculated as a sum of all three scores. Unpaired student t-tests were used to compare histological scores, BMI, and age between the two groups. All tests were two-tailed and p-values less than 0.05 were considered significant. There is no significant difference between the two groups in sex ( p= 0.55). In agreement with our recent study, high levels of miR-503HG (group 8) are associated with old age ( p= 0.02), and a trend of higher BM ( p= 0.07). Notably, high levels of miR-503HG are significantly correlated with muscle atrophy ( p= 0.001) and a total muscle wasting score ( p= 0.03) from histological assessment. These findings suggest the increased levels of H19X-encoded ncRNAs in human skeletal muscle are associated with muscle mass loss and potential sarcopenia. The results of our study may provide insight into the underlying role of H19X-encoded ncRNAs in the pathogenesis of geriatric muscle loss.

The research was funded by the University of Houston internal fund to enhance and advance research (to YL).

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.
Metabolomic analysis of equine skeletal muscle during high-intensity interval exercise: a comparison of two different rest intervals
Authors: Takahashi Kenya , Mukai Kazutaka , Takahashi Yuji , Ebisuda Yusaku , Hatta Hideo , Kitaoka Yu
Published: May 2023

High-intensity exercise training is accepted as an effective strategy to induce training adaptations. However, physiological responses to this type of exercise are not fully elucidated. In this study, using metabolomics techniques, we investigated metabolite network responses to high-intensity interval exercise performed with 2 different rest intervals. In a randomized crossover design, 8 Thoroughbred horses performed high-intensity interval exercise on a treadmill. After warm-up exercise at 3.5 m/s for 3 min, followed by 1.7 m/s for 1 min, horses performed three 1 min bouts of high-intensity exercise at the speed eliciting their maximal oxygen uptake, separated by 15- or 2-min of walking at 1.7 m/s. Gluteus medius muscles were taken before and after bout-1 and bout-3 exercise, and used for metabolomic analysis. A similar increase in plasma lactate concentration was observed in each bout of exercise with 15-min rest interval (bout-1: Δ11.8 ± 0.8 mmol/L, bout-2: Δ10.3 ± 0.7 mmol/L, bout-3: Δ9.0 ± 0.9 mmol/L). An increase in plasma lactate concentration progressively diminished during exercise with 2-min rest interval (bout-1: Δ12.5 ± 1.6 mmol/L, bout-2: Δ4.2 ± 0.2 mmol/L, bout-3: Δ2.9 ± 0.3 mmol/L). Arterial oxygen saturation decreased to the same extent in each bout of exercise with 15-min rest interval (bout-1: Δ-3.1 ± 0.5%, bout-2: Δ-3.7 ± 0.4%, bout-3: Δ-3.9 ± 0.7%). In contrast, a decrease in arterial oxygen saturation progressively increased as exercise was repeated with 2-min rest interval (bout-1: Δ-3.9 ± 0.7%, bout-2: Δ-6.0 ± 0.8%, bout-3: Δ-7.7 ± 0.9%). Among 99 detected metabolites as a result of metabolomic analysis, 21 and 18 metabolites (e.g., phosphocreatine, glycolytic intermediates, and tricarboxylic acid cycle intermediates) significantly changed during exercise of bout-1 and bout-3 with 15-min rest interval. No metabolites significantly changed in bout-3 with 2-min rest interval. The current observations suggest a shift towards oxidative metabolism from substrate phosphorylation during repeated bouts of high-intensity exercise with shortened rest interval, even though exercise intensity and duration are the same in each bout.

This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant numbers 20H04071 and 21K21249) and by the Yamaha Motor Foundation for Sports.

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.
The Role of Skeletal Muscle Nrf2 on Cardiac Function in Mice
Authors: Wang Lucas , Dhyani Neha , Rudebush Tara , Gao Lie , Zucker Irving
Published: May 2023

Introduction: Excessive oxidant stress has been shown to damage cardiac tissue and result in impaired cardiac function. Animals with chronic heart failure (CHF) exhibit lower levels of antioxidant enzymes in many tissues including the heart, brain, and skeletal muscle (SkM). Nrf2 is a ubiquitous master transcription factor that regulates antioxidant proteins during enhanced oxidative stress. Earlier studies from this laboratory showed that exercise training was cardioprotective following ischemia reperfusion injury in mice. This protective effect was abrogated in mice in which the Nrf2 gene was deleted selectively in skeletal muscle. Given that skeletal muscle is approximately 40% of body weight and in light of recent findings on skeletal muscle derived extracellular vesicles, we sought to determine if up and downregulation of Nrf2 in skeletal muscle altered cardiac function. We hypothesized that skeletal muscle knockout of Nrf2 would impair cardiac function and the response to the beta 1 agonist dobutamine. Materials and Methods: Experiments were carried out in 37 males iMS-Keap1flox/flox and iMS-Nrf-2flox/flox (i.e. SkM specific) mice. Gene deletion was conditional upon the administration of the estrogen receptor agonist tamoxifen at 3 months of age; floxed mice given vehicle instead of tamoxifen were considered WT. The mice were assigned to 4 groups: Keap1 knockout (KO) (10), Keap1 WT (8), Nrf-2 KO (11), and Nrf-2 WT (8). Results: Keap1 deletion resulted in an increase in skeletal muscle hemoxygenase 1 (HO1) (p = 0.0286) while Nrf2 deletion resulted in a reduction in HO1 (p = 0.0286). However, there were no changes in the level of HO1 or other antioxidant proteins in the heart. Cardiac function was assessed with high frequency echocardiography (Vevo 3100). Systolic and diastolic function were analyzed. Up and downregulation of skeletal muscle Nrf2 did not evoke any change in either systolic or diastolic function. Conclusions: Previous studies have shown that Nrf2 upregulation salvaged cardiac function in mice subjected to either myocardial infarction or thoracic aortic constriction. Therefore, it may be that our lack of an effect of SkM specific Nrf2 manipulation is due to this study being carried out in normal animals and not in a disease setting such as CHF. In future work, this effect will be examined in mice with cardiac dysfunction.

Supported by P0162222 and SURF from the APS

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.
The interaction between early-life exposure to perfluorooctane sulfonate and aging in mice
Authors: Ninomiya Ayane , Amano Izuki , Haijima Asahi , Koibuchi Noriyuki
Published: May 2023

It has been reported that the exposure to environmental chemicals including endocrine-disrupting chemicals in early life can cause developmental diseases in children. We previously reported that the lactational exposure to perfluorooctane sulfonate (PFOS) caused the impairment in the cognitive and motor functions in adult male mice. However, little is known how the early-life PFOS exposure affects such brain functions in aged subjects. The present study investigated the prolonged effects of PFOS on cognitive function, anxiety, and social behavior using aged male mice (> 365 postnatal day). Mice were exposed to PFOS (1 mg / kg body weight) during the lactational period. In the visual discrimination test, both control and PFOS groups showed a decrease in the learning curve. There is no difference in % correct between groups. In the object location test, there were no changes in both short- and long-term memory. In the object recognition test, long-term memory was attenuated in the PFOS group. The test battery for anxiety (elevated-plus maze test, light and dark chamber test, marble burying test) detected no difference between groups. In the three-chamber social interaction test, PFOS-exposed mice showed an avoidance to interact with a novel mouse, which was not observed during the young-adult period. These results indicate that the PFOS mainly affects social activity during aging.

Nothing to disclose

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.
Exogenous Thyroxine Increases Cardiac Nrf2 and the Potential to Upregulate Nrf2-Mediated Antioxidant Defense Mechanisms in Insulin Resistant OLETF rats
Authors: Mendez Dora , Soñanez-Organis José Guadalupe , Vazquez-Anaya Guillermo , Nakano Daisuke , Nishiyama Akira , Ortiz Rudy
Published: May 2023

Cardiovascular disease (CVD) is the leading cause of death among individuals with Type II diabetes (T2D) with approximately 30 million people afflicted within the United States. Diabetic cardiomyopathy is defined as cardiovascular dysfunction induced by diabetic complications such as sustained hyperglycemia and insulin resistance. During insulin resistance the heart undergoes a metabolic shift in which fatty acids (FA) accounts for about 99% of the ATP production. Some major consequences of a metabolic shift with impaired glucose tolerance can cause an increase in reactive oxygen species (ROS), lipotoxicity, mitochondrial dysfunction, ultimately leading to cardiovascular dysfunction. We have previously shown thyroid hormones (THs) increase GLUT4 translocation in cardiac tissue, indicating the potential to improve the impaired glucose metabolism in the heart. THs have also been shown to improve oxidative injury and increase antioxidant defense systems yet contradicting data exists demonstrating THs induce oxidative stress. Thus, the effects of THs on redox biology and oxidative stress are incongruent and warrant further investigation. Insulin resistant, Otsuka Long Evans Tokushima Fatty (OLETF) rats were used to assess the effects of exogenous thyroxine (T4) on oxidative damage and antioxidant defense in cardiac tissue. Rats were assigned to four groups: 1) lean, Long Evans Tokushima Otsuka (LETO; n=6), 2) LETO + T4 (8 μg/100g BM/d × 5 wks; n=7), 3) untreated OLETF (n=6), and 4) OLETF + T4 (n=7). T4 increased NADPH oxidase (NOX) NOX2 mRNA in both treated LETO (2.04 ± 0.6) and OLETF (2.02 ± 0.6) compared to LETO control (1 ± 0.2). T4 further increased NOX4 mRNA in OLETF by 78% compared to untreated OLETF. In addition, T4 increased Nuclear factor-erythroid factor 2-related factor 2 (Nrf2) protein expression in OLETF by 45% compared to untreated OLETF. These data suggest that the potential for an oxidizing environment in the insulin resistant OLETF rat is increased and T4 has the cardioprotective potential to increase Nrf2-mediated antioxidant defense mechanisms.

APS Porter Fellowship and American Heart Association grant # 946746.

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.
Delta economy of walking is not associated with body mass index in physically inactive adults
Authors: Beaumont Josh , Adams Marc , Gaesser Glenn , Angadi Siddhartha
Published: May 2023

PURPOSE: Published data on the relationship between body mass index (BMI; kg/m2) and energy cost of walking is inconsistent. The aim of this study was to determine whether the increased energy expenditure (EE) that occurs with increased walking speed (defined as delta economy) is associated with BMI. The primary hypothesis was that BMI does not influence delta economy. METHODS: Insufficiently active adults (total n = 187[GG1], males n = 87, females n = 100, BMI = 20.0-39.5 kg/m2,18-60 years) walked on the treadmill at 2, 3, and 4 miles per hour (mph) while ventilation and gas exchange were measured with an indirect calorimetry system (Jaeger Oxycon Mobile) for determination of oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory exchange ratio (RER). VO2 and RER were used to calculate EE (w/kg). Each subject walked for six minutes at each speed. Only the last three minutes of EE per stage were used after verification of steady state. Delta economy was captured by analyzing the slope of change of VO2 across walking speeds. Two methodologies were employed to quantify the slope: a novel technique using polynomial random coefficient regression (PRCR) and the traditional delta economy (TDE) method of calculating change in EE for a change in speed. Two key PRCR components were generated: linear and quadratic coefficients. TDE was determined for three speed changes: 2-3 mph, 3-4 mph, and 2-4 mph. The relationship with each of these to BMI was examined via Pearson product-moment correlation with α set at 0.05. RESULTS: BMI was not associated with either the linear ( r = 0.01, p = 0.87) or quadratic ( r = 0.08, p = 0.28) PRCR coefficients. There was no relationship between BMI and TDE at any of the speed intervals: 2-3 mph ( r = 0.07, p = 0.32), 3-4 mph ( r = 0.05, p = 0.53), or 2-4 mph ( r = 0.01, p = 0.87). CONCLUSION: In this sample of inactive adults, BMI did not influence traditional delta economy or the linear and quadratic coefficients from the PRCR model. Consequently, our results indicate that the considerable between-subject variability in all measures of walking economy is not affected by BMI. A strength of this study is the large sample size, which reduces the likelihood of sampling bias that might be present in previously published studies with much smaller sample sizes.

This analysis was conducted on a baseline dataset collected as part of a project funded from a grant from the National Cancer Institute at the National Institutes of Health (R01CA198915).

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.
Roles of the nuclear receptor corepressor 1 (NCoR1) and the silencing mediator of retinoid and thyroid hormone receptors (SMRT) in the developing brain
Authors: Amano Izuki , Ninomiya Ayane , Kawabata-Iwakawa Reika , Ritter Megan , Hollenberg Anthony , Koibuchi Noriyuki
Published: May 2023

The nuclear receptor corepressor 1 (NCoR1) and the silencing mediator of retinoic acid and thyroid hormone (SMRT) are critical coregulators of the nuclear receptor (e.g., thyroid hormone receptors and retinoic acid receptors), mediating transcriptional repression via histone deacetylation. Although they are highly homologous and have similar nuclear receptor interaction domains, they have different roles in different organs. Recently, de novo genetic variants in nuclear corepressors were found in pediatric patients with neurodevelopmental disorders. Thus, we generated the mouse models to understand the role of NCOR1 and SMRT in the central nervous system. We used the mice with conditional NCoR1 or SMRT (NCoR1lox/lox or SMRTlox/lox) alleles in combination with the mice that express Cre recombinase in a neuronal specific fashion (Snap25-Ires2-Cre). First, we performed a battery of behavioral tests to screen behavioral phenotype of mice. We found that hypoactivity, social deficits, and mild anxiety in neuronal specific NCoR1 or SMRT KO mice. In addition, NCoR1 KO mice showed high learning abilities in pairwise visual discrimination task. Next, we performed RNA-sequencing analysis with amygdala from postnatal day 21 to investigate gene expression mediated by NCoR1 and SMRT. We found that 449 genes were upregulated by SMRT deletion, whereas only 8 genes were upregulated by NCoR1 deletion. Overall, our data demonstrate for the first time that NCoR1 and SMRT have separate functions in the central nervous system.

JSPS Grant-in-Aid for Early-Career Scientists 19K16486, 21K15340

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.