bluuebunny/crossref_metadata_2025_split huggingface dataset:
Act88F pseudo-acetylation of lysine 50 (K50) negatively regulates muscle function in Drosophila
Authors: Godoy Luis , Lopez Adrian , Stewart Travis , Madan Aditi , Baker Josh , Cammarato Anthony , Ferguson Bradley 
Published: May 2024

Non-histone post-translational modifications (PTMs) are an increasingly important area of study that contribute to our understanding for protein function in the control of health and disease. Protein PTMs, such as acetylation, are emerging as key regulators of striated muscle function, yet our understanding of how non-histone protein acetylation affects muscle physiology remains fragmentary. Previous reports from our lab identified lysine (K) 52 of skeletal muscle alpha actin (ACTA1) to be acetylated, yet no reports have shown a role for ACTA1 acetylation in muscle function. Act88F is 93% homologous to ACTA1 and K50 is identical to K52 of ACTA1. Thus, for these studies, we mutated K50 with a glutamine (Q) on the Act88F gene in the indirect flight muscle (IFM) of Drosophila to mimic acetylation. We examined physiological function (i.e. flight and climbing) as well as biophysical changes between acetylated Act88F and the associated myofibrillar proteins involved in contraction and relaxation (myosin, tropomyosin, and troponin). We report that Act88F K50Q pseudo-acetylation resulted in a flightless phenotype and decreased climbing ability. In addition, we report that Act88F K50Q flies had increased IFM damage as examined via fluorescent imaging. Interestingly, Act88F K50Q did not change actin-myosin binding, actin sliding velocity, or Ca2+ sensitivity in actin-motility assays. However, Act88F pseudo-acetylation did decrease actin filament length, but only after interacting with myosin, implying that Act88F acetylation increases actin filament breaking. These data suggest that Act88F acetylation at K50 worsens muscle function by destabilizing filamentous actin, resulting in muscle tearing and damage to the IFM, which results in loss of flight. This work suggests that actin acetylation, at least on lysine 50, in response to environmental stressors or diet could greatly change muscle function and sarcomere integrity. This research was funded by the Dennis Meiss & Janet Ralston Fund for Nutri-epigenetic Research, the National Institute for General Medical Sciences (NIGMS) of the NIH (P20 GM130459), the National Heart, Lung, and Blood Institute of the NIH (R15 HL143496), National Institute of Aging of the NIH (R21 AG077248) and NSF EPSCOR Track II (OIA-1826801) to B.S.F. This is the full abstract presented at the American Physiology Summit 2024 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 Normalizes Decreased Heart Rate in Insulin Resistant OLETF Rats
Authors: Mendez Dora A. , Pacher Pal , Ortiz Rudy M. 
Published: May 2024

Diabetic cardiomyopathy (DCM) is defined as heart failure in the absence of overt clinical coronary artery disease, valvular disease, hypertension, and dyslipidemia in diabetic patients. Patients with T2DM display left ventricular dysfunction, fibrosis, and abnormal cell signaling leading to diastolic and systolic dysfunction. Increased left ventricular mass and fibrosis potentially leads to abnormal diastolic function. Substantial data exists demonstrating both insulin-dependent and non-insulin dependent diabetes impairs left ventricular function. During insulin resistance, a metabolic shift occurs favoring fatty acid metabolism at the expense of impaired glucose metabolism, leading to lipotoxicity, increased oxidative stress, and inflammation. Thyroid hormones have shown to be cardioprotective. We have previously shown exogenous thyroxine treatment increased GLUT4 translocation and nuclear factor erythroid 2-related factor 2 (Nrf2) in cardiac tissue, demonstrating the potential to improve glucose metabolism and increase antioxidant defense mechanisms. Insulin resistant, Otsuka Long Evans Tokushima Fatty (OLETF) rats were used to assess the effects of exogenous thyroxine (T4) on left ventricular cardiac function and hemodynamics to assess if the previously observed improvements in cellular metabolism translated to functional improvements. Rats were assigned to three groups: (1) lean, Long Evans Tokushima Otsuka (LETO; n=7), (2) untreated OLETF (n=6), and (3) OLETF + T4 (8 μg/100g BM/d × 6 wks, n=7). Left ventricular function was measured by the pressure-volume system. Heart mass increased in untreated OLETF (1.46 ± 0.08) and treated OLETF (1.61 ± 0.16) compared to LETO (1.19 ± 0.08). Cardiac output (CO) and stroke volume were 26% and 56% greater in untreated OLETF compared to LETO. Heart rate (HR) was 27% lesser in untreated OLETF compared to LETO. While exogenous T4 did not alter CO and SV compared to untreated OLETF, it did normalize HR to LETO levels. The differences in CO between LETO and OLETF suggest that elevated T4 alters the mechanisms (SV vs HR) by which CO is elevated during MetS. The changes may be compensatory to accommodate the cardiac hypertrophy observed in the strain. American Heart Association Award # 946746 APS Porter Physiology Development Fellow (2nd year). This is the full abstract presented at the American Physiology Summit 2024 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 Obesity- and Aging-Mediated Increase of Body Weight and Blood Pressure
Authors: Di Sole Francesca , Babich Victor , Li Jung , Barnes Maria J 
Published: May 2024

The rate of obesity is steadily increasing world-wide, and obesity may predispose to chronic kidney disease (CKD) via direct pathway or through its complications such as hypertension. Furthermore, incidence of CKD is affected by aging and obesity accelerates aging especially in association with its complications. Specifically, the relationship between obesity and aging in controlling CKD progression has not been well-defined. To address this gap in knowledge, we generated a diet-induced obesity mouse model of 52-58-week-old animals and started the characterization of the model by measuring body weight and blood pressure in male and female mice. We studied four groups of mice: first and second groups were male mice, fed 60% high-fat (HF) diet or 10% low-fat (LH) diet for 19 weeks. Third and fourth groups were female mice, fed HF or LF diet for the same number of weeks. A gain in body weight was measured in male mice on HF when compared to male mice on LF diet and was associated with a significant diet-dependent increase (about 30%) in blood pressure. The body weight gain in female mice was more pronounced than in male mice (62% female vs. 54% male). The blood pressure was higher in female mice than in age-matched male mice in control conditions and was not affected by the diet. These findings suggest sex differences in the increase of body weight and blood pressure mediated by diet-induced obesity in mice of 52-58 weeks of age. In summary, our mouse model mimics the phenotype seen in humans and its characterization is valuable to aid the understanding of the relationship of determinants that control the progression of kidney diseases. Des Moines University IOER Research & Grant Award. This is the full abstract presented at the American Physiology Summit 2024 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.
Compatibility of eugenol anesthesia with classroom physiology experiments on nerve and muscle of frogs
Authors: Rees Katherine , Foucrier Skye , Sekhon Ryan , Blank Jason 
Published: May 2024

Frogs serve as valuable model organisms for studying physiological responses of nerve, skeletal muscle and the heart in undergraduate biology labs. Heretofore, induced hypothermia has been the preferred technique for pain and stress reduction prior to euthanasia by pithing. However, AVMA guidelines discourage hypothermia for restraint or euthanasia of amphibians and advocate anesthetic overdose as preferable to pithing alone. Unfortunately, the primary anesthetic used in fish and other aquatic invertebrates, MS-222, blocks normal nerve and muscle function in leopard frogs and renders them useless for classroom physiology experiments, as demonstrated by Medler (2019). Eugenol is a safe and affordable anesthetic that is effective in amphibians. We sought to test the hypothesis that eugenol anesthesia is compatible with classroom nerve and muscle experiments on frogs. Bullfrogs and leopard frogs were immersed in a bath of eugenol suspended in tap water at 275 to 350 mg/L. At various time points, a four step reflex test was performed including tests of righting response, superficial pain reflex, deep pain reflex, and corneal blink reflex. Once all reflexes were absent, the frog was euthanized by pithing and the gastrocnemius muscle was prepared for force recordings. The sciatic nerve was stimulated with a bipolar stimulating electrode while gastrocnemius force was measured using an isometric force transducer. The threshold voltage eliciting a muscle contraction and the peak isometric twitch force were recorded at 15 minute intervals for 2 hours. Control frogs were sedated by immersion in ice water for 20 to 30 minutes, pithed when reflexes were substantially weakened, and then subjected to the same stimulation protocol and force measurements. At these doses, eugenol reliably induces loss of reflexes in 20 to 35 minutes and neuromuscular preparations maintain the ability to respond to electrical stimulation. Preliminary results suggest that eugenol may produce a modest elevation of threshold voltage and a modest reduction in maximum twitch force compared to control frogs euthanized without chemical anesthesia. Eugenol may be an effective anesthetic to prepare bullfrogs and leopard frogs for classroom experiments on nerve and muscle. Funding was provided by the Bill and Linda Frost Fund. This is the full abstract presented at the American Physiology Summit 2024 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.
Novel regulation of kidney function by gastrointestinal hormones
Authors: Peresztegi Lena , Peti-Peterdi Anna , Becerra Calderon Alejandra , Izuhara Audrey , Deepak Sachin , Gyarmati Georgina , Peti-Peterdi Janos 
Published: May 2024

The control of whole-body energy metabolism involves intricate crosstalk between multiple organ systems including the gut and the brain that play well-recognized roles in this process. However, the important contributions and mechanisms by other organs are poorly understood. Errors in metabolic regulation can lead to human metabolic diseases including diabetes and obesity that affect 75% of the population and can lead to significant comorbidities. Improving our mechanistic understanding of multi-organ metabolic crosstalk in health and disease is essential for developing highly effcient and new therapeutic approaches. Macula densa (MD) cells in the kidney are chief regulators of renal blood flow and tissue remodeling. We hypothesized that the kidney is a major player in body metabolism via a new mechanism of gut-kidney crosstalk that involves the gut hormones gastrin and cholecystokinine (CCK) activating intrarenal, MD-specific mechanisms to increase blood flow and filtration, progenitor cells and tissue growth factors. High-resolution MD bulk and single-cell transcriptome analysis was performed from freshly isolated, enriched MD cells using MD-GFP mouse kidneys. Single cell MD Ca2+ signaling was analyzed in vivo using intravital multiphoton microscopy (MPM) of Sox2-GT mice that express the ratiometric Ca2+ reporter GCaMP6f/tdTomato in all renal cells. The altered expression of MD specific markers in response to gastrin/CCK8 stimuli was studied using western blot and the novel MDgeo immortalized cell line cultured in vitro. RNA sequencing and transcriptome analysis identified the gastrin/CCK receptor Cckbr as one of the highest expressed genes in MD versus control kidney cells. Intravital multiphoton imaging of Sox2-GCaMP6 reporter mouse kidneys revealed robust and entirely MD cell-specific calcium signaling in response to systemic gastrin/CCK injection. Using the novel MDgeo immortalized cell line cultured in vitro, CCK8 treatment led to 3-fold increases in MD cell synthesis of Prostaglandin E2 (PGE2)-generating COX2 and CCN1 that are established mediators of MD-induced glomerular hyperfiltration and tissue remodeling, respectively. Chronic treatment of Ren1d-Confetti mice with Darunavir, an HIV protease inhibitor significantly increased plasma CCK levels, Ren+ mesenchymal progenitor cell number and clonality, renal cell proliferation and tissue hypertrophy. This study uncovered new regulatory mechanisms of systemic metabolism especially the role of MD cells in the kidney. Repurposing the commonly used HIV drug Darunavir for kidney and metabolic diseases may provide therapeutic benefit for millions of patients worldwide. DK064234, DK123564, DK135290. This is the full abstract presented at the American Physiology Summit 2024 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.
Comparative anoxia responses of hatchling and juvenile western painted turtles (Chrysemys picta bellii)
Authors: Membreno Nelson , Warren Daniel 
Published: May 2024

The western painted turtle ( Chrysemys picta bellii) is the most anoxia-tolerant tetrapod known, with adults capable of surviving anoxia for more than 170 days at 3°C. However, hatchling painted turtles are known to have an anoxia tolerance of just 40 days at 3°C. It is believed that the reduced mineralization of the hatchling shell likely limits their buffering capacity, but other aspects of their physiology, such as anaerobic metabolic rate and glycogen stores could be limiting as well. We hypothesize that one year-old juveniles, with more mineralized shells, would tolerate anoxia longer than recently hatched turtles. Thirty-five juvenile and hatchling turtles were gradually cold-acclimated from 20°C to 3°C and then placed inside individual cages. Three aquaria (37.85L) each contained eight juvenile and eight hatchling turtles. Eleven control juvenile and hatchling turtles were sampled and flash-frozen for future analysis of tissue glycogen, lactate, and carbonate. The remaining turtles were then submerged in anoxic water and their limb withdrawal reflex tested daily for a loss of response. When half of each developmental group became unresponsive, the remaining responsive turtles were then sampled. The hatchling and juvenile turtles lost their withdrawal reflex after 39.3 ±1.2 days and 42.3 ±2.6 days, respectively, indicating there was no significant difference in anoxia tolerance between the developmental groups. Powdered whole-body turtle samples showed similar total glucose and glycogen levels in juveniles (30.484 μmol/g tissue and 4.875 μmol/g tissue) and hatchlings (27.301 μmol/g tissue μmol/g tissue and 4.718 μmol/g tissue), respectively. Plasma samples showed that juveniles tended to have slightly higher free glucose and lactate (15.160 mmol/L and 6.317 mmol/L) compared to hatchlings (11.118 mmol/L and 5.531 mmol/L), respectively. There was no interaction between anoxia tolerance and life stage. These results suggest that tissue glycogen stores, and not buffering capacity, limits the anoxia tolerance of young turtles. NSF CAREER grant to DEW. This is the full abstract presented at the American Physiology Summit 2024 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 Investigation of the Cavernous Nerve
Authors: Villarmán Julio 
Published: May 2024

Objectives: To investigate the presence or absence of post-ganglionic cell bodies within erectile tissue. The presence of intramural cell bodies will indicate parasympathetic features. The absence of intramural cell bodies will indicate sympathetic features. Methods:Rabbit monoclonal anti-Neun Alexa488 Immunofluorescence staining on tissue sections from dissections to target neuronal nuclei in the positive controls and erectile tissue sample. This is the full abstract presented at the American Physiology Summit 2024 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.
Chronic kidney disease is accompanied by behavioral deficits in rodents
Authors: Di Sole Francesca , Babich Victor , Kornstad Abigail , Tefft Kristin , Duric Vanja 
Published: May 2024

Clinical reports indicate a bidirectional relationship between mental illness and chronic systemic disease. Kidney injury and inflammation have been linked to brain dysfunction and alterations in learning and memory, as well as development of anxiety and depression, however, the underlying neurophysiological mechanisms remain elusive. In the current study, we investigated whether a chronic kidney disease (CKD) state is suffcient to produce deficits in rodent stress behaviors using a mild or severe model of CKD. Male rats were exposed to either 21 days of 0.75% adenine diet (AD) (model of mild CKD), or a combination of AD with unilateral nephrectomy (AD/Unx), prior to the start of AD (model of severe CKD). Control rats received sham surgery and remained on normal diet/chow throughout the experimental paradigm. CKD development in the rat models was determined by a significant increase in serum creatinine used as index for kidney function. Behavioral testing results demonstrate that mild CKD model, especially in combination with unilateral nephrectomy (severe CKD model), is accompanied by anhedonia (i.e., decreased sucrose preference) and increased anxiety-like behaviors in the novelty-suppressed feeding, open field and elevated plus maze tests. These findings suggest that impairment of kidney functionality is suffcient to increase behavioral emotionality in rodents consistent with development of depressive-like and anxiogenic phenotype. Ongoing studies are focused on identifying neurophysiological mechanisms linking renal disease with neurological abnormalities. Furthering our understanding of these mechanisms may aid in the development of improved treatments and prevention strategies for management of mental health comorbidities associated with kidney disease. Des Moines University IOER Research & Grant Award. This is the full abstract presented at the American Physiology Summit 2024 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 Previous Dietary and Exercise Education on Knowledge of Obesity and its Comorbidities: Case Study on a College Campus
Authors: Ames Olivia , Smith Katelyn , Sharma Naveen 
Published: May 2024

Greater than 40% of the adult U.S. population is estimated to be clinically obese based on body mass index (BMI) ≥ 30 kg/m2. Obesity is associated with several debilitating comorbidities that impact both physical and mental health including cardiovascular disease, type 2 diabetes, cancer, and depression. A college community is not immune to obesity, but with a typically younger and more active population the prevalence of obesity is generally lower on campus than the neighboring area. We hypothesized that a formal education of diet and exercise would be strongly associated with reduced obesity, and moreover an increased knowledge of obesity-linked comorbidities. College students were surveyed on their educational background, obesity and associated comorbidity knowledge, as well as anthropometric information including height and weight. Correlations were analyzed to determine links between education, obesity knowledge, and BMI. We received completed surveys from 158 students with an average age of 20.5 ± 3.0 years and BMI of 24.5 ± 5.1 kg/m2. Students with formalized education in diet and exercise were more informed about current nutritional and physical activity guidelines than those students who had not received similar education. Despite this disparity, both groups of students were similarly knowledgeable about obesity and its comorbidities. Additionally, there was no difference in the self-reported BMIs between these two groups of students. Based on our survey, the prevalence of obesity was 10.8%, much lower than the national average. We conclude that a formal education in diet and exercise did not lead to differences in weight status or obesity knowledge amongst students on this college campus. This suggests that on-campus health promotion initiatives regarding obesity would be equally beneficial to all students regardless of educational background. Honors Program; Herbert H. & Grace A. College of Health Professions; Offce of Graduate Studies Central Michigan University. This is the full abstract presented at the American Physiology Summit 2024 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.