bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a) in regulating mitochondrial energy effciency in skeletal muscle
Authors: Karasawa Takuya , Choi Ran Hee , Meza Cesar , Funai Katsuhiko 
Published: May 2024

Previous studies have shown that exercise training improves mitochondrial energy effciency in skeletal muscle, but the molecular mechanism is unclear. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a) is a transcriptional co-activator that coordinately regulates exercise-induced mitochondrial biogenesis and quality control. This study aimed to test the hypothesis that PGC-1a is involved in the improvement of mitochondrial energy effciency in skeletal muscle by using a skeletal muscle-specific PGC-1a overexpression mouse model. Ten to twelve-week-old skeletal muscle-specific PGC-1a transgenic mice (MCK-PGC-1a) and their wildtype littermates (WT) were used. Protein levels of oxidative phosphorylation (OXPHOS) subunits in skeletal muscle were determined by Western blot analysis. The rate of O2 consumption ( JO2) and ATP production ( JATP) in isolated mitochondria from skeletal muscle were evaluated using high-resolution respirometry and fluorometry, respectively, and mitochondrial energy effciency (ATP produced per O2 consumed, or P/O) was calculated. Overexpression of PGC-1a in skeletal muscle did not affect body weights and muscle weights. Consistent with previous studies, MCK-PGC-1a mice had significantly higher OXPHOS protein content than WT mice. On the other hand, JO2, JATP, and P/O in isolated muscle mitochondria were not different between genotypes. Our results suggest that exercise training-induced improvement in muscle mitochondrial energy effciency is not mediated by PGC-1a. This research is supported by NIH grant DK107397 to K.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.
Spontaneous Bursts of Muscle Sympathetic Nerve Activity Reduce Femoral Arterial Compliance in Humans
Authors: Young Benjamin , Kissell Claire , Conley Rie , Vranish Jennifer , Credeur Daniel , Holwerda Seth , Fadel Paul 
Published: May 2024

Previous studies in rodents have demonstrated tonic sympathetic restraint of arterial compliance. To date, studies in humans have examined sympathetic restraint of compliance via either reflexively or pharmacologically manipulating sympathetic vasoconstriction and measuring resultant changes in compliance. The extent to which spontaneous bursts of muscle sympathetic nerve activity (MSNA) dynamically regulate arterial compliance in humans on a beat-by-beat basis remains unknown. Herein, we hypothesized that femoral arterial compliance would be transiently reduced following spontaneous bursts of MSNA. Further, we hypothesized that the magnitude of reduction in arterial compliance would be graded to the MSNA burst amplitude (index of net neural outflow). Beat-to-beat blood pressure (BP; Finometer), heart rate (ECG), MSNA (peroneal microneurography), and femoral artery blood flow (duplex Doppler ultrasound) were continuously measured over 10-20 minutes of quiet supine rest in 27 young, healthy men (age: 22 ± 1 years, resting MSNA burst frequency: 11 ± 5 bursts/minute). Customized labview programs were used to time-align neural cardiovascular variables with ultrasound data sampled at 30Hz, enabling the quantification of arterial compliance on a beat-by-beat basis defined as the change in arterial cross-sectional area divided by the change in blood pressure over the cardiac cycle. Bursts of MSNA were tracked for 10 cardiac cycles and changes in arterial compliance were quantified using signal-averaging for all bursts, and subsequently, for bursts of MSNA when sub-classified based on amplitude into quartiles (Q1= smallest 25% of bursts, Q4= largest 25% of bursts). Reductions in arterial compliance were significantly greater following cardiac cycles with bursts of MSNA compared to cardiac cycles without bursts of MSNA (bursts: -5.1 ± 0.6% vs. non-bursts: -0.8 ± 0.2%, p<0.001). Further, reductions in compliance appeared to be graded to MSNA burst amplitude (Q1: -6.5 ± 0.8%; Q4: -9.1 ± 1.3%, P=0.051). The latency (i.e., number of heartbeats) to nadir arterial compliance following bursts of MSNA was 4.2 ± 0.6 cardiac cycles. Collectively, these findings suggest that the sympathetic nervous system dynamically regulates femoral arterial compliance on a beat-to-beat basis. College of Nursing and Health Innovation, University of Texas at Arlington. 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.
Integrating Health Policy Into Undergraduate Physiology: A Pedagogical Framework
Authors: Redden John , Divino Jeffrey 
Published: May 2024

Evidence-based health policies save lives. Rising to meet the global health challenges of the 21st century (e.g., the climate crisis, infectious diseases, health inequity) will require more scientists to participate in the policymaking process. However, few opportunities exist for STEM students to learn how their scientific knowledge can be applied to policy, or how they can shape the policies that govern science in the United States. Additionally, although scientific expertise is necessary to create effective health policies, it is not suffcient. For example, many scientifically sound policies (e.g., masking, vaccination) fail in the implementation phases because they are not communicated effectively to their intended audience. Here we share a pedagogical framework for integrating health policy into existing undergraduate physiology courses using examples from Anatomy and Physiology, Physiological Model Systems, and Public Communication of Physiology. This framework empowers students to develop procedural knowledge about state and federal policymaking, discuss examples of biomedical scientists and healthcare workers contributing to policy and rulemaking, link course curricula to current legislation proposed at the state or federal level, and advocate using their scientific knowledge and lived experiences as scientists. It also incorporates foundational science communication training that goes beyond the commonly used deficit framework (i.e., “educating the public”), and instead emphasizes dialogue (e.g., listening to stakeholders), rhetorical strategy (e.g., storytelling), trust-building, discrete goal setting, and positionality. Lastly, we provide preliminary evidence that using this health policy toolbox leads to student empowerment in policy and advocacy, development of practical communication skills applicable to their future careers, and deep affective connections to their physiology coursework. This project was supported by the Alan R. Bennett College of Liberal Arts and Sciences Public Health Policy Research Fund at the University of Connecticut. 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.
PNA5, a Novel Glycosylated Angiotensin 1-7 Treatment Improves Infarct Size and Fibrotic Remodeling in Ischemic Reperfusion Injury
Authors: Piepho Arian , Hoyer-Kimura Christina , Hay Meredith , Methajit Methawasin , Polt Robin , Fricks Joshua , Salcedo Victoria 
Published: May 2024

Background: Reperfusion during an acute ischemic event is of paramount importance to rescue cardiac tissue. Paradoxically, reperfusion of the ischemic tissue promotes further cardiac injury. Increased reactive oxidative species (ROS) and inflammation contribute to ischemic reperfusion injury (IR). PNA5, a glycosylated analog of angiotensin-(1-7), decreases ROS and inflammation. The purpose of this study is to indicate if PNA5 treatment has the ability to reduce infarct (IN) size and improve cardiac remodeling in IR. We hypothesize that PNA5 will improve fibrosis and diminish IN size in IR. Methods: 3-month-old male mice (C57BI/6J) underwent IR surgery. Mice were anesthetized and the left anterior descending artery was litigated for 45 minutes. Ischemic areas were then reperfused. Mice were immediately injected with PNA5 (subcutaneously s.c. at 100μg/kg, n=11) or with saline as control (n=11). Injections were continued daily with PNA5 or saline for 8-weeks. At the end of treatment, mice were sacrificed. Upon sacrifice, hearts were re-ligated and perfused with Evans Blue to identify the areas at risk (AAR). Hearts were stained with 2-3-4-triphenyltetrazolium chloride to show IN area. IN size and AAR were determined using Image J. Paraffn-embedded hearts were stained with Picrosirius Red for fibrosis. Fibrosis was measured as a ratio of collagen to total tissue area for 17 regions in the left ventricle (LV). Values are represented as mean ± standard error of mean. Results: PNA5-treated mice IN size was significantly decreased compared to saline-treated mice. (IN/AAR: IR-Saline 0.17± 0.02; PNA5 0.10± 0.01, p=0.005; IN/LV: IR-Saline 0.08± 0.01; PNA5 0.05±0.01; p=0.002, student’s T-test). PNA5 reduced fibrosis in the LV compared to IR-saline mice Conclusions: These results indicate PNA5 as a potential therapeutic treatment for IR as it improves IN size and fibrotic remodeling in IR. [Formula: see text] Supported by NIA U01AG066623 to MH. 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.
Effects of p300 inhibition on prostate cancer cell growth
Authors: Kunkel Olivia , Horn Andrew , Wallace Nicholas , Behnke Bradley 
Published: May 2024

Background: Radiation is a central component of many anti-cancer therapy regimens, utilized for more than half of all cancer patients. Despite advances in the delivery and success of radiation treatment, many individuals express, or will develop, radioresistance, a major contributor to treatment failure and malignant progression. While the etiology of radioresistance is complex, it may be mediated in part by expression of p300, a histone acetyltransferase known to facilitate DNA repair. We hypothesized that inhibition of p300 would increase radiosensitivity of prostate cancer cells in vitro. Methods: Human prostate adenocarcinoma (PC-3) cells were grown in tissue culture flasks incubated at 37° C with 5% CO2. Cells were randomized to receive 1 μM CCS 1477, a selective inhibitor of p300, or vehicle for 1 hour prior to a single treatment of 0 Gy (NR+ or NR-, respectively) or 2 Gy radiation (R+ or R-, respectively). Four hours after radiation, cells were seeded into 100 mm diameter tissue culture dishes and incubated for 10 days. Cells were then stained, and colonies > 50 cells were counted to determine clonogenic survival. Cell survival was corrected for plating effciency and group comparisons were made using a two-way ANOVA. Results: Results were determined from the average of 3 separate experiments. Compared to non-radiated controls (NR-), survival of R- was reduced to 47%, while survival of R+ was reduced to 32%. However, there was no significant difference between % survival of R- and R+. Conclusions: In vitro, 1 μM exposure to CCS 1477 does not reduce clonogenic survival in PC-3 cells subjected to 2 Gy radiation. The duration of exposure and concentration of CCS 1477 may not be adequate to elicit significant improvements in radiosensitivity of PC-3 cells to 2 Gy radiation. Future experiments will explore the effects of varying durations of exposure and concentrations of CCS 1477. Additionally, it remains to be determined whether CCS 1477 improves radiosensitivity in other cancer cell lines (e.g., breast cancer). Johnson Cancer Research Center. 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.
Gestational Long Term High-Altitude Hypoxia and Metabolomic Reprogramming in Uterine Arteries of Adult Sheep
Authors: Cosper Justis , Zhang Lubo , La Frano Michael , Wilson Sean 
Published: May 2024

Long term hypoxic stress during pregnancy causes a reduction in uterine blood flow, compromising oxygen and nutrient delivery to the fetus. There are multiple epigenetic factors involved in the structural and functional impairments that underlie the impairments in uterine arterial function. Evidence indicates that oxidative stress plays an important role to the decrements in blood flow following high altitude pregnancy. The purpose of the current study was to test the hypothesis that changes in oxylipin and endocannabinoid signaling are important to the increases in oxidative stress along with changes in glucose and fat metabolism. To further understand the mechanisms associated with disruption of uterine artery blood flow due to high altitude pregnancy, we examined a high altitude pregnant sheep model. Pregnant and non-pregnant sheep were housed either at low (700m) or high altitude (3801 meters) for 110+ days of pregnancy. Uterine arteries were excised from pregnant and non-pregnant sheep and targeted as well as untargeted metabolomic analyses were performed to test the hypothesis that hypoxia increases oxidative stress and reduces oxidative metabolism. Enrichment analysis of the metabolites show that hypoxia impacted several key biochemical pathways. At high altitude there were decreases in Alpha Linolenic Acid and Linoleic Acid Metabolism along with reductions in Pyruvate Metabolism and antioxidants. Further to this, there was an increase in the metabolism of Arachidonic Acid, Glycerolipids, and Methionine, which are linked to inflammation, cell signaling, and cell growth. Fully understanding how increased oxidative stress and inflammatory pathways along with decreased antioxidant capacity and changes in cellular metabolism is tied to malformations in uterine arterial structure and function following high altitude gestation is an active area of investigation. This work was supported by the National Institutes of Health Grants NIH R01HL155295, R01HL149608, R03HD098477, P01HD083132, and U24DK097154. Additional support was provided by the Loma Linda University School of Medicine and West Coast Metabolomics Center. 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.
Prenatal transportation stress and sex influence the metabolomic profile of the liver of 28-day-old Brahman bulls and heifers
Authors: Welsh Thomas H. , Tolleson Douglas R. , Cardoso Rodolfo , Haigrove Thomas , Riley David , Long Charles , Perry George 
Published: May 2024

Prenatal transportation stress (PNS) reportedly induced differential DNA methylation of genes related to behavior, immune function, stress response, and metabolism in Brahman heifer and bull calves (doi:10.1093/jas/skz368). The objective of the present experiment was to conduct a metabolomics analysis of liver samples of 25-day-old beef calves to identify biochemicals and determine effects of PNS and sex classification. Mature Brahman cows artificially inseminated to the same Brahman sire were assigned to be either Control (n=35; not transported) or PNS (n=37; 2 h of transportation at 60, 80, 100, 120, and 140±5 d of gestation). Livers were obtained from 16 Control (8 bulls and 8 heifers) and 16 PNS (8 bulls and 8 heifers) calves that were humanely euthanized at 25±2 d of age. Liver samples (200 mg) were submitted to Metabolon, Inc. to identify metabolites by ultra-high-performance liquid chromatography/tandem high resolution/accurate mass spectrometry chromatography methods. An estimate of the false discovery rate was calculated and following log transformation, two-way ANOVA was used to identify significant interactions and biochemicals that differed significantly ( p ≤ 0.05). Principal component analysis (PCA) was also used to compare PNS and sex effects. A total of 851 biochemicals were identified and categorized; this report emphasizes energy pathways and lipid mediators of inflammation. PNS increased 45 metabolites and decreased 21 whereas 23 were increased and 30 decreased in bulls versus heifers. Significant interaction of PNS and sex was noted for 33 metabolites. Glucose did not differ due to PNS; however, it was increased in bulls versus heifers. Maltotriose and maltose were higher in PNS, and it was greater in heifers than bulls. Lactate was higher in bulls than heifers. Lipid mediators of inflammation were elevated in PNS calves. to our knowledge this is the first report on the liver metabolome of prenatally stressed calves. These observations suggest an influence of prenatal stress and sex on liver metabolomics within 1 month of age in cattle. USDA NIFA Award No. 2019-67015-29573. 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.
Investigating the role of Vitamins in Prostate cancer risk among African Americans
Authors: An William , Ukoli Flora , Raynes Edilberto 
Published: May 2024

Background & Aims: Previous studies have shown certain vitamins and minerals are associated with a reduced risk of prostate cancer. In this study, we assess whether vitamins will have an effect on prostate cancer risk among African Americans. Methods: A case-control study was conducted in Washington, District of Columbia and Nashville, Tennessee. There were 264 participants involved in the study. The participants were divided into 3 groups: prostate cancer (n=56), elevated PSA (n=377) and control (n=163). Dietary intake was measured by using a validated food frequency questionnaire. Food items rich in vitamin D, vitamin E, selenium, and lycopene were identified. Chi square tests were performed to evaluate the association between vitamins and prostate cancer risk. Results: There is a statistically significant association between the consumption of certain food items such as beef, pork, eggs and decreased prostate cancer risk (p<.05). There is also a statistically significant association between the consumption of salmon, cod liver oil, peanuts, mushrooms, orange juice and prostate cancer risk increase (p<.05). When aggregated, there was no significant correlation between the consumption of vitamin D, vitamin E, lycopene, selenium and decreased prostate cancer risk. Conclusions: Results of our case-control study suggest dietary restriction of certain meats as prostate cancer risk reduction strategy cannot be suggested. Increasing annual intake of food high in vitamin D, vitamin E, selenium, and lycopene cannot be suggested as a way to decrease prostate cancer risk. Diet modification interventions should focus on dietary moderations. Center of Excellence COE/Offce of Dean, Meharry Medical College School of Medicine, Grant Number: D34HP16299. 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.
Changes of Inflammatory Cytokines after 4-week and 8-week Aerobic Exercise in Hispanic Obese Females
Authors: Yoemans Kylie , Park Kyung-Shin , Gutierrez Monica , Chavarria Raul , Rodriguez Marielise , Park Jeffrey 
Published: May 2024

Recent studies have insuffcient data to support the effects of exercise on inflammatory cytokines independent from weight loss. Thus, a reduction in fat mass is required to induce decreases in markers of pro-inflammatory cytokines. PURPOSE: Changes in inflammatory cytokines following 4-weeks and 8-weeks of aerobic exercise were measured in this study to find if exercise is an independent determinant on changes in inflammatory cytokines in middle-aged Hispanic obese females. Methods: 35 obese females were randomly assigned to either exercise (EX, N=16) or control (CON, N=19) group. The exercise group performed moderate intensity aerobic exercise on the treadmill for 60 minutes at 55% of VO2max for 8 weeks (3 days/week). Body composition measurement with dual-energy X-ray absorptiometry and blood collection were conducted before and after the 4th week and 8th week of the intervention (PRE, 4W, and 8W). Blood samples were used to measure levels of tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and adiponectin. Two-way repeated measures ANOVA and Tukey post hoc tests were used for data analysis. RESULTS: Following 8 weeks of aerobic exercise intervention, participants had significantly reduced body mass index (34.2±4.6 mean±SD → 33.7±4.7, P=.035), %body fat (42.1±5.2% → 41.4±5.3, P=.014) and TNF-α (4.57±.24pg/mL mean±SE → 4.14±.31, P=.019) as compared to PRE. EX also observed a decrease in TNF-α (4.57±.24 → 4.29±.28, P=.033) when changes in body weight and %body fat were not observed after 4 weeks of aerobic exercise. CRP and adiponectin were unaltered in EX. CON showed no significant changes in any variables at 4W and 8W. CONCLUSION: It is suggested reductions in inflammatory cytokines are associated with fat loss; however, significant change in TNF- α at 4W when no change in %body fat is observed this indicates that moderate aerobic exercises may reduce level of inflammation independent from fat loss. This change is further improved when fat loss occurs at 8W. Therefore, it is plausible that moderate aerobic exercises may independently reduce risks of obesity-associated disorders in middle-aged Hispanic obese females. Results of this study suggest that longer periods of exercise training with fat loss may be required to induce significant changes in CRP and adiponectin in middle-aged obese females. TAMIU University Research Grant. 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.