bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gold nanoparticles-conjugation of irisin enhances therapeutic effect by improving cardiac function and attenuating inflammation in sepsis
Authors: Wang Lijiang , Kulthinee Supaporn , zhao Yu , Yano Nahiro , zhang Ling , Wen Huai , Zhao Ting 
Published: May 2024

Introduction: Irisin is considered to be a promising therapeutic approach for cardiac depression and inflammatory disorders. The short half-life of irisin impeded its use and drug effcacy in the treatment. Objective: This study aimed to examine if pegylated gold nanoparticles-conjugated to irisin would improve therapeutic effects in cecal ligation and puncture (CLP)-induced sepsis in mice. Method: Recombinant irisin were conjugated to a pegylated gold nanoparticle, which was given to mice exposed to CLP. The cecal ligation procedure and sham on mice were operated and assigned to one of following five groups: I) CLP group: The mouse models underwent the CLP surgical procedure and received only vehicle saline treatment (n= 5); II) CLP + soluble Irisin: The mouse underwent the CLP and received an i.m (TA) injection of 1 ug of soluble irisin into each leg (n= 5); III) CLP + Gold nanoparticle-conjugated to Irisin: The mouse models underwent the CLP and received an i.m (TA) injection of 1 μg of Gold nanoparticle-irisin via intramuscular injection (TA) into each leg w (n= 5); IV) CLP + Gold nanoparticles- conjugated to IgG: The mouse underwent the CLP and received an i.m (TA) injection of gold nanoparticles conjugated to IgG (n=5). V) Sham: The mouse underwent the surgical operation without conducting the CLP (n=10). The post-operated animals were observed for one week, and survival rates were estimated. Echocardiography was performed to measure cardiac function at 12 hours following CLP. TUNEL was employed to detect apoptosis in both cardiac and skeletal muscles; histology was conducted to assess tissue injury in muscles. Enzyme linked immunosorbent assay (ELISA) was conducted to examine release of interleukin 6 (IL6) and the tumor necrosis factor (TNF) alpha. Results: Compared to the CLP control, soluble irisin treatment improved cardiac function recovery, as indicated by the fractional shortening (FS) and ejection fraction (EF). Irisin treatment exhibited reduced IL6 and TNF-alpha release in association with less apoptosis, lower muscle injury index and improved survival post-CLP. However, compared to soluble irisin treatment, gold nanoparticles-conjugated to irisin showed a significant improvement in cardiac function, suppression of apoptosis, reduced IL6 and TNF-alpha releases, decreased muscle injury and an improved survival rate of post-CLP. Conclusion: This study reveals that gold nanoparticles-conjugated irisin can serve to improve irisin’s therapeutic effects over a longer course of treatment. National Institute of General MedicalSciences (R01GM 141339); National Heart, Lung, andBlood Institute Grants (R01 HL089405). 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.
Meeting the Needs of Underrepresented Female Students Using Innovative Molecular Models
Authors: Lester King Adrienne , de la Cruz Jennifer , Johnson Cassandra 
Published: May 2024

The underrepresentation of women in science, technology, engineering, and math (STEM) fields is of national concern. Research shows that females begin to lose confidence in their math and science abilities in middle school and it worsens in high school. Developing and leveraging young women’s interest in these topics via active learning activities and hands on models can encourage pursuit of STEM degrees in college. The MIT Edgerton Center Models and Curriculum was incorporated into the EMPOWER Program, a four-week program engaging female research scholars in 10th-12th grade in a summer fellowship that provided hands-on research experience focused on in-depth understanding of how exposures to toxic environmental insults in the urban environment impact health and alter biologic processes. The models were used to teach about DNA/RNA and protein synthesis. The models are designed to teach processes, in addition to structure. They are made to be manipulated so learners can perform cellular functions with their own hands. We hypothesized that using a hands on activity would increase engagement and learning about the Central Dogma of Life. Methods: Participants were guided through exercises using the models. Students (n=5) and teachers (n=2) utilized the MIT Edgerton Center Models of DNA/RNA and protein synthesis. Results/Discussion: Surveys were completed at the end of the program to determine student’s perceived impact on their learning and overall experience using the hands-on models. A Likert scale was used to assess student learning. On a scale of 1 to 5, with 5 representing strongly agree, all participants strongly agreed the models helped them learn more about DNA/RNA and proteins. Conclusion: Innovative molecular models increased student engagement and learning creating an environment for student centered learning. NIEHS Project Number: 5R25ES030240-03. 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 impact of a single high-fat meal on indices of cerebrovascular function & health
Authors: Perry Ken A. , Ortiz Alison , Kolade John O. , Shah Prarthi J. , Patik Jordan C. , Brothers R. Matthew 
Published: May 2024

High-fat diets contribute to elevated risk for cardiovascular, cerebrovascular, metabolic, and neurocognitive diseases with reduced vascular health being a contributing factor. It is well documented that a single high-fat meal (HFM) reduces peripheral vascular function. Despite the elevated risk for/prevalence of cerebrovascular and neurocognitive disease with a high-fat diet, the impact of a single HFM on cerebrovascular function/health is less known. Cerebrovascular pulsatility index (PI) (measure of cerebral vascular stiffness) and cerebral autoregulation (ability of the cerebral vasculature to maintain constant blood flow during changes in arterial blood pressure) are indices of cerebral vascular function/health that are impaired in populations with elevated disease risk. To our knowledge, the impact of a HFM on these indices have not been studied. Accordingly, this study tested the hypothesis that a single HFM will blunt cerebrovascular function/health as indexed by increased PI and transfer function gain. Methods: Fifteen individuals (13 male; age: 28±11yr; BMI: 24±4 kg/m²) participated. Measures were made before and 2hr post-consumption of a HFM (990 kcal, 55g fat, 89g CHO, 35 g protein, 2120 mg sodium) which was purchased from McDonald’s. The HFM consisted of the following: 1 Sausage Biscuit, 1 Egg McMuffn, 2 hash browns, and 1 bottle of water. Continuous measures of beat-to-beat blood pressure and middle cerebral artery blood velocity (MCAV) were obtained during a minimum of 6-min quiet supine rest. Pulsatility index (measure of cerebrovascular stiffness) was calculated as MCAVsystolic − MCAVdiastolic / MCAVmean. Cerebral autoregulation was calculated as transfer function gain between spontaneous beat-to-beat changes in mean blood pressure and MCAVmean. Results: Cerebrovascular stiffness (PI) was increased following the HFM (pre: 0.81±0.12, post: 0.92±0.15; p<0.001). Cerebrovascular autoregulation indexed as transfer function gain was elevated following the HFM in the very low, low, and high frequency ranges ( p=0.01 for all). Pulsatility index and transfer function gain were correlated in the low frequency range before (R=0.77, p<0.01) and after (R=0.64, p=0.02) the HFM. Conclusion: These preliminary data indicate that a single HFM reduces indices of cerebral vascular function/health. Lastly, there is a positive relationship between PI and transfer function gain. Future work will continue to build upon these findings in a larger data set and will consider the impact of long-term exposure to a traditional HFM diet. Funding: The University of Texas at Arlington College of Nursing and Health Innovation and Institutional Start up Funds to Dr. Brothers. 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.
AGPAT3 deficiency impairs adipocyte differentiation and leads to a lean phenotype in mice
Authors: Zhou Hongyi , Chen Weiqin 
Published: May 2024

Acylglycerophosphate acyltransferases (AGPATs) catalyze the de novo formation of phosphatidic acid to synthesize glycerophospholipids and triglycerides. AGPATs demonstrate unique physiological roles despite a similar biochemical function. AGPAT3 is highly expressed in the testis, kidney, and liver, with intermediate expression in adipose tissue. Loss of Agpat3 is associated with reproductive abnormalities and visual dysfunction. However, the role of AGPAT3 in adipose tissue and whole-body metabolism has not been investigated. We found that male Agpat3-KO mice exhibited reduced body weights with decreased white and brown adipose tissue mass. Such changes were less pronounced in the female Agpat3-KO mice. Agpat3-KO mice have reduced plasma insulin growth factor 1 (IGF1) and insulin levels and diminished circulating lipid metabolites. They manifested intact glucose homeostasis and insulin sensitivity despite a lean phenotype. Agpat3-KO mice maintained an energy balance with normal food intake, energy expenditure, and physical activity, except for increased water intake. Their adaptive thermogenesis was also normal despite reduced brown adipose mass and triglyceride content. Mechanistically, Agpat3 was elevated during mouse and human adipogenesis and enriched in adipocytes. Agpat3-knockdown 3T3-L1 cells and Agpat3-deficient mouse embryonic fibroblasts (MEFs) have impaired adipogenesis in vitro. Interestingly, pioglitazone treatment rescued the adipogenic deficiency in Agpat3 deficient cells. We conclude that AGPAT3 regulates adipogenesis and adipose development. It is possible that adipogenic impairment in Agpat3 deficient cells potentially leads to reduced adipose mass. Findings from this work support the unique role of AGPAT3 in adipose tissue. This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases [1R56 DK135657] and the National Heart, Lung and Blood Institute [2R01HL132182-01] to W.C. 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 At-Risk Drinking on Ambulatory Blood Pressure in Young Adults
Authors: Pham Jonathan , Chang Keng-Yu , Haun Tabitha , Truong Preston , Gil Alfredo , Phan Kelly , Liu Zhaoli 
Published: May 2024

Introduction: At-risk drinking is associated with an increased risk of cardiovascular diseases (CVD) even in young adults. However, this association is mainly based on offce blood pressure (BP) measurement. Ambulatory BP monitoring captures diurnal variation in BP and is a more sensitive CVD predictor than offce BP. Therefore, the purpose of this study is to investigate the effects of at-risk drinking on ambulatory BP in young healthy adults with normal offce BP. Method: A total of 20 healthy men and women (21-35 years), non-smokers, were included in this cross-sectional study. All participants had an offce BP lower than 130/80 mmHg. Using the US Alcohol Use Disorders Identification Test (USAUDIT), at-risk drinkers were defined as those having a total USAUDIT score higher than 7 for men (6 for women). All participants underwent 24-hour ambulatory BP monitoring (Oscar 2™, SunTech Medical®). To investigate the vascular mechanisms underlying the effects of at-risk drinking on ambulatory blood pressure, aortic arterial stiffness and wave reflection were measured as pulse wave velocity (PWV) and augmentation index (AIx) by using SphygmoCor XCEL system (AtCor Medical). Results: No differences were found in age and BMI between at-risk drinkers (n=10) vs. low-risk drinkers (n=10; mean ± SD for age: 26.7 ± 3.7 vs. 26.6 ± 4.3 years, P>0.99 and BMI: 24.5 ± 2.4 vs. 23.8 ± 2.9 kg/m2, P=0.6). At-risk drinkers had a higher total USAUDIT score (10.6 ± 2.7 vs. 1.4 ± 1.2, p<0.001). While there was no difference between at-risk drinkers and low-risk drinkers in 24-hour, daytime, and nighttime systolic and diastolic BP (P≥0.5), at-risk drinkers had a higher blood pressure morning surge compared to low-risk drinkers (systolic: 34 ± 10 vs. 22 ± 6 mmHg, P=0.014 and diastolic: 29 ± 9 vs. 15 ± 4 mmHg, P=0.002). No significant difference was found in PWV (5.7 ± 0.6 Vs. 5.5 ± 0.7 m/sec, P=0.4) and AIx (8 ± 8 Vs. 15 ± 11, P=0.1). Conclusion: Our results indicate that despite similar offce BP, young adult at-risk drinkers had higher BP morning surge, an independent risk factor for cardiovascular events, than low-risk drinkers. These findings provide implications in using USAUDIT and out-of-offce BP measurements for cardiovascular disease risk assessment. This work was supported by NIAAA AA028537 to CLH. 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.
TRIM Enhances Angiogenesis in Dystrophic Muscle 140 Days Post Treatment
Authors: Naman Alexandra , Kendra Jacob , Brow Richard , Segal Steven , Morton Aaron 
Published: May 2024

Background: Duchenne Muscular Dystrophy (DMD) causes limb muscle dysfunction and impaired mobility while promoting ischemia in effected muscles. For treatment, we developed a novel biomaterial, Time Release Ion Matrix (TRIM), that promotes angiogenesis and enhances muscle structure and function in dystrophic (D2. mdx) mice at 14- and 70-days post injection (dpi). Whether TRIM remains effective at 140 dpi is unknown. Hypothesis: At 140 dpi in D2. mdx mice TRIM will: 1) enhance isometric force and myofiber cross-sectional area (CSA) of the tibialis anterior (TA) muscle; and 2) stimulate angiogenic growth factors and increase vascularity. Methods: The right and left TA of adult male D2. mdx mice (male, n=7-8, age 7 months) were injected with saline alone (control) or 250 μg of TRIM suspended in saline. At 140 dpi, the left TA muscle was isolated for in situ muscle force measurements and histological analysis; the right TA was frozen for biochemical analysis. Muscle cross-sections were immunostained for laminin (myofiber borders), DAPI (nuclei), and CD31 (endothelial cells). Vascular endothelial growth factor (VEGF) ELISA and immunoblots were performed on muscle homogenates. Results: No difference in peak isometric force was recorded between groups at 140 dpi (means ± SE: TRIM, 65.4 ± 2.7g; Saline, 62.7 ± 1.5g; P= 0.34). TRIM enhanced the relative frequency of myofibers >1000 μm2 by 27% vs. saline (TRIM, 56 ± 2%; Saline, 44 ± 3%; P= 0.006). DAPI staining revealed a 36% increase in central nuclei indicating myofiber regeneration (TRIM, 30.0 ± 1.7%; Saline, 22.0% ± 2.5; P=0.02). Microvessel area (CD31 staining, μm2) was 2.5-fold greater in treated TA’s (TRIM, 131 ± 12 μm2; Saline, 53 ± 6 μm2, P=0.0001). In muscle homogenates, TRIM had no effect on [VEGF] (TRIM, 102 ± 5%; Saline, 100 ± 4%; P= 0.79), while STAT3 activation was greater (TRIM, 129 ± 11%; Saline, 100 ± 7%; P= 0.04). Conclusion: At 140 days following injection of TRIM into the TA muscle of dystrophic mice, peak isometric force was unchanged while myofiber CSA was enhanced. Furthermore, TRIM promotes angiogenic growth factors and muscle vascularity, which should promote the ability to sustain physical activity. University of Missouri Coulter Biomedical Accelerator (SSS), American Physiological Society SURF (AGN), Texas A&M Department of Kinesiology and Sport Management (ABM). 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.
Flipped Team-based Learning as Universal Design for Learning Physiology
Authors: Terson de Paleville Daniela 
Published: May 2024

Universal Design for Learning (UDL) is an educational framework to guide the design of learning environments that are both accessible and challenging. The UDL follows three principles: Multiple means of engagement, multiple means of representation, multiple means of action and expression Lessons plan using UDL anticipates various learning styles, different interests, academic backgrounds, disability status, age, gender, race, and ethnicity. Constructivism is a learner-centered theory of learning in which the instructor is considered a facilitator. In social constructivism, learning is facilitated through interactions with peers and instructors who can guide and support learning. Team-based learning (TBL) is an example of social constructivism. In this session, participants will learn how to implement the various stages of TBL for Biomedical Sciences that could be easily translated into other disciplines. Michelsen & Sweet introduced the essential elements of TBL as a guide for instructors to implement this approach in higher education courses. The main goal of TBL is "ensuring that students have the opportunity to practice course concepts to solve a problem." The model presented by Michelsen consists of 5-7 learning modules that follow three-step cycles: 1) preparation step (pre-class). This step was created as "flipped" classroom with a variety of learning methods, assessments and virtual labs with immediate feedback to facilitate preparedness for step two 2) Step two is class readiness assurance; in this step, students take a two-step quiz process. First, students complete a quiz individually and submit their answers in scantron form. Subsequently, students re-take the quiz using the Immediate Feedback Assessment Technique (IF-AT) as a team. Afterwards, students can challenge any questions they may have missed. Then, the instructor spends the last 10-15 minutes of the class for a short lecture to clarify misconceptions and review the questions. The readiness assurance portion lasts between 45-75 minutes. Finally, 3) step 3 is called "Application of Course Concepts," in which application assignments are given to the teams. This period takes 1-4 hours, and thus, the most significant component of TBL is application. We hypothesize that flipped TBL can be effectively used as a UDL for undergraduate and graduate physiology courses. Undergraduate and graduate students report better understanding of concepts, engagement, and inclusion after participating on a TBL course. Conclusion: Flipped TBL is a powerful and effective teaching strategy to create an inclusive environment in physiology courses. APS Teaching Career Enhancement Award and University of Louisville Department of Physiology. 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.
Mitochondria Regulate Spatiotemporal Ca2+ Dynamics Between Cellular Compartments Affecting the Intrinsic Excitability of Vasopressin Neurons
Authors: Kirchner Matthew , Stern Javier 
Published: May 2024

Calcium (Ca2+) is a critical secondary messenger in all neurons that coordinates important mechanisms of cell physiology. In vasopressin (VP) neurons of supraoptic nucleus (SON) it’s required for somatodendritic release of VP and the slow afterhyperpolarization (sAHP), both of which coordinate neuronal output and thus control stimulus-secretion coupling. Recently, our lab demonstrated that VP sAHPs require endoplasmic reticulum (ER) Ca2+ for activation and that mitochondrial Ca2+ buffering shapes the spatiotemporal trajectory. We also have recent data demonstrating electrotonic segregation between cell compartments. Given the Ca2+ dependence of somatodendritic release and sAHPs, delineation of somatodendritic release from axonal release, and the decoupling of somatic and dendritic electrontonic properties, we hypothesized that calcium dynamics also may be compartmentally segregated as well. Utilizing patch clamp electrophysiology, live calcium imaging, and focal UV uncaging, we probed the spatiotemporal trajectory of rapidly evoked Ca2+ responses in VP neuron somas and dendrites with corresponding membrane potential. UV Ca2+ uncaging at the soma evokes a membrane sAHP and robust increase in cytosolic Ca2+ that propagates into the dendrites. Conversely, Ca2+ uncaged in dendrites propagates bidirectionally from the UV flash but does not penetrate the soma; no membrane hyperpolarization was observed under these conditions. Disabling mitochondrial Ca2+ buffering with Ru360 in the pipette amplifies Ca2+ signasl and sAHPs in somas and dendrites; Ca2+ uncaging in dendrites penetrates soma and can evoke sAHPs under these circumstances. Together, these results suggest that under normal conditions, Ca2+ movement between compartments in VP neurons is unidirectional (soma to dendrite), and that sAHP channels require somatic Ca2+ increases. Moreover, Ca2+ uptake by mitochondria is a critical mechanism that tightly controls the magnitude and progagation of dendritic Ca2+ signals between dendritic and somatic compartments, thus playing an important role in regulating intrinsic mechanisms and ultimately, their neuronal output. NIH K99HL168434 (M.K.K.); R01 HL162575-01 (J.E.S.). 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.