bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of Gasdermin D Pore Formation to NLRP3 Inflammasome Product Secretion and Pyroptosis in Podocytes during Obesity-Induced Glomerulopathy
Authors: Huang Dandan , Ren Jenna , Zou Yao , Kidd Jason , Gehr Todd , Li Pin-Lan , Li Guangbi 
Published: May 2024

NLRP3 inflammasome activation in podocytes has been reported to play an important role in the development of glomerular inflammation and sclerosis during obesity. Although, the molecular mechanism mediating the secretion of NLRP3 inflammasome products to induce local inflammatory response remains poorly understood. Given that gasdermin D (GSDMD) has been found to form oligomeric pores on plasma membrane for release of inflammasome product and execution of pyroptosis, the present study tested whether GSDMD pore contributes to NLRP3 inflammasome product secretion and pyroptosis in podocytes and thereby initiates glomerular inflammation and sclerosis in obesity-induced glomerulopathy (ORG). By Western blot analysis, we demonstrated that palmitic acid (PA) as an obesity-related danger factor dose-dependently stimulated the reduction of total GSDMD and elevation of cleaved GSDMD (GSDMD-NT) in podocytes. In vivo, glomerular decrease in total GSDMD and increase in GSDMD-NT were remarkable in wild type (WT/WT) mice on high-fat diet (HFD) compared to control mice. Urinary excretion of NLRP3 inflammasome products was also significantly increased by HFD treatment. Moreover, we found that pre-treatment with amitriptyline or MCC950 blocked NLRP3 inflammasome activation as well as GSDMD pore formation on plasma membrane of podocytes, while disulfiram prevented GSDMD pore formation without affecting NLRP3 inflammasome activation. Since acid sphingomyelinase (ASM)-ceramide signaling pathway plays a vital role in the development of ORG, we examined whether ASM activity determines GSDMD pore formation in podocytes. By atom force microscopy, a 3D topography map of a single podocyte was generated, and pore-like structures were observed in the membrane of PA-treated WT/WT podocytes. Podocytes lacking Smpd1 (gene code of ASM) gene did not show pore formation, but Smpd1 gene overexpression amplified PA-induced pore formation in podocytes. Moreover, it was found that HFD-induced GSDMD cleavage and pyroptosis in glomeruli were blocked by Smpd1 gene deletion in Smpd1−/− mice. On the contrary, podocyte-specific Smpd1 gene overexpression amplified GSDMD-NT production and pyroptosis in glomeruli. Correspondingly, HFD-induced podocyte foot process effacement and glomerular sclerosis in mice were inhibited by Smpd1 gene knockout but exaggerated by podocyte-specific Smpd1 gene overexpression. Taken together, our findings suggest that ASM-ceramide signaling pathway may control GSDMD pore formation in podocytes to determine glomerular inflammation and sclerosis in ORG. This study was supported by NIH grants DK054927 and DK120491. 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.
Cardiac autonomic function in young healthy Hispanic/Latino adults
Authors: Dalve Ashlesha , Perez Justo , Nyarko Ruby , Fatahimeiabadi Zahra , Dombroski Lindsay , Kaur Jasdeep 
Published: May 2024

The Hispanic/Latino (H/La) population in the US experiences a notably high incidence of hypertension. Recent epidemiological findings reveal that more than 50% of H/La men over the age of 20 years suffer from high blood pressure. Even among adolescents aged 8 to 17 years, H/La youth exhibit the highest prevalence of hypertension compared to other racial groups. This significantly elevates the risk of cardiovascular diseases across the lifespan of this population. H/La is the largest ethnic minority in the US, constituting 19.1% of the current population, and is projected to make up 1/3rd of the US population by 2050. As such, it is crucial to study the potential mechanism responsible for the health disparities in this population. In this study, we investigated the cardiac autonomic function by assessing the baroreflex sensitivity (BRS) and heart rate variability (HRV) in young, healthy H/La and non-Hispanic white (NHW) individuals. We hypothesized that the cardiac autonomic function (BRS and HRV) will be impaired in young healthy H/La as compared to the healthy NHW adults. Ten minutes of resting beat-to-beat blood pressure (BP; finger plethysmography) and heart rate (ECG) were measured in 14 young healthy H/La adults (11 men, 3 women) and 14 age-, sex- and weight-matched NHW adults [age (H/La: 20 ± 2yr; NHW: 22 ± 4yr; mean ± SD, p=0.32); BMI (H/La: 24 ± 2 kg/m2; NHW: 24 ± 2 kg/m2; p = 0.92); positive family history of hypertension (H/La: 21.4%; NHW: 21.4%). The resting heart rate (H/La = 59 ± 5 bpm; NHW = 55 ± 6 bpm; p = 0.12), systolic BP (H/La = 107 ± 6 mmHg; NHW = 111 ± 6 mmHg; p = 0.14) and diastolic BP (H/La = 61 ± 5 mmHg; NHW = 63 ± 6 mmHg; p = 0.46) were similar in both the groups. The respiratory rate (H/La = 14 ± 3 bpm; NHW = 14 ± 3 bpm; p = 0.41) and the sample data used (H/La = 591 ± 59 beats; NHW = 554 ± 63 beats; p = 0.12) for both the populations were similar. We found that BRS (overall gain; H/La = 24 ± 6 ms/mmHg; NHW = 27 ± 10 ms/mmHg; p = 0.39) and heart rate variability (root mean square of successive differences between normal heart beats; RMSSD, H/La = 82 ± 29 ms; NHW = 102 ± 48 ms; p = 0.101) were not significantly different between the two groups. These data suggest that baroreflex sensitivity and heart rate variability are not different between young, healthy H/La and NHW adults. Supported by Kinesiology and Health Education UT Austin Start-up Account 19-2635-91. 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.
Engineering of Genetically Encoded Calcium Channel Blockers
Authors: Liu Xiaoxuan , Zhou Yubin 
Published: May 2024

Calcium Release-Activated Calcium (CRAC) channel is a highly Ca2+-selective store-operated channel constituted by two-component mediators (STIM and ORAI) and controls a wide range of cellular functions in various tissues. Gain-of-function (GoF) mutations of CRAC channel cause excessive Ca2+ entry, which can lead to serious diseases such as tubular aggregate myopathy and Stormorken syndrome (TAM/STRMK). To solve this problem and to gain precise control of the CRAC channel, we have designed both an optogenetic and a chemogenetic strategy for engineering of CRAC channel blockers (designated Opto-CRAB and Chemo-CRAB), which can mediate Ca2+ influx and Ca2+-dependent signaling such as NFAT induced gene expression and T cell activation. Beyond in vitro applications, both Opto-CRAB and Chemo-CRAB have been applied in vivo experiments in a zebrafish model of Stormorken syndrome that resulted in the mitigation of thrombocytopenia and hemorrhage in light and chemical dependent manners. Welch Foundation (BE-1913-20220331 to Y.Z.), Leukemia & Lymphoma Society (LLS6680-24 to Y.Z.), the National Institutes of Health (R01GM144986 to Y.Z. and R21AI174606 to Y.Z.). 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.
A New Cell Type in Pulmonary Veins
Authors: Tang Yashu , Chen Yen-Lin , Bazaz Abhishek , Delancey Rachel , Daneva Zdravka , Sonkusare Swapnil K. 
Published: May 2024

Pulmonary veins (PVs) carry oxygenated blood from lungs back to the heart and may play an important role in preventing blood backflow from the left atrium. Previous studies show that large PVs exhibit spontaneously pulsatile contractions in cardiomyocyte-like manner. However, the contractions of small PVs have not been investigated. We hypothesized that Ca2+ signaling mechanisms in the myocytes mediate small PV contractions. Small, 4th-order PVs from C57BL6 mice were obtained and imaged. Pressurized PVs showed ryanodine receptor-dependent Ca2+ signals and spontaneous contractions. Light sheet fluorescence microscopy and immunostaining showed the expression of troponin C, a cardiomyocyte marker, in the myocyte layer of small PVs, which was not observed in the pulmonary arteries, vena cava, or mesenteric veins. Based on these results, we termed these cells cardiomyocyte-like (CML) cells. In the study of mice with Myh11 Cre-driven tdTomato expression, Myh11 expression was observed in CML cells in small PVs, which was not seen in the smooth muscle cells (SMC) of small PAs. Endothelial protrusions crossing the connective tissue layer into the CML layer were also observed in PVs. Previous studies showed PV remodeling in pulmonary hypertension (PH), and impaired Ca2+ signaling in PAs contribute to higher pulmonary arterial pressure in PH. We further hypothesized that ryanodine receptor (RyR) Ca2+ signals in CML cells are impaired in PH. Results show that RyR Ca2+ signaling was reduced in CML cells of PH mice (injected with Su5416, subjected to chronic hypoxic conditions). Overall, our findings identify a new cell type in small PVs. Moreover, our data show that RyR Ca2+ signals in CML cells underlie spontaneous contractions in small PV, and are impaired in PH. We propose that RyR signaling mechanisms in CML cells may be possible targets for therapy in pulmonary vascular disorders. This work was supported by funding from the National Institute of Health to Swapnil Sonkusare (R01:HL146914, R01:HL157407). 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, episodic nicotine exposure enhances the hypoxic ventilatory response in adult female rats
Authors: Wollman Lila , Fale Megan , Fregosi Ralph 
Published: May 2024

It is well known that cigarette smoking causes lung disease and damages the airways. However, we know little about the direct role of nicotine, the primary addictive component of tobacco, in the development of smoking- related diseases. Along with promoting cancer cell proliferation and airway inflammation, nicotine can modulate central respiratory control, increasing the rate and depth of breathing through mechanisms that are not well understood. In addition, cigarette smoking is associated with obstructive sleep apnea, a sleep-related breathing disorder that is marked by reduced brainstem respiratory motor output. Despite these examples indicating that chronic nicotine exposure in adulthood may alter central respiratory control, there is no published research that directly tests this hypothesis. We exposed male and female adult rats to nicotine for four weeks through their drinking water and then used whole body plethysmography to test the hypothesis that chronic, episodic nicotine exposure alters restful breathing and the hypoxic ventilatory response (HVR), a critical respiratory chemoreflex. We measured tidal volume (TV) and frequency of breathing at rest, and during a 5- minute episode of hypoxia (10% oxygen/balance nitrogen). Total ventilation (VE/VCO2) was calculated as TV X Frequency and normalized to carbon dioxide production, to account for changes in metabolism, and body weight. For both males and females, comparisons were made between groups and across trials using a 2-way ANOVA and Tukey’s post-hoc test. In male rats, nicotine exposure significantly decreased overall ventilation at rest in one of three trials (Trial 1 VE/VCO2: Nicotine exposed, 30.7±7.5 mL/min/100g, Control, 44.3±6.4 mL/min/100g, p=0.0183), but had no effect on breathing during hypoxia. In female rats, nicotine exposure had no effect on breathing at rest, however, overall ventilation during hypoxia was enhanced in nicotine exposed rats compared to controls in two of three trials (Trial 1 VE/VCO2: Nicotine exposed, 106.8±20.6 mL/min/100g, Control, 79.8±5.1 mL/min/100g, p=0.049; Trial 3 VE/VCO2: Nicotine exposed, 101.6±9.9 mL/min/100g, Control, 68.1±10.9 mL/min/100g, p=0.007). Overall, these results suggest that chronic nicotine exposure triggers plasticity in the chemoreflex pathway mediating the HVR in a sex specific manner and further studies are warranted to understand the implications of this finding. 1K99HL164973-02. 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.
A proteome perspective on adaptive responses to physiological challenges in marine mammals
Authors: Khudyakov Jane 
Published: May 2024

While most mammals decrease energy expenditure while fasting, marine mammals such as northern elephant seals fast for several months while undergoing energy-intensive life history stages (e.g., postnatal development, molting, reproduction). Energy for these functions is provided by mobilization of large energy stores in blubber, which is driven by elevation of stress hormone levels across the fast. We used a proteome approach to examine potential mechanisms regulating fasting metabolism and responses to experimental stress challenges in elephant seals. We compared five proteome datasets and identified proteins that were altered by both fasting and experimental stress challenges across multiple life history stages and tissues in seals. These included lipid and hormone transport proteins (e.g., apolipoproteins, corticosteroid-binding globulin, transthyretin), acute phase proteins (e.g., alpha-2-macroglobulin, haptoglobin), antioxidant enzymes (e.g., glutathione peroxidase 3, catalase), adipokines (e.g., mimecan), and metabolic enzymes (e.g., fatty acid synthase, long chain fatty acid CoA ligase), among others. We suggest that these proteins may function as part of a core adaptive responses to physiological challenges in marine mammals. However, our ability to identify components of these responses has been hindered by several practical and technical challenges, and we will discuss the limitations and considerations for using a proteome approach in comparative physiology studies based on our experience. This research was funded by University of the Pacific and Offce of Naval Research. 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.
Using Hissing Cockroaches to Teach Animal Physiology: Course Based Undergraduate Research Experiences
Authors: Contreras Heidy 
Published: May 2024

Early student engagement in research has been shown to improve several student outcomes such as critical thinking, problem-solving and increased confidence in scientific aptitude. However, providing every student with access to traditional research experiences is diffcult. Course-based undergraduate research experiences (CUREs) are a good alternative to traditional research experiences since they are designed to provide students with hands-on research opportunities in scientific inquiry. CUREs have been shown to be a more inclusive entry point to scientific research as they break down barriers faced by many students, especially those faced by underrepresented first generation college students. Student's that participate in CUREs have shown gains similar to those obtained from traditional research experiences including improved research skills, self-effcacy, and an intent to persist in science. In this study, we developed a CURE in an Animal Physiology course at the University of La Verne, a small HSI liberal arts college in Southern California. As part of this CURE, students were trained on handling hissing cockroaches, and worked on this model systems to answer a question on the effects of different environmental factors on the metabolic rates of these ectotherms. Students developed their own hypothesis, designed an experiment, collected and analyzed data, drew conclusions, and presented their findings through an oral presentation. We measured student learning outcomes and affective student gains. 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 eosinophilia on high fat diet-induced obesity and airway hyperresponsiveness
Authors: Proskocil Becky , Calco Gina , Jacoby David , Fryer Allison , Nie Zhenying 
Published: May 2024

Hypothesis/Rationale: Eosinophils contribute to both adipose tissue metabolic homeostasis in obesity and airway hyperresponsiveness in asthma, but the role of eosinophils in obesity-related airway hyperresponsiveness is not understood. Considering that metabolic disorders increase the susceptibility to airway hyperresponsiveness in obese individuals, we investigated whether adipose eosinophils play a protective role in obesity-related airway hyperresponsiveness. Methods: Wild type (WT) and transgenic mice that overexpress interleukin 5 in peripheral T cells (+IL5T) were fed a high fat (61.6% fat) or normal chow (13.6% fat) diet for 19 weeks. Body weight, body fat, fasting glucose and insulin, and bronchoconstriction in response to inhaled serotonin were measured. The number of eosinophils were counted using flow cytometry in lung, adipose, and blood from transgenic WT and +IL5T mice with GFP-expressing eosinophils. Data: High fat diet significantly increased body weight and body fat in both WT and +IL5T mice, however +IL5T mice gained less weight and body fat than the WT mice. High fat diet increased fasting glucose, fasting insulin, and nerve-mediated airway responsiveness to inhaled serotonin in only the WT mice. On a normal chow diet, +IL5T mice had significantly more eosinophils in lung, blood, and adipose, and high fat diet further increased eosinophils in +IL5T adipose tissue. Acute administration of 1.29 U/kg (i.p.) insulin to a WT mouse on a normal chow diet significantly potentiated airway hyperresponsiveness to inhaled serotonin. Summary of results: Eosinophils in adipose tissue prevented high fat diet increases in circulating glucose and insulin, resulting in less body weight and body fat. This reduction in insulin by eosinophils in adipose tissue prevented obesity-related airway hyperresponsiveness. Conclusions: Insulin is a key modulator of obesity-related airway hyperresponsiveness. Eosinophils in adipose tissue play an important role in preventing obesity-related airway hyperresponsiveness by modulating insulin levels. Funding: NIH HL164474, NIH HL163087. 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.
Brachial Artery Flow-mediated Dilation Is Associated with Pulmonary Vascular Structure Among Patients with Chronic Obstructive Pulmonary Disease
Authors: D'Souza Andrew , Collins Sophie , Kuss Madeline , Kirby Miranda , Smith Benjamin , Bok Eli , Fuhr Desi 
Published: May 2024

Background: Accumulating evidence indicates that pulmonary vascular insults, particularly at the level of the endothelium, may contribute to the pathogenesis of COPD. Further, the mechanism(s) underpinning pulmonary vascular remodeling/dysfunction in COPD may also contribute to systemic vascular dysfunction. Indeed, brachial artery flow-mediated dilation (FMD; an assessment of systemic vascular endothelial function) is inversely associated with emphysema among patients with COPD. However, it remains unclear whether systemic vascular function is related to pulmonary vascular structure in COPD. Thus, we aimed to evaluate the relationships between FMD and computed tomography (CT)-derived emphysema and pulmonary vascular structure in patients with mild-to-severe COPD. We hypothesized that FMD would be inversely related with CT-derived emphysema severity, and positively related with pulmonary vascular structure. Methods: 36 individuals with COPD (16 females, age: 69±6 years, FEV1: 62±19 %predicted) completed three experimental days: Day 1: Enrollment and full pulmonary function test. Day 2: Chest CT scan to quantify emphysema severity (LAA-950), total vessel volume (TVV), and the volume of vessels with a cross sectional area of <5mm2 (BV5) and between 5-10mm2 (BV5-10). Day 3: Brachial artery FMD (5-minute forearm occlusion followed by 3-minute reactive hyperemia). FMD was allometrically scaled and corrected for the prevailing shear stimulus (shear rate area under the curve). Results: FMD was not correlated with LAA-950, (r2=0.09; P=0.09); however, positive relationships were observed between FMD and TVV normalized to total lung volume (r2=0.24; P<0.01), as well as BV5-10 (r2=0.34; P<0.01). FMD was not correlated to BV5 (r2=0.09, P=0.10). Conclusion: Collectively, these preliminary data indicate that, among patients with COPD, impaired pulmonary vascular structure is associated with attenuated systemic vascular function; suggesting an interplay between the pulmonary and systemic vasculature in the pathogenesis of COPD. Supported by the Canadian Institutes for Health Research, the Canadian Respiratory Research Network, and the “Fondation Baxter et Alma Ricard”. 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.