bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exacerbated cardiac dysfunction after myocardial infarction in offspring from obese parents
Authors: Omoto Ana Carolina Mieko , da Silva Alexandre , Hall John E. , Dai Xuemei , Larson Kylie , Ladnier Emily , Mouton Alan 
Published: May 2024

The prevalence of obesity in women of reproductive age is increasing rapidly, and children from obese mothers are at higher risk of developing cardiovascular diseases in adulthood. Acute myocardial infarction (MI) is one of the leading causes of death worldwide with more than one million deaths per year in the U.S. alone. Using a model of parental obesity with male and female Sprague-Dawley rats fed a high fat diet (HFD) prior to mating, and dams maintained on the HFD during gestation and lactation, we found that male and female offspring from these obese parents have multiple metabolic abnormalities early in life (3 weeks old), and that male, but not female, offspring have impaired diastolic function associated with reduced cardiac SIRT3 expression and mitochondrial biogenesis. At 24 weeks of age, male offspring from obese parents exhibit increased blood pressure. To examine if offspring from obese parents are at greater risk of death and worse cardiac function after MI, male and female lean offspring fed a normal diet (ND) born from ND fed lean parents (ND-Offs, n=5-6/sex) and lean offspring fed ND born from HFD fed obese parents (HFD-Offs, n=6-11/sex) were submitted to a permanent left descending coronary artery ligation to induce MI at 12 weeks of age. Twenty-four-hour survival rate post-MI surgery was examined and cardiac function was measured by intraventricular catheterization with a Millar catheter on day 7 post-MI. Compared to ND-Offs, male and female HFD-Off born from obese HFD-fed parents exhibited reduced survival rate (male: 60% vs 100% and female: 55% vs. 83% for HFD-Offs and ND-Offs, respectively) and increased ventricular fibrillation post-MI. At day 7 post-MI, we observed reduced +dP/dtmax in male, but not female, HFD-Offs compared to ND-Offs (6,554±25 vs. 8,253±440 mmHg/sec in males and 7,962±557 vs. 7,668±890 mmHg/sec in females, for HFD-Offs and ND-Offs, respectively) despite similar infarct size in all groups (~40% of the total left ventricle circumference). We found no major differences in -dP/dtmin or tau (indices of diastolic function) between groups. Thus, parental obesity is associated with increased mortality rate in their offspring after induction of MI and worse systolic function in male, but not female, offspring even when offspring are fed a healthy diet after weaning and remain lean. NIDDK 1R01121411 (do Carmo), HL1630376 (da Silva/do Carmo), NIGMS P20GM104357 (Hall), P30GM149404 (Hall) and U54GM115428 (Hall). 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.
Obesity increases cardiovascular strain during passive heat stress in middle-aged women
Authors: Wolf S. Tony , Kenney W. Larry 
Published: May 2024

Heat waves are becoming more frequent and severe, and cardiovascular events are a contributing cause in most heat-related deaths. Obesity is reported in over 40% of adults over the age of 40 yrs, and is associated with greater heat-related mortality, although the precise mechanisms are not well-understood. To determine whether obesity increases heat-related cardiovascular vulnerability in middle-aged women, this study examined cardiovascular responses to passive whole-body heat stress in four obese (54 ± 11 yr; BMI: 33.1 ± 2.8) and four non-obese (55 ± 5 yr; BMI: 23.6 ± 0.8) middle-aged women. Red cell flux was measured at each site by laser-Doppler flowmetry (LDF) while reflex vasodilation was induced via whole-body heating using a water-perfused suit. After a 1.0°C rise in gastrointestinal temperature (ΔTgi), local skin temperature was increased to 43°C to elicit a maximal vasodilation response. Cutaneous vascular conductance was calculated (CVC = LDF/mean arterial pressure) and expressed as a percentage of maximum (%CVCmax) for each ΔTgi of 0.1°C. Heart rate (HR) was measured continuously and blood pressure (BP) was measured at each ΔTgi of 0.1°C, and rate pressure product (RPP; HR x systolic BP) was calculated as an index of cardiac strain. Percent body fat was measured with dual x-ray absorptiometry (DXA). Time to reach a ΔTgi of 1.0°C was not different between groups (Obese: 65 ± 16 min; Non-obese: 63 ± 13 min; p = 0.85). There was no group difference in CVCmax (Obese: 2.5 ± 0.6; Non-obese: 2.01 ± 0.3; p = 0.19). Likewise, there were no group differences in %CVCmax at baseline or any point throughout local heating (all p ≥ 0.47). RPP was not different between groups at baseline (Obese: 8840 ± 1160; Non-obese: 7492 ± 1081; p > 0.99), but increased to a greater degree in obese women such that there was a significant difference at ΔTgi of 1.0°C (Obese: 14162 ± 1910; Non-obese: 11393 ± 3448; p = 0.05). Further, %BF was directly related to peak RPP (p = 0.03; r = 0.75), but not resting RPP (p = 0.16). Obese women demonstrated an exaggerated RPP response for a given rise in %CVC (p < 0.0001, r = 0.82) relative to non-obese women (p = 0.21, r = 0.19; difference between slopes = 0.002). These data suggest that although thermoregulatory responses are preserved in obese middle-aged women relative to their non-obese counterparts, cardiovascular strain may be exaggerated in obese women for a given magnitude of thermoregulatory response, potentially contributing to increased heat-related mortality. This work was supported by NIH F32 AG079581 (STW) and a seed grant from the University of Georgia Obesity Research Initiative (STW). 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.
Role of CRF1 and CRF2 Receptors in Stress-induced Increase of Intestinal Epithelial Permeability in the Mouse Colon
Authors: Liu Sumei , Sargent Caroline , Broman Lauren , Yao Daniel 
Published: May 2024

Background and Aims: Stress is known to increase intestinal permeability, which may contribute to the development of irritable bowel syndrome (IBS) and other intestinal disorders. Corticotropin releasing factor (CRF) has been proven to mediate stress-induced changes in gut function, such as increased colonic motility, ion secretion, and intestinal permeability. Actions of CRF are mediated by two G-protein coupled receptors, CRF1 and CRF2; both are expressed in the intestine. However, the roles of the CRF1 and CRF2 receptors in stress-induced increase of intestinal epithelial permeability remain unknown. Methods: Adult male and female C57BL/6 mice were restrained (1h/d) for five consecutive days. The selective CRF1 and CRF2 receptor antagonists were injected intraperitoneally 15 min prior to the restraint stress. Control mice were kept in their home cages without restraint. After the last restraint stress/control session, the proximal colon was removed, and the mucosa/submucosa preparations were dissected and mounted onto the Ussing Chamber System for the measurement of intestinal permeability. Transepithelial resistance (TER) and FITC-inulin (4kD) flux across the colonic epithelium were used as indicators of paracellular permeability. Horseradish peroxidase (HRP, 40kD) flux was used to measure transcellular permeability. Results: Restraint stress did not alter TER or FITC-inulin flux in male mice. Pretreatment with the CRF1 receptor antagonist NBI 27914 or the CRF2 receptor antagonist antisauvagine-30 had no effect on TER or FITC-inulin flux in male mice. In female mice, restraint stress significantly reduced TER and increased FITC-inulin flux in the proximal colon, which were blocked by NBI 27914 but not by antisauvagine-30. Restraint stress significantly increased HRP flux in both male and female mice. In male mice, pretreatment with NBI 27914 significantly reduced stress-evoked increase of HRP flux, while antisauvagine-30 had no effect. In female mice, both NBI 27914 and antisauvagine-30 significantly reduced stress-evoked increase of HRP flux. Conclusions: Stress evokes different changes in epithelial permeability in the proximal colon of male and female mice. In male mice, stress does not influence paracellular permeability but increases transcellular permeability, which is mediated by the CRF1 receptor. In female mice, stress increases both transcellular and paracellular permeability. Stress-induced increase of paracellular permeability was mediated by the CRF1 receptor, but the increased transcellular permeability was mediated by both CRF1 and CRF2 receptors. University of Wisconsin-La Crosse Undergraduate Research Grant (CS and LB). 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.
Embedding undergraduate Research Experience in Human Physiology Labs at Salt Lake Community College
Authors: Taylor Kristen , Mendoza Evelyn , Stosich Feldman Jo 
Published: May 2024

We completely overhauled the laboratory portion (BIOL 2425) of our Human Physiology course at Salt Lake Community College. Our objective was to create a laboratory component that allows students to explore Human Physiology more deeply through iterative and connected projects that scaffold into a group Course-based Undergraduate Research Experience (CURE). We report the results from seven semesters of weekly student assessments. Our findings suggest that implementing this CURE increases undergraduate involvement in research and helps students achieve a deeper understanding of Human Physiology concepts. The Allen Foundation SLCC School of Science, Math, and Engineering. 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.
Fibrotic Fibro-Adipogenic Progenitors Produce an Altered Extracellular Matrix that Impairs Myogenesis
Authors: Loomis Taryn , Wohlgemuth Ross , Smith Lucas 
Published: May 2024

Introduction: Fibrosis is the pathological accumulation of extracellular matrix (ECM) components, impairing tissue function. In skeletal muscle, the main source of ECM deposition are fibro-adipogenic progenitors (FAPs). FAPs can signal to muscle satellite cells (MuSCs) through soluble factors and ECM deposition. FAPs are more highly activated into myofibroblasts in fibrotic conditions, but how this affects their signaling to MuSCs is unknown. Cell-derived matrices (CDMs) can be synthesized from FAPs to investigate their ECM deposition. The goal of this study was to understand how FAPs are signaling to MuSCs through their ECM deposition. We hypothesized that FAPs isolated from mdx mice, a model for skeletal muscle fibrosis, would have increased collagen deposition compared to wt FAPs and would produce a matrix that reduces myogenesis. Methods: FAPs were isolated from the lower limb muscles of wt and mdx mice. FAPs were plated in media containing 50μM ascorbic acid to promote collagen deposition for 2 weeks in order to synthesize CDMs. CDMs were imaged using second harmonic generation (SHG) imaging to visualize collagen organization. Some CDMs were solubilized and replated to create a flat protein coating of matrix. MuSCs were then plated on the CDMs, solubilized matrix, in a transwell co-culture with FAPs, and on plastic in differentiation media for 5 days. Results: There was a significant negative correlation between the level of FAP activation into myofibroblasts and the MuSC differentiation index, independent of if the FAPs were isolated from wt or mdx mice. SHG images revealed CDMs derived from mdx FAPs had less aligned collagen fibrils compared to wt CDMs. Conclusions: High activation into myofibroblasts is often an indicator of a fibrotic FAP phenotype. The negative correlation between myofibroblasts and MuSC differentiation found here indicates this phenotype impairs myogenesis. FAPs in transwell co-culture did not have a significant effect on MuSC differentiation, highlighting the importance of ECM deposition rather than soluble signaling is important in FAP signaling to MuSCs. Targeting FAPs activation into myofibroblasts provides a therapeutic target to attenuate fibrosis and improve regeneration in skeletal muscle. Research reported in this publication was supported by the National Institute Of Arthritis And Musculoskeletal And Skin Diseases of the National Institutes of Health under Award Number F31AR082700. The content is solely the responsibility of the authors and does not necessarily represent the offcial views of the National Institutes of Health. 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.
Modulation by Astrocytes of AMPA Currents in the NTS Neurons of Mice Is Reduced by Short Term-Sustained Hypoxia
Authors: Accorsi-Mendonça Daniela , Lima-Silveira Ludmila , Machado Benedito H 
Published: May 2024

Hypoxia due to reduction in the partial pressure of oxygen in the arterial blood (PaO2) activates the afferents of peripheral chemoreflex to produce cardiovascular and respiratory adjustments to bring PaO2 back to the normal range. Herein we evaluated the possible changes of astrocytic modulation on glutamatergic transmission in NTS neurons of mice submitted to short term-sustained hypoxia (SH). To reach this goal, we used Male C57Bl/6J mice (18-20g), which were submitted to SH (FiO2 0.1) or normoxia for 24 hours. Brainstem slices and whole-cell patch clamp technique were used to evaluate the synaptic transmission in NTS neurons. The intracellular calcium concentration in NTS astrocytes was evaluated by multiphoton microscopy and transgenic Aldh-CRE-GCAMP6f mice (Institutional Ethical Committee Approvals: #016/2018 and #1109/2022R1). SH increased the amplitude of TS-evoked AMPA currents [control: -72.8 ± 13.3 pA ( n = 12) vs SH: -120 ± 14.4 pA ( n = 21)] in NTS neurons with no changes on the rise- or decay-time. SH also increased the amplitude [control: 35.88 ± 7.9 pA ( n = 12) vs SH: 72.74 ± 15.47 pA ( n = 10)] and decay time [control: 61.8 ± 15.2 ms ( n = 9) vs SH: 286 ± 86.7 ms ( n = 10)] of TS evoked-NMDA currents in neurons, while the amplitude of extrasynaptic NMDA currents [control: 28.7 ± 7.4 pA ( n = 10) vs SH: 24.7 ± 3.2 pA ( n = 7)] was not affected. Perfusion with fluoracetate (FAC), a glial metabolism inhibitor, decreased the amplitude of TS-evoked AMPA currents in control group [aCSF: -54.29 ± 16.1 pA vs aCSF + FAC: -24.43 ± 6.82 pA ( n =9)] without affecting AMPA currents in SH neurons [aCSF: -124.5 ± 35.27 pA vs aCSF + FAC: -130.5 ± 50.16 pA ( n =8)]. The passive properties of astrocytes did not change after SH [RMP: -83.73 ± 11.85 mV ( n =10) vs −83.63 ± 11.86 mV ( n =10); Rinput: 123 ± 127.5 MΩ ( n =9) vs 208 ± 212.7 MΩ ( n =10)]. The increase in intracellular calcium concentration induced by AMPA in the astrocytes of control and SH mice was similar [Control: 112.8 ± 15.41 ΔF/F0 (n=68 ROIs) vs SH: 56.38 ± 18.31 ΔF/F0 (n=13 ROIs)]. The data shows that SH increased the evoked glutamatergic currents in NTS neurons of mice, probably due to a reduction in the astrocytic modulation of excitatory transmission by mechanisms apparently independent of astrocytic intracellular calcium. FAPESP (2018/15957-2, 2018/02336-0 and 2022/05237-8), CNPq (309338/2020-4) and CAPES-PROEX (23038.006922/2021-31). 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.
Impaired excitability of nucleus tractus solitarius neurons in a neonatal rat model of hyperbilirubinemia
Authors: Mayer Catherine , Rickman Nicholas , Bearer Cynthia , MacFarlane Peter 
Published: May 2024

Hyperbilirubinemia is associated with multiple morbidities including apnea of prematurity in preterm infants. Bilirubin, a byproduct of hemoglobin breakdown, is not excreted normally and results in high circulating levels giving rise to a state of hyperbilirubinemia. Free bilirubin (not bound to albumin) can cross the blood-brain barrier and be neurotoxic. Prior studies have shown that a systemic injection of bilirubin accumulates in the brainstem and is associated with an impaired ventilatory response to hypercapnia and an augmented hypoxic ventilatory depression. Here, using the Gunn rat model of endogenous hyperbilirubinemia, we investigated its effects on the excitability of neurons of the nucleus tractus solitarius (NTS). The homozygous Gunn rat (jj) model of hyperbilirubinemia lacks uridine diphosphate-glucuronosyltransferase-1A1, an enzyme which is needed to catabolize bilirubin. Heterozygous Nj Gunn rat pups were used for control. On postnatal (P) day 5, Nj and jj rat pups received either a 200mg/kg intraperitoneal injection of sulfadimethoxine (SDMX), which dissociates bilirubin from albumin resulting in increased levels of circulating free bilirubin, or an equivalent amount of saline as a vehicle control. Whole cell patch clamp was performed on NTS neurons two days later (P7) to assess characteristics of evoked excitatory postsynaptic currents (eEPSC).The amplitude of the evoked stimulus response to a 20Hz stimulus train was significantly increased in NTS neurons from jj+saline pups when compared to cells from Nj+saline and Nj+SDMX animals (p<0.05). This increased amplitude was no longer present after SDMX treatment of jj pups. Additionally, jj+saline NTS neurons did not exhibit any failure to solitary tract stimulation, whereas SDMX treatment significantly increased the failure rate during a 20Hz stimulus train (jj+saline =0.0%±0.0, jj+SDMX= 18.63%±8.82, p<0.05). Comparison of failure rate of jj+saline to Nj+saline (6.63%±3.12, p<0.05) was also statistically significant. The hyper-responsive NTS neurons of jj+saline rats may be an adaptive response to the deleterious effects of circulating (bound and unbound) bilirubin. However, the impaired response of neurons in jj+SDMX rats may reflect neurotoxic effects of increased free bilirubin leading to impaired neurotransmission. The latter is consistent with the high failure rate of NTS neurons in jj+SDMX rats. These data may have implications for impaired respiratory control mechanisms involved in mediating essential vagally mediated ventilatory defense responses to hypoxemia and may contribute to the apnea of prematurity associated with hyperbilirubinemia in preterm infants. William and Lois Briggs Endowment. 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.
Enteral Agonism of the Farnesoid X Receptor-Fibroblast Growth Factor 19 Axis Prevents Cholestasis in TPN-Fed Piglets
Authors: Elefson Sarah , Vonderho Caitlin , Melendez Hebeib Valeria , Stoll Barbara , Mohammad Mahmoud , Chacko Shaji , Guthrie Gregory 
Published: May 2024

Total parenteral nutrition (TPN) administration provides necessary nutrients to infants who cannot tolerate enteral feedings. However, the use of TPN can result in cholestasis which can cause parenteral nutrition-associated liver diseases. Previous mitigation strategies for cholestasis have included administering bile acids enterally to encourage normal bile acid metabolism. The objective of this study was to determine if treatment of either ursodeoxycholic acid (UDCA), Tropifexor (TPX), or fibroblast growth factor 19 (FGF19) will prevent cholestasis in a piglet TPN model through the activation of the farnesoid X receptor (FXR)-FGF19 axis. We hypothesize that UDCA will have minimum effects on FXR while TPX, a potent FXR agonist, will significantly affect the FXR pathway, and FGF19 will reduce bile acid synthesis to alleviate cholestasis. Piglets received TPN for 3 weeks and were treated enterally with either UDCA (25 mg/kg*day) or TPX (7.5 μg/kg*day) with minimal milk-based formula (12 mL/kg*day), or daily intravenous FGF19 (0.25 mg/d) injection. Body weight gain was not different after 3 weeks. Plasma markers of cholestasis such as of total bile acids, bilirubin, and gamma-glutamyl transferase were lower in pigs that received TPX compared to the control treatment at the end of the study. Circulating levels of FGF19 and tissue concentrations of total bile acids were not different across treatments. In the ileum, TPX increased mRNA expression of FGF19, ileal lipid binding protein, and organic solute transporter α compared to the control pigs. All treatments reduced the mRNA expression of apical sodium-dependent bile acid transporter compared to the control treatment. TPX also increased mRNA expression of small heterodimer protein and bile salt export pump in the liver. Overall, we conclude that UDCA and FGF19 had minimal effects on cholestasis, whereas TPX prevented cholestasis in part via activation of the FXR-FGF19 axis in TPN fed piglets. NIDDK R01-DK094616 K01 DK129408 T32 NIH grant DK07664. 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.