bluuebunny/crossref_metadata_2025 huggingface dataset:
Catalyst Interaction in Unitized Regenerative Fuel Cells
Authors: Maletzko A. , Villa E. D. Gomez , Kintzel B. , Fietzek H. , Schmidt G. , Christen J. , Veit P. , Kühne P. , Bornet Aline , Arenz Matthias , Melke J.
Published: May 2024

Unitized regenerative fuel cells have emerged as promising energy conversion and storage systems for various applications. However, in order to optimize their efficiency, it is crucial to enhance the performance of the bifunctional catalyst. This study aims to provide deeper insights into the electrochemical behavior and performance of the bifunctional catalyst. Several electrocatalysts were prepared and evaluated using rotating disc electrode measurements. The primary focus was placed on investigating the interaction between Pt, Ir, and the support material, antimony doped tin oxide (ATO), and their impact on the oxygen evolution reaction and oxygen reduction reaction. Among the analyzed catalysts, Pt black mixed with synthesized IrO2 supported on developed ATO exhibited the highest performance, considering the results from both the fuel cell and electrolyzer systems.
Understanding the Mechanisms of the Gβ5/R7-RGS Complex in Pain Transmission through Single Cell mRNA Profiling
Authors: Mokhasi Neha , Staples Jenna , Zhang Jianhua , Degner Katherine , Pandey Mritunjay , Simonds William
Published: May 2024

The dorsal root ganglion (DRG) and trigeminal ganglion (TG) contain cell bodies of the peripheral sensory neurons that transmit pain signals from different parts of body to the central nervous system. Peripheral neuropathy and trigeminal neuralgia are common painful conditions that can be caused by pathologies affecting these nerves. Current clinical treatment of these conditions often relies on anticonvulsant drugs with significant neurological side effects. Lack of effective treatments of these conditions highlights the need for better therapeutic approaches. GNB5 encodes the protein Gβ5, a divergent member of the G protein β family, that binds with members (RGS6, 7, 9 and 11) of the R7 subfamily of the regulators of G signaling (R7-RGS) to form obligate Gβ5/R7-RGS complexes. The Gβ5/R7-RGS complex proteins are expressed primarily in neurons including those in the DRG and TG. They function as GTPase-Activating Proteins (GAP) to dampen signaling downstream of Gi/o-coupled receptors. Studies in our lab demonstrated that Adv-Cre+/−; Gnb5fl/fl mice lacking Gnb5 in sensory neurons have significantly reduced mechanical, thermal and chemical nociception. However, RGS7-Cre+/−; Gnb5fl/fl mice lacking Gnb5 in Rgs7 expressing neurons exhibited only diminished mechanical nociception. Additionally, treatment with GABA-B receptor antagonist 2- hydroxysaclofen abolished the inhibition of mechanical nociception in both Advillin- Cre+/-; Gnb5fl/fl and Rgs7-Cre+/-; Gnb5fl/fl mice, implicating the involvement of GABA-B receptor signaling in Gβ5/Rgs7-associated mechanical nociception. To further understand the cellular and molecular mechanisms of Gβ5/R7-RGS complex-mediated nociception, we analyzed and compared the expression profiles of the Gβ5/R7-RGS genes in DRG and TG through bioinformatic analysis of publicly available scRNAseq datasets and in situ hybridization of selected genes using RNAscope technology. We found high levels of Gnb5 expression across all sensory neuron cell types while the expressions of members of R7-RGS subfamily showed distinctive patterns among these neuron cell types. Single cell clustering analysis using known neuronal markers revealed that Rgs7 and Rgs11 were highly expressed in majority of neuron types, while Rgs6 and Rgs9 were represented in smaller, more distinct clusters. These results suggest that particular members of R7-RGS gene family might play distinct roles in different types of nociception, a finding that warrants further investigation into the individual mechanisms of each member of this gene family in pain transmission.

NIDDK Intramural Research Program ZIA DK043304-29.

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.
β-arrestin1/2 are essential for embryonic lymphatic vessel development
Authors: Tian Yanna , Kistner Bryan , Dy Danica , Douglas Elizabeth , Caron Kathleen M
Published: May 2024

Lymphatic dysfunction can lead to fetal loss due to interstitial edema known as hydrops fetalis during development and lymphedema in adulthood. Lymphedema affects an estimated 250 million individuals worldwide, yet there is no effective treatment available. Numerous studies have established G protein-coupled receptors (GPCRs) as key lymphangiogenic signaling pathways and ideal druggable therapeutical targets. β-arrestins (β-arrestin 1 and 2) are ubiquitously expressed cytosolic adaptor proteins which perform a wide range of functions in GPCR pathways, such as promoting agonist-induced internalization and forming signaling scaffolds with internalized GPCRs in endosomes. However, the roles of β-arrestins in lymphatic vessel development and function remain undefined. We hypothesize that β-arrestin1/2 are essential in embryonic lymphatic vessel development. To test this hypothesis, I used an inducible β-arrestin1fl/fl (Arrb1 fl/fl), β-arrestin2fl/fl (Arrb2 fl/fl);Prox1 CreERT2 mouse line. β-arrestin1 and 2 were deleted by oral gavage of tamoxifen at embryonic day 10.5 (E10.5) and E12.5, critical points for developmental lymphangiogenesis. Compared to Arrb1/2fl/flembryos, the Arrb1/2fl/fl;Prox1CreERT2 embryos exhibit profound hydrops fetalis, subcutaneous hemorrhages, and increased embryonic lethality between E14.5 and E16.5. At E15.5, the Arrb1/2fl/fl;Prox1CreERT2 embryos with edema show decreased weight indicating growth restriction compared to controls. Jugular lymphatic sacs are enlarged and filled with blood in Arrb1/2fl/fl;Prox1CreERT2 embryos compared to controls. Dermal lymphatic vessel length in the Arrb1/2fl/fl;Prox1CreERT2 embryos is shorter than controls. Collectively, our results demonstrate that loss of β-arrestin1/2 expression in lymphatics causes mid-gestational arrest in lymphatic development and fetal growth restriction, indicating that β-arrestins are required for developmental lymphangiogenesis in mammals.

American Physiological Society postdoctoral Fellowship (to YT) and NIH R01 HL129086 (to KMC).

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.
Brown Fat: A Beta Way to Burn Calories, but Which Beta?
Authors: Ewell Taylor , Bomar Matthew , Brown David , Cyphers Reagan , Kwarteng Beatrice , Thomson David , Johnson Blair
Published: May 2024

Brown fat is a thermogenic tissue that may have therapeutic value for the treatment of obesity and diabetes. That brown fat is under sympathetic control is indisputable, but considerable controversy exists as to which of the beta-adrenergic receptor subtypes, b1AR, b2AR or b3AR, is the primary regulator. The purpose of the current study was to determine if co-administration of the b3AR agonist, mirabegron, would increase energy expenditure and brown fat activation more than non-selective bAR stimulation (isoproterenol) alone. 14 healthy, active young adults (8 males, 6 females) participated in a randomized crossover study. Energy expenditure in a temperature-controlled room (22.1 deg C, 48.5% relative humidity) was determined at rest and after ingestion of placebo or mirabegron (100mg), prior to intravenous administration of isoproterenol (30 minutes at 6, 12, and 24 ng/kg fat free mass/min). Brown fat activity was estimated using supraclavicular skin temperature assessed via infrared thermography. Baseline energy expenditure was not different ( P=0.42) prior to placebo (1487±106 kcal/day; (mean±SE)) and mirabegron (1424±104 kcal/day). Non-selective bAR stimulation increased energy expenditure above baseline (11.6±5.5, 15.2±6.3 and 20.1±6.0%; P<0.05); additional b3AR stimulation did not augment this response (18.0±3.8, 23.2±4.2 and 27.8±4.5%; P>0.05). Baseline supraclavicular skin temperature was not different ( P=0.95) prior to placebo (35.004±0.967◦C) and mirabegron (34.992±0.967◦C). Only the greatest dose of non-selective bAR stimulation increased supraclavicular skin temperature above baseline (0.236±0.082◦C); additional b3AR stimulation did not augment this response (0.100±0.082◦C; P=0.09). Co-administration of a b3AR agonist did not increase energy expenditure and brown fat activation more than non-selective bAR stimulation alone. These preliminary data imply that the b3AR might not be the primary regulator of brown fat activation in humans.

Offce of Naval Research N00014-21-1-2276.

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.
Stimulation of Naïve Adipose-Derived Stem Cells with Mesenteric Lymph from Chronic Alcohol-Fed Rats Induces IL-33 Release Associated with Cellular Necrosis
Authors: Weaver Kourtney , Molina Patricia , Souza-Smith Flavia
Published: May 2024

Our studies show that chronic alcohol feeding in rodents induced mesenteric lymphatic leakage into surrounding perilymphatic adipose tissue (PLAT) that was associated with increased fat regulatory T cells (fTregs), that were not increased in the circulation, suggesting local expansion of fTregs in PLAT. Increased visceral fTregs are implicated in age-associated insulin resistance. The IL-33 receptor, ST2, has been implicated in fTreg cell development and is critical for their accumulation in PLAT. IL-33 is released upon cell death by visceral adipose tissue stromal or adipose derived stem cells (ADSCs) and acts as an alarmin to signal tissue damage. Whether lymphatic leakage in alcohol-fed animals results in death of ADSCs, release of IL-33, and activation of the IL-33/ST2 signaling pathway leading to PLAT fTreg accumulation has yet to be explored. Here, we tested the hypothesis that stimulation of naïve ADSCs with lymph from chronic alcohol-fed animals would lead to increased IL-33 via cell death. Male Fischer 344 rats were randomized to a Lieber-DeCarli liquid diet containing 36% of calories from alcohol or pair-fed an isocaloric diet for 10 weeks (N=10/group). Mesenteric lymph was collected from anesthetized alcohol- and pair-fed animals via the lymph fistula technique. PLAT ADSCs, isolated from age-matched, naïve, chow-fed rats were cultured until adherent and stimulated with 5% v/v lymph from alcohol- or pair-fed animals for 24 hrs. Supernatant was collected, and IL-33 concentration was measured by commercially available ELISA. Adherent ADSCs were stained with 7-AAD and CytoCalcein fluorescent dyes to assess cell viability using fluorescence microscopy. Viable and necrotic cells were counted using QuPath software. Statistical differences were assessed using one-way ANOVA in GraphPad Prism. Results show a 2.5-fold increase in the concentration of IL-33 in supernatant of ADSCs stimulated with lymph from alcohol-fed animals compared to ADSCs stimulated with lymph from pair-fed animals. In addition, ADSC necrosis was 4-fold greater in wells stimulated with lymph from alcohol-fed animals than in those stimulated with control lymph or vehicle. In contrast, lymph stimulation of ADSCs from control-fed animals did not show a significant increase in IL-33 release as compared to vehicle treated controls. These data indicate presence of mediators that induce IL-33 release in lymph from alcohol-fed animals and support the hypothesized involvement of the IL-33/ST2 pathway in chronic alcohol associated ADSC cell death.

Supported by K01AA026640 (FSS), 1F30AA030909-01 (KW), 5T32AA007577-23 (PM).

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.
Biological factors and self-perception of stress in relation to freeze-like response in humans
Authors: Kucera Jan , Vit Michal , Lenart Peter , Novak Jan , Zlamal Filip , Reguli Zdenko , Bugala Martin
Published: May 2024

Many animals react to threatening stimuli such as a predator attacks by freezing. However, little experimental research investigated freeze response in humans. Here, we have employed practices commonly used in self-defense training to create two unique scenarios simulating armed physical threat. Sixty healthy men volunteers divided into three groups of twenty (untrained, trained but unexperienced, trained and experienced) underwent these scenarios accompanied by measurement of biochemical, physiological, and psychological markers of stress. Our results show that untrained individuals exhibit stronger freezing reactions, while highly skilled participants display the lowest propensity for freezing, especially in high-intensity scenarios. Moreover, the study shows variations in anxiety levels and selected biomarkers, with cortisol and osteocalcin showing different patterns in low and high-intensity scenarios, and suggests a complex interplay between these factors, electrodermal activity, and stress perception.

The project was primarily supported by the project 22-36623S from the Grant Agency of the Czech Republic. The project was supported by the project MUNI/A/1403/2018 Evaluation of self-defense scenario training and stress tolerance among students of study program SESB and ASESB by Masaryk University, Grant Agency of Masaryk University, Faculty of Sports Studies.

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 T Cell Migration from the Spleen to the Kidney in Mice at Baseline and in Response to Angiotensin II Infusion
Authors: Benson Lance , Pollock Jennifer
Published: May 2024

Decades of research has indicated that T cells contribute to the development of hypertension and target organ damage. There is a critical role of spleen-derived T cells in angiotensin II-mediated hypertension and kidney damage in mice. Splenectomy abolished sex differences in the development of hypertension in spontaneously hypertensive rats, suggesting sex differences in the spleen-kidney immune axis. It is well-appreciated that immune cells migrate from different tissues to infiltrate organs. However, whether there are sex differences in T cell migration from the spleen to the kidney remained unexplored. Thus, we hypothesized that male mice would show higher immune cell migration from the spleen to the kidney at baseline and in response to angiotensin II infusion when compared to female mice. To quantify T cell migration in male and female mice, we utilized Kikume Green-Red (KikGR) transgenic mice that ubiquitously express the kikume green protein in all cells throughout the body, and this protein can be stably photoconverted to kikume red with exposure to 405 nm blue light. We specifically photoconverted mouse spleens with 10-minute exposure to blue light and infused angiotensin II via mini-pump implantation (490 ng/kg*min) in half of the photoconverted mice. After 3 days post-photoconversion, all mice were sacrificed, and both kidneys were removed for analysis via spectral flow cytometry to determine spleen-derived infiltrating immune cells (CD45+, KikRed+ cells) as well as spleen-derived T cells (CD45+, KikRed+, CD3+) in the kidney. There were no differences in the immune cell profiles found between left and right kidneys within each sex (p = 0.8 [male kidneys] and 0.8292 [female kidneys], n = 6-10 kidneys per group). At baseline, we found significantly increased spleen-derived immune cells in the kidneys of male compared to female mice (P = 0.0173, n = 3-5 per group). In addition, sex was a significant factor in spleen-derived T cell percentages within the kidney (Two-Way ANOVA, P = 0.029, n = 3-5 mice). In response to 3 days of angiotensin II infusion, spleen-derived immune cells were significantly higher in the kidneys of males compared to females (P = 0.0499, n = 3-5 mice). We conclude that there is reduced immune cell migration to the kidney from the spleen at baseline and in response to angiotensin II infusion in female mice, which may contribute to the lower blood pressure and kidney damage observed in female mice.

NIH TL1 DK139566 to LNB, NIH R01 DK134562 to JSP.

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.
Early or late phase cardiac remodelling in metabolic syndrome heart characterized with SQT or LQT
Authors: Billur Deniz , Durak Aysegul , Olgar Yusuf , Tuncay Erkan , Turan Belma
Published: May 2024

Cardiac conduction abnormalities are the main disorders in metabolic syndrome (MetS), however, their mechanisms are not known yet. Although ventricular arrhythmia pathogenesis reflects the time course of cardiomyocyte action potentials (APs) associated with QT-interval duration, recent studies emphasize the role of intercellular crosstalk between cardiomyocytes and nonmyocytes via passive (electrotonic)-conduction. Therefore, considering the possible intercellular interactions between cardiomyocytes and nonmyocytes as electrophysiological contributors to cardiac-conduction, we hypothesized an early-cardiac-remodeling which is characterized by short QT-interval (SQT) via contributions and modulations of changes in the expressions and localizations of nonmyocytes to the ventricular APs in an early-stage MetS hearts. Significant increases in MetS (14-16 weeks) heart rates and SQT, shortened AP duration with a strong response to β-adrenergic stimulation in the contractile activity of the papillary muscles were determined. The patch-clamp analysis of ventricular cardiomyocytes showed that voltage-dependent Na+-channel currents were increased with decreased L-type Ca2+-channel (LTCC) currents and unchanged K+-channel currents. A hemichannel protein of connexin 43 (Cx43) was highly localized into intercalated discs while phospho-Cx43 was densely localized laterally on the sarcolemma and cytosol with increased total expression levels. A marked high-level positively-stained α-SMA and CD68 cells in interfibrillar spaces of the heart were prominently localized and distributed, implying the possible contributions of myofibroblasts and macrophages to both shortened APs and abnormal electrical conduction in an early-stage MetS heart.Our data propose a previously unrecognized pathway for induction of SQT in the heart: This pathway may include not only the contribution of short ventricular-APs via ionic-mechanisms but also increasing contributions of the electrotonic-cardiomyocyte depolarization, spontaneous electrical activity-associated fast heterogeneous impulse conduction in the heart via non-myocytes. Overall, SQT in early cardiac remodeling may arise with increased interactions between cardiomyocytes and non-myocytes, through increasing contributions of passive-conduction by non-myocytes.

TUBITAK SBAG-119S661 & 222S502.

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.
Comparison of acute glucose responses following combined arm and leg cycling in non and pre-diabetic males
Authors: Smith Bryan , Skillrud Linnea , Krause Alexa
Published: May 2024

Prolonged and chronic sedentary behavior contributes to negative metabolic health conditions. Recent research has shown that a single bout of combined arm and leg cycling (CALC) can improve acute glucose metabolism in non-diabetic college aged adults. If a short bout of CALC can improve glucose metabolism in individuals that are non-diabetic then one could hypothesize that a short bout of CALC may improve glucose metabolism in individuals that are pre-diabetic. We hypothesized that short bouts of CALC would result in a greater decrease in the 60-min total (tAUC) area under the curve in pre-diabetic compared to non-diabetic males. PURPOSE: To compare acute glucose responses following a short bout of CALC in non and pre-diabetic males. METHODS: College age males were recruited for this trial. Diabetes status was based upon a fasting blood glucose measurement taken after an overnight 12 hour fast. Participants completed three randomized experimental trials. Two of the experimental trials consisted of a 1-min (1M) or 5-min (5M) bout of CALC at a self-selected pace. The third trial was a non-exercise control (CON) trial. Immediately following both exercise trials and during the CON trial, participants completed a 60-min oral glucose tolerance test. A 2-way (diabetes status vs trial) repeated measures ANOVA was done to determine if there were any significant differences between the two groups and the three trials for the tAUC during the 60-min OGTT. RESULTS: A total of 18 college age males completed this study. Fasting blood glucose was 94.0 ± 3.7 and 108.1 ± 4.6 mg/dl for the non (n=8, 21.4 ± 2.4 yrs) and pre-diabetics (n = 10, 22.6 ± 3.9 yrs) participants respectively. There was a significant interaction between trials and diabetes status (p = 0.04) for tAUC. Follow-up analysis showed that within the pre-diabetic group, tAUC was significantly lower in the 5-min trial compared to the CON trial (113.7 ± 22.5 mg/dl, p > 0.001). Within the pre-diabetic group, the tAUC for the 1M trial was not significantly different from the CON or 5M trials. Within the non-diabetic group, there were no significant differences in tAUC between the three trials. CONCLUSIONS: The results of this study indicate that a 5M bout of CALC done at a self-selected pace may have the ability to acutely improve glucose metabolism in college age pre-diabetic males when compared to non-diabetic males.

Supported by a SIUE Graduate School Research Grant for Graduate Students, the School of Education, Health, and Human Behavior Dean's Grant, and the Undergraduate Research and Creative Activities Program.

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.
Setmelanotide Administration Improves Cardiac Systolic Function in Sirtuin-3 Deficient Mice
Authors: Nelson Benjamin , Omoto Ana C. M , Espinoza Micaela , Nall John , Chen Jian-Xiong , Zeng Heng , do Carmo Jussara
Published: May 2024

We previously showed that activation of the brain leptin-melanocortin system, particularly melanocortin-4 receptors (MC4R), markedly improves cardiac function in experimental models of heart failure (HF) via mechanisms that are still poorly understood. Sirtuin 3 (Sirt3) is an important regulator of mitochondrial oxidative phosphorylation and deficiency of Sirt3 has been implicated in cardiovascular diseases. We recently found increased Sirt3 expression as well as increased levels of NAD+, the main Sirt3 activator, in cardiomyocytes of rats treated with chronic intracerebroventricular infusion of leptin at a dose that does not spill over into the systemic circulation. Therefore, we hypothesized that stimulation of Sirt3 activity is required for the improvement of cardiac function during activation of the brain leptin-MC4R axis. To test this hypothesis, we first examined if chronic MC4R activation, using an MC4R agonist, setmelanotide, improves cardiac function in naïve Sirt3-deficient (Sirt3-KO) mice. Baseline cardiac function was assessed by echocardiography (VisualSonics-VEVO3100®) in male and female Sirt3-KO and wild-type (WT) control mice (n=5/group) at 20 weeks of age, and then weekly during setmelanotide treatment (2 mg/kg/day — i.p. via osmotic minipump model 1002) for 3 weeks. Chronic MC4R activation with setmelanotide transiently reduced food intake in both groups and promoted weight loss in Sirt3-KO mice. Setmelanotide treatment improved systolic function in WT mice as evidenced by increases in ejection fraction and fractional shortening (EF: 52.8±4.4 vs. 72.4±4.4%; FS: 26.9±2.7 vs. 42.8±6.4%, for baseline vs. week 3, respectively) and other measures of systolic function including circumferential and longitudinal strains. Despite showing a tendency for reduced systolic function compared to WT controls at baseline, Sirt3-KO mice also exhibited improvement in systolic function with setmelanotide administration (EF: 44.1±1.8 vs. 65.3±2.9% and FS: 21.4±1.0 vs. 35.1±2.1%). No major changes were observed in measures of diastolic function. These results suggest that in a non-HF model, MC4R activation does not require stimulation of Sirt3 to improve indices of systolic function.

(1R01HL163076, 1R01DK121411, P20GM104357, P30GM149404, U54GM115428, and AHA-835218).

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.
Comparison effects of Natural and Artificial lighting on selected blood physiological variables of broilers grown to 56 days of age
Authors: Olanrewaju Hammed , MAGEE CHRISTOPHER , Collier Stephanie , Linhoss John , Baker-Cook Bethany , Purswell Joseph
Published: May 2024

Light is one of the major enviro-climatic factors in poultry houses that influences physiology and metabolic processes and impact poultry welfare, health, production and behaviors. This study compared the effects of natural and artificial lighting on selected blood physiological variables of broilers grown to 56 days of age. In each of the two trials, a total of 704 (352 males/352 females) 1-d- old Ross x Ross 708 chicks were obtained from a commercial hatchery on day of hatch. The design structure was a randomized complete block design with two treatments and eight replications per trial. Birds were equally and randomly distributed into 16 environmentally controlled rooms in groups of 44 (22 males/22 females) per room. Thus, each of the two treatments were represented by eight rooms with total of sixteen replicates. Temperature and RH on d 1 were maintained at 90 ± 2.1°F and 50 ± 5%, respectively across all treatments rooms. Temperature was decreased by 4 °F per week until it reached 66 °F at 56 d of age. Feed and water were provided ad libitum. Birds were provided a four phase-feeding program (Starter: 0-14 d, Grower: 15-28 d, Finisher: 29-42 d, and Withdrawal: 43-56 d). Blood samples (3 ml) were collected from the brachial wing vein of 3 males and 3 females birds per room on d 28, 42, and 56 which were then analyzed immediately for whole blood physiological variables. Blood plasma samples were analyzed for T3, T4, and corticosterone concentrations. Results showed that artificial light significantly increased sO2 (P < 0.049), SaO2 (P < 0.031), and decreased RHb (P < 0.044) which may be due to slight difference in body weights, but the changes were all within physiological ranges for this species. In addition, blood glucose and plasma corticosterone concentrations were not affected by treatments, signify a similar level of physiological stress between the two light types. In conclusion, physiological variables examined in this study were unaffected by both natural and artificial lighting. However, birds exposed to artificial lighting had slightly increased body weight in comparison with birds reared under natural lighting, which may have a significant impact in commercial poultry production.

USDA Agricultural Research Service.

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.
Does diphenhydramine exert a sex-dependent effect on sudomotor responses during exertional heat stress?
Authors: Newhouse Douglas , Lefebvre KarLee , Mihalcin Emily , Nucci Mario , Ravanelli Nicholas
Published: May 2024

Introduction: The first-generation H1 antihistamine diphenhydramine hydrochloride (DPH) is a potent antimuscarinic agent which may compromise sweat output during heat stress. DPH consumption prior to exertional heat stress could further suppress the sweating response in females due to their lower postjunctional cholinergic sensitivity of the sweat glands relative to males. Objective and Hypothesis: The purpose of the present study was to test the hypothesis that DPH would reduce sweating to a greater extent in females relative to males due to differences in cholinergic sensitivity at the sweat gland. Methods: Equal groups (10 per group) of males (24±3 y; 82.6±10.1 kg; 182±5 cm) and females (22±3 y, 67.7±7.8 kg, 171±6 cm) completed two experimental trials presented in a randomized double-blind fashion. Upon arrival to lab, participants consumed either i) a placebo (PLA) pill or ii) 50 mg DPH and then rested in a room maintained at ~29.5°C & 35% RH for 2 hours before conducting a 60-minute treadmill march at a fixed rate of heat production relative to body surface area (~245 W/m2). Rectal temperature (Trec), local sweat rate of the forearm (LSR), and whole body sweat loss (WBSL) were measured. Sex-segregated analysis was conducted for each outcome variable as the difference between PLA and DPH. Results: Baseline Trec did not differ within sex between PLA and DPH (males: -0.10±0.26°C; females: -0.05±0.33°C, P=0.70), however a higher absolute baseline Trec was observed in females compared to males (P=0.006). In comparison to PLA, DPH did not exert a sex-dependent effect on ΔTrec following 60-min of exercise (males: 0.04±0.11°C; females: 0.02±0.37°C, P=0.90). No sex-dependent effect on the onset of sweating was observed between DPH and PLA (males: -0.4±2.6 min; females: 0.6±2.4 min, P=0.34). DPH did not exert a sex-dependent effect on LSR at steady-state (males: 0.03±0.25 mg/cm2/min; females: -0.01±0.21 mg/cm2/min, P=0.71). Lastly, no sex-dependent effect on WBSL was observed between PLA and DPH (males: 14±34 g; females: 6±43 g, P=0.98). Conclusion: Current evidence suggests that sex does not independently modulate the sweating response during exertional heat stress following the consumption of 50 mg of DPH.

This research is supported by Dr. Ravanelli’s Research Seed Grant from the Centre for Research in Occupational Safety & Health, and Dr. Ravanelli’s Natural Sciences and Engineering Research Council of Canada Discovery Grant (PIN#2022-05096).

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 rotenone induced Parkinson’s disease on respiration and swallowing rate in drinking rats
Authors: Good Taylor , Wojtas Ireneusz , Gould Francois
Published: May 2024

Parkinson’s disease is a neurodegenerative disorder known to cause dysphagia, the major contributor to mortality via aspiration pneumonia. The neurological basis of swallowing dysfunction in Parkinson patients is poorly understood. To explore the mechanisms of swallowing dysfunction, we studied the impact of rotenone treatment on respiration rate and swallowing rate in liquid-drinking rats. We hypothesized that rotenone treatment will cause a decrease in respiratory and swallowing rate compared to untreated liquid-drinking rats. Six rats were injected with 2.75 mg/kg/day intraperitoneal rotenone for 16 days to create the parkinsonian phenotype and subsequently recorded with 200fps video fluoroscopy during barium-infused liquid drinking. Before the first injection and on day 4, 7, 10 and 16, the number of swallows and number of breaths in a ten second period of continuous drinking were scored. The data was then analyzed using Analysis of Variance to determine whether the rotenone injections impacted the respiration or swallowing rate. Rotenone injections led to a decrease in respiration rate (p=0.03), but no change in swallowing rate over a 16-day period (p>0.05). Immunohistochemistry of the dorsolateral striatum of rats that received rotenone treatment for 8 days and 16 days showed significant reduction in tyrosine hydroxylase (TH) immunofluorescence with increased impact due to prolonged treatment (Kruskal Wallis test, p<0.001). TH is the rate limiting step of catecholamine synthesis from tyrosine, confirming that rotenone is affecting dopamine production in this model of Parkinson’s disease. These results indicated that rotenone induced parkinsonian treatment has differential impacts on different brainstem mediated processes, swallowing and respiration. Thus, swallow-respiration coordination is likely impacted in these animals, potentially increasing risk of airway protection failure.

Internal Rowan funding to F. Gould supported this work.

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.
Sulfonylureas Compromise Microvascular Flow in Mouse Skeletal Muscle
Authors: El-Lakany Mohammed A. , Kowalewska Paulina M. , Ellis Christopher G. , Welsh Donald G.
Published: May 2024

Sulfonylureas are among the most prescribed oral anti-hyperglycaemics, particularly in low- and middle-income countries. Sulfonylureas are insulin secretagogues through blocking ATP-sensitive potassium channels (KATP) in β-cells of the pancreas. Despite wide usage, sulfonylureas are associated with increased cardiovascular disease morbidity and all-cause mortality, with ill-defined mechanisms. We tested the hypothesis that glyburide could block KATP channels in the microvasculature, thereby disrupting tissue oxygen demand-supply balance. We further investigated the contribution of other potassium channels to capillary-to-arteriole signalling. Experiments were conducted using an in-vivo anesthetized mouse skeletal muscle preparation (extensor digitorum longus, EDL); exteriorized and situated at in-situ length, overtop an oxygen-permeable membrane covering a gas chamber, and bathed in PlasmaLyte. C57BL/6 mice were employed (n=6-8). Brightfield images were captured at two wavelengths: oxygen-dependent and oxygen-independent, enabling the simultaneous determination of capillary hemodynamics and RBC oxygen content. Low oxygen challenges were achieved by dropping oxygen levels in the gas chamber from 7% to 2% for 3 minutes. Challenges were conducted before (control) and after drugs were added to bathing solution. Parameters were obtained before the challenge (baseline), during the challenge (2 regions) and after the challenge (recovery). Statistical significance was determined using a paired Student’s t-test. Target channels localization was investigated using immunofluorescence in formalin-fixed EDL. Oxygen challenges augmented EDL surface capillary hematocrit and RBC velocity and supply rate, while reducing RBC oxygen saturation. Incubation of the EDL with 10 μM glyburide decreased the baseline RBC supply rate (p<0.05 vs control) and blunted the magnitude of capillary responses to the oxygen challenge (p<0.05 vs control). Immunofluorescence confirmed the localization of KATP channels in EDL capillaries. Normal capillary responses were obtained when small and intermediate conductance or inward rectifier potassium channels were neutralized. This implies minimal or no contribution of these channels in oxygen signaling in the microvasculature. This data begins to elucidate the acute and direct effects of systemic KATP blockers on capillary-to-arteriole conducted signaling, which is likely key to optimal tissue oxygen regulation. Further experiments are warranted to confirm this conclusion.

This work was supported by the Natural Science and Engineering Research Council of Canada (NSERC, RGPIN/04659-2017), an Ontario Graduate Scholarship (M.A.E) and a CIHR doctoral award (M.A.E).

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 Role of Renal Medullary Bilirubin and Biliverdin Reductase in Ang II Induced Hypertension
Authors: Arthur Gertrude , Stec David
Published: May 2024

Previous studies have demonstrated the importance of renal medullary heme oxygenase-1 (HO-1) in blood pressure response to angiotensin II. However, the role of the HO metabolite, bilirubin, in this response remains unknown. The goal of the present study was to test the hypothesis that generation of bilirubin in the renal medulla plays an important role in the regulation of blood pressure in response to angiotensin II. Twenty-week-old male C57Bl/6J mice were implanted with intrarenal medullary interstitial (IRMI) catheters following unilateral nephrectomy. After this time, biliverdin IXα was specifically infused into the kidney (3.6 mg/day) for 3 days prior to implantation with an osmotic minipump delivering angiotensin II (1000 ng/kg/min). Blood pressure was recorded for 3 days, 1 week after minipump infusion, in conscious mice. IRMI infusion of biliverdin significantly decreased blood pressure as compared to mice infused with vehicle (118 ± 4 vs. 158 ± 2 mmHg, p<0.05). To further explore the antihypertensive role of renal medullary bilirubin generation, mice with specific deletion of biliverdin reductase-A (BVRA) in the thick ascending loop of Henle (TALH) were generated by crossing BVRAflox/flox mice with Tamm-Horsfall Cre (THP-Cre) mice. THP-Cre/BVRAflox/flox mice exhibited specific deletion of BVRA in the TALH by co-immunostaining with endogenous THP protein. THP-Cre/BVRAflox/flox mice did not exhibit any differences in baseline blood pressure as compared to BVRAflox/flox mice (108 ± 2 vs. 108 ± 2 mmHg). However, angiotensin-II infusion resulted in significantly higher blood pressure measured in conscious mice 7 days after implantation in THP-Cre/BVRAflox/flox as compared to BVRAflox/flox mice (152 ± 2 vs. 140 ± 3 mmHg, p<0.05). These results demonstrate an important role for renal medullary bilirubin and biliverdin reductase in the blood pressure response to angiotensin II. Strategies which increase renal medullary bilirubin/biliverdin reductase levels could be novel antihypertensive therapies. Future studies will examine the mechanistic link between bilirubin and electrolyte transporters in the kidney, specifically, the Na+-K+-2Cl2 cotransporter (NKCC2), which is a major transporter of electrolyte in the thick ascending limb and is known to play a role in Ang II-induced hypertension.

This work was supported by National Institutes of Health grants (RO1-HL088421 to DS).

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.
Age-Related Loss of Phrenic Motor Neurons in Rats
Authors: Alabdulqadar Aliyah , Fogarty Matthew , Dasgupta Debanjali , Mantilla Carlos B. , Sieck Gary C.
Published: May 2024

The diaphragm muscle (DIAm) is the major inspiratory muscle. Neural control of DIAm activation involves recruitment of phrenic motor neurons. Activation of the DIAm during breathing involes recruitment of fatigue resistant motor units comprising smaller PhMNs and type I and IIa muscle fibers. More force, but infrequent non-ventilatory behaviors of the DIAm involes the recruitment of fatigable motor units comprising larger PhMNs and type IIx/IIb fibers. This study investigated the role of brain derived neurotrophic factor (BDNF) signaling, through its high-affnity receptor, tropomyosin receptor kinase B (TrkB.FL), in the survival of PhMNs in young (6 months old) and old (24 months old) Sprague Dawley rats. Previous research in Fischer 344 rats revealed an age-related loss of larger PhMNs. We hypothesize that both BDNF/TrkB signaling and PhMN activity are crucial for PhMN survival, but that the influence of BDNF/TrkB decreases with age due to reduced TrkB.FL expression. PhMNs were retrogradely labeled and imaged using 3D confocal microscopy in both young and old rats. We found a similar reduction in larger PhMNs in Sprague Dawley rats as previously observed in Fischer 344 rats. In contrast to younger rats, intrathecal BDNF treatment did not induce phosphorylation of the transcription factor CREB at Serine133 in older rats, consistent with reduced TrkB.FL expression and signaling in older rats. In both old age and following TrkB kinase inhibition, smaller PhMNs survived perhaps due to the continued activation driving pCREB, while larger PhMNs may require BDNF/TrkB signaling to maintain pCREB and survival.

Research Supported by NIH R01 grants AG44615, HL146114 and R56-HL166204.

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.
Exploration of the Propagation of Hippocampal Theta Oscillations in Freely Moving Rats
Authors: Lovett Sarah , Qin Yu , Zhao Ben , Kochis Sam , Hershkowitz Sean , Kennedy Jack , Besosa Cristina
Published: May 2024

Comprehending the mechanisms by which theta waves propagate across the hippocampus is of utmost importance in understanding various aspects of cognition in rodent models. A popular argument made by those studying hippocampal rhythms is that they are synchronous throughout the medial temporal lobe. However, recent studies have concluded that theta oscillations travel as waves along the septotemporal axis of the hippocampus. Our experimental goal was to derive a relationship between theta oscillations in the anterior and posterior regions of the hippocampus by examining local field potential in freely moving rats. We trained a mixed-sex cohort of five Fisher Brown Norway hybrid rats to run on a circular track for a food reward and implanted them with an intracranial silicon probe in the CA1 region of the anterior dorsal hippocampus (AP: -2.8 ML: 1.5 DV: 4.0) and the CA1 region of the posterior parietal hippocampus (AP: -5.6 ML: 4.2 DV: 4.5). After a recovery period, the rats were reintroduced to the circular track where data was collected from each site. This poster presents the activity of traveling dentate spikes, ripples, theta, and gamma within these hippocampal regions.

R01MH126236 1R01MH109548-01A1.

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 Alcohol-related Cardiomyopathy
Authors: Harris Nicholas , Edavettal Joshua , Bysani Chandrasekar , Gardner Jason D.
Published: May 2024

Alcohol-related Cardiomyopathy (ACM) manifests in humans with a significant history of alcohol use and is characterized by ventricular dilation and cardiac function impairment. Although the most common age group for ACM is males between the ages of 30-55, women require a lesser lifetime alcohol exposure to develop ACM than men. The objective of this study is to assess sexual differences in a mouse model of chronic plus binge alcohol consumption. We hypothesize that female mice exposed to chronic plus binge alcohol will not develop as severe cardiac dysfunction as their male counterparts. In this study, male (n=19) and female (n=14) C57BL/6J mice were provided chronic plus binge alcohol feeding. After 5 days of acclimation to the liquid diet, mice are fed ad libitum 5% ethanol (EtOH) liquid or isocaloric control liquid diet for 30 days. At 10 and 30 days, mice received an oral binge dose of EtOH (5 g/kg body weight), or isocaloric maltose dextrin solution (9 g/kg body weight). Noninvasive cardiac structural and functional data were obtained via echocardiography at baseline and following binges. After 30 days, cardiac hemodynamics was measured by open chest left ventricle catheterization. Two-way ANOVA with Tukey’s post hoc analysis was performed for each cardiac parameter, and significance was defined as p<0.05. Male EtOH mice exhibited a significant decrease in stroke work (1119 ± 297 mmHg/mL when compared to male controls, 1622 ± 365 mmHg/mL; p= 0.03). Female EtOH mice had a nonsignificant decrease in stroke work (1242 ± 374 mmHg/mL when compared to female controls, 1423 ± 469 mmHg/mL; p= 0.80). Maximum left ventricular pressure was decreased 20% in male EtOH mice (p=0.003) but increased 10% in female EtOH mice (p=0.46). The maximum rate of pressure change within the ventricle was 24% lower in the male EtOH mice (p=0.02) and 9% higher in female EtOH mice (p=0.87). The minimum rate of pressure change within the ventricle was 24% higher in male EtOH mice (p=0.02) and 17% lower in female ETOH mice (p=0.44). After 30 days of EtOH exposure, male mice showed significant systolic and diastolic dysfunction. Female mice on the other hand, did not show substantial cardiac dysfunction after chronic plus binge ethanol exposure. Further experiments involving qPCR of proinflammatory and profibrotic markers will elucidate the molecular mechanism of sex differences in ACM development.

R21AA029747 (JG & CB) & T32AA007577.

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.
Theta Phase Precession and the Dynamics of Spatiotemporal Asymmetry in Hippocampal Place Fields
Authors: Qin Yu , Zhao Ben , Lovett Sarah , Besosa Cristina , Kennedy Jack , Burke Sara , Maurer Andrew
Published: May 2024

A consistently observed characteristic of hippocampal place fields is the shifting of the field's center of mass and the subsequent development of asymmetry. This is evidenced by the expansion of the place field in an asymmetric manner over repeated traversals, wherein a rat's initial entry into the field prompts a low firing rate that substantially increases as it exits. Our study delves deeper into these spatiotemporal asymmetries of place field spiking, specifically examining their relationship with theta oscillations and disentangling the effects from environmental factors. Analysis of neuronal data from a T-maze alternation task revealed a distinct non-uniform firing pattern of place cells. This pattern was markedly skewed in relation to the phases of theta cycles, indicating a phase precession effect. We found that as the rat navigates through the place field, there is a systematic advancement of spike timing, with action potentials tending to cluster in the early phases of theta during the exit phase of the field. Such temporal coordination of spikes suggests that the timing of neural activity within theta cycles is as integral as spatial location, influencing the dynamics of place field expansion and potentially affecting the hippocampal local field potential. This discovery underscores the role of theta phase precession in spatial encoding, proposing a novel temporal component that could underpin the cognitive map within the hippocampus.

R01 MH126236 R01 AG055544.

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.