bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of the clock protein BMAL1, diet, and sex on purinergic receptor expression in the distal nephron
Authors: Johnston Jermaine , Costello Hannah , Wingo Charles , Gumz Michelle , Crislip Gene 
Published: May 2023

The circadian clock protein BMAL1 is a core component of the intrinsic molecular clock mechanism that governs circadian rhythms. We use a kidney-specific Bmal1 knockout mouse model (KS-BMAL1KO) with loss of BMAL1 expression in the distal segments of the kidney. When placed on a potassium-deficient, high salt diet (0K+HS), male KS-BMAL1KO mice do not show an elevation in blood pressure compared to their littermate controls (CNTL), suggesting a protective effect due to loss of BMAL1 in the distal nephron. A low K+ diet predisposes to salt-sensitive hypertension by a high salt diet, in part due to increased sodium retention. Our lab has previously shown that inappropriately high ENaC activity in mice on a high salt diet is due in part to impaired purinergic signaling. The purinergic signaling pathway regulates water and electrolytes in the kidney via purinergic receptors (P2) and our gene expression data show their oscillation in a circadian manner in the kidney. We hypothesized that BMAL1 in distal segments contributes to the regulation of P2 receptor expression. Kidneys from male and female KS-BMAL1KO and CNTL mice were harvested at zeitgeber time (ZT) 0 or ZT12 from mice on a normal or a 0K+HS diet for 10 days. RNA was isolated from the renal medulla and prepared for RNA sequencing (5-9 pooled samples for males, 4-8 for females). Expression levels of P2X and P2Y receptor transcripts were examined. Loss of BMAL1 in distal segments modified P2 receptor expression, as KS-BMAL1KO mice exhibited lower P2Y14 gene expression than CNTL after 0K+HS in both males (78 ± 0, n=7 vs. 49.5 ± 0.7 CPM, n=7, P<.05) and females (85.5 ± 3.5 n=4 vs. 46 ± 8.5 CPM, n=4, P<.05). 0K+HS diet increased P2X7 in CNTL mice compared to normal diet in both males (88.5 ± 9.2, n=5 vs. 189.50 ± 33.2 CPM 114.1, n=7, P<.05) and females (79.5 ± 3.5, n=5 vs. 130.50 ± 3.5 CPM, n=4, P<.05) with no difference in genotype (P=NS). Sex differences were also apparent, as P2Y2 also increased following 0K+HS, but only in male CNTL (327.5 ± 27.6, n=5 vs. 499 ± 24 CPM, n=7, P<.05) and KS-BMAL1KO mice (264 ± 41, n=6 vs. 510 ± 11.3 CPM n=7, P<.05), without a genotype difference. These results support our hypothesis that BMAL1 in distal segments of the nephron contributes to the regulation of selective P2 receptors in the renal medulla, potentially modulating P2 receptor expression through interactions with circadian clock-, dietary- and sex-dependent factors. Our work is supported by the NIH, NIDDK, ASN, and AHA. This is the full abstract presented at the American Physiology Summit 2023 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.
Association between depressive symptomatology and central arterial stiffness in healthy young adults
Authors: Sirotnik Brianna , O'Leary Deborah , Iannarelli Nathaniel , Dempster Kylie , Wade Terrance 
Published: May 2023

Depression symptomology is linked with incident cardiovascular disease (CVD). Increased central arterial stiffness represents a potential mechanism connecting depression and increased cardiovascular risk. Therefore, the objective of this study was to examine the association between depressive symptomology and central arterial stiffness in healthy young adults without cardiovascular disease. The study tested the hypothesis that higher depressive symptomology is associated with greater central arterial stiffness. Using existing data from the Niagara Longitudinal Heart Study (NLHS), a sample of 293 young adults (22.5±1.71 years; 55% female) was included. Depressive symptomology (Centre for Epidemiological Studies Depression Scale; CESD), central arterial stiffness (carotid-femoral pulse wave velocity; cfPWV), beat-by-beat mean arterial pressure (MAP; finger photoplethysmography), and heart rate (HR; electrocardiogram) were measured. Multiple linear regression analyses were used to examine the association between depressive symptomology and cfPWV, adjusting for age, sex, body mass index, physical activity, smoking status, MAP, and HR. Depressive symptomology was categorized as low (CESD score < 16), moderate (CESD score ≥16 and < 26), and high (CESD score ≥ 26), where low symptomology was used as the reference group. After adjusting for covariates, high depressive symptomology was predictive of a faster cfPWV (β = 0.134, p = 0.026), whereas moderate depressive symptomology was not (β = 0.053, p = 0.365). These findings suggest that high depressive symptomatology is associated with a faster cfPWV, signifying elevated central arterial stiffness. Therefore, central arterial stiffness may act as a mechanism connecting depression to CVD. Future research should aim to decipher the causal direction between depression and cfPWV. This work was supported by the Canadian Institute of Health Research (CIHR) and Brock University. This is the full abstract presented at the American Physiology Summit 2023 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.
Cardiorespiratory Capacity and Body Composition are Improved with Concomitant Moderate Intensity or High-intensity Interval Training During Doxorubicin Treatment
Authors: Nguyen Branden , Baumfalk Dryden , Dowllah Imtiaz , Boeno Franccesco , Smuder Ashley 
Published: May 2023

Doxorubicin (DOX) is a highly effective chemotherapeutic agent used to treat a variety of solid tumor malignancies including breast cancer. However, following DOX treatment breast cancer patients often suffer from reduced cardiorespiratory capacity and weight gain with increased body fat. These adverse changes following DOX treatment increase the risk of developing cardiovascular disease, thus, increasing patient mortality. In this regard, exercise has been shown to be effective in improving cardiorespiratory capacity and body composition. Therefore, using a clinically translational rodent model of DOX treatment we determined whether participation in moderate intensity aerobic training or high intensity interval training (HIIT) during treatment is sufficient to prevent these adverse effects. The DOX dosing protocol was administered in adult female Sprague-Dawley rats following a standard clinical treatment regimen (i.e., intravenous infusion of DOX once every 3 weeks for 4 total cycles, cumulative dose of ~160 mg/m2). Rats prescribed exercise training followed current exercise guidelines for cancer patients. Moderate exercise consisted of treadmill running at ~70% VO2max 1 hour/day 3x/week. HIIT consisted of 4x4 minute bouts of running at ~90% VO2max 3x/week. Dependent measures were assessed prior to the initiation of DOX treatment and one-week following the last cycle. Similar to patients, DOX reduced cardiorespiratory capacity and increased fat mass in sedentary rats. However, moderate intensity exercise and HIIT improved exercise tolerance, reduced fat mass and increased lean mass in DOX treated rats. These findings mimic the clinical effects of DOX on cardiorespiratory capacity and body composition in breast cancer patients and demonstrate that exercise training during treatment can reduce these negative effects of DOX chemotherapy. Funding NIH R01 HL144858 This is the full abstract presented at the American Physiology Summit 2023 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.
Effect of hypokalemia and right atrial stretch on atrial arrhythmogenesis with aging
Authors: Cayton Jessica , Nourian Zahra , Lambert Michelle , Domeier Timothy 
Published: May 2023

Atrial Fibrillation (AF) is the most common sustained arrhythmia, and more than 2.7 million people are living with AF in the United States. The elderly are at greatest risk for AF with prevalence estimated at ~10% in individuals over the age of 80. The aged myocardium is subjected to chronic stretch, and atrial muscle stretch is an established risk factor for atrial arrhythmogenesis. Low potassium levels associate with arrhythmias and increase cardiovascular mortality by up to 10-fold. The goal of this investigation was to test factors leading to changes in rhythm and rate in an aging C57BL/6 mouse model. To test these factors, we used isolated hearts with combined cannulation of the aorta and superior vena cava in a modified right-sided working heart perfusion technique. Hearts of Aged (25-29 month) male (n=12) and female (n=14) C57BL/6 mice were subjected to normal Krebs-Henseleit buffer control conditions (control, 6 mM K+) followed by 30 minutes of right-atrial stretch (12 cmH20 right atrial preload), hypokalemia (2 mM K+), or combined stretch and hypokalemia. Heart rate and incidence of atrial arrhythmias were monitored using right-atrial placement of an intracardiac electrocardiogram. Under control conditions average heart rate across all groups was 248±13 BPM with no incidence of atrial tachycardia, fibrillation, or flutter. There were modest (P>0.05) differences in rate and rhythm with stretch (n=8), but hypokalemia decreased (P=0.001) heart rate by 20% and 4/8 hearts exhibited spontaneous atrial tachycardia/fibrillation/flutter. Hearts with combined hypokalemia and stretch exhibited normal heart rate (97% of control) and 5/10 hearts exhibited spontaneous atrial tachycardia/fibrillation/flutter. Observed atrial arrhythmias were present in hearts of both Aged male mice and Aged female mice. In conclusion, the aged mouse atria exhibit arrhythmias in response to hypokalemia and increases in right-atrial preload under hypokalemic conditions. The aged C57BL/6 mouse model is therefore useful for pre-clinical studies of atrial arrhythmogenesis. JC was funded by 2T32 OD011126 and the project was funded by NIH R01 HL136292 and University of Missouri School of Medicine TRIUMPH award (Domeier) This is the full abstract presented at the American Physiology Summit 2023 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.
Combined acute intermittent hypoxia and task specific training with hypercapnia improve breathing capacity after chronic cervical spinal cord injury
Authors: Gonzalez-Rothi Elisa , Gonzalez-Rothi Elisa , Berschel Mackenzie , Molyneaux Alex , Mitchell Gordon 
Published: May 2023

Therapeutic acute intermittent hypoxia (tAIH) is simple, safe, and effective means of inducing respiratory motor plasticity and improving breathing in rodent models of acute cervical spinal cord injury (SCI). Unfortunately, tAIH effects on breathing function are less effective with chronic injury. On the other hand, tAIH restores non-respiratory (limb) motor function with chronic SCI, but only when combined with task specific training (TST). The efficacy of combined tAIH and respiratory TST on breathing ability in rodent models (or humans) with chronic SCI has not been investigated. Here, we explore the potential for tAIH and respiratory TST to increase breathing ability; we further differentiate automatic vs. volitional TST, since the ability to sustain independent breathing is dependent on automatic (and not volitional) breathing function, which relies on distinct neural pathways. Hypercapnia is a powerful respiratory stimulant, increasing breathing via (automatic) chemoreceptor feedback, independent of voluntary control. Thus, we explore the impact of 7 days of tAIH (10, 5-min episodes of 10.5% O2) combined with automatic, hypercapnia-induced TST (30 min, 9% inspired CO2) on breathing in unanesthetized rats with chronic (7-8 weeks) C2 spinal hemisection. In preliminary analyses, breathing capacity (i.e., ventilatory response to maximal chemoreflex activation) increased following treatment with daily AIH combined with hypercapnia (i.e., respiratory TST) in rats with chronic C2 hemisection (~17% increase). Similar improvements in breathing function were not observed with tAIH or respiratory TST alone. These are the first studies to investigate the therapeutic efficacy of combined tAIH and respiratory TST targeting automatic breathing. These initial results indicate that, similar to non-respiratory motor systems, pairing tAIH with TST improves breathing function in rodents with chronic cervical SCI. Craig H. Neilsen Foundation (SCIRP891379), NIH HL147554, and the McKnight Brain Institute This is the full abstract presented at the American Physiology Summit 2023 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 brief online single session intervention increases undergraduate confidence speaking out in an active learning physiology course
Authors: Cooper Katelyn , Cohen Katherine , Ghosh Arka , Busch Carly 
Published: May 2023

Increasingly, college physiology courses are transitioning from traditional lecture to active learning because students learn more and fail less when they engage in their learning through activities and discussions in class. Fear of negative evaluation (FNE), defined as a student’s sense of dread associated with being unfavorably evaluated while participating in a social situation, discourages undergraduates from participating in small group discussions, whole class discussions, and conversing one-on-one with instructors. FNE disproportionately impacts women, persons excluded because of their ethnicity or race (PEERs), LGBTQ+ individuals, and those coming from low socioeconomic backgrounds. To equip undergraduates with skills to cope with fear of negative evaluation and bolster their confidence, clinical psychologists and biology education researchers developed Project Engage, a digital, self-guided single-session intervention for college students. It teaches students strategies for coping with and reducing fear of negative evaluation by providing biologically-informed psychoeducation, utilizing interactive elements for engagement, and generating a personalized action plan. In a study of 300 upper-level physiology students, participants randomized to complete Project Engage reported greater increases in overall confidence in engaging in small group discussions (p < 0.01), whole class discussions (p < 0.001) and one-on-one interactions with instructors (p<0.05), from baseline to immediate post-intervention, compared to participants in an active control condition. This work provides a foundation for a freely-available, easily accessible intervention to bolster student confidence contributing in class, with the hope of creating more equitable active learning physiology courses. NSF grant #2141681 This is the full abstract presented at the American Physiology Summit 2023 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.
Steady-state intracellular pH and recovery from NH3/NH4+-induced intracellular acid loads in primary cultures of rat hippocampal neurons and astrocytes
Authors: Ruffin Vernon , Boron Walter 
Published: May 2023

Intracellular pH (pHi) homeostasis is of vital importance because pHi fluctuations alter the net charge on intracellular weak acids and bases (e.g., amino-acid residues of proteins, metabolic intermediates, solutes like inorganic phosphate), and can result in cellular dysfunction. The rate of pHi change (dpHi/dt) is determined by the balance between acid loading (e.g., metabolic production of H+, influx of H+, efflux of HCO3 − via transmembrane proteins of the SLC4 family) and acid extrusion (e.g., efflux of H+ via Na-H exchangers in the SLC9 family, influx of HCO3 − by members of the SLC4 family). A powerful approach for studying pHi regulation is to impose an acute intracellular acid load using the NH4 +/NH3 prepulse technique, and then assess dpHi/dt during the subsequent pHi recovery. Using two such prepulses and recoveries (twin pulses), one can compare 2 experimental conditions. The goal of the present study is to develop a data-analysis approach that facilitates a meaningful presentation of all twin-pulse experiments in a data set. Using primary cultures (~2 weeks) of embryonic (E18–E20) rat hippocampal neurons and astrocytes on coverslips, we loaded cells with the ratiometric pH-sensitive fluorescent dye BCECF, subjected the cells to twin NH4 +/NH3 pulses, and calibrated BCECF at the end of each experiment with nigericin at pH=7.0. A standard 12-point nigericin calibration curve allowed us to compute pHi vs. time. Because we studied cells in 21% O2 but the nominal absence of CO2/HCO3 −, the pHi recoveries mainly reflect Na-H exchange. We fitted the pHi-recovery time course with a double exponential (DExp) to reduce bias. Nevertheless, in both neurons and astrocytes plots of dpHi/dt vs. pHi appeared rather linear, indicating that the pHi recoveries were “quasi” single exponential (SExp). To exploit the near-linearity, for each pHi recovery, we fitted the plot of dpHi/dt vs pHi with a line, the slope of which is the quasi-single exponential rate constant (kqSExp), and the x-intercept of which is the asymptotic pHi of the recovery. We summarize the twin pHi recoveries from individual cells as miniature plots (“thumbnails”) in which we display, for each recovery, both the dpHi/dt values (from the DExp fit of pHi vs. time) vs. pHi and the line of best fit for these dpHi/dt values vs. pHi. A single figure can replicate such twin-pulse experiments from many dozens of cells, so that a reader, at a glance, can surmise the essentials of each pHi recovery. The present work provides background data for additional work in which we studied pHi recoveries at a reduced [O2], with or without CO2/HCO3 −. R01 NS018400, R01 HL160857, R01 DK128315 This is the full abstract presented at the American Physiology Summit 2023 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.
Dietary vitamin D supplementation partially rescues heart rate in Ts65Dn mice, a model of Down syndrome
Authors: DeRuisseau Keith , Derfel Silas , MacDonald Jessica , DeRuisseau Lara 
Published: May 2023

Down syndrome is the most common developmental and intellectual disability that leads to co-morbidities including lower heart rate and blood pressure. We previously showed that Ts65Dn mice also display reduced heart rate and blood pressure compared to wild-type (WT) colony controls. Lower serum Vitamin D (VitD) levels have been reported among individuals with Ds. In other populations, VitD is a regulator of nitric oxide synthase and a known modulator of cardiovascular outcomes. VitD effects on cardiovascular physiology in Ds is unknown. In this preliminary study, we hypothesized that Ts65Dn mice supplemented with VitD would display improved heart rate compared to Ts65Dn mice on a control diet. Two-month old male Ts65Dn mice were placed onto a control diet (1IU VitD/g; n=4) or VitD supplemented diet (50IU/g; n=5) for two weeks and subsequently tested for resting heart rate. Mice were fitted with a MouseOx neck collar to monitor heart rate while freely moving within the cage. After habituation to the collar, heart rate was recorded for 30 minutes in the light cycle. Heart rate in Ts65Dn on the control diet was 510±67 bpm vs. 636±78 on the VitD diet (p=.038; t-test). As expected, WT (n=5; control diet) displayed a higher heart rate of 729±62 bpm. These preliminary data reveal a partial rescue of resting heart rate in Ts65Dn following VitD supplementation. Future studies can evaluate serum VitD levels, nitric oxide synthase, and cardiovascular metrics including blood pressure, heart rate, and pulse wave velocity in Ts65Dn and WT mice supplemented with dietary VitD. This work was supported by NIH R21HD099573 This is the full abstract presented at the American Physiology Summit 2023 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.
Assessment of the Response of Young and Aged Sarcospan-Deficient Mice to Nutrient Excess
Authors: Olateju Bolade , Rahimi Kahmini Aida , Valera Isela , Reis Gisienne , Samarah Luaye , Mumbi Florence , Mohammadipour Nazanin , Parvatiyar Michelle 
Published: May 2023

This study follows up on human genome-wide association studies that have identified variants in the SSPN locus. This locus encodes the protein sarcospan that segregates with several anthropometric traits. One of these traits includes an increase in waist circumference. In this study, we compared the response of young and old SSPN-deficient (SSPN-/-) and WT control mice to high fat diet (HFD) (60% fat). The HFD was initiated in 2 month and 1 year old male and female for 4 months and 5 months respectively. This study showed that SSPN-deficiency provided partial protection from weight gain in young male mice when compared to age-matched WT mice and a significantly smaller increase in body weight (BW) compared to controls. Also, young female SSPN-/- mice gained 50% less BW than WT age matched mice compared to controls and visceral WAT fat pad weights were significantly lower. To examine whether these differences are lost in aging (e.g. due to hormonal decline), we subjected 12-month old WT and SSPN-/- mice to 5 months of HFD and assessed anthropometric traits, blood lipids, glucose tolerance, body composition, and alterations of cytokine/adipokine/chemokine levels in blood serum and adipose tissue. There were signs of inflammation/fibrosis in young WT male WAT. This was largely absent in SSPN-/- mice. Interestingly, a specific subset of upregulated inflammatory mediators was found in WT WAT including leptin. However, another distinct subset of adipokines/chemokines were upregulated including adiponectin in SSPN-/- WAT. Therefore, we are investigating whether SSPN affects obesity-associated inflammatory signaling in adipocytes that influences adipose tissue expansion and ectopic triglyceride accumulation in the liver. FDOH JEK 21K12 This is the full abstract presented at the American Physiology Summit 2023 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.