bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-associated impairment in swallow function is concomitant with nucleus ambiguus motor neuron death in Fischer 344 rats
Authors: Fogarty Matthew 
Published: May 2024

The nucleus ambiguus contains motor neurons (MNs) innervating the muscles of the larynx, pharynx and oesophagus. Many of the motor units these muscles are comprised of are fast fatigueable units — highly vulnerable to neurodegeneration. Loss of the MNs or damage to the nerves innervating the muscles of the larynx, pharynx and oesophagus may impair swallow, vocalization and/or respiratory functions. Of particular importance, human patients with deficits in swallow are at risk of sequelae such as aspiration pneumonia and malnutrition. In aged male Fischer 344-Brown Norway crosses, age-associated loss of nucleus ambiguus MNs contributes to vocalisation deficits. Here, we use female and male Fischer 344 (F344) at young (6-months old) and old (24-months old) to evaluate swallow function and nucleus ambiguus MN survival. Swallow function was evaluated under anesthesia by delivering an 0.3 mL bolus of water to the base of the tongue and videoing the number of subsequent swallows. A pressure catheter was inserted into the oesophagus to evaluate the incidence and duration of wallow-associated apneas and the magnitude of the schluckatmung in 30 s following bolus delivery. Following functional evaluations, rats were euthanized, perfused with paraformaldehyde and brainstem tissue cryopreserved, sectioned and stained with Nissl to stereologically evaluate the number of nucleus ambiguus MNs. In old age, we observed an ~30% reduction in the number of swallows per delivery of the water bolus and an increased incidence and duration of swallow apnea. Schluckatmung was not affected by age. The number of nucleus ambiguus MNs was reduced by ~20% in old F344 rats, with MN size unaffected. We propose that swallow evaluations are a robust readout of oropharyngeal behaviour, with deficits concomitant with MN death. These findings are similar to age-associated weakness in other skeletal muscle being related to MN death. It is likely that the mechanisms underpinning fast fatigue motor unit MN death in brainstem and spinal pools are similar. This research was funded by 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.
Sex difference in cardiac autonomic function in African American adults
Authors: Nyarko Ruby , Dalve Ashlesha , Perez Justo , Fatahimeiabadi Zahra , Dombroski Lindsay , Fadel Paul , Kaur Jasdeep 
Published: May 2024

African American (AA) individuals in the United States have the highest prevalence of hypertension, with an age-adjusted prevalence of 55.8% in AA men and 56.9% in women. Compared to other racial groups, the AA population also has a two- to three-fold higher mortality rate resulting from hypertension-related causes. Furthermore, AA men exhibit a higher mortality rate than AA women. Previous studies have demonstrated sex differences in some biological mechanisms linked to the increased cardiovascular disease risk in the AA population —such as impaired vascular function and elevated oxidative stress. However, it is unknown whether sex differences are present in baroreflex sensitivity (BRS) and heart rate variability (HRV), which are key mechanisms that may contribute to the pathogenesis and clinical outcomes of hypertension. Herein, we tested the hypothesis that young AA men exhibit impaired cardiac autonomic function (spontaneous BRS and HRV) compared to AA women. We studied 26 young normotensive AA adults (13 women) [Age (men: 22 ± 3; and women: 19 ± 1yr; mean ± SD, p = 0.03); BMI (men: 24 ± 3; and women: 24 ± 2 kg/m2; p = 0.92)]. Heart rate (HR; ECG) and beat-to-beat blood pressure (BP; finger plethysmography) were continuously recorded during 10 min of rest to assess HRV and cardiac BRS. Resting HR (men, 61 ± 8; and women: 65 ± 9 bpm; p = 0.18), diastolic BP (men, 66 ± 6; and women: 65 ± 5 mmHg; p = 0.48) and respiratory rate (men, 17 ± 3; and women, 17 ± 3 bpm; p = 0.97) were similar between the groups. Mean BP and systolic BP were higher in AA men, though within the normotensive range for both groups [mean BP (men: 84 ± 5; and women: 76 ± 5 mmHg; p = 0.001); SBP (men: 119 ± 4; and women: 103 ± 7 mmHg; p < 0.001)]. HRV [root mean square of successive differences between normal heartbeats (RMSSD); men, 113 ± 78; and women, 79 ± 43 ms; p = 0.18] and cardiac BRS (overall gain; men, 25 ± 13; and women, 28 ± 12 ms/mmHg; p = 0.66) were not different between groups. These results indicate that BRS and HRV, which are markers of cardiac autonomic regulation, do not differ based on sex among young normotensive African American individuals. Supported by: Kinesiology and Health Education UT Austin Start-up Account 19-2635-91; and TACSM 2023 Student Research Development Award. 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.
Trpv4 Mechanosensing Mediates Valvular Interstitial Cell Differentiation to Myofibroblast
Authors: Mukherjee Pritha , Mahanty Manisha , Dutta Bidisha , Rahaman Shaik O. 
Published: May 2024

Aortic valve stenosis (AVS) is a heart disease that gradually worsens, marked by the fibrosis, inflammation, and stiffening of the aortic valve leaflets, which results in obstructed blood flow and increased pressure on the left ventricle. This condition is associated with a significantly high risk of death. As AVS progresses, valvular interstitial cells (VICs) transform into myofibroblasts due to various soluble and physical cues, leading to detrimental changes in the surrounding cellular matrix. The transformation of VICs into myofibroblasts and the subsequent stiffening of the aortic valve are key factors in the advancement of AVS. Published work by our group and others show that Trpv4 (Transient Receptor Potential subfamily V member 4), a mechanosensitive, calcium-permeant channel/receptor, is activated by a range of soluble and physical stimuli. In mice, Trpv4 deficiency is associated with fibrosis and inflammation. In this study, we tested the hypothesis that Trpv4 regulates the transformation of VICs into myofibroblasts. Our research yielded several key findings: 1) Trpv4 is active in mouse VICs; 2) blocking Trpv4 activity in VICs prevents their transformation into myofibroblasts when exposed to TGF or matrix stiffness; 3) Trpv4 is needed for traction force generation in VICs as determined by traction force microscopy; and 4) Trpv4 residues 100 to 130 are required for myofibroblast differentiation and traction force generation. Altogether, our results highlight the crucial role of Trpv4 mechanosensing in regulating the transformation of VICs to myofibroblasts, a central process in AVS. We believe these findings could lead to novel Trpv4-targeted treatments to mitigate the effects of AVS. NIH (R01 AI172086) grant to Shaik O. Rahaman. 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 the regulation of salt appetite in Spontaneously Hypertensive Rats after loss of interoceptive input from the kidney
Authors: Veiga Amanda , Almutlaq Rawan , Ruiz Lauar Mariana , Ross Jaryd , Osborn John , Emy Nishi Erika , Dayton Alex 
Published: May 2024

The average American consumes 3,400 mg/day of sodium, 1000mg over the American Heart Association’s recommended maximum daily allowance. Excessive salt intake accelerates the progression of many diseases including hypertension, congestive heart failure, and chronic kidney disease. Reducing sodium intake has beneficial effects on a population level and in at risk patients. In previous studies we have shown that afferent renal nerves are involved in the regulation of sodium intake in DOCA hypertensive rats. Like DOCA hypertensive rats, Spontaneously Hypertensive rats (SHR) are a model with increased salt appetite. Here, we tested the hypothesis that afferent renal nerves regulate sodium intake in SHR. Secondarily, it is well documented that estrogens modulate salt intake. To examine the effect of sex on sodium intake we compared salt-appetite between male and female SHR. Bilateral afferent renal denervation (ARDN) was performed using the periaxonal application of 33mM capsaicin. In sham rats the renal arteries were isolated but not treated. Mean arterial blood pressure (MAP) was assessed using radiotelemetry, with the catheter implanted in the femoral artery. Four groups of rats were studied: male SHR-sham (n=9), female SHR-sham (n=3), male SHR+ARDN (n=8) and female SHR+ARDN (n=4). All rats were given ad libitum access to two bottles, one containing dH2O and the other containing 1.8% NaCl. The bottle position was rotated, and fluid intake was recorded daily for 21-days. ARDN caused a significant reduction in 1.8% intake in female but not male SHR rats (p=0.02, female SHR-sham v female SHR-ARDN, p>0.99 male SHR v male SHR-ARDN). This effect was specific for saline intake, water intake was not altered by ARDN in the female SHR (p=0.3). The female SHR drank more saline than male SHR when normalized to body weight (p=0.04 female SHR-sham v male SHR-sham). MAP was not reduced by ARDN in the male SHR (p=0.39), and ongoing studies are examining MAP in response to ARDN in female SHR. The data presented demonstrate for the first time that ARDN decreases salt appetite in female but not male SHR. We also found that baseline saline intake was higher in female SHR than male SHR. In future studies we will examine the renal mechanisms underlying these sex differences. Together, these data suggest that reduced sodium intake may offer an additional therapeutic benefit of renal denervation in female patients with hypertension and cardiovascular disease. LE is funded by R01HL152166; ACV is funded by FAPESP. 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.
TRPM3-mediated inhibition of active Na-K transport by the ocular lens epithelium
Authors: Shahidullah Mohammad , Rahman Faiz Ur , Shiels Alan , Delamere Nicholas 
Published: May 2024

Purpose: The TRPM3 channel is selectively expressed in the lens epithelium, a monolayer at the anterior lens surface, but undetectable in fiber cells that make up the lens bulk. A point mutation in TRPM3 gene (substitution of isoleucine by methionine at codon 65; I65M) causes early onset autosomal dominant cataract in humans and in mice. From studies on transgenic mice, it is apparent the I65M TRPM3 mutation disrupts lens Na-K homeostasis. However, the normal role of lens TRPM3 in the lens is currently unknown. Here, we explore the lens response to TRPM3 activation. Methods: Studies were carried out using intact mouse lenses, cultured mouse lens epithelial cells and a human lens epithelium cell line (HLEB3). Active Na-K transport was studied by using rubidium (Rb) as a tracer for potassium entry. Rb was detected by atomic absorption spectrophotometry. Intracellular calcium was measured in nonconfluent single cells by Fura-2 ratiometric imaging. Results: Rb uptake was measured over a period of 10 min in intact mouse lenses exposed to a TRPM3 agonist CIM0216 (10 μM). CIM0216 reduced the rate of Rb uptake by ~20% (Ctrl 6.4±0.4 vs CIM 4.5±0.4 mmoles/kg lens dry weight/10 min, n=7, p<.01). The concentration dependence of the response to CIM0216 (1 to 50 μM) was examined in primary cultured mouse lens epithelium and Rb uptake was reduced by CIM0216 concentrations > 10 μM. The TRPM3 agonist reduced Rb uptake to a similar extent (~20%) in mouse lens epithelium, HLEB3 cells and HLEB3 cells that had been stably transfected with the I65M mutant TRPM3. However, the mutant cells responded to CIM0216 at a 10-fold lower concentration than WT mouse and HLEB3 cells. The Rb uptake response to CIM0216 was significantly inhibited by a TRPM3 antagonist, primidone (50 μM), and was abolished when cells were bathed in calcium-free solution. To study calcium entry, Fura2-loaded mouse lens epithelial cells were exposed to the TRPM3 agonist pregnenolone (100 μM). Pregnenolone caused an immediate increase in cytoplasmic calcium that was inhibited by primidone (Peak calcium concentration Ctrl 201±37 vs primidone 137±8 nM, n=5, p<.001). In cultures lens epithelium, agents that increase cellular cAMP, including IBMX, forskolin and 8p-CPT-cAMP, all caused a marked reduction of Rb uptake. Conclusions: TRPM3 activation causes a significant reduction in the rate of active Na-K transport and the response is associated with calcium entry. Because most lens Rb uptake is ouabain-sensitive, the response points to Na,K-ATPase inhibition. Studies are under way to test whether the Na-K transport response to TRPM3 activation involves cAMP signaling. This work was supported by NIH grants R01EY029171 and R01EY009532. 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.
Non-invasive Blood Glucose Monitoring Using a Radiofrequency Sensor and a Machine Learning Model
Authors: Klyve Dominic , Anderson James , Curie Kaptain , Ward Carl , Pandya Kinara , Somers Virend 
Published: May 2024

Diabetes Mellitus (DM) affects over 530 million people globally and is a condition characterized by high blood glucose (BG) that can result in severe long-term health consequences if poorly managed. To mitigate the risks associated with DM, it is crucial to regulate BG levels through regular monitoring. Current methods of monitoring BG come with drawbacks in the form of pain and expense. With the rapid increase in prevalence of DM, there is an increasing need for economical, accurate, and non-invasive continuous measures of BG. Here we present a validation for a novel sensor that rapidly scans through a wide range of radio frequencies (RF) and uses machine learning (ML) techniques for the purpose of non-invasive BG measurement. After model training, the RF sensor and ML techniques employed in this study can predict BG at a level significantly better than chance, as shown below. Data were collected from 13 healthy participants over a series of tests lasting 2 – 3 hours. During each test, participants placed their forearm on an RF sensor that measured their BG levels using sweeps across the 500 MHz – 1500 MHz range at 0.1 MHz intervals. Participants ingested 37.5 grams of glucose solution to generate BG readings across normoglycemic and hyperglycemic ranges. Each sweep took approximately 22 seconds, including a one second pause between sweeps. Across 110 tests, we collected 3,311 BG observations. Concurrent measurements from a Continuous Glucose Monitor (CGM) were taken as reference. Data were divided using a 60-20-20 (training-validation-test) split and trained on a Light Gradient-Boosting Machine (lightGBM) model to predict BG values. A ‘blind’ evaluation of model performance was determined using the held-out test dataset. We predicted BG values in the held-out test dataset with a Mean Absolute Relative Difference (MARD) of 10.8% in the normoglycemic range and 15.9% in the hyperglycemic range (11.27% overall MARD). These results were significantly better than a chance model (two-sample t-test, p <0.01). In a Surveillance Error Grid analysis of model accuracy, 89.0% of predictions fell in Risk Level 0, 10.1% in Risk Level 1, and 0.9% in Risk Level 2. These results demonstrate that the novel RF sensor and ML techniques described can predict a reference BG value in the population under study. More research is underway to refine and expand these methods using a gold-standard blood glucose reference device and among a broader participant population with an expanded glucose range. DK and VS are consultants for and own stock in Know Labs. JA and KC are employed by and have stock options in Know Labs. CW and KP are consultants for Know Labs. NA. 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 Influence of Cholesterol on Resting Brain Blood Flow and Cognition in Middle-Aged Adults
Authors: Decker Kevin , Sanjana Faria , Rizzi Nicholas , Kramer Mary , Cerjanic Alexander , Johnson Curtis , Martens Christopher 
Published: May 2024

Total cholesterol increases with age, with peak values observed in middle-aged adults (50-64 years old). Middle-aged adults are vulnerable to experiencing future cognitive decline, in which the concurrent reductions in resting brain blood flow with aging have been linked to cognitive impairments. PURPOSE: To determine the influence of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol on resting brain blood flow and cognition in middle-aged adults (50-64 years old). Methods: LDL and HDL cholesterol were measured in 18 healthy adults (57 ± 4 years old). Resting cerebral and hippocampal blood flow were assessed using a pseudo-continuous arterial spin labeling (pCASL) sequence from the Human Connectome Project inside a Siemens Prisma 3T MRI scanner. Cognitive function was assessed using the Hopkins Verbal Learning Test (HVLT) and the National Institute of Health (NIH) Toolbox’s Flanker Inhibitory Control and Attention Test and Pattern Comparison Processing Speed Test. The influence of cholesterol on resting brain blood flow and cognition was analyzed using Pearson correlations. Results: LDL cholesterol (123 ± 23 mg/dL) was negatively correlated with resting cerebral (70.1 ± 12.5 ml.100g−1.min−1; r = -0.78, p = 0.0001) and hippocampal (67.6 ± 13.1 ml.100g−1.min−1; r = -0.74, p = 0.0005) blood flow. There were no significant associations for HDL cholesterol (67 ± 17 mg/dL) on resting cerebral (r = -0.03, p = 0.9) nor hippocampal (r = -0.04, p = 0.9) blood flow. Among the cognitive function tests, only hippocampal-dependent memory retention from the HVLT was positively associated with HDL cholesterol (r = 0.51, p = 0.03). A follow-up analysis revealed participants with a higher resting brain blood flow presented a tendency for higher scores in the Pattern Comparison Processing Speed Test (r = 0.44, p = 0.06). CONCLUSION: LDL cholesterol, a cardiometabolic risk factor, was negatively associated with resting cerebral and hippocampal blood flow whereas the potentially cardioprotective factor HDL cholesterol was not. HDL cholesterol was positively associated with memory-related outcomes. Our results suggest cholesterol may impact resting brain blood flow and should be considered a target in preventing or delaying age-related memory loss. Further data are required to elucidate the underlying mechanisms. SIGNIFANCE: The cardiometabolic effects of cholesterol may have additional implications on cerebrovascular and brain health. NIH/NIGMS - P20 GM113125. 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.
Vimentin Expression Following Mechanical Overload Induced Skeletal Muscle Hypertrophy Appears To Be Satellite Cell Dependent
Authors: Godwin Joshua , Michel Max , Fruge Andrew , Kavazis Andreas , Fry Christopher , Mobley brooks , Roberts Michael 
Published: May 2024

Introduction: Vimentin (VIM) is an intermediate filament that plays a key role in development and regeneration of various tissue types. However, the expression of VIM during skeletal muscle hypertrophy has not been fully elucidated. Therefore, the purpose of this study was to determine the response of VIM following mechanical overload (MOV) with or without the presence of satellite cells. Methods: Pax7-DTA mice (age 4mo) were subjected to 3, 10 or 20 days of synergist ablation to induce overload of the plantaris muscle, time matched sham surgery mice served as controls. Following overload, the plantaris was removed and either sectioned for immunohistochemistry (IHC) or placed in Trizol for later RNA/protein isolation. Satellite cell depletion was confirmed via IHC to determine Pax7+ cells. VIM expression was also examined via RT-qPCR, western blotting, and IHC. Data were checked for normality via Shapiro-Wilks tests and two-way ANOVAs were performed with Tukey post-hoc tests. Results: In the Pax7-DTA mice, VIM expression revealed a significant Group, Time, and Group x time interaction (all P < 0.001). Further analysis revealed VIM expression was significantly upregulated in satellite cell intact mice after 3, 10, and 20 days of overload (all P < 0.001). VIM expression in the satellite cell depleted mice was non-responsive to 3 and 10 days of MOV (P = 0.964, and P = 0.984, respectively), however VIM expression following 20 days of MOV in satellite cell depleted mice was significantly increased compared to sham mice (P = 0.0047). Conclusion: VIM expression is responsive to hypertrophic stimuli and appears to be satellite cell dependent in the early stages of skeletal muscle hypertrophy. Funding was provided through discretionary funds for Michael Roberts at Auburn University. 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.