bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring Body Composition and Functional Strength: Implications for the Clinical Assessment of Skeletal Muscle
Authors: Anderson Garret , Garcia Cedric J. , Sweed Tyler , Medler Scott 
Published: May 2024

Skeletal muscle represents the largest single component of the body, comprising up to 50% of total mass in healthy individuals. Body composition assessment has largely focused on overweight and obese individuals, but healthy skeletal muscle is also an important indicator of health and wellbeing. We hypothesized that estimates of lean body mass and empirical measures of functional strength should be directly correlated with one another. In the current study, we estimated body composition using two different field methods. Bioimpedance spectroscopy (BIS) employs 256 frequencies of low energy electrical current to estimate body composition. We used BIS (Impedimed SFB7) to determine percent body fat and fat free mass in physically active volunteers, ranging in age from 18 – 62 years. In addition, we used the Jackson and Pollock 3-site skin fold method to estimate these parameters from the same individuals. We also measured functional strength with a whole body dynamometer to determine mid-thigh pull strength, and a grip dynamometer to assess grip strength (Baseline Evaluation Instruments). Data collected from more than 75 men and women revealed significant correlations between fat-free mass (FFM) and both measures of functional strength. Interestingly, men and women fell along the same trend line, with women exhibiting similar strength for a given FFM. Moreover, functional strength standardized to FFM provides an objective measure of relative strength that was not different between men and women. The American Medical Association released a new policy statement about body mass index (BMI) in June of 2023, highlighting that BMI is an imprecise measure of body composition and recommending that alternative measures, such as more precise measurement of body composition, also be used. Indeed, we found that for individuals with a BMI of less than 30, there was direct relationship between FFM and functional strength. By contrast, percent body fat was not correlated with BMI within this range. We suggest that FFM and functional strength could be used to assess healthy weight, in conjunction with BMI. These measures could also be used to screen for sarcopenia, cachexia, and other conditions associated with significant muscle loss. Skeletal muscle represents an often underappreciated component of health and a more precise assessment of muscle mass and strength should be used as a measure of overall health. This work was supported by a Keenan Award at St. Bonaventure 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.
Distinct Neuronal Populations in the Bed Nuclei of the Stria Terminalis (BNST) Control IL1-β - mediated Stress Responses
Authors: Hashimoot Okito , Hepler Tyler , Tynan Aisling , Tracey Kevin J. , Chavan Sangeeta S. 
Published: May 2024

The immune and nervous systems are intricately linked. However, mechanistic pathways linking cytokine-mediated stress networks in the brain to peripheral immune and cardiac functions remain poorly understood. Here, we identify a specific population of neurons in the bed nucleus of the stria terminalis (BNST), which shape diverse responses to interleukin-1β (IL-1β)-mediated stress phenotype. Using activity-dependent cell labeling in mice, we identify distinct neuronal ensembles in the BNST that are active in response to IL-1β. Interestingly, re-exposure of mice to acute restraint stress results in the labeling of same populations in the BNST that were responsive to IL-1β administration. Chemogenetic reactivation of these IL-1β-responsive neuronal subsets in the BNST is suffcient to broadly retrieve the stress-induced responses. Specifically, reactivation of these IL-1β -responsive neurons in the BNST recapitulates tachycardia and inflammation induced by acute restraint stress, whereas specific ablation of IL-1β-responsive neurons in the BNST attenuates stress-induced serum IL-6 levels and IL-1β-induced tachycardia. Our data define a neuronal population in the BNST that is both necessary and suffcient for mediating IL-1β-associated stress responses, revealing a role for BNST coordination of inflammatory responses. Supported in part by grants from NIH, NIGMS, 1R35 GM118182 to KT and 1R01AR083159-01 to SC. 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.
Long-Term Intrauterine Hypoxia Disrupts Calcium Sparks in Middle Cerebral Arterial Myocytes of Fetal Sheep
Authors: Nelapudi Nikitha , Boskind Madison , Mallari David , Chan Michelle , Romero Monica , Zhang Lubo , Blood Arlin 
Published: May 2024

Local activation of ryanodine receptors (RyRs) on the sarcoplasmic reticulum in vascular smooth muscle cells (VSMCs) generates rapid subcellular changes in cellular Ca2+ that are commonly known as Ca2+ sparks. These Ca2+ sparks are well regarded for their role in the autoregulation of vascular contractility and cerebral blood flow through activation of potassium channels and feedback modulation of the membrane potential. Gestational hypoxia disrupts cerebrovascular development, increasing the risk of intracranial hemorrhage and stroke in the newborn. Due to the role of RyR’s in regulating neonatal cerebrovascular blood flow, understanding intracellular Ca2+ release patterns in VSMCs can offer insight into hypoxia-related perinatal cerebrovascular disease. The central aim of this study is to determine the extent to which gestational hypoxia disrupts RyR activity. This was achieved through examination of RyR activity in VSMCs of fetal ovine middle cerebral arteries (MCAs). MCAs were isolated from term fetal sheep (~140 days of gestation) delivered by cesarean section from ewes held at low- (700 m) and high-altitude conditions (3801 m) for 100+ days of gestation. Arteries were bathed in a physiological buffer with 5 mm K+ (control) or were treated with either 30 mM K+ (30K), to depolarize myocytes and increase Ca2+ spark events, in the presence or absence of 10 μM ryanodine, to block RyR mediated Ca2+ release. Ca2+ spark activity was measured in situ using line scan confocal microscopy fluorescence imaging techniques. Automated analysis of Ca2+ sparks in the records was conducted using SparkLab 5.8. Membrane depolarization with 30K increased Ca2+ spark activity. Long term hypoxia, however, reduced spark activity in the 30K group. Ryanodine attenuated Ca2+ spark activity in both low- and high-altitude groups. Hypoxia’s influence on the spatial and temporal aspects of Ca2+ sparks in fetal myocytes varied. These findings corroborate previous evidence demonstrating that long-term hypoxia attenuates Ca2+ spark activity. The disruption in Ca2+ spark activity could impact brain blood flow in the neonate, potentially impacting brain development and the likelihood of a traumatic event. R01HL155295, R01HL149608, Advanced Imaging and Microscopy Core Loma Linda University School of Medicine. 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.
Amyloid β reduces mechanical sensation by attenuating the function of TRPV4 channels in rat small dorsal root ganglion neurons
Authors: Fukazawa Ayumi , Hori Amane , Estrada Juan , Kim Han Kyul , Iwamoto Gary , Smith Scott , Vongpatanasin Wanpen 
Published: May 2024

Amyloid β (Aβ) is well known to be a key trigger for the progression of Alzheimer's disease and dementia. Aβ forms oligomers that develop into amyloid plaques, causing neuronal death and dysfunction. Aβ-induced neuronal dysfunction has been reported in peripheral neurons as well as in the brain. We previously reported that transient receptor potential vanilloid 4 (TRPV4) channels play an important role in mechanical sensation in sensory neurons innervating skeletal muscle. However, to date, it remains unclear whether Aβ modulates mechanosensation or TRPV4 channel activity in peripheral sensory neurons. As such, we hypothesized that Aβ acutely impairs the response of small dorsal root ganglion (DRG) neurons to mechanical stimuli by attenuating the function of TRPV4 channels. Purpose: The aim of this investigation was to determine the effects of Aβ1-40 and 1-42 on mechanosensation in small DRG neurons. Method: In in vitro whole-cell patch clamp recordings from cultured rat DRG neurons (Sprague-Dawley rat, n = 4, body weight: 316 ± 57 g), mechanically-activated (MA) current amplitudes or GSK1016790A (a selective agonist of TRPV4, 1 μM)-induced inward currents were measured before and 5 min after application of either HEPES buffered solution (control), Aβ1-40 (2.5 ng/μL), Aβ1-42 (2.5 ng/μL) or Aβ1-40/42 solution (2.5 ng/μL, respectively). Results: MA current amplitude was significantly decreased 5 min after application of both Aβ1-40 (Before vs. After: -71.7 ± 14.5 vs. -13.5 ± 4.8 pA. P < 0.01) and Aβ1-42 (Before vs. After: -63.7 ± 16.2 vs. -14.5 ± 5.9 pA. P < 0.05) while HEPES application did not alter MA currents (Before vs. After: -69.5 ± 17.9 ± -66.2 ± 13.9 pA. P = 0.36). Likewise, GSK1016790A-induced inward current was significantly suppressed by Aβ1-40/42 solution (Fold change in total charge transfer: HEPES vs. Aβ1-40/42: 0.92 ± 0.47 vs. 0.33 ± 0.06. P < 0.05). Conclusion: The data demonstrate that both Aβ1-40 and 1-42 suppress 1) the cellular response to mechanical stimulation and 2) TRPV4 currents in rat small DRG neurons. These findings suggest that both Aβ1-40 and 1-42 attenuate mechanical sensation in DRG neurons by inhibiting TRPV4 channels. Supported by NIH HL-151632 and JSPS 23KJ2207. 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.
Multi-modal Magnetic Resonance Imaging to Assess Cerebrovascular Function in Atrial Fibrillation Patients
Authors: Walsh Harvey , Morgan Catherine , Webster Mark , Lip Gregory , Dubowitz David , Fisher James 
Published: May 2024

Atrial fibrillation (AF) is associated with an increased risk of cognitive decline, dementia, and stroke. Low cerebral blood flow (CBF) and low cerebrovascular carbon dioxide reactivity (CVRCO2) are associated with poor brain health outcomes. In the current study we employed magnetic resonance imaging (MRI) to quantify resting CBF and CVRCO2 in patients with AF and age-matched normal sinus rhythm (NSR) controls. We hypothesised that both resting CBF and CVRCO2 would be lower in patients with AF. Patients with AF (n=11, 65±14 years, 2 women) and NSR (n=12, 63±9 years, 7 women) underwent arterial spin labelling (ASL) at rest, and blood oxygen level-dependent (BOLD) MRI during a single-step increase in partial pressure of carbon dioxide (measured by end-tidal carbon dioxide (PETCO2)) induced by changing the fraction of inspired CO2 to 5% (21% O2, balance N2). Region of interest time courses were extracted with grey matter, middle cerebral artery, and posterior cerebral artery territory masks. CVRCO2 was defined as the percentage change (%Δ) in BOLD signal vs %Δ in PETCO2. Baseline CBF was not different between NSR and AF in grey matter (62±17 vs. 58±10 ml/min/100g, respectively; p=0.226), middle cerebral artery (59±16 vs. 56±14 ml/min/100g; p=0.361) and posterior cerebral artery (61±17 vs 53±15 ml/min/100g; p=0.138) territories. BOLD-derived CVRC02 was not different between NSR and AF groups in grey matter (0.11±0.04 vs. 0.12±0.03 %ΔBOLD/%ΔmmHg, respectively; p=0.372), middle cerebral artery (0.09±0.04 vs. 0.10±0.03 %ΔBOLD/%ΔmmHg; p=0.405) and posterior cerebral artery (0.13±0.04 vs. 0.14±0.05 %ΔBOLD/%ΔmmHg; p=0.367) territories. Collectively, these pilot data suggest that MRI-derived cerebrovascular CO2 responsiveness is not different in patients with AF and age-matched NSR controls that have similar resting CBF. Further investigations are required to extend these preliminary findings to a larger cohort to fully elucidate the effects of AF on cerebrovascular function. Support provided by the Royal Society of New Zealand Te Apārangi Marsden Fund (19-UOA-170). 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.
Characterization of Middle Cerebral Artery Velocity Kinetics in Response to Isometric Handgrip Exercise in Healthy Adults
Authors: Baron John , Pearson Andrew , Corkery Adam , Loggie Nicole A. , Fico Brandon G. , Moir M. Erin , Narayanan Shrey 
Published: May 2024

Cerebral blood flow (CBF) is known to increase in response to both dynamic and isometric exercise. However, middle cerebral artery blood velocity (MCAv) kinetics in response to small-muscle isometric exercise, and sex differences in this kinetic response, require further investigation. Previous work suggests that MCAv response times to stressors may be indicative of cerebrovascular function, so the kinetics of this response to isometric exercise would add to the understanding of cerebrovascular health. The objective of this study was to characterize MCAv kinetics in response to isometric handgrip exercise and investigate potential sex differences in the response. We expected that MCAv at baseline would be higher in females than in males. However, we hypothesized that this sex difference would disappear during isometric handgrip exercise. In addition, we hypothesized that the time constant (τ) would be shorter in females compared with males, with a higher maximum response amplitude in females compared with males. Twenty-six healthy older adults with an average age of 56.8 ± 5.0 years (11 male (M) – aged 59.4 ± 4.8 years; 15 female (F) – aged 54.6 ± 4.1 years) completed an isometric handgrip exercise protocol. The exercise protocol consisted of the following: 1) performing a maximum voluntary contraction (MVC) with a handgrip device in the participants’ left hand (on a separate visit); 2) performing a sustained contraction until failure at 40% of the participant’s MVC. MCAv was continuously measured at rest and during handgrip exercise. The time constant was calculated as 63% of the time until steady-state MCAv during handgrip exercise. There was a trend for higher MCAv at baseline (57.8 ± 11.0 cm/s) in females (61.5 ± 11.2 cm/s) compared with males (53.6 ± 9.6 cm/s) that did not reach significance (p=0.08). There were no significant differences between the sexes for max amplitude of MCAv response to isometric handgrip exercise (M: 20.7 ± 11.1 cm/s; F: 15.4 ± 10.0 cm/s; p = 0.24) or time constant (M: 20.5 ± 9.8 sec; F: 18.6 ± 11.3 sec; p = 0.65). These results suggest no significant differences in MCAv between males and females at baseline. There also appear to be no significant sex differences in the kinetic response of MCAv to handgrip exercise. Future work could model MCAv kinetics in response to isometric handgrip exercise. The relationship between age and MCAv kinetics could also be investigated, along with the effect of menopause on MCAv kinetics in females. American Heart Association (19IPLOI34680015; JNB); American Heart Association COVID Supplement (19IPLOI34680015; JNB). 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.
Cdc42 Rho GTPase Activity Sustains Epithelial Barrier Function in the Cystic Fibrosis Intestine
Authors: Woode Rowena , Young Sarah , Williams Estela , Ericsson Aaron , Clarke Lane 
Published: May 2024

Increased paracellular permeability is a common manifestation of cystic fibrosis (CF) intestinal disease in people with CF and in CF mouse models. Increased paracellular permeability has been found in CF airway epithelium cultured in the absence of inflammatory factors, suggesting an inherent defect in CF epithelial barrier function (Weiser et al., Cell Physiol Biochem. 2011;28(2):289-96). CF transmembrane conductance regulator knockout ( Cftr KO) mouse intestinal crypts demonstrate an increase in epithelial cell proliferation, which correlates with an alkaline intracellular pH (pHi), a pHi-dependent increase in lateral cell membrane localization of the Wnt transducer Disheveled (Dvl), and increased Wnt/β-catenin signaling (Strubberg et al., Cell Mol Gastroenterol Hepatol. 2017 Dec 7;5(3):253-271). We hypothesized that the alkaline pHi of Cftr KO crypts also facilitates Dvl-dependent noncanonical Wnt signaling to increase Rho GTPase activity and thereby tight junction remodeling during increased proliferation. In Dvl2-eGFP rescue mice, Dvl2-eGFP intensity near the apical membrane of Cftr KO enteroid crypts was greater versus wild-type (WT) at both the crypt base and the transit-amplifying zone. Immunofluorescence studies of both freshly isolated crypts and early passage enteroids also found increased accumulation of the Rho GTPase Cdc42 at the tight junctions of Cftr KO versus WT crypts. Live imaging revealed a small increase in leak pathway permeability (3kD dextran) in Cftr KO as compared to WT murine enteroids. Increased leak permeability and Cdc42 tight junction localization were normalized in Cftr KO enteroids by suppressing proliferation through inhibition of Wnt/β-catenin signaling. There was no difference in Cdc42 expression in Cftr KO fresh crypts or enteroids, but initial studies show increased Cdc42 GTP-loaded activity in Cftr KO enteroids relative to WT. Similarly, CFTR KO human intestinal epithelial Caco-2 cells, which also show an alkaline pHi, increased Wnt/β-catenin signaling and a hyperproliferative phenotype, demonstrated a significant increase in GTP-loaded Cdc42 activity compared to WT cells. Inhibition of Cdc42 activity with ML141 (R&D Systems) resulted in a significant disruption of the Cftr KO epithelial barrier, whereas WT enteroid permeability was not affected by Cdc42 inhibition, Wnt inhibition or Wnt3a-induced proliferation. We conclude that increased Cdc42 Rho GTPase activity is cell-autonomous and is necessary for maintaining barrier integrity of the Cftr KO crypt epithelium. This work was supported by the Cystic Fibrosis Foundation grant CLARKE20G0 and the Crohn’s and Colitis Foundation grant #693938. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
A New Genetic Mouse Model of Lean NAFLD Uncovers a Sexual Dimorphism for Hepatic Damages and Cardiometabolic Impairments
Authors: Clapatiuc Valentin , Burelle Charlotte , Deschênes Sonia , Cuillerier Alexanne , De Loof Marine , Higgins Marie-Ève , Boel Hugues 
Published: May 2024

Background: The prevalence of non alcoholic fatty liver disease (NAFLD) is ~30% higher in the obese population. However, among patients living with NAFLD, 40% are not obese and half of them are lean. Although being mostly studied in obese individuals, the progression of NAFLD in lean patients may involve cardiac manifestations as well. Our hypothesis states that lean NAFLD patients also develop cardiac complications, independently of pre-existent metabolic disruptions, mechanisms of which remain to be fully understood, especially when considering the sexual dimorphism of the disease. Method: To address the underlying mechanisms of the progression of NAFLD independently of obesity, we used a murine model of hepatic mitochondrial deficiency, achieved through a hepato-specific knockout (KO) of Lrpprc. KO mice thus develop microvesicular steatosis without obesity in both sexes which was extensively characterized at the molecular and metabolic level in liver, plasma and heart. Our results unveiled a sex-dependent hepatic and cardiac phenotypic remodeling. KO male mice, to a greater extent than females, showed sustained fasting hypoglycemia and increased insulin sensitivity. Males also showed a more inflammatory hepatic profile characterized by a significant increase of F4/80 staining in immunohistological analyses (3-fold). Furthermore, only males exhibited an increase in the circulating hepatokine FGF21 (1.74-fold) and an increase in VLDLs lipoproteins while HDLs lipoproteins were decreased. In contrast, KO females showed a modest and global decrease of the lipoprotein profile. As such, sex differences occurred also in the heart since only males showed diastolic dysfunction while females’ cardiac function remained unaffected despite mitochondrial defects such as impairments in mitochondrial biogenesis, dynamics and oxidative capacities. Noteworthy, we also observed a significant and inverse correlation between glycemia and an index for cardiac relaxation only in males. Conclusion: Overall, this study underscores the value of this model for NAFLD without obesity where sex-dependent damage in the liver, the plasma and the heart are highlighted. Canadian Institutes of Health Research (CIHR), Montreal Heart Institute Foundation, Heart and Stroke Foundation of Canada, Cardiometabolic Health, Diabetes and Obesity Research Network. 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.