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Diclofenac-eugenol modulation of Kv7 and TRPV1 ion channels bioRxiv. Physiol. Pub Date : 2024-03-17 Adrian Rivera-Ruedas, Alejandro Rafael Medina-Vilchis, Juan Jose Romero-Tovar, Gema Rosa Cristobal-Mondragon, Victor De la Rosa
Pharmacological targeting of ion channels represents a crucial avenue for pain management. Among these, the Kv7 family of ion channels plays a significant role controlling neuronal excitability and the generation and propagation of pain-related nerve impulses, thus mitigating excessive electrical signaling and curtailing the exaggerated transmission of pain signals. Pain management strategies often
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Human circulatory system response to changes in alveolar pressure and lung volume bioRxiv. Physiol. Pub Date : 2024-03-17 Yury S. Semenov, Alexander I. Dyachenko, Ivan S. Melnikov, Rustam N. Zaripov
The response of hemodynamic parameters in healthy volunteers to changes in alveolar pressure and lung volume was studied by noninvasive methods during respiratory maneuvers similar to Valsalva and Müller maneuvers (in a sitting position and lying on the back horizontally). The following lung volumes and values of pressure (relative to atmospheric pressure) were considered in various combinations: total
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Quantification of healthspan in aging mice: Introducing FAMY and GRAIL bioRxiv. Physiol. Pub Date : 2024-03-17 Dudley W Lamming
The population around the world is graying, and as many of these individuals will spend years suffering from the burdens of age associated diseases, understanding how to increase healthspan, defined as the period of life free from disease and disability, is an urgent priority of geroscience research. The lack of agreed-upon quantitative metrics for measuring healthspan in aging mice has slowed progress
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Selectivity and evolution of Aqp10 in solute permeability influenced by pore molecular weight bioRxiv. Physiol. Pub Date : 2024-03-17 Ayumi Nagashima, Kazutaka Ushio, Hidenori Nishihara, Jin Akimoto, Akira Kato, Tadaomi Furuta
Aqp10 is an aquaglyceroporin that transports not only water but also uncharged low-molecular-weight compounds. We previously demonstrated the evolution of solute permeability in Aqp10 paralogs and showed that the urea and boric acid permeabilities of Aqp10.2 were much weaker than those of Aqp10.1 and plesiomorphic Aqp10s. However, the molecular mechanism responsible for the weak permeability of Aqp10
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A matter of food and substrain: obesogenic diets induce differential severity of cardiac remodeling and diastolic dysfunction in C57Bl/6J and C57Bl/6N substrains bioRxiv. Physiol. Pub Date : 2024-03-17 Lorena Cascarano, Hrag Esfahani, Pierre Michel, Caroline Bouzin, Chantal Dessy, Jean-Luc Balligand, Lauriane Y.M. Michel
The prevalence of metabolic syndrome in cardiac diseases such as heart failure with preserved ejection fraction (HFpEF) prompts the scientific community to investigate its adverse effects on cardiac function and remodeling and its associated mechanisms. However, the choice of a preclinical model of obesity-induced cardiac remodeling has proven more challenging with inconsistencies often found in very
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Dynamics of endogenous and water cortisol release in Asian Seabass Lates calcarifer after acute stress in a farm scale recirculating aquaculture system bioRxiv. Physiol. Pub Date : 2024-03-17 Marie Ruoyun Tan, Khin Moh Moh Aung, Nur Asinah binte Mohamed Salleh, Jolin Yean Ai Tan, Kai Xin Chua, Gaynah Javier Doblado, Kai Lin Chua, Valarie Tham, Jovian Jing Lin, Vindhya Chaganty, Dinah Mardhiana Yusoff, Shubha Vij, Xiaodi Su, Laura Sutarlie, Caroline Lei Wee
Stress in farmed fish is associated with poor feeding, slow growth, disease, and mortality. Therefore, it is essential to closely monitor the stress levels in fish to optimize farming practices which could then enhance productivity and welfare in aquaculture operations. Cortisol, a stress hormone that can be found in the blood, is a reliable biomarker for evaluating fish stress. As blood sampling is
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Thoracic epidural blockade after myocardial infarction benefits from anti-arrhythmic pathways mediated in part by parasympathetic modulation bioRxiv. Physiol. Pub Date : 2024-03-16 Jonathan D Hoang, Valerie YH Van Weperen, Ki-Woon Kang, Neil Jani, Mohammed Amer Swid, Christopher A Chan, Zulfiqar Ali Lokhandwala, Robert L. Lux, Marmar Vaseghi
Background: Thoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachyarrhythmias (VT) in small case-series of patients with refractory VT and cardiomyopathy. However, its electrophysiological and autonomic effects in diseased hearts remain unclear and its use after myocardial infarction (MI) is limited by concerns for potential RV dysfunction. Methods: MI was created
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Strategies for Inducing and Validating Zinc Deficiency and Zinc Repletion bioRxiv. Physiol. Pub Date : 2024-03-15 Tara-Yesomi Wenegieme, Dalia Elased, Jananie Rockwood, Khanzada Hasrat, Kelia McMichael, Andrea Marshall, Kit Neikirk, Annet Kirabo, Khalid Elased, Antentor Hinton, Clintoria R Williams
Given the growing interest in the role of zinc in the onset and progression of diseases, there is a crucial demand for reliable methods to modulate zinc homeostasis. Using a dietary approach, we provide validated strategies to alter whole-body zinc in mice, applicable across species. For confirmation of zinc status, animal growth rates as well as plasma and urine zinc levels were evaluated. The accessible
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Comparing physiological impacts of positive pressure ventilation versus self-breathing via a versatile cardiopulmonary model incorporating a novel alveoli opening mechanism bioRxiv. Physiol. Pub Date : 2024-03-15 Manuel T Cabeleira, Vijai Anand Dharmalingam, Claire Black, Samiran Ray, Nicholas Ovenden, Vanessa Diaz
Mathematical models can be used to generate high-fidelity simulations of the cardiopulmonary system. Such models, when applied to real patients, can provide valuable insights into underlying physiological processes that are hard for clinicians to observe directly. In this work, we propose a novel modelling strategy capable of generating scenario-specific cardiopulmonary simulations to replicate the
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Muscle fiber Myc is dispensable for muscle growth and forced expression severely perturbs homeostasis bioRxiv. Physiol. Pub Date : 2024-03-14 Daniel J Ham, Michelangelo Semeraro, Bianca Manuela Berger, Shuo Lin, Eleonora Maino, Filippo Oliveri, Markus A Ruegg
The oncogenic transcription factor Myc stimulates many growth processes including cell cycle progression and ribosome biogenesis. Myc expression is low in adult skeletal muscle, but is upregulated upon growth stimuli. Furthermore, muscle fiber Myc overexpression recapitulates many aspects of growth-related gene expression, suggesting Myc may mediate pro-growth responses to anabolic stimuli, such as
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A perfusion-independent high-throughput method to isolate liver sinusoidal endothelial cells bioRxiv. Physiol. Pub Date : 2024-03-14 Anna Babin-Ebell, Yifang Mao, Tinja Baljkas, Franziska Pilz, Manuel Winkler, Sina Kuerschner, Marlene Hoffarth, Sergij Goerdt, Philipp-Sebastian Reiners-Koch, Mahak Singhal
Liver sinusoidal endothelial cells (LSECs) critically regulate homeostatic liver function and liver pathogenesis. However, the isolation of LSECs remains a major technological bottleneck in studying molecular mechanisms governing LSEC functions. Current techniques to isolate LSECs, relying on perfusion-dependent liver digestion, are cumbersome with limited throughput. We here describe a perfusion-independent
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Non-physiologic interaction of MG53 with insulin receptor and lack of evidence for MG53's role in controlling insulin-stimulated Akt phosphorylation in muscle, heart and liver tissues. bioRxiv. Physiol. Pub Date : 2024-03-13 Kyung Eun Lee, Miyuki Nishi, Jongsoo Kim, Takashi Murayama, Zachary Dawson, Xiaoliang Wang, Xinyu Zhou, Tao Tan, Chuanxi Cai, Hiroshi Takeshima, Ki Ho Park
Rationale: MG53's known function in facilitating tissue repair and anti-inflammation has broad applications to regenerative medicine. There is controversy regarding MG53's role in the development of type 2 diabetes mellitus (T2DM). Objective: This study aims to address this controversy - whether MG53's myokine function contributes to inhibition of insulin signaling in muscle, heart, and liver tissues
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Enhanced Ca2+-Driven Arrhythmias in Female Patients with Atrial Fibrillation: Insights from Computational Modeling bioRxiv. Physiol. Pub Date : 2024-03-13 Xianwei Zhang, Yixuan Wu, Charlotte Smith, William E. Louch, Stefano Morotti, Dobromir Dobrev, Eleonora Grandi, Haibo Ni
Background and Aims. Substantial sex-based differences have been reported in atrial fibrillation (AF), with female patients experiencing worse symptoms, increased complications from drug side effects or ablation, and elevated risk of AF-related stroke and mortality. Recent studies revealed sex-specific alterations in AF-associated Ca2+ dysregulation, whereby female cardiomyocytes more frequently exhibit
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Downregulation of NR4A3 During Inactivity Alters Glucose Metabolism and Impairs Translation in Human Skeletal Muscle bioRxiv. Physiol. Pub Date : 2024-03-13 Jonathon AB. Smith, Brendan M Gabriel, Anna Krook, Juleen R. Zierath, Nicolas J Pillon
Background: Physical activity promotes health, whereas inactivity is associated with metabolic impairment. The transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3) is a pleiotropic regulator of skeletal muscle exercise adaptation and metabolism. However, the consequence of lower NR4A3 expression remains largely unexplored. We investigated the impact of NR4A3 downregulation on
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The Kv2.2 channel mediates the inhibition of Prostaglandin E2 on glucose-stimulated insulin secretion in pancreatic β/-cells bioRxiv. Physiol. Pub Date : 2024-03-13 Chengfang Pan, Ying Liu, Liangya Wang, Wen-Yong Fan, Yunzhi Ni, Xuefeng Zhang, Di Wu, Chenyang Li, Jin Li, Zhaoyang Li, Rui Liu, Changlong Hu
Prostaglandin E2 (PGE2) is an endogenous inhibitor of glucose-stimulated insulin secretion (GSIS) and plays an important role in pancreatic β-cell dysfunction in type 2 diabetes mellitus (T2DM). This study aimed to explore the underlying mechanism by which PGE2 inhibits GSIS. Our results showed that PGE2 inhibited Kv2.2 channels via increasing PKA activity in HEK293T cells overexpressed with Kv2.2
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Intestinal barrier function in the naked mole-rat: an emergent model for gastrointestinal insights bioRxiv. Physiol. Pub Date : 2024-03-12 Javier Aguilera-Lizarraga, Anne Ritoux, David Bulmer, Ewan St. John Smith
The intestinal barrier plays a crucial role in homeostasis, both by facilitating absorption of nutrients and fluids, and providing a tight shield to prevent the invasion by either pathogen or commensal microorganisms. Intestinal barrier malfunction is associated with systemic inflammation, oxidative stress, and decreased insulin sensitivity, which may lead to the dysregulation of other tissues. Therefore
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Nucleobindin-1 (Nucb1) disruption affects feeding, metabolism, and glucose homeostasis in mice in an age-, sex-, diet- and light cycle-dependent manner bioRxiv. Physiol. Pub Date : 2024-03-12 Atefeh Nasri, Emilio J Velez, Jithine Jayakumar Rajeswari, Azadeh Hatef, Suraj Unniappan
Background: Nesfatin-1 (NESF-1), encoded in the calcium and DNA binding protein (Nucleobindin 2, NUCB2) is an orphan ligand with metabolic effects. Recently, our lab provided evidence for a NESF-1-like peptide (NLP) in a NUCB2-related precursor, NUCB1, in zebrafish and rodents. This research aims to determine whether endogenous NUCB1 is critical for energy homeostasis. Methods and Main Findings: Global
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Bridging geometric morphometrics to medical anatomy: An example from an experimental study of the human smile bioRxiv. Physiol. Pub Date : 2024-03-12 Fred L Bookstein, John T. Kent, Balvinder S. Khambay, Kanti V. Mardia
The method of Cartesian transformations introduced by D'Arcy Thompson a century ago in his celebrated book On Growth and Form precipitated an important development in 20th-century biometrics: a fusion of the geometrical and biological approaches to morphology. Some decades later this fusion, in turn, spun off another multidisciplinary focus, statistical shape analysis, that bridges between biostatistics
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Deletion of Robo4 worsens neuroinflammation and motor coordination in a mouse model of Alzheimer's disease bioRxiv. Physiol. Pub Date : 2024-03-12 Abigail E Cullen, Nicholas Winder, Byron Lee, Sahana Krishna Kumaran, Nayantara Arora, Julia Wolf, Randy Woltjer, Ashley Walker
Declines in vascular integrity are potential contributors to Alzheimer's disease (AD) as these result in increased blood-brain barrier permeability and, as a consequence, accelerate neuroinflammation and cognitive impairment. Roundabout guidance receptor 4 (Robo4) is primarily expressed in endothelial cells and stabilizes the vasculature, and thus, has the potential to protect the brain in AD. To study
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Mean exercise torque is a critical factor influencing neuromuscular fatigability induced by exhausting contractions bioRxiv. Physiol. Pub Date : 2024-03-12 Loic Lebesque, Gil Scaglioni, Patrick Manckoundia, Alain Martin
PURPOSE: To get a more detailed description of neuromuscular fatigability, maximal torque sustainability (i.e., the ability to maintain a high torque level) can be assessed in addition to the classically used maximal voluntary contraction (MVC). Since this parameter appears to be affected by mean exercise torque (MET), the present study aims to examine the relationship between MET and neuromuscular
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Hypothalamic hormone deficiency enables physiological anorexia bioRxiv. Physiol. Pub Date : 2024-03-11 Sarah M Mohr, Rafael Dai Pra, Maryann P Platt, Viktor V Feketa, Marya Shanabrough, Luis Varela, Ashley Kristant, Haoran Cao, Dana K Merriman, Tamas L Horvath, Sviatoslav N Bagriantsev, Elena O Gracheva
Mammalian hibernators survive prolonged periods of cold and resource scarcity by temporarily modulating normal physiological functions, but the mechanisms underlying these adaptations are poorly understood. The hibernation cycle of thirteen-lined ground squirrels (Ictidomys tridecemlineatus) lasts for 5-7 months and comprises weeks of hypometabolic, hypothermic torpor interspersed with 24-48-hour periods
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FGF21 deletion mildly exacerbates hepatic dysfunction in MASH diet and alcohol fed rats bioRxiv. Physiol. Pub Date : 2024-03-11 Peter Aldiss, Malte Hasle Nielsen, Hayley Burm, Denise Oró, Henrik H Hansen, Michael Feigh, Matthew P Gillum
Objective: Fibroblast growth factor 21 (FGF21) is a hepatokine that improves dyslipidemia, steatosis, inflammation, and fibrosis. FGF21 analogues are in clinical development as treatments for metabolic and alcohol-associated liver disease, creating a need for new models to help understand FGF21 physiology and drug mechanisms of action. The aim of this study was to create and initially characterize
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Effect of 10 days of unilateral lower limb suspension on knee extensors neuromuscular function and spinal excitability bioRxiv. Physiol. Pub Date : 2024-03-11 Loic Lebesque, Marco Narici, Alain Martin, Giuseppe De Vito, Fabio Sarto, Gil Scaglioni
Introduction. The reduction in mechanical loading applied on the lower limb has numerous detrimental consequences on neuromuscular function. While muscle mass and strength are known to be altered, changes in motoneuronal function remain poorly investigated. Methods. Ten young healthy males (19-28 years old) underwent 10 days of unilateral lower limb suspension (ULLS) to simulate muscle disuse. Modulation
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T cell cholesterol transport is a metabolic checkpoint that links intestinal immune responses to dietary lipid absorption bioRxiv. Physiol. Pub Date : 2024-03-11 Yajing Gao, John Paul Kennelly, Xu Xiao, Emily Whang, Alessandra Ferrari, Alexander H Bedard, Julia J Mack, Alexander H Nguyen, Thomas Weston, Lauren F Uchiyama, Min Sub Lee, Stephen Young, Steven J Bensinger, Peter Tontonoz
The intrinsic pathways that control membrane organization in immune cells and the impact of such pathways on cellular function are not well defined. Here we report that the non-vesicular cholesterol transporter Aster-A links plasma membrane (PM) cholesterol availability in T cells to immune signaling and systemic metabolism. Aster-A is recruited to the PM during T-cell receptor (TCR) activation, where
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General Capillary Endothelial Cells Undergo Reprogramming into Arterial Endothelial Cells in Pulmonary Hypertension through HIF-2α/Notch4 Pathway bioRxiv. Physiol. Pub Date : 2024-03-10 Bin Liu, Dan Yi, Xiaomei Xia, Karina Ramirez, Hanqiu Zhao, Yanhong Cao, Ankit Tripathi, Ryan Dong, Anton Gao, Hongxu Ding, Shenfeng Qiu, Vladimir V Kalinichenko, Michael B Fallon, Zhiyu Dai
Pulmonary arterial hypertension (PAH) is characterized by a progressive increase of pulmonary vascular resistance and obliterative pulmonary vascular remodeling that result in right heart hypertrophy, failure, and premature death. The underlying mechanisms of loss of distal capillary endothelial cells (ECs) and obliterative vascular lesion formation remain unclear. Our recent single-cell RNA sequencing
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Leucine Rich Repeat Kinase 2 is not required for lysozyme expression in intestinal Paneth cells bioRxiv. Physiol. Pub Date : 2024-03-08 Anna Tasegian, Dina Dikovskaya, Molly Scott, Tom Helps, Tosca Meus, Mairi H McLean, Mahima Swamy
Genetic variants in Leucine-rich Repeat Kinase 2 (LRRK2) gene have been linked to Parkinson's disease (PD) and are also associated with inflammatory bowel diseases (IBD), specifically Crohn's disease (CD), a transmural inflammation that can affect the entire length of the gastrointestinal tract and is commonly seen in the ileum. In ileal CD, defects in specialized intestinal epithelial cells known
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Low-frequency hearing thresholds improve as high-frequency hearing sensitivity deteriorates between young adulthood and middle age in normally hearing people bioRxiv. Physiol. Pub Date : 2024-03-07 Tatiana Izmaylova, Jaime Undurraga, Paul F Sowman
Hearing sensitivity changes throughout a person's lifetime. This work aimed to describe changes in pure-tone audiometric (PTA) thresholds that occur in the transition from young adulthood to middle age in 121 adults with normal or nearly normal hearing. Results showed that older people had worse high-frequency (4000-8000 Hz) thresholds and better low-frequency (125-500 Hz) thresholds than younger individuals
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Sympathetic Motor Neuron Dysfunction is a Missing Link in Age-Associated Sympathetic Overactivity bioRxiv. Physiol. Pub Date : 2024-03-07 Lizbeth de la Cruz, Derek Bui, Claudia M Moreno, Oscar Vivas
Overactivity of the sympathetic nervous system is a hallmark of aging. The cellular mechanisms behind this overactivity remain poorly understood, with most attention paid to likely central nervous system components. In this work, we hypothesized that aging also affects the function of motor neurons in the peripheral sympathetic ganglia. To test this hypothesis, we compared the electrophysiological
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Particulate Contamination of Human Placenta: Plastic and Non-Plastic bioRxiv. Physiol. Pub Date : 2024-03-06 Rewa W Zurub, Shannon A Bainbridge, Luna Rahman, Sabina Halappanavar, Mike Wade
Recent evidence indicates that the human womb is contaminated with a variety of particulate contaminants. Microplastics (MPs, tiny plastic particles (<5 mm) generated by the breakdown of larger plastic products in the environment) accumulation in human placenta has recently been described. In addition, recent evidence has correlated the number of air pollution particulates in term placentas to the
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Time dependent changes in feeding behavior and energy balance associated with weight gain in mice fed obesogenic diets bioRxiv. Physiol. Pub Date : 2024-03-05 Payam A. Fathi, Michelle B. Bales, Julio E. Ayala
Obesity is characterized by dysregulated homeostatic mechanisms resulting in positive energy balance, yet when this dysregulation occurs is unknown. We assessed the time course of alterations to behaviors promoting weight gain in male and female mice switched to obesogenic 60% or 45% high fat diet (HFD). Switching mice to obesogenic diets promotes transient bouts of hyperphagia during the first 2 weeks
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Chronic infection alters pathogen virulence, microbiome composition, and fly physiology across generations. bioRxiv. Physiol. Pub Date : 2024-03-05 Krystal Maya-Maldonado, Nichole A Broderick
In many insects, parents and offspring share the same environment. Thus, an infection in the parents has the potential to influence offspring defenses. Moreover, infection can also affect other host aspects, including the microbiome, development, and reproduction. To better understand the intergenerational impacts of infection, we assessed the effects of challenge by the gut pathogen Pseudomonas entomophila
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Mammalian Cell Models of the Distal Convoluted Tubule: A Systematic Review of Cell Lines, Culture Condition and Gene Expression bioRxiv. Physiol. Pub Date : 2024-03-04 Chutong Zhong, Zhen Sun, Alessandra Grillo, Stephen B Walsh, Keith Siew
This review examines the crucial role of human cellular models in renal physiology research, with a specific focus on the distal convoluted tubule (DCT). It aims to provide a comprehensive summary of the origins, culture practices, and genetic studies associated with commonly employed DCT cell models. To achieve this, a systematic literature review was performed on Europe PMC, employing a Boolean search
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Intermittent protein restriction elevates food intake and plasma ghrelin in male mice bioRxiv. Physiol. Pub Date : 2024-03-04 Karin Linnea Volcko, Hamid Taghipourbibalan, James E McCutcheon
Low-protein diets affect body weight, body composition, food intake, and food preferences in mice. Furthermore, single periods of protein restriction can have lasting effects on these parameters. We sought to examine the effect of multiple, short, bouts of protein restriction, relative to long-term maintenance on either a control (NR) or protein-restricted (PR) diet. We found that male mice experiencing
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Metformin treatment results in distinctive skeletal muscle mitochondrial remodeling in rats with different intrinsic aerobic capacities bioRxiv. Physiol. Pub Date : 2024-03-04 Matthew P Bubak, Arik Davidyan, Colleen L O'Reilly, Samim A Mondal, Jordan Kest, Stephen M Doidge, Agnieszka Katarzyna Borowik, Michael T Taylor, Evelina Voloviceva, Michael T Kinter, Steven Loyal Britton, Lauren G Koch, Michael B Stout, Tommy L Lewis, Benjamin F Miller
The rationale for the use of metformin as a treatment to slow aging was largely based on data collected from metabolically unhealthy individuals. For healthspan extension metformin will also be used in periods of good health. To understand potential context specificity of metformin treatment on skeletal muscle, we used a rat model (HCR/LCR) with a divide in intrinsic aerobic capacity. Outcomes of metformin
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Comparison of a novel potentiator of CFTR channel activity to ivacaftor in ameliorating mucostasis caused by cigarette smoke in primary human bronchial airway epithelial cells bioRxiv. Physiol. Pub Date : 2024-03-04 Adrian C Tanjala, Jia Xin Jiang, Paul D.W. Eckford, Mohabir Ramjeesingh, Canhui Li, Ling Jun Huan, Gabrielle Langeveld, Claire Townsend, Daniel Paone, Jakob Busch Petersen, Roman Pekhletski, LiPing Tang, Vamsee Raju, Steven M Rowe, Christine Bear
Background: Cystic Fibrosis causing mutations in the gene CFTR, reduce the activity of the CFTR channel protein, and leads to mucus aggregation, airway obstruction and poor lung function. A role for CFTR in the pathogenesis of other muco-obstructive airway diseases such as Chronic Obstructive Pulmonary Disease (COPD) has been well established. The CFTR modulatory compound, Ivacaftor (VX-770), potentiates
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Insulin-mediated suppression of fatty acid release predicts whole-body insulin resistance of glucose uptake and skeletal muscle insulin receptor activation bioRxiv. Physiol. Pub Date : 2024-03-04 Michael Schleh, Benjamin Ryan, Cheehoon Ahn, Alison Ludzki, Douglas Van Pelt, Lisa Pitchford, Olivia Chugh, Austin T Luker, Kathryn E Luker, Dmitri Samovski, Nada Abumrad, Charles Burant, Jeffrey Horowitz
To examine factors underlying why most, but not all adults with obesity exhibit impaired insulin-mediated glucose uptake, we compared: 1) rates of fatty acid (FA) release from adipose tissue, 2) skeletal muscle lipid droplet (LD) characteristics, and 3) insulin signaling events in skeletal muscle collected from cohorts of adults with obesity with 'HIGH' versus 'LOW' insulin sensitivity for glucose
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Respiration-Triggered Olfactory Stimulation Reduces Obstructive Sleep Apnea Symptoms Severity: A Prospective Pilot Study bioRxiv. Physiol. Pub Date : 2024-03-04 Ofer Perl, Lilach Kemer, Amit Green, Nissim Arish, Yael Corcos, Anat Arzi, Yaron Dagan
Study Objectives: Obstructive sleep apnea (OSA) is a prevalent sleep-disordered breathing condition characterized by repetitive reduction in breathing during sleep. Current standard of care for OSA management is continuous positive air pressure (CPAP) devices, which often suffer from low tolerance due to limited adherence. Capitalizing on the unique neurocircuitry of the olfactory system and its retained
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Beyond Kaftrio: mechanistic insights to maximize N1303K-CFTR rescue bioRxiv. Physiol. Pub Date : 2024-03-03 Iwona Pranke, Valeria Capurro, Benoit Chevalier, Emanuela Pesce, Valeria Tomati, Cristina Pastorino, Aurelie Hatton, Saik Urien, Mariateresa Lena, Elise Dreano, Renata Bocciardi, Federico Zara, Stefano Pantano, Vito Terlizzi, Cristina Lucanto, Stefano Costa, Laura Claut, Valeria Dacco, Piercarlo Poli, Massimo Maschio, Benedetta Fabrizzi, Nicole Caporelli, Marco Cipolli, Sonia Volpi, Vincent Jung, Kevin
Abstract Introduction N1303K is the fourth most frequent Cystic Fibrosis (CF) causing mutation. People with CF (pwCF) clinical status can be improved by Elexacaftor(ELX)/Tezacaftor(TEZ)/Ivacaftor (ETI) combotherapy. We investigated the mechanism underlying N1303K-CFTR rescue. Methods N1303K-CFTR expression and maturation was evaluated by Western Blot in cell lines and Human Nasal Epithelial Primary
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Suppressing mortality and curbing cellular damage by targeting VHL bioRxiv. Physiol. Pub Date : 2024-03-03 Wei Jiang, Yimin Cao, Yue Xue, Yichun Ji, Benjamin Y. Winer, Mengqi Zhang, Neel S Singhal, Jonathan Pierce, Song Chen, Dengke K. Ma
Mortality rate increases with age and can accelerate upon extrinsic or intrinsic damage to individuals. Identifying factors and mechanisms that curb the population mortality rate has wide-ranging implications. Here, we show that targeting the VHL-1 (Von Hippel-Lindau) protein suppresses C. elegans mortality caused by distinct factors, including elevated reactive oxygen species, temperature, and APOE4
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Voluntary co-contraction of ankle muscles alters motor unit discharge characteristics and reduces estimates of persistent inward currents bioRxiv. Physiol. Pub Date : 2024-03-03 Matheus M. Gomes, Sophia T. Jenz, James A. Beauchamp, Francesco Negro, C.J. Heckman, Gregory E.P. Pearcey
Motoneuronal persistent inward currents (PICs) are both facilitated by neuromodulatory inputs and highly sensitive to local inhibitory circuits (e.g., Ia reciprocal inhibition). Methods aimed to increase group Ia reciprocal inhibition from the antagonistic muscle have been successful in decreasing PICs, and the diffuse actions of neuromodulators released during activation of remote muscles have increased
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Estimation of the Achilles tendon twist in vivo by individual triceps surae muscle stimulation bioRxiv. Physiol. Pub Date : 2024-03-03 Laura Lecompte, Marion Crouzier, Stéphane Baudry, Benedicte Vanwanseele
The Achilles tendon (AT) is comprised of three distinct subtendons, each arising from the one of the three heads of the triceps surae muscles: gastrocnemius medialis (GM), gastrocnemius lateralis (GL) and soleus (SOL). These subtendons exhibit a twisted structure, classified as low (Type I), medium (Type II), and high (Type III) twist, based on cadaveric studies. Nevertheless, the in-vivo investigation
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Survival of tardigrades (Hypsibius exemplaris) to subzero temperatures depends on exposure intensity, duration, and ice-nucleation—as shown by large-scale mortality dye-based assays bioRxiv. Physiol. Pub Date : 2024-03-02 Ana M Lyons, Kevin T Roberts, Caroline M Williams
Tardigrades are an emerging model system for understanding a diversity of environmental stress responses, yet few studies describe the physiology of cold tolerance in hydrated, active tardigrades. Here, we develop methods to screen tardigrades for survival in a high-throughput manner, to investigate the impacts of several key environmental conditions on survival. The visualization of SYTOX Green uptake
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3D Transcranial ultrasound localization microscopy reveals major arteries in the sheep brain bioRxiv. Physiol. Pub Date : 2024-03-02 Antoine Coudert, Louise Denis, Arthur Chavignon, Sylvain Bodard, Mickael Naveau, Palma Pro Sistiaga, Romaric Saulnier, Cyrille Orset, Denis Vivien, Christine Chappard, Olivier Couture
Objective Stroke, a leading cause of mortality and disability globally, demands swift and accurate diagnosis for effective treatment. Although MRI and CT scans serve as conventional methods, their accessibility remains a challenge, prompting exploration into alternative, portable, and non-ionizing imaging solutions like ultrasound with reduced costs. While Ultrasound Localization Microscopy (ULM) displays
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Sterile kidney tissue injury induces neutrophil swarming in lung alveolar capillaries bioRxiv. Physiol. Pub Date : 2024-03-02 Yohei Komaru, Liang Ning, Carine Lama, Anusha Suresh, Eirini Kefaloyianni, Mark J Miller, Andreas Herrlich
Sterile tissue injury, such as by acute kidney injury, is common in the clinic and frequently associated with respiratory compromise and hypoxemia. We previously described signaling components released by the injured kidney that drive a remote inflammatory response in the lung. How this caused the resultant hypoxemia remained unclear. Here, we report that sterile kidney tissue injury induces rapid
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Prothrombin Knockdown Protects Podocytes and Reduces Proteinuria in Glomerular Disease bioRxiv. Physiol. Pub Date : 2024-03-02 Amanda P Waller, Katelyn J Wolfgang, Iva Pruner, Zachary S Stevenson, Eman Abdelghani, Kaushik Muralidharan, Tasha K Wilkie, Angela R Blissett, Edward P Calomeni, Tatyana A Vetter, Sergey V Brodsky, William E Smoyer, Marvin T Nieman, Bryce A Kerlin
Chronic kidney disease (CKD) is a leading cause of death, and its progression is driven by glomerular podocyte injury and loss, manifesting as proteinuria. Proteinuria includes urinary loss of coagulation zymogens, cofactors, and inhibitors. Importantly, both CKD and proteinuria significantly increase the risk of thromboembolic disease. Prior studies demonstrated that anticoagulants reduced proteinuria
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Human Foot Force Informs Balance Control Strategies when Standing on a Narrow Beam bioRxiv. Physiol. Pub Date : 2024-03-01 Kaymie Shiozawa, Marta Russo, Jongwoo Lee, Neville Hogan, Dagmar Sternad
Despite the abundance of studies on the control of standing balance, insights about the roles of biomechanics and neural control have been limited. Previous work introduced an analysis combining the direction and orientation of ground reaction forces. The intersection point of the lines of actions of these forces exhibited a consistent pattern across healthy, young subjects when computed for different
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Methods for imaging intracellular calcium signals in the mouse mammary epithelium in 2- and 3-dimensions bioRxiv. Physiol. Pub Date : 2024-03-01 Mathilde Folacci, Silke B Chalmers, Felicity M Davis
The mammary gland has a central role in optimal mammalian development and survival. Contractions of smooth muscle-like basal (or myoepithelial) cells in the functionally mature mammary gland in response to oxytocin are essential for milk ejection and are tightly regulated by intracellular calcium (Ca2+). Using mice expressing a genetically encoded Ca2+ indicator (GCaMP6f), we present in this chapter
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Hydroxysteroid 17-beta dehydrogenase 13 (Hsd17b13) knockdown attenuates liver steatosis in high-fat diet obese mice bioRxiv. Physiol. Pub Date : 2024-03-01 Shehroz Mahmood, Nicola Z Morrice, Dawn Thompson, Sara Milanizadeh, Sophie Wilson, Philip D Whitfield, George D Mcilroy, Justin J Rochford, Nimesh Mody
Hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) loss-of-function gene variants are associated with decreased risk of 'metabolic dysfunction-associated steatotic liver disease' (MASLD). Our RNA-seq analysis of steatotic liver from obese mice -/+ Fenretinide treatment identified major beneficial effects of Fenretinide on hepatic gene expression including Hsd17b13. We sought to determine the relationship
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Prenatal Exposure to Environmentally Relevant Low Dosage Dibutyl Phthalate Reduces Placental Efficiency in CD-1 Mice bioRxiv. Physiol. Pub Date : 2024-03-01 Tasha Pontifex, Xinran Yang, Ayna Tracy, Kimberlie Burns, Zelieann Craig, Chi Zhou
Introduction: Dibutyl phthalate (DBP), a phthalate congener, is widely utilized in consumer products and medication coatings. Women of reproductive age have a significant burden of DBP exposure through consumer products, occupational exposure, and medication. Prenatal DBP exposure is associated with adverse pregnancy/fetal outcomes and cardiovascular diseases in the offspring. However, the mechanisms
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Oolonghomobisflavans from Camellia sinensis disaggregate tau fibrils across Alzheimer's disease models bioRxiv. Physiol. Pub Date : 2024-03-01 Chatrawee Duangjan, Xinmin Chang, Paul Matthew Seidler, Sean P Curran
Alzheimer's disease (AD) is a common debilitating neurodegenerative disease with limited treatment options. Amyloid-beta (AB) and tau fibrils are well-established hallmarks of AD, which can induce oxidative stress, neuronal cell death, and are linked to disease pathology. Here, we describe the effects of Oolonghomobisflavan A (OFA) and Oolonghomobisflavan B (OFB) on tau fibril disaggregation and prionogenic
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Genetic regulation and targeted reversal of lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension bioRxiv. Physiol. Pub Date : 2024-03-01 Lloyd D Harvey, Mona Alotaibi, Hee-Jung Janice Kim, Yi-Yin Tai, Ying Tang, Wei Sun, Wadih El Khoury, Chen-Shan C Woodcock, Yassmin Al Aaraj, Claudette M St. Croix, Donna B Stolz, Jiyoung Lee, Mary Hongying Cheng, Tae-Hwi Schwantes-An, Ankit A Desai, Michael W Pauciulo, William C Nichols, Amy Webb, Robert Lafyatis, Mehdi Nouraie, Haodi Wu, Jeffrey G McDonald, Caroline Chauvet, Susan Cheng, Ivet Bahar
Vascular inflammation critically regulates endothelial cell (EC) pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulation of lysosomal activity and cholesterol metabolism have known inflammatory roles in disease, but their relevance to PAH is unclear. In human pulmonary arterial ECs and in PAH, we found that inflammatory cytokine induction of the nuclear receptor coactivator
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High-Resolution Spatial Transcriptomic Atlas of Mouse Soleus Muscle: Unveiling Single Cell and Subcellular Heterogeneity in Health and Denervation bioRxiv. Physiol. Pub Date : 2024-02-29 Jer-En Hsu, Lloyd Ruiz, Yongha Hwang, Steve Guzman, Chun-Seok Cho, Weiqiu Cheng, Yichen Si, Peter Macpherson, Mitchell Schrank, Goo Jun, Hyun-Min Kang, Myungjin Kim, Susan Brooks, Jun Hee Lee
Skeletal muscle is essential for both movement and metabolic processes, characterized by a complex and ordered structure. Despite its importance, a detailed spatial map of gene expression within muscle tissue has been challenging to achieve due to the limitations of existing technologies, which struggle to provide high-resolution views. In this study, we leverage the Seq-Scope technique, an innovative
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A method for correcting systematic error in PO2 measurement to improve measures of oxygen supply capacity bioRxiv. Physiol. Pub Date : 2024-02-28 Alexander W Timpe, Brad A Seibel
An organism's oxygen supply capacity (α) can be measured as a ratio of the metabolic rate (MR) and the critical oxygen partial pressure (Pc). However, this metric is sensitive to errors in the measurement of PO2, especially at low PO2 where the ratio of instrument error to environmental oxygen is magnified. Consequently, the oxygen supply capacity of animals, particularly those that evolved in low-oxygen
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Corticosterone in very young seabird chicks (Rissa tridactyla) is sensitive to environmental variability and responds rapidly and robustly to external challenges bioRxiv. Physiol. Pub Date : 2024-02-28 Z Morgan Benowitz-Fredericks, Alexis P. Will, Sierra N. Pete, Shannon Whelan, Alexander S. Kitaysky
In birds, patterns of development of the adrenocortical response to stressors vary among individuals, types of stressors, and species. Since there are benefits and costs of exposure to elevated glucocorticoids, this variation is presumably a product of selection such that animals modulate glucocorticoid secretion in contexts where doing so increases their fitness. In this study, we evaluated hypot
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Metabolic control of adaptive β-cell proliferation by the protein deacetylase SIRT2 bioRxiv. Physiol. Pub Date : 2024-02-28 Matthew Wortham, Bastian Ramms, Chun Zeng, Jacqueline R Benthuysen, Somesh Sai, Dennis P Pollow, Fenfen Liu, Michael Schlichting, Austin R Harrington, Bradley Liu, Thazha P Prakash, Elaine C Pirie, Han Zhu, Siyouneh Baghdasarian, Johan Auwerx, Orian S. Shirihai, Maike Sander
Selective and controlled expansion of endogenous β-cells has been pursued as a potential therapy for diabetes. Ideally, such therapies would preserve feedback control of β-cell proliferation to avoid excessive β-cell expansion and an increased risk of hypoglycemia. Here, we identified a regulator of β-cell proliferation whose inactivation results in controlled β-cell expansion: the protein deacetylase
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Short periods of decreased water flow may modulate long-term ocean acidification in reef-building corals bioRxiv. Physiol. Pub Date : 2024-02-28 Catarina P. P. Martins, Susana M. Simancas-Giraldo, Patrick Schubert, Marlene Wall, Christian Wild, Thomas Wilke, Maren Ziegler
Ocean acidification (OA) poses a major threat to reef-building corals. Although water flow variability is common in coral reefs and modulates coral physiology, the interactive effects of flow and OA on corals remain poorly understood. Therefore, we performed a three-month OA experiment investigating the effect of changes in flow on coral physiology. We exposed the reef-building corals Acropora cytherea
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Identifying HRV and EEG correlates of well-being using ultra-short, portable, and low-cost measurements bioRxiv. Physiol. Pub Date : 2024-02-28 Cedric Cannard, Arnaud Delorme, Helane Wahbeh
Wearable electroencephalography (EEG) and electrocardiography (ECG) devices may offer a non-invasive, user-friendly, and cost-effective approach for assessing well-being (WB) in real-world settings. However, challenges remain in dealing with signal artifacts (such as environmental noise and movements) and identifying robust biomarkers. We evaluated the feasibility of using portable hardware to identify
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Steeper or Faster? Impacts of Similar-intensity Running Conditions on Heart Rate Variability bioRxiv. Physiol. Pub Date : 2024-02-28 Vivian MCA ElDash, Ingrid Machado Cusin Ahmed ElDash, Fernando Silveira Marques, Jose E S Natali, Jose Guilherme Chaui-Berlinck
Increases in speed or slope promote different adjustments in the locomotor system and lead to a higher heart rate (HR). Because heart rate variability (HRV) is known to respond to exercise intensity and to biomechanical stimuli, we aimed to answer whether HRV would be sensitive to changes in speed and/or slope under similar HR. We hypothesize that HRV would depend solely on HR. To test this hypothesis
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Paced Breathing With a Prolonged Inspiratory Period Increases Sympathetic Activity: A Heart and Brain Analysis bioRxiv. Physiol. Pub Date : 2024-02-27 Miguel S. Joaquim, Carlos Moreira
Paced breathing exercises with prolonged exhalation have been commonly used to reduce stress and anxiety by stimulating parasympathetic activity. However, increasing sympathetic activity may also provide benefits such as increased alertness and energy levels. In this work, we investigate the physiological impact of an 80-second breathing exercise with a prolonged inspiratory period of 6 seconds followed
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What Does Large-scale Electrodermal Sensing Reveal? bioRxiv. Physiol. Pub Date : 2024-02-27 Daniel McDuff, Seamus Thomson, Samy Abdel-Ghaffar, Isaac Galatzer-Levy, Ming-Zher Poh, Jake Sunshine, Andrew Barakat, Conor Heneghan, Lindsey Sunden
Electrodermal activity (EDA) is a physiological measure that is used to index sympathetic arousal in response to stressors and other perturbations. However, EDA is underutilized in real-world, population-level research and clinical practice because of a paucity of remote measurement capabilities on commodity devices. The current study examined the capabilities of continuous remote measurement of EDA