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Cardiac fibroblasts play a pivotal role in maintaining heart homeostasis by depositing extracellular matrix (ECM) to provide structural support for the myocardium, vasculature, and neuronal network and by contributing to essential physiological processes. In response to injury such as myocardial infarction or pressure overload, fibroblasts become activated, leading to increased ECM production that can ultimately drive left ventricular remodeling and progress to heart failure. Recently, the American Journal of Physiology-Heart and Circulatory Physiology issued a call for papers on cardiac fibroblasts that yielded articles with topics spanning fibroblast physiology, technical considerations, signaling pathways, and interactions with other cell types. This mini-review summarizes those articles and places the new findings in the context of what is currently known for cardiac fibroblasts and what future directions remain. [ABSTRACT FROM AUTHOR]

In recent years, there has been a burgeoning interest in exploring the nuances of animal stress physiology, particularly in relation to parameters such as sex and behavioral phenotype-dependent variations, which is crucial for understanding phenotypic variation and its role in evolutionary selection. However, a significant dearth remains in how chronic stressors affect organismal stress physiology concerning the aforesaid parameters. This void is even wider pertaining to the response of peripheral tissues, such as the skin, the organ with the highest surface contact area with the environment. Hence, we behaviorally grouped the zebrafishes based on their boldness and the body condition, whole body cortisol response, along with examining the transcriptional response, global DNA methylome, and oxidative DNA damage in the skin upon chronic crowding. Upon baseline conditions, clear distinction between bold and shy phenotypes was found, particularly in males. The boldness index score distribution exhibited greater uniformity in males than in females. Regarding the body condition response to chronic crowding, shy males showed a significant relative decline compared with their bold counterparts, while this trend did not hold true for females. qPCR data revealed distinctive expression patterns in key genes that play critical roles in cellular processes such as stress-mediated gene regulation, immune response, oxidative stress protection, and maintenance of genomic integrity through epigenetic modifications across behavioral phenotypes and sexes under both with and without chronic crowding stress. Global DNA methylation levels significantly declined only in chronically crowded shy males, and sex/behavioral phenotype-dependent trends in oxidative DNA damage were identified. NEW & NOTEWORTHY: This paper analyzes the response of zebrafish to crowding stress through a new approach focused on the peripheral response dynamics of the skin, the main mucosal tissue, and involving sex and behavioral phenotype influences. Shy males showed significant distress as observed by body condition, physiological and transcriptional response, and global DNA methylation. Nuances in stress response across behavioral phenotypes and sex indicate a genetic and behavioral specificity and further inherent epigenetic regulatory dimension. [ABSTRACT FROM AUTHOR]

Angiotensin II (ANG II) is known to play an important role in regulating renal hemodynamics. We sought to quantify this effect in an in vivo rat model with high‐resolution renal arterial (RA) impedance. This study examines the effects of ANG II and its type 1 receptor blocker telmisartan (TELM) on RA impedance. In baroreflex-deactivated rats, we measured RA pressure (Pr) and blood flow (Fr) during random ventricular pacing to induce pressure fluctuation at three different mean Pr (60, 80, and 100 mmHg). We then estimated RA impedance as the transfer function from Fr to Pr. The RA impedance was found to align with a three‐element Windkessel model consisting of proximal (Rp) and distal (Rd) resistance and compliance (C). Our study showed Rd reflected the composite characteristics of afferent and efferent arterioles. Rd increased with increasing Pr under the baseline condition with a slope of 1.03 ± 0.21 (× 10−1) min·mL−1. ANG II significantly increased the slope by 0.72 ± 0.29 (× 10−1) min·mL−1 (P < 0.05) without affecting the intercept. TELM significantly reduced the intercept by 34.49 ± 4.86 (× 10−1) mmHg·min·mL−1 (P < 0.001) from the baseline value of 37.93 ± 13.36 (× 10−1) mmHg·min·mL−1, whereas it did not affect the slope. In contrast, Rp was less sensitive than Rd to ANG II or TELM, suggesting Rp may represent the characteristics of elastic large arteries. Our findings provide valuable insights into the influence of ANG II on the dynamics of the renal vasculature. NEW & NOTEWORTHY: This present method of quantifying high-resolution renal arterial impedance could contribute to elucidating the characteristics of renal vasculature influenced by physiological mechanisms, renal diseases, or pharmacological effects. The present findings help construct a lumped-parameter renal hemodynamic model that reflects the influence of angiotensin II. [ABSTRACT FROM AUTHOR]

The maternal cardiovascular system undergoes functional and structural adaptations during pregnancy and postpartum to support increased metabolic demands of offspring and placental growth, labor, and delivery, as well as recovery from childbirth. Thus, pregnancy imposes physiological stress upon the maternal cardiovascular system, and in the absence of an appropriate response it imparts potential risks for cardiovascular complications and adverse outcomes. The proportion of pregnancy-related maternal deaths from cardiovascular events has been steadily increasing, contributing to high rates of maternal mortality. Despite advances in cardiovascular physiology research, there is still no comprehensive understanding of maternal cardiovascular adaptations in healthy pregnancies. Furthermore, current approaches for the prognosis of cardiovascular complications during pregnancy are limited. Machine learning (ML) offers new and effective tools for investigating mechanisms involved in pregnancy-related cardiovascular complications as well as the development of potential therapies. The main goal of this review is to summarize existing research that uses ML to understand mechanisms of cardiovascular physiology during pregnancy and develop prediction models for clinical application in pregnant patients. We also provide an overview of ML platforms that can be used to comprehensively understand cardiovascular adaptations to pregnancy and discuss the interpretability of ML outcomes, the consequences of model bias, and the importance of ethical consideration in ML use. [ABSTRACT FROM AUTHOR]

Polyamines are molecules with multiple amino groups that are essential for cellular function. The major polyamines are putrescine, spermidine, spermine, and cadaverine. Polyamines are important for posttranscriptional regulation, autophagy, programmed cell death, proliferation, redox homeostasis, and ion channel function. Their levels are tightly controlled. High levels of polyamines are associated with proliferative pathologies such as cancer, whereas low polyamine levels are observed in aging, and elevated polyamine turnover enhances oxidative stress. Polyamine metabolism is implicated in several pathophysiological processes in the nervous, immune, and cardiovascular systems. Currently, manipulating polyamine levels is under investigation as a potential preventive treatment for several pathologies, including aging, ischemia/reperfusion injury, pulmonary hypertension, and cancer. Although polyamines have been implicated in many intracellular mechanisms, our understanding of these processes remains incomplete and is a topic of ongoing investigation. Here, we discuss the regulation and cellular functions of polyamines, their role in physiology and pathology, and emphasize the current gaps in knowledge and potential future research directions. [ABSTRACT FROM AUTHOR]

The appropriate growth of the neurons, accurate organization of their synapses, and successful neurotransmission are indispensable for sensorimotor activities. These processes are highly dynamic and tightly regulated. Extensive genetic, molecular, physiological, and behavioral studies have identified many molecular candidates and investigated their roles in various neuromuscular processes. In this article, we show that Beadex (Bx), the Drosophila LIM only (LMO) protein, is required for motor activities and neuromuscular growth of Drosophila. The larvae bearing Bx7, a null allele of Bx, and the RNAi-mediated neuronal-specific knockdown of Bx show drastically reduced crawling behavior, a diminished synaptic span of the neuromuscular junctions (NMJs) and an increased spontaneous neuronal firing with altered motor patterns in the central pattern generators (CPGs). Microarray studies identified multiple targets of Beadex that are involved in different cellular and molecular pathways, including those associated with the cytoskeleton and mitochondria that could be responsible for the observed neuromuscular defects. With genetic interaction studies, we further show that Highwire (Hiw), a negative regulator of synaptic growth at the NMJs, negatively regulates Bx, as the latter's deficiency was able to rescue the phenotype of the Hiw null mutant, HiwDN. Thus, our data indicate that Beadex functions downstream of Hiw to regulate the larval synaptic growth and physiology. NEW & NOTEWORTHY: A novel role for Beadex (Bx) regulates the larval neuromuscular junction (NMJ) structure and function in a tissue-specific manner. Bx is expressed in a subset of Toll-6-expressing neurons and is involved in regulating synaptic span and physiology, possibly through its negative interaction with Highwire (Hiw). The findings of this study provide insights into the molecular mechanisms underlying NMJ development and function and warrant further investigation to understand the role of Bx in these processes fully. [ABSTRACT FROM AUTHOR]

The gut microbiome, a complex assembly of microorganisms, significantly impacts human health by influencing nutrient absorption, the immune system, and disease response. These microorganisms form a dynamic ecosystem that is critical to maintaining overall well-being. Prebiotics and probiotics are pivotal in regulating gut microbiota composition. Prebiotics nourish beneficial bacteria and promote their growth, whereas probiotics help maintain balance within the microbiome. This intricate balance extends to several aspects of health, including maintaining the integrity of the gut barrier, regulating immune responses, and producing metabolites crucial for metabolic health. Dysbiosis, or an imbalance in the gut microbiota, has been linked to metabolic disorders such as type 2 diabetes, obesity, and cardiovascular disease. Impaired gut barrier function, endotoxemia, and low-grade inflammation are associated with toll-like receptors influencing proinflammatory pathways. Short-chain fatty acids derived from microbial fermentation modulate anti-inflammatory and immune system pathways. Prebiotics positively influence gut microbiota, whereas probiotics, especially Lactobacillus and Bifidobacterium strains, may improve metabolic outcomes, such as glycemic control in diabetes. It is important to consider strain-specific effects and study variability when interpreting these findings, highlighting the need for further research to optimize their therapeutic potential. The aim of this report is therefore to review the role of the gut microbiota in metabolic health and disease and the effects of prebiotics and probiotics on the gut microbiome and their therapeutic role, integrating a broad understanding of physiological mechanisms with a clinical perspective. [ABSTRACT FROM AUTHOR]

Blood flow to the active muscles and arterial blood pressure (ABP) increase during dynamic exercise, whereas blood flow to inactive organs (e.g., splanchnic organs and inactive limbs) declines. Aging leads to exaggerated ABP responses to exercise in females, but whether this is related to greater splanchnic vasoconstriction is unknown. This study sought to clarify the effect of aging in females on celiac artery blood flow during dynamic light-intensity exercise. Twelve healthy young females (YF: 20 ± 2 yr, mean ± SD) and 12 healthy older females (OF: 71 ± 4 yr) performed dynamic knee-extension and knee-flexion exercises at 30% of heart rate reserve for 4 min. The absolute changes from baseline (Δ) for mean arterial blood pressure (MAP), celiac artery mean blood flow (celMBF), and celiac vascular conductance (celVC) during exercise were calculated. ABP was measured using an automated sphygmomanometer, and celMBF was recorded by Doppler ultrasonography. The increase in MAP during exercise was greater in OF than in YF (YF: +14 ± 7 mmHg, OF: +24 ± 13 mmHg, P = 0.028). The celMBF decreased during exercise in both groups, but there was no significant difference in the response between YF and OF (YF: −93.0 ± 66.1 mL/min, OF: −89.6 ± 64.0 mL/min, P = 0.951). The celVC also decreased during exercise and remained lower than baseline during exercise. However, the response was not different between YF and OF (YF: −1.8 ± 1.0 mL/min/mmHg, OF: −1.5 ± 0.6 mL/min/mmHg, P = 0.517). These results demonstrate that aging in females has minimal influence on splanchnic artery hemodynamic responses during dynamic light-intensity exercise, suggesting that exaggerated ABP responses during exercise in OF are not due to greater splanchnic vasoconstriction. NEW & NOTEWORTHY: During exercise, the splanchnic arteries vasoconstrict, contributing to blood flow redistribution and the blood pressure response. Blood pressure responses to exercise are exaggerated with aging in females; however, the physiological mechanism responsible has not been clarified. We show that celiac artery blood flow changes during light-intensity dynamic exercise do not differ with age in females. This indicates the exaggerated blood pressure to exercise with aging is likely not due to a difference in splanchnic vasoconstriction. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is extremely prevalent among hospitalizations and presents a significant risk for the development of chronic kidney disease and increased mortality. Ischemia caused by shock, trauma, and transplant are common causes of AKI. To attenuate ischemic AKI therapeutically, we need a better understanding of the physiological and cellular mechanisms underlying damage. Instances of ischemia are most damaging in proximal tubule epithelial cells (PTECs) where hypoxic signaling cascades, and perhaps more rapidly, posttranslational modifications (PTMs), act in concert to change cellular metabolism. Here, we focus on the effects of the understudied PTM, lysine succinylation. We have previously shown a protective effect of protein hypersuccinylation on PTECs after depletion of the desuccinylase sirtuin5. General trends in the results suggested that hypersuccinylation led to upregulation of peroxisomal activity and was protective against kidney injury. Included in the list of changes was the Parkinson's-related deglycase Park7. There is little known about any links between peroxisome activity and Park7. In this study, we show in vitro and in vivo that Park7 has a crucial role in protection from AKI and upregulated peroxisome activity. These data in combination with published results of Park7's protective role in cardiovascular damage and chronic kidney disease lead us to hypothesize that succinylation of Park7 may ameliorate oxidative damage resulting from AKI and prevent disease progression. This novel mechanism provides a potential therapeutic mechanism that can be targeted. NEW & NOTEWORTHY Succinylation is an understudied posttranslational modification that has been shown to increase peroxisomal activity. Furthermore, increased peroxisomal activity has been shown to reduce oxidative stress and protect proximal tubules after acute kidney injury. Analysis of mass spectrometry succinylomic and proteomic data reveals a novel role for Parkinson's related Park7 in mediating Nrf2 antioxidant response after kidney injury. This novel protection pathway provides new insights for kidney injury prevention and development of novel therapeutics. [ABSTRACT FROM AUTHOR]

The kidneys maintain fluid-electrolyte balance and excrete waste in the presence of constant fluctuations in plasma volume and systemic blood pressure. The kidneys perform these functions to control capillary perfusion and glomerular filtration by modulating the mechanisms of autoregulation. An effect of these modulations are spontaneous, natural fluctuations in glomerular perfusion. Numerous other mechanisms can lead to fluctuations in perfusion and flow. The ability to monitor these spontaneous physiological fluctuations in vivo could facilitate the early detection of kidney disease. The goal of this work was to investigate the use of resting-state magnetic resonance imaging (rsMRI) to detect spontaneous physiological fluctuations in the kidney. We performed rsMRI of rat kidneys in vivo over 10 min, applying motion correction to resolve time series in each voxel. We observed spatially variable, spontaneous fluctuations in rsMRI signal between 0 and 0.3 Hz, in frequency bands associated with autoregulatory mechanisms. We further applied rsMRI to investigate changes in these fluctuations in a rat model of diabetic nephropathy. Spectral analysis was performed on time series of rsMRI signals in the kidney cortex and medulla. The power from spectra in specific frequency bands from the cortex correlated with severity of glomerular pathology caused by diabetic nephropathy. Finally, we investigated the feasibility of using rsMRI of the human kidney in two participants, observing the presence of similar, spatially variable fluctuations. This approach may enable a range of preclinical and clinical investigations of kidney function and facilitate the development of new therapies to improve outcomes in patients with kidney disease. NEW & NOTEWORTHY This work demonstrates the development and use of resting-state MRI to detect low-frequency, spontaneous physiological fluctuations in the kidney consistent with previously observed fluctuations in perfusion and potentially due to autoregulatory function. These fluctuations are detectable in rat and human kidneys, and the power of these fluctuations is affected by diabetic nephropathy in rats. [ABSTRACT FROM AUTHOR]

Maternal mortality rates are at an all-time high across the world and are set to increase in subsequent years. Cardiovascular disease is the leading cause of death during pregnancy and postpartum, especially in the United States. Therefore, understanding the physiological changes in the cardiovascular system during normal pregnancy is necessary to understand disease-related pathology. Significant systemic and cardiovascular physiological changes occur during pregnancy that are essential for supporting the maternal-fetal dyad. The physiological impact of pregnancy on the cardiovascular system has been examined in both experimental animal models and in humans. However, there is a continued need in this field of study to provide increased rigor and reproducibility. Therefore, these guidelines aim to provide information regarding best practices and recommendations to accurately and rigorously measure cardiovascular physiology during normal and cardiovascular disease-complicated pregnancies in human and animal models. [ABSTRACT FROM AUTHOR]

Historically, programs of physical education and sport were housed in gymnasium buildings on academic campuses. As physical education evolved to the more scientifically focused successor departments of exercise science and kinesiology, faculty specialization developed in the physiology of exercise. With time, some faculty broadened their research to study the integrative physiology of other biological states and stressors. Through this series of events, a small group of integrative physiologists was formed in the Carlson Gymnasium at the University of Colorado Boulder during the 1990s with the goal of conducting novel biomedical research. The challenges were daunting: no contemporary core laboratory facilities, lack of temperature control, piercing external noise, pests, regular flooding, electrical power outages, and lack of funds for renovation. Despite these obstacles, the group established an innovative program of translational physiological research ranging from high-throughput molecular analyses to cell models to rodent studies to clinical trials in humans. These investigators supported their work with grant awards from the National Institutes of Health (NIH), Department of Defense, National Aeronautics and Space Administration (NASA), American Heart Association, and private research foundations totaling ∼$80 M in direct costs from the late 1980s to 2020. Collectively, the faculty and their laboratory personnel published ∼950 articles in peer-reviewed scientific journals. Over that period, 379 undergraduate students, 340 graduate students, 84 postdoctoral fellows, and dozens of junior research faculty received scientific training in Carlson, supported by >$21 M in extramural funding. What was accomplished by this handful of integrative physiologists speaks to the importance of the qualities of the investigators rather than their research facilities in determining scientific success. [ABSTRACT FROM AUTHOR]

Here we demonstrate how data from the clinical pulmonary function lab can help students learn about the principle of airway-parenchymal interdependence. We examined the relationship between airway conductance (Gaw) and lung volume (thoracic gas volume, TGV) in 48 patients: 17 healthy; 20 with emphysema, expected to have reduced airway-parenchymal interdependence; and 11 with pulmonary fibrosis, expected to have increased airway-parenchymal interdependence. Our findings support these expectations, with the slope of Gaw vs. TGV being steeper among those with pulmonary fibrosis and flatter among those with emphysema, compared to the slope of the healthy group. This type of analytic approach, using real-world patient data readily available from any pulmonary function laboratory, can be used to explore other fundamental principles of respiratory physiology. NEW & NOTEWORTHY: This report demonstrates how common data obtained from the clinical pulmonary function testing laboratory can be used to illustrate important principles of respiratory physiology. Here we show how the relationship between airway conductance and lung volume across different disease states reflects intrinsic differences in airway-parenchymal interdependence. [ABSTRACT FROM AUTHOR]

The advent of artificial intelligence (AI)-powered language models presents new opportunities and challenges in education. By teaching students how to craft prompts that elicit insightful responses, faculty can scaffold activities where AI acts as a supplemental resource to amplify critical thinking and support student learning. Ongoing dialogue and iteration focused on ethical usage norms can achieve the right balance between emerging technology and foundational skills development. With care and intention, AI-assisted study tactics offer students personalized support while adhering to academic standards. While AI-powered tools provide many positive opportunities, students and faculty need to learn about and use them responsibly and ethically, not as replacements for required thinking and effort. Before implementing these AI tools for studying biology, there are several key things to discuss with students. This article outlines several ways that students can employ these tools to support better learning along with a set of guidelines for all to be wary of when implementing these in an academic setting. NEW & NOTEWORTHY: Utilizing of artificial intelligence tools offers a promising new technology to support student learning. This article outlines several ways that students can employ these tools to support better learning along with a set of guidelines for all to be wary of when implementing these in an academic setting. [ABSTRACT FROM AUTHOR]

Emotional intelligence (EI) has a positive correlation with the academic performance of medical students. However, why there is a positive correlation needs further exploration. We hypothesized that the capability of answering higher-order knowledge questions (HOQs) is higher in students with higher EI. Hence, we assessed the correlation between EI and the capability of medical students to answer HOQs in physiology. First-year undergraduate medical students (n = 124) from an Indian medical college were recruited as a convenient sample. EI was assessed by the Schutte Self-Report Emotional Intelligence Test (SSEIT), a 33-item self-administered validated questionnaire. A specially designed objective examination with 15 lower-order and 15 higher-order multiple-choice questions was conducted. The correlation between the examination score and the EI score was tested by Pearson's correlation coefficient. Data from 92 students (33 females and 59 males) with a mean age of 20.14 ± 1.87 yr were analyzed. Overall, students got a percentage of 53.37 ± 14.07 in the examination, with 24.46 ± 9.1 in HOQs and 28.91 ± 6.58 in lower-order knowledge questions (LOQs). They had a mean score of 109.58 ± 46.2 in SSEIT. The correlation coefficient of SSEIT score with total marks was r = 0.29 (P = 0.0037), with HOQs was r = 0.41 (P < 0.0001), and with LOQs was r = 0.14 (P = 0.19). Hence, there is a positive correlation between EI and the capability of medical students to answer HOQs in physiology. This study may be the foundation for further exploration of the capability of answering HOQs in other subjects. NEW & NOTEWORTHY: This study assessed the correlation between emotional intelligence (EI) and the capability of medical students to answer higher-order knowledge questions (HOQs) in the specific context of physiology. The finding reveals one of the multifaceted dimensions of the relationship between EI and academic performance. This novel perspective opens the door to further investigations to explore the relationship in other subjects and other dimensions to understand why students with higher EI have higher academic performance. [ABSTRACT FROM AUTHOR]

Diabetes mellitus and obesity are major public health issues that significantly impact the health care system. The next generation of health care providers will need a deep understanding of the pathophysiology of these diseases if we are to prevent, treat, and eventually cure these diseases and ease the burden on patients and the health care system. Physiology core concepts are a set of core principles, or "big ideas," identified by physiology educators that are thought to promote long-term retention, create a deeper understanding, and help with formation of critical thinking skills. Here we describe our scaffolded teaching approach in an upper year undergraduate pathophysiology course to educate students about these two diseases and discuss how learning about the basis of these highly integrative diseases from the biochemical to whole body level is a meaningful tool in the physiology educator toolbox to reinforce physiology core concepts. This teaching strategy is designed to engage students in the scientific process and hone their problem-solving skills such that they are hopefully equipped to treat and eventually cure these diseases as they move forward in their careers. NEW & NOTEWORTHY: Students often struggle with integration of physiological systems. Type 2 diabetes mellitus and obesity are two related diseases that are useful to explore the interdependence of physiological systems and multiple physiology core concepts. Deep learning about these diseases has the potential to dramatically improve the health care system of the future. [ABSTRACT FROM AUTHOR]

In response to COVID-19, educators rapidly pivoted to new and innovative ways of delivering lecture material. The ability to host synchronous lectures on platforms like Zoom gave students continued access to classroom material in the face of an ongoing pandemic. The purpose of this study was to investigate the differences in exam scores between students attending a physiology class (PHSL3051) synchronously via Zoom or asynchronously by viewing recorded lectures posted after class. Students in PHSL3051 were evaluated with four unit exams and one cumulative final exam. Although pooled analysis of all students showed that synchronous lecture viewing positively predicted exam scores, this positive association was even larger when the data were analyzed by gender and ethnicity. For female-identified students and students of color (SOC), attending lectures synchronously was associated with average scores on every unit exam that were higher by 2.7–7.4 percentage points. Moreover, the greater a student's synchronous participation in the course throughout the semester, the better that student's performance on the cumulative final exam was likely to be. These data highlight the need to better understand how different groups of undergraduate students select and respond to different assessment methods used in the same course, which may have long-term effects on their overall performance at 4-year institutions. NEW & NOTEWORTHY: This study examined the relationship between lecture attendance (synchronous or asynchronous) and exam scores throughout the semester. Although everyone in the course benefited from synchronous lecture attendance, our data indicated that students of color (SOC) and female-identified students benefited most. SOC and female-identified students who participated synchronously had even higher mean scores on all exams within the course compared with SOC and female-identified students who participated asynchronously by watching recordings of the same lectures. [ABSTRACT FROM AUTHOR]

The study aims to develop a novel methodology to demonstrate the vestibulo-ocular reflex (VOR) and nystagmus by caloric stimulation in an undergraduate medical physiology laboratory. The experimental setup involved two sets of electrodes: one set positioned laterally to both eyes, and another set positioned vertically over either the right or left eye. The caloric method is used to stimulate ears, which involves irrigation of warm (44°C) and cold (30°C) water into the ears while maintaining a temperature difference of approximately ±7°C from the body temperature. The changes in chorioretinal potential were calibrated to angular displacement by a two-point calibration method, and angular velocity was derived after taking the first-time derivative. The results obtained from the digital data acquisition system were compared to the traditional instrument used in our Otorhinolaryngology Department [Interacoustics Videonystagmography (VNG) System for hospitals, medical grade] for the normal subject's data. No significant differences in angular velocity were noted (P > 0.05). The cold stimuli elicit a more pronounced VOR compared to the warm stimuli. It has been consistently observed that the onset of nystagmus occurs approximately 20 s after irrigation, reaching its peak intensity between 45 and 90 s, and gradually diminishing until it ceases after approximately 200 s. Our developed methodology enables the recording and quantification of nystagmus using easily accessible equipment. This study serves the goal of visualizing the physiological process of VOR and thereby fulfills the goal of an effective teaching tool for demonstrating to undergraduate medical students. NEW & NOTEWORTHY: We developed a novel methodology to demonstrate and visualize the most common and important physiological phenomenon like the vestibulo-ocular reflex as a teaching module for undergraduate students. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis examined the physiological mechanisms responsible for lower peak exercise leg oxygen uptake (V̇ o 2) in patients with chronic disease. Studies measuring peak leg V̇ o 2 (primary outcome) and its physiological determinants during large (cycle) or small muscle mass exercise (single-leg knee extension, SLKE) in patients with chronic disease were included in this meta-analysis. Pooled estimates for each outcome were reported as a weighted mean difference (WMD) between chronic disease and controls. We included 10 studies that measured peak leg V̇ o 2 in patients with chronic disease (n = 109, mean age: 45 yr; encompassing chronic obstructive pulmonary disease, COPD, heart failure with reduced ejection fraction, HFrEF, or chronic renal failure, RF) and age-matched controls (n = 88). In pooled analysis, peak leg V̇ o 2 (WMD; −0.23 L/min, 95% CI: −0.32 to −0.13), leg oxygen (O2) delivery (WMD: −0.27 L/min, 95% CI: −0.37 to −0.17), and muscle O2 diffusive conductance (WMD: −5.2 mL/min/mmHg, 95% CI: −7.1 to −3.2) were all significantly lower during cycle and SLKE exercise in chronic disease versus controls. These results highlight that during large and small muscle mass exercise in patients with COPD, HFrEF, or RF, there is no single factor causing peak V̇ o 2 limitations. Specifically, the lower peak V̇ o 2 in these pathologies is due to not only the expected impairments in convective O2 delivery but also impairments in muscle oxygen diffusive transport from capillary to mitochondria. Whether impaired muscle O2 transport is caused solely by inactivity or additional muscle pathology remains in question. NEW & NOTEWORTHY: Peripheral (skeletal muscle and vasculature) factors contribute significantly to reduced exercise capacity during both large and small muscle mass exercise in chronic diseases such as COPD, HFrEF, or RF and should be important targets of therapy in addition to the primary organs (lungs, heart, and kidneys) affected by disease. [ABSTRACT FROM AUTHOR]

Ground-level ozone (O3) is a potent air pollutant well recognized to acutely induce adverse respiratory symptoms and impairments in pulmonary function. However, it is unclear how the hyperpnea of exercise may modulate these effects, and the subsequent consequences on exercise performance. We tested the hypothesis that pulmonary function and exercise capability would be diminished, and symptom development would be increased during peak real-world levels of O3 exposure compared with room air. Twenty aerobically trained participants [13 M, 7 F; maximal O2 uptake (V̇ o 2max), 64.1 ± 7.0 mL·kg−1·min−1] completed a three-visit double-blinded, randomized crossover trial. Following a screening visit, participants were exposed to 170 ppb O3 or room air (<10 ppb O3) on separate visits during exercise trials, consisting of a 25-min moderate-intensity warmup, 30-min heavy-intensity bout, and a subsequent time-to-exhaustion (TTE) performance test. No differences in O2 uptake or ventilation were observed during submaximal exercise between conditions. During the TTE test, we observed significantly lower end-exercise O2 uptake (−3.2 ± 4.3%, P = 0.004), minute ventilation (−3.2 ± 6.5%, P = 0.043), tidal volume (−3.6 ± 5.1%, P = 0.008), and a trend toward lower exercise duration in O3 compared with room air (−10.8 ± 26.5%, P = 0.092). As decreases in O2 uptake and alterations in respiratory pattern were also present at matched time segments between conditions, a limitation of oxygen transport seems likely during maximal exercise. A more comprehensive understanding of the direct mechanisms that limit oxygen transport during exercise in high-pollutant concentrations is key for mitigating performance changes. NEW & NOTEWORTHY: We demonstrate that in highly trained endurance athletes, exposure to peak real-world levels of O3 air pollution (170 ppb) significantly diminishes O2 uptake along with corresponding changes in ventilation during maximal exercise. As no differences were observed during extended submaximal exercise, a combined effect of effective dose of pollution and exercise intensity on severity of responses seems likely. [ABSTRACT FROM AUTHOR]

Mice with skeletal muscle-specific and inducible double knockout of the lysine acetyltransferases, p300 (E1A binding protein p300) and CBP (cAMP-response element-binding protein binding protein), referred to as i-mPCKO, demonstrate a dramatic loss of contractile function in skeletal muscle and ultimately die within 7 days. Given that many proteins involved in ATP generation and cross-bridge cycling are acetylated, we investigated whether these processes are dysregulated in skeletal muscle from i-mPCKO mice and, thus, whether they could underlie the rapid loss of muscle contractile function. Just 4–5 days after inducing knockout of p300 and CBP in skeletal muscle from adult i-mPCKO mice, there was ∼90% reduction in ex vivo contractile function in the extensor digitorum longus (EDL) and a ∼65% reduction in in vivo ankle dorsiflexion torque, as compared with wild type (WT; i.e., Cre negative) littermates. Despite this profound loss of contractile force in i-mPCKO mice, there were no genotype-driven differences in fatigability during repeated contractions, nor were there genotype differences in mitochondrial-specific pathway enrichment of the proteome, intermyofibrillar mitochondrial volume, or mitochondrial respiratory function. As it relates to cross-bridge cycling, remarkably, the overt loss of contractile function in i-mPCKO muscle was reversed in permeabilized fibers supplied with exogenous Ca2+ and ATP, with active tension being similar between i-mPCKO and WT mice, regardless of Ca2+ concentration. Actin-myosin motility was also similar in skeletal muscle from i-mPCKO and WT mice. In conclusion, neither mitochondrial abundance/function, nor actomyosin cross-bridge cycling, are the underlying driver of contractile dysfunction in i-mPCKO mice. NEW & NOTEWORTHY: The mechanism underlying dramatic loss of muscle contractile function with inducible deletion of both E1A binding protein p300 (p300) and cAMP-response element-binding protein binding protein (CBP) in skeletal muscle remains unknown. Here, we find that impairments in mitochondrial function or cross-bridge cycling are not the underlying mechanism of action. Future work will investigate other aspects of excitation-contraction coupling, such as Ca2+ handling and membrane excitability, as contractile function could be rescued by permeabilizing skeletal muscle, which provides exogenous Ca2+ and bypasses membrane depolarization. [ABSTRACT FROM AUTHOR]

Larsucosterol, a potent endogenous epigenetic regulator, has been reported to play a significant role in lipid metabolism, inflammatory responses, and cell survival. The administration of larsucosterol has demonstrated a reduction in lipid accumulation within hepatocytes and the attenuation of inflammatory responses induced by lipopolysaccharide (LPS) and TNFα in macrophages, alleviating LPS- and acetaminophen (ATMP)-induced multiple organ injury, and decreasing mortalities in animal models. Results from phase 1 and 2 clinical trials have shown that larsucosterol has potential as a biomedicine for the treatment of acute and chronic liver diseases. Recent evidence suggests that larsucosterol is a promising candidate for treating alcohol-associated hepatitis with positive results from a phase 2a clinical trial, and for metabolic dysfunction-associated steatohepatitis (MASH) from a phase 1b clinical trial. In this review, we present a culmination of our recent research efforts spanning two decades. We summarize the discovery, physiological and pharmacological mechanisms, and clinical applications of larsucosterol. Furthermore, we elucidate the pathophysiological pathways of metabolic dysfunction-associated steatotic liver diseases (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), and acute liver injuries. A central focus of the review is the exploration of the therapeutic potential of larsucosterol in treating life-threatening conditions, including acetaminophen overdose, endotoxin shock, MASLD, MASH, hepatectomy, and alcoholic hepatitis. [ABSTRACT FROM AUTHOR]

Pressure overload-induced hypertrophy compromises cardiac stretch-induced compliance (SIC) after acute volume overload (AVO). We hypothesized that SIC could be enhanced by physiological hypertrophy induced by pregnancy's chronic volume overload. This study evaluated SIC-cardiac adaptation in pregnant women with or without cardiovascular risk (CVR) factors. Thirty-seven women (1st trimester, 1stT) and a separate group of 31 (3rd trimester, 3rdT) women [healthy or with CVR factors (obesity and/or hypertension and/or with gestational diabetes)] underwent echocardiography determination of left ventricular end-diastolic volume (LVEDV) and E/e' before (T0), immediately after (T1), and 15 min after (T2; SIC) AVO induced by passive leg elevation. Blood samples for NT-proBNP quantification were collected before and after the AVO. Acute leg elevation significantly increased inferior vena cava diameter and stroke volume from T0 to T1 in both 1stT and 3rdT, confirming AVO. LVEDV and E/e' also increased immediately after AVO (T1) in both 1stT and 3rdT. SIC adaptation (T2, 15 min after AVO) significantly decreased E/e' in both trimesters, with additional expansion of LVEDV only in the 1stT. NT-pro-BNP increased slightly after AVO but only in the 1stT. CVR factors, but not parity or age, significantly impacted SIC cardiac adaptation. A distinct functional response to SIC was observed between 1stT and 3rdT, which was influenced by CVR factors. The LV of 3rdT pregnant women was hypertrophied, showing a structural limitation to dilate with AVO, whereas the lower LV filling pressure values suggest increased diastolic compliance. NEW & NOTEWORTHY The sudden increase of volume overload triggers an acute myocardial stretch characterized by an immediate rise in contractility by the Frank-Starling mechanism, followed by a progressive increase known as the slow force response. The present study is the first to characterize echocardiographically the stretch-induced compliance (SIC) mechanism in the context of physiological hypertrophy induced by pregnancy. A distinct functional adaptation to SIC was observed between first and third trimesters, which was influenced by cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Phosphodiesterases (PDEs) are a superfamily of enzymes that hydrolyze cyclic nucleotides, including cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Both cyclic nucleotides are critical secondary messengers in the neurohormonal regulation in the cardiovascular system. PDEs precisely control spatiotemporal subcellular distribution of cyclic nucleotides in a cell- and tissue-specific manner, playing critical roles in physiological responses to hormone stimulation in the heart and vessels. Dysregulation of PDEs has been linked to the development of several cardiovascular diseases, such as hypertension, aneurysm, atherosclerosis, arrhythmia, and heart failure. Targeting these enzymes has been proven effective in treating cardiovascular diseases and is an attractive and promising strategy for the development of new drugs. In this review, we discuss the current understanding of the complex regulation of PDE isoforms in cardiovascular function, highlighting the divergent and even opposing roles of PDE isoforms in different pathogenesis. [ABSTRACT FROM AUTHOR]

High-level athletic performances may be a proxy for the trajectory of optimal function of human biology with advanced aging and the differences between males and females. Males are faster, stronger, and more powerful than females and these physical attributes decline dramatically with advanced aging for both sexes. Experimental mechanistic studies determine the physiological mechanisms for these sex and age differences in human physical performance. The assumption however, that real-world performances solely reflect the biological and physiological differences between the sexes and with advanced aging, even among elite athletes, is not complete. This review presents evidence that an integrated approach encompassing analysis of real-world data and experimental mechanistic studies is necessary to determine the biological and sociocultural factors attributed to the limits of performance with aging and between males and females. First, experimental studies are presented that focus on the sex and age differences in performance fatigability that determine the physiological mechanisms of absolute and relative exercise performance. Second, analysis of current and historical real-world data including world records, and performances of elite, collegiate, and competitive age-group athletes are highlighted. These data illustrate that the upper limits of physical performance that have changed historically, and other factors such as sociocultural influences, explain the widening of the sex and age gaps in human performance observed in real-world data even in present-day performances. These approaches have broader significance when applied to understanding the impact of the historically low representation of females and minority groups in biomedical research on health outcomes. [ABSTRACT FROM AUTHOR]

Estradiol and estrogen receptor α (ERα) have been shown to be important for the maintenance of skeletal muscle strength in females; however, little is known about the roles of estradiol and ERα in male muscle. The purpose of this study was to determine if skeletal muscle ERα is required for optimal contractility in male mice. We hypothesize that reduced ERα in skeletal muscle impairs contractility in male mice. Skeletal muscle-specific knockout (skmERαKO) male mice exhibited reduced strength across multiple muscles and several contractile parameters related to force generation and kinetics compared with wild-type littermates (skmERαWT). Isolated EDL muscle-specific isometric tetanic force, peak twitch force, peak concentric and peak eccentric forces, as well as the maximal rates of force development and relaxation were 11%–21% lower in skmERαKO compared with skmERαWT mice. In contrast, isolated soleus muscles from skmERαKO mice were not affected. In vivo peak torque of the anterior crural muscles was 20% lower in skmERαKO compared with skmERαWT mice. Muscle masses, contractile protein contents, fiber types, phosphorylation of the myosin regulatory light chain, and caffeine-elicited force did not differ between muscles of skmERαKO and skmERαWT mice, suggesting that strength deficits were not due to size, composition, or calcium release components of muscle contraction. These results indicate that in male mice, reduced skeletal muscle ERα blunts contractility to a magnitude similar to that previously reported in females; however, the mechanism may be sexually dimorphic. NEW & NOTEWORTHY: We comprehensively measured in vitro and in vivo contractility of leg muscles with reduced estrogen receptor α (ERα) in male mice and reported that force generation and contraction kinetics are impaired. In contrast to findings in females, phosphorylation of myosin regulatory light chain cannot account for low force production in male skeletal muscle ERα knockout mice. These results indicate that ERα is required for optimal contractility in males and females but via sexually dimorphic means. [ABSTRACT FROM AUTHOR]

There have been ongoing efforts by federal agencies and scientific communities since the early 1990s to incorporate sex and/or gender in all aspects of cardiovascular research. Scientific journals provide a critical function as change agents to influence transformation by encouraging submissions for topic areas, and by setting standards and expectations for articles submitted to the journal. As part of ongoing efforts to advance sex and gender in cardiovascular physiology research, the American Journal of Physiology-Heart and Circulatory Physiology recently launched a call for papers on Considering Sex as a Biological Variable. This call was an overwhelming success, resulting in 78 articles published in this collection. This review summarizes the major themes of the collection, including Sex as a Biological Variable Within: Endothelial Cell and Vascular Physiology, Cardiovascular Immunity and Inflammation, Metabolism and Mitochondrial Energy, Extracellular Matrix Turnover and Fibrosis, Neurohormonal Signaling, and Cardiovascular Clinical and Epidemiology Assessments. Several articles also focused on establishing rigor and reproducibility of key physiological measurements involved in cardiovascular health and disease, as well as recommendations and considerations for study design. Combined, these articles summarize our current understanding of sex and gender influences on cardiovascular physiology and pathophysiology and provide insight into future directions needed to further expand our knowledge. [ABSTRACT FROM AUTHOR]

Certain deep-diving marine mammals [i.e., northern elephant seal (Mirounga angustirostris), Weddell seal (Leptonychotes weddellii)] have blood carbon monoxide (CO) levels that are comparable with those of chronic cigarette smokers. Most CO produced in humans is a byproduct of heme degradation, which is released when red blood cells (RBCs) are destroyed. Elevated CO can occur in humans when RBC lifespan decreases. The contribution of RBC turnover to CO concentrations in marine mammals is unknown. Here, we report the first RBC lifespans in two healthy marine mammal species with different diving capacities and heme stores, the shallow-diving bottlenose dolphin (Tursiops truncatus) and deep-diving beluga whale (Delphinapterus leucas), and we relate the lifespans to the levels of CO in blood and breath. The belugas, with high blood heme stores, had the longest mean RBC lifespan compared with humans and bottlenose dolphins. Both cetacean species were found to have three times higher blood CO content compared with humans. The estimated CO production rate from heme degradation indicates some marine mammals may have additional mechanisms for CO production, or delay CO removal from the body, potentially from long-duration breath-holds. [ABSTRACT FROM AUTHOR]

The article titled "From promise to success: AJP-Cell Physiology's journey of accomplishments and future vision" discusses the achievements and future plans of the American Journal of Physiology: Cell Physiology. The journal has successfully expanded its content by introducing new topics and collaborating with guest editors. It has also increased its visibility across medical disciplines and attracted submissions from clinicians focused on basic science. The journal plans to further improve by focusing on cutting-edge scientific advancements, implementing a fast-track review process, and increasing diversity of submissions. The article also discusses strategies such as attending conferences, increasing communication with editors and members, and transitioning to an open-access publication model. The author expresses gratitude to the committee, editors, and staff for their contributions. [Extracted from the article]

One aspect of effective scientific writing in physiology is the ability to select the correct words or short phrases to use when developing your narratives. This task is made difficult because many commonly used terms have seemingly viable alternatives, leading to confusion, uncertainty, and possible misuse of those words and phrases. In this perspective, we attempt to provide general guidance when selecting between or among options for commonly confused and misused terms in scientific writing. We have organized inaccurate, confusing, commonly misused, and misleading words and phrases into separate tables categorized as general language, demographic descriptors, general science, physiological sciences, and exercise physiology. Our modest hope is that the current perspective facilitates effective writing and encourages discussion regarding the importance of clarity in writing. [ABSTRACT FROM AUTHOR]

Applying blood flow restriction (BFR) during low-load exercise induces beneficial adaptations of the myotendinous and neuromuscular systems. Despite the low mechanical tension, BFR exercise facilitates a localized hypoxic environment and increase in metabolic stress, widely regarded as the primary stimulus for tissue adaptations. First evidence indicates that low-load BFR exercise is effective in promoting an osteogenic response in bone, although this has previously been postulated to adapt primarily during high-impact weight-bearing exercise. Besides studies investigating the acute response of bone biomarkers following BFR exercise, first long-term trials demonstrate beneficial adaptations in bone in both healthy and clinical populations. Despite the increasing number of studies, the physiological mechanisms are largely unknown. Moreover, heterogeneity in methodological approaches such as biomarkers of bone metabolism measured, participant and study characteristics, and time course of measurement renders it difficult to formulate accurate conclusions. Furthermore, incongruity in the methods of BFR application (e.g., cuff pressure) limits the comparability of datasets and thus hinders generalizability of study findings. Appropriate use of biomarkers, effective BFR application, and befitting study design have the potential to progress knowledge on the acute and chronic response of bone to BFR exercise and contribute toward the development of a novel strategy to protect or enhance bone health. Therefore, the purpose of the present synthesis review is to 1) evaluate current mechanistic evidence; 2) discuss and offer explanations for similar and contrasting data findings; and 3) create a methodological framework for future mechanistic and applied research. [ABSTRACT FROM AUTHOR]

The baroreflex is a powerful physiological mechanism for rapidly adjusting heart rate in response to changes in blood pressure. Spontaneous baroreflex sensitivity (BRS) has been shown to decrease with age. However, studies of sex differences in these age-related changes are rare. Here we investigated several markers of spontaneous baroreflex function in a large sample of healthy individuals. Cardiovascular signals were recorded in the supine position under carefully controlled resting conditions. After quality control, n = 980 subjects were divided into five age groups [age < 30 yr (n = 612), 30-39 yr (n = 140), 40-49 yr (n = 95), 50-59 yr (n = 61), and >60 yr (n = 72)]. Spontaneous baroreflex function was assessed in the time domain (bradycardic and tachycardic slope) and in the frequency domain in the low- and high-frequency band (LF-a, HF-a) applying the transfer function. General linear models showed a significant effect of factor age (P < 0.001) and an age - sex interaction effect (P < 0.05) on each indicator of the baroreflex function. Simple main effects showed a significantly higher BRS as indicated by tachycardic slope, LF-a and HF-a in middle-aged women compared with men (30-39 yr) and higher LF-a, bradycardic and tachycardic slope in men compared with women of the oldest age group (>60 yr). Changes in BRS over the lifespan suggest that baroreflex function declines more slowly but earlier in life in men than in women. Our findings could be linked to age-related changes in major sex hormone levels, suggesting significant implications for diverse cardiovascular outcomes and the implementation of targeted preventive strategies. [ABSTRACT FROM AUTHOR]

Wavelet analysis (WA) provides superior time-frequency decomposition of complex signals than conventional spectral analysis tools. To illustrate its usefulness in assessing transient phenomena, we applied a custom-developed WA algorithm to laser-Doppler (LD) signals of the cutaneous microcirculation measured at glabrous (finger pulp) and nonglabrous (forearm) sites during early recovery after dynamic exercise. This phase, importantly contributing to the establishment of thermal homeostasis after exercise cessation, has not been adequately explored because of its complex, transient form. Using WA, we decomposed the LD signals measured during the baseline and early recovery into power spectra of characteristic frequency intervals corresponding to endothelial nitric oxide (NO)-dependent, neurogenic, myogenic, respiratory, and cardiac physiological influence. Assessment of relative power (RP), defined as the ratio between the median power in the frequency interval and the median power of the total spectrum, revealed that endothelial NO-dependent (5.87 early recovery; 1.53 baseline; P = 0.005; Wilcoxon signed-rank test) and respiratory (0.71 early recovery; 0.40 baseline; P = 0.001) components were significantly increased, and myogenic component (1.35 early recovery; 1.83 baseline; P = 0.02) significantly decreased during early recovery in the finger pulp. In the forearm, only the RP of the endothelial NO-dependent (1.90 early recovery; 0.94 baseline; P = 0.009) component was significantly increased. WA presents an irreplaceable tool for the assessment of transient phenomena. The relative contribution of the physiological mechanisms controlling the microcirculatory response in the early recovery phase appears to differ in glabrous and nonglabrous skin when compared with baseline; moreover, the endothelial NO-dependent influence seems to play an important role. [ABSTRACT FROM AUTHOR]

Conserved in female reproduction across all mammalian species is the estrous cycle and its regulation by the hypothalamic-pituitary- gonadal (HPG) axis, a collective of intersected hormonal events that are crucial for ensuring uterine fertility. Nonetheless, knowledge of the direct mediators that synchronously shape the uterine microenvironment for successive yet distinct events, such as the transit of sperm and support for progressive stages of preimplantation embryo development, remain principally defi- cient. Toward understanding the timed endometrial outputs that permit luminal events as directed by the estrous cycle, we used Bovidae as a model system to uniquely surface sample and study temporal shifts to in vivo endometrial transcripts that encode for proteins destined to be secreted. The results revealed the full quantitative profile of endometrial components that shape the uterine luminal microenvironment at distinct phases of the estrous cycle (estrus, metestrus, diestrus, and proestrus). In interpreting this comprehensive log of stage-specific endometrial secretions, we define the "uterine secretory cycle" and extract a predictive understanding of recurring physiological actions regulated within the uterine lumen in anticipation of sperm and preimplantation embryonic stages. This repetitive microenvironmental preparedness to sequentially provide operative support was a stable intrinsic framework, with only limited responses to sperm or embryos if encountered in the lumen within the cyclic time period. In uncovering the secretory cycle and unraveling realistic biological processes, we present novel foundational knowledge of terminal effectors controlled by the HPG axis to direct a recurring sequence of vital functions within the uterine lumen. NEW & NOTEWORTHY This study unravels the recurring sequence of changes within the uterus that supports vital functions (sperm transit and development of preimplantation embryonic stages) during the reproductive cycle in female Ruminantia. These data present new systems knowledge in uterine reproductive physiology crucial for setting up in vitro biomimicry and artificial environments for assisted reproduction technologies for a range of mammalian species. [ABSTRACT FROM AUTHOR]

Skeletal muscle is a highly complex tissue that is studied by scientists from a wide spectrum of disciplines, including motor control, biomechanics, exercise science, physiology, cell biology, genetics, regenerative medicine, orthopedics, and engineering. Although this diversity in perspectives has led to many important discoveries, historically, there has been limited overlap in discussions across fields. This has led to misconceptions and oversimplifications about muscle biology that can create confusion and potentially slow scientific progress across fields. The purpose of this synthesis paper is to bring together research perspectives across multiple muscle fields to identify common assumptions related to muscle fiber type that are points of concern to clarify. These assumptions include 1) classification by myosin isoform and fiber oxidative capacity is equivalent, 2) fiber cross-sectional area (CSA) is a surrogate marker for myosin isoform or oxidative capacity, and 3) muscle force-generating capacity can be inferred from myosin isoform. We address these three fiber-type traps and provide some context for how these misunderstandings can and do impact experimental design, computational modeling, and interpretations of findings, from the perspective of a range of fields. We stress the dangers of generalizing findings about "muscle fiber types" among muscles or across species or sex, and we note the importance for precise use of common terminology across the muscle fields. [ABSTRACT FROM AUTHOR]

Exercise in hypoxia increases immune responses compared with normoxic exercise, and while Toll-like receptor 4 (TLR4) is implicated in these responses, its regulation remains undefined. The purpose of this study was to 1) investigate TLR4 regulation during workload-matched endurance exercise in normoxic and hypoxic conditions in vivo and 2) determine the independent effects of hypoxia and muscle contractions on TLR4 expression in vitro. Eight recreationally active men cycled for 1 h at 65% of their V̇O2max in normoxia (630 mmHg) and in hypobaric hypoxia (440 mmHg). Exercise in normoxia decreased TLR4 expressed on peripheral blood mononuclear cells (PBMCs), had no effect on the expression of inhibitor of κBα (IκBα), and increased the concentration of soluble TLR4 (sTLR4) in circulation. In contrast, exercise in hypoxia decreased the expression of TLR4 and IκBα in PBMCs, and sTLR4 in circulation. Markers of physiological stress were higher during exercise in hypoxia, correlating with markers of intestinal barrier damage, circulating lipopolysaccharides (LPS), and a concurrent decrease in circulating sTLR4, suggesting heightened TLR4 activation, internalization, and degradation in response to escalating physiological strain. In vitro, both hypoxia and myotube contractions independently, and in combination, reduced TLR4 expressed on C2C12 myotubes, and these effects were dependent on hypoxia-inducible factor 1 (HIF-1). In summary, the regulation of TLR4 varies depending on the physiological stress during exercise. To our knowledge, our study provides the first evidence of exercise-induced effects on sTLR4 in vivo and highlights the essential role of HIF-1 in the reduction of TLR4 during contraction and hypoxia in vitro. [ABSTRACT FROM AUTHOR]

The American Journal of Physiology: Lung Cellular & Molecular Physiology is offering their Editorial Board Fellowship Program to enhance peer review and train future leaders in respiratory physiology. Fellows receive mentoring on manuscript evaluation and editorial processing, attend board meetings, and contribute to journal initiatives. The program has been successful, with previous fellows publishing numerous manuscripts and remaining involved with the journal. The application process for the next round of the fellowship program will open in May 2024. Additionally, the document includes a list of grants and disclosures related to various research projects in physiology, as well as references to articles published in the journal on topics such as kidney physiology, lung surfactant, and the effects of substances on lung function. [Extracted from the article]

Kidney organoids are three-dimensional structures generated from pluripotent stem cells (PSCs) that are capable of recapitulating the major structures of mammalian kidneys. As this technology is expected to be a promising tool for studying renal biology, drug discovery, and regenerative medicine, the functional capacity of kidney organoids has emerged as a critical question in the field. Kidney organoids produced using several protocols harbor key structures of native kidneys. Here, we review the current state, recent advances, and future challenges in the functional characterization of kidney organoids, strategies to accelerate and enhance kidney organoid functions, and access to PSC resources to advance organoid research. The strategies to construct physiologically relevant kidney organoids include the use of organ-on-a-chip technologies that integrate fluid circulation and improve organoid maturation. These approaches result in increased expression of the major tubular transporters and elements of mechanosensory signaling pathways suggestive of improved functionality. Nevertheless, continuous efforts remain crucial to create kidney tissue that more faithfully replicates physiological conditions for future applications in kidney regeneration medicine and their ethical use in patient care. NEW & NOTEWORTHY Kidney organoids are three-dimensional structures derived from stem cells, mimicking the major components of mammalian kidneys. Although they show great promise, their functional capacity has become a critical question. This review explores the advancements and challenges in evaluating and enhancing kidney organoid function, including the use of organ-on-chip technologies, multiomics data, and in vivo transplantation. Integrating these approaches to further enhance their physiological relevance will continue to advance disease modeling and regenerative medicine applications. [ABSTRACT FROM AUTHOR]

This is a memoir of my experiences in learning and teaching Physiology. It begins in 1962 when I entered the University of Washington as a medical student and began research in a physiology laboratory, which led to a Ph.D. degree in Physiology and Biophysics to go with my M.D. degree in 1968. At this time, both groups of students participated in the same physiology course containing both lectures and laboratories. After postdoctoral research at the NIH and in Cambridge, UK, in 1973 I joined the faculty of the Department of Physiology, University of California, San Francisco where I participated in the teaching of medical students and graduate students for nearly 15 years. By this time, the teaching of medical and graduate students had largely separated. In 1987, I moved to the University of Michigan as Professor and Chair of Physiology where my role in teaching was organizational as well as participatory for the next 35 years. In this work, I compare the teaching of medical students as well as graduate students and focus on how it has changed over this 60-year period. Over this time both medical and graduate Ph.D. education have become more integrative. Medical education is now taught in organ blocks rather than courses, and I participated in organizing the teaching of the gastrointestinal block. At Michigan, there is no longer a separate medical school class in Physiology, and graduate students enter a combined, "Program in Biomedical Science" for a year before choosing a mentor and department. NEW & NOTEWORTHY Teaching remains an important part of the career of academic physiologists. It is important for schools offering the Ph.D. to provide instruction and experience in teaching. The American Physiology Society has developed new programs to assist teachers and many universities have centers on learning and teaching. [ABSTRACT FROM AUTHOR]

A well-developed mental model is crucial for effectively studying physiology core concepts. However, mental models can be difficult for students to represent and for instructors to evaluate and correct. Systems modeling as a visualization cognitive tool may facilitate mental model development. On the other hand, evidence of mental model development may also be represented verbally, in writing, and therefore, be evaluated. In this study, analysis of writing prompt completions illustrated progress in physician assistant student mental model formation of physiology core concepts, such as homeostasis and cell-cell communication, over time. Two cohorts of physician assistant students were invited to voluntarily submit completions of writing prompts five times over 16 months. Sessions included submissions pre- and post-small group systems modeling participation. Word frequency and word association cluster dendrogram analyses were conducted on submissions using the tm text mining package in R to provide insight into progressive changes in core concepts of word use and associations. Students demonstrated expanded core concepts systems thinking over time. This was apparent through the increased use of systems process terms, such as homeostasis, in submissions immediately following systems modeling activities. Students also increasingly included terms and associations emphasizing cell-cell communication and systems integration. The inclusion of these concepts within student mental models was demonstrably enhanced by participation in systems modeling activities. NEW & NOTEWORTHY This study applies text mining, an artificial intelligence form of natural language processing, to evaluate a series of physiology student-written prompt completions. Text mining of student writing in physiology has not yet been reported in the literature. Through the application of this technique, longitudinal trends in student development of mental models of core concepts were identified and visualized through word frequency distributions and cluster dendrograms. [ABSTRACT FROM AUTHOR]

Conserved in female reproduction across all mammalian species is the estrous cycle and its regulation by the hypothalamic-pituitary-gonadal (HPG) axis, a collective of intersected hormonal events that are crucial for ensuring uterine fertility. Nonetheless, knowledge of the direct mediators that synchronously shape the uterine microenvironment for successive yet distinct events, such as the transit of sperm and support for progressive stages of preimplantation embryo development, remain principally deficient. Toward understanding the timed endometrial outputs that permit luminal events as directed by the estrous cycle, we used Bovidae as a model system to uniquely surface sample and study temporal shifts to in vivo endometrial transcripts that encode for proteins destined to be secreted. The results revealed the full quantitative profile of endometrial components that shape the uterine luminal microenvironment at distinct phases of the estrous cycle (estrus, metestrus, diestrus, and proestrus). In interpreting this comprehensive log of stage-specific endometrial secretions, we define the "uterine secretory cycle" and extract a predictive understanding of recurring physiological actions regulated within the uterine lumen in anticipation of sperm and preimplantation embryonic stages. This repetitive microenvironmental preparedness to sequentially provide operative support was a stable intrinsic framework, with only limited responses to sperm or embryos if encountered in the lumen within the cyclic time period. In uncovering the secretory cycle and unraveling realistic biological processes, we present novel foundational knowledge of terminal effectors controlled by the HPG axis to direct a recurring sequence of vital functions within the uterine lumen. NEW & NOTEWORTHY This study unravels the recurring sequence of changes within the uterus that supports vital functions (sperm transit and development of preimplantation embryonic stages) during the reproductive cycle in female Ruminantia. These data present new systems knowledge in uterine reproductive physiology crucial for setting up in vitro biomimicry and artificial environments for assisted reproduction technologies for a range of mammalian species. [ABSTRACT FROM AUTHOR]

This study assessed the physiological, performance, nutritional intake, and training characteristics of a 92-yr-old four-time master world champion indoor male rower. Body composition was assessed via bioelectrical impedance. Oxygen uptake, carbon dioxide production, ventilation, and heart rate were measured at rest and during a 2,000-m time trial on a rowing ergometer. Maximal power was assessed to compute anaerobic power reserve. Training included - 30 km/wk on the rowing ergometer. Herein, 70% of distances were covered at light intensities (RPE, 10-12), 20% at hard (RPE, 13-17), and 10% at near maximal or maximal (RPE, 17-20). Resistance training was performed during - 2 sessions/wk, and involved three sets of dumbbell lunges, rows, and curls, respectively, taken close (or to) failure. Dietary intake was high in protein [2.3 ± 0.1 g·kg-1 lean body mass (LBM)], conferring a caloric intake of 33.4 ± 1.7 kcal·kg-1 LBM. The participant demonstrated muscle mass of 47.7 kg, fat mass of 9.1 kg (15.4% body fat), forced vital capacity of 3.36 L, time constant (s) to steady state of 30.2 s, peak relative oxygen pulse of 0.18 ([mL·O2/beats/min]/kg), peak heart rate of 153 beats/min, and maximum power of 220 W (140 W anaerobic power reserve). This 92-yr-old athlete demonstrated remarkably fast oxygen uptake kinetics, akin to values for a healthy young adult, indicating well-developed and/or maintained cardiopulmonary function. The high values for cardiopulmonary function, muscle mass, metabolic efficiency, and maximum power output may infer the pliability of these systems to maintain high functionality at an advanced age. [ABSTRACT FROM AUTHOR]

AT-hook DNA-binding motif-containing protein 1 (AHDC1) is a causal gene of intellectual disability/developmental delay in humans. The biological role of AHDC1 is unclear. Recently, some clues from AHDC1 mutation carriers hinted that AHDC1 may participate in body-weight regulation. In this first metabolic phenotype study of Ahdc1 deficiency, we generated a Ahdc1-defi- cienct mouse line and found that Ahdc1 deficiency in both male and female mice led to adiposity from weaning and obesity characterized by reduced energy expenditure and respiratory quotient, with progressive development of hyperleptinemia, insulin resistance, abnormal glycolipid metabolism, and fatty liver. Our findings show that Ahdc1 is a novel key regulator of obesity and energy metabolism, which provides new insight into the physiological mechanisms of obesity. [ABSTRACT FROM AUTHOR]

The array of ion channels and transporters expressed in cell membranes, collectively referred to as the transportome, is a complex and multifunctional molecular machinery; in particular, at the plasma membrane level it finely tunes the exchange of biomolecules and ions, acting as a functionally adaptive interface that accounts for dynamic plasticity in the response to environmental fluctuations and stressors. The transportome is responsible for the definition of membrane potential and its variations, participates in the transduction of extracellular signals, and acts as a filter for most of the substances entering and leaving the cell, thus enabling the homeostasis of many cellular parameters. For all these reasons, physiologists have long been interested in the expression and functionality of ion channels and transporters, in both physiological and pathological settings and across the different domains of life. Today, thanks to the high-throughput technologies of the postgenomic era, the omics approach to the study of the transportome is becoming increasingly popular in different areas of biomedical research, allowing for a more comprehensive, integrated, and functional perspective of this complex cellular apparatus. This article represents a first effort for a systematic review of the scientific literature on this topic. Here we provide a brief overview of all those studies, both primary and meta-analyses, that looked at the transportome as a whole, regardless of the biological problem or the models they used. A subsequent section is devoted to the methodological aspect by reviewing the most important public databases annotating ion channels and transporters, along with the tools they provide to retrieve such information. Before conclusions, limitations and future perspectives are also discussed. [ABSTRACT FROM AUTHOR]

Most explanations for the relationship between body size and metabolism invoke physical constraints; such explanations are evolutionarily inert, limiting their predictive capacity. Contemporary approaches to metabolic rate and life history lack the pluralism of foundational work. Here, we call for reforging of the lost links between optimization approaches and physiology. [ABSTRACT FROM AUTHOR]

Artificial intelligence in health care has experienced remarkable innovation and progress in the last decade. Significant advancements can be attributed to the utilization of artificial intelligence to transform physiology data to advance health care. In this review, we explore how past work has shaped the field and defined future challenges and directions. In particular, we focus on three areas of development. First, we give an overview of artificial intelligence, with special attention to the most relevant artificial intelligence models. We then detail how physiology data have been harnessed by artificial intelligence to advance the main areas of health care: automating existing health care tasks, increasing access to care, and augmenting health care capabilities. Finally, we discuss emerging concerns surrounding the use of individual physiology data and detail an increasingly important consideration for the field, namely the challenges of deploying artificial intelligence models to achieve meaningful clinical impact. [ABSTRACT FROM AUTHOR]

The primary structure of the thiazide-sensitive NaCl cotransporter (NCC) was resolved 30 years ago by the molecular identification of the cDNA encoding this cotransporter, from the winter’s flounder urinary bladder, following a functional expression strategy. This review outlines some aspects of how the knowledge about thiazide diuretics and NCC evolved, the history of the cloning process, and the expansion of the SLC12 family of electroneutral cotransporters. The diseases associated with activation or inactivation of NCC are discussed, as well as the molecular model by which the activity of NCC is regulated. The controversies in the field are discussed as well as recent publication of the three-dimensional model of NCC obtained by cryo-electron microscopy, revealing not only the amino acid residues critical for Na + and Cl- translocation but also the residues critical for polythiazide binding to the transporter, opening the possibility for a new era in thiazide diuretic therapy. [ABSTRACT FROM AUTHOR]

Australia-wide consensus was reached on seven core concepts of physiology. The "movement of substances" core concept with the descriptor "the movement of substances (ions or molecules) is a fundamental process that occurs at all levels of organization in the organism" was unpacked by a team of three Australian physiology educators from the Delphi Task Force into hierarchical levels. There were 10 themes and 23 subthemes arranged in a hierarchy, some 3 levels deep. Using a 5-point Likert scale, the unpacked core concept was then rated for level of importance for students to understand (ranging from 1 = Essential to 5 = Not Important) and level of difficulty for students (ranging from 1 = Very Difficult to 5 = Not Difficult) by the 23 physiology educators from different Australian universities, all with a broad range of teaching and curriculum experience. Survey data were analyzed using a one-way ANOVA to compare between and within concept themes. The main themes all were rated on average as important. There was a wide range of difficulty ratings and more variation for this concept compared with the other core concepts. This may in part be due to the physical forces such as gravity, electrochemistry, resistance, and thermodynamics that underpin this concept, which in themselves are inherently complex. Separation of concepts into subthemes can help prioritize learning activities and time spent on difficult concepts. Embedding of core concepts across curricula will allow commonality and consistency between programs of study and inform learning outcomes, assessment, and teaching and learning activities. NEW & NOTEWORTHY This article unpacks the core concept of the "movement of substances" within the body, with the aim to produce a resource that will help guide the teaching of physiology at tertiary education institutes in Australia. The concept introduces fundamental knowledge of the factors that drive substance movement and then applies them in physiological contexts. [ABSTRACT FROM AUTHOR]

Students in an animal physiology course are required to have completed prerequisite cell biology and genetics courses that include discussion of basic properties and functions of the cell membrane. However, while many students remember basic information about membrane structure, they often have difficulty relating that structure to membrane functions, such as vesicular transport, active transport, osmosis, and current flow across the membrane. To better understand what students recall about the cell membrane, students were given an open-ended prompt to draw what they know about the structure and function of the animal cell membrane. This activity was repeated 1-2 weeks after finishing discussion of the cell membrane in class, with an emphasis on the concepts of membrane transport and a related core concept, flow along gradients. Student responses were analyzed using the conceptual framework for the "cell membrane" core concept published by Michael and Modell (Michael J, Modell H. Adv Physiol Educ 43: 373-377, 2019). Before covering this content in class, the majority of submissions included a representation of the cell membrane as a phospholipid bilayer, and a high percentage also included membrane proteins or the fluid mosaic model. Similar percentages of students included these concepts in the postcoverage drawing. However, other components of the conceptual framework were included less frequently or not at all before covering the content in class but improved dramatically afterward. This activity provides information about what students recall from prior coursework and which concepts need to be revisited, and it can provide a complementary assessment of student understanding of the core concept of the cell membrane. NEW & NOTEWORTHY Student-constructed drawings can give insight into student understanding, and misunderstandings, of core concepts about the cell membrane. [ABSTRACT FROM AUTHOR]