Showing papers in "Physiology in 2019"
TL;DR: Extracellular vesicles, cell-derived membrane structures, are secreted after fusion of endosomes with the plasma membrane (exosomes) or shed from the plasma membranes (microvesicles).
Abstract: Extracellular vesicles (EVs), cell-derived membrane structures, are secreted after fusion of endosomes with the plasma membrane (exosomes) or shed from the plasma membrane (microvesicles). EVs play...
224 citations
TL;DR: The ways in which animals and human populations are likely to respond to increased extreme heat are described, how to study those responses is suggested, and the importance of those studies for countering the devastating impacts of climate change is reflected.
Abstract: A consequence of climate change is the increased frequency and severity of extreme heat waves. This is occurring now as most of the warmest summers and most intense heat waves ever recorded have been during the past decade. In this review, I describe the ways in which animals and human populations are likely to respond to increased extreme heat, suggest how to study those responses, and reflect on the importance of those studies for countering the devastating impacts of climate change.
221 citations
TL;DR: How this process is regulated and how it is associated with insulin-degrading enzyme in the liver are summarized should lead to building more effective therapeutic strategies against metabolic syndrome.
Abstract: Upon its secretion from pancreatic β-cells, insulin reaches the liver through the portal circulation to exert its action and eventually undergo clearance in the hepatocytes. In addition to insulin ...
144 citations
TL;DR: Emerging evidence suggests that inflammation in the central and peripheral immune system may link metabolic syndrome to major depressive disorder, and available data is synthesized to support this view and identify critical areas for future investigation.
Abstract: Metabolic syndrome and major depression are two of the most common and debilitating disorders worldwide, occurring with significant rates of comorbidity. Recent studies have uncovered that each of ...
108 citations
TL;DR: Evidence is provided to support a central role for ribosome biogenesis in skeletal muscle growth during postnatal development and in response to resistance exercise training.
Abstract: The ribosome is the enzymatic macromolecular machine responsible for protein synthesis. The rates of protein synthesis are primarily dependent on translational efficiency and capacity. Ribosome bio...
92 citations
TL;DR: Current controversies in the field of mitochondrial biogenesis are examined to highlight some important methodological issues that need to be addressed to resolve existing conflicts.
Abstract: It is well established that different types of exercise can provide a powerful stimulus for mitochondrial biogenesis. However, there are conflicting findings in the literature, and a consensus has ...
91 citations
TL;DR: Heat tolerance limits, pathways of evaporative heat dissipation that permit the defense of body temperature during heat exposure, and mechanisms operating at tissue, cellular, and molecular levels are reviewed.
Abstract: Understanding the heat tolerances of small mammals and birds has taken on new urgency with the advent of climate change. Here, we review heat tolerance limits, pathways of evaporative heat dissipat...
82 citations
TL;DR: A remarkable correlation between phenotype of a chemosensory unit (glomus cell-sensory afferent) with a distinct component of the reflex response is claimed, which could permit differential modulation of distinct chemoreflex responses, a strategy ideal for therapeutic exploitation.
Abstract: The carotid body has emerged as a therapeutic target for cardio-respiratory-metabolic diseases. With the expansive functions of the chemoreflex, we sought mechanisms to explain differential control...
76 citations
TL;DR: A review of research into the mechanisms of and heterogeneity in adaptations to resistance exercise training beyond differences in exercise prescription highlights the current knowledge and emphasizes knowledge gaps that require future attention.
Abstract: Older adults undergoing age-related decrements in muscle health can benefit substantially from resistance exercise training, a potent stimulus for whole muscle and myofiber hypertrophy, neuromuscular performance gains, and improved functional mobility. With the use of advancing technologies, research continues to elucidate the mechanisms of and heterogeneity in adaptations to resistance exercise training beyond differences in exercise prescription. This review highlights the current knowledge in these areas and emphasizes knowledge gaps that require future attention of the field.
76 citations
TL;DR: In this article, the authors review mechanisms for resolution of organ fibrosis and discuss the potential for reversibility and restoration of near-normal tissue architecture and organ function, as well as the potential of reversibility of tissue structures.
Abstract: Fibrosis is a dynamic process with the potential for reversibility and restoration of near-normal tissue architecture and organ function. Herein, we review mechanisms for resolution of organ fibros...
69 citations
TL;DR: Lower resting heart rate and high autonomic vagal activity are strongly associated with superior exercise capacity, maintenance of which is essential for general well-being and healthy aging.
Abstract: Lower resting heart rate and high autonomic vagal activity are strongly associated with superior exercise capacity, maintenance of which is essential for general well-being and healthy aging. Recen...
TL;DR: Critical to progress is a mechanistic understanding of multi-level controls of target organs, disease adaptation, and impact of neuromodulation to restore organ function.
Abstract: Autonomic nerves are attractive targets for medical therapies using electroceutical devices because of the potential for selective control and few side effects. These devices use novel materials, electrode configurations, stimulation patterns, and closed-loop control to treat heart failure, hypertension, gastrointestinal and bladder diseases, obesity/diabetes, and inflammatory disorders. Critical to progress is a mechanistic understanding of multi-level controls of target organs, disease adaptation, and impact of neuromodulation to restore organ function.
TL;DR: Examples of recently identified molecular mechanisms of muscle atrophy are discussed and how they highlight an immense need and opportunity for focused biochemical investigations and further unbiased discovery work.
Abstract: Skeletal muscle atrophy proceeds through a complex molecular signaling network that is just beginning to be understood. Here, we discuss examples of recently identified molecular mechanisms of musc...
TL;DR: Novel targeted fluorescent biosensors provide key insights into very local nanodomains of cAMP and PKA activity, and how they respond differently to β-adrenergic activation in cardiac myocytes.
Abstract: Novel targeted fluorescent biosensors provide key insights into very local nanodomains of cAMP and PKA activity, and how they respond differently to β-adrenergic activation in cardiac myocytes. Thi...
TL;DR: Airway nerves represent a mechanistically and therapeutically important aspect that requires better highlighting in the context of diseases such as asthma, and current understanding of how plasticity occurs and contributions of plasticity to asthma are described.
Abstract: Airway nerves represent a mechanistically and therapeutically important aspect that requires better highlighting in the context of diseases such as asthma. Altered structure and function (plasticity) of afferent and efferent airway innervation can contribute to airway diseases. We describe established anatomy, current understanding of how plasticity occurs, and contributions of plasticity to asthma, focusing on target-derived growth factors (neurotrophins). Perspectives toward novel treatment strategies and future research are provided.
TL;DR: This review moves beyond understanding intracellular lipotoxic outcomes and outlines the consequences of lipotoxicity on protein secretion and inter-tissue "cross talk," and the impact this exerts on systemic metabolism.
Abstract: Obesity-associated comorbidities include non-alcoholic fatty liver disease, Type 2 diabetes, and cardiovascular disease. These diseases are associated with accumulation of lipids in non-adipose tis...
TL;DR: Studies using intravital microscopy have demonstrated that platelet release occurs in the lung from bone marrow megakaryocytes that embolize into the lung circulation.
Abstract: Megakaryocytes are normal cellular components of the blood returning to the heart and entering the lungs, and historical data has pointed to a role of the lungs in platelet production. Recent studi...
TL;DR: The physico-chemical constraints imposed by water and air are reviewed, and it is shown how that the advantages of combining control of ventilation and acid-base status are only available to the most obligate of air-breathing fish, thus highlighting promising avenues for research.
Abstract: Air-breathing in vertebrates has evolved many times among the bony fish while in water. Its appearance has had a fundamental impact on the regulation of ventilation and acid-base status. We review ...
TL;DR: Preclinical studies that strongly support a role for oxidative stress in development and maintenance of hypertension in male animals, based on depressor responses to antioxidants, particularly tempol and apocynin are highlighted.
Abstract: One of the mechanisms responsible for blood pressure (BP) regulation is thought to be oxidative stress. In this review, we highlight preclinical studies that strongly support a role for oxidative stress in development and maintenance of hypertension in male animals, based on depressor responses to antioxidants, particularly tempol and apocynin. In females, oxidative stress seems to be important in the initial development of hypertension. However, whether maintenance of hypertension in females is mediated by oxidative stress is not clear. In clinical studies, pharmacological intervention to reduce BP with antioxidants has conflicting results, mostly negative. This review will discuss the uncertainties regarding blood pressure control and oxidative stress and potential reasons for these outcomes.
TL;DR: How brain organoids have been used to study neurodevelopmental disease and their potential for both technological advancement and therapeutic development are considered.
Abstract: Brain organoids recapitulate in vitro the specific stages of in vivo human brain development, thus offering an innovative tool by which to model human neurodevelopmental disease. We review here how...
TL;DR: Muscle architectural gearing is an emerging example of this process, where shape changes and radial forces appear to be important across scales of organization.
Abstract: Muscle contraction is a three-dimensional process, as anyone who has observed a bulging muscle knows. Recent studies suggest that the three-dimensional nature of muscle contraction influences its m...
TL;DR: The increase in SNGFR is determined by the dynamics of nephron loss, total remaining GFR, the body's excretory demand, and the functional capacity to sustain single nephrons hyperfunction.
Abstract: A deficit or loss in the number of nephrons, the functional unit of the kidney, can induce compensatory growth and hyperfunction of remaining nephrons. An increase in single nephron glomerular filt...
TL;DR: Physiologists should play a prominent role in exploring complementary avenues and also define alternatives in ratio-based investigations of cardiovascular investigations.
Abstract: Cardiovascular investigations often involve ratio-based metrics or differences: ejection fraction, arterial pressure augmentation index, coronary fractional flow reserve, pulse pressure. Focusing on a single number (ratio or difference) implies that information is lost. The lost companions constitute a well-defined but thus far unrecognized class, having additive value, a physical dimension, and often a physiological meaning. Physiologists should play a prominent role in exploring these complementary avenues and also define alternatives.
TL;DR: Spastic cerebral palsy, despite the name, is not consistently identifiable by specific brain lesions, so animal models of CP must advance beyond risk factors to etiologies, including both the brain and spinal cord.
Abstract: Spastic cerebral palsy (CP), despite the name, is not consistently identifiable by specific brain lesions. CP animal models focus on risk factors for development of CP, yet few reproduce the diagno...
TL;DR: Feedback from discrete skin regions on both surfaces of the human foot has revealed that neuromechanical responses are highly topographically organized and contribute to "sensory guidance" of the authors' limbs during locomotion.
Abstract: Humans and cats share many characteristics pertaining to the neural control of locomotion, which has enabled the comprehensive study of cutaneous feedback during locomotion. Feedback from discrete ...
TL;DR: It is argued that mimicry of natural hibernation will be critical to overcome the innate limitations of human physiology for long-duration space travel.
Abstract: Suspended animation for deep-space travelers is moving out of the realm of science fiction. Two approaches are considered: the first elaborates the current medical practice of therapeutic hypothermia; the second invokes the cascade of metabolic processes naturally employed by hibernators. We explore the basis and evidence behind each approach and argue that mimicry of natural hibernation will be critical to overcome the innate limitations of human physiology for long-duration space travel.
TL;DR: The motoneurons that generate all motor output in rodents are very different in rodents compared with humans, being smaller and much more excitable, in contrast, feline mot oneurons are more similar to those in humans.
Abstract: Appropriate scaling of motor output from mouse to humans is essential. The motoneurons that generate all motor output are, however, very different in rodents compared with humans, being smaller and much more excitable. In contrast, feline motoneurons are more similar to those in humans. These scaling differences need to be taken into account for the use of rodents for translational studies of motor output.
TL;DR: This review explores both CRISPR-mediated editing and dead Cas approaches as potential therapeutic strategies for multiple NMDs and considers therapeutic considerations, including delivery and off-target effects.
Abstract: This is a review describing advances in CRISPR/Cas-mediated therapies for neuromuscular disorders (NMDs). We explore both CRISPR-mediated editing and dead Cas approaches as potential therapeutic strategies for multiple NMDs. Last, therapeutic considerations, including delivery and off-target effects, are also discussed.
TL;DR: The biomechanics of the lunge feeding mechanism in rorqual whales that underlies their extraordinary foraging performance and gigantic body size are reviewed.
Abstract: The largest animals are baleen filter feeders that exploit large aggregations of small-bodied plankton. Although this feeding mechanism has evolved multiple times in marine vertebrates, rorqual wha...
TL;DR: The supporting evidence for three pro-arrhythmic mechanisms in athletic human cohorts and animal models are considered, featuring current controversies, emerging data, and future directions of relevance to the translational research agenda.
Abstract: Athletes are prone to supraventricular rhythm disturbances including sinus bradycardia, heart block, and atrial fibrillation. Mechanistically, this is attributed to high vagal tone and cardiac elec...