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Annual Review of Physiology

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https://www.readbyqxmd.com/read/30256727/evolved-mechanisms-of-aerobic-performance-and-hypoxia-resistance-in-high-altitude-natives
#1
Grant B McClelland, Graham R Scott
Comparative physiology studies of high-altitude species provide an exceptional opportunity to understand naturally evolved mechanisms of hypoxia resistance. Aerobic capacity (VO2 max) is a critical performance trait under positive selection in some high-altitude taxa, and several high-altitude natives have evolved to resist the depressive effects of hypoxia on VO2 max. This is associated with enhanced flux capacity through the O2 transport cascade and attenuation of the maladaptive responses to chronic hypoxia that can impair O2 transport...
September 26, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/30256726/central-mechanisms-for-thermoregulation
#2
S F Morrison, K Nakamura
Maintenance of a homeostatic body core temperature is a critical brain function accomplished by a central neural network. This orchestrates a complex behavioral and autonomic repertoire in response to environmental temperature challenges or declining energy homeostasis and in support of immune responses and many behavioral states. This review summarizes the anatomical, neurotransmitter, and functional relationships within the central neural network that controls the principal thermoeffectors: cutaneous vasoconstriction regulating heat loss and shivering and brown adipose tissue for heat production...
September 26, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/30256725/evolving-concepts-of-mitochondrial-dynamics
#3
Gerald W Dorn
The concept that mitochondria are highly dynamic is as widely accepted as it is untrue for a number of important contexts. Healthy mitochondria of the most energy-dependent and mitochondrial-rich mammalian organ, the heart, only rarely undergo fusion or fission and are seemingly static within cardiac myocytes. Here, we revisit mitochondrial dynamism with a fresh perspective developed from the recently discovered multifunctionality of mitochondrial fusion proteins and newly defined mechanisms for direct cross talk between mitochondrial dynamics, biogenesis, quality control, and trafficking pathways...
September 26, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/30216743/cysteine-based-redox-sensing-and-its-role-in-signaling-by-cyclic-nucleotide-dependent-kinases-in-the-cardiovascular-system
#4
Friederike Cuello, Philip Eaton
Oxidant molecules are produced in biological systems and historically have been considered causal mediators of damage and disease. While oxidants may contribute to the pathogenesis of disease, evidence continues to emerge that shows these species also play important regulatory roles in health. A major mechanism of oxidant sensing and signaling involves their reaction with reactive cysteine thiols within proteins, inducing oxidative posttranslational modifications that can couple to altered function to enable homeostatic regulation...
September 14, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/30216742/maintenance-of-skeletal-muscle-mitochondria-in-health-exercise-and-aging
#5
David A Hood, Jonathan M Memme, Ashley N Oliveira, Matthew Triolo
Mitochondria are critical organelles responsible for regulating the metabolic status of skeletal muscle. These organelles exhibit remarkable plasticity by adapting their volume, structure, and function in response to chronic exercise, disuse, aging, and disease. A single bout of exercise initiates signaling to provoke increases in mitochondrial biogenesis, balanced by the onset of organelle turnover carried out by the mitophagy pathway. This accelerated turnover ensures the presence of a high functioning network of mitochondria designed for optimalATPsupply, with the consequence of favoring lipid metabolism, maintaining muscle mass, and reducing apoptotic susceptibility over the longer term...
September 14, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/29433415/mechanical-protein-unfolding-and-degradation
#6
Adrian O Olivares, Tania A Baker, Robert T Sauer
AAA+ proteolytic machines use energy from ATP hydrolysis to degrade damaged, misfolded, or unneeded proteins. Protein degradation occurs within a barrel-shaped self-compartmentalized peptidase. Before protein substrates can enter this peptidase, they must be unfolded and then translocated through the axial pore of an AAA+ ring hexamer. An unstructured region of the protein substrate is initially engaged in the axial pore, and conformational changes in the ring, powered by ATP hydrolysis, generate a mechanical force that pulls on and denatures the substrate...
February 10, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/29433414/unraveling-the-mechanobiology-of-extracellular-matrix
#7
Viola Vogel
Cells need to be anchored to extracellular matrix (ECM) to survive, yet the role of ECM in guiding developmental processes, tissue homeostasis, and aging has long been underestimated. How ECM orchestrates the deterioration of healthy to pathological tissues, including fibrosis and cancer, also remains poorly understood. Inquiring how alterations in ECM fiber tension might drive these processes is timely, as mechanobiology is a rapidly growing field, and many novel mechanisms behind the mechanical forces that can regulate protein, cell, and tissue functions have recently been deciphered...
February 10, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/29433413/the-work-of-titin-protein-folding-as-a-major-driver-in-muscle-contraction
#8
Edward C Eckels, Rafael Tapia-Rojo, Jamie Andrés Rivas-Pardo, Julio M Fernández
Single-molecule atomic force microscopy and magnetic tweezers experiments have demonstrated that titin immunoglobulin (Ig) domains are capable of folding against a pulling force, generating mechanical work that exceeds that produced by a myosin motor. We hypothesize that upon muscle activation, formation of actomyosin cross bridges reduces the force on titin, causing entropic recoil of the titin polymer and triggering the folding of the titin Ig domains. In the physiological force range of 4-15 pN under which titin operates in muscle, the folding contraction of a single Ig domain can generate 200% of the work of entropic recoil and occurs at forces that exceed the maximum stalling force of single myosin motors...
February 10, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/29195055/neuromuscular-junction-formation-aging-and-disorders
#9
Lei Li, Wen-Cheng Xiong, Lin Mei
Synapses, the fundamental unit in neuronal circuits, are critical for learning and memory, perception, thinking, and reaction. The neuromuscular junction (NMJ) is a synapse formed between motoneurons and skeletal muscle fibers that is covered by Schwann cells (SCs). It is essential for controlling muscle contraction. NMJ formation requires intimate interactions among motoneurons, muscles, and SCs. Deficits in NMJ formation and maintenance cause neuromuscular disorders, including congenital myasthenic syndrome and myasthenia gravis...
February 10, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/29195054/bacterial-mechanosensors
#10
Charles D Cox, Navid Bavi, Boris Martinac
Bacteria represent one of the most evolutionarily successful groups of organisms to inhabit Earth. Their world is awash with mechanical cues, probably the most ancient form of which are osmotic forces. As a result, they have developed highly robust mechanosensors in the form of bacterial mechanosensitive (MS) channels. These channels are essential in osmoregulation, and in this setting, provide one of the simplest paradigms for the study of mechanosensory transduction. We explore the past, present, and future of bacterial MS channels, including the alternate mechanosensory roles that they may play in complex microbial communities...
February 10, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/29166242/dynamism-of-an-astrocyte-in-vivo-perspectives-on-identity-and-function
#11
Kira E Poskanzer, Anna V Molofsky
Astrocytes are an abundant and evolutionarily conserved central nervous system cell type. Despite decades of evidence that astrocytes are integral to neural circuit function, it seems as though astrocytic and neuronal biology continue to advance in parallel to each other, to the detriment of both. Recent advances in molecular biology and optical imaging are being applied to astrocytes in new and exciting ways but without fully considering their unique biology. From this perspective, we explore the reasons that astrocytes remain enigmatic, arguing that their responses to neuronal and environmental cues shape form and function in dynamic ways...
February 10, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/29166241/two-classes-of-secreted-synaptic-organizers-in-the-central-nervous-system
#12
Michisuke Yuzaki
Research in the last two decades has identified many synaptic organizers in the central nervous system that directly regulate the assembly of pre- and/or postsynaptic molecules, such as synaptic vesicles, active zone proteins, and neurotransmitter receptors. They are classified into secreted factors and cell adhesion molecules, such as neurexins and neuroligins. Certain secreted factors are termed extracellular scaffolding proteins (ESPs) because they are components of the synaptic extracellular matrix and serve as a scaffold at the synaptic cleft...
February 10, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/29144825/salt-hypertension-and-immunity
#13
A Justin Rucker, Nathan P Rudemiller, Steven D Crowley
The link between inappropriate salt retention in the kidney and hypertension is well recognized. However, growing evidence suggests that the immune system can play surprising roles in sodium homeostasis, such that the study of inflammatory cells and their secreted effectors has provided important insights into salt sensitivity. As part of the innate immune system, myeloid cells have diverse roles in blood pressure regulation, ranging from prohypertensive actions in the kidney, vasculature, and brain, to effects in the skin that attenuate blood pressure elevation...
February 10, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/29131758/titin-gene-and-protein-functions-in-passive-and-active-muscle
#14
Wolfgang A Linke
The thin and thick filaments of muscle sarcomeres are interconnected by the giant protein titin, which is a scaffolding filament, signaling platform, and provider of passive tension and elasticity in myocytes. This review summarizes recent insight into the mechanisms behind how titin gene mutations cause hereditary cardiomyopathy and how titin protein is mechanically active in skeletal and cardiac myocytes. A main theme is the evolving role of titin as a modulator of contraction. Topics include strain-sensing via titin in the sarcomeric A-band as the basis for length-dependent activation, titin elastic recoil and refolding of titin domains as an energy source, and Ca2+ -dependent stiffening of titin stretched during eccentric muscle contractions...
February 10, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/29125794/sr-b1-a-unique-multifunctional-receptor-for-cholesterol-influx-and-efflux
#15
Wen-Jun Shen, Salman Azhar, Fredric B Kraemer
The scavenger receptor, class B type 1 (SR-B1), is a multiligand membrane receptor protein that functions as a physiologically relevant high-density lipoprotein (HDL) receptor whose primary role is to mediate selective uptake or influx of HDL-derived cholesteryl esters into cells and tissues. SR-B1 also facilitates the efflux of cholesterol from peripheral tissues, including macrophages, back to liver. As a regulator of plasma membrane cholesterol content, SR-B1 promotes the uptake of lipid soluble vitamins as well as viral entry into host cells...
February 10, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/29120692/epithelial-na-channel-regulation-by-extracellular-and-intracellular-factors
#16
Thomas R Kleyman, Ossama B Kashlan, Rebecca P Hughey
Epithelial Na+ channels (ENaCs) are members of the ENaC/degenerin family of ion channels that evolved to respond to extracellular factors. In addition to being expressed in the distal aspects of the nephron, where ENaCs couple the absorption of filtered Na+ to K+ secretion, these channels are found in other epithelia as well as nonepithelial tissues. This review addresses mechanisms by which ENaC activity is regulated by extracellular factors, including proteases, Na+ , and shear stress. It also addresses other factors, including acidic phospholipids and modification of ENaC cytoplasmic cysteine residues by palmitoylation, which enhance channel activity by altering interactions of the channel with the plasma membrane...
February 10, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/29068766/the-role-of-autophagy-in-the-heart
#17
Sebastiano Sciarretta, Yasuhiro Maejima, Daniela Zablocki, Junichi Sadoshima
Autophagy is an evolutionarily conserved mechanism by which cytoplasmic elements are degraded intracellularly. Autophagy has also emerged as a major regulator of cardiac homeostasis and function. Autophagy preserves cardiac structure and function under baseline conditions and is activated during stress, limiting damage under most conditions. It reduces injury and preserves cardiac function during ischemia. It also reduces chronic ischemic remodeling and mediates the cardiac adaptation to pressure overload by restricting misfolded protein accumulation, mitochondrial dysfunction, and oxidative stress...
February 10, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/29068765/mechanisms-of-renal-fibrosis
#18
Benjamin D Humphreys
Tubulointerstitial fibrosis is a chronic and progressive process affecting kidneys during aging and in chronic kidney disease (CKD), regardless of cause. CKD and renal fibrosis affect half of adults above age 70 and 10% of the world's population. Although no targeted therapy yet exists to slow renal fibrosis, a number of important recent advances have clarified the cellular and molecular mechanisms underlying the disease. In this review, I highlight these advances with a focus on cells and pathways that may be amenable to therapeutic targeting...
February 10, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/29029594/chemoreceptors-in-the-gut
#19
S Steensels, I Depoortere
The gastrointestinal tract represents the largest interface between the human body and the external environment. It must continuously monitor and discriminate between nutrients that need to be assimilated and harmful substances that need to be expelled. The different cells of the gut epithelium are therefore equipped with a subtle chemosensory system that communicates the sensory information to several effector systems involved in the regulation of appetite, immune responses, and gastrointestinal motility. Disturbances or adaptations in the communication of this sensory information may contribute to the development or maintenance of disease...
February 10, 2018: Annual Review of Physiology
https://www.readbyqxmd.com/read/29029593/lymphatic-dysfunction-leukotrienes-and-lymphedema
#20
Xinguo Jiang, Mark R Nicolls, Wen Tian, Stanley G Rockson
The lymphatic system is essential for the maintenance of tissue fluid homeostasis, gastrointestinal lipid absorption, and immune trafficking. Whereas lymphatic regeneration occurs physiologically in wound healing and tissue repair, pathological lymphangiogenesis has been implicated in a number of chronic diseases such as lymphedema, atherosclerosis, and cancer. Insight into the regulatory mechanisms of lymphangiogenesis and the manner in which uncontrolled inflammation promotes lymphatic dysfunction is urgently needed to guide the development of novel therapeutics: These would be designed to reverse lymphatic dysfunction, either primary or acquired...
February 10, 2018: Annual Review of Physiology
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