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A Razor's Edge: Vascular Responses to Acute Inflammatory Lung Injury/Acute Respiratory Distress Syndrome Annu. Rev. Physiol. (IF 18.2) Pub Date : 2024-02-12 David R. Price, Joe G.N. Garcia
Historically considered a metabolically inert cellular layer separating the blood from the underlying tissue, the endothelium is now recognized as a highly dynamic, metabolically active tissue that is critical to organ homeostasis. Under homeostatic conditions, lung endothelial cells (ECs) in healthy subjects are quiescent, promoting vasodilation, platelet disaggregation, and anti-inflammatory mechanisms
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Transcellular Barriers to Glucose Delivery in the Body Annu. Rev. Physiol. (IF 18.2) Pub Date : 2024-02-12 Amira Klip, Katrien De Bock, Philip J. Bilan, Erik A. Richter
Glucose is the universal fuel of most mammalian cells, and it is largely replenished through dietary intake. Glucose availability to tissues is paramount for the maintenance of homeostatic energetics and, hence, supply should match demand by the consuming organs. In its journey through the body, glucose encounters cellular barriers for transit at the levels of the absorbing intestinal epithelial wall
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The Role of the Microbiome in the Etiopathogenesis of Colon Cancer Annu. Rev. Physiol. (IF 18.2) Pub Date : 2024-02-12 Geniver El Tekle, Natalia Andreeva, Wendy S. Garrett
Studies in preclinical models support that the gut microbiota play a critical role in the development and progression of colorectal cancer (CRC). Specific microbial species and their corresponding virulence factors or associated small molecules can contribute to CRC development and progression either via direct effects on the neoplastic transformation of epithelial cells or through interactions with
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Orchestration of the Adipose Tissue Immune Landscape by Adipocytes Annu. Rev. Physiol. (IF 18.2) Pub Date : 2024-02-12 David Bradley, Tuo Deng, Dharti Shantaram, Willa A. Hsueh
Obesity is epidemic and of great concern because of its comorbid and costly inflammatory-driven complications. Extensive investigations in mice have elucidated highly coordinated, well-balanced interactions between adipocytes and immune cells in adipose tissue that maintain normal systemic metabolism in the lean state, while in obesity, proinflammatory changes occur in nearly all adipose tissue immune
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Arterial Stiffness: From Basic Primers to Integrative Physiology Annu. Rev. Physiol. (IF 18.2) Pub Date : 2024-02-12 Véronique Regnault, Patrick Lacolley, Stéphane Laurent
The elastic properties of conductance arteries are one of the most important hemodynamic functions in the body, and data continue to emerge regarding the importance of their dysfunction in vascular aging and a range of cardiovascular diseases. Here, we provide new insight into the integrative physiology of arterial stiffening and its clinical consequence. We also comprehensively review progress made
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Exosome-Mediated Impact on Systemic Metabolism Annu. Rev. Physiol. (IF 18.2) Pub Date : 2024-02-12 Karina Cunha e Rocha, Wei Ying, Jerrold M. Olefsky
Exosomes are small extracellular vesicles that carry lipids, proteins, and microRNAs (miRNAs). They are released by all cell types and can be found not only in circulation but in many biological fluids. Exosomes are essential for interorgan communication because they can transfer their contents from donor to recipient cells, modulating cellular functions. The miRNA content of exosomes is responsible
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Intestinal Tuft Cells: Morphology, Function, and Implications for Human Health Annu. Rev. Physiol. (IF 18.2) Pub Date : 2024-02-12 Jennifer B. Silverman, Paige N. Vega, Matthew J. Tyska, Ken S. Lau
Tuft cells are a rare and morphologically distinct chemosensory cell type found throughout many organs, including the gastrointestinal tract. These cells were identified by their unique morphologies distinguished by large apical protrusions. Ultrastructural data have begun to describe the molecular underpinnings of their cytoskeletal features, and tuft cell–enriched cytoskeletal proteins have been
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The Coding Logic of Interoception Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-12-07 Ruiqi L. Wang, Rui B. Chang
Interoception, the ability to precisely and timely sense internal body signals, is critical for life. The interoceptive system monitors a large variety of mechanical, chemical, hormonal, and pathological cues using specialized organ cells, organ innervating neurons, and brain sensory neurons. It is important for maintaining body homeostasis, providing motivational drives, and regulating autonomic,
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A Balancing Act: Learning from the Past to Build a Future-Focused Opioid Strategy Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-11-29 Sarah Warren Gooding, Jennifer L. Whistler
The harmful side effects of opioid drugs such as respiratory depression, tolerance, dependence, and abuse potential have limited the therapeutic utility of opioids for their entire clinical history. However, no previous attempt to develop effective pain drugs that substantially ameliorate these effects has succeeded, and the current opioid epidemic affirms that they are a greater hindrance to the field
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Metabolic Rewiring and Communication: An Integrative View of Kidney Proximal Tubule Function Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-11-28 Maria Chrysopoulou, Markus M. Rinschen
The kidney proximal tubule is a key organ for human metabolism. The kidney responds to stress with altered metabolite transformation and perturbed metabolic pathways, an ultimate cause for kidney disease. Here, we review the proximal tubule's metabolic function through an integrative view of transport, metabolism, and function, and embed it in the context of metabolome-wide data-driven research. Function
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Mitochondrial Dysfunction in Kidney Tubulopathies Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-11-28 Charlotte A. Hoogstraten, Joost G. Hoenderop, Jeroen H.F. de Baaij
Mitochondria play a key role in kidney physiology and pathology. They produce ATP to fuel energy-demanding water and solute reabsorption processes along the nephron. Moreover, mitochondria contribute to cellular health by the regulation of autophagy, (oxidative) stress responses, and apoptosis. Mitochondrial abundance is particularly high in cortical segments, including proximal and distal convoluted
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Regulating Striated Muscle Contraction: Through Thick and Thin Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-11-06 Elisabetta Brunello, Luca Fusi
Force generation in striated muscle is primarily controlled by structural changes in the actin-containing thin filaments triggered by an increase in intracellular calcium concentration. However, recent studies have elucidated a new class of regulatory mechanisms, based on the myosin-containing thick filament, that control the strength and speed of contraction by modulating the availability of myosin
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Transcendent Aspects of Proton Channels Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-11-06 Thomas E. DeCoursey
A handful of biological proton-selective ion channels exist. Some open at positive or negative membrane potentials, others open at low or high pH, and some are light activated. This review focuses on common features that result from the unique properties of protons. Proton conduction through water or proteins differs qualitatively from that of all other ions. Extraordinary proton selectivity is needed
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The Effects of Psychedelics on Neuronal Physiology Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-11-06 Cassandra J. Hatzipantelis, David E. Olson
Psychedelics are quite unique among drugs that impact the central nervous system, as a single administration of a psychedelic can both rapidly alter subjective experience in profound ways and produce sustained effects on circuits relevant to mood, fear, reward, and cognitive flexibility. These remarkable properties are a direct result of psychedelics interacting with several key neuroreceptors distributed
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Structure, Function, and Regulation of the Junctophilin Family Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-11-06 Duane D. Hall, Hiroshi Takeshima, Long-Sheng Song
In both excitable and nonexcitable cells, diverse physiological processes are linked to different calcium microdomains within nanoscale junctions that form between the plasma membrane and endo-sarcoplasmic reticula. It is now appreciated that the junctophilin protein family is responsible for establishing, maintaining, and modulating the structure and function of these junctions. We review foundational
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Adipose Tissue in Cardiovascular Disease: From Basic Science to Clinical Translation Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-11-06 Murray D. Polkinghorne, Henry W. West, Charalambos Antoniades
The perception of adipose tissue as a metabolically quiescent tissue, primarily responsible for lipid storage and energy balance (with some endocrine, thermogenic, and insulation functions), has changed. It is now accepted that adipose tissue is a crucial regulator of metabolic health, maintaining bidirectional communication with other organs including the cardiovascular system. Additionally, adipose
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Molecular Crowding: Physiologic Sensing and Control Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-11-06 Arohan R. Subramanya, Cary R. Boyd-Shiwarski
The cytoplasm is densely packed with molecules that contribute to its nonideal behavior. Cytosolic crowding influences chemical reaction rates, intracellular water mobility, and macromolecular complex formation. Overcrowding is potentially catastrophic; to counteract this problem, cells have evolved acute and chronic homeostatic mechanisms that optimize cellular crowdedness. Here, we provide a physiology-focused
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BK Channelopathies and KCNMA1-Linked Disease Models Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-10-31 Andrea L. Meredith
Novel KCNMA1 variants , encoding the BK K+ channel, are associated with a debilitating dyskinesia and epilepsy syndrome. Neurodevelopmental delay, cognitive disability, and brain and structural malformations are also diagnosed at lower incidence. More than half of affected individuals present with a rare negative episodic motor disorder, paroxysmal nonkinesigenic dyskinesia (PNKD3). The mechanistic
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Phosphoinositide Regulation of TRP Channels: A Functional Overview in the Structural Era Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-10-23 Tibor Rohacs
Transient receptor potential (TRP) ion channels have diverse activation mechanisms including physical stimuli, such as high or low temperatures, and a variety of intracellular signaling molecules. Regulation by phosphoinositides and their derivatives is their only known common regulatory feature. For most TRP channels, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] serves as a cofactor required
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Mechanosensing by Vascular Endothelium Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-10-20 Xin Rui Lim, Osama F. Harraz
Mechanical forces influence different cell types in our bodies. Among the earliest forces experienced in mammals is blood movement in the vascular system. Blood flow starts at the embryonic stage and ceases when the heart stops. Blood flow exposes endothelial cells (ECs) that line all blood vessels to hemodynamic forces. ECs detect these mechanical forces (mechanosensing) through mechanosensors, thus
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The Mineralocorticoid Receptor in the Vasculature: Friend or Foe? Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-10-03 Jaime Ibarrola, Iris Z. Jaffe
Originally described as the renal aldosterone receptor that regulates sodium homeostasis, it is now clear that mineralocorticoid receptors (MRs) are widely expressed, including in vascular endothelial and smooth muscle cells. Ample data demonstrate that endothelial and smooth muscle cell MRs contribute to cardiovascular disease in response to risk factors (aging, obesity, hypertension, atherosclerosis)
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Pericytes and the Control of Blood Flow in Brain and Heart Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-02-10 Thomas A. Longden, Guiling Zhao, Ashwini Hariharan, W. Jonathan Lederer
Pericytes, attached to the surface of capillaries, play an important role in regulating local blood flow. Using optogenetic tools and genetically encoded reporters in conjunction with confocal and multiphoton imaging techniques, the 3D structure, anatomical organization, and physiology of pericytes have recently been the subject of detailed examination. This work has revealed novel functions of pericytes
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Flipping Off and On the Redox Switch in the Microcirculation Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-02-10 Máté Katona, Mark T. Gladwin, Adam C. Straub
Resistance arteries and arterioles evolved as specialized blood vessels serving two important functions: ( a) regulating peripheral vascular resistance and blood pressure and ( b) matching oxygen and nutrient delivery to metabolic demands of organs. These functions require control of vessel lumen cross-sectional area (vascular tone) via coordinated vascular cell responses governed by precise spatial-temporal
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Molecular Physiology of TRPV Channels: Controversies and Future Challenges Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-02-10 Tamara Rosenbaum, León D. Islas
The ability to detect stimuli from the environment plays a pivotal role in our survival. The molecules that allow the detection of such signals include ion channels, which are proteins expressed in different cells and organs. Among these ion channels, the transient receptor potential (TRP) family responds to the presence of diverse chemicals, temperature, and osmotic changes, among others. This family
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Polycystin Channel Complexes Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-02-10 Orhi Esarte Palomero, Megan Larmore, Paul G. DeCaen
Polycystin subunits can form hetero- and homotetrameric ion channels in the membranes of various compartments of the cell. Homotetrameric polycystin channels are voltage- and calcium-modulated, whereas heterotetrameric versions are proposed to be ligand- or autoproteolytically regulated. Their importance is underscored by variants associated with autosomal dominant polycystic kidney disease and by
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Mechanisms of Protein Trafficking and Quality Control in the Kidney and Beyond Annu. Rev. Physiol. (IF 18.2) Pub Date : 2023-02-10 Jillian L. Shaw, Juan Lorenzo Pablo, Anna Greka
Numerous trafficking and quality control pathways evolved to handle the diversity of proteins made by eukaryotic cells. However, at every step along the biosynthetic pathway, there is the potential for quality control system failure. This review focuses on the mechanisms of disrupted proteostasis. Inspired by diseases caused by misfolded proteins in the kidney (mucin 1 and uromodulin), we outline the
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Proprioception: A New Era Set in Motion by Emerging Genetic and Bionic Strategies? Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-11-19 Paul D. Marasco, Joriene C. de Nooij
The generation of an internal body model and its continuous update is essential in sensorimotor control. Although known to rely on proprioceptive sensory feedback, the underlying mechanism that transforms this sensory feedback into a dynamic body percept remains poorly understood. However, advances in the development of genetic tools for proprioceptive circuit elements, including the sensory receptors
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The Role of the Gut Microbiota in the Relationship Between Diet and Human Health Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-11-14 Bryce K. Perler, Elliot S. Friedman, Gary D. Wu
The interplay between diet, the gut microbiome, and host health is complex. Diets associated with health have many similarities: high fiber, unsaturated fatty acids, and polyphenols while being low in saturated fats, sodium, and refined carbohydrates. Over the past several decades, dietary patterns have changed significantly in Westernized nations with the increased consumption of calorically dense
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Lung Cell Atlases in Health and Disease Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-11-09 Taylor S. Adams, Arnaud Marlier, Naftali Kaminski
The human lung cellular portfolio, traditionally characterized by cellular morphology and individual markers, is highly diverse, with over 40 cell types and a complex branching structure highly adapted for agile airflow and gas exchange. While constant during adulthood, lung cellular content changes in response to exposure, injury, and infection. Some changes are temporary, but others are persistent
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Fatty Acid Transport and Signaling: Mechanisms and Physiological Implications Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-11-08 Dmitri Samovski, Miriam Jacome-Sosa, Nada A. Abumrad
Long-chain fatty acids (FAs) are components of plasma membranes and an efficient fuel source and also serve as metabolic regulators through FA signaling mediated by membrane FA receptors. Impaired tissue FA uptake has been linked to major complications of obesity, including insulin resistance, cardiovascular disease, and type 2 diabetes. Fatty acid interactions with a membrane receptor and the initiation
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Neural Mechanisms That Make Perceptual Decisions Flexible Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-11-07 Gouki Okazawa, Roozbeh Kiani
Neural mechanisms of perceptual decision making have been extensively studied in experimental settings that mimic stable environments with repeating stimuli, fixed rules, and payoffs. In contrast, we live in an ever-changing environment and have varying goals and behavioral demands. To accommodate variability, our brain flexibly adjusts decision-making processes depending on context. Here, we review
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Molecular and Cellular Mechanisms of Salt Taste Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-11-05 Akiyuki Taruno, Michael D. Gordon
Salt taste, the taste of sodium chloride (NaCl), is mechanistically one of the most complex and puzzling among basic tastes. Sodium has essential functions in the body but causes harm in excess. Thus, animals use salt taste to ingest the right amount of salt, which fluctuates by physiological needs: typically, attraction to low salt concentrations and rejection of high salt. This concentration-valence
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Transformation of Our Understanding of Breathing Control by Molecular Tools Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-11-02 Kevin Yackle
The rhythmicity of breath is vital for normal physiology. Even so, breathing is enriched with multifunctionality. External signals constantly change breathing, stopping it when under water or deepening it during exertion. Internal cues utilize breath to express emotions such as sighs of frustration and yawns of boredom. Breathing harmonizes with other actions that use our mouth and throat, including
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Metabolic Recruitment in Brain Tissue Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-10-21 L.F. Barros, I. Ruminot, T. Sotelo-Hitschfeld, R. Lerchundi, I. Fernández-Moncada
Information processing imposes urgent metabolic demands on neurons, which have negligible energy stores and restricted access to fuel. Here, we discuss metabolic recruitment, the tissue-level phenomenon whereby active neurons harvest resources from their surroundings. The primary event is the neuronal release of K+that mirrors workload. Astrocytes sense K+in exquisite fashion thanks to their unique
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Multiple Facets of Cellular Homeostasis and Regeneration of the Mammalian Liver Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-10-21 Stacey S. Huppert, Robert E. Schwartz
Liver regeneration occurs in response to diverse injuries and is capable of functionally reestablishing the lost parenchyma. This phenomenon has been known since antiquity, encapsulated in the Greek myth where Prometheus was to be punished by Zeus for sharing the gift of fire with humanity by having an eagle eat his liver daily, only to have the liver regrow back, thus ensuring eternal suffering and
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Myostatin: A Skeletal Muscle Chalone Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-10-21 Se-Jin Lee
Myostatin (GDF-8) was discovered 25 years ago as a new transforming growth factor-β family member that acts as a master regulator of skeletal muscle mass. Myostatin is made by skeletal myofibers, circulates in the blood, and acts back on myofibers to limit growth. Myostatin appears to have all of the salient properties of a chalone, which is a term proposed over a half century ago to describe hypothetical
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Endothelial to Mesenchymal Transition in Health and Disease Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-10-21 Yang Xu, Jason C. Kovacic
The endothelium is one of the largest organ systems in the body, and data continue to emerge regarding the importance of endothelial cell (EC) dysfunction in vascular aging and a range of cardiovascular diseases (CVDs). Over the last two decades and as a process intimately related to EC dysfunction, an increasing number of studies have also implicated endothelial to mesenchymal transition (EndMT) as
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Insulin Clearance in Health and Disease Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-10-19 Sonia M. Najjar, Sonia Caprio, Amalia Gastaldelli
Insulin action is impaired in type 2 diabetes. The functions of the hormone are an integrated product of insulin secretion from pancreatic β-cells and insulin clearance by receptor-mediated endocytosis and degradation, mostly in liver (hepatocytes) and, to a lower extent, in extrahepatic peripheral tissues. Substantial evidence indicates that genetic or acquired abnormalities of insulin secretion or
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Intracellular Ion Control of WNK Signaling Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-10-13 Elizabeth J. Goldsmith, Aylin R. Rodan
The with no lysine (K) (WNK) kinases are an evolutionarily ancient group of kinases with atypical placement of the catalytic lysine and diverse physiological roles. Recent studies have shown that WNKs are directly regulated by chloride, potassium, and osmotic pressure. Here, we review the discovery of WNKs as chloride-sensitive kinases and discuss physiological contexts in which chloride regulation
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Endoplasmic Reticulum–Plasma Membrane Junctions as Sites of Depolarization-Induced Ca2+Signaling in Excitable Cells Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-10-06 Rose E. Dixon, James S. Trimmer
Membrane contact sites between endoplasmic reticulum (ER) and plasma membrane (PM), or ER-PM junctions, are found in all eukaryotic cells. In excitable cells they play unique roles in organizing diverse forms of Ca2+signaling as triggered by membrane depolarization. ER-PM junctions underlie crucial physiological processes such as excitation-contraction coupling, smooth muscle contraction and relaxation
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Infectious and Inflammatory Pathways to Cough Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-09-28 Kubra F. Naqvi, Stuart B. Mazzone, Michael U. Shiloh
Coughing is a dynamic physiological process resulting from input of vagal sensory neurons innervating the airways and perceived airway irritation. Although cough serves to protect and clear the airways, it can also be exploited by respiratory pathogens to facilitate disease transmission. Microbial components or infection-induced inflammatory mediators can directly interact with sensory nerve receptors
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Iron and the Pathophysiology of Diabetes Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-09-22 Alexandria V. Harrison, Felipe Ramos Lorenzo, Donald A. McClain
High iron is a risk factor for type 2 diabetes mellitus (T2DM) and affects most of its cardinal features: decreased insulin secretion, insulin resistance, and increased hepatic gluconeogenesis. This is true across the normal range of tissue iron levels and in pathologic iron overload. Because of iron's central role in metabolic processes (e.g., fuel oxidation) and metabolic regulation (e.g., hypoxia
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Extracellular Vesicles as Central Mediators of COPD Pathophysiology Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Derek W. Russell, Kristopher R. Genschmer, J. Edwin Blalock
Chronic obstructive pulmonary disease (COPD) is a complex, heterogeneous, smoking-related disease of significant global impact. The complex biology of COPD is ultimately driven by a few interrelated processes, including proteolytic tissue remodeling, innate immune inflammation, derangements of the host-pathogen response, aberrant cellular phenotype switching, and cellular senescence, among others.
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Vaping and Lung Inflammation and Injury Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Jin-Ah Park, Laura E. Crotty Alexander, David C. Christiani
The use of electronic (e)-cigarettes was initially considered a beneficial solution to conventional cigarette smoking cessation. However, paradoxically, e-cigarette use is rapidly growing among nonsmokers, including youth and young adults. In 2019, this rapid growth resulted in an epidemic of hospitalizations and deaths of e-cigarette users (vapers) due to acute lung injury; this novel disease was
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Mechanisms Underlying Calcium Nephrolithiasis Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 R.T. Alexander, D.G. Fuster, H. Dimke
Nephrolithiasis is a worldwide problem with increasing prevalence, enormous costs, and significant morbidity. Calcium-containing kidney stones are by far the most common kidney stones encountered in clinical practice, and thus, hypercalciuria is the greatest risk factor for kidney stone formation. Hypercalciuria can result from enhanced intestinal absorption, increased bone resorption, or altered renal
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Innate Bacteriostatic Mechanisms Defend the Urinary Tract Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Jose A. Munoz, Anne-Catrin Uhlemann, Jonathan Barasch
Urinary tract infection (UTI) is the most common type of urogenital disease. UTI affects the urethra, bladder, ureter, and kidney. A total of 13.3% of women, 2.3% of men, and 3.4% of children in the United States will require treatment for UTI. Traditionally, bladder (cystitis) and kidney (pyelonephritis) infections are considered independently. However, both infections induce host defenses that are
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How Many Cell Types Are in the Kidney and What Do They Do? Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Michael S. Balzer, Tibor Rohacs, Katalin Susztak
The kidney maintains electrolyte, water, and acid-base balance, eliminates foreign and waste compounds, regulates blood pressure, and secretes hormones. There are at least 16 different highly specialized epithelial cell types in the mammalian kidney. The number of specialized endothelial cells, immune cells, and interstitial cell types might even be larger. The concerted interplay between different
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Under the Radar: Strategies Used by Helicobacter pylori to Evade Host Responses Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Akriti Prashar, Mariana I. Capurro, Nicola L. Jones
The body depends on its physical barriers and innate and adaptive immune responses to defend against the constant assault of potentially harmful microbes. In turn, successful pathogens have evolved unique mechanisms to adapt to the host environment and manipulate host defenses. Helicobacter pylori (Hp), a human gastric pathogen that is acquired in childhood and persists throughout life, is an example
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Paligenosis: Cellular Remodeling During Tissue Repair Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Jeffrey W. Brown, Charles J. Cho, Jason C. Mills
Complex multicellular organisms have evolved specific mechanisms to replenish cells in homeostasis and during repair. Here, we discuss how emerging technologies (e.g., single-cell RNA sequencing) challenge the concept that tissue renewal is fueled by unidirectional differentiation from a resident stem cell. We now understand that cell plasticity, i.e., cells adaptively changing differentiation state
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Mitochondria and Inflammatory Bowel Diseases: Toward a Stratified Therapeutic Intervention Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Gwo-tzer Ho, Arianne L. Theiss
Mitochondria serve numerous critical cellular functions, rapidly responding to extracellular stimuli and cellular demands while dynamically communicating with other organelles. Mitochondrial function in the gastrointestinal epithelium plays a critical role in maintaining intestinal health. Emerging studies implicate the involvement of mitochondrial dysfunction in inflammatory bowel disease (IBD). This
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Cerebral Vascular Dysfunctions Detected in Human Small Vessel Disease and Implications for Preclinical Studies Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Joanna M. Wardlaw, Helene Benveniste, Anna Williams
Cerebral small vessel disease (SVD) is highly prevalent and a common cause of ischemic and hemorrhagic stroke and dementia, yet the pathophysiology is poorly understood. Its clinical expression is highly varied, and prognostic implications are frequently overlooked in clinics; thus, treatment is currently confined to vascular risk factor management. Traditionally, SVD is considered the small vessel
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Mitochondrial H+ Leak and Thermogenesis Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Ambre M. Bertholet, Yuriy Kirichok
Mitochondria of all tissues convert various metabolic substrates into two forms of energy: ATP and heat. Historically, the primary focus of research in mitochondrial bioenergetics was on the mechanisms of ATP production, while mitochondrial thermogenesis received significantly less attention. Nevertheless, mitochondrial heat production is crucial for the maintenance of body temperature, regulation
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Physiological Functions of CRAC Channels Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Scott M. Emrich, Ryan E. Yoast, Mohamed Trebak
Store-operated Ca2+ entry (SOCE) is a ubiquitous Ca2+ signaling pathway that is evolutionarily conserved across eukaryotes. SOCE is triggered physiologically when the endoplasmic reticulum (ER) Ca2+ stores are emptied through activation of inositol 1,4,5-trisphosphate receptors. SOCE is mediated by the Ca2+ release-activated Ca2+ (CRAC) channels, which are highly Ca2+ selective. Upon store depletion
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Pericyte Control of Blood Flow Across Microvascular Zones in the Central Nervous System Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 David A. Hartmann, Vanessa Coelho-Santos, Andy Y. Shih
The vast majority of the brain's vascular length is composed of capillaries, where our understanding of blood flow control remains incomplete. This review synthesizes current knowledge on the control of blood flow across microvascular zones by addressing issues with nomenclature and drawing on new developments from in vivo optical imaging and single-cell transcriptomics. Recent studies have highlighted
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The Diverse Physiological Functions of Mechanically Activated Ion Channels in Mammals Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Kate Poole
Many aspects of mammalian physiology are mechanically regulated. One set of molecules that can mediate mechanotransduction are the mechanically activated ion channels. These ionotropic force sensors are directly activated by mechanical inputs, resulting in ionic flux across the plasma membrane. While there has been much research focus on the role of mechanically activated ion channels in touch sensation
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Adrenergic Regulation of Calcium Channels in the Heart Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Arianne Papa, Jared Kushner, Steven O. Marx
Each heartbeat is initiated by the action potential, an electrical signal that depolarizes the plasma membrane and activates a cycle of calcium influx via voltage-gated calcium channels, calcium release via ryanodine receptors, and calcium reuptake and efflux via calcium-ATPase pumps and sodium-calcium exchangers. Agonists of the sympathetic nervous system bind to adrenergic receptors in cardiomyocytes
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Cardiomyocyte Microtubules: Control of Mechanics, Transport, and Remodeling Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Keita Uchida, Emily A. Scarborough, Benjamin L. Prosser
Microtubules are essential cytoskeletal elements found in all eukaryotic cells. The structure and composition of microtubules regulate their function, and the dynamic remodeling of the network by posttranslational modifications and microtubule-associated proteins generates diverse populations of microtubules adapted for various contexts. In the cardiomyocyte, the microtubules must accommodate the unique
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Cardiac Transverse Tubules in Physiology and Heart Failure Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Katharine M. Dibb, William E. Louch, Andrew W. Trafford
In mammalian cardiac myocytes, the plasma membrane includes the surface sarcolemma but also a network of membrane invaginations called transverse (t-) tubules. These structures carry the action potential deep into the cell interior, allowing efficient triggering of Ca2+ release and initiation of contraction. Once thought to serve as rather static enablers of excitation-contraction coupling, recent
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Inflammatory Modulation of Hematopoiesis: Linking Trained Immunity and Clonal Hematopoiesis with Chronic Disorders Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Triantafyllos Chavakis, Ben Wielockx, George Hajishengallis
Inflammation-adapted hematopoietic stem and progenitor cells (HSPCs) have long been appreciated as key drivers of emergency myelopoiesis, thereby enabling the bone marrow to meet the elevated demand for myeloid cell generation under various stress conditions, such as systemic infection, inflammation, or myelosuppressive insults. In recent years, HSPC adaptations were associated with potential involvement
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Sepsis-Induced Immunosuppression Annu. Rev. Physiol. (IF 18.2) Pub Date : 2022-02-10 Lisa K. Torres, Peter Pickkers, Tom van der Poll
Sepsis is expected to have a substantial impact on public health and cost as its prevalence increases. Factors contributing to increased prevalence include a progressively aging population, advances in the use of immunomodulatory agents to treat a rising number of diseases, and immune-suppressing therapies in organ transplant recipients and cancer patients. It is now recognized that sepsis is associated