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  • Neuropathic pain: From mechanisms to treatment
    Physiol. Rev. (IF 25.588) Pub Date : 2020-06-25
    Nanna Brix Finnerup; Rohini Kuner; Troels Staehelin Jensen

    Neuropathic pain caused by a lesion or disease of the somatosensory nervous system is a common chronic pain condition with major impact on quality of life. Examples include trigeminal neuralgia, painful polyneuropathy, postherpetic neuralgia and central poststroke pain. Most patients complain of an ongoing or intermittent spontaneous pain of e.g. burning, pricking, squeezing quality, which may be accompanied

  • Nongenomic Actions of Thyroid Hormone: the Integrin Component
    Physiol. Rev. (IF 25.588) Pub Date : 2020-06-25
    Paul J Davis; Shaker A Mousa; Hung-Yun Lin

    The extracellular domain of plasma membrane integrin αvβ3 contains a cell surface receptor for thyroid hormone analogues. The receptor is largely expressed and activated in tumor cells and rapidly dividing endothelial cells. The principal ligand for this receptor is L-thyroxine (T4), usually regarded only as a prohormone for 3,5,3'-triiodo-L-thyronine (T3), the hormone analogue that expresses thyroid

  • Cellular circuits in the brain and their modulation in acute and chronic pain.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-06-11
    Rohini Kuner,Thomas Kuner

    Chronic, pathological pain remains a global health problem and a challenge to basic and clinical sciences. A major obstacle to preventing, treating or reverting chronic pain has been that the nature of neural circuits underlying the diverse components of the complex, multidimensional experience of pain is not well understood. Moreover, chronic pain involves diverse maladaptive plasticity processes

  • CRISPR-tools for physiology & cell state changes - potential of transcriptional engineering and epigenome editing.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-06-11
    Christopher Breunig,Anna Köferle,Andrea Neuner,Maximilian Wiesbeck,Valentin Baumann,Stefan H Stricker

    Given the large amount of genome-wide data that has been collected during the last decades a good understanding of how and why cells change during development, homeostasis and disease might be expected. Unfortunately, the opposite is true; Triggers that cause cellular state changes remain elusive and the underlying molecular mechanisms are poorly understood. Although genes with the potential to influence

  • SARS-CoV-2 and COVID-19: between pathophysiology complexity and therapeutic uncertainty.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-06-04
    Stefano Romagnoli,Adriano Peris,A Raffaele De Gaudio,Pierangelo Geppetti

    First isolated in China in early 2020, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for the ongoing pandemic of Coronavirus Disease 2019 (COVID-19). The disease has been spreading rapidly across the globe, with the largest burden falling on China, Europe and the United States. COVID-19 is a new clinical syndrome characterized by respiratory symptoms

    Physiol. Rev. (IF 25.588) Pub Date : 2020-05-28
    Giulia Biffi,David A Tuveson

    Efforts to develop anti-cancer therapies have largely focused on targeting the epithelial compartment, despite the presence of non-neoplastic stromal components that substantially contribute to the progression of the tumor. Indeed, cancer cell survival, growth, migration and even dormancy are influenced by the surrounding tumor microenvironment (TME). Within the TME, cancer-associated fibroblasts (CAFs)

  • An Ounce of Prevention May Prevent Hospitalization.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-05-15
    Andrew B Barker,Brant M Wagener

    Physiological Reviews, Volume 100, Issue 3, Page 1347-1348, July 2020.

  • Molecular Physiology and Pathophysiology of Bilirubin Handling by the Blood, Liver, Intestine, and Brain in the Newborn.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-05-13
    Thor W R Hansen,Ronald J Wong,David K Stevenson

    Bilirubin is the end product of heme catabolism formed during a process that involves oxidation-reduction reactions and conserves iron body stores. Unconjugated hyperbilirubinemia is common in newborn infants, but rare later in life. The basic physiology of bilirubin metabolism, such as production, transport, and excretion, has been well described. However, in the neonate, numerous variables related

  • Cardiac Mechano-Electric Coupling: Acute Effects of Mechanical Stimulation on Heart Rate and Rhythm.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-05-07
    T Alexander Quinn,Peter Kohl

    The heart is vital for biological function in almost all chordates, including human. It beats continually throughout our life, supplying the body with oxygen and nutrients while removing waste products. If it stops - so does life. The heartbeat involves precise coordination of the activity of billions of individual cells, as well as their swift and well-coordinated adaption to changes in physiological

  • Phosphate Transport in Epithelial and Nonepithelial Tissue.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-04-30
    Nati Hernando,Kenneth B Gagnon,Eleanor D Lederer

    Phosphate is an essential nutrient for life and is a critical component of bone formation, a major signaling molecule, and structural component of cell walls. Phosphate is also a component of high-energy compounds (i.e. AMP, ADP, and ATP), and essential for nucleic acid helical structure (i.e. RNA and DNA). Phosphate plays a central role in the process of mineralization, normal serum levels being associated

  • The Renal Physiology of Pendrin-Positive Intercalated Cells.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-04-29
    Susan M Wall,Jill W Verlander,Cesar A Romero

    Intercalated cells (ICs) are found in the connecting tubule and the collecting duct. Of the three IC subtypes identified, type B intercalated cells are one of the best characterized and known to mediate Cl- absorption and HCO3- secretion, largely through the anion exchanger pendrin. This exchanger is thought to act in tandem with the Na+-dependent Cl-/HCO3- exchanger, NDCBE, to mediate net NaCl absorption

    Physiol. Rev. (IF 25.588) Pub Date : 2020-04-23
    Roberto Papait,Simone Serio,Gianluigi Condorelli

    Gene expression is needed for the maintenance of heart function under normal conditions and in response to stress. Each cell type of the heart has a specific program controlling transcription. Different types of stress induce modifications of these programs, and if prolonged, can lead to altered cardiac phenotype and, eventually, to heart failure. The transcriptional status of a gene is regulated by

  • Glial connexins and pannexins in the healthy and diseased brain.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-04-23
    Christian Ba Giaume,Christian C Naus,Juan Carlos Saez,Luc Leybaert

    Over the past several decades a large amount of data have established that glial cells, the main cell population in the brain, dynamically interact with neurons and thus impact their activity and survival. One typical feature of glia is their marked expression of several connexins, the membrane proteins forming intercellular gap junction channels and hemichannels. Pannexins, which have a tetraspan

  • The Female Response to Seminal Fluid.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-01-30
    John E Schjenken,Sarah A Robertson

    Seminal fluid is often assumed to have just one function in mammalian reproduction, delivering sperm to fertilize oocytes. But seminal fluid also transmits signaling agents that interact with female reproductive tissues to facilitate conception and .pregnancy. Upon seminal fluid contact, female tissues initiate a controlled inflammatory response that affects several aspects of reproductive function

  • Microenvironmental Determinants of Pancreatic Cancer.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-04-16
    Elisabeth Hessmann,Sören M Buchholz,Ihsan Ekin Demir,Shiv K Singh,Thomas M Gress,Volker Ellenrieder,Albrecht Neesse

    Pancreatic ductal adenocarcinoma (PDAC) belongs to the most lethal solid tumors in humans. A histological hallmark feature of PDAC is the pronounced tumor microenvironment (TME) that dynamically evolves during tumor progression. The TME consists of different non-neoplastic cells such as cancer-associated fibroblasts (CAFs), immune cells, endothelial cells and neurons. Furthermore, abundant extracellular

  • Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-03-27
    Hong-Long Ji,Runzhen Zhao,Sadis Matalon,Michael A Matthay

    Patients with hypertension, diabetes, coronary heart disease, cerebrovascular illness, chronic obstructive pulmonary disease, and kidney dysfunction have worse clinical outcomes when infected with SARS-CoV-2, for unknown reasons. The purpose of this review is to summarize the evidence for the existence of elevated plasmin(ogen) in COVID-19 patients with these comorbid conditions. Plasmin, and other

  • Brain Lateralization: A Comparative Perspective
    Physiol. Rev. (IF 25.588) Pub Date : 2020-04-01
    Onur Güntürkün; Felix Ströckens; Sebastian Ocklenburg

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  • Impact of Respiratory Syncytial Virus Infection on the Host Cell: Implications for Antiviral Strategies
    Physiol. Rev. (IF 25.588) Pub Date : 2020-03-26
    Mengjie Hu; Marie A Bogoyevitch; David A Jans

    Respiratory syncytial virus (RSV) is one of the leading causes of viral respiratory tract infection in infants, the elderly and the immunocompromised worldwide, causing more deaths each year than influenza. Years of research into RSV since its discovery over 60 years ago have elucidated detailed mechanisms of the host-pathogen interface. RSV infection elicits widespread transcriptomic and proteomic

  • Are We meeting the Promise of Endotypes and Precision Medicine in Asthma.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-03-26
    Anuradha Ray,Matthew Camiolo,Anne Fitzpatrick,Marc Gauthier,Sally E Wenzel

    While the term "asthma" has long been known to describe heterogeneous groupings of patients, only recently have data evolved which enable a molecular understanding of the clinical differences. The evolution of transcriptomics (and other 'omics platforms) and improved statistical analyses in combination with large clinical cohorts opened the door for molecular characterization of pathobiologic processes

  • Emerging approaches for restoration of hearing and vision
    Physiol. Rev. (IF 25.588) Pub Date : 2020-03-19
    Sonja Kleinlogel; Christian Vogl; Marcus Jeschke; Jakob Neef; Tobias Moser

    Impairments of vision and hearing are highly prevalent conditions limiting the quality of life and presenting a major socioeconomic burden. For long, retinal and cochlear disorders have remained intractable for causal therapies, with sensory rehabilitation limited to glasses, hearing aids, and electrical cochlear or retinal implants. Recently, the application of gene therapy and optogenetics to eye

  • The Urothelium: Life in a Liquid Environment.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-03-19
    Marianela G Dalghi,Nicolas Montalbetti,Marcelo D Carattino,Gerard Apodaca

    The urothelium, which lines the renal pelvis, ureters, urinary bladder, and proximal urethra, forms a high resistance but adaptable barrier that surveils its mechanochemical environment and communicates changes to underlying tissues including afferent nerve fibers and the smooth muscle. The goal of this review is to summarize new insights into urothelial biology and function that have occurred in the

  • Physiology and Pathophysiology of Itch
    Physiol. Rev. (IF 25.588) Pub Date : 2020-03-16
    Ferda Cevikbas; Ethan A. Lerner

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  • Ion Channels Controlling Circadian Rhythms in Suprachiasmatic Nucleus Excitability.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-03-12
    Jenna R M Harvey,Amber E Plante,Andrea L Meredith

    Animals synchronize to the environmental day-night cycle by means of an internal circadian clock in the brain. In mammals, this timekeeping mechanism is housed in the suprachiasmatic nucleus (SCN) of the hypothalamus and is entrained by light input from the retina. The output of the SCN is a neural code for circadian time, which arises from the collective activity of neurons within the SCN circuit

  • Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-10-31
    Karel Talavera,Justyna B Startek,Julio Alvarez-Collazo,Brett Boonen,Yeranddy A Alpizar,Alicia Sanchez,Robbe Naert,Bernd Nilius

    The transient receptor potential ankyrin (TRPA) channels are Ca2+-permeable nonselective cation channels remarkably conserved through the animal kingdom. Mammals have only one member, TRPA1, which is widely expressed in sensory neurons and in non-neuronal cells (such as epithelial cells and hair cells). TRPA1 owes its name to the presence of 14 ankyrin repeats located in the NH2 terminus of the channel

  • Origin and Evolution of the Neuroendocrine Control of Reproduction in Vertebrates, With Special Focus on Genome and Gene Duplications.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-10-18
    Sylvie Dufour,Bruno Quérat,Hervé Tostivint,Catherine Pasqualini,Hubert Vaudry,Karine Rousseau

    In humans, as in the other mammals, the neuroendocrine control of reproduction is ensured by the brain-pituitary gonadotropic axis. Multiple internal and environmental cues are integrated via brain neuronal networks, ultimately leading to the modulation of the activity of gonadotropin-releasing hormone (GnRH) neurons. The decapeptide GnRH is released into the hypothalamic-hypophysial portal blood system

  • mRNA Metabolism in Cardiac Development and Disease: Life After Transcription.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-11-21
    Chen Gao,Yibin Wang

    The central dogma of molecular biology illustrates the importance of mRNAs as critical mediators between genetic information encoded at the DNA level and proteomes/metabolomes that determine the diverse functional outcome at the cellular and organ levels. Although the total number of protein-producing (coding) genes in the mammalian genome is ~20,000, it is evident that the intricate processes of cardiac

  • Stiffness Sensing by Cells.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-11-21
    Paul A Janmey,Daniel A Fletcher,Cynthia A Reinhart-King

    Physical stimuli are essential for the function of eukaryotic cells, and changes in physical signals are important elements in normal tissue development as well as in disease initiation and progression. The complexity of physical stimuli and the cellular signals they initiate are as complex as those triggered by chemical signals. One of the most important, and the focus of this review, is the effect

  • Revisiting the Functional Anatomy of the Human Brain: Toward a Meta-Networking Theory of Cerebral Functions.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-02-20
    Guillaume Herbet,Hugues Duffau

    For more than one century, brain processing was mainly thought in a localizationist framework, in which one given function was underpinned by a discrete, isolated cortical area, and with a similar cerebral organization across individuals. However, advances in brain mapping techniques in humans have provided new insights into the organizational principles of anatomo-functional architecture. Here, we

  • Physiology of the Endometrium and Regulation of Menstruation.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-02-07
    Hilary O D Critchley,Jacqueline A Maybin,Gregory M Armstrong,Alistair R W Williams

    The physiological functions of the uterine endometrium (uterine lining) are preparation for implantation, maintenance of pregnancy if implantation occurs, and menstruation in the absence of pregnancy. The endometrium thus plays a pivotal role in reproduction and continuation of our species. Menstruation is a steroid-regulated event, and there are alternatives for a progesterone-primed endometrium,

  • From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-02-07
    Anna Le Tortorec,Giulia Matusali,Dominique Mahé,Florence Aubry,Séverine Mazaud-Guittot,Laurent Houzet,Nathalie Dejucq-Rainsford

    The male genital tract (MGT) is the target of a number of viral infections that can have deleterious consequences at the individual, offspring, and population levels. These consequences include infertility, cancers of male organs, transmission to the embryo/fetal development abnormalities, and sexual dissemination of major viral pathogens such as human immunodeficiency virus (HIV) and hepatitis B virus

  • Muscle Toxicity of Drugs: When Drugs Turn Physiology into Pathophysiology.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-11-21
    Lando Janssen,Neeltje A E Allard,Christiaan G J Saris,Jaap Keijer,Maria T E Hopman,Silvie Timmers

    Drugs are prescribed to manage or prevent symptoms and diseases, but may sometimes cause unexpected toxicity to muscles. The symptomatology and clinical manifestations of the myotoxic reaction can vary significantly between drugs and between patients on the same drug. This poses a challenge on how to recognize and prevent the occurrence of drug-induced muscle toxicity. The key to appropriate management

  • Renal Autocrine and Paracrine Signaling: A Story of Self-protection.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-01-30
    Jens Leipziger,Helle Praetorius

    Autocrine and paracrine signaling in the kidney adds an extra level of diversity and complexity to renal physiology. The extensive scientific production on the topic precludes easy understanding of the fundamental purpose of the vast number of molecules and systems that influence the renal function. This systematic review provides the broader pen strokes for a collected image of renal paracrine signaling

  • Phylogenic determinants of cardiovascular frailty, focus on hemodynamics and arterial smooth muscle cells.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-01-30
    Jean-Baptiste Michel

    The evolution of the circulatory system from invertebrates to mammals has involved the passage from an open system to a closed in-parallel system via a closed in-series system, accompanying the increasing complexity and efficiency of life's biological functions. The archaic heart enables pulsatile motion waves of hemolymph in invertebrates, and the in-series circulation in fish occurs with only an

  • Pathogenesis of HIV-Related Lung Disease: Immunity, Infection, and Inflammation.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-10-10
    Sushma K Cribbs,Kristina Crothers,Alison Morris

    Despite anti-retroviral therapy (ART), human immunodeficiency virus-1 (HIV)-related pulmonary disease continues to be a major cause of morbidity and mortality for people living with HIV (PLWH). The spectrum of lung diseases has changed from acute opportunistic infections resulting in death to chronic lung diseases for those with access to ART. Chronic immune activation and suppression can result in

  • Connexins: Key Players in the Control of Vascular Plasticity and Function.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-04-01
    Ulrich Pohl

    Of the 21 members of the connexin family, 4 (Cx37, Cx40, Cx43, and Cx45) are expressed in the endothelium and/or smooth muscle of intact blood vessels to a variable and dynamically regulated degree. Full-length connexins oligomerize and form channel structures connecting the cytosol of adjacent cells (gap junctions) or the cytosol with the extracellular space (hemichannels). The different connexins

  • The Physiology of the Gastric Parietal Cell.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-10-31
    Amy C Engevik,Izumi Kaji,James R Goldenring

    Parietal cells are responsible for gastric acid secretion, which aids in the digestion of food, absorption of minerals, and control of harmful bacteria. However, a fine balance of activators and inhibitors of parietal cell-mediated acid secretion is required to ensure proper digestion of food, while preventing damage to the gastric and duodenal mucosa. As a result, parietal cell secretion is highly

  • Stem Cells and the Differentiation Hierarchy in Mammary Gland Development.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-09-20
    Nai Yang Fu,Emma Nolan,Geoffrey J Lindeman,Jane E Visvader

    The mammary gland is a highly dynamic organ that undergoes profound changes within its epithelium during puberty and the reproductive cycle. These changes are fueled by dedicated stem and progenitor cells. Both short- and long-lived lineage-restricted progenitors have been identified in adult tissue as well as a small pool of multipotent mammary stem cells (MaSCs), reflecting intrinsic complexity within

  • Mechanisms and Consequences of Oxygen and Carbon Dioxide Sensing in Mammals.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-09-20
    Eoin P Cummins,Moritz J Strowitzki,Cormac T Taylor

    Molecular oxygen (O2) and carbon dioxide (CO2) are the primary gaseous substrate and product of oxidative phosphorylation in respiring organisms, respectively. Variance in the levels of either of these gasses outside of the physiological range presents a serious threat to cell, tissue, and organism survival. Therefore, it is essential that endogenous levels are monitored and kept at appropriate concentrations

  • Pavlovian Conditioning of Immunological and Neuroendocrine Functions.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-08-22
    Martin Hadamitzky,Laura Lückemann,Gustavo Pacheco-López,Manfred Schedlowski

    The phenomenon of behaviorally conditioned immunological and neuroendocrine functions has been investigated for the past 100 yr. The observation that associative learning processes can modify peripheral immune functions was first reported and investigated by Ivan Petrovic Pavlov and his co-workers. Their work later fell into oblivion, also because so little was known about the immune system's function

  • Methylglyoxal, a Highly Reactive Dicarbonyl Compound, in Diabetes, Its Vascular Complications, and Other Age-Related Diseases.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-09-20
    C G Schalkwijk,C D A Stehouwer

    The formation and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl compound, has been implicated in the pathogenesis of type 2 diabetes, vascular complications of diabetes, and several other age-related chronic inflammatory diseases such as cardiovascular disease, cancer, and disorders of the central nervous system. MGO is mainly formed as a byproduct of glycolysis and, under physiological

  • Current Principles of Motor Control, with Special Reference to Vertebrate Locomotion.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-09-12
    Sten Grillner,Abdeljabbar El Manira

    The vertebrate control of locomotion involves all levels of the nervous system from cortex to the spinal cord. Here, we aim to cover all main aspects of this complex behavior, from the operation of the microcircuits in the spinal cord to the systems and behavioral levels and extend from mammalian locomotion to the basic undulatory movements of lamprey and fish. The cellular basis of propulsion represents

  • Extracellular Nucleotides and P2 Receptors in Renal Function.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-08-22
    Volker Vallon,Robert Unwin,Edward W Inscho,Jens Leipziger,Bellamkonda K Kishore

    The understanding of the nucleotide/P2 receptor system in the regulation of renal hemodynamics and transport function has grown exponentially over the last 20 yr. This review attempts to integrate the available data while also identifying areas of missing information. First, the determinants of nucleotide concentrations in the interstitial and tubular fluids of the kidney are described, including mechanisms

  • Sensory Processing at Ribbon Synapses in the Retina and the Cochlea.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-08-02
    Tobias Moser,Chad P Grabner,Frank Schmitz

    In recent years, sensory neuroscientists have made major efforts to dissect the structure and function of ribbon synapses which process sensory information in the eye and ear. This review aims to summarize our current understanding of two key aspects of ribbon synapses: 1) their mechanisms of exocytosis and endocytosis and 2) their molecular anatomy and physiology. Our comparison of ribbon synapses

  • SIRT6, a Mammalian Deacylase with Multitasking Abilities.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-08-22
    Andrew R Chang,Christina M Ferrer,Raul Mostoslavsky

    Mammalian sirtuins have emerged in recent years as critical modulators of multiple biological processes, regulating cellular metabolism, DNA repair, gene expression, and mitochondrial biology. As such, they evolved to play key roles in organismal homeostasis, and defects in these proteins have been linked to a plethora of diseases, including cancer, neurodegeneration, and aging. In this review, we

  • Free Fatty Acid Receptors in Health and Disease.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-09-05
    Ikuo Kimura,Atsuhiko Ichimura,Ryuji Ohue-Kitano,Miki Igarashi

    Fatty acids are metabolized and synthesized as energy substrates during biological responses. Long- and medium-chain fatty acids derived mainly from dietary triglycerides, and short-chain fatty acids (SCFAs) produced by gut microbial fermentation of the otherwise indigestible dietary fiber, constitute the major sources of free fatty acids (FFAs) in the metabolic network. Recently, increasing evidence

  • Regulation of the Renal NaCl Cotransporter and Its Role in Potassium Homeostasis.
    Physiol. Rev. (IF 25.588) Pub Date : 2020-01-01
    Ewout J Hoorn,Martin Gritter,Catherina A Cuevas,Robert A Fenton

    Daily dietary potassium (K+) intake may be as large as the extracellular K+ pool. To avoid acute hyperkalemia, rapid removal of K+ from the extracellular space is essential. This is achieved by translocating K+ into cells and increasing urinary K+ excretion. Emerging data now indicate that the renal thiazide-sensitive NaCl cotransporter (NCC) is critically involved in this homeostatic kaliuretic response

  • Evolving and Expanding the Roles of Mitophagy as a Homeostatic and Pathogenic Process.
    Physiol. Rev. (IF 25.588) Pub Date : 2019-01-01
    Åsa B Gustafsson,Gerald W Dorn

    The central functions fulfilled by mitochondria as both energy generators essential for tissue homeostasis and gateways to programmed apoptotic and necrotic cell death mandate tight control over the quality and quantity of these ubiquitous endosymbiotic organelles. Mitophagy, the targeted engulfment and destruction of mitochondria by the cellular autophagy apparatus, has conventionally been considered

  • Activin A in Mammalian Physiology.
    Physiol. Rev. (IF 25.588) Pub Date : 2018-12-13
    Enrrico Bloise,Pasquapina Ciarmela,Cynthia Dela Cruz,Stefano Luisi,Felice Petraglia,Fernando M Reis

    Activins are dimeric glycoproteins belonging to the transforming growth factor beta superfamily and resulting from the assembly of two beta subunits, which may also be combined with alpha subunits to form inhibins. Activins were discovered in 1986 following the isolation of inhibins from porcine follicular fluid, and were characterized as ovarian hormones that stimulate follicle stimulating hormone

  • The Activity of Peptides of the Calcitonin Family in Bone.
    Physiol. Rev. (IF 25.588) Pub Date : 2018-12-13
    Dorit Naot,David S Musson,Jillian Cornish

    Calcitonin was discovered over 50 yr ago as a new hormone that rapidly lowers circulating calcium levels. This effect is caused by the inhibition of calcium efflux from bone, as calcitonin is a potent inhibitor of bone resorption. Calcitonin has been in clinical use for conditions of accelerated bone turnover, including Paget's disease and osteoporosis; although in recent years, with the development

  • Lower Body Negative Pressure: Physiological Effects, Applications, and Implementation.
    Physiol. Rev. (IF 25.588) Pub Date : 2018-12-13
    Nandu Goswami,Andrew Philip Blaber,Helmut Hinghofer-Szalkay,Victor A Convertino

    This review presents lower body negative pressure (LBNP) as a unique tool to investigate the physiology of integrated systemic compensatory responses to altered hemodynamic patterns during conditions of central hypovolemia in humans. An early review published in Physiological Reviews over 40 yr ago (Wolthuis et al. Physiol Rev 54: 566-595, 1974) focused on the use of LBNP as a tool to study effects

  • Corrigendum.
    Physiol. Rev. (IF 25.588) Pub Date : 2018-11-18

  • Induced Pluripotent Stem Cells and Their Use in Human Models of Disease and Development.
    Physiol. Rev. (IF 25.588) Pub Date : 2018-10-18
    Peter Karagiannis,Kazutoshi Takahashi,Megumu Saito,Yoshinori Yoshida,Keisuke Okita,Akira Watanabe,Haruhisa Inoue,Jun K Yamashita,Masaya Todani,Masato Nakagawa,Mitsujiro Osawa,Yoshimi Yashiro,Shinya Yamanaka,Kenji Osafune

    The discovery of somatic cell nuclear transfer proved that somatic cells can carry the same genetic code as the zygote, and that activating parts of this code are sufficient to reprogram the cell to an early developmental state. The discovery of induced pluripotent stem cells (iPSCs) nearly half a century later provided a molecular mechanism for the reprogramming. The initial creation of iPSCs was

  • From Molecules to Mechanisms: Functional Proteomics and Its Application to Renal Tubule Physiology.
    Physiol. Rev. (IF 25.588) Pub Date : 2018-09-06
    Markus M Rinschen,Kavee Limbutara,Mark A Knepper,D Michael Payne,Trairak Pisitkun

    Classical physiological studies using electrophysiological, biophysical, biochemical, and molecular techniques have created a detailed picture of molecular transport, bioenergetics, contractility and movement, and growth, as well as the regulation of these processes by external stimuli in cells and organisms. Newer systems biology approaches are beginning to provide deeper and broader understanding

  • DEPTOR at the Nexus of Cancer, Metabolism, and Immunity.
    Physiol. Rev. (IF 25.588) Pub Date : 2018-06-14
    Alexandre Caron,David M Briscoe,Denis Richard,Mathieu Laplante

    DEP domain-containing mechanistic target of rapamycin (mTOR)-interacting protein (DEPTOR) is an important modulator of mTOR, a kinase at the center of two important protein complexes named mTORC1 and mTORC2. These highly studied complexes play essential roles in regulating growth, metabolism, and immunity in response to mitogens, nutrients, and cytokines. Defects in mTOR signaling have been associated

  • The Oxytocin Receptor: From Intracellular Signaling to Behavior.
    Physiol. Rev. (IF 25.588) Pub Date : 2018-06-14
    Benjamin Jurek,Inga D Neumann

    The many facets of the oxytocin (OXT) system of the brain and periphery elicited nearly 25,000 publications since 1930 (see FIGURE 1 , as listed in PubMed), which revealed central roles for OXT and its receptor (OXTR) in reproduction, and social and emotional behaviors in animal and human studies focusing on mental and physical health and disease. In this review, we discuss the mechanisms of OXT expression

  • Pharmacology of Adenosine Receptors: The State of the Art.
    Physiol. Rev. (IF 25.588) Pub Date : 2018-06-01
    Pier Andrea Borea,Stefania Gessi,Stefania Merighi,Fabrizio Vincenzi,Katia Varani

    Adenosine is a ubiquitous endogenous autacoid whose effects are triggered through the enrollment of four G protein-coupled receptors: A1, A2A, A2B, and A3. Due to the rapid generation of adenosine from cellular metabolism, and the widespread distribution of its receptor subtypes in almost all organs and tissues, this nucleoside induces a multitude of physiopathological effects, regulating central nervous

  • CLC Chloride Channels and Transporters: Structure, Function, Physiology, and Disease.
    Physiol. Rev. (IF 25.588) Pub Date : 2018-05-31
    Thomas J Jentsch,Michael Pusch

    CLC anion transporters are found in all phyla and form a gene family of eight members in mammals. Two CLC proteins, each of which completely contains an ion translocation parthway, assemble to homo- or heteromeric dimers that sometimes require accessory β-subunits for function. CLC proteins come in two flavors: anion channels and anion/proton exchangers. Structures of these two CLC protein classes

  • Endosomal and Phagosomal SNAREs.
    Physiol. Rev. (IF 25.588) Pub Date : 2018-05-24
    Ilse Dingjan,Peter T A Linders,Danielle R J Verboogen,Natalia H Revelo,Martin Ter Beest,Geert van den Bogaart

    The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein family is of vital importance for organelle communication. The complexing of cognate SNARE members present in both the donor and target organellar membranes drives the membrane fusion required for intracellular transport. In the endocytic route, SNARE proteins mediate trafficking between endosomes and phagosomes

  • Physiology of Astroglia.
    Physiol. Rev. (IF 25.588) Pub Date : 2018-01-20
    Alexei Verkhratsky,Maiken Nedergaard

    Astrocytes are neural cells of ectodermal, neuroepithelial origin that provide for homeostasis and defense of the central nervous system (CNS). Astrocytes are highly heterogeneous in morphological appearance; they express a multitude of receptors, channels, and membrane transporters. This complement underlies their remarkable adaptive plasticity that defines the functional maintenance of the CNS in

  • Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa.
    Physiol. Rev. (IF 25.588) Pub Date : 2018-01-20
    Robert Dantzer

    Because of the compartmentalization of disciplines that shaped the academic landscape of biology and biomedical sciences in the past, physiological systems have long been studied in isolation from each other. This has particularly been the case for the immune system. As a consequence of its ties with pathology and microbiology, immunology as a discipline has largely grown independently of physiology

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