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Annu Rev Physiol 2019 Feb;81:335-357

Murdoch Children's Research Institute, Parkville, Victoria 3052, Australia; email:

Human kidney tissue can now be generated via the directed differentiation of human pluripotent stem cells. This advance is anticipated to facilitate the modeling of human kidney diseases, provide platforms for nephrotoxicity screening, enable cellular therapy, and potentially generate tissue for renal replacement. All such applications will rely upon the accuracy and reliability of the model and the capacity for stem cell-derived kidney tissue to recapitulate both normal and diseased states. Read More

Annu Rev Physiol 2019 Feb;81:113-137

Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA; email:

Ca- and voltage-gated K channels of large conductance (BK channels) are expressed in a diverse variety of both excitable and inexcitable cells, with functional properties presumably uniquely calibrated for the cells in which they are found. Although some diversity in BK channel function, localization, and regulation apparently arises from cell-specific alternative splice variants of the single pore-forming α subunit ( KCa1.1, Kcnma1, Slo1) gene, two families of regulatory subunits, β and γ, define BK channels that span a diverse range of functional properties. Read More

Annu Rev Physiol 2019 Feb;81:483-503

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China; email: ,

Endothelial cell (EC) metabolism is important for health and disease. Metabolic pathways, such as glycolysis, fatty acid oxidation, and amino acid metabolism, determine vasculature formation. These metabolic pathways have different roles in securing the production of energy and biomass and the maintenance of redox homeostasis in vascular migratory tip cells, proliferating stalk cells, and quiescent phalanx cells, respectively. Read More

Annu Rev Physiol 2019 Feb;81:429-452

Medical Research Council, Laboratory of Molecular Biology, Cambridge University, Cambridgeshire CB2 0QH, United Kingdom; email:

Although, as the major organ of gas exchange, the lung is considered a nonlymphoid organ, an interconnected network of lung-resident innate cells, including epithelial cells, dendritic cells, macrophages, and natural killer cells is crucial for its protection. These cells provide defense against a daily assault by airborne bacteria, viruses, and fungi, as well as prevent the development of cancer, allergy, and the outgrowth of commensals. Our understanding of this innate immune environment has recently changed with the discovery of a family of innate lymphoid cells (ILCs): ILC1s, ILC2s, and ILC3s. Read More

Annu Rev Physiol 2019 Feb;81:359-373

University of Montreal and Nephrology Service, Research Center, Hôpital du Sacré-Coeur de Montreal, Montreal, Quebec H4J 1C5, Canada; email:

Recent experiments using optogenetic tools facilitate the identification and functional analysis of thirst neurons and vasopressin-producing neurons. Four major advances provide a detailed anatomy and physiology of thirst, taste for water, and arginine-vasopressin (AVP) release: ( a) Thirst and AVP release are regulated by the classical homeostatic, interosensory plasma osmolality negative feedback as well as by novel, exterosensory, anticipatory signals. These anticipatory signals for thirst and vasopressin release concentrate on the same homeostatic neurons and circumventricular organs that monitor the composition of blood. Read More

Annu Rev Physiol 2019 Feb;81:89-111

Department of Biology, Ecology and Earth Science, University of Calabria, 87036 Arcavacata di Rende (CS), Italy.

Maternal cardiovascular changes during pregnancy include an expansion of plasma volume, increased cardiac output, decreased peripheral resistance, and increased uteroplacental blood flow. These adaptations facilitate the progressive increase in uteroplacental perfusion that is required for normal fetal growth and development, prevent the development of hypertension, and provide a reserve of blood in anticipation of the significant blood loss associated with parturition. Each woman's genotype and phenotype determine her ability to adapt in response to molecular signals that emanate from the fetoplacental unit. Read More

Annu Rev Physiol 2019 Feb;81:309-333

Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA; email:

The current unidimensional paradigm of kidney disease detection is incompatible with the complexity and heterogeneity of renal pathology. The diagnosis of kidney disease has largely focused on glomerular filtration, while assessment of kidney tubular health has notably been absent. Following insult, the kidney tubular cells undergo a cascade of cellular responses that result in the production and accumulation of low-molecular-weight proteins in the urine and systemic circulation. Read More

Annu Rev Physiol 2019 Feb;81:505-534

Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA; email:

Abnormal blood and lymphatic vessels create a hostile tumor microenvironment characterized by hypoxia, low pH, and elevated interstitial fluid pressure. These abnormalities fuel tumor progression, immunosuppression, and treatment resistance. In 2001, we proposed a novel hypothesis that the judicious use of antiangiogenesis agents-originally developed to starve tumors-could transiently normalize tumor vessels and improve the outcome of anticancer drugs administered during the window of normalization. Read More

Annu Rev Physiol 2019 Feb;81:535-560

VIB-Center for Cancer Biology and Department of Oncology, KU Leuven, Leuven B-3000 Belgium; email:

Research over the last decades has provided strong evidence for the pivotal role of the tumor-associated blood and lymphatic vasculature in supporting immunoevasion and in subverting T cell-mediated immunosurveillance. Conversely, tumor blood and lymphatic vessel growth is in part regulated by the immune system, with infiltrating innate as well as adaptive immune cells providing both immunosuppressive and various angiogenic signals. Thus, tumor angiogenesis and escape of immunosurveillance are two cancer hallmarks that are tightly linked and interregulated by cell constituents from compartments secreting both chemokines and cytokines. Read More

Annu Rev Physiol 2019 Feb 10;81:607-627. Epub 2018 Dec 10.

Centre of Inflammation and Metabolism/Centre for Physical Activity Research (CIM/CFAS), Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark; email:

Physical inactivity is one of the leading health problems in the world. Strong epidemiological and clinical evidence demonstrates that exercise decreases the risk of more than 35 different disorders and that exercise should be prescribed as medicine for many chronic diseases. The physiology and molecular biology of exercise suggests that exercise activates multiple signaling pathways of major health importance. Read More

Annu Rev Physiol 2019 Feb 28;81:375-402. Epub 2018 Nov 28.

Department of Medicine, Yale School of Medicine, New Haven, Connecticut 06520, USA; email:

Regulated cell death is a major mechanism to eliminate damaged, infected, or superfluous cells. Previously, apoptosis was thought to be the only regulated cell death mechanism; however, new modalities of caspase-independent regulated cell death have been identified, including necroptosis, pyroptosis, and autophagic cell death. As an understanding of the cellular mechanisms that mediate regulated cell death continues to grow, there is increasing evidence that these pathways are implicated in the pathogenesis of many pulmonary disorders. Read More

Annu Rev Physiol 2019 Feb 28;81:453-482. Epub 2018 Nov 28.

Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, NY 10065, USA; email:

Mitochondria are an iconic distinguishing feature of eukaryotic cells. Mitochondria encompass an active organellar network that fuses, divides, and directs a myriad of vital biological functions, including energy metabolism, cell death regulation, and innate immune signaling in different tissues. Another crucial and often underappreciated function of these dynamic organelles is their central role in the metabolism of the most abundant and biologically versatile transition metals in mammalian cells, iron. Read More

Annu Rev Physiol 2019 Feb 28;81:139-164. Epub 2018 Nov 28.

Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email:

Branched chain amino acids (BCAAs) are building blocks for all life-forms. We review here the fundamentals of BCAA metabolism in mammalian physiology. Decades of studies have elicited a deep understanding of biochemical reactions involved in BCAA catabolism. Read More

Annu Rev Physiol 2019 Feb 28;81:403-428. Epub 2018 Nov 28.

Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA; email:

The lung is often overlooked as a metabolically active organ, yet biochemical studies have long demonstrated that glucose utilization surpasses that of many other organs, including the heart, kidney, and brain. For most cells in the lung, energy consumption is relegated to performing common cellular tasks, like mRNA transcription and protein translation. However, certain lung cell populations engage in more specialized types of energy-consuming behaviors, such as the beating of cilia or the production of surfactant. Read More

Annu Rev Physiol 2019 Feb 12;81:211-233. Epub 2018 Nov 12.

Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA; email:

Pancreatic cancer is characterized by an extensive fibroinflammatory reaction that includes immune cells, fibroblasts, extracellular matrix, vascular and lymphatic vessels, and nerves. Overwhelming evidence indicates that the pancreatic cancer microenvironment regulates cancer initiation, progression, and maintenance. Pancreatic cancer treatment has progressed little over the past several decades, and the prognosis remains one of the worst for any cancer. Read More

Annu Rev Physiol 2019 Feb 7;81:585-605. Epub 2018 Nov 7.

Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore; email:

It is increasingly clear that mechanotransduction pathways play important roles in regulating fundamental cellular functions. Of the basic mechanical functions, the determination of cellular morphology is critical. Cells typically use many mechanosensitive steps and different cell states to achieve a polarized shape through repeated testing of the microenvironment. Read More

Annu Rev Physiol 2019 Feb 31;81:235-259. Epub 2018 Oct 31.

Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email:

At the most fundamental level, the bowel facilitates absorption of small molecules, regulates fluid and electrolyte flux, and eliminates waste. To successfully coordinate this complex array of functions, the bowel relies on the enteric nervous system (ENS), an intricate network of more than 500 million neurons and supporting glia that are organized into distinct layers or plexi within the bowel wall. Neuron and glial diversity, as well as neurotransmitter and receptor expression in the ENS, resembles that of the central nervous system. Read More

Annu Rev Physiol 2019 Feb 31;81:165-188. Epub 2018 Oct 31.

Department of Pathology and Laboratory Medicine, Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, California 90272, USA; email:

Phospholipids are major constituents of biological membranes. The fatty acyl chain composition of phospholipids determines the biophysical properties of membranes and thereby affects their impact on biological processes. The composition of fatty acyl chains is also actively regulated through a deacylation and reacylation pathway called Lands' cycle. Read More

Annu Rev Physiol 2019 Feb 31;81:261-284. Epub 2018 Oct 31.

Visceral Pain Research Group, College of Medicine and Public Health, Centre for Neuroscience, Flinders University, Bedford Park, South Australia 5042, Australia; email:

Most of us live blissfully unaware of the orchestrated function that our internal organs conduct. When this peace is interrupted, it is often by routine sensations of hunger and urge. However, for >20% of the global population, chronic visceral pain is an unpleasant and often excruciating reminder of the existence of our internal organs. Read More

Annu Rev Physiol 2019 Feb 24;81:189-209. Epub 2018 Oct 24.

Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; email: ,

The gastrointestinal mucosa, structurally formed by the epithelium and lamina propria, serves as a selective barrier that separates luminal contents from the underlying tissues. Gastrointestinal mucosal wound repair is orchestrated by a series of spatial and temporal events that involve the epithelium, recruited immune cells, resident stromal cells, and the microbiota present in the wound bed. Upon injury, repair of the gastrointestinal barrier is mediated by collective migration, proliferation, and subsequent differentiation of epithelial cells. Read More

Annu Rev Physiol 2019 Feb 24;81:43-62. Epub 2018 Oct 24.

Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; email:

In the nervous system, ATP is co-stored in vesicles with classical transmitters and released in a regulated manner. ATP from the intracellular compartment can also exit the cell through hemichannels and following shear stress or membrane damage. In the past 30 years, the action of ATP as an extracellular transmitter at cell-surface receptors has evolved from somewhat of a novelty that was treated with skepticism to purinergic transmission being accepted as having widespread important functional roles mediated by ATP-gated ionotropic P2X receptors (P2XRs). Read More

Annu Rev Physiol 2019 Feb 26;81:561-583. Epub 2018 Sep 26.

Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada; email:

Comparative physiology studies of high-altitude species provide an exceptional opportunity to understand naturally evolved mechanisms of hypoxia resistance. Aerobic capacity (VOmax) 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 VOmax. This is associated with enhanced flux capacity through the O transport cascade and attenuation of the maladaptive responses to chronic hypoxia that can impair O transport. Read More

Annu Rev Physiol 2019 Feb 26;81:285-308. Epub 2018 Sep 26.

Department of Integrative Physiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.

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. Read More

Annu Rev Physiol 2019 Feb 26;81:1-17. Epub 2018 Sep 26.

Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA; email:

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. Read More

Annu Rev Physiol 2019 Feb 14;81:63-87. Epub 2018 Sep 14.

King's College London, School of Cardiovascular Medicine and Sciences, The British Heart Foundation Centre of Excellence, The Rayne Institute, St. Thomas' Hospital, London SE1 7EH, United Kingdom; email:

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. Read More

Annu Rev Physiol 2019 Feb 14;81:19-41. Epub 2018 Sep 14.

Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, M3J 1P3, Canada; email:

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. Read More

Annu Rev Physiol 2018 02;80:413-429

Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; email:

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. Read More

Annu Rev Physiol 2018 02;80:353-387

Laboratory of Applied Mechanobiology, Institute of Translational Medicine, Department for Health Sciences and Technology, ETH Zürich, CH-8093 Zürich, Switzerland; email:

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. Read More

Annu Rev Physiol 2018 02;80:327-351

Department of Biological Sciences, Columbia University, New York, NY 10027, USA; email: ,

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. Read More

Annu Rev Physiol 2018 02 1;80:159-188. Epub 2017 Dec 1.

Department of Neuroscience, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA; email:

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. Read More

Annu Rev Physiol 2018 02 1;80:71-93. Epub 2017 Dec 1.

Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia; email: , ,

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. Read More

Annu Rev Physiol 2018 02 20;80:143-157. Epub 2017 Nov 20.

Weill Institute for Neurosciences, University of California, San Francisco, California 94143; email:

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. Read More

Annu Rev Physiol 2018 02 20;80:243-262. Epub 2017 Nov 20.

Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; email:

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. Read More

Annu Rev Physiol 2018 02 16;80:283-307. Epub 2017 Nov 16.

Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina 27710, USA; email:

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. Read More

Annu Rev Physiol 2018 02 13;80:389-411. Epub 2017 Nov 13.

Institute of Physiology II, University of Münster, 48149 Münster, Germany; email:

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. Read More

Annu Rev Physiol 2018 02 10;80:95-116. Epub 2017 Nov 10.

Division of Endocrinology, Gerontology and Metabolism, Stanford University School of Medicine, Stanford, California 94305; email:

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. Read More

Annu Rev Physiol 2018 02 9;80:263-281. Epub 2017 Nov 9.

Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA; email:

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. Read More

Annu Rev Physiol 2018 02 25;80:1-26. Epub 2017 Oct 25.

Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey 07103, USA; email:

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. Read More

Annu Rev Physiol 2018 02 25;80:309-326. Epub 2017 Oct 25.

Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA; email:

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. Read More

Annu Rev Physiol 2018 02 13;80:117-141. Epub 2017 Oct 13.

Translational Research Center for Gastrointestinal Disorders, KU Leuven, 3000 Leuven, Belgium; email:

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. Read More

Annu Rev Physiol 2018 02 13;80:49-70. Epub 2017 Oct 13.

Stanford University School of Medicine, Stanford, California 94305, USA; email:

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. Read More

Annu Rev Physiol 2018 02 27;80:189-217. Epub 2017 Sep 27.

Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA; email:

The exteroceptive somatosensory system is important for reflexive and adaptive behaviors and for the dynamic control of movement in response to external stimuli. This review outlines recent efforts using genetic approaches in the mouse to map the spinal cord circuits that transmit and gate the cutaneous somatosensory modalities of touch, pain, and itch. Recent studies have revealed an underlying modular architecture in which nociceptive, pruritic, and innocuous stimuli are processed by distinct molecularly defined interneuron cell types. Read More

Annu Rev Physiol 2018 02 22;80:219-241. Epub 2017 Sep 22.

Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97239, USA; email:

In recent years, the population of neurons in the ventral tegmental area (VTA) and substantia nigra (SN) has been examined at multiple levels. The results indicate that the projections, neurochemistry, and receptor and ion channel expression in this cell population vary widely. This review centers on the intrinsic properties and synaptic regulation that control the activity of dopamine neurons. Read More

Annu Rev Physiol 2018 02 20;80:27-48. Epub 2017 Sep 20.

Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain; email:

Aging, the main risk factor for cardiovascular disease (CVD), is becoming progressively more prevalent in our societies. A better understanding of how aging promotes CVD is therefore urgently needed to develop new strategies to reduce disease burden. Atherosclerosis and heart failure contribute significantly to age-associated CVD-related morbimortality. Read More

Annu Rev Physiol 2017 02;79:209-236

Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, New Haven, Connecticut 06520; email:

The hypothalamus is an evolutionarily conserved brain structure that regulates an organism's basic functions, such as homeostasis and reproduction. Several hypothalamic nuclei and neuronal circuits have been the focus of many studies seeking to understand their role in regulating these basic functions. Within the hypothalamic neuronal populations, the arcuate melanocortin system plays a major role in controlling homeostatic functions. Read More

Annu Rev Physiol 2017 02;79:291-312

Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; email:

The lack of accessibility to normal and diseased human intestine and the inability to separate the different functional compartments of the intestine even when tissue could be obtained have held back the understanding of human intestinal physiology. Clevers and his associates identified intestinal stem cells and established conditions to grow "mini-intestines" ex vivo in differentiated and undifferentiated conditions. This pioneering work has made a new model of the human intestine available and has begun making contributions to the understanding of human intestinal transport in normal physiologic conditions and the pathophysiology of intestinal diseases. Read More

Annu Rev Physiol 2017 02;79:449-469

Section of Nephrology, Department of Internal Medicine, Yale University, New Haven, Connecticut 06520; email:

Acute kidney injury (AKI) is a growing global health concern, yet no treatment is currently available to prevent it or to promote kidney repair after injury. Animal models demonstrate that the macrophage is a major contributor to the inflammatory response to AKI. Emerging data from human biopsies also corroborate the presence of macrophages in AKI and their persistence in progressive chronic kidney disease. Read More

Annu Rev Physiol 2017 02;79:471-494

Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10065; email:

Inflammasomes are key inflammatory signaling platforms that detect microbial substances, sterile environmental insults, and molecules derived from host cells. Activation of the inflammasome promotes caspase-1-mediated secretion of proinflammatory cytokines interleukin (IL)-1β and IL-18 and pyroptosis. Recent developments in this field demonstrate the crucial role of the inflammasome in a wide range of disease models. Read More

Annu Rev Physiol 2017 02;79:261-289

Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut 06510; email:

Active iodide (I) transport in both the thyroid and some extrathyroidal tissues is mediated by the Na/I symporter (NIS). In the thyroid, NIS-mediated I uptake plays a pivotal role in thyroid hormone (TH) biosynthesis. THs are key during embryonic and postembryonic development and critical for cell metabolism at all stages of life. Read More

Annu Rev Physiol 2017 02;79:335-356

Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109; email:

The tongue is an elaborate complex of heterogeneous tissues with taste organs of diverse embryonic origins. The lingual taste organs are papillae, composed of an epithelium that includes specialized taste buds, the basal lamina, and a lamina propria core with matrix molecules, fibroblasts, nerves, and vessels. Because taste organs are dynamic in cell biology and sensory function, homeostasis requires tight regulation in specific compartments or niches. Read More