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    2055 results match your criteria Annual Review of Physiology [Journal]

    1 OF 42

    Aging in the Cardiovascular System: Lessons from Hutchinson-Gilford Progeria Syndrome.
    Annu Rev Physiol 2017 Sep 20. Epub 2017 Sep 20.
    Cardiovascular Molecular and Genetic Pathophysiology, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, 28029 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

    POMC Neurons: From Birth to Death.
    Annu Rev Physiol 2017 Feb;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

    The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology.
    Annu Rev Physiol 2017 Feb;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

    Macrophages in Renal Injury and Repair.
    Annu Rev Physiol 2017 Feb;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

    Inflammasomes: Key Mediators of Lung Immunity.
    Annu Rev Physiol 2017 Feb;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

    The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications.
    Annu Rev Physiol 2017 Feb;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

    Tongue and Taste Organ Biology and Function: Homeostasis Maintained by Hedgehog Signaling.
    Annu Rev Physiol 2017 Feb;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

    Trefoil Factor Peptides and Gastrointestinal Function.
    Annu Rev Physiol 2017 Feb 15;79:357-380. Epub 2016 Dec 15.
    Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio 45267; email:
    Trefoil factor (TFF) peptides, with a 40-amino acid motif and including six conserved cysteine residues that form intramolecular disulfide bonds, are a family of mucin-associated secretory molecules mediating many physiological roles that maintain and restore gastrointestinal (GI) mucosal homeostasis. TFF peptides play important roles in response to GI mucosal injury and inflammation. In response to acute GI mucosal injury, TFF peptides accelerate cell migration to seal the damaged area from luminal contents, whereas chronic inflammation leads to increased TFF expression to prevent further progression of disease. Read More

    The Link Between Angiogenesis and Endothelial Metabolism.
    Annu Rev Physiol 2017 Feb 15;79:43-66. Epub 2016 Dec 15.
    Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
    Angiogenesis has traditionally been viewed from the perspective of how endothelial cells (ECs) coordinate migration and proliferation in response to growth factor activation to form new vessel branches. However, ECs must also coordinate their metabolism and adapt metabolic fluxes to the rising energy and biomass demands of branching vessels. Recent studies have highlighted the importance of such metabolic regulation in the endothelium and uncovered core metabolic pathways and mechanisms of regulation that drive the angiogenic process. Read More

    Mitochondrial Dysfunction in Lung Pathogenesis.
    Annu Rev Physiol 2017 Feb 7;79:495-515. Epub 2016 Dec 7.
    Departments of Anesthesiology and Pathology, Duke University School of Medicine, Durham, North Carolina 27710; email:
    Remarkable new roles for mitochondria in calcium handling, apoptosis, heme turnover, inflammation, and oxygen and nutrient sensing have been discovered for organelles that were once thought to be simple energy converters. Although deficits in mitochondrial function are often associated with energy failure and apoptosis, working cells maintain a mitochondrial reserve that affords the organelles distinct homeostatic sensing and regulatory abilities in lung cells. As primary intracellular sources of oxidants, mitochondria serve as critical monitors and modulators of vital oxidation-reduction processes, including mitochondrial biogenesis, mitophagy, inflammasome activation, cell proliferation, and prevention of fibrosis. Read More

    Microglia in Physiology and Disease.
    Annu Rev Physiol 2017 Feb 7;79:619-643. Epub 2016 Dec 7.
    Cellular Neurosciences, Max Delbrück Centre for Molecular Medicine in the Helmholtz Association, Berlin 13092, Germany; email:
    As the immune-competent cells of the brain, microglia play an increasingly important role in maintaining normal brain function. They invade the brain early in development, transform into a highly ramified phenotype, and constantly screen their environment. Microglia are activated by any type of pathologic event or change in brain homeostasis. Read More

    Macrophages and the Recovery from Acute and Chronic Inflammation.
    Annu Rev Physiol 2017 Feb 7;79:567-592. Epub 2016 Dec 7.
    Department of Cell Biology and Molecular Genetics, Maryland Pathogen Research Institute, University of Maryland, College Park, Maryland 20742; email:
    In recent years, researchers have devoted much attention to the diverse roles of macrophages and their contributions to tissue development, wound healing, and angiogenesis. What should not be lost in the discussions regarding the diverse biology of these cells is that when perturbed, macrophages are the primary contributors to potentially pathological inflammatory processes. Macrophages stand poised to rapidly produce large amounts of inflammatory cytokines in response to danger signals. Read More

    Mechanisms of Organ Injury and Repair by Macrophages.
    Annu Rev Physiol 2017 Feb 7;79:593-617. Epub 2016 Dec 7.
    Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; email: ,
    Macrophages regulate tissue regeneration following injury. They can worsen tissue injury by producing reactive oxygen species and other toxic mediators that disrupt cell metabolism, induce apoptosis, and exacerbate ischemic injury. However, they also produce a variety of growth factors, such as IGF-1, VEGF-α, TGF-β, and Wnt proteins that regulate epithelial and endothelial cell proliferation, myofibroblast activation, stem and tissue progenitor cell differentiation, and angiogenesis. Read More

    Senescence in COPD and Its Comorbidities.
    Annu Rev Physiol 2017 Feb 9;79:517-539. Epub 2016 Dec 9.
    National Heart and Lung Institute, Imperial College, London SW3 6LY, United Kingdom; email:
    Chronic obstructive pulmonary disease (COPD) is regarded as a disease of accelerated lung aging. This affliction shows all of the hallmarks of aging, including telomere shortening, cellular senescence, activation of PI3 kinase-mTOR signaling, impaired autophagy, mitochondrial dysfunction, stem cell exhaustion, epigenetic changes, abnormal microRNA profiles, immunosenescence, and a low-grade chronic inflammation (inflammaging). Many of these pathways are driven by chronic exogenous and endogenous oxidative stress. Read More

    Coronary Artery Development: Progenitor Cells and Differentiation Pathways.
    Annu Rev Physiol 2017 Feb 9;79:1-19. Epub 2016 Dec 9.
    Department of Biology, Stanford University, Stanford, California 94305; email:
    Coronary artery disease (CAD) is the number one cause of death worldwide and involves the accumulation of plaques within the artery wall that can occlude blood flow to the heart and cause myocardial infarction. The high mortality associated with CAD makes the development of medical interventions that repair and replace diseased arteries a high priority for the cardiovascular research community. Advancements in arterial regenerative medicine could benefit from a detailed understanding of coronary artery development during embryogenesis and of how these pathways might be reignited during disease. Read More

    Developmental Mechanisms of Aortic Valve Malformation and Disease.
    Annu Rev Physiol 2017 Feb 9;79:21-41. Epub 2016 Dec 9.
    Departments of Genetics, Pediatrics, and Medicine (Cardiology), Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York 10461; email:
    Normal aortic valves are composed of valve endothelial cells (VECs) and valve interstitial cells (VICs). VICs are the major cell population and have distinct embryonic origins in the endocardium and cardiac neural crest cells. Cell signaling between the VECs and VICs plays critical roles in aortic valve morphogenesis. Read More

    Three Pillars for the Neural Control of Appetite.
    Annu Rev Physiol 2017 Feb 28;79:401-423. Epub 2016 Nov 28.
    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147; email:
    The neural control of appetite is important for understanding motivated behavior as well as the present rising prevalence of obesity. Over the past several years, new tools for cell type-specific neuron activity monitoring and perturbation have enabled increasingly detailed analyses of the mechanisms underlying appetite-control systems. Three major neural circuits strongly and acutely influence appetite but with notably different characteristics. Read More

    The Physiology and Molecular Underpinnings of the Effects of Bariatric Surgery on Obesity and Diabetes.
    Annu Rev Physiol 2017 Feb 28;79:313-334. Epub 2016 Nov 28.
    Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109; email:
    Bariatric surgeries, such as Roux-en-Y gastric bypass and vertical sleeve gastrectomy, produce significant and durable weight loss in both humans and rodents. Recently, these surgical interventions have also been termed metabolic surgery because they result in profound metabolic improvements that often surpass the expected improvement due to body weight loss alone. In this review we focus on the weight-loss independent effects of bariatric surgery, which encompass energy expenditure and macronutrient preference, the luminal composition of the gut (i. Read More

    Regulation of Mammalian Oocyte Meiosis by Intercellular Communication Within the Ovarian Follicle.
    Annu Rev Physiol 2017 Feb 14;79:237-260. Epub 2016 Nov 14.
    Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut 06030; email: ,
    Meiotic progression in mammalian preovulatory follicles is controlled by the granulosa cells around the oocyte. Cyclic GMP (cGMP) generated in the granulosa cells diffuses through gap junctions into the oocyte, maintaining meiotic prophase arrest. Luteinizing hormone then acts on receptors in outer granulosa cells to rapidly decrease cGMP. Read More

    A Critical and Comparative Review of Fluorescent Tools for Live-Cell Imaging.
    Annu Rev Physiol 2017 Feb 16;79:93-117. Epub 2016 Nov 16.
    Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80303; email:
    Fluorescent tools have revolutionized our ability to probe biological dynamics, particularly at the cellular level. Fluorescent sensors have been developed on several platforms, utilizing either small-molecule dyes or fluorescent proteins, to monitor proteins, RNA, DNA, small molecules, and even cellular properties, such as pH and membrane potential. We briefly summarize the impressive history of tool development for these various applications and then discuss the most recent noteworthy developments in more detail. Read More

    Anoctamins/TMEM16 Proteins: Chloride Channels Flirting with Lipids and Extracellular Vesicles.
    Annu Rev Physiol 2017 Feb 16;79:119-143. Epub 2016 Nov 16.
    Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322; email:
    Anoctamin (ANO)/TMEM16 proteins exhibit diverse functions in cells throughout the body and are implicated in several human diseases. Although the founding members ANO1 (TMEM16A) and ANO2 (TMEM16B) are Ca(2+)-activated Cl(-) channels, most ANO paralogs are Ca(2+)-dependent phospholipid scramblases that serve as channels facilitating the movement (scrambling) of phospholipids between leaflets of the membrane bilayer. Phospholipid scrambling significantly alters the physical properties of the membrane and its landscape and has vast downstream signaling consequences. Read More

    The Integrative Physiology of Insect Chill Tolerance.
    Annu Rev Physiol 2017 Feb 16;79:187-208. Epub 2016 Nov 16.
    Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada.
    Cold tolerance is important in defining the distribution of insects. Here, we review the principal physiological mechanisms underlying homeostatic failure during cold exposure in this diverse group of ectotherms. When insects are cooled sufficiently, they suffer an initial loss of neuromuscular function (chill coma) that is caused by decreased membrane potential and reduced excitability of the neuromuscular system. Read More

    Neural Mechanisms for Predicting the Sensory Consequences of Behavior: Insights from Electrosensory Systems.
    Annu Rev Physiol 2017 Feb 13;79:381-399. Epub 2016 Oct 13.
    Department of Neuroscience and Kavli Institute for Brain Science, Columbia University Medical Center, New York, NY 10032; email:
    Perception of the environment requires differentiating between external sensory inputs and those that are self-generated. Some of the clearest insights into the neural mechanisms underlying this process have come from studies of the electrosensory systems of fish. Neurons at the first stage of electrosensory processing generate negative images of the electrosensory consequences of the animal's own behavior. Read More

    Macrophage Polarization.
    Annu Rev Physiol 2017 Feb 21;79:541-566. Epub 2016 Oct 21.
    Departments of Infectious Diseases and Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105; email:
    Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and the normal tissue environment. Three broad pathways control polarization: epigenetic and cell survival pathways that prolong or shorten macrophage development and viability, the tissue microenvironment, and extrinsic factors, such as microbial products and cytokines released in inflammation. Read More

    Vascular and Immunobiology of the Circulatory Sphingosine 1-Phosphate Gradient.
    Annu Rev Physiol 2017 Feb 21;79:67-91. Epub 2016 Oct 21.
    Vascular Biology Program, Department of Surgery, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts 02115; email: ,
    Vertebrates are endowed with a closed circulatory system, the evolution of which required novel structural and regulatory changes. Furthermore, immune cell trafficking paradigms adapted to the barriers imposed by the closed circulatory system. How did such changes occur mechanistically? We propose that spatial compartmentalization of the lipid mediator sphingosine 1-phosphate (S1P) may be one such mechanism. Read More

    Receptor-Mediated Endocytosis in the Proximal Tubule.
    Annu Rev Physiol 2017 Feb 28;79:425-448. Epub 2016 Oct 28.
    Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261; email: ,
    Cells lining the proximal tubule (PT) of the kidney are highly specialized for apical endocytosis of filtered proteins and small bioactive molecules from the glomerular ultrafiltrate to maintain essentially protein-free urine. Compromise of this pathway results in low molecular weight (LMW) proteinuria that can progress to end-stage kidney disease. This review describes our current understanding of the endocytic pathway and the multiligand receptors that mediate LMW protein uptake in PT cells, how these are regulated in response to physiologic cues, and the molecular basis of inherited diseases characterized by LMW proteinuria. Read More

    The Central Control of Energy Expenditure: Exploiting Torpor for Medical Applications.
    Annu Rev Physiol 2017 Feb 28;79:167-186. Epub 2016 Oct 28.
    Department of Biomedical and Neuromotor Sciences, Physiology Division, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; email:
    Autonomic thermoregulation is a recently acquired function, as it appears for the first time in mammals and provides the brain with the ability to control energy expenditure. The importance of such control can easily be highlighted by the ability of a heterogeneous group of mammals to actively reduce metabolic rate and enter a condition of regulated hypometabolism known as torpor. The central neural circuits of thermoregulatory cold defense have been recently unraveled and could in theory be exploited to reduce energy expenditure in species that do not normally use torpor, inducing a state called synthetic torpor. Read More

    Huxleys' Missing Filament: Form and Function of Titin in Vertebrate Striated Muscle.
    Annu Rev Physiol 2017 Feb 28;79:145-166. Epub 2016 Oct 28.
    Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona 86011-4185; email:
    Although superthin filaments were inferred from early experiments on muscle, decades passed before their existence was accepted. Phylogenetic analyses suggest that titin, the largest known protein, first appeared in the common ancestor of chordates and nematodes and evolved rapidly via duplication. Twitchin and projectin evolved later by truncation. Read More

    Vascular Growth Factors and Glomerular Disease.
    Annu Rev Physiol 2016 ;78:437-61
    Feinberg Cardiovascular Research Institute and Division of Nephrology and Hypertension, Northwestern University, Chicago, Illinois 60611; email: ,
    The glomerulus is a highly specialized microvascular bed that filters blood to form primary urinary filtrate. It contains four cell types: fenestrated endothelial cells, specialized vascular support cells termed podocytes, perivascular mesangial cells, and parietal epithelial cells. Glomerular cell-cell communication is critical for the development and maintenance of the glomerular filtration barrier. Read More

    Regulation of Renal Electrolyte Transport by WNK and SPAK-OSR1 Kinases.
    Annu Rev Physiol 2016 ;78:367-89
    Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City 14080, Mexico; email:
    The discovery of four genes responsible for pseudohypoaldosteronism type II, or familial hyperkalemic hypertension, which features arterial hypertension with hyperkalemia and metabolic acidosis, unmasked a complex multiprotein system that regulates electrolyte transport in the distal nephron. Two of these genes encode the serine-threonine kinases WNK1 and WNK4. The other two genes [kelch-like 3 (KLHL3) and cullin 3 (CUL3)] form a RING-type E3-ubiquitin ligase complex that modulates WNK1 and WNK4 abundance. Read More

    Long-Term Potentiation: From CaMKII to AMPA Receptor Trafficking.
    Annu Rev Physiol 2016 ;78:351-65
    Department of Cellular and Molecular Pharmacology and.
    For more than 20 years, we have known that Ca(2+)/calmodulin-dependent protein kinase (CaMKII) activation is both necessary and sufficient for the induction of long-term potentiation (LTP). During this time, tremendous effort has been spent in attempting to understand how CaMKII activation gives rise to this phenomenon. Despite such efforts, there is much to be learned about the molecular mechanisms involved in LTP induction downstream of CaMKII activation. Read More

    The Role of PVH Circuits in Leptin Action and Energy Balance.
    Annu Rev Physiol 2016 ;78:207-21
    Division of Endocrinology, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan 48105; email:
    Although it has been known for more than a century that the brain controls overall energy balance and adiposity by regulating feeding behavior and energy expenditure, the roles for individual brain regions and neuronal subtypes were not fully understood until recently. This area of research is active, and as such our understanding of the central regulation of energy balance is continually being refined as new details emerge. Much of what we now know stems from the discoveries of leptin and the hypothalamic melanocortin system. Read More

    Supramolecular Organization of Respiratory Complexes.
    Annu Rev Physiol 2016 16;78:533-61. Epub 2015 Dec 16.
    Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain; email:
    Since the discovery of the existence of superassemblies between mitochondrial respiratory complexes, such superassemblies have been the object of a passionate debate. It is accepted that respiratory supercomplexes are structures that occur in vivo, although which superstructures are naturally occurring and what could be their functional role remain open questions. The main difficulty is to make compatible the existence of superassemblies with the corpus of data that drove the field to abandon the early understanding of the physical arrangement of the mitochondrial respiratory chain as a compact physical entity (the solid model). Read More

    ADAM Proteases and Gastrointestinal Function.
    Annu Rev Physiol 2016 19;78:243-76. Epub 2015 Nov 19.
    Cell Biology, Stem Cells, and Development Program and.
    A disintegrin and metalloproteinases (ADAMs) are a family of cell surface proteases that regulate diverse cellular functions, including cell adhesion, migration, cellular signaling, and proteolysis. Proteolytically active ADAMs are responsible for ectodomain shedding of membrane-associated proteins. ADAMs rapidly modulate key cell signaling pathways in response to changes in the extracellular environment (e. Read More

    Regulation of Vascular and Renal Function by Metabolite Receptors.
    Annu Rev Physiol 2016 19;78:391-414. Epub 2015 Nov 19.
    Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; email:
    To maintain metabolic homeostasis, the body must be able to monitor the concentration of a large number of substances, including metabolites, in real time and to use that information to regulate the activities of different metabolic pathways. Such regulation is achieved by the presence of sensors, termed metabolite receptors, in various tissues and cells of the body, which in turn convey the information to appropriate regulatory or positive or negative feedback systems. In this review, we cover the unique roles of metabolite receptors in renal and vascular function. Read More

    Role of Intestinal HIF-2α in Health and Disease.
    Annu Rev Physiol 2016 19;78:301-25. Epub 2015 Nov 19.
    Department of Molecular & Integrative Physiology and.
    The intestine is supported by a complex vascular system that undergoes dynamic and transient daily shifts in blood perfusion, depending on the metabolic state. Moreover, the intestinal villi have a steep oxygen gradient from the hypoxic epithelium adjacent to the anoxic lumen to the relative higher tissue oxygenation at the base of villi. Due to the daily changes in tissue oxygen levels in the intestine, the hypoxic transcription factors hypoxia-inducible factor (HIF)-1α and HIF-2α are essential in maintaining intestinal homeostasis. Read More

    Mito-Morphosis: Mitochondrial Fusion, Fission, and Cristae Remodeling as Key Mediators of Cellular Function.
    Annu Rev Physiol 2016 19;78:505-31. Epub 2015 Nov 19.
    Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, 35129 Padova, Italy; email: ,
    Permanent residency in the eukaryotic cell pressured the prokaryotic mitochondrial ancestor to strategize for intracellular living. Mitochondria are able to autonomously integrate and respond to cellular cues and demands by remodeling their morphology. These processes define mitochondrial dynamics and inextricably link the fate of the mitochondrion and that of the host eukaryote, as exemplified by the human diseases that result from mutations in mitochondrial dynamics proteins. Read More

    Glucocorticoid Signaling: An Update from a Genomic Perspective.
    Annu Rev Physiol 2016 30;78:155-80. Epub 2015 Nov 30.
    Hospital for Special Surgery, The David Rosensweig Genomics Center, New York, NY 10021; email:
    Glucocorticoid hormones (GC) regulate essential physiological functions including energy homeostasis, embryonic and postembryonic development, and the stress response. From the biomedical perspective, GC have garnered a tremendous amount of attention as highly potent anti-inflammatory and immunosuppressive medications indispensable in the clinic. GC signal through the GC receptor (GR), a ligand-dependent transcription factor whose structure, DNA binding, and the molecular partners that it employs to regulate transcription have been under intense investigation for decades. Read More

    Ceramide Signaling and Metabolism in Pathophysiological States of the Lung.
    Annu Rev Physiol 2016 30;78:463-80. Epub 2015 Nov 30.
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, National Jewish Health, Denver, Colorado 80206; email: ,
    Following the discovery of ceramide as the central signaling and metabolic relay among sphingolipids, studies of its involvement in lung health and pathophysiology have exponentially increased. In this review, we highlight key studies in the context of recent progress in metabolomics and translational research methodologies. Evidence points toward an important role for the ceramide/sphingosine-1-phosphate rheostat in maintaining lung cell survival, vascular barrier function, and proper host response to airway microbial infections. Read More

    Cortico-Basal Ganglia Circuit Function in Psychiatric Disease.
    Annu Rev Physiol 2016 30;78:327-50. Epub 2015 Nov 30.
    The Gladstone Institutes, University of California, San Francisco, California 94158; email: ,
    Circuit dysfunction models of psychiatric disease posit that pathological behavior results from abnormal patterns of electrical activity in specific cells and circuits in the brain. Many psychiatric disorders are associated with abnormal activity in the prefrontal cortex and in the basal ganglia, a set of subcortical nuclei implicated in cognitive and motor control. Here we discuss the role of the basal ganglia and connected prefrontal regions in the etiology and treatment of obsessive-compulsive disorder, anxiety, and depression, emphasizing mechanistic work in rodent behavioral models to dissect causal cortico-basal ganglia circuits underlying discrete behavioral symptom domains relevant to these complex disorders. Read More

    Exosomes: Fundamental Biology and Roles in Cardiovascular Physiology.
    Annu Rev Physiol 2016 30;78:67-83. Epub 2015 Nov 30.
    Cedars-Sinai Heart Institute, Los Angeles, California 90048; email:
    Exosomes are nanosized membrane particles that are secreted by cells that transmit information from cell to cell. The information within exosomes prominently includes their protein and RNA payloads. Exosomal microRNAs in particular can potently and fundamentally alter the transcriptome of recipient cells. Read More

    Pathophysiology and Mechanisms of Nonalcoholic Fatty Liver Disease.
    Annu Rev Physiol 2016 30;78:181-205. Epub 2015 Nov 30.
    European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France; email: ,
    Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders characterized by abnormal hepatic fat accumulation, inflammation, and hepatocyte dysfunction. Importantly, it is also closely linked to obesity and the metabolic syndrome. NAFLD predisposes susceptible individuals to cirrhosis, hepatocellular carcinoma, and cardiovascular disease. Read More

    Understanding the Physiology of FGF21.
    Annu Rev Physiol 2016 19;78:223-41. Epub 2015 Nov 19.
    Department of Medicine, Harvard Medical School, and Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215; email:
    Fibroblast growth factor 21 (FGF21) is a peptide hormone that is synthesized by several organs and regulates energy homeostasis. Excitement surrounding this relatively recently identified hormone is based on the documented metabolic beneficial effects of FGF21, which include weight loss and improved glycemia. The biology of FGF21 is intrinsically complicated owing to its diverse metabolic functions in multiple target organs and its ability to act as an autocrine, paracrine, and endocrine factor. Read More

    Roles and Regulation of Renal K Channels.
    Annu Rev Physiol 2016 11;78:415-35. Epub 2015 Dec 11.
    Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201; email:
    More than two dozen types of potassium channels, with different biophysical and regulatory properties, are expressed in the kidney, influencing renal function in many important ways. Recently, a confluence of discoveries in areas from human genetics to physiology, cell biology, and biophysics has cast light on the special function of five different potassium channels in the distal nephron, encoded by the genes KCNJ1, KCNJ10, KCNJ16, KCNMA1, and KCNN3. Research aimed at understanding how these channels work in health and go awry in disease has transformed our understanding of potassium balance and provided new insights into mechanisms of renal sodium handling and the maintenance of blood pressure. Read More

    The Microbiome and the Respiratory Tract.
    Annu Rev Physiol 2016 2;78:481-504. Epub 2015 Nov 2.
    Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109; email:
    Although the notion that "the normal lung is free from bacteria" remains common in textbooks, it is virtually always stated without citation or argument. The lungs are constantly exposed to diverse communities of microbes from the oropharynx and other sources, and over the past decade, novel culture-independent techniques of microbial identification have revealed that the lungs, previously considered sterile in health, harbor diverse communities of microbes. In this review, we describe the topography and population dynamics of the respiratory tract, both in health and as altered by acute and chronic lung disease. Read More

    Systemic Nutrient and Stress Signaling via Myokines and Myometabolites.
    Annu Rev Physiol 2016 2;78:85-107. Epub 2015 Nov 2.
    Division of Developmental Biology, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105; email:
    Homeostatic systems mount adaptive responses to meet the energy demands of the cell and to compensate for dysfunction in cellular compartments. Such surveillance systems are also active at the organismal level: Nutrient and stress sensing in one tissue can lead to changes in other tissues. Here, we review the emerging understanding of the role of skeletal muscle in regulating physiological homeostasis and disease progression in other tissues. Read More

    The Neural Basis of Long-Distance Navigation in Birds.
    Annu Rev Physiol 2016 2;78:133-54. Epub 2015 Nov 2.
    Department of Biopsychology, Institute of Cognitive Neuroscience, Faculty of Psychology, Ruhr-University Bochum, D-44780 Bochum, Germany; email:
    Migratory birds can navigate over tens of thousands of kilometers with an accuracy unobtainable for human navigators. To do so, they use their brains. In this review, we address how birds sense navigation- and orientation-relevant cues and where in their brains each individual cue is processed. Read More

    The Biochemistry and Physiology of Mitochondrial Fatty Acid β-Oxidation and Its Genetic Disorders.
    Annu Rev Physiol 2016 14;78:23-44. Epub 2015 Oct 14.
    Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, University of Amsterdam, 1100 DE Amsterdam, The Netherlands; email:
    Mitochondrial fatty acid β-oxidation (FAO) is the major pathway for the degradation of fatty acids and is essential for maintaining energy homeostasis in the human body. Fatty acids are a crucial energy source in the postabsorptive and fasted states when glucose supply is limiting. But even when glucose is abundantly available, FAO is a main energy source for the heart, skeletal muscle, and kidney. Read More

    DNA Damage and Repair in Vascular Disease.
    Annu Rev Physiol 2016 6;78:45-66. Epub 2015 Oct 6.
    Division of Cardiovascular Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom; email: ,
    DNA damage affecting both genomic and mitochondrial DNA is present in a variety of both inherited and acquired vascular diseases. Multiple cell types show persistent DNA damage and a range of lesions. In turn, DNA damage activates a variety of DNA repair mechanisms, many of which are activated in vascular disease. Read More

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