The Role of Thyroid Hormone in the Innate and Adaptive Immune Response during Infection.
This article provides an overview of the mechanisms by which thyroid hormones affect the innate and adaptive immune response during infection. The influence of thyroid hormone on the most important players of the innate [neutrophils, macrophages, natural killer (NK) cells, and dendritic cells (DCs)] and adaptive immune system (B- and T-lymphocytes) is reviewed here based on both clinical and preclinical studies. The effects of modulation of the immune system by drugs, such as monoclonal antibodies, tyrosine kinase inhibitors, and interferons on thyroid function, are beyond the scope of this article. Thyroid hormones regula...
Source: Comprehensive Physiology - September 26, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Basal Ganglia-A Motion Perspective.
Authors: Grillner S, Robertson B, Kotaleski JH Abstract The basal ganglia represent an ancient part of the nervous system that have remained organized in a similar way over the last 500 million years and are of importance for our ability to determine which actions to choose at any given moment in time. Salient or reward stimuli act via the dopamine system and contribute to motor or procedural learning (reinforcement learning). The input stage of the basal ganglia, the striatum, is shaped by glutamatergic input from the cortex and thalamus and by the dopamine system. All intrinsic neurons of the striatum are GABAerg...
Source: Comprehensive Physiology - September 26, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake.
Authors: Merz KE, Thurmond DC Abstract The skeletal muscle is the largest organ in the body, by mass. It is also the regulator of glucose homeostasis, responsible for 80% of postprandial glucose uptake from the circulation. Skeletal muscle is essential for metabolism, both for its role in glucose uptake and its importance in exercise and metabolic disease. In this article, we give an overview of the importance of skeletal muscle in metabolism, describing its role in glucose uptake and the diseases that are associated with skeletal muscle metabolic dysregulation. We focus on the role of skeletal muscle in peripheral...
Source: Comprehensive Physiology - September 19, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Human Skin Microcirculation.
Authors: Cracowski JL, Roustit M Abstract The anatomy and physiology of the microcirculation in human skin are complex. Normal cutaneous microcirculation is organized in two parallel plexuses with capillary loops extending perpendicularly from the superficial plexus. The physiological regulation of cutaneous microcirculation includes specific sympathetic activation, which causes vasoconstriction through the release of norepinephrine, neuropeptide Y, and ATP. A sympathetic cholinergic system is mainly involved in vasodilation through the co-transmission of acetylcholine, vasoactive intestinal peptide, and pituitary ...
Source: Comprehensive Physiology - September 19, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Asthma and Lung Mechanics.
This article will discuss in detail the pathophysiology of asthma from the point of view of lung mechanics. In particular, we will explain how asthma is more than just airflow limitation resulting from airway narrowing but in fact involves multiple consequences of airway narrowing, including ventilation heterogeneity, airway closure, and airway hyperresponsiveness. In addition, the relationship between the airway and surrounding lung parenchyma is thought to be critically important in asthma, especially as related to the response to deep inspiration. Furthermore, dynamic changes in lung mechanics over time may yield import...
Source: Comprehensive Physiology - September 19, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Current State and Evidence of Cellular Encapsulation Strategies in Type 1 Diabetes.
This article will provide essential considerations concerning the physicochemical properties of the most commonly used biomaterials, relevant aspects of the immune response to bioencapsulation, current encapsulation strategies, potential implantation sites for encapsulated cell therapies and, finally, a comprehensive review on the current state of clinical translation. © 2020 American Physiological Society. Compr Physiol 10:839-878, 2020. PMID: 32941683 [PubMed - in process] (Source: Comprehensive Physiology)
Source: Comprehensive Physiology - September 19, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Ventilation/Perfusion Relationships and Gas Exchange: Measurement Approaches.
This article discusses the measurement of V ˙ A / Q ˙ matching with three broad classes of techniques: (i) those based in gas exchange, such as the multiple inert gas elimination technique (MIGET); (ii) those derived from imaging techniques such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), magnetic resonance imaging (MRI), computed tomography (CT), and electrical impedance tomography (EIT); and (iii) fluorescent and radiolabeled microspheres. The focus is on the physiological basis of these techniques that provide quantitative information for research purposes rather than q...
Source: Comprehensive Physiology - September 19, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Roles of Noncoding RNAs in Islet Biology.
Authors: Guay C, Jacovetti C, Bayazit MB, Brozzi F, Rodriguez-Trejo A, Wu K, Regazzi R Abstract The discovery that most mammalian genome sequences are transcribed to ribonucleic acids (RNA) has revolutionized our understanding of the mechanisms governing key cellular processes and of the causes of human diseases, including diabetes mellitus. Pancreatic islet cells were found to contain thousands of noncoding RNAs (ncRNAs), including micro-RNAs (miRNAs), PIWI-associated RNAs, small nucleolar RNAs, tRNA-derived fragments, long non-coding RNAs, and circular RNAs. While the involvement of miRNAs in islet function and i...
Source: Comprehensive Physiology - September 19, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Internet of Things (IoT) System and Field Sensors for Exercise Intensity Measurements.
Authors: Masuki S, Morikawa M, Nose H Abstract Although exercise training according to individual peak aerobic capacity ( V ˙ o2peak ) has been recommended at all ages, sensors available in the field are limited. The most popular sensors in the field are pedometers, but they cannot be used to monitor exercise intensity. Instead, although heart rate (HR) monitors are broadly available in the field to estimate exercise intensity, HR responses to exercise vary by individual according to physical fitness and environmental conditions, which hinders the precise measurement of energy expenditure. These issues make it di...
Source: Comprehensive Physiology - September 19, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Physiology of Extracorporeal Gas Exchange.
Authors: Bartlett RH Abstract Circulating venous blood outside the body, through an artificial lung (membrane oxygenator), and returning oxygenated blood to the patient is extracorporeal gas exchange. Oxygen and carbon dioxide exchange in a membrane lung is controlled by regulating blood flow, blood composition, and device design. With this control, lung function can be replaced for weeks by artificial organs. © 2020 American Physiological Society. Compr Physiol 10:879-891, 2020. PMID: 32941687 [PubMed - in process] (Source: Comprehensive Physiology)
Source: Comprehensive Physiology - September 19, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Leptin: Master Regulator of Biological Functions that Affects Breathing.
Authors: Gauda EB, Conde S, Bassi M, Zoccal DB, Almeida Colombari DS, Colombari E, Despotovic N Abstract Obesity is a global epidemic in developed countries accounting for many of the metabolic and cardiorespiratory morbidities that occur in adults. These morbidities include type 2 diabetes, sleep-disordered breathing (SDB), obstructive sleep apnea, chronic intermittent hypoxia, and hypertension. Leptin, produced by adipocytes, is a master regulator of metabolism and of many other biological functions including central and peripheral circuits that control breathing. By binding to receptors on cells and neurons in t...
Source: Comprehensive Physiology - September 19, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Bone Marrow Microvasculature.
This article provides an overview of the afferent, exchange and efferent vessels in bone and marrow and presents the morphological layout of these blood vessels regarding blood flow dynamics. In addition, this article discusses how bone blood vessels participate in bone development, maintenance, and repair. Further, mechanical loading-induced bone adaptation is presented regarding interstitial fluid flow and pressure, as regulated by the vascular system. The role of the sympathetic nervous system is discussed in relation to blood vessels and bone. Finally, vascular participation in bone accrual with intermittent parathyroi...
Source: Comprehensive Physiology - September 19, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Using Deep Brain Stimulation to Unravel the Mysteries of Cardiorespiratory Control.
This article charts the history of deep brain stimulation (DBS) as applied to alleviate a number of neurological disorders, while in parallel mapping the electrophysiological circuits involved in generating and integrating neural signals driving the cardiorespiratory system during exercise. With the advent of improved neuroimaging techniques, neurosurgeons can place small electrodes into deep brain structures with a high degree accuracy to treat a number of neurological disorders, such as movement impairment associated with Parkinson's disease and neuropathic pain. As well as stimulating discrete nuclei and monitoring auto...
Source: Comprehensive Physiology - September 19, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Retinal Physiology and Circulation: Effect of Diabetes.
Authors: Wright WS, Eshaq RS, Lee M, Kaur G, Harris NR Abstract In this article, we present a discussion of diabetes and its complications, including the macrovascular and microvascular effects, with the latter of consequence to the retina. We will discuss the anatomy and physiology of the retina, including aspects of metabolism and mechanisms of oxygenation, with the latter accomplished via a combination of the retinal and choroidal blood circulations. Both of these vasculatures are altered in diabetes, with the retinal circulation intimately involved in the pathology of diabetic retinopathy. The later stages of d...
Source: Comprehensive Physiology - September 19, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Systemic and Central Amylin, Amylin Receptor Signaling, and Their Physiological and Pathophysiological Roles in Metabolism.
This article in the Neural and Endocrine Section of Comprehensive Physiology discusses the physiology and pathophysiology of the pancreatic hormone amylin. Shortly after its discovery in 1986, amylin has been shown to reduce food intake as a satiation signal to limit meal size. Amylin also affects food reward, sensitizes the brain to the catabolic actions of leptin, and may also play a prominent role in the development of certain brain areas that are involved in metabolic control. Amylin may act at different sites in the brain in addition to the area postrema (AP) in the caudal hindbrain. In particular, the sensitizing eff...
Source: Comprehensive Physiology - September 19, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Evolutionary Physiology and Genomics in the Highly Adaptable Killifish (Fundulus heteroclitus).
Authors: Crawford DL, Schulte PM, Whitehead A, Oleksiak MF Abstract By investigating evolutionary adaptations that change physiological functions, we can enhance our understanding of how organisms work, the importance of physiological traits, and the genes that influence these traits. This approach of investigating the evolution of physiological adaptation has been used with the teleost fish Fundulus heteroclitus and has produced insights into (i) how protein polymorphisms enhance swimming and development; (ii) the role of equilibrium enzymes in modulating metabolic flux; (iii) how variation in DNA sequences and mR...
Source: Comprehensive Physiology - March 13, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Oxidative Stress in Pulmonary Fibrosis.
Authors: Otoupalova E, Smith S, Cheng G, Thannickal VJ Abstract Oxidative stress has been linked to various disease states as well as physiological aging. The lungs are uniquely exposed to a highly oxidizing environment and have evolved several mechanisms to attenuate oxidative stress. Idiopathic pulmonary fibrosis (IPF) is a progressive age-related disorder that leads to architectural remodeling, impaired gas exchange, respiratory failure, and death. In this article, we discuss cellular sources of oxidant production, and antioxidant defenses, both enzymatic and nonenzymatic. We outline the current understanding of...
Source: Comprehensive Physiology - March 13, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Lung Endothelial Transcytosis.
Authors: Jones JH, Minshall RD Abstract Transcytosis of macromolecules through lung endothelial cells is the primary route of transport from the vascular compartment into the interstitial space. Endothelial transcytosis is mostly a caveolae-dependent process that combines receptor-mediated endocytosis, vesicle trafficking via actin-cytoskeletal remodeling, and SNARE protein directed vesicle fusion and exocytosis. Herein, we review the current literature on caveolae-mediated endocytosis, the role of actin cytoskeleton in caveolae stabilization at the plasma membrane, actin remodeling during vesicle trafficking, and ...
Source: Comprehensive Physiology - March 13, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Glucagon-Like Peptide-1: Actions and Influence on Pancreatic Hormone Function.
Authors: Davis EM, Sandoval DA Abstract GLP-1 was described as an incretin over 30 years ago. GLP-1 is encoded by the preproglucagon gene (Gcg), which is expressed in the intestine, the pancreas, and the central nervous system. GLP-1 activates GLP-1 receptors (GLP-1r) on the β-cell to induce insulin secretion in a glucose-dependent manner. GLP-1 also inhibits α-cell secretion of glucagon. As few, if any, GLP-1r are expressed on α-cells, indirect regulation, via β- or δ-cell products has been thought to be the primary mechanism by which GLP-1 inhibits glucagon secretion. However, recent w...
Source: Comprehensive Physiology - March 13, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Mechanisms of Regulation of Transporters of Amino Acid Absorption in Inflammatory Bowel Diseases.
Authors: Singh S, Arthur S, Sundaram U Abstract Intestinal absorption of dietary amino acids/peptides is essential for protein homeostasis, which in turn is crucial for maintaining health as well as restoration of health from significant diseases. Dietary amino acids/peptides are absorbed by unique transporter processes present in the brush border membrane of absorptive villus cells, which line the entire length of the intestine. To date, the only nutrient absorptive system described in the secretory crypt cells in the mammalian intestine is the one that absorbs the amino acid glutamine. Majority of the amino acid ...
Source: Comprehensive Physiology - March 13, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Single-Cell Transcriptomic Analysis.
Authors: Zheng Z, Chen E, Lu W, Mouradian G, Hodges M, Liang M, Liu P, Lu Y Abstract Single-cell sequencing measures the sequence information from individual cells using optimized single-cell isolation protocols and next-generation sequencing technologies. Recent advancement in single-cell sequencing has transformed biomedical research, providing insights into diverse biological processes such as mammalian development, immune system function, cellular diversity and heterogeneity, and disease pathogenesis. In this article, we introduce and describe popular commercial platforms for single-cell RNA sequencing, general...
Source: Comprehensive Physiology - March 13, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Anatomical Markers of Activity in Hypothalamic Neurons.
This article includes discussion of methodological limitations and the power of combining approaches to understand neuronal function. © 2020 American Physiological Society. Compr Physiol 10:549-575, 2020. PMID: 32163202 [PubMed - as supplied by publisher] (Source: Comprehensive Physiology)
Source: Comprehensive Physiology - March 13, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

GPCRs, G Proteins, and Their Impact on β-cell Function.
This article highlights the following aspects of GPCR-G protein biology of the islet. First, it overviews our current understanding of the identity of a wide variety of G protein regulators and their modulatory roles in GPCR-G protein-effector coupling, which is requisite for optimal β-cell function under physiological conditions. Second, it describes evidence in support of novel, noncanonical, GPCR-independent mechanisms of activation of G proteins in the islet. Third, it highlights the evidence indicating that abnormalities in G protein function lead to islet β-cell dysregulation and demise under the duress of ...
Source: Comprehensive Physiology - March 13, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Chromosomal Substitution Strategies to Localize Genomic Regions Related to Complex Traits.
Authors: Cowley AW, Dwinell MR Abstract Chromosomal substitution strategies provide a powerful tool to anonymously reveal the relationship between DNA sequence variants and a normal or disease phenotype of interest. Even in this age of CRISPR-Cas9 genome engineering, the knockdown or overexpression of a gene provides relevant information to our understanding of complex disease only when a close association of an allelic variant with the phenotype has first been established. Limitations of genetic linkage approaches led to the development of more efficient breeding strategies to substitute chromosomal segments from ...
Source: Comprehensive Physiology - March 13, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Effects of Perinatal Hyperoxia on Breathing.
This article focuses on the effects of normobaric hyperoxia during the perinatal period on breathing in humans and other mammals, with an emphasis on the neural control of breathing during hyperoxia, after return to normoxia, and in response to subsequent hypoxic and hypercapnic challenges. Acute hyperoxia typically evokes an immediate ventilatory depression that is often, but not always, followed by hyperpnea. The hypoxic ventilatory response (HVR) is enhanced by brief periods of hyperoxia in adult mammals, but the limited data available suggest that this may not be the case for newborns. Chronic exposure to mild-to-moder...
Source: Comprehensive Physiology - March 13, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Mitochondria in the Pulmonary Vasculature in Health and Disease: Oxygen-Sensing, Metabolism, and Dynamics.
Authors: Dasgupta A, Wu D, Tian L, Xiong PY, Dunham-Snary KJ, Chen KH, Alizadeh E, Motamed M, Potus F, Hindmarch CCT, Archer SL Abstract In lung vascular cells, mitochondria serve a canonical metabolic role, governing energy homeostasis. In addition, mitochondria exist in dynamic networks, which serve noncanonical functions, including regulation of redox signaling, cell cycle, apoptosis, and mitochondrial quality control. Mitochondria in pulmonary artery smooth muscle cells (PASMC) are oxygen sensors and initiate hypoxic pulmonary vasoconstriction. Acquired dysfunction of mitochondrial metabolism and dynamics contr...
Source: Comprehensive Physiology - March 13, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Role of Glia in the Regulation of Sleep in Health and Disease.
Authors: Garofalo S, Picard K, Limatola C, Nadjar A, Pascual O, Tremblay MÈ Abstract Sleep is a naturally occurring physiological state that is required to sustain physical and mental health. Traditionally viewed as strictly regulated by top-down control mechanisms, sleep is now known to also originate locally. Glial cells are emerging as important contributors to the regulation of sleep-wake cycles, locally and among dedicated neural circuits. A few pioneering studies revealed that astrocytes and microglia may influence sleep pressure, duration as well as intensity, but the precise involvement of these two ...
Source: Comprehensive Physiology - March 13, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Development of the Pituitary Gland.
Authors: Alatzoglou KS, Gregory LC, Dattani MT Abstract The development of the anterior pituitary gland occurs in distinct sequential developmental steps, leading to the formation of a complex organ containing five different cell types secreting six different hormones. During this process, the temporal and spatial expression of a cascade of signaling molecules and transcription factors plays a crucial role in organ commitment, cell proliferation, patterning, and terminal differentiation. The morphogenesis of the gland and the emergence of distinct cell types from a common primordium are governed by complex regulato...
Source: Comprehensive Physiology - March 13, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Orexin in Respiratory and Autonomic Regulation, Health and Diseases.
Authors: Barnett S, Li A Abstract Orexin neurons, located in the hypothalamus, produce orexin-A and orexin-B neuropeptides and send widespread projections throughout the central nervous system, including many nuclei that are critically involved in sleep-wake, cardiorespiratory, and autonomic regulation. Significant progress has been made to better understand the roles of orexins in the control of breathing and autonomic functions since the discovery of orexins in 1998. Orexin neurons are CO2 /pH chemosensitive and blockade of orexin receptors with orexin receptor antagonists can significantly attenuate ventilatory ...
Source: Comprehensive Physiology - March 13, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Bioengineering the Blood-gas Barrier.
This article reviews the key features of the blood-gas barrier that enable achievement of the necessary design criteria and describes the mechanical environment to which the barrier is exposed. It then focuses on the biological and mechanical components of the barrier that preserve integrity during homeostasis, but which may be compromised in certain pathophysiological states, leading to disease. Finally, this article summarizes recent key advances in efforts to engineer the blood-gas barrier ex vivo, using the platforms of lung-on-a-chip and tissue-engineered whole lungs. © 2020 American Physiological Society. Compr ...
Source: Comprehensive Physiology - March 13, 2020 Category: Physiology Tags: Compr Physiol Source Type: research

Cphy logo.
CPHY LOGO. Compr Physiol. 2019 Dec 18;10(1):1-2 Authors: PMID: 31853939 [PubMed - in process] (Source: Comprehensive Physiology)
Source: Comprehensive Physiology - December 20, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Gut Microbiome and Modulation of CNS Function.
Authors: Osadchiy V, Martin CR, Mayer EA Abstract Preclinical evidence strongly suggests a role for the gut microbiome in modulating the host central nervous system function and behavior. Several communication channels have been identified that enable microbial signals to reach the brain and that enable the brain to influence gut microbial composition and function. In rodent models, endocrine, neural, and inflammatory signals generated by gut microbes can alter brain structure and function, while autonomic nervous system activity can affect the microbiome by modulating the intestinal environment and by directly reg...
Source: Comprehensive Physiology - December 20, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Sex, Gender, and Sex Hormones in Pulmonary Hypertension and Right Ventricular Failure.
Authors: Hester J, Ventetuolo C, Lahm T Abstract Pulmonary hypertension (PH) encompasses a syndrome of diseases that are characterized by elevated pulmonary artery pressure and pulmonary vascular remodeling and that frequently lead to right ventricular (RV) failure and death. Several types of PH exhibit sexually dimorphic features in disease penetrance, presentation, and progression. Most sexually dimorphic features in PH have been described in pulmonary arterial hypertension (PAH), a devastating and progressive pulmonary vasculopathy with a 3-year survival rate
Source: Comprehensive Physiology - December 20, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Intestinal Absorption of Bile Acids in Health and Disease.
Authors: Ticho AL, Malhotra P, Dudeja PK, Gill RK, Alrefai WA Abstract The intestinal reclamation of bile acids is crucial for the maintenance of their enterohepatic circulation. The majority of bile acids are actively absorbed via specific transport proteins that are highly expressed in the distal ileum. The uptake of bile acids by intestinal epithelial cells modulates the activation of cytosolic and membrane receptors such as the farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1), which has a profound effect on hepatic synthesis of bile acids as well as glucose and lipid metabolism. Ex...
Source: Comprehensive Physiology - December 20, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Lung Diffusing Capacities (DL ) for Nitric Oxide (NO) and Carbon Monoxide (CO): The Evolving Story.
Authors: D R Borland C, B Hughes JM Abstract Nitric oxide and carbon monoxide diffusing capacities (DLNO and DLCO ) obey Fick's First Law of Diffusion and the basic principles of chemical kinetic theory. NO gas transfer is dominated by membrane diffusion (DM ), whereas CO transfer is limited by diffusion plus chemical reaction within the red cell. Marie Krogh, who pioneered the single-breath measurement of DLCO in 1915, believed that the combination of CO with red cell hemoglobin (Hb) was instantaneous. Roughton and colleagues subsequently showed, in vitro, that the reaction rate was finite, and prolonged in the pr...
Source: Comprehensive Physiology - December 20, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Respiratory Health Effects of Exposure to Ambient Particulate Matter and Bioaerosols.
Authors: Mack SM, Madl AK, Pinkerton KE Abstract Researchers have been studying the respiratory health effects of ambient air pollution for more than 70 years. While air pollution as a whole can include gaseous, solid, and liquid constituents, this article focuses only on the solid and liquid fractions, termed particulate matter (PM). Although PM may contain anthropogenic, geogenic, and/or biogenic fractions, in this article, particles that originate from microbial, fungal, animal, or plant sources are distinguished from PM as bioaerosols. Many advances have been made toward understanding which particle and exposur...
Source: Comprehensive Physiology - December 20, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Gut Peptide Agonism in the Treatment of Obesity and Diabetes.
Authors: Grandl G, Novikoff A, DiMarchi R, Tschöp MH, Müller TD Abstract Obesity is a global healthcare challenge that gives rise to devastating diseases such as the metabolic syndrome, type-2 diabetes (T2D), and a variety of cardiovascular diseases. The escalating prevalence of obesity has led to an increased interest in pharmacological options to counteract excess weight gain. Gastrointestinal hormones such as glucagon, amylin, and glucagon-like peptide-1 (GLP-1) are well recognized for influencing food intake and satiety, but the therapeutic potential of these native peptides is overall limited by a sh...
Source: Comprehensive Physiology - December 20, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Gastric Peptides-Gastrin and Somatostatin.
Authors: Schubert ML, Rehfeld JF Abstract Gastric acid secretion (i) facilitates digestion of protein as well as absorption of micronutrients and certain medications, (ii) kills ingested microorganisms, including Helicobacter pylori, and (iii) prevents bacterial overgrowth and enteric infection. The principal regulators of acid secretion are the gastric peptides gastrin and somatostatin. Gastrin, the major hormonal stimulant for acid secretion, is synthesized in pyloric mucosal G cells as a 101-amino acid precursor (preprogastrin) that is processed to yield biologically active amidated gastrin-17 and gastrin-34. Th...
Source: Comprehensive Physiology - December 20, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Exercise Countermeasures to Neuromuscular Deconditioning in Spaceflight.
Authors: English KL, Bloomberg JJ, Mulavara AP, Ploutz-Snyder LL Abstract The mechanical unloading of spaceflight elicits a host of physiological adaptations including reductions in muscle mass, muscle strength, and muscle function and alterations in central interpretation of visual, vestibular, and proprioceptive information. Upon return to a terrestrial, gravitational environment, these result in reduced function and performance, the potential consequences of which will be exacerbated during exploration missions to austere and distant destinations such as the moon and Mars. Exercise is a potent countermeasure to ...
Source: Comprehensive Physiology - December 20, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Pulmonary Circulation in Obesity, Diabetes, and Metabolic Syndrome.
Authors: Khaing P, Pandit P, Awsare B, Summer R Abstract Obesity, diabetes mellitus, and the metabolic syndrome are important risk factors for the development of cardiovascular disease, with significant impact on human morbidity and mortality. Several decades of research have accumulated considerable knowledge about the mechanisms by which metabolic conditions precipitate systemic cardiovascular diseases. In short, these mechanisms are thought to involve changes in the external environment of vascular cells, which are mediated by the pro-inflammatory effects of adipokines, free fatty acids, and hyperglycemia. Thus,...
Source: Comprehensive Physiology - December 20, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Redox Regulation of the Microcirculation.
Authors: Kadlec AO, Gutterman DD Abstract The microcirculation maintains tissue homeostasis through local regulation of blood flow and oxygen delivery. Perturbations in microvascular function are characteristic of several diseases and may be early indicators of pathological changes in the cardiovascular system and in parenchymal tissue function. These changes are often mediated by various reactive oxygen species and linked to disruptions in pathways such as vasodilation or angiogenesis. This overview compiles recent advances relating to redox regulation of the microcirculation by adopting both cellular and function...
Source: Comprehensive Physiology - December 20, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Aging and Physiological Lessons from Master Athletes.
Authors: Tanaka H, Tarumi T, Rittweger J Abstract Sedentary aging is often characterized by physical dysfunction and chronic degenerative diseases. In contrast, masters athletes demonstrate markedly greater physiological function and more favorable levels of risk factors for cardiovascular disease, osteoporosis, frailty, and cognitive dysfunction than their sedentary counterparts. In many cases, age-related deteriorations of physiological functions as well as elevations in risk factors that are typically observed in sedentary adults are substantially attenuated or even absent in masters athletes. Older masters athl...
Source: Comprehensive Physiology - December 20, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Regulation of Cell Cycle Entry and Exit: A Single Cell Perspective.
Authors: Coller HA Abstract The transition between proliferating and quiescent states must be carefully regulated to ensure that cells divide to create the cells an organism needs only at the appropriate time and place. Cyclin-dependent kinases (CDKs) are critical for both transitioning cells from one cell cycle state to the next, and for regulating whether cells are proliferating or quiescent. CDKs are regulated by association with cognate cyclins, activating and inhibitory phosphorylation events, and proteins that bind to them and inhibit their activity. The substrates of these kinases, including the retinoblasto...
Source: Comprehensive Physiology - December 20, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Dissecting Epistatic QTL for Blood Pressure in Rats: Congenic Strains versus Heterogeneous Stocks, a Reality Check.
Authors: Rapp JP, Joe B Abstract Advances in molecular genetics have provided well-defined physical genetic maps and large numbers of genetic markers for both model organisms and humans. It is now possible to gain a fundamental understanding of the genetic architecture underlying quantitative traits, of which blood pressure (BP) is an important example. This review emphasizes analytical techniques and results obtained using the Dahl salt-sensitive (S) rat as a model of hypertension by presenting results in detail for three specific chromosomal regions harboring genetic elements of increasing complexity controlling ...
Source: Comprehensive Physiology - November 7, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Chromaffin Cells of the Adrenal Medulla: Physiology, Pharmacology, and Disease.
This article attempts to provide an updated account of well-established features of the molecular processes regulating CC function, and a survey of the as-yet-unsolved but important questions relating to CC function and dysfunction that have been the subject of intense research over the past 15 years. Examples of CCs as a model system to understand the molecular mechanisms associated with neurodegenerative diseases are also provided. Published 2019. Compr Physiol 9:1443-1502, 2019. PMID: 31688964 [PubMed - in process] (Source: Comprehensive Physiology)
Source: Comprehensive Physiology - November 7, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Physical Exercise in the Oldest Old.
Authors: Valenzuela PL, Castillo-García A, Morales JS, Izquierdo M, Serra-Rexach JA, Santos-Lozano A, Lucia A Abstract Societies are progressively aging, with the oldest old (i.e., those aged>80-85 years) being the most rapidly expanding population segment. However, advanced aging comes at a price, as it is associated with an increased incidence of the so-called age-related conditions, including a greater risk for loss of functional independence. How to combat sarcopenia, frailty, and overall intrinsic capacity decline in the elderly is a major challenge for modern medicine, and exercise appears to be a p...
Source: Comprehensive Physiology - November 7, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Neural Mechanisms of Binaural Processing in the Auditory Brainstem.
Authors: Yin TCT, Smith PH, Joris PX Abstract Spatial hearing, and more specifically the ability to localize sounds in space, is one of the most studied and best understood aspects of hearing. Because there is no coding of acoustic space at the receptor organ, physiological sensitivity to spatial aspects of sounds first emerges in the central nervous system. Much progress has been made in the identification and characterization of the circuits in the auditory brainstem that create sensitivity to binaural and monaural cues toward acoustic space. We review the progress over the past third of a century, with a focus o...
Source: Comprehensive Physiology - November 7, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Role of Complement and Complement-Related Adipokines in Regulation of Energy Metabolism and Fat Storage.
This article highlights advances in knowledge regarding the role of these adipokines in energy regulation of adipose tissue through modulating lipogenic and lipolytic pathways. Several adipokines will be discussed including adipsin, Factor H, properdin, C3a, Acylation-Stimulating Protein, C1q/TNF-related proteins, and response gene to complement-32 (RGC-32). Interactions between these factors will be described considering their immune-metabolic roles in the adipose tissue microenvironment and their potential contribution to progression of adiposity and metabolic dysfunction. The differential expression and the role of comp...
Source: Comprehensive Physiology - November 7, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Neuroendocrine Regulation of Male Sexual Behavior.
Authors: Hull EM, Dominguez JM Abstract The major brain areas that control males' sexual motivation and performance include the amygdala, the bed nucleus of the stria terminalis (BNST), the medial preoptic area (MPOA), and paraventricular nucleus (PVN) of the hypothalamus, as well as the mesolimbic dopamine (DA) system. The MPOA, PVN, and brain stem and spinal nuclei control the genital reflexes. Sensory and motor aspects are integrated and elicited by the amygdala, BNST, MPOA, PVN, and the mesolimbic and nigrostriatal DA tracts, which are integral for other social behaviors, as well. Developmental hormonal effects...
Source: Comprehensive Physiology - November 7, 2019 Category: Physiology Tags: Compr Physiol Source Type: research

Physiology of the Incretin Hormones, GIP and GLP-1-Regulation of Release and Posttranslational Modifications.
Authors: Holst JJ, Albrechtsen NJW, Rosenkilde MM, Deacon CF Abstract The focus of this article is on the analysis of the release and postrelease fate of the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Their actions are dealt with to the extent that they are linked to their secretion. For both hormones, their posttranslational processing is analyzed in detail, because of its importance for the understanding of the molecular heterogeneity of the hormones. Methods of analysis, in particular regarding measurements in plasma from in vivo experiments, are discussed in det...
Source: Comprehensive Physiology - November 7, 2019 Category: Physiology Tags: Compr Physiol Source Type: research