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Physiological Reviews

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https://www.readbyqxmd.com/read/29897294/deptor-at-the-nexus-of-cancer-metabolism-and-immunity
#1
Alexandre Caron, David M Briscoe, Denis Richard, Mathieu Laplante
DEP domain-containing mechanistic target of rapamycin (mTOR)-interacting protein (DEPTOR) is an important modulator of mTOR, a kinase at the center of two important protein complexes named mTORC1 and mTORC2. These highly studied complexes play essential roles in regulating growth, metabolism, and immunity in response to mitogens, nutrients, and cytokines. Defects in mTOR signaling have been associated with the development of many diseases, including cancer and diabetes, and approaches aiming at modulating mTOR activity are envisioned as an attractive strategy to improve human health...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29897293/the-oxytocin-receptor-from-intracellular-signaling-to-behavior
#2
Benjamin Jurek, Inga D Neumann
The many facets of the oxytocin (OXT) system of the brain and periphery elicited nearly 25,000 publications since 1930 (see FIGURE 1 , as listed in PubMed), which revealed central roles for OXT and its receptor (OXTR) in reproduction, and social and emotional behaviors in animal and human studies focusing on mental and physical health and disease. In this review, we discuss the mechanisms of OXT expression and release, expression and binding of the OXTR in brain and periphery, OXTR-coupled signaling cascades, and their involvement in behavioral outcomes to assemble a comprehensive picture of the central and peripheral OXT system...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29897292/human-olfactory-receptors-novel-cellular-functions-outside-of-the-nose
#3
Désirée Maßberg, Hanns Hatt
Olfactory receptors (ORs) are not exclusively expressed in the olfactory sensory neurons; they are also observed outside of the olfactory system in all other human tissues tested to date, including the testis, lung, intestine, skin, heart, and blood. Within these tissues, certain ORs have been determined to be exclusively expressed in only one tissue, whereas other ORs are more widely distributed in many different tissues throughout the human body. For most of the ectopically expressed ORs, limited data are available for their functional roles...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29873596/angiotensin-ii-signal-transduction-an-update-on-mechanisms-of-physiology-and-pathophysiology
#4
Steven J Forrester, George W Booz, Curt D Sigmund, Thomas M Coffman, Tatsuo Kawai, Victor Rizzo, Rosario Scalia, Satoru Eguchi
The renin-angiotensin-aldosterone system plays crucial roles in cardiovascular physiology and pathophysiology. However, many of the signaling mechanisms have been unclear. The angiotensin II (ANG II) type 1 receptor (AT1 R) is believed to mediate most functions of ANG II in the system. AT1 R utilizes various signal transduction cascades causing hypertension, cardiovascular remodeling, and end organ damage. Moreover, functional cross-talk between AT1 R signaling pathways and other signaling pathways have been recognized...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29848236/pharmacology-of-adenosine-receptors-the-state-of-the-art
#5
Pier Andrea Borea, Stefania Gessi, Stefania Merighi, Fabrizio Vincenzi, Katia Varani
Adenosine is a ubiquitous endogenous autacoid whose effects are triggered through the enrollment of four G protein-coupled receptors: A1 , A2A , A2B , and A3 . Due to the rapid generation of adenosine from cellular metabolism, and the widespread distribution of its receptor subtypes in almost all organs and tissues, this nucleoside induces a multitude of physiopathological effects, regulating central nervous, cardiovascular, peripheral, and immune systems. It is becoming clear that the expression patterns of adenosine receptors vary among cell types, lending weight to the idea that they may be both markers of pathologies and useful targets for novel drugs...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29845874/clc-chloride-channels-and-transporters-structure-function-physiology-and-disease
#6
Thomas J Jentsch, Michael Pusch
CLC anion transporters are found in all phyla and form a gene family of eight members in mammals. Two CLC proteins, each of which completely contains an ion translocation parthway, assemble to homo- or heteromeric dimers that sometimes require accessory β-subunits for function. CLC proteins come in two flavors: anion channels and anion/proton exchangers. Structures of these two CLC protein classes are surprisingly similar. Extensive structure-function analysis identified residues involved in ion permeation, anion-proton coupling and gating and led to attractive biophysical models...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29790818/endosomal-and-phagosomal-snares
#7
Ilse Dingjan, Peter T A Linders, Danielle R J Verboogen, Natalia H Revelo, Martin Ter Beest, Geert van den Bogaart
The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein family is of vital importance for organelle communication. The complexing of cognate SNARE members present in both the donor and target organellar membranes drives the membrane fusion required for intracellular transport. In the endocytic route, SNARE proteins mediate trafficking between endosomes and phagosomes with other endosomes, lysosomes, the Golgi apparatus, the plasma membrane, and the endoplasmic reticulum. The goal of this review is to provide an overview of the SNAREs involved in endosomal and phagosomal trafficking...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29767564/interorgan-metabolic-crosstalk-in-human-insulin-resistance
#8
Sofiya Gancheva, Tomas Jelenik, Elisa Álvarez-Hernández, Michael Roden
Excessive energy intake and reduced energy expenditure drive the development of insulin resistance and metabolic diseases such as obesity and type 2 diabetes mellitus. Metabolic signals derived from dietary intake or secreted from adipose tissue, gut, and liver contribute to energy homeostasis. Recent metabolomic studies identified novel metabolites and enlarged our knowledge on classic metabolites. This review summarizes the evidence of their roles as mediators of interorgan crosstalk and regulators of insulin sensitivity and energy metabolism...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29767563/integrative-physiology-of-pneumonia
#9
Lee J Quinton, Allan J Walkey, Joseph P Mizgerd
Pneumonia is a type of acute lower respiratory infection that is common and severe. The outcome of lower respiratory infection is determined by the degrees to which immunity is protective and inflammation is damaging. Intercellular and interorgan signaling networks coordinate these actions to fight infection and protect the tissue. Cells residing in the lung initiate and steer these responses, with additional immunity effectors recruited from the bloodstream. Responses of extrapulmonary tissues, including the liver, bone marrow, and others, are essential to resistance and resilience...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29717933/the-keap1-nrf2-system-a-thiol-based-sensor-effector-apparatus-for-maintaining-redox-homeostasis
#10
Masayuki Yamamoto, Thomas W Kensler, Hozumi Motohashi
The Kelch-like ECH-associated protein 1-NF-E2-related factor 2 (KEAP1-NRF2) system forms the major node of cellular and organismal defense against oxidative and electrophilic stresses of both exogenous and endogenous origins. KEAP1 acts as a cysteine thiol-rich sensor of redox insults, whereas NRF2 is a transcription factor that robustly transduces chemical signals to regulate a battery of cytoprotective genes. KEAP1 represses NRF2 activity under quiescent conditions, whereas NRF2 is liberated from KEAP1-mediated repression on exposure to stresses...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29717932/gestational-hypoxia-and-developmental-plasticity
#11
Charles A Ducsay, Ravi Goyal, William J Pearce, Sean Wilson, Xiang-Qun Hu, Lubo Zhang
Hypoxia is one of the most common and severe challenges to the maintenance of homeostasis. Oxygen sensing is a property of all tissues, and the response to hypoxia is multidimensional involving complicated intracellular networks concerned with the transduction of hypoxia-induced responses. Of all the stresses to which the fetus and newborn infant are subjected, perhaps the most important and clinically relevant is that of hypoxia. Hypoxia during gestation impacts both the mother and fetal development through interactions with an individual's genetic traits acquired over multiple generations by natural selection and changes in gene expression patterns by altering the epigenetic code...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29717931/-re-generating-human-beta-cells-status-pitfalls-and-perspectives
#12
Luc Baeyens, Marie Lemper, Willem Staels, Sofie De Groef, Nico De Leu, Yves Heremans, Michael S German, Harry Heimberg
Diabetes mellitus results from disturbed glucose homeostasis due to an absolute (type 1) or relative (type 2) deficiency of insulin, a peptide hormone almost exclusively produced by the beta cells of the endocrine pancreas in a tightly regulated manner. Current therapy only delays disease progression through insulin injection and/or oral medications that increase insulin secretion or sensitivity, decrease hepatic glucose production, or promote glucosuria. These drugs have turned diabetes into a chronic disease as they do not solve the underlying beta cell defects or entirely prevent the long-term complications of hyperglycemia...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29717930/myoediting-toward-prevention-of-muscular-dystrophy-by-therapeutic-genome-editing
#13
Yu Zhang, Chengzu Long, Rhonda Bassel-Duby, Eric N Olson
Muscular dystrophies represent a large group of genetic disorders that significantly impair quality of life and often progress to premature death. There is no effective treatment for these debilitating diseases. Most therapies, developed to date, focus on alleviating the symptoms or targeting the secondary effects, while the underlying gene mutation is still present in the human genome. The discovery and application of programmable nucleases for site-specific DNA double-stranded breaks provides a powerful tool for precise genome engineering...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29717929/specialized-proresolving-mediators-in-innate-and-adaptive-immune-responses-in-airway-diseases
#14
Nandini Krishnamoorthy, Raja-Elie E Abdulnour, Katherine H Walker, Braden D Engstrom, Bruce D Levy
Airborne pathogens and environmental stimuli evoke immune responses in the lung. It is critical to health that these responses be controlled to prevent tissue damage and the compromise of organ function. Resolution of inflammation is a dynamic process that is coordinated by biochemical and cellular mechanisms. Recently, specialized proresolving mediators (SPMs) have been identified in resolution exudates. These molecules orchestrate anti-inflammatory and proresolving actions that are cell type specific. In this review, we highlight SPM biosynthesis, the influence of SPMs on the innate and adaptive immune responses in the lung, as well as recent insights from SPMs on inflammatory disease pathophysiology...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29717928/impact-of-the-autonomic-nervous-system-on-the-skeleton
#15
Florent Elefteriou
It is from the discovery of leptin and the central nervous system as a regulator of bone remodeling that the presence of autonomic nerves within the skeleton transitioned from a mere histological observation to the mechanism whereby neurons of the central nervous system communicate with cells of the bone microenvironment and regulate bone homeostasis. This shift in paradigm sparked new preclinical and clinical investigations aimed at defining the contribution of sympathetic, parasympathetic, and sensory nerves to the process of bone development, bone mass accrual, bone remodeling, and cancer metastasis...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29717927/food-intake-and-eating-behavior-after-bariatric-surgery
#16
Werd Al-Najim, Neil G Docherty, Carel W le Roux
Obesity is an escalating global chronic disease. Bariatric surgery is a very efficacious treatment for obesity and its comorbidities. Alterations to gastrointestinal anatomy during bariatric surgery result in neurological and physiological changes affecting hypothalamic signaling, gut hormones, bile acids, and gut microbiota, which coalesce to exert a profound influence on eating behavior. A thorough understanding of the mechanisms underlying eating behavior is essential in the management of patients after bariatric surgery...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29537337/intracellular-camp-sensor-epac-physiology-pathophysiology-and-therapeutics-development
#17
William G Robichaux, Xiaodong Cheng
This review focuses on one family of the known cAMP receptors, the exchange proteins directly activated by cAMP (EPACs), also known as the cAMP-regulated guanine nucleotide exchange factors (cAMP-GEFs). Although EPAC proteins are fairly new additions to the growing list of cAMP effectors, and relatively "young" in the cAMP discovery timeline, the significance of an EPAC presence in different cell systems is extraordinary. The study of EPACs has considerably expanded the diversity and adaptive nature of cAMP signaling associated with numerous physiological and pathophysiological responses...
April 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29537336/the-prokineticins-neuromodulators-and-mediators-of-inflammation-and-myeloid-cell-dependent-angiogenesis
#18
Lucia Negri, Napoleone Ferrara
The mammalian prokineticins family comprises two conserved proteins, EG-VEGF/PROK1 and Bv8/PROK2, and their two highly related G protein-coupled receptors, PKR1 and PKR2. This signaling system has been linked to several important biological functions, including gastrointestinal tract motility, regulation of circadian rhythms, neurogenesis, angiogenesis and cancer progression, hematopoiesis, and nociception. Mutations in PKR2 or Bv8/PROK2 have been associated with Kallmann syndrome, a developmental disorder characterized by defective olfactory bulb neurogenesis, impaired development of gonadotropin-releasing hormone neurons, and infertility...
April 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29513146/the-biology-of-regeneration-failure-and-success-after-spinal-cord-injury
#19
Amanda Phuong Tran, Philippa Mary Warren, Jerry Silver
Since no approved therapies to restore mobility and sensation following spinal cord injury (SCI) currently exist, a better understanding of the cellular and molecular mechanisms following SCI that compromise regeneration or neuroplasticity is needed to develop new strategies to promote axonal regrowth and restore function. Physical trauma to the spinal cord results in vascular disruption that, in turn, causes blood-spinal cord barrier rupture leading to hemorrhage and ischemia, followed by rampant local cell death...
April 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29488822/neuronal-cell-death
#20
Michael Fricker, Aviva M Tolkovsky, Vilmante Borutaite, Michael Coleman, Guy C Brown
Neuronal cell death occurs extensively during development and pathology, where it is especially important because of the limited capacity of adult neurons to proliferate or be replaced. The concept of cell death used to be simple as there were just two or three types, so we just had to work out which type was involved in our particular pathology and then block it. However, we now know that there are at least a dozen ways for neurons to die, that blocking a particular mechanism of cell death may not prevent the cell from dying, and that non-neuronal cells also contribute to neuronal death...
April 1, 2018: Physiological Reviews
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