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ATP-gated P2X receptors in Health and Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194056 Year: Pages: 172 DOI: 10.3389/978-2-88919-405-6 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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Extracellular ATP is currently recognized as one of the most widely distributed neurotransmitters and neuromodulators in the peripheral and central nervous system. ATP-gated P2X receptors are expressed by neurons, glial and many other non-neuronal cells and represent an attractive target for therapeutic interventions. Diverse molecular and cellular mechanisms have been identified for P2X receptor functioning, including the ability to enlarge the size of the ion pore associated with the release of several key immune molecules. A major recent breakthrough was the determination of the X-ray crystal structures of zebrafish P2X4 receptor in ATP-bound and ATP-free states. The P2X receptor research field is rapidly growing, as evidenced by the almost 2000 papers published in the last 5 years. However, despite the fundamental signalling function of extracellular ATP in the nervous system, the widespread roles of P2X receptors have not been widely elucidated and presented in textbooks. In this volume of papers we aim to gather a collection of high quality papers, detailing the latest insights from the most accomplished international P2X receptor researchers. Importantly, basic research into P2X receptors has a strong translational impact and our collection of articles could be a valuable guide for the development of new pharmacological and biotechnological tools addressing the function of P2X receptors. Within this collection we plan to cover receptor structure-function relationships, receptors trafficking, to highlight the special properties of P2X receptors and their pharmacological profiles, and to describe the translational aspects of cellular ATP signaling in pain and in other neurological and vascular diseases.

CaMKII in Cardiac Health and Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192991 Year: Pages: 165 DOI: 10.3389/978-2-88919-299-1 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Medicine (General) --- Therapeutics --- Science (General)
Added to DOAB on : 2015-12-10 11:59:07
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The calcium-calmodulin dependent protein kinases (CaMKs) are a broadly expressed family of calcium-sensitive intracellular kinases, which are responsible for transducing cytosolic calcium signals into phosphorylation-based regulation of proteins and physiological functions. As the multifunctional member of the family, CaMKII has become the most prominent for its roles in the central nervous system and heart, where it controls a diverse range of calcium-dependent processes; from learning and memory at the neuronal synapse, to cellular growth and death in the myocardium. In the heart, CaMKII directly regulates many of the most important ion channels and calcium handling proteins, and controls the expression of an ever-increasing number of transcripts and their downstream products. Functionally, these actions are thought to orchestrate many of the electrophysiologic and contractile adaptations to common cardiac stressors, such as rapid pacing, chronic adrenergic stimulation, and oxidative challenge. In the context of disease, CaMKII has been shown to contribute to a remarkably wide variety of cardiac pathologies, of which heart failure (HF) is the most conspicuous. Hyperactivity of CaMKII is an established contributor to pathological cardiac remodeling, and is widely thought to directly promote arrhythmia and contractile dysfunction during HF. Moreover, several non-failing arrhythmia-susceptible phenotypes, which result from specific genetic channelopathies, functionally mimic constitutive channel phosphorylation by CaMKII. Because CaMKII contributes to both the acute and chronic manifestations of major cardiac diseases, but may be only minimally required for homeostasis in the absence of chronic stress, it has come to be one of the most promising therapeutic drug targets in cardiac biology. Thus, development of more specific and deliverable small molecule antagonists remains a key priority for the field. Here we provide a selection of articles to summarize the state of our knowledge regarding CaMKII in cardiac health and disease, with a particular view to highlighting recent developments in CaMKII activation, and new targets in CaMKII-mediated control of myocyte physiology.

The truth in complexes: why unraveling ion channel multi-protein signaling nexuses is critical for understanding the function of the nervous system

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194452 Year: Pages: 160 DOI: 10.3389/978-2-88919-445-2 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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In the search for simple explanations of the natural world, its complicated textures are often filed down to a smoothened surface of our liking. The impetus for this Research Topic was borne out of a need to re-ignite interest in the complex – in this case in the context of ion channels in the nervous system. Ion channels are the large proteins that form regulated pores in the membranes of cells and, in the brain, are essential for the transfer, processing and storage of information. These pores full of twists and turns themselves are not just barren bridges into cells. More and more we are beginning to understand that ion channels are like bustling medieval bridges (packed with apartments and shops) rather than the more sleek modern variety – they are dynamic hubs connected with many structures facilitating associated activities. Our understanding of these networks continues to expand as our investigative tools advance. Together these articles highlight how the complexity of ion channel signaling nexuses is critical to the proper functioning of the nervous system.

Mitochondria: the cell powerhouse and nexus of stress

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192830 Year: Pages: 121 DOI: 10.3389/978-2-88919-283-0 Language: English
Publisher: Frontiers Media SA
Subject: Biology --- Physiology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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Mitochondrion, a sub-cellular organelle originated from primary endosymbiosis, plays a vital role in energy metabolism of eukaryotic cells. The transfer of electrons through the electron transport chain (ETC) to molecular oxygen accompanied by the extrusion of protons from the matrix generate an electrochemical gradient across the inner mitochondrial membrane (IMM) that is used for ATP synthesis by oxidative phosphorylation. Despite many aspects of ATP synthesis have been delineated, regulatory mechanisms responsible for energy synthesis and transfer still remain to be uncovered. In addition to energy function, mitochondria play a crucial role in cell metabolism under both physiological and pathological conditions through their participation in many intracellular signaling pathways. Studies over the last 30 years provide strong evidence that mitochondria are the nexus of various stresses which initiate cell death through apoptosis, oncosis, necrosis and autophagy depending on the severity of the stress and cellular energy status. The release of several pro-apoptotic proteins such as cytochrome c, Smac/DIABLO, AIF, endonuclease G from intermembrane space initiates both caspase-dependent and caspase-independent apoptosis. The formation of the mitochondrial permeability transition pore in the IMM promotes cell death mostly through necrosis whereas a mild stress activates autophagy. Due to their critical roles in both cell death and survival mitochondria have been widely considered as an important target for various pharmacological and conditional therapeutic approaches. Currently, a large number of mitochondria-targeted agents are suggested to prevent (in ischemia reperfusion injury, cardiovascular, neurodegenerative and other diseases) or stimulate (in various cancers) cell death. This Research Topic focuses on the role of mitochondria in the regulation of cell metabolism and signaling under physiological and pathological conditions. Studies performed on cultured cells and isolated organs/tissues using different animal and cellular models of various diseases are also included and discussed.

Salinity Tolerance in Plants: Mechanisms and Regulation of Ion Transport

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453696 Year: Pages: 243 DOI: 10.3389/978-2-88945-369-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Botany
Added to DOAB on : 2018-02-27 16:16:45
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Life presumably arose in the primeval oceans with similar or even greater salinity than the present ocean, so the ancient cells were designed to withstand salinity. However, the immediate ancestors of land plants most likely lived in fresh, or slightly brackish, water. The fresh/brackish water origins might explain why many land plants, including some cereals, can withstand moderate salinity, but only 1 – 2 % of all the higher plant species were able to re-discover their saline origins again and survive at increased salinities close to that of seawater. From a practical side, salinity is among the major threats to agriculture, having been one of the reasons for the demise of the ancient Mesopotamian Sumer civilisation and in the present time causing huge annual economic losses of over 10 billion USD. The effects of salinity on plants include osmotic stress, disruption of membrane ion transport, direct toxicity of high cytoplasmic concentrations of sodium and chloride on cellular processes and induced oxidative stress. Ion transport is the crucial starting point that determines salinity tolerance in plants. Transport via membranes is mediated mostly by the ion channels and transporters, which ensure selective passage of specific ions. The molecular and structural diversity of these ion channels and transporters is amazing. Obtaining the detailed descriptions of distinct ion channels and transporters present in halophytes, marine algae and salt-tolerant fungi and then progressing to the cellular and the whole organism mechanisms, is one of the logical ways to understand high salinity tolerance. Transfer of the genes from halophytes to agricultural crops is a means to increase salt tolerance of the crops. The theoretical scientific approaches involve protein chemistry, structure-function relations of membrane proteins, synthetic biology, systems biology and physiology of stress and ion homeostasis. At the time of compiling this e-book many aspects of ion transport under salinity stress are not yet well understood. The e-book has attracted researchers in ion transport and salinity tolerance. We have combined our efforts to achieve a wider, more detailed understanding of salt tolerance in plants mediated by ion transport, to understand present and future ways to modify and manipulate ion transport and salinity tolerance and also to find natural limits for the modifications.

Inter-cellular Electrical Signals in Plant Adaptation and Communication

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455218 Year: Pages: 120 DOI: 10.3389/978-2-88945-521-8 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Botany --- Physiology
Added to DOAB on : 2019-01-23 14:53:42
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Plants use the Sun's energy to synthesize the basic biomolecules that make up all the organic matter of all organisms of terrestrial ecosystems, including ourselves. Therefore, understanding their adaptive mechanisms to variations of environmental factors, both biotic and abiotic, is fundamental, and particularly relevant in the current context of rapid climate change. Some of the most important adaptive mechanisms of plants are the electrical and chemical signaling systems for the exchange of information between proximally and distally located cells. These signalling systems allow plants to dynamically coordinate the activities of all cells under a diversity of situations. In this Research Topic, we present eight articles that bring up new hypothesis and data to understand the mechanisms of systemic electrical signaling and the central role that it plays in adapting the whole plant to different stresses, as well as new findings on intracellular calcium and nitric oxide-based signaling pathways under stress, which could be extrapolated to non-plant research.

Toxins in Drug Discovery and Pharmacology

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ISBN: 9783038428619 9783038428626 Year: Pages: XII, 304 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Public Health
Added to DOAB on : 2018-05-04 11:37:49
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Venoms from marine and terrestrial animals (cone snails, scorpions, spiders, snakes, centipedes, cnidarian, etc.) can be seen as untapped cocktails of biologically active compounds that are being increasingly recognized as a new emerging source of peptide-based therapeutics. Venomous animals are considered to be specialized predators that have evolved the most sophisticated peptide chemistry and neuropharmacology for their own biological purposes by producing venoms that contain a structural and functional diversity of neurotoxins. These neurotoxins appear to be highly selective ligands for a wide range of ion channels and receptors. Therefore, they represent interesting lead compounds for the development of analgesics, anti-cancer drugs, drugs for neurological disorders such as multiple sclerosis, Parkinson' s disease, Alzheimer' s disease, and other therapeutics.This Special Issue of Toxins aims to provide a comprehensive look at toxins and toxin-inspired leads and will focus on the mechanisms of action, structure–function relationships, and evolution of pharmacologically interesting venom components, including the most recent developments related to the emergence of venoms as an underutilized source of highly evolved bioactive peptides with clinical potential.

Ionic Liquid Crystals

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ISBN: 9783039210862 / 9783039210879 Year: Pages: 108 DOI: 10.3390/books978-3-03921-087-9 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Technology (General) --- Chemical Engineering
Added to DOAB on : 2019-06-26 08:44:06
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In this book we have collected a series of state-of-the art papers written by specialists in the field of ionic liquid crystals (ILCs) to address key questions concerning the synthesis, properties, and applications of ILCs. New compounds exhibiting ionic liquid crystalline phases are presented, both of calamitic as well as discotic type. Their dynamic and structural properties have been investigated with a series of experimental techniques including differential scanning calorimetry, polarized optical spectroscopy, X-ray scattering, and nuclear magnetic resonance, impedance spectroscopy to mention but a few. Moreover, computer simulations using both fully atomistic and highly coarse-grained force fields have been presented, offering an invaluable microscopic view of the structure and dynamics of these fascinating materials.

Quantum Nonlocality

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ISBN: 9783038979487 / 9783038979494 Year: Pages: 238 DOI: 10.3390/books978-3-03897-949-4 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Physics (General)
Added to DOAB on : 2019-06-26 08:44:06
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This book presents the current views of leading physicists on the bizarre property of quantum theory: nonlocality. Einstein viewed this theory as “spooky action at a distance” which, together with randomness, resulted in him being unable to accept quantum theory. The contributions in the book describe, in detail, the bizarre aspects of nonlocality, such as Einstein–Podolsky–Rosen steering and quantum teleportation—a phenomenon which cannot be explained in the framework of classical physics, due its foundations in quantum entanglement. The contributions describe the role of nonlocality in the rapidly developing field of quantum information. Nonlocal quantum effects in various systems, from solid-state quantum devices to organic molecules in proteins, are discussed. The most surprising papers in this book challenge the concept of the nonlocality of Nature, and look for possible modifications, extensions, and new formulations—from retrocausality to novel types of multiple-world theories. These attempts have not yet been fully successful, but they provide hope for modifying quantum theory according to Einstein’s vision.

Keywords

quantum nonlocality --- quantum mechanics --- Stern–Gerlach experiment --- quantum measurement --- pre- and post-selected systems --- retro-causal channel --- channel capacity --- channel entropy --- axioms for quantum theory --- PR box --- nonlocal correlations --- classical limit --- retrocausality --- quantum correlations --- quantum bounds --- nonlocality --- tsallis entropy --- ion channels --- selectivity filter --- quantum mechanics --- non-linear Schrödinger model --- biological quantum decoherence --- non-locality --- parity measurements --- entanglement --- pigeonhole principle --- controlled-NOT --- semiconductor nanodevices --- quantum transport --- density-matrix formalism --- Wigner-function simulations --- nonlocal dissipation models --- steering --- entropic uncertainty relation --- general entropies --- Bell’s theorem --- Einstein–Podolsky–Rosen argument --- local hidden variables --- local realism --- no-signalling --- parallel lives --- local polytope --- quantum nonlocality --- communication complexity --- optimization --- KS Box --- PR Box --- Non-contextuality inequality --- discrete-variable states --- continuous-variable states --- quantum teleportation of unknown qubit --- hybrid entanglement --- collapse of the quantum state --- quantum nonlocality --- communication complexity --- quantum nonlocality --- Bell test --- device-independent --- p-value --- hypothesis testing --- nonsignaling --- EPR steering --- quantum correlation --- non-locality --- entanglement --- uncertainty relations --- nonlocality --- entanglement --- quantum

TRP Channels in Health and Disease

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ISBN: 9783039210824 / 9783039210831 Year: Pages: 266 DOI: 10.3390/books978-3-03921-083-1 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General)
Added to DOAB on : 2019-06-26 08:44:07
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Almost 25 years ago, the first mammalian transient receptor potential (TRP) channel was cloned and published. TRP channels now represent an extended family of 28 members fulfilling multiple roles in the living organism. Identified functions include control of body temperature, transmitter release, mineral homeostasis, chemical sensing, and survival mechanisms in a challenging environment. The TRP channel superfamily covers six families: TRPC with C for “canonical”, TRPA with A for “ankyrin”, TRPM with M for “melastatin”, TRPML with ML for “mucolipidin”, TRPP with P for “polycystin”, and TRPV with V for “vanilloid”. Over the last few years, new findings on TRP channels have confirmed their exceptional function as cellular sensors and effectors. This Special Book features a collection of 8 reviews and 7 original articles published in “Cells” summarizing the current state-of-the-art on TRP channel research, with a main focus on TRP channel activation, their physiological and pathophysiological function, and their roles as pharmacological targets for future therapeutic options.

Keywords

ion channel --- TRPC --- small molecules --- calcium --- chemical probes --- TRPV1 --- TRPV2 --- TRPV3 --- TRPV4 --- mucosal epithelium --- ulcerative colitis --- inflammatory bowel disease --- TRPM4 channel --- cardiovascular system --- physiology --- pathophysiology --- TRPC6 --- elementary immunology --- inflammation --- calcium --- sodium --- neutrophils --- lymphocytes --- endothelium --- platelets --- human medulla oblongata --- cuneate nucleus --- dorsal column nuclei --- TRPV1 --- calcitonin gene-related peptide --- substance P --- TRP channels --- calcium signaling --- salivary glands --- xerostomia --- radiation --- inflammation --- transient receptor potential channels --- TRPC3 pharmacology --- channel structure --- lipid mediators --- photochromic ligands --- transient receptor potential --- TRPC3 --- mGluR1 --- GABAB --- EPSC --- Purkinje cell --- cerebellum --- toxicology --- TRP channels --- organ toxicity --- chemicals --- pollutants --- chemosensor --- TRPM7 --- kinase --- inflammation --- lymphocytes --- calcium signalling --- SMAD --- TH17 --- hypersensitivity --- regulatory T cells --- thrombosis --- graft versus host disease --- 2D gel electrophoresis --- AP18 --- HEK293 --- HSP70 --- MALDI-TOF MS(/MS) --- nanoHPLC-ESI MS/MS --- proteomics --- sulfur mustard --- TRPA1 --- TRPC channels --- diacylglycerol --- TRPC4 --- TRPC5 --- NHERF --- TRP channel --- TRPY1 --- Saccharomyces cerevisiae --- calcium --- manganese --- oxidative stress --- ion channels --- overproduction --- production platform --- protein purification --- Saccharomyces cerevisiae --- sensors --- transient receptor potential (TRP) channels --- yeast --- adipose tissue --- bioavailable --- menthol --- topical --- TRPM8 --- n/a

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