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The regulation of angiogenesis by tissue cell-macrophage interactions

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193172 Year: Pages: 113 DOI: 10.3389/978-2-88919-317-2 Language: English
Publisher: Frontiers Media SA
Subject: Physiology --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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Angiogenesis is the physiological process where new blood vessels grow from existing ones, in order to replenish tissues suffering from inadequate blood supply. Perhaps the most studied angiogenic process occurs in solid tumors whose growing mass and expanding cells create a constant demand for additional supply of oxygen and nutrients for survival. However, other physiological and clinical conditions, such as wound healing, ischemic events, autoimmune and age-related diseases also involve angiogenesis. Angiogenesis is a well-structured process that begins when oxygen and nutrients are depleted, leading to the release of chemokines and growth factors that attract immune cells, particularly macrophages and endothelial cells to the site. Macrophages that are recruited to the site, as well as tissue cells and endothelial cells, secrete pro-angiogenic mediators that affect endothelial cells and promote angiogenesis. These mediators include growth factors such as vascular endothelial cell growth factor (VEGF), matrix metalloproteinases (MMPs), as well as low levels of mediators that are usually seen as pro-inflammatory but are pro-angiogenic when secreted in low levels (e.g. nitric oxide (NO) and TNFa). Thus, macrophages play a major role in angiogenesis. Macrophages exhibit high plasticity and are capable of shifting between different activation modes and functions according to their changing microenvironment. Small differences in the composition of activating factors (e.g. TLR ligands such as LPS, anti-inflammatory cytokines, ECM molecules) in the microenvironment may differently activate macrophages to yield classically activated macrophages (or M1 macrophages) that can kill pathogen and tumor cells, alternatively activated macrophages (or M2 macrophages) that secrete antiinflammatory cytokines, resolution macrophages (rM?) that are involved in the resolution of inflammation, or regulatory macrophages (e.g. Myeloid-Derived Suppressor Cells - MDSCs) that control the function of other immune cells. In fact, macrophages may be activated in a spectrum of subsets that may differently contribute to angiogenesis, and in particular non-classically activated macrophages such as tumor-associated macrophages (TAMs) and Tie2-expressing monocytes (TEMs) can secrete high amounts of pro-angiogenic factors (e.g. VEGF, MMPs) or low levels of pro-inflammatory mediators (e.g. NO or TNFa) resulting in pro-angiogenic effects. Although the importance of macrophages as major contributors and regulators of the angiogenic process is well documented, less is known about the interactions between macrophages and other cell types (e.g. tumor cells, normal epithelial cells, endothelial cells) that regulate angiogenesis. We still have only limited understanding which proteins or complexes mediate these interactions and whether they require cell-cell contact (e.g. through integrins) or soluble factors (e.g. the EGF-CSF-1 loop), which signaling pathways are triggered in each of the two corresponding cell types, and how this leads to secretion of pro- or antiangiogenic factors in the microenvironment. The regulation of such interactions and through them of angiogenesis, whether through post-translational modifications of proteins or via the involvement of microRNA, is still unclear. The goal of this Research Topic is to highlight these interactions and their regulation in the context of both physiological and pathological conditions.

Inhibitory Function in Auditory Processing

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196678 Year: Pages: 231 DOI: 10.3389/978-2-88919-667-8 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2016-08-16 10:34:25
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There seems little doubt that from the earliest evolutionary beginnings, inhibition has been a fundamental feature of neuronal circuits - even the simplest life forms sense and interact with their environment, orienting or approaching positive stimuli while avoiding aversive stimuli. This requires internal signals that both drive and suppress behavior. Traditional descriptions of inhibition sometimes limit its role to the suppression of action potential generation. This view fails to capture the vast breadth of inhibitory function now known to exist in neural circuits. A modern perspective on inhibitory signaling comprises a multitude of mechanisms. For example, inhibition can act via a shunting mechanism to speed the membrane time constant and reduce synaptic integration time. It can act via G-protein coupled receptors to initiate second messenger cascades that influence synaptic strength. Inhibition contributes to rhythm generation and can even activate ion channels that mediate inward currents to drive action potential generation. Inhibition also appears to play a role in shaping the properties of neural circuitry over longer time scales. Experience-dependent synaptic plasticity in developing and mature neural circuits underlies behavioral memory and has been intensively studied over the past decade. At excitatory synapses, adjustments of synaptic efficacy are regulated predominantly by changes in the number and function of postsynaptic glutamate receptors. There is, however, increasing evidence for inhibitory modulation of target neuron excitability playing key roles in experience-dependent plasticity. One reason for our limited knowledge about plasticity at inhibitory synapses is that in most circuits, neurons receive convergent inputs from disparate sources. This problem can be overcome by investigating inhibitory circuits in a system with well-defined inhibitory nuclei and projections, each with a known computational function. Compared to other sensory systems, the auditory system has evolved a large number of subthalamic nuclei each devoted to processing distinct features of sound stimuli. This information once extracted is then re-assembled to form the percept the acoustic world around us. The well-understood function of many of these auditory nuclei has enhanced our understanding of inhibition's role in shaping their responses from easily distinguished inhibitory inputs. In particular, neurons devoted to processing the location of sound sources receive a complement of discrete inputs for which in vivo activity and function are well understood. Investigation of these areas has led to significant advances in understanding the development, physiology, and mechanistic underpinnings of inhibition that apply broadly to neuroscience. In this series of papers, we provide an authoritative resource for those interested in exploring the variety of inhibitory circuits and their function in auditory processing. We present original research and focused reviews touching on development, plasticity, anatomy, and evolution of inhibitory circuitry. We hope our readers will find these papers valuable and inspirational to their own research endeavors.

Interplay between NO Signalling, ROS, and the Antioxidant System in Plants

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450695 Year: Pages: 206 DOI: 10.3389/978-2-88945-069-5 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Botany --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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Over the last decades, nitric oxide (NO) has emerged as an essential player in redox signalling. Reactive oxygen species (ROS) also act as signals throughout all stages of plant life. Because they are potentially harmful for cellular integrity, ROS and NO levels must be tightly controlled, especially by the classical antioxidant system and additional redox-active metabolites and proteins. Recent work provided evidence that NO and ROS influence each other’s biosynthesis and removal. Moreover, novel signalling molecules resulting from the chemical reaction between NO, ROS and plant metabolites have been highlighted, including N2O3, ONOO-, NO2, S-nitrosoglutathione and 8-NO2 cGMP. They are involved in diverse plant physiological processes, the best characterized being stomata regulation and stress defense. Taken together, these new data demonstrate the complex interactions between NO, ROS signalling and the antioxidant system. This Frontiers in Plant Science Research Topic aims to provide an updated and complete overview of this important and rapidly expanding area through original article and detailed reviews.

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.

Signal Transduction in Stomatal Guard Cells

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451678 Year: Pages: 105 DOI: 10.3389/978-2-88945-167-8 Language: English
Publisher: Frontiers Media SA
Subject: Botany --- Science (General)
Added to DOAB on : 2017-08-28 14:01:09
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Stomata, the tiny pores on leaf surface, are the gateways for CO2 uptake during photosynthesis as well as water loss in transpiration. Further, plants use stomatal closure as a defensive response, often triggered by elicitors, to prevent the entry of pathogens. The guard cells are popular model systems to study the signalling mechanism in plant cells. The messengers that mediate closure upon perception of elicitors or microbe associated molecular patterns (MAMPs) are quite similar to those during ABA effects. These components include reactive oxygen species (ROS), nitric oxide (NO), cytosolic pH and intracellular Ca2+. The main components are ROS, NO and cytosolic free Ca2+. The list extends to others, such as G-proteins, protein phosphatases, protein kinases, phospholipids and ion channels. The sequence of these signalling components and their interaction during stomatal signalling are complex and quite interesting. The present e-Book provides a set of authoritative articles from ‘Special Research Topic’ on selected areas of stomatal guard cells. In the first set of two articles, an overview of ABA and MAMPs as signals is presented. The next set of 4 articles, emphasize the role of ROS, NO, Ca2+ as well as pH, as secondary messengers. The next group of 3 articles highlight the recent advances on post-translational modification of guard cell proteins, with emphasis on 14-3-3 proteins and MAPK cascades. The last article described the method to isolate epidermis of grass species and monitor stomatal responses to different signals. Our e-Book is a valuable and excellent source of information for all those interested in guard cell function as well as signal transduction in plant cells.

Extracellular Nucleotides in the Regulation of Kidney Functions

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195046 Year: Pages: 77 DOI: 10.3389/978-2-88919-504-6 Language: English
Publisher: Frontiers Media SA
Subject: Physiology --- Science (General)
Added to DOAB on : 2015-12-03 13:02:24
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ATP is normally regarded as the major source of fuel for the energy-demanding processes within cells; however, ATP and other nucleotides (such as ADP, UTP, UDP) can be released from cells, where they act as autocrine or paracrine signaling molecules to affect cellular and tissue functions. In response to various stimuli, ATP and other nucleotides are released from cells in a regulated fashion, either by exocytosis of nucleotide-containing vesicles, or through channels in the plasma membrane. This process occurs in virtually every organ or cell in the body. The cellular effects of these extracellular nucleotides are mediated through specific membrane receptors (P2X and P2Y). These nucleotide signals can be terminated by rapid degradation of the ligand molecules by ecto-nucleotidases (e.g., NTPDases and NPPs). Many of the molecular components essential to nucleotide signaling have been cloned and characterized in detail, and their crystal structures are beginning to emerge. The collected data on extracellular nucleotides suggest a vivid and dynamic signaling system that is modulated by the expression and sensitivity of specific receptors on cells, and by the regulated release and extracellular degradation of ATP and other nucleotides; thus creating a microenvironment of highly regulated paracrine or autocrine control mechanisms. Within the kidney, extracellular nucleotides have emerged as potent modulators of glomerular, tubular, and microvascular functions. These functions include, but are not limited to, tubular transport of water and sodium, tubuloglomerular feedback and auto-regulation, regulation of blood pressure and the microcirculation, oxidative stress, and cell proliferation/ necrosis/apoptosis. Moreover, studies have also uncovered the interaction of nucleotide signaling with other mediators of renal function, such as vasopressin, aldosterone, nitric oxide, prostaglandins, angiotensin II, and the ATP-break down product adenosine. These insights have provided a more comprehensive and cohesive picture of the role of extracellular nucleotides in the regulation of renal function in health and disease. The availability of transgenic mouse models of the key proteins involved in nucleotide signaling has markedly enhanced our understanding of the physiological and pathophysiological roles of the different components of the system in the kidney. Although at a preliminary stage, the pathophysiological significance of this system in the kidney holds the key for the development of an entirely new class of drugs for the treatment of disease conditions, including disorders of water and/or sodium homeostasis, hypertension, acute kidney injury, etc. Thus, the regulation of renal function by extracellular nucleotides is clearly emerging as a distinct field and discipline in renal physiology and pathophysiology that has the potential to develop new drug treatments. In this e-book, we bring together a spectrum of excellent papers by leading experts in the field which present and discuss the latest developments and state-of-the-art technologies.Last but not least, we thank all the authors for contributing their valuable work and the Frontiers in Physiology Editorial Office for bringing out this e-book.

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