Download or read book Functional and Mechanistic Characterization of Bacterial Nitric Oxide Signaling Pathways written by Minxi Rao and published by . This book was released on 2016 with total page 96 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nitric oxide (NO) is a well-established signaling molecule and cytotoxic agent in mammals. NO is synthesized by nitric oxide synthase (NOS) by macrophages at high concentrations as a key part of the host immune response, and at low concentrations in endothelial and neuronal cells as a signaling agent. In endothelial cells, the primary NO receptor is soluble guanylate cyclase (sGC), which contains a heme-nitric oxide/oxygen binding domain (H-NOX). Selective binding of NO to the H-NOX domain is responsible for activation of sGC. Thus, the mammalian NO signaling system involves NO synthesis by NOS, and NO sensing by the H-NOX domain of sGC. NOS and H-NOX proteins have also been identified in a number of bacterial species, including pathogens. Putative roles for bacterial NOS proteins include protection against oxidative stress and antibiotics, while bacterial H-NOX proteins have been shown to govern processes such as biofilm formation and bioluminescence via interactions with signaling proteins such as diguanylate cyclases (DGC) or histidine kinases (HK). Here, various aspects of NO signaling from three different organisms are characterized: the marine alphaproteobacterium Silicibacter sp. TrichCH4B; the soil-dwelling gammaproteobacterium Shewanella oneidensis, and the marine cyanobacterium Synechococcus sp. PCC 7335. This work and other recent studies seek to understand not only the diverse roles for NO in bacteria, but also the molecular mechanisms of bacterial NO signaling. Silicibacter sp. TrichCH4B is the first bacterial organism discovered to contain both an NOS and H-NOX, thus capable of both NO synthesis and sensing, analogous to mammalian systems. The H-NOX protein from Silicibacter is found in an operon adjacent to an HK, forming part of a two-component phospho-relay signaling network. The response regulator of the network was identified to be a diguanylate cyclase (DGC), which is inactivated upon phosphorylation and establishes the link between NO and intracellular cyclic-di-GMP levels, and consequently biofilm formation. It was also determined that Silicibacter NOS activity is stimulated by a signaling protein from an algal symbiont, Trichodesmium erythraeum, which is a major marine nitrogen fixer. Thus, in the presence of Trichodesmium, the increase in NOS activity results in Silicibacter biofilm formation and poising the two species for nutrient exchange, revealing a novel role for NO in interspecies communication and symbiosis. Given the diverse processes governed by NO/H-NOX signaling, it is crucial to understand the molecular mechanism by which H-NOX regulates HK autophosphorylation activity, the most common outcome of a NO-bound H-NOX. Here, the interaction and signal transduction between the H-NOX-HK signaling pair from Shewanella oneidensis are characterized. Binding kinetics measurements and analytical gel filtration revealed that NO-bound H-NOX has a tighter affinity for the HK, compared with H-NOX in the unliganded state, correlating binding affinity with kinase inhibition. Kinase activity assays with a panel of binding-deficient H-NOX mutants further reveal that while formation of the H-NOX-HK protein complex is required to stabilize the HK, H-NOX conformational changes upon NO binding are necessary for HK inhibition. Characterization of H-NOX proteins has led to an increased understanding of bacterial NO sensing. However, NO production in bacteria is less well-understood, and here the NOS protein from Synechococcus sp. PCC 7335 is characterized. Mammalian NOS proteins are comprised of a P450-like heme/oxidase domain responsible for catalysis, and a reductase domain responsible for electron transfer. While most bacterial NOS proteins discovered to date contain only the heme/oxidase domain, Synechococcus NOS contains both the oxidase and reductase domains, and additionally contains a predicted globin domain resembling bacterial flavohemoglobins. Spectroscopic and biochemical characterization of the globin indicated a possible role in redox communication in this novel class of bacterial NOS enzymes.

Download or read book Functional and Mechanistic Characterization of Bacterial H NOX Nitric Oxide Signaling Systems written by Lars Plate and published by . This book was released on 2013 with total page 141 pages. Available in PDF, EPUB and Kindle. Book excerpt: The gaseous free radical nitric oxide (NO) is firmly established as a unique signaling agent in nature. Eukaryotes employ this freely diffusible molecule in low transient concentrations as a cardiovascular signaling agent and neurotransmitter. Macrophages produce higher, cytotoxic concentrations of NO to serve as an integral piece of the host-defense against pathogens. NO signaling in vertebrates is well characterized and involves the Heme-Nitric oxide/Oxygen binding (H-NOX) domain of soluble guanylate cyclase (sGC) as a selective NO sensor. H-NOX domains are also present in many bacteria including a number of pathogens. Bacterial H-NOX proteins are often found in the same operon as signaling proteins such as histidine kinases, suggesting a role for H-NOX proteins as sensors in prokaryotic NO signaling pathways. H-NOX-dependent control of histidine kinase autophosphorylation has been demonstrated, but little was known about the biological role or output of H-NOX two-component signaling pathways in bacteria. Here, molecular details of a bacterial H-NOX signaling network in Shewanella oneidensis are presented. NO regulates biofilm formation by controlling the levels of the bacterial secondary messenger cyclic diguanosine monophosphate (cyclic-di-GMP) through an unusually complex multi-component signaling network. Homologous pathways exist in the pathogen Vibrio cholerae and in additional gammaproteobacteria. This work and other recent studies highlight a more general role for NO in restructuring bacterial communal behavior, influencing motility and biofilm formation, host-symbiont interactions, and quorum sensing. The connectivity of the signaling network in S. oneidensis was mapped by phosphotransfer profiling, which demonstrated signal integration from two histidine kinases and branching to three response regulators: HnoB, HnoC, and HnoD. Phosphodiesterase assays showed that a feed-forward loop between HnoB and HnoD response regulators with phosphodiesterase domains and phosphorylation-mediated activation intricately regulated c-di-GMP levels. In vivo phenotypic characterization established a direct link between NO signaling and increased biofilm formation. Cellular adhesion in biofilms may provide a general protection mechanism for bacteria against high concentrations of reactive and damaging NO. HnoC functions as transcription factor controlling expression of the signaling components in the network. Mechanistic studies of HnoC revealed an unprecedented regulation mechanism, involving phosphorylation-induced dissociation of the response regulator tetramer. The transcriptional feedback loop created by HnoC further regulates the dynamics of the H-NOX signaling network in response to NO stimuli. One of the phosphotransfer targets of the H-NOX-associated histidine kinase in the signaling network in S. oneidensis and V. cholerae contains a HD-GYP domain: a predicted but poorly characterized phosphodiesterase domain for cyclic-di-GMP hydrolysis. The HnoD HD-GYP domains contain degenerate residues that cause them to be catalytically inactive. To understand the functional consequence of the degeneracy and to gain general insights on the catalytic mechanism of HD-GYP domains, two catalytically active HD-GYP enzymes were characterized. The enzymes contained a binuclear iron center, and reconstitution experiments demonstrated that a heterovalent Fe(III)-Fe(II) cluster is likely required for catalysis. The absence of the metal-coordination site in HnoD eliminates any phosphodiesterase activity. The prevalence of orphan H-NOX/histidine kinase pairs highlights the necessity for improved methods to map connectivities in two-component signaling. The identity of cognate response regulator(s) is needed to define the biological function of the signaling system. Analogous to approaches in eukaryotic kinases, protein engineering was applied to histidine kinases to permit the use of unnatural ATP analogs as substrates, which are unreactive with other enzymes. Analog-sensitive alleles of two model histidine kinases were developed, and the phosphotransfer transfer reactions to their respective response regulators were optimized. Additionally, a panel of kinase inhibitors was screened for specificity against the analog-sensitive alleles. The analog-sensitive histidine kinases could become useful for in situ identification of phosphotransfer partners of orphan histidine kinases.

Download or read book Enteric Glia written by Brian D. Gulbransen and published by Biota Publishing. This book was released on 2014-07-01 with total page 72 pages. Available in PDF, EPUB and Kindle. Book excerpt: The enteric nervous system (ENS) is a complex neural network embedded in the gut wall that orchestrates the reflex behaviors of the intestine. The ENS is often referred to as the “little brain” in the gut because the ENS is more similar in size, complexity and autonomy to the central nervous system (CNS) than other components of the autonomic nervous system. Like the brain, the ENS is composed of neurons that are surrounded by glial cells. Enteric glia are a unique type of peripheral glia that are similar to astrocytes of the CNS. Yet enteric glial cells also differ from astrocytes in many important ways. The roles of enteric glial cell populations in the gut are beginning to come to light and recent evidence implicates enteric glia in almost every aspect of gastrointestinal physiology and pathophysiology. However, elucidating the exact mechanisms by which enteric glia influence gastrointestinal physiology and identifying how those roles are altered during gastrointestinal pathophysiology remain areas of intense research. The purpose of this e-book is to provide an introduction to enteric glial cells and to act as a resource for ongoing studies on this fascinating population of glia. Table of Contents: Introduction / A Historical Perspective on Enteric Glia / Enteric Glia: The Astroglia of the Gut / Molecular Composition of Enteric Glia / Development of Enteric Glia / Functional Roles of Enteric Glia / Enteric Glia and Disease Processes in the Gut / Concluding Remarks / References / Author Biography

Download or read book How Tobacco Smoke Causes Disease written by United States. Public Health Service. Office of the Surgeon General and published by . This book was released on 2010 with total page 728 pages. Available in PDF, EPUB and Kindle. Book excerpt: This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.

Download or read book Nitric Oxide Protocols written by Aviv Hassid and published by Humana. This book was released on 2004-06-11 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: A collection of cutting-edge techniques for measuring nitric oxide and the enzyme that produces it in biological tissues and fluids. These readily reproducible methods can be used to measure novel nitric oxide-related products such as protein nitration and nitrosation, as well as to express nitric oxide synthase in basic research and gene therapy using viral vectors.

Download or read book M1 M2 Macrophages The Arginine Fork in the Road to Health and Disease written by Charles Dudley Mills and published by Frontiers Media SA. This book was released on 2015-03-23 with total page 281 pages. Available in PDF, EPUB and Kindle. Book excerpt: Macrophages have unique and diverse functions necessary for survival. And, in humans (and other species), they are the most abundant leukocytes in tissues. The Innate functions of macrophages that are best known are their unusual ability to either “Kill” or “Repair”. Since killing is a destructive process and repair is a constructive process, it was stupefying how one cell could exhibit these 2 polar – opposite functions. However, in the late 1980’s, it was shown that macrophages have a unique ability to enzymatically metabolize Arginine to Nitric Oxide (NO, a gaseous non – specific killer molecule) or to Ornithine (a precursor of polyamines and collagen for repair). The dual Arginine metabolic capacity of macrophages provided a functional explanation for their ability to kill or repair. Macrophages predominantly producing NO are called M1 and those producing Ornithine are called M2. M1 and M2 – dominant responses occur in lower vertebrates, and in T cell deficient vertebrates being directly driven by Damage and Pathogen Associated Molecular Patterns (DAMP and PAMP). Thus, M1 and M2 are Innate responses that protect the host without Adaptive Immunity. In turn, M1/M2 is supplanting previous models in which T cells were necessary to “activate” or “alternatively activate” macrophages (the Th1/Th2 paradigm). M1 and M2 macrophages were named such because of the additional key findings that these macrophages stimulate Th1 and Th2 – like responses, respectively. So, in addition to their unique ability to kill or repair, macrophages also govern Adaptive Immunity. All of the foregoing would be less important if M1 or M2 – dominant responses were not observed in disease. But, they are. The best example to date is the predominance of M2 macrophages in human tumors where they act like wound repair macrophages and actively promote growth. More generally, humans have become M2 – dominant because sanitation, antibiotics and vaccines have lessened M1 responses. And, M2 dominance seems the cause of ever - increasing allergies in developed countries. Obesity represents a new and different circumstance. Surfeit energy (e.g., lipoproteins) causes monocytes to become M1 dominant in the vessel walls causing plaques. Because M1 or M2 dominant responses are clearly causative in many modern diseases, there is great potential in developing the means to selectively stimulate (or inhibit) either M1 or M2 responses to kill or repair, or to stimulate Th1 or Th2 responses, depending on the circumstance. The contributions here are meant to describe diseases of M1 or M2 dominance, and promising new methodologies to modulate the fungible metabolic machinery of macrophages for better health.

Download or read book cGMP Generators Effectors and Therapeutic Implications written by Harald H. H. W. Schmidt and published by Springer Science & Business Media. This book was released on 2008-12-17 with total page 581 pages. Available in PDF, EPUB and Kindle. Book excerpt: After the discovery of endogenous NO formation in the late '80s and the 1998 Nobel Prize in Physiology or Medicine, many researchers and physicians again became interested in the NO/sGC interaction and cGMP-dependent signaling. This book is an enthusiastic celebration of cyclic guanosine monophosphate (cGMP) and amply illustrates the importance of this field of science to patients and the way in which the field has evolved. It is exclusively devoted to this exciting and important signaling molecule, addressing all recent advances in understanding guanylate cyclase regulation, NO/sGC interactions, cGMP effector mechanisms and their pathophysiological and pharmacological implications. Particular attention will also be given to clinical applications of the novel cGMP-elevating drugs which are on the horizon, thus spanning the continuum from basic science to clinic.

Download or read book Endotoxin in Health and Disease written by Helmut Brade and published by CRC Press. This book was released on 2020-10-28 with total page 968 pages. Available in PDF, EPUB and Kindle. Book excerpt: Offering a basis for further research into the interactions of hosts and pathogens, this work gathers up-to-date findings, and details basic structures, functions and immunology. It provides descriptions of a variety of experimental endotoxin neutralizing agents, as well as a guide to clinical research initiatives and the latest treatments.

Download or read book Bacterial Wilt Disease written by Philippe Prior and published by Springer Science & Business Media. This book was released on 2013-06-29 with total page 451 pages. Available in PDF, EPUB and Kindle. Book excerpt: Jointly published with INRA, Paris. Bacterial wilt, caused by Ralstonia solanacearum, is a very destructive plant disease that attacks over 450 different species, including many of the most important economic crop plants. Often endemic, the bacterium transmits through the soil, penetrates the plant root system and eventually causes irreversible wilting and death. This book summarizes the current information on bacterial wilt for both the basic research community and for concerned professionals who are faced with the disease in the field, offering the latest approaches to diagnosis and control of the disease. Emphasis is placed on integrated and biologically sustainable control methods. Also presented is the most recent genetic/biochemical research exploring the interaction between the bacterium and its plant host at the molecular level.

Download or read book Nitric Oxide Sensing written by Sagarika Bhattacharya and published by CRC Press. This book was released on 2021-09-16 with total page 117 pages. Available in PDF, EPUB and Kindle. Book excerpt: Although nitric oxide (NO) is an important biological signaling molecule, its free-radical electronic configuration makes it a most reactive molecule and the scariest colorless gas causing immense environmental and health hazards. Detection of NO levels in biological samples and in the atmosphere is therefore crucial. In the past few years, extensive efforts have been devoted to developing many active sensors and effective devices for detecting and quantifying atmospheric NO, NO generated in biological samples, and NO exhaled in the human breath. This book provides a concrete summary of recent state-of-the-art small-molecule probes and novel carbon nanomaterials used for chemical, photoluminescent, and electrochemical NO detection. One chapter is especially dedicated to the available devices used for detecting NO in the human breath that indirectly infers to lung inflammation. The authors with expertise in diverse dimensions have attempted to cover almost all areas of NO sensing.

Download or read book Critical Needs and Gaps in Understanding Prevention Amelioration and Resolution of Lyme and Other Tick Borne Diseases written by Institute of Medicine and published by National Academies Press. This book was released on 2011-07-01 with total page 560 pages. Available in PDF, EPUB and Kindle. Book excerpt: A single tick bite can have debilitating consequences. Lyme disease is the most common disease carried by ticks in the United States, and the number of those afflicted is growing steadily. If left untreated, the diseases carried by ticks-known as tick-borne diseases-can cause severe pain, fatigue, neurological problems, and other serious health problems. The Institute of Medicine held a workshop October 11-12, 2010, to examine the state of the science in Lyme disease and other tick-borne diseases.

Download or read book Methods in Nitric Oxide Research written by Martin Feelisch and published by . This book was released on 1996-06-04 with total page 746 pages. Available in PDF, EPUB and Kindle. Book excerpt: This handbook describes methods for the measurement and investigation of nitric oxide. The topics discussed include the metabolism of substrates and cofactors, the detection of nitrogen oxides, the detection of nitrogen oxide synthase activity, and the detection of adducts and reaction products.

Download or read book Preterm Birth written by Institute of Medicine and published by National Academies Press. This book was released on 2007-05-23 with total page 791 pages. Available in PDF, EPUB and Kindle. Book excerpt: The increasing prevalence of preterm birth in the United States is a complex public health problem that requires multifaceted solutions. Preterm birth is a cluster of problems with a set of overlapping factors of influence. Its causes may include individual-level behavioral and psychosocial factors, sociodemographic and neighborhood characteristics, environmental exposure, medical conditions, infertility treatments, and biological factors. Many of these factors co-occur, particularly in those who are socioeconomically disadvantaged or who are members of racial and ethnic minority groups. While advances in perinatal and neonatal care have improved survival for preterm infants, those infants who do survive have a greater risk than infants born at term for developmental disabilities, health problems, and poor growth. The birth of a preterm infant can also bring considerable emotional and economic costs to families and have implications for public-sector services, such as health insurance, educational, and other social support systems. Preterm Birth assesses the problem with respect to both its causes and outcomes. This book addresses the need for research involving clinical, basic, behavioral, and social science disciplines. By defining and addressing the health and economic consequences of premature birth, this book will be of particular interest to health care professionals, public health officials, policy makers, professional associations and clinical, basic, behavioral, and social science researchers.

Download or read book Vanadium Catalysis written by Manas Sutradhar and published by Royal Society of Chemistry. This book was released on 2020-11-05 with total page 526 pages. Available in PDF, EPUB and Kindle. Book excerpt: Vanadium is one of the more abundant elements in the Earth’s crust and exhibits a wide range of oxidation states in its compounds making it potentially a more sustainable and more economical choice as a catalyst than the noble metals. A wide variety of reactions have been found to be catalysed by homogeneous, supported and heterogeneous vanadium complexes and the number of applications is growing fast. Bringing together the research on the catalytic uses of this element into one essential resource, including theoretical perspectives on proposed mechanisms for vanadium catalysis and an overview of its relevance in biological processes, this book is a useful reference for industrial and academic chemists alike.

Download or read book The Perfect Slime written by Hans-Curt Flemming and published by IWA Publishing. This book was released on 2016-09-15 with total page 336 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Perfect Slime presents the latest state of knowledge and all aspects of the Extracellular Polymeric Substances, (EPS) matrix – from the ecological and health to the antifouling perspectives. The book brings together all the current material in order to expand our understanding of the functions, properties and characteristics of the matrix as well as the possibilities to strengthen or weaken it. The EPS matrix represents the immediate environment in which biofilm organisms live. From their point of view, this matrix has paramount advantages. It allows them to stay together for extended periods and form synergistic microconsortia, it retains extracellular enzymes and turns the matrix into an external digestion system and it is a universal recycling yard, it protects them against desiccation, it allows for intense communication and represents a huge genetic archive. They can remodel their matrix, break free and eventually, they can use it as a nutrient source. The EPS matrix can be considered as one of the emergent properties of biofilms and are a major reason for the success of this form of life. Nevertheless, they have been termed the “black matter of biofilms” for good reasons. First of all: the isolation methods define the results. In most cases, only water soluble EPS components are investigated; insoluble ones such as cellulose or amyloids are much less included. In particular in environmental biofilms with many species, it is difficult to impossible isolate, separate the various EPS molecules they are encased in and to define which species produced which EPS. The regulation and the factors which trigger or inhibit EPS production are still very poorly understood. Furthermore: bacteria are not the only microorganisms to produce EPS. Archaea, Fungi and algae can also form EPS. This book investigates the questions, What is their composition, function, dynamics and regulation? What do they all have in common?

Download or read book Metalloenzymes in Denitrification written by Isabel Moura and published by Royal Society of Chemistry. This book was released on 2016-11-15 with total page 468 pages. Available in PDF, EPUB and Kindle. Book excerpt: The reduction of nitrate to nitrogen by metalloenzymes is a vital step in the nitrogen cycle. The importance of this pathway has inspired efforts to understand in greater depth the mechanisms involved. This book presents and discusses the latest information on multiple aspects of denitrification. Written by recognized specialists in the field, this book describes the bioinorganic aspects and the key enzymes involved in denitrification, including their structure, function and mechanisms. Active site modelling, novel methodologies for monitoring denitrification in vivo and biotechnological methods for water treatment are discussed. The book also focusses on the environmental implications of denitrification, such nitrate accumulation and the release of nitrous oxide into the atmosphere from excessive fertiliser use. An important topic in many biological, environmental and agricultural contexts, this book will aid teaching and help bioinorganic chemists and biotechnologists gain an up-to-date picture of the science behind the denitrification process.

Download or read book Nitric Oxide and Inflammation written by Daniela Salvemini and published by Springer. This book was released on 2013-03-11 with total page 308 pages. Available in PDF, EPUB and Kindle. Book excerpt: Literally thousands of papers have been published on nitric oxide over the past ten years. But there is no single monograph available that has previously attempted to summarize the important features of the roles of nitric oxide in inflammation. The voluminous literature regarding the incredible range of chemical and biological effects of nitric oxide and reactive nitrogen oxide species, RNOS, may present a tangle of confusing information to the researcher. This volume brings together experts from nitric oxide and inflammation research and presents a concise up-to-date overview as well as future aspects of this rapidly growing field.