The Experts below are selected from a list of 234 Experts worldwide ranked by ideXlab platform
Irina Kareva - One of the best experts on this subject based on the ideXlab platform.
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Normal Wound Healing and Tumor Angiogenesis as a Game of Competitive Inhibition
PLOS ONE, 2016Co-Authors: Irina Kareva, Abdo Abou-slaybi, Oliver Dodd, Olga Dashevsky, Giannoula KlementAbstract:Both normal wound healing and tumor angiogenesis are mitigated by the sequential, carefully orchestrated release of growth stimulators and inhibitors. These regulators are released from platelet clots formed at the sites of activated endothelium in a temporally and spatially controlled manner, and the order of their release depends on their affinity to glycosaminoglycans (GAG) such as heparan sulfate (HS) within the extracellular matrix, and platelet open canallicular system. The formation of vessel sprouts, triggered by angiogenesis regulating factors with lowest affinities for heparan sulfate (e.g. VEGF), is followed by vessel-stabilizing PDGF-B or bFGF with medium affinity for HS, and by inhibitors such as PF-4 and TSP-1 with the highest affinities for HS. The invasive wound-like edge of growing tumors has an overabundance of angiogenesis stimulators, and we propose that their abundance out-competes angiogenesis inhibitors, effectively preventing Inhibition of angiogenesis and vessel maturation. We evaluate this hypothesis using an experimentally motivated agent-based model, and propose a general theoretical framework for understanding mechanistic similarities and differences between the processes of normal wound healing and pathological angiogenesis from the point of view of Competitive Inhibition.
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Normal wound healing and tumor angiogenesis as a game of Competitive Inhibition
2014Co-Authors: Irina KarevaAbstract:The process of normal wound healing and the process of tumor angiogenesis share a number of common characteristics, which has led to tumors being referred to as “wounds that do not heal”. Both processes are mitigated by growth factors, which are sequentially released from platelets at the wound site in an order that depends on their affinity to glycosaminoglycans within the extracellular matrix. Growth factors with lowest affinities (e.g. VEGF) commence formation of new blood vessels, followed by vessel-stabilizing cytokines with medium affinity (e.g. PDGF and bFGF), and followed by release of angiogenesis inhibitors with highest affinities (e.g. PF-4 and TSP-1). We propose that continual release of stimulators and stabilizers that often accompanies tumor growth prevents termination of the wound healing process through Competitive Inhibition. That is, cytokines with lower affinities out-compete inhibitors for binding sites on cells’ surface (as they will be released first from the platelet), effectively preventing vessel pruning. This hypothesis is evaluated using an experimentally validated agent-based model, and the results provide a mechanistic explanation for the differences between normal wound healing and pathological angiogenesis, as well as the angiogenesis occurring in dormant and actively growing tumors.
Sudha Chakrapani - One of the best experts on this subject based on the ideXlab platform.
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high resolution structures of multiple 5 ht3ar setron complexes reveal a novel mechanism of Competitive Inhibition
eLife, 2020Co-Authors: Sandip Basak, Arvind Kumar, Steven Ramsey, Eric Gibbs, Abhijeet Kapoor, Marta Filizola, Sudha ChakrapaniAbstract:Serotonin receptors (5-HT3AR) play a crucial role in regulating gut movement, and are the principal target of setrons, a class of high-affinity Competitive antagonists, used in the management of nausea and vomiting associated with radiation and chemotherapies. Structural insights into setron-binding poses and their inhibitory mechanisms are just beginning to emerge. Here, we present high-resolution cryo-EM structures of full-length 5-HT3AR in complex with palonosetron, ondansetron, and alosetron. Molecular dynamic simulations of these structures embedded in a fully-hydrated lipid environment assessed the stability of ligand-binding poses and drug-target interactions over time. Together with simulation results of apo- and serotonin-bound 5-HT3AR, the study reveals a distinct interaction fingerprint between the various setrons and binding-pocket residues that may underlie their diverse affinities. In addition, varying degrees of conformational change in the setron-5-HT3AR structures, throughout the channel and particularly along the channel activation pathway, suggests a novel mechanism of Competitive Inhibition.
Craig S. Criddle - One of the best experts on this subject based on the ideXlab platform.
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Kinetics of Competitive Inhibition and cometabolism in the biodegradation of benzene, toluene, and p‐xylene by two Pseudomonas isolates.
Biotechnology and Bioengineering, 1993Co-Authors: Myung-keun Chang, Thomas C. Voice, Craig S. CriddleAbstract:Two Pseudomonas species (designated strains B1 and X1) were isolated from an aerobic pilot-scale fluidized bed reactor treating groundwater containing benzene, toluene, and p-xylene (BTX). Strain B1 grew with benzene and toluene as the sole sources of carbon and energy, and it cometabolized p-xylene in the presence of toluene. Strain X1 grew on toluene and p-xylene, but not benzene. In single substrate experiments, the appearance of biomass lagged the consumption of growth substrates, suggesting that substrate uptake may not be growth-rate limiting for these substrates. Batch tests using paired substrates (BT, TX, or BX) revealed Competitive Inhibition and cometabolic degradation patterns. Competitive Inhibition was modeled by adding a Competitive Inhibition term to the Monod expression. Cometabolic transformation of nongrowth substrate (p-xylene) by strain B1 was quantified by coupling xylene transformation to consumption of growth substrate (toluene) during growth and to loss of biomass during the decay phase. Coupling was achieved by defining two transformation capacity terms for the cometabolizing culture: one that relates consumption of growth substrate to the consumption of nongrowth substrate, and second that relates consumption of biomass to the consumption of nongrowth substrate. Cometabolism increased decay rates, and the observed yield for strain B1 decreased in the presence of p-xylene. © 1993 Wiley & Sons, Inc.
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kinetics of Competitive Inhibition and cometabolism in the biodegradation of benzene toluene and p xylene by two pseudomonas isolates
Biotechnology and Bioengineering, 1993Co-Authors: Myung-keun Chang, Thomas C. Voice, Craig S. CriddleAbstract:Two Pseudomonas species (designated strains B1 and X1) were isolated from an aerobic pilot-scale fluidized bed reactor treating groundwater containing benzene, toluene, and p-xylene (BTX). Strain B1 grew with benzene and toluene as the sole sources of carbon and energy, and it cometabolized p-xylene in the presence of toluene. Strain X1 grew on toluene and p-xylene, but not benzene. In single substrate experiments, the appearance of biomass lagged the consumption of growth substrates, suggesting that substrate uptake may not be growth-rate limiting for these substrates. Batch tests using paired substrates (BT, TX, or BX) revealed Competitive Inhibition and cometabolic degradation patterns. Competitive Inhibition was modeled by adding a Competitive Inhibition term to the Monod expression. Cometabolic transformation of nongrowth substrate (p-xylene) by strain B1 was quantified by coupling xylene transformation to consumption of growth substrate (toluene) during growth and to loss of biomass during the decay phase. Coupling was achieved by defining two transformation capacity terms for the cometabolizing culture: one that relates consumption of growth substrate to the consumption of nongrowth substrate, and second that relates consumption of biomass to the consumption of nongrowth substrate. Cometabolism increased decay rates, and the observed yield for strain B1 decreased in the presence of p-xylene. © 1993 Wiley & Sons, Inc.
Laurent Billon - One of the best experts on this subject based on the ideXlab platform.
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Determination of the rate constants of recombination of macroradicals and stable radicals via the Competitive-Inhibition method
Polymer Science Series B, 2013Co-Authors: O. V. Borisova, M. Yu. Zaremskii, Vladimir B. Golubev, A. V. Plutalova, Oleg V. Borisov, Laurent BillonAbstract:The rate constants of recombination, k X, of propagating radicals with nitroxides in pseudoliving radical polymerization are determined via the Competitive-Inhibition method with the use of ESR spectroscopy. This method is applicable to determination of k X in the reactions of propagating radicals of styrene, acrylic acid, and methyl methacrylate with two stable radicals, the nitroxide diethylphosphono-2,2-dimethylpropyl nitroxide and the phenoxide galvinoxyl. The values of k X determined at 50°C increase in the following sequence: diethylphosphono-2,2-dimethylpropyl nitroxide-TEMPO-galvinoxyl. The selectivity of the low-activity propagating radicals of styrene in reactions with stable radicals is shown.
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Determination of the rate constants of recombination of macroradicals and stable radicals via the Competitive-Inhibition method
Polymer Science Series B, 2013Co-Authors: O. V. Borisova, M. Yu. Zaremskii, Vladimir B. Golubev, A. V. Plutalova, Oleg V. Borisov, Laurent BillonAbstract:cited By 2International audienceThe rate constants of recombination, k X, of propagating radicals with nitroxides in pseudoliving radical polymerization are determined via the Competitive-Inhibition method with the use of ESR spectroscopy. This method is applicable to determination of k X in the reactions of propagating radicals of styrene, acrylic acid, and methyl methacrylate with two stable radicals, the nitroxide diethylphosphono-2,2-dimethylpropyl nitroxide and the phenoxide galvinoxyl. The values of k X determined at 50 C increase in the following sequence: diethylphosphono-2,2-dimethylpropyl nitroxide-TEMPO-galvinoxyl. The selectivity of the low-activity propagating radicals of styrene in reactions with stable radicals is shown. © 2013 Pleiades Publishing, Ltd
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Determination of the rate constants of recombination of macroradicals and stable radicals via the Competitive-Inhibition method
Polymer Science - Series B, 2013Co-Authors: O. V. Borisova, M. Yu. Zaremskii, Vladimir B. Golubev, A. V. Plutalova, Oleg V. Borisov, Laurent BillonAbstract:The rate constants of recombination, k X, of propagating radicals with nitroxides in pseudoliving radical polymerization are determined via the Competitive-Inhibition method with the use of ESR spectroscopy. This method is applicable to determination of k X in the reactions of propagating radicals of styrene, acrylic acid, and methyl methacrylate with two stable radicals, the nitroxide diethylphosphono-2,2-dimethylpropyl nitroxide and the phenoxide galvinoxyl. The values of k X determined at 50 C increase in the following sequence: diethylphosphono-2,2-dimethylpropyl nitroxide-TEMPO-galvinoxyl. The selectivity of the low-activity propagating radicals of styrene in reactions with stable radicals is shown. © 2013 Pleiades Publishing, Ltd.
Sandip Basak - One of the best experts on this subject based on the ideXlab platform.
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high resolution structures of multiple 5 ht3ar setron complexes reveal a novel mechanism of Competitive Inhibition
eLife, 2020Co-Authors: Sandip Basak, Arvind Kumar, Steven Ramsey, Eric Gibbs, Abhijeet Kapoor, Marta Filizola, Sudha ChakrapaniAbstract:Serotonin receptors (5-HT3AR) play a crucial role in regulating gut movement, and are the principal target of setrons, a class of high-affinity Competitive antagonists, used in the management of nausea and vomiting associated with radiation and chemotherapies. Structural insights into setron-binding poses and their inhibitory mechanisms are just beginning to emerge. Here, we present high-resolution cryo-EM structures of full-length 5-HT3AR in complex with palonosetron, ondansetron, and alosetron. Molecular dynamic simulations of these structures embedded in a fully-hydrated lipid environment assessed the stability of ligand-binding poses and drug-target interactions over time. Together with simulation results of apo- and serotonin-bound 5-HT3AR, the study reveals a distinct interaction fingerprint between the various setrons and binding-pocket residues that may underlie their diverse affinities. In addition, varying degrees of conformational change in the setron-5-HT3AR structures, throughout the channel and particularly along the channel activation pathway, suggests a novel mechanism of Competitive Inhibition.
