scholarly journals Considerations for improved performance of competition association assays analysed with the Motulsky–Mahan's “kinetics of competitive binding” model

2019 ◽  
Vol 176 (24) ◽  
pp. 4731-4744
Author(s):  
Victoria Georgi ◽  
Alexey Dubrovskiy ◽  
Stephan Steigele ◽  
Amaury E. Fernández‐Montalván
Keyword(s):  
Competitive Binding ◽  
Binding Model ◽  
Improved Performance ◽  
Kinetics Of

scholarly journals Distinct roles for dopamine clearance mechanisms in regulating behavioral flexibility

2021 ◽  
Author(s):  
Clio Korn ◽  
Thomas Akam ◽  
Kristian H. R. Jensen ◽  
Cristiana Vagnoni ◽  
Anna Huber ◽  
...  
Keyword(s):  
Decision Making ◽  
Behavioral Flexibility ◽  
Dopamine Neurons ◽  
Nucleus Accumbens Core ◽  
Comt Inhibition ◽  
Improved Performance ◽  
Dopamine Signaling ◽  
Precise Relationship ◽  
And Behavior ◽  
Kinetics Of

AbstractDopamine plays a crucial role in adaptive behavior, and dysfunctional dopamine is implicated in multiple psychiatric conditions characterized by inflexible or inconsistent choices. However, the precise relationship between dopamine and flexible decision making remains unclear. One reason is that, while many studies have focused on the activity of dopamine neurons, efficient dopamine signaling also relies on clearance mechanisms, notably the dopamine transporter (DAT), which predominates in striatum, and catechol-O-methyltransferase (COMT), which predominates in cortex. The exact locus, extent, and timescale of the effects of DAT and COMT are uncertain. Moreover, there is limited data on how acute disruption of either mechanism affects flexible decision making strategies mediated by cortico-striatal networks. To address these issues, we combined pharmacological modulation of DAT and COMT with electrochemistry and behavior in mice. DAT blockade, but not COMT inhibition, regulated sub-second dopamine release in the nucleus accumbens core, but surprisingly neither clearance mechanism affected evoked release in prelimbic cortex. This was not due to a lack of sensitivity, as both amphetamine and atomoxetine changed the kinetics of sub-second release. In a multi-step decision making task where mice had to respond to reversals in either reward probabilities or the choice sequence to reach the goal, DAT blockade selectively impaired, and COMT inhibition improved, performance after reward reversals, but neither manipulation affected the adaptation of choices after action-state transition reversals. Together, our data suggest that DAT and COMT shape specific aspects of behavioral flexibility by regulating different aspects of the kinetics of striatal and cortical dopamine, respectively.

scholarly journals Competitive binding predicts nonlinear responses of olfactory receptors to complex mixtures

2019 ◽  
Vol 116 (19) ◽  
pp. 9598-9603 ◽  
Author(s):  
Vijay Singh ◽  
Nicolle R. Murphy ◽  
Vijay Balasubramanian ◽  
Joel D. Mainland
Keyword(s):  
Olfactory Receptors ◽  
Competitive Binding ◽  
Complex Mixtures ◽  
Biophysical Model ◽  
Target Color ◽  
Receptor Binding Site ◽  
Binding Model ◽  
Vast Number ◽  
Nonlinear Responses ◽  
Odorant Molecule

In color vision, the quantitative rules for mixing lights to make a target color are well understood. By contrast, the rules for mixing odorants to make a target odor remain elusive. A solution to this problem in vision relied on characterizing receptor responses to different wavelengths of light and subsequently relating these responses to perception. In olfaction, experimentally measuring receptor responses to a representative set of complex mixtures is intractable due to the vast number of possibilities. To meet this challenge, we develop a biophysical model that predicts mammalian receptor responses to complex mixtures using responses to single odorants. The dominant nonlinearity in our model is competitive binding (CB): Only one odorant molecule can attach to a receptor binding site at a time. This simple framework predicts receptor responses to mixtures of up to 12 monomolecular odorants to within 15% of experimental observations and provides a powerful method for leveraging limited experimental data. Simple extensions of our model describe phenomena such as synergy, overshadowing, and inhibition. We demonstrate that the presence of such interactions can be identified via systematic deviations from the competitive-binding model.

scholarly journals EPR studies of intermolecular interactions and competitive binding of drugs in a drug–BSA binding model

2016 ◽  
Vol 18 (32) ◽  
pp. 22531-22539 ◽  
Author(s):  
Y. Akdogan ◽  
M. Emrullahoglu ◽  
D. Tatlidil ◽  
M. Ucuncu ◽  
G. Cakan-Akdogan
Keyword(s):  
Intermolecular Interactions ◽  
Epr Spectroscopy ◽  
Competitive Binding ◽  
Drug Binding ◽  
Promising Technique ◽  
Binding Model ◽  
Bsa Binding

EPR spectroscopy is a very promising technique to understand the details of drug binding and competitive drug binding to proteins.

scholarly journals A competitive binding model predicts nonlinear responses of olfactory receptors to complex mixtures

2018 ◽  
Author(s):  
Vijay Singh ◽  
Nicolle R. Murphy ◽  
Vijay Balasubramanian ◽  
Joel D. Mainland
Keyword(s):  
Olfactory Receptors ◽  
Competitive Binding ◽  
Complex Mixtures ◽  
Biophysical Model ◽  
Target Color ◽  
Receptor Binding Site ◽  
Binding Model ◽  
Vast Number ◽  
Nonlinear Responses ◽  
Odorant Molecule

In color vision, the quantitative rules for mixing lights to make a target color are well understood. By contrast, the rules for mixing odorants to make a target odor remain elusive. A solution to this problem in vision relied on characterizing receptor responses to different wavelengths of light and subsequently relating these responses to perception. In olfaction, experimentally measuring receptor responses to a representative set of complex mixtures is intractable due to the vast number of possibilities. To meet this challenge, we develop a biophysical model that predicts mammalian receptor responses to complex mixtures using responses to single odorants. The dominant nonlinearity in our model is competitive binding (CB): only one odorant molecule can attach to a receptor binding site at a time. This simple framework predicts receptor responses to mixtures of up to twelve monomolecular odorants to within 15% of experimental observations and provides a powerful method for leveraging limited experimental data. Simple extensions of our model describe phenomena such as synergy, overshadowing, and inhibition. We demonstrate that the presence of such interactions can be identified via systematic deviations from the competitive binding model.

Interaction of beta2-Glycoprotein I with Members of the Low Density Lipoprotein Receptor Family.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2646-2646
Author(s):  
Menno van Lummel ◽  
Maarten T.T. Pennings ◽  
Ronald H.W.M. Derksen ◽  
Erik Westein ◽  
Peter J. Lenting ◽  
...  
Keyword(s):  
Family Members ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Binding Kinetics ◽  
Binding Model ◽  
Glycoprotein I ◽  
Domain V ◽  
Kinetics Of ◽  
Site Binding ◽  
Receptor Family

Abstract The antiphospholipid syndrome (APS) is a non-inflammatory disease characterized by arterial and/or venous thrombosis and/or pregnancy morbidity in the presence of auto-antibodies that recognize beta2-glycoprotein I (beta2GPI) bound to cardiolipin. We have previously demonstrated that dimerization of beta2GPI by auto-antibodies induces platelet activation. This effect has been shown to be mediated by apoER2′. Here, we show that dimeric beta2GPI, and not plasma beta2GPI interacts with three different LDL-receptor family members; apolipoprotein E receptor 2′ (apoER2′), the low LDL-receptor related protein (LRP) and megalin. Interaction between dimeric beta2GPI and apoER2′ was best described with a one-site binding model (KD(app) 25 nM), whereas for LRP and megalin the interaction with dimeric beta2GPI was best described with a two-site binding model, representing a high- (3.1 nM) and a low-affinity site (192.1 and 241.2 nM, respectively). Binding kinetics of a dimeric beta2GPI mutant, that binds poorly to anionic phospholipids were similar to the binding kinetics of full length dimeric beta2GPI for all three LDL-receptor family members. Upon deletion of domain I or domain II of dimeric beta2GPI no changes in the binding kinetics were observed. Deletion of domain V however, significantly decreased the affinity for apoER2′, LRP and megalin. In conclusion, our data show that dimeric beta2GPI can interact with different LDL-receptor family members. This interaction is dependent on a recognition site in domain V of beta2GPI, which does not overlap with the phospholipid-binding site.

scholarly journals Cytokine Kinetics in Febrile Neutropenic Children: Insights on the Usefulness as Sepsis Biomarkers, Influence of Filgrastim, and Behavior of the IL-23/IL-17 Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Orlei Ribeiro de Araujo ◽  
Reinaldo Salomão ◽  
Milena Karina Coló Brunialti ◽  
Dafne Cardoso Bourguignon da Silva ◽  
Andreza Almeida Senerchia ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Mixed Models ◽  
Inflammatory Responses ◽  
Assessment Model ◽  
Risk Assessment Model ◽  
Gm Csf ◽  
Early Biomarkers ◽  
Improved Performance ◽  
And Behavior ◽  
Kinetics Of

Background.The study aimed to describe the kinetics of various cytokines from day 1 to day 14 of the onset of fever in neutropenic children and to evaluate their performances as discriminators of sepsis in the first 24 hours of fever, the possible influence of filgrastim, and the functioning of the IL-23/IL-17 axis.Methods.IL-1β, TNF-α, IL-10, IL-12/23p40, IL-21, IL-6, IL-8, IL-17, G-CSF, and GM-CSF were measured in plasma on days 1, 2, 3, 5, and 14 from the onset of fever in 35 patients.Results.Thirteen patients (37.1%) developed sepsis. In mixed models, IL-6, IL-8, IL-10, and G-CSF showed higher estimated means in septic patients (P<0.005), and IL-12/23p40 and IL-17 in nonseptic patients (P<0.05). On day 1, IL-6, IL-8, and IL-10 appeared upregulated in patients who received filgrastim. Only IL-6, IL-8, IL-10, and procalcitonin were useful as discriminators of sepsis. Associating the markers with each other or to a risk assessment model improved performance.Conclusions.Cytokines kinetics showed proinflammatory and anti-inflammatory responses similar to what is described in nonneutropenic patients. IL-8, IL-6, IL-10, and procalcitonin are useful as early biomarkers of sepsis. Filgrastim upregulates expression of these markers, and we observed deficiency in the IL-23-IL-17 axis accompanying sepsis.

Kinetics of Competitive Binding with Application to Thrombin Complexes

1997 ◽  
Vol 252 (2) ◽  
pp. 326
Author(s):  
William J. Wedemeyer ◽  
Robert W. Ashton ◽  
Harold A. Scheraga
Keyword(s):  
Competitive Binding ◽  
Kinetics Of
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