Dose-Response Analysis Using R

Ritz, Christian; Jensen, Signe Marie; Gerhard, Daniel; Streibig, J. C.

doi:10.1201/b21966

Cited by 116 publications

(127 citation statements)

References 28 publications

Supporting

Mentioning

126

Contrasting

Order By: Relevance

“…The half maximal (50%) inhibitory concentration IC 50 of the selected compounds was calculated by measuring the activity as described before for at least ten data points in the concentration range of 0 μM to 200 μM of the inhibitory compound in at least triplicates. A four-parameter log-logistic dose-response curve was then globally fitted to the individual replicates using the R software collection [27] and the R package “drc” [28] as proposed by assessment of Akaike’s information criterion (AIC) [29, 30]. PPDK was incubated for 10 min with the inhibitors before each measurement.…”

Section: Methodsmentioning

confidence: 99%

Small-molecule inhibition of pyruvate phosphate dikinase targeting the nucleotide binding site

Minges

Groth

2017

PLoS ONE

View full text Add to dashboard Cite

Pyruvate phosphate dikinase (PPDK) is an essential enzyme of C4 photosynthesis in plants, catalyzing the ATP-driven conversion of pyruvate to phosphoenolpyruvate (PEP). It is further used by some bacteria and unicellular protists in the reverse, ATP-forming direction. Many weed species use C4 photosynthesis in contrast to world’s major crops, which are C3 plants. Hence inhibitors of PPDK may be used as C4-specific herbicides. By screening a library of 80 commercially available kinase inhibitors, we identified compounds derived from bisindolylmaleimide (bisindolylmaleimide IV, IC50 = 0.76 ± 0.13 μM) and indirubin (indirubin-3’-monoxime, IC50 = 4.2 ± 0.9 μM) that showed high inhibitory potency towards PPDK and are among the most effective PPDK inhibitors described today. Physiological studies on leaf tissues of a C4 model plant confirmed in vivo inhibition of C4-driven photosynthesis by these substances. Moreover, comparative docking studies of non-inhibitory bisindolylmaleimide derivatives suggest that the selectivity towards PPDK may be increased by addition of functional groups to the core structure.

show abstract

Section: Methodsmentioning

confidence: 99%

Small-molecule inhibition of pyruvate phosphate dikinase targeting the nucleotide binding site

Minges

Groth

2017

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Liess et al, 2016) given that typically at least two parameters are F I G U R E 3 Guidelines for the selection of a null model for prediction of joint stressor effects on individuals (or populations, but see end of section 3 for caveats). SMOA, stressor mode of action (see glossary); CS, correlation of sensitivities; SE, stressoreffect relationship; ET, effect type; ES, effect size estimated (slope and intercept in a linear model or steepness and inflection point in the most parsimonious log-logistic model, which is sigmoidal; for details, see Ritz, Baty, Streibig, & Gerhard, 2016). Stressor sensitivity correlations for simple addition, dominance and multiplicative null model conceptualized under the perspective of sequential stressor action (cf.…”

Section: Issues Of Study De Sign and Cross-stud Y Variabilitymentioning

confidence: 99%

Advancing understanding and prediction in multiple stressor research through a mechanistic basis for null models

Schäfer

Piggott

2018

Global Change Biology

158

210

View full text Add to dashboard Cite

Global environmental change is driven by multiple anthropogenic stressors. Conservation and restoration require understanding the individual and joint action of these stressors to evaluate and prioritize management measures. To date, most studies on multiple stressor effects have sought to identify potential stressor interactions, defined as deviations from null models, and related meta-analyses have focused on quantifying the relative proportion of stressor interactions across studies. These studies have provided valuable insights about the complexity of multiple stressor effects, but remain largely devoid of a theoretical framework for null model selection and prediction of effects. We suggest that multiple stressor research would benefit by (1) integrating and developing additional null models and (2) selecting null models based on their mechanistic assumptions of the stressor mode of action and organism sensitivities as well as stressor-effect relationships for individuals and populations. We present a range of null models and outline their underlying assumptions and application in multiple stressor research. Moving beyond mere description requires multiple stressor research to shift its focus from identifying statistically significant interactions to the use and development of mechanistic (null) models. Justified selection of the appropriate null model is a first step to achieve this.

show abstract

“…Data from 48-hpd readings were fitted to a 4-parameter log-logistic concentration-response model with the lower bound set to 0 using the R package drc (Ritz et al 2015). The response f occurring as a result of concentration x is modeled as in Equation 1, where c is the lower bound value (set to 0), d is the upper bound value, b determines slope steepness, and e is the concentration achieving 50% of maximum efficacy (EC50).…”

Section: Calculation Of Extract Potencymentioning

confidence: 99%

Aryl hydrocarbon receptor‐mediated activity of gas‐phase ambient air derived from passive sampling and an in vitro bioassay

McDonough

Franks

Hahn

et al. 2019

Enviro Toxic and Chemistry

View full text Add to dashboard Cite

The gaseous fraction of hydrophobic organic contaminants (HOCs) in ambient air appears to be responsible for a significant portion of aryl hydrocarbon receptor (AhR)‐mediated activity, but the majority of compounds contributing to this activity remain unidentified. The present study investigated the use of polyethylene passive samplers to isolate gaseous HOCs from ambient air for use in in vitro bioassays and to improve our understanding of the toxicological relevance of the gaseous fraction of ambient air in urban and residential environments. Concentrations of polycyclic aromatic hydrocarbons (PAHs) and organic flame retardants were measured in polyethylene passive sampler extracts. Extracts were also analyzed using an in vitro bioassay to measure AhR‐mediated activity. Bioassay‐derived benzo[a]pyrene (BaP) equivalents (BaP‐Eqbio), a measure of potency of HOC mixtures, were greatest in the downtown Cleveland area and lowest at rural/residential sites further from the city center. The BaP‐Eqbio was weakly correlated with concentrations of 2‐ring alkyl/substituted PAHs and one organophosphate flame retardant, ethylhexyl diphenyl phosphate. Potency predicted based on literature‐derived induction equivalency factors (IEFs) explained only 2 to 23% of the AhR‐mediated potency observed in bioassay experiments. Our results suggests that health risks of gaseous ambient air pollution predicted using data from targeted chemical analysis may underestimate risks of exposure, most likely due to augmentation of potency by unmonitored chemicals in the mixture, and the lack of relevant IEFs for many targeted analytes. Environ Toxicol Chem 2019;38:748–759. © 2019 SETAC

show abstract

Dose-Response Analysis Using R

Cited by 116 publications

References 28 publications

Small-molecule inhibition of pyruvate phosphate dikinase targeting the nucleotide binding site

Small-molecule inhibition of pyruvate phosphate dikinase targeting the nucleotide binding site

Advancing understanding and prediction in multiple stressor research through a mechanistic basis for null models

Aryl hydrocarbon receptor‐mediated activity of gas‐phase ambient air derived from passive sampling and an in vitro bioassay

Contact Info

Product

Resources

About