ReviewEnvironmental health perspectives2014
Molecular signaling network motifs provide a mechanistic basis for cellular threshold responses.
Review in Environmental health perspectives, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed.
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- Octamethylcyclotetrasiloxane (D4) lacks endocrine disruptive potential via estrogen pathways.Archives of toxicology · 2025Article
- Using availableFrontiers in pharmacology · 2023Article
- An updated gene regulatory network reconstruction of multidrug-resistant Pseudomonas aeruginosa CCBH4851.Memorias do Instituto Oswaldo Cruz · 2022Article
- A Simple Toxicokinetic Model Exhibiting Complex Dynamics and Nonlinear Exposure Response.Risk analysis : an official publication of the Society for Risk Analysis · 2020Article
- Precise determination of input-output mapping for multimodal gene circuits using data from transient transfection.PLoS computational biology · 2020Article
- Human-relevant potency threshold (HRPT) for ERα agonism.Archives of toxicology · 2018Article
- Bridging the Data Gap FromFrontiers in public health · 2018Review
- Dynamics of the Gene Regulatory Network of HIV-1 and the Role of Viral Non-coding RNAs on Latency Reversion.Frontiers in physiology · 2018Article
- Uncertainties in biological responses that influence hazard and risk approaches to the regulation of endocrine active substances.Integrated environmental assessment and management · 2017Article
- How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- The Influence of Human Interindividual Variability on the Low-Dose Region of Dose-Response Curve Induced by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Primary B Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Adaptive Posttranslational Control in Cellular Stress Response Pathways and Its Relationship to Toxicity Testing and Safety Assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2015Review
- Toxicology: a discipline in need of academic anchoring--the point of view of the German Society of Toxicology.Archives of toxicology · 2015Article
- The human toxome project.ALTEX · 2015Article
- Synthetic biology for pharmaceutical drug discovery.Drug design, development and therapy · 2015Review
- Contributions of DNA repair and damage response pathways to the non-linear genotoxic responses of alkylating agents.Mutation research. Reviews in mutation researchReview
- Low-Dose Dose-Response for In Vitro Nrf2-ARE Activation in Human HepG2 Cells.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
backgroundIncreasingly, there is a move toward using in vitro toxicity testing to assess human health risk due to chemical exposure. As with in vivo toxicity testing, an important question for in vitro results is whether there are thresholds for adverse cellular responses. Empirical evaluations may show consistency with thresholds, but the main evidence has to come from mechanistic considerations.
objectivesCellular response behaviors depend on the molecular pathway and circuitry in the cell and the manner in which chemicals perturb these circuits. Understanding circuit structures that are inherently capable of resisting small perturbations and producing threshold responses is an important step towards mechanistically interpreting in vitro testing data.
methodsHere we have examined dose-response characteristics for several biochemical network motifs. These network motifs are basic building blocks of molecular circuits underpinning a variety of cellular functions, including adaptation, homeostasis, proliferation, differentiation, and apoptosis. For each motif, we present biological examples and models to illustrate how thresholds arise from specific network structures. DISCUSSION AND
conclusionIntegral feedback, feedforward, and transcritical bifurcation motifs can generate thresholds. Other motifs (e.g., proportional feedback and ultrasensitivity)produce responses where the slope in the low-dose region is small and stays close to the baseline. Feedforward control may lead to nonmonotonic or hormetic responses. We conclude that network motifs provide a basis for understanding thresholds for cellular responses. Computational pathway modeling of these motifs and their combinations occurring in molecular signaling networks will be a key element in new risk assessment approaches based on in vitro cellular assays.
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