Activation dynamics of creative intuition

2010 ◽  
Author(s):  
Kristin Grunewald ◽  
Jared M. Novick ◽  
Henk J. Haarmann
Keyword(s):  
Activation Dynamics

scholarly journals Cell type–dependent bimodal p53 activation engenders a dynamic mechanism of chemoresistance

2018 ◽  
Vol 4 (12) ◽  
pp. eaat5077 ◽  
Author(s):  
Ruizhen Yang ◽  
Bo Huang ◽  
Yanting Zhu ◽  
Yang Li ◽  
Feng Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cellular Response ◽  
Resistance Mechanism ◽  
Genetic Mutation ◽  
Single Cell Imaging ◽  
Regulatory Module ◽  
Response To Chemotherapy ◽  
Activation Dynamics ◽  
Inhibitory Strength ◽  
P53 Activation

Studies of drug resistance mostly characterize genetic mutation, and we know much less about phenotypic mechanisms of drug resistance, especially at a quantitative level. p53 is an important mediator of cellular response to chemotherapy, but even p53 wild-type cells vary in drug sensitivity for unclear reasons. Here, we elucidated a new resistance mechanism to a DNA-damaging chemotherapeutic through bimodal modulation of p53 activation dynamics. By combining single-cell imaging with computational modeling, we characterized a four-component regulatory module, which generates bimodal p53 dynamics through coupled feed-forward and feedback, and found that the inhibitory strength between ATM and Mdm2 determined the differential modular output between drug-sensitive and drug-resistant cancer cell lines. We further showed that the combinatorial inhibition of Mdm2 and Wip1 was an effective strategy to alter p53 dynamics in resistant cancer cells and sensitize their apoptotic response. Our results point to p53 pulsing as a potentially druggable mechanism that mediates chemoresistance.

scholarly journals Limits on information transduction through amplitude and frequency regulation of transcription factor activity

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Anders S Hansen ◽  
Erin K O'Shea
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Frequency Regulation ◽  
Regulation Of Transcription ◽  
Limited Information ◽  
Dynamic Information ◽  
Extrinsic Noise ◽  
Intensity Information ◽  
Single Target ◽  
Activation Dynamics

Signaling pathways often transmit multiple signals through a single shared transcription factor (TF) and encode signal information by differentially regulating TF dynamics. However, signal information will be lost unless it can be reliably decoded by downstream genes. To understand the limits on dynamic information transduction, we apply information theory to quantify how much gene expression information the yeast TF Msn2 can transduce to target genes in the amplitude or frequency of its activation dynamics. We find that although the amount of information transmitted by Msn2 to single target genes is limited, information transduction can be increased by modulating promoter cis-elements or by integrating information from multiple genes. By correcting for extrinsic noise, we estimate an upper bound on information transduction. Overall, we find that information transduction through amplitude and frequency regulation of Msn2 is limited to error-free transduction of signal identity, but not signal intensity information.

scholarly journals Modeling of Rifampicin-Induced CYP3A4 Activation Dynamics for the Prediction of Clinical Drug-Drug Interactions from In Vitro Data

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e70330 ◽  
Author(s):  
Fumiyoshi Yamashita ◽  
Yukako Sasa ◽  
Shuya Yoshida ◽  
Akihiro Hisaka ◽  
Yoshiyuki Asai ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Activation Dynamics ◽  
Vitro Data ◽  
Clinical Drug ◽  
In Vitro Data

Localized Rac Activation Dynamics Visualized in Living Cells

Science ◽  
2000 ◽  
Vol 290 (5490) ◽  
pp. 333-337 ◽  
Author(s):  
V. S. Kraynov
Keyword(s):  
Living Cells ◽  
Activation Dynamics

Integrating Three Views of Arf1 Activation Dynamics

2004 ◽  
Vol 337 (4) ◽  
pp. 969-983 ◽  
Author(s):  
Charles H. Robert ◽  
Jacqueline Cherfils ◽  
Liliane Mouawad ◽  
David Perahia
Keyword(s):  
Activation Dynamics

Odorant Receptor 7D4 Activation Dynamics

2018 ◽  
Vol 130 (17) ◽  
pp. 4644-4648 ◽  
Author(s):  
Claire A. de March ◽  
Jérémie Topin ◽  
Elise Bruguera ◽  
Gleb Novikov ◽  
Kentaro Ikegami ◽  
...  
Keyword(s):  
Odorant Receptor ◽  
Activation Dynamics
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