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Dynamical predictors of an imminent phenotypic switch in bacteria.

ABSTRACT: Single cells can stochastically switch across thresholds imposed by regulatory networks. Such thresholds can act as a tipping point, drastically changing global phenotypic states. In ecology and economics, imminent transitions across such tipping points can be predicted using dynamical early warning indicators. A typical example is 'flickering' of a fast variable, predicting a longer-lasting switch from a low to a high state or vice versa. Considering the different timescales between metabolite and protein fluctuations in bacteria, we hypothesized that metabolic early warning indicators predict imminent transitions across a network threshold caused by enzyme saturation. We used stochastic simulations to determine if flickering predicts phenotypic transitions, accounting for a variety of molecular physiological parameters, including enzyme affinity, burstiness of enzyme gene expression, homeostatic feedback, and rates of metabolic precursor influx. In most cases, we found that metabolic flickering rates are robustly peaked near the enzyme saturation threshold. The degree of fluctuation was amplified by product inhibition of the enzyme. We conclude that sensitivity to flickering in fast variables may be a possible natural or synthetic strategy to prepare physiological states for an imminent transition.

SUBMITTER: Wang H

PROVIDER: S-EPMC5730990 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Dynamical predictors of an imminent phenotypic switch in bacteria.

Wang Huijing H Ray J Christian J JCJ

Physical biology 20170629 4

Single cells can stochastically switch across thresholds imposed by regulatory networks. Such thresholds can act as a tipping point, drastically changing global phenotypic states. In ecology and economics, imminent transitions across such tipping points can be predicted using dynamical early warning indicators. A typical example is 'flickering' of a fast variable, predicting a longer-lasting switch from a low to a high state or vice versa. Considering the different timescales between metabolite ...[more]

PMID: 28597843

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Project description:Adults experiencing homelessness are more likely to have an alcohol use disorder compared to adults in the general population. Although shelter-based treatments are common, completion rates tend to be poor, suggesting a need for more effective approaches that are tailored to this understudied and underserved population. One barrier to developing more effective treatments is the limited knowledge of the triggers of alcohol use among homeless adults. This paper describes the use of ecological momentary assessment (EMA) to identify predictors of "imminent drinking" (i.e., drinking within the next 4 h), among a sample of adults experiencing homelessness and receiving health services at a homeless shelter. A total of 78 mostly male (84.6%) adults experiencing homelessness (mean age = 46.6) who reported hazardous drinking completed up to five EMAs per day over 4 weeks (a total of 4557 completed EMAs). The study used machine learning techniques to create a drinking risk algorithm that predicted 82% of imminent drinking episodes within 4 h of the first drink of the day, and correctly identified 76% of nondrinking episodes. The algorithm included the following 7 predictors of imminent drinking: urge to drink, having alcohol easily available, feeling confident that alcohol would improve mood, feeling depressed, lower commitment to being alcohol free, not interacting with someone drinking alcohol, and being indoors. The research team used the results to develop intervention content (e.g., brief tailored messages) that will be delivered when imminent drinking is detected in an upcoming intervention phase. Specifically, we created three theoretically grounded message tracks focused on urge/craving, social/availability, and negative affect/mood, which are further tailored to a participant's current drinking goal (i.e., stay sober, drink less, no goal) to support positive change. To our knowledge, this is the first study to develop tailored intervention messages based on likelihood of imminent drinking, current drinking triggers, and drinking goals among adults experiencing homelessness.

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Dynamical predictors of an imminent phenotypic switch in bacteria.

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Dynamical predictors of an imminent phenotypic switch in bacteria.

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