Dataset Information

Clb3-centered regulations are recurrent across distinct parameter regions in minimal autonomous cell cycle oscillator designs.

ABSTRACT: Some biological networks exhibit oscillations in their components to convert stimuli to time-dependent responses. The eukaryotic cell cycle is such a case, being governed by waves of cyclin-dependent kinase (cyclin/Cdk) activities that rise and fall with specific timing and guarantee its timely occurrence. Disruption of cyclin/Cdk oscillations could result in dysfunction through reduced cell division. Therefore, it is of interest to capture properties of network designs that exhibit robust oscillations. Here we show that a minimal yeast cell cycle network is able to oscillate autonomously, and that cyclin/Cdk-mediated positive feedback loops (PFLs) and Clb3-centered regulations sustain cyclin/Cdk oscillations, in known and hypothetical network designs. We propose that Clb3-mediated coordination of cyclin/Cdk waves reconciles checkpoint and oscillatory cell cycle models. Considering the evolutionary conservation of the cyclin/Cdk network across eukaryotes, we hypothesize that functional ("healthy") phenotypes require the capacity to oscillate autonomously whereas dysfunctional (potentially "diseased") phenotypes may lack this capacity.

SUBMITTER: Mondeel TDGA

PROVIDER: S-EPMC7125140 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Clb3-centered regulations are recurrent across distinct parameter regions in minimal autonomous cell cycle oscillator designs.

Mondeel Thierry D G A TDGA Ivanov Oleksandr O Westerhoff Hans V HV Liebermeister Wolfram W Barberis Matteo M

NPJ systems biology and applications 20200403 1

Some biological networks exhibit oscillations in their components to convert stimuli to time-dependent responses. The eukaryotic cell cycle is such a case, being governed by waves of cyclin-dependent kinase (cyclin/Cdk) activities that rise and fall with specific timing and guarantee its timely occurrence. Disruption of cyclin/Cdk oscillations could result in dysfunction through reduced cell division. Therefore, it is of interest to capture properties of network designs that exhibit robust oscil ...[more]

PMID: 32245958

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Project description:BackgroundOnly a minority of people with eating disorders receive evidence-based psychological treatment. This is especially true for those with recurrent binge eating because the shame that accompanies binge eating affects help seeking and there is a shortage of therapists to provide psychological treatments. Digital programme-led interventions have the potential to overcome both barriers.ObjectiveThis study examined the acceptability and effectiveness of a new digital programme-led intervention directly based on enhanced cognitive behaviour therapy (CBT-E), which is an empirically supported psychological treatment for eating disorders.MethodsOne hundred and ten adults with recurrent binge eating (self-reporting characteristics consistent with binge eating disorder, bulimia nervosa, and similar conditions) were recruited through an advertisement on the website of the UK's national eating disorder charity, Beat. The intervention, called Digital CBTe, comprised 12 sessions over 8-12 weeks delivered autonomously (i.e., without external support). Participants completed self-report outcome measures of eating disorder features and secondary impairment at baseline, post-intervention, and 6-month follow-up.ResultsMost participants identified as female, White, and were living in the United Kingdom. Most participants (85%) self-reported features that resembled binge eating disorder, and the rest self-reported features that resembled bulimia nervosa (8%) and atypical bulimia nervosa (7%). On average, participants reported that the onset of their eating disorder was more than twenty years ago. Sixty-three percent of the participants completed Digital CBTe (i.e., completed active treatment sessions). Those who completed all sessions and the post-intervention assessment (n = 55, 50%) reported significant decreases in binge eating, eating disorder psychopathology, and secondary impairment at post-intervention. These improvements were maintained at follow-up. Large effect sizes were observed for all these outcomes using a completer analysis and post-intervention data (d = 0.91-1.43). Significant improvements were also observed for all outcomes at post-intervention in the intent-to-treat analysis, with medium-to-large effect sizes.DiscussionA substantial proportion of those who completed Digital CBTe and the post-intervention assessment experienced marked improvements. This provides promising data to support the conduct of a fully powered trial to test the clinical and cost-effectiveness of autonomous Digital CBTe.

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Clb3-centered regulations are recurrent across distinct parameter regions in minimal autonomous cell cycle oscillator designs.

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Clb3-centered regulations are recurrent across distinct parameter regions in minimal autonomous cell cycle oscillator designs.

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