By Ruediger Thul, Tomas C. Bellamy, H. Llewelyn Roderick (auth.), Miguel Maroto, Nicholas A. M. Monk (eds.)
MIGUEL MAROTO, PhD, is a MRC occupation improvement Fellow and Lecturer on the collage of Dundee, united kingdom. He obtained his PhD in Biochemistry and Molecular Biology from the dep. of Biochemistry of the Universidad Autonoma of Madrid, Spain. His learn pursuits contain investigating the biochemical foundation of other signalling mechanisms implicated within the acquisition of particular mobile fates in the course of vertebrate improvement. over the past years he has been implicated within the research of the mechanism of the molecular clock enthusiastic about the keep an eye on of the method of somitogenesis.
NICK MONK, PhD, is an affiliate Professor and Reader in utilized arithmetic on the collage of Nottingham, united kingdom. Having got his Ph.D. in theoretical physics from the collage of London, his examine replaced concentration to centre at the mathematical and computational modelling of organic platforms. specific parts of curiosity contain development formation, developmental biology, advanced community dynamics and mechanisms of intercellular signalling.
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Bootman MD, Berridge M], Roderick HL. Calcium signalling: More messengers, more channels, more complexity. Curr BioI 2002; 12(16):R563-565. 3. Berridge M], Rapp PE. A comparative survey of the function, mechanism and control of cellular oscillators. ] Exp BioI 1979; 81:217-279. 4. Berridge M]. Calcium oscillations. ] BioI Chern 1990; 265(17):9583-9586. 5. Thomas AP, Bird GS, Hajnoczky G et al. Spatial and temporal aspects of cellular calcium signaling. FASEB] 1996; 10(13):1505-1517. 6. Berridge M].
Negative feedback loops: structure and dynamics. A) p53-Mdm2 Negative feedback. p53 is a transcription factor that increases Mdm2 expression. Mdm2 is a E3 ligase protein that binds to p53, ubiquitinates it and targets it for degradation. B) Negative feedback loop dynamics. Negative feedback loops can give rise to a number of different behaviors depending on the relative values of feedback parameters; monotonic increase (top), damped oscillations (middle) or undamped/sustained (bottom) oscillations.
The mean height and width of the pulses was constant, however, and did not depend on the damage level. In the population studies, the pulses in different cells were averaged together, giving an appearance of damped oscillations (Fig. 4B). These findings suggest that the behavior of the p53 feedback loop can be thought as 'digital' as opposed to 'analog'. In analog circuits stronger input leads to higher and wider output. In contrast, in the p53-Mdm2 negative feedback, it is the number of p53 pulses, and not their amplitude and duration that depends on the level of input.