8,991 research outputs found
Circadian rhythm and cell population growth
Molecular circadian clocks, that are found in all nucleated cells of mammals,
are known to dictate rhythms of approximately 24 hours (circa diem) to many
physiological processes. This includes metabolism (e.g., temperature, hormonal
blood levels) and cell proliferation. It has been observed in tumor-bearing
laboratory rodents that a severe disruption of these physiological rhythms
results in accelerated tumor growth. The question of accurately representing
the control exerted by circadian clocks on healthy and tumour tissue
proliferation to explain this phenomenon has given rise to mathematical
developments, which we review. The main goal of these previous works was to
examine the influence of a periodic control on the cell division cycle in
physiologically structured cell populations, comparing the effects of periodic
control with no control, and of different periodic controls between them. We
state here a general convexity result that may give a theoretical justification
to the concept of cancer chronotherapeutics. Our result also leads us to
hypothesize that the above mentioned effect of disruption of circadian rhythms
on tumor growth enhancement is indirect, that, is this enhancement is likely to
result from the weakening of healthy tissue that are at work fighting tumor
growth
Quantitative analysis of regulatory flexibility under changing environmental conditions
The circadian clock controls 24-h rhythms in many biological processes, allowing appropriate timing of biological rhythms relative to dawn and dusk. Known clock circuits include multiple, interlocked feedback loops. Theory suggested that multiple loops contribute the flexibility for molecular rhythms to track multiple phases of the external cycle. Clear dawn- and dusk-tracking rhythms illustrate the flexibility of timing in Ipomoea nil. Molecular clock components in Arabidopsis thaliana showed complex, photoperiod-dependent regulation, which was analysed by comparison with three contrasting models. A simple, quantitative measure, Dusk Sensitivity, was introduced to compare the behaviour of clock models with varying loop complexity. Evening-expressed clock genes showed photoperiod-dependent dusk sensitivity, as predicted by the three-loop model, whereas the one- and two-loop models tracked dawn and dusk, respectively. Output genes for starch degradation achieved dusk-tracking expression through light regulation, rather than a dusk-tracking rhythm. Model analysis predicted which biochemical processes could be manipulated to extend dusk tracking. Our results reveal how an operating principle of biological regulators applies specifically to the plant circadian clock
Integrative biological simulation praxis: Considerations from physics, philosophy, and data/model curation practices
Integrative biological simulations have a varied and controversial history in
the biological sciences. From computational models of organelles, cells, and
simple organisms, to physiological models of tissues, organ systems, and
ecosystems, a diverse array of biological systems have been the target of
large-scale computational modeling efforts. Nonetheless, these research agendas
have yet to prove decisively their value among the broader community of
theoretical and experimental biologists. In this commentary, we examine a range
of philosophical and practical issues relevant to understanding the potential
of integrative simulations. We discuss the role of theory and modeling in
different areas of physics and suggest that certain sub-disciplines of physics
provide useful cultural analogies for imagining the future role of simulations
in biological research. We examine philosophical issues related to modeling
which consistently arise in discussions about integrative simulations and
suggest a pragmatic viewpoint that balances a belief in philosophy with the
recognition of the relative infancy of our state of philosophical
understanding. Finally, we discuss community workflow and publication practices
to allow research to be readily discoverable and amenable to incorporation into
simulations. We argue that there are aligned incentives in widespread adoption
of practices which will both advance the needs of integrative simulation
efforts as well as other contemporary trends in the biological sciences,
ranging from open science and data sharing to improving reproducibility.Comment: 10 page
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