Animal cells within a tissue typically display a striking regularity in their size. To date, the molecular mechanisms that control this uniformity are still unknown. We have previously shown that size uniformity in animal cells is promoted, in part, by size-dependent regulation of G1 length. To identify the molecular mechanisms underlying this process, we performed a large-scale small molecule screen and found that the p38 MAPK pathway is involved in coordinating cell size and cell cycle progression. Small cells display higher p38 activity and spend more time in G1 than larger cells. Inhibition of p38 MAPK leads to loss of the compensatory G1 length extension in small cells, resulting in faster proliferation, smaller cell size and increased size heterogeneity. We propose a model wherein the p38 pathway responds to changes in cell size and regulates G1 exit accordingly, to increase cell size uniformity.

Single-cell analysis is pivotal to deciphering complex phenomena like heterogeneity, bistability, and asynchronous oscillations, where a population ensemble cannot represent individual behaviors. Bulk cell-free systems, despite having unique advantages of manipulation and characterization of biochemical networks, lack the essential single-cell information to understand a class of out-of-steady-state dynamics including cell cycles. Here, by encapsulating Xenopus egg extracts in water-in-oil microemulsions, we developed artificial cells that are adjustable in sizes and periods, sustain mitotic oscillations for over 30 cycles, and function in forms from the simplest cytoplasmic-only to the more complicated ones involving nuclear dynamics, mimicking real cells. Such innate flexibility and robustness make it key to studying clock properties like tunability and stochasticity. Our results also highlight energy as an important regulator of cell cycles. We demonstrate a simple, powerful, and likely generalizable strategy of integrating strengths of single-cell approaches into conventional in vitro systems to study complex clock functions.

SUMMARY Robust biological oscillators retain the critical ability to function in the presence of environmental perturbations. Although central architectures that support robust oscillations have been extensively studied, networks containing the same core vary drastically in their potential to oscillate, and it remains elusive what peripheral modifications to the core contribute to this functional variation. Here, we have generated a complete atlas of two- and three-node oscillators computationally, then systematically analyzed the association between network structure and robustness. We found that, while certain core topologies are essential for producing a robust oscillator, local structures can substantially modulate the robustness of oscillations. Notably, local nodes receiving incoherent or coherent inputs respectively promote or attenuate the overall network robustness in an additive manner. We validated these relationships in larger-scale networks reflective of real biological oscillators. Our findings provide an explanation for why auxiliary structures not required for oscillation are evolutionarily conserved and suggest simple ways to evolve or design robust oscillators.

Background Self-sustained oscillations are a ubiquitous and vital phenomenon in living systems. From primitive single-cellular bacteria to the most sophisticated organisms, periodicities have been observed in a broad spectrum of biological processes such as neuron firing, heart beats, cell cycles, circadian rhythms, etc. Defects in these oscillators can cause diseases from insomnia to cancer. Elucidating their fundamental mechanisms is of great significance to diseases, and yet challenging, due to the complexity and diversity of these oscillators. Results Approaches in quantitative systems biology and synthetic biology have been most effective by simplifying the systems to contain only the most essential regulators. Here, we will review major progress that has been made in understanding biological oscillators using these approaches. The quantitative systems biology approach allows for identification of the essential components of an oscillator in an endogenous system. The synthetic biology approach makes use of the knowledge to design the simplest, de novo oscillators in both live cells and cell-free systems. These synthetic oscillators are tractable to further detailed analysis and manipulations. Conclusion With the recent development of biological and computational tools, both approaches have made significant achievements.

High-quality guided development and environmental forcing are two routes for China’s green development, and each has different focuses and outcomes. The aim of this study is to clarify coordinated mechanisms to reveal the reasons and determine paths for China’s green development. A research framework for synergetic evolution is established, and the Haken model is applied to analyze the different effects of high-quality development that guide resource- and environmental-forcing mechanisms. This research showed that: (1) the preferred route and key factor in China’s green development is high-quality developmental guidance; (2) high-quality development and environmental-forcing mechanisms are non-coordinated, and while the former might coordinate with the latter, the latter does not; (3) mutual promotion of high-quality developmental guidance and the resource mechanism was not observed; (4) the critical point coordinated value is 0.5686 for China’s green development. Eastern China possesses a relatively high level of green development, while the north, east, west, and central areas of the country still have much progress to make.