However, signaling pathways involve extensive crosstalk and feedforward as well as feedback loops resulting in complex, nonlinear intracellular signaling networks, whose topologies are often context-specific and altered in diseases [1].

Both signaling pathways are tightly interlinked and several mechanisms have been proposed for feedback loops within and crosstalk between PI3K and MAPK signaling (S2—S3 Tables).

For example, it was shown that within the MAPK signaling pathway a negative feedback loop is triggered by ERK or p9ORSK targeting SOS [4], and a positive feedback loop operates from ERK to

The candidate mechanisms within model 4_8_12 generate crosstalk as well as feedforward and feedback loops within the network structure leading to robust network behavior.

At first glance, model 4_8_12 includes three feedback loops (Fig 6A).

Within the PI3K pathway, the edge PI3K to Gabl closes a positive feedback loop .

Notably, these mechanisms give rise to two positive and two negative feedback loops , each containing species from both the PI3K and MAPK pathways.

Notably, in some cases, the qualitative response is not restricted by the model structure: If a path between the inhibited and measured species includes a negative feedback loop , or if paths of both signs exist between the two nodes, the actual response depends on the strength of the different mechanism and, thus, cannot be predicted by a purely qualitative model.

1 (C) illustrates this aspect by including a feedback loop from the action to decision systems that is missing from both serial and parallel models.

The dependence of the action focus upon both the accumulated information and the current movement and location is characteristic of embodied choice models, because such models require a feedback loop from action to decision systems.

Model 1 serially initiates action after decision completion; Model 2 is parallel by allowing changes of mind in the decision system after the action initiates; Model 3 has action preparation operating in parallel with decision system, with also some aspects of embodiment by using action completion for decision completion; and Model 4 is fully embodied with a feedback loop from the action to decision systems, encompassing both action preparation and commitment.

Embodied choice models, here exemplified by Model 4, include both action preparation and a feedback loop from action to decision systems that, while allowing changes of mind, also produce a commitment effect: changes of mind become less likely as the action nears completion.

Here we found that a parallel model of action preparation (Model 3) early in the decision process approached the performance of the original DDM for relatively long response times; meanwhile, a feedback loop from action to decision gave a commitment effect necessary to achieve response speeds close to the minimum action time (Model 4).

Prolonged survival of starving cells by a RpoS-mediated negative feedback loop

Importantly, with this repression, a negative feedback loop among RpoS, substrate concentration and cell growth is formed as depicted in Fig.

The negative feedback loop suggested above may play a similar role, providing a mechanism for a gradual change of NCFU observed in the first phase of the survival kinetics (Fig.