Fold-Change Dynamics of ERK Nuclear Entry in Individual Living Cells
Using endogenously tagged ERK2 protein, Alon and coworkers show that nuclear ERK2 levels vary strongly among clonal cells. In most cells, EGF stimulation causes a precise fold-change in ERK2 followed by a return to starting levels. Therefore, downstream genes may respond to relative, not absolute, changes in ERK2. Preview by Ferrell.

The Wnt Pathway Follows Weber's Law in Sensory Physiology
Weber's Law describes how sensory signal discrimination adjusts to background levels. Goentoro and Kirschner show that, in the canonical Wnt signaling pathway, cells do not simply sense the level of β-catenin, but compute the ratio of β-catenin before and after ligand stimulation, in line with Weber’s law. In this way, they suppress noise and extend their range of sensitivity. Preview by Ferrell.

The Incoherent Feedforward Loop Can Provide a Weber’s Law Response
How might a transcriptional circuit respond to the fold-change rather than the absolute level of an activator? Transcriptional circuits would need to remember the basal level of the activator and compare that to the new level. The Kirschner/Alon groups demonstrate theoretically that one recurrent network motif can perform this temporal comparison. Preview by Ferrell.

Hydroxyl Radicals Mediate Bacterial Cell Death Following Replication Inhibition by Hydroxyurea
Hydroxyurea has been used for decades to block DNA replication by inhibiting ribonucleotide reductase. Walker and colleagues combine a systems biology approach with genetic and physiological experiments to show that blocking DNA replication with hydroxyurea causes a chain of events that leads to hydroxyl radical production and cell death. Preview by Bollenbach and Kishony.

Stabilizing Proteins by In Vivo Selection
Many proteins are unstable and it is often unclear why. Bardwell and colleagues developed an approach to stabilize proteins by directly linking protein stability to antibiotic resistance. This allowed them to select for stabilizing mutations and to obtain clues about the basis for protein instability. Preview by Wiseman and Kelly.

Reverse Engineering Cancer Pathway Perturbations
Cancers result from perturbations to diverse cellular pathways. Tavazoie and colleagues show that these pathways and the regulatory sequences that modulate them can be identified from global gene expression profiles. The authors’ approach provides a network-level understanding of cancer pathways, a crucial first step for therapeutic intervention and drug-target discovery. Preview by Prensner and Chinnaiyan.