Reversible and Noisy Progression towards a Commitment Point Enables Adaptable and Reliable Cellular Decision-Making

Cells must make reliable decisions under fluctuating extracellular conditions, but also be flexible enough to adapt to such changes. How cells reconcile these seemingly contradictory requirements through the dynamics of cellular decision-making is poorly understood. To study this issue we quantitatively measured gene expression and protein localization in single cells of the model organism Bacillus subtilis during the progression to spore formation. We found that sporulation proceeded through noisy and reversible steps towards an irreversible, all-or-none commitment point. Specifically, we observed cell-autonomous and spontaneous bursts of gene expression and transient protein localization events during sporulation. Based on these measurements we developed mathematical population models to investigate how the degree of reversibility affects cellular decision-making. In particular, we evaluated the effect of reversibility on the 1) reliability in the progression to sporulation, and 2) adaptability under changing extracellular stress conditions. Results show that reversible progression allows cells to remain responsive to long-term environmental fluctuations. In contrast, the irreversible commitment point supports reliable execution of cell fate choice that is robust against short-term reductions in stress. This combination of opposite dynamic behaviors (reversible and irreversible) thus maximizes both adaptable and reliable decision-making over a broad range of changes in environmental conditions. These results suggest that decision-making systems might employ a general hybrid strategy to cope with unpredictably fluctuating environmental conditions

Turn-over orbital septal flap and levator recession for upper-eyelid retraction secondary to thyroid eye disease

BackgroundA turn-over septal flap has been reported as a spacer for levator lengthening in a single case report. This study reports the preliminary outcomes of this technique in a series of patients with upper-lid retraction (ULR) associated with thyroid eye disease (TED) causing symptomatic exposure keratopathy (EK).MethodsRetrospective, multicenter study of 12 eyelids of 10 patients with TED undergoing a transcutaneous levator-lengthening technique using the reflected orbital septum (OS) as a spacer. Change in palpebral aperture (PA) and contour, position of the skin crease (SC), symptoms of EK, and complications were recorded.ResultsThe average age was 47.5 years. Two patients were excluded, as their septa were found to be very thin at surgery. At an average of 13 months postoperatively, the PA was reduced by 2.5 mm on average (PConclusionsThe turn-over orbital septal flap technique may be a viable option as an autogenous spacer for the treatment of ULR in TED. This technique may be possible in cases where the OS has been opened by previous surgery but may not be feasible in patients in whom the septum is very thin.A Watanabe, PN Shams, N Katori, S Kinoshita and D Selv