Genetic Evidence for a Phosphorylation-Independent Signal Transduction Mechanism within the Bacillus subtilis Stressosome

The stressosome is a 1.8 MDa cytoplasmic complex that controls diverse bacterial signaling pathways. Its role is best understood in Bacillus subtilis, where it activates the σ(B) transcription factor in response to a variety of sharp environmental challenges, including acid, ethanol, heat or salt stress. However, details of the signaling mechanism within the stressosome remain uncertain. The core of the complex comprises one or more members of the RsbR co-antagonist family together with the RsbS antagonist protein, which binds the RsbT kinase in the absence of stress. As part of the response, RsbT first phosphorylates the RsbRA co-antagonist on T171 and then RsbS on S59; this latter event correlates with the stress-induced release of RsbT to activate downstream signaling. Here we examine the in vivo consequence of S59 phosphorylation in a model strain whose stressosome core is formed solely with the RsbRA co-antagonist and RsbS. A phosphorylation-deficient S59A substitution in RsbS blocked response to mild stress but had declining impact as stress increased: with strong ethanol challenge response with S59A was 60% as robust as with wild type RsbS. Genetic analysis narrowed this S59-independent activation to the stressosome and established that significant signaling still occurred in a strain bearing both the T171A and S59A substitutions. We infer that S59 phosphorylation increases signaling efficiency but is not essential, and that a second (or underlying) mechanism of signal transduction prevails in its absence. This interpretation nullifies models in which stressosome signaling is solely mediated by control of RsbT kinase activity toward S59

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