Tai Chi for Disease Activity and Flexibility in Patients with Ankylosing Spondylitis—A Controlled Clinical Trial

We investigated the effects of tai chi on disease activity, flexibility and depression in patients with ankylosing spondylitis (AS). We allocated 40 patients to either a tai chi treatment group or a no-treatment control group. The tai chi group performed 60 min of tai chi twice weekly for eight consecutive weeks and 8 weeks of home-based tai chi, after which the group showed significant improvement in disease activity and flexibility compared to the control group. All outcome measures were significantly lower in the tai chi group than they were during pre-treatment, while they did not change in the control group. These findings suggest that tai chi can improve disease activity and flexibility for patients with AS. Tai chi is an easily accessible therapy for patients and, as such, may be an effective intervention for AS. However, we cannot completely discount the possibility that the placebo effect was responsible for the improvement

Degradation of the membrane-localized virulence activator TcpP by the YaeL protease in Vibrio cholerae

A common mechanism inhibiting the activity of transcription factors is their sequestration to the membrane until they are needed, at which point they are released from the membrane by proteolysis. Acting in contrast to this inhibition mechanism are virulence regulators of Vibrio cholerae, the ToxR and TcpP proteins, which are localized to the inner membrane of the cell, where they bind promoter DNA and activate gene expression. TcpP is rapidly degraded in the absence of another protein, TcpH. We used a genetic screen to identify regulators of TcpP stability and identified the YaeL membrane-localized zinc metalloprotease as responsible for degrading TcpP in the absence of TcpH. In Escherichia coli, DegS and YaeL cooperate to degrade RseA, an antisigma factor that sequesters σ(E) to the inner membrane, thereby inhibiting the activity of σ(E). When yaeL was disrupted in a V. cholerae tcpH mutant, we observed accumulation of a lower molecular weight species of TcpP. This observation is consistent with TcpP being partially degraded in the absence of YaeL. A mutant lacking both DegS and YaeL continued to accumulate the TcpP degradation product, indicating that protease other than DegS is acting before YaeL in degrading TcpP. The YaeL-dependent degradation pathway is active in TcpH(+) cells under conditions that are not favorable for virulence gene activation. This work expands the knowledge of YaeL-dependent processing in the bacterial cell and reveals an unexpected layer of virulence gene regulation in V. cholerae

Inhibition of regulated proteolysis by RseB

The Escherichia coli envelope-stress response is a sensor system that increases transcription of stress genes in the cytoplasm when misfolded porins are detected in the periplasm. This response is initiated by DegS cleavage of the periplasmic domain of RseA, a transmembrane protein. Additional proteolysis of transmembrane and cytoplasmic portions of RseA then frees the σ(E) transcription factor, which directs the transcriptional response. We show that RseB protein, a known negative regulator, inhibits proteolysis by DegS in vitro by binding tightly to the periplasmic domain of RseA. Inhibition of DegS cleavage requires RseB binding to a conserved region near the C terminus of the poorly structured RseA domain, but the RseA sequences that mediate DegS recognition and RseB binding do not overlap directly. Although DegS cleavage of RseA is normally activated by binding of the C termini of porins to the PDZ domain of DegS, RseB inhibition is independent of this activation mechanism

Crystal structure of RseB and a model of its binding mode to RseA

The bacterial envelope stress response senses stress signals in the extracytoplasmic compartment, and activates σE-dependent transcription by degrading its antisigma factor RseA. RseB, a binding partner of RseA, plays a pivotal role in regulating this response, but its molecular mechanism is not understood. We therefore determined the crystal structure of Escherichia coli RseB at a resolution of 2.4 Å. RseB is composed of two domains linked by a flexible linker and forms a loosely packed dimer with two grooves on each side. This structural feature is confirmed by small-angle scattering in solution. Analysis of the binding of various RseA mutants to RseB allowed us to identify the major RseB-binding motif in RseA. These data, coupled with analysis of small-angle scattering of the RseA/RseB complex in solution, leads us to propose that two RseAs bind to the grooves of the dimeric RseB by conserved residues. The implications for modulating proteolytic cleavage of RseA are discussed