Calpain-Mediated Processing of Adenylate Cyclase Toxin Generates a Cytosolic Soluble Catalytically Active N-Terminal Domain

Bordetella pertussis, the whooping cough pathogen, secretes several virulence factors among which adenylate cyclase toxin (ACT) is essential for establishment of the disease in the respiratory tract. ACT weakens host defenses by suppressing important bactericidal activities of the phagocytic cells. Up to now, it was believed that cell intoxication by ACT was a consequence of the accumulation of abnormally high levels of cAMP, generated exclusively beneath the host plasma membrane by the toxin N-terminal catalytic adenylate cyclase (AC) domain, upon its direct translocation across the lipid bilayer. Here we show that host calpain, a calcium-dependent Cys-protease, is activated into the phagocytes by a toxin-triggered calcium rise, resulting in the proteolytic cleavage of the toxin N-terminal domain that releases a catalytically active "soluble AC''. The calpain-mediated ACT processing allows trafficking of the "soluble AC'' domain into subcellular organella. At least two strategic advantages arise from this singular toxin cleavage, enhancing the specificity of action, and simultaneously preventing an indiscriminate activation of cAMP effectors throughout the cell. The present study provides novel insights into the toxin mechanism of action, as the calpain-mediated toxin processing would confer ACT the capacity for a space- and time-coordinated production of different cAMP "pools'', which would play different roles in the cell pathophysiology.

Nonlinear Fluid Damping In Structure-Wake Oscillators In Modeling Vortex-Induced Vibrations

A Nonlinear Fluid Damping (NFD) in the form of the square-velocity is applied in the response analysis of Vortex-induced Vibrations (VIV). Its nonlinear hydrodynamic effects oil the coupled wake and structure oscillators are investigated. A comparison between the coupled systems with the linear and nonlinear fluid dampings and experiments shows that the NFD model can well describe response characteristics, such as the amplification of body displacement at lock-in and frequency lock-ill, both at high and low mass ratios. Particularly, the predicted peak amplitude of the body in the Griffin plot is ill good agreement with experimental data and empirical equation, indicating the significant effect of the NFD on the structure motion.

Flow-induced vibrations of long circular cylinders modeled by coupled nonlinear oscillators

The dynamics of long slender cylinders undergoing vortex-induced vibrations (VIV) is studied in this work. Long slender cylinders such as risers or tension legs are widely used in the field of ocean engineering. When the sea current flows past a cylinder, it will be excited due to vortex shedding. A three-dimensional time domain model is formulated to describe the response of the cylinder, in which the in-line (IL) and cross-flow (CF) deflections are coupled. The wake dynamics, including in-line and cross-flow vibrations, is represented using a pair of non-linear oscillators distributed along the cylinder. The wake oscillators are coupled to the dynamics of the long cylinder with the acceleration coupling term. A non-linear fluid force model is accounted for to reflect the relative motion of cylinder to current. The model is validated against the published data from a tank experiment with the free span riser. The comparisons show that some aspects due to VIV of long flexible cylinders can be reproduced by the proposed model, such as vibrating frequency, dominant mode number, occurrence and transition of the standing or traveling waves. In the case study, the simulations show that the IL curvature is not smaller than CF curvature, which indicates that both IL and CF vibrations are important for the structural fatigue damage.

Two-dimensional Vortex-induced Vibrations of Submerged Floating Tunnel Tethers

A vortex-induced vibration (VIV) model is presented for predicting the nonlinear dynamic response of submerged floating tunnel (SFT) tethers which are subjected to wave, current and tunnel oscillatory displacements at their upper end in horizontal and vertical directions. A nonlinear fluid force formula is introduced in this model, and the effect of the nonlinearity of tether is investigated. First, the tunnel is stationary and the tether vibrates due to the vortices shedding. The calculated results show that the cross-flow amplitude of VIV decreases compared with the linear model. However the in-line amplitude of VIV increases. Next, the periodical oscillation of tunnel is considered. The oscillation caused by wave forces plays the roles of parametric exciter and forcing exciter to the VIV of tether. The time history of displacement of the tether mid-span is obtained by the proposed model. It is shown that the in-line amplitude increases obviously and the corresponding frequency is changed. The cross-flow amplitude exhibits a periodic behavior.

Whales and Sonar: Environmental Exemptions for the Navy's Mid-Frequency Active Sonar Training.

Mid-frequency active (MFA) sonar emits pulses of sound from an underwater transmitter to help determine the size, distance, and speed of objects. The sound waves bounce off objects and reflect back to underwater acoustic receivers as an echo. MFA sonar has been used since World War II, and the Navy indicates it is the only reliable way to track submarines, especially more recently designed submarines that operate more quietly, making them more difficult to detect. Scientists have asserted that sonar may harm certain marine mammals under certain conditions, especially beaked whales. Depending on the exposure, they believe that sonar may damage the ears of the mammals, causing hemorrhaging and/or disorientation. The Navy agrees that the sonar may harm some marine mammals, but says it has taken protective measures so that animals are not harmed. (PDF contains 20 pages)