Mammalian Toll-like receptors (TLRs) are expressed on innate immune cells and respond to the membrane components of Gram-positive or Gram-negative bacteria. When activated, they convey signals to transcription factors that orchestrate the inflammatory response. However, the intracellular signaling events following TLR activation are largely unknown. Here we show that TLR2 stimulation by Staphylococcus aureus induces a fast and transient activation of the Rho GTPases Rac1 and Cdc42 in the human monocytic cell line THP-1 and in 293 cells expressing TLR2. Dominant-negative Rac1N17, but not dominant-negative Cdc42N17, block nuclear factor-kappa B (NF-kappa B) transactivation. S. aureus stimulation causes the recruitment of active Rac1 and phosphatidylinositol-3 kinase (PI3K) to the TLR2 cytosolic domain. Tyrosine phosphorylation of TLR2 is required for assembly of a multiprotein complex that is necessary for subsequent NF-kappa B transcriptional activity. A signaling cascade composed of Rac1, PI3K and Akt targets nuclear p65 transactivation independently of I kappa B alpha degradation. Thus Rac1 controls a second, I kappa B-independent, pathway to NF-kappa B activation and is essential in innate immune cell signaling via TLR2.

Rho kinases (ROCKs), the first Rho effectors to be described, are serine/threonine kinases that are important in fundamental processes of cell migration, cell proliferation and cell survival. Abnormal activation of the Rho/ROCK pathway has been observed in various disorders of the central nervous system. Injury to the adult vertebrate brain and spinal cord activates ROCKs, thereby inhibiting neurite growth and sprouting. Inhibition of ROCKs results in accelerated regeneration and enhanced functional recovery after spinal-cord injury in mammals, and inhibition of the Rho/ROCK pathway has also proved to be efficacious in animal models of stroke, inflammatory and demyelinating diseases, Alzheimer's disease and neuropathic pain. ROCK inhibitors therefore have potential for preventing neurodegeneration and stimulating neuroregeneration in various neurological disorders.

Abstract. Soil samples from arable land were investigated for their exchange of carbonyl sulfide (COS) with the atmosphere under controlled conditions using dynamic cuvettes in a climate chamber. The investigated soil type acted as a significant sink for the trace gas COS. Atmospheric COS mixing ratios, temperature, and soil water content were found to be the physicochemical parameters controlling the uptake. Emission was never observed under conditions representative of a natural environment. The observed compensation point (i.e., an ambient concentration where the consumption and production balance each other and the net flux is zero) for the uptake was about 53 parts per trillion. Uptake rates ranged between 1.5 and 10.3 pmol m -2 s -•. The consumption of COS by the soil sample depended on the physiological activity of the microorganisms in the soil, as indicated by a clear optimum temperature and by a drastic inhibition in the presence of the enzyme inhibitor 6-ethoxy-2-benzothiazole-2-sulfonamide (EZ), a specific inhibitor for carbonic anhydrase.