Effect of the phase state of lipids on their interaction with cobra cytotoxin

Interaction between cytotoxin of the Central Asia cobra venom and dimiristoylphosphatidylcholine bilayer depending on its phase state was studied by ESR with spin label. A conclusion can be drawn that the efficiency of cytotoxin effect on the membranes depends on their phase state. Cytotoxin molecules are incorporated into myophile region of the bilayer, only if the latter is in the liquid crystal state. The interaction between cytotoxins and lipids of the bilayer in a gel state is in the main conditioned by electrostatic forces.     

A climate for contemporary evolution

A new study of divergence in freshwater fish provides strong evidence of rapid, temperature-mediated adaptation. This study is particularly important in the ongoing debate over the extent and significance of evolutionary response to climate change because divergence has occurred in relatively few generations in spite of ongoing gene flow and in the aftermath of a significant genetic bottleneck, factors that have previously been considered obstacles to evolution. Climate change may thus be more likely to foster contemporary evolutionary responses than has been anticipated, and I argue here for the importance of investigating their possible occurrence.     

Growth-induced mass flows in fungal networks

Cord-forming fungi form extensive networks that continuously adapt to maintain an efficient transport system. As osmotically driven water uptake is often distal from the tips, and aqueous fluids are incompressible, we propose that growth induces mass flows across the mycelium, whether or not there are intrahyphal concentration gradients. We imaged the temporal evolution of networks formed by Phanerochaete velutina, and at each stage calculated the unique set of currents that account for the observed changes in cord volume, while minimizing the work required to overcome viscous drag. Predicted speeds were in reasonable agreement with experimental data, and the pressure gradients needed to produce these flows are small. Furthermore, cords that were predicted to carry fast-moving or large currents were significantly more likely to increase in size than cords with slow-moving or small currents. The incompressibility of the fluids within fungi means there is a rapid global response to local fluid movements. Hence velocity of fluid flow is a local signal that conveys quasi-global information about the role of a cord within the mycelium. We suggest that fluid incompressibility and the coupling of growth and mass flow are critical physical features that enable the development of efficient, adaptive biological transport networks.     

Deadly liaisons: fatal attraction between CCN matricellular proteins and the tumor necrosis factor family of cytokines

Recent studies have revealed an unexpected synergism between two seemingly unrelated protein families: CCN matricellular proteins and the tumor necrosis factor (TNF) family of cytokines. CCN proteins are dynamically expressed at sites of injury repair and inflammation, where TNF cytokines are also expressed. Although TNFα is an apoptotic inducer in some cancer cells, it activates NFκB to promote survival and proliferation in normal cells, and its cytotoxicity requires inhibition of de novo protein synthesis or NFκB signaling. The presence of CCN1, CCN2, or CCN3 overrides this requirement and unmasks the apoptotic potential of TNFα, thus converting TNFα from a proliferation-promoting protein into an apoptotic inducer. These CCN proteins also enhance the cytotoxicity of other TNF cytokines, including LTα, FasL, and TRAIL. Mechanistically, CCNs function through integrin α₆β₁ and the heparan sulfate proteoglycan (HSPG) syndecan-4 to induce reactive oxygen species (ROS) accumulation, which is essential for apoptotic synergism. Mutant CCN1 proteins defective for binding α₆β₁-HSPGs are unable to induce ROS or apoptotic synergism with TNF cytokines. Further, knockin mice that express an α₆β₁-HSPG-binding defective CCN1 are blunted in TNFα- and Fas-mediated apoptosis, indicating that CCN1 is a physiologic regulator of these processes. These findings implicate CCN proteins as contextual regulators of the inflammatory response by dictating or enhancing the cytotoxicity of TNFα and related cytokines.