Mannose Binding Lectin Is Required for Alphavirus-Induced Arthritis/Myositis

Mosquito-borne alphaviruses such as chikungunya virus and Ross River virus (RRV) are emerging pathogens capable of causing large-scale epidemics of virus-induced arthritis and myositis. The pathology of RRV-induced disease in both humans and mice is associated with induction of the host inflammatory response within the muscle and joints, and prior studies have demonstrated that the host complement system contributes to development of disease. In this study, we have used a mouse model of RRV-induced disease to identify and characterize which complement activation pathways mediate disease progression after infection, and we have identified the mannose binding lectin (MBL) pathway, but not the classical or alternative complement activation pathways, as essential for development of RRV-induced disease. MBL deposition was enhanced in RRV infected muscle tissue from wild type mice and RRV infected MBL deficient mice exhibited reduced disease, tissue damage, and complement deposition compared to wild-type mice. In contrast, mice deficient for key components of the classical or alternative complement activation pathways still developed severe RRV-induced disease. Further characterization of MBL deficient mice demonstrated that similar to C3−/− mice, viral replication and inflammatory cell recruitment were equivalent to wild type animals, suggesting that RRV-mediated induction of complement dependent immune pathology is largely MBL dependent. Consistent with these findings, human patients diagnosed with RRV disease had elevated serum MBL levels compared to healthy controls, and MBL levels in the serum and synovial fluid correlated with severity of disease. These findings demonstrate a role for MBL in promoting RRV-induced disease in both mice and humans and suggest that the MBL pathway of complement activation may be an effective target for therapeutic intervention for humans suffering from RRV-induced arthritis and myositis

Some observations of diatoms under turbulence

The effect of turbulence on several freshwater diatom taxa was investigated and our findings are described herein. We have compared diatom morphology in shallow natural systems that experience turbulence due to wind and in river/waterfall systems where turbulence is due to high flow rates. We have also introduced turbulence into diatom laboratory cultures by mechanical shaking and by forcing air into the media. In particular, we have studied diatoms in five independent environments or cultures: the freshwater diatoms Tabellaria and Eunotia in equatorial lakes experiencing extreme seasonal variability in depth; two freshwater diatom monocultures of Aulacoseira granulata var angustissima and Melosira varians in the laboratory; and a freshwater diatom community possessing equal amounts (by number) of elongated and non-elongated diatoms (mostly Nitzschia and mostly Cyclotella, respectively) in the laboratory. We have demonstrated the effect of turbulence on freshwater diatom frustule morphologies and, perhaps more importantly, the effect of turbulence on freshwater diatom species population after controlled perturbation of the organisms’ environment. It has been widely reported that symmetry is often preferred in biological evolution, however here we have observed a preference towards asymmetry for the survival of diatoms in the presence of environmental stress (in particular, turbulence). We also note that to date there have been no systematic attempts to manipulate diatom frustules using external stimuli. We therefore present a proof-of-concept study in order to demonstrate: (i) that diatom morphologies can be manipulated by controlled simple external triggers (chemical and physical) (ii) that population balance (i.e. natural selection) can be controlled via simple external triggers (chemical and physical). This approach could open up an entire new field of future studies wherein controlled environmental perturbations are used to manipulate the structure, form, growth and reproduction of biological species