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BackgroundNeuroinflammation regulates both disease pathogenesis and repair in multiple sclerosis. In early multiple sclerosis lesion development, neuroinflammation causes demyelination and axonal injury, the likely final common determinant of disability. Here we report the identification of a novel neuroinflammatory mediator, Disabled-2 (Dab2). Dab2 is an intracellular adaptor protein with previously unknown function in the central nervous system.ResultsWe report that Dab2 is up-regulated in lesional macrophages/microglia in the spinal cord in murine experimental autoimmune encephalomyelitis, a model of multiple sclerosis. We demonstrate that dab2 expression is positively correlated with experimental autoimmune encephalomyelitis disease severity during the acute disease phase. Furthermore, dab2-deficient mice have a less severe experimental autoimmune encephalomyelitis disease course and suffer less neuroinflammation and less axonal injury than their wild-type littermates. We demonstrate that dab2 expression is strongly associated with the expression of inducible nitric oxide synthase. We further demonstrate that Dab2 is expressed at the protein level by macrophages in early acute human multiple sclerosis lesions and that this correlates with axonal injury.ConclusionsTogether, these results suggest that endogenous Dab2 exacerbates central nervous system inflammation, potentially acting to up-regulate reactive oxygen species expression in macrophages and microglia, and that it is of potential pathogenic relevance in Multiple Sclerosis.

The composite fouling of calcium oxalate monohydrate (COM) and amorphous silica (SiO 2 ) were investigated in a dynamic system under subcooled flow-boiling and a novel but simple continuous evaporation setup to simulate the operation cycle in latter effects of sugar mill evaporators. Simulated solutions with various COM to SiO 2 supersaturation (SS) ratios as well as those of pure COM and SiO 2 were tested for comparative studies. The results demonstrated that COM fouling resistances began to rise shortly after the experiment started with the highest extent of fouling exhibited at an initial COM concentration of 50 ppm (initial COM SS ∼ 2.6). The fouling resistance of SiO 2 (500 ppm) began to rise at a theoretical silica supersaturation level of 5.3. SiO 2 fouling involved the deposition of two silica species, that is, dissolved monomeric silica and colloidal silica particles, with colloidal silica particles being more prevalent at SiO 2 supersaturation. In the binary systems, the synergistic effect of COM on composite fouling occurred at an intermediate concentration of COM (50 ppm) whereas antagonism was obtained at either low or high COM concentration (20 or 100 ppm). The observed variations in the extent of composite fouling may be partly attributed both to the changes in the magnitude of interfacial energy barrier between the surface of the particle and the wall and to the physical properties of the fouling species such as particle size. Instrumental analysis (SEM-EDS and XRD) was used to investigate structure and composition of scale. The presence of COM and its cementing effect in the composite scale from [COM] ) 50 ppm were confirmed.