If involved may have contributed to the variability in clinical outcomes we observed among vaccinated ferrets and to the variability in reporting the association in humans. Our experiment assessed the unique context of heterologous but homosubtypic pandemic H1N1 challenge. It has been suggested that original antigenic sin as an aspect of the cross-reactive, non-neutralizing antibody required for ADE applies when antigenic differences of less than 33�C42% exist across related but distinct prime-boost strains ; amino acid differences in the HA1 between the 2008�C09 seasonal and 2009 pandemic H1 antigens were within this range with much closer homology across the HA2. However, without better understanding of the underlying mechanisms or specific virologic interactions we cannot speculate whether the same association could apply to other emerging heterologous or hetero-subtypic variants; the antigenic distance and other criteria required to define or forecast that likelihood remain unknown. In summary, although these ferret findings cannot be considered conclusive in explaining earlier human observations from Canada, they support the hypothesis that prior receipt of 2008�C09 TIV may have had direct, adverse effects on Apdm09 illness. Both human and ferret findings from Canada are consistent with observations elsewhere of enhanced disease following heterologous influenza challenge in vaccinated swine. Given the potential implications for informing influenza immuno-epidemiology and public health response to other emerging viruses, these signals warrant further in-depth evaluation and a search for possible mechanistic UNC669 explanations. As shown in various microarray studies of multiple sclerosis and its experimental models, gene expression profiling represents a potent and hypothesis-free method to analyze the complex pathogenesis of demyelination. However, these transcriptomic studies use diverse methodologies, focus on different pathomechanisms and commonly display a low overlap of differentially expressed genes. Meta-analyses are more powerful in detecting true qualitative effects and avoid rare and heterogeneous, thus less reliable outcomes. Furthermore, meta-analyses efficiently tackle the publication bias which shifts the focus of single microarray studies on individual high scoring pathways. Histologically, MS lesions are characterized by a variable degree of demyelination, remyelination, inflammation, gliosis, and axonal injury. In fact, based on morphology, four different patterns have been described in actively demyelinating MS lesions, indicating different pathomechanisms and a heterogenous etiology of the disease. While T cell and macrophage infiltration is present in all of these patterns, a marked loss of oligodendrocytes is observed only in pattern III and IV. The discriminating feature of pattern I and II is prominent deposition of immunoglobulins and complement, which are found solely in pattern II. Although oligodendrocyte death is observed in both patterns III and IV, apoptotic oligodendrocytes are exclusively observed in pattern III. The suggested etiologic heterogeneity of MS is reflected by the abundance and diversity of experimental models of demyelination. These Tubeimoside-I include immune-mediated, virus-induced, genetic, and toxic models. Experimental autoimmune encephalomyelitis represents a traditional immune-mediated MS model which is classically induced by encephalitogenic antigens. The susceptibility to EAE and the course of the disease varies among animal species, strain as well as the used antigen. Myelin oligodendrocyte glycoprotein -induced EAE exhibits a disease course which is dependent on the dose and the used species and strain.