structural model obtained from the soaked crystal revealed density in the active site matching the product diethyl thiophosphate, in a known product binding mode. This establishes that the crystal structure observed here is capable of hydrolysing malathion at rapid rates. To investigate whether this increase in activity was a result of relieving the steric hindrance that was inhibiting substrate turnover in the wild-type enzyme, we performed substrate docking with malathion and the engineered Ser308Leu/Tyr309Ala variant. These results confirmed that the widening of the active site that occurs as a result of these mutations allows productive substrate binding and vastly improved turnover rates. It also explains the reduced turnover of paraoxon : Gomisin-D previous work has established that the interaction between the aromatic group of Tyr309 and the aromatic group of paraoxon, which is lost in this mutant, enhances catalysis. Ergosterol Multiple sclerosis is the most frequent chronic inflammatory disease of the central nervous system. Although the pathological features of this chronic demyelinating disease are well established, li le is currently known about the complex mechanisms that lead to the inflammatory process associated with MS. Chronic persistence of Epstein-Barr Virus infected cells in the peripheral circulation and/or in the CNS, possibly associated with lytic viral reactivation, has received increasing a ention during recent years as a potential cause of MS onset and progression. Previous investigations focused mainly on determining the presence of EBV latently infected B lymphocytes within the brain tissue and/or direct viral presence in the CSF. However, results have been highly discordant, with some authors reporting the presence of EBV-infected cells in the vast majority of MS cases, whilst others have failed to demonstrate the presence of EBV or showed positivity in only a minority of MS brain tissues or CSFs. A recent focused experts workshop on the detection of EBV in MS brain highlighted the possibility that divergent results may be due, at least in part, to technical issues, including methodological approaches and differences in the sensitivity and specificity of the various, mostly “in house”, detection assays used. These conclusions are likely to apply also to CSF studies. This study addressed the possibility that the presence of EBV could have been missed in some of the previous studies, due to the pre-analytical and analytical methodologies applied to sample processing and analysis. Standardized commercial methods were used in this study to obtain both high-yield automated recovery of microbial nucleic acids from different clinical matrices and accurate quantification of EBV EBNA-1 gene, using a previously described Real-Time PCR assay. Moreover, a larger sample volume of CSF, as compared to most previous studies, was analyzed in order to increase the sensitivity of detection. Furthermore, in order to establish whether the presence of the virus was associated to latently infected cells or to viral lytic reactivation, EBV DNA detection was performed on both cell-free and cell-associated CSF fractions obtained from relapsing-remi ing MS patients at the onset of a clinical relapse and compared to controls, affected by non-inflammatory or other inflammatory neurological diseases.