Neuropsychopharmacology (2012) 37, 2332-2344; doi:10.1038/npp.2012.88; published online 6 June 2012″
“A review of the epidemiological literature linking pesticides to cancers in occupational studies worldwide was conducted, with particular focus on those articles published after the release of IARC Monograph 53 (1991): Occupational Exposures in Insecticide Applications and Some Pesticides. Important new data are now available. Chemicals in every major functional class of pesticides including insecticides, herbicide, fungicides, and fumigants have been observed to have significant associations with an array of cancer

sites. Moreover, associations were observed with specific chemicals in many chemical classes of pesticides such as chlorinated, organophosphate, and carbamate ICG-001 mw insecticides and phenoxy acid and triazine herbicides. However, AZD6244 in vivo not every chemical in these classes was found to be carcinogenic in humans. Twenty-one pesticides identified subsequent to the last IARC

review showed significant exposure-response associations in studies of specific cancers while controlling for major potential confounders. This list is not an exhaustive review and many of these observations need to be evaluated in other epidemiological studies and in conjunction with data from toxicology and cancer biology. Nonetheless, it is reasonable and timely for the scientific community to provide a multidisciplinary expert review and evaluation of these pesticides and their potential to produce cancer in occupational settings.”
“Influenza A (H5N1) virus is one of the world’s greatest pandemic threats. Neuraminidase (NA) inhibitors, oseltamivir and zanamivir, prevent the spread of influenza, but drug-resistant viruses have reduced their effectiveness. Resistance depends on the binding properties of NA-drug complexes. Key residue mutations within the active site of NA glycoproteins diminish binding, thereby resulting in drug resistance. We performed molecular SB-3CT simulations and calculations to characterize the mechanisms of H5N1 influenza virus resistance to oseltamivir and predict potential drug-resistant mutations. We examined two resistant NA

mutations, H274Y and N294S, and one non-drug-resistant mutation, E119G. Six-nanosecond unrestrained molecular dynamic simulations with explicit solvent were performed using NA-oseltamivir complexes containing either NA wild-type H5N1 virus or a variant. MM_PBSA techniques were then used to rank the binding free energies of these complexes. Detailed analyses indicated that conformational change of E276 in the Pocket 1 region of NA is a key source of drug resistance in the H274Y mutant but not in the N294S mutant.”
“The target-independent identification of viral pathogens using ‘shotgun’ metagenomic sequencing is an emerging approach with potentially wide applications in clinical diagnostics, public health monitoring, and viral discovery.