Influenza A virus is a major human and animal pathogen with the potential to cause catastrophic loss of life. Influenza virus reproduces rapidly, mutates frequently, and occasionally crosses species barriers. The recent emergence of swine-origin influenza H1N1 and avian influenza related to highly pathogenic forms of the human virus has highlighted the urgent need for new effective treatments. I describe two crystal structures of complexes made by fragments of PA and PB1, and PB1 and PB2. These novel interfaces are surprisingly small, yet they play a crucial role in regulating the 250 kDa polymerase complex, and are completely conserved among swine, avian and human influenza viruses. Given their importance to viral replication and strict conservation, the PA/PB1 and PB1/PB2 interfaces appear to be promising targets for novel anti-influenza drugs of use against all strains of influenza A virus. It is hoped that the structures presented here will assist the search for such compounds.
Imaging mass spectrometry (IMS) visualizes the distribution of a wide range of biomolecules in cells and tissue sections. IMS can analyze a variety of biomolecules including unexpected metabolites, without labels in a non-targeted way. We developed AP-MALDI (atmospheric pressure matrix assisted laser desorption/ionization) which is equipped with an atmospheric pressure ion-source chamber. It allows us to analyze flesh samples with minimal loss of intrinsic water or volatile compounds.
We introduce the original and present concepts of cell assembly in the working brain and discuss the problem of dynamic size of it. A local cell assembly consisting of closely neighboring neurons was especially difficult to be detected because of spike overlapping of neighboring neurons. We developed a unique technique of spike-sorting that employed independent component analysis and showed that most of closely neighboring neurons in the monkey prefrontal cortex had dynamic and sharp synchrony of firing reflecting local cell assemblies. We propose that real features of cell assemblies could contribute to development of brain-machine interfaces and neuro-rehabilitation.