The I86M mutation of WSN PA subunit also reduced replication and transcription, although the reduced level of cRNA was not statistically significant. It has previously been shown that the position 86 locates in the 4th alpha helix which is exposed to the surface of the PA subunit, indicating that this region may be associated with the RNA binding. In summary, we show that particular combination of subunits of influenza RNA polymerase can modulate its thermal sensitivity. In addition, position 114 of the PA subunit is involved in conferring stability to thermal stresses. How does influenza A virus adapt to MG132 Proteasome inhibitor various hosts that possess different body temperatures? We propose, given the evidence presented in this paper, that in the emergence of new pandemic viruses the subunit of RNA polymerase are reassorted and/or mutated to allow adaptation of the virus to the differing temperature of the new host. Pramipexole is a dopamine D2 receptor subfamily agonist. It was introduced for treating motor symptoms in patients with idiopathic Parkinson’s disease and has been shown to be effective by various clinical trials. In addition, various studies have recently found antidepressive effects of pramipexole not only in patients with PD complicated by depressive state, but also in depressive patients without parkinsonian symptoms. Its antidepressive effects have been also shown in animal experiments. The D2R subfamily consists of D2,D 3, and D4 receptor subtypes. Pramipexole is active mainly at D2 and D3 receptors, and compared with other dopamine agonists, it is unique in that the binding affinity for D3 receptors is higher than that for D2 receptors. Kvernmo et al. reported that binding affinities for cloned human D2 and D3 receptors of pramipexole were 3.9 and 0.5 nmol/L, respectively. The distribution of D3 receptors in the brain is different from that of D2 receptors. Compared with D2 receptors, D3 receptors are predominantly located in extrastriatal regions including the mesolimbic dopamine system involved in mood and behavior. On the other hand, although both D2 and D3 receptors in the striatum are much more abundant than those in other regions, the D2 receptor density is higher than the D3 receptor density in the striatum. Stimulation of D2 and D3 receptors appears to induce different effects. There are growing evidences that D3 receptors may play a role in the pathogenesis of depression because of their pharmacology and distribution in the brain, although the exact mechanism remains unknown. The mechanism of antidepressive effects and extrastriatal binding sites of pramipexole are also unknown, and no study has investigated this issue. These effects have been speculated to occur by means of activation of D2R subfamily, especially the D3 receptor subtype, in the mesolimbic dopamine system. Therefore, we aimed to determine the binding sites of pramipexole in the extrastriatal dopaminergic regions by using 11C-FLB 457 positron emission tomography scanning for quantification of D2/D3 receptors in extrastriatal brain regions.