Previous publications using 1997 H5N1/PR8 clade 3 LOUREIRIN-B reassortant viruses generated by Subbarao and colleagues were not lethal for mice. Therefore, we were expecting the clade 1 and clade 2 reassortant viruses to also be non-lethal and to be able to culture viruses from lungs of infected mice to compare the efficacy of each vaccine based only upon reduction of virus titers. Instead, we found both the clade 1 and clade 2 reassortant viruses to cause precipitous weight loss and to be lethal for mice. Pimozide However, lethality was only observed in mice infected under deep anesthetic, since mice infected under lighter anesthesia conditions showed less dramatic weight loss and no mortality. Therefore, we speculate that these reassortant viruses are lethal under conditions when the virus is allowed to infect the lower respiratory tract. All organisms have stress responses that allow them to sense and respond to damaging conditions by 
altering gene expression. An additional level of complexity is introduced when the inducing signal is sensed on one side of a membrane and that information must be communicated across the membrane for a response to be generated. In Gram-negative bacteria this intercompartmental signaling is required to maintain the cell envelope, which consists of the inner and outer membranes, periplasmic space, and peptidoglycan layer. The cell envelope is a complex, dynamic compartment that is crucial for the survival of the cell. It is not a static structure and can be remodeled in response to environmental conditions. The chemical environment of the cell envelope is distinct from that of the cytoplasm. The envelope lacks ATP, is oxidizing, and can be subject to fluctuations in ionic strength due to passive diffusion of small molecules through outer membrane porins. As such, Gram-negative bacteria possess stress responses that are uniquely targeted to the cell envelope. Involuntary movements, or dyskinesias, represent a debilitating complication of L-3,4-dihydroxyphenylalanine therapy for Parkinson’s disease, experienced, ultimately, by the vast majority of the patients. The past few years have seen unprecedented progress towards better understanding of the underlying neural mechanisms of existing L-dopa-induced dyskinesia. LID has been associated with a sequence of events that include pulsatile stimulation of striatal dopamine receptors, downstream changes in striatal proteins and genes, abnormalities in non-dopaminergic transmitter systems all of which combine to produce alterations in the neuronal firing patterns that signal between the basal ganglia and the cortex. However, the very first molecular events thought to be responsible for the establishment of LID and generally grouped under the term of ”priming”are poorly known. Priming is classically defined as the process by which the brain becomes sensitized such that administration of dopaminergic therapy modifies the response to subsequent dopaminergic treatments. In this way, over time, with repeated treatment, the chance of dopaminergic stimulation eliciting LID is increased and once LID has been established, the severity of dyskinesia increases. Study of immediate-early gene expression has unraveled that a single administration of a DA agonist induces a complex striatal response, including components of homeostatic response to excessive stimulation as well as genes subserving cellular and synaptic plasticity. Puzzlingly enough, while those earlier studies have focused on gene expression, the actual end-products of genes, i.e. the proteins, have not been studied extensively in these models and the priming effect remains almost a mystery.