Surprisingly little is known about how these markers change differentially over time according to such Lomitapide Mesylate factors as disease severity or the host’s baseline immune status, or how quickly they return to the pre-infection state. A second goal will be to compare the prognostic value of biomarkers in infection due to Apdm09 virus to that found in infection with other influenza viruses. It is unclear at present whether these correlations observed with Apdm09 virus infection reflect broad-based host response pathways that can be applied, for example, universally to influenza A virus infections as a whole, or whether more discrete differences in various cytokine response patterns will emerge as different subtypes are examined further. These and other types of analyses should be readily possible under the bounds of these ongoing studies. Our studies support the general idea that neurons must maintain a relatively narrow range of TDP-43 expression and that disruption of TDP-43 autoregulatory mechanisms is likely to instigate the neurodegenerative process. Interestingly, TDP-43 induced neuron dysfunction does not appear to involve caspase activation, which is similar to results observed upon misexpression of polyglutamine-expanded Huntingtin fragment. Thus, although degenerative changes are observed in both photoreceptor neurons and motor neurons in TDP-43 transgenic Drosophila, paralysis and death in these flies may not be attributable to neuron death per se, but rather a consequence of severely perturbed neuronal function secondary to wholesale changes in gene regulation. This is consistent with reports in the literature that TDP-43 regulates the Drosophila neuromuscular junction. Our study is one of several recent reports examining the impact of TDP-43 misexpression on neuronal gene expression and RNA splicing. Microarray analysis revealed hundreds of gene expression changes in GMR-Gal4/UAS-TDP-43 flies as compared to controls. A number of these genes are functionally related and are implicated in neurodegenerative processes. Mitochondrial and redox genes such as Ucp4b and the cytochrome P450 homologs contribute to cellular oxidative homeostasis, disruption of which has been implicated in neurodegenerative disease, including SOD1 ALS. Additionally, we found numerous cell cycle regulatory genes upregulated in TDP-43 flies. Some of these genes, such as string and greatwall, were also found to be altered in A-T flies, and mutations of these two genes Albaspidin-AA rescued A-T phenotypes. We similarly found that string mutation rescued our TDP-43induced lifespan defect, though for unknown reasons only in female flies. These findings suggest that cell cycle activation and progression in neurons may be important in the pathogenesis of ALS and other neurodegenerative diseases, as put forward by others. Additionally, we found that TDP-43 upregulated a number of Notch target genes, implying activation of this cell differentiation pathway in vivo. Notch activation has previously been implicated in prion disease, suggesting a potential common mechanism with ALS; intriguingly, the C-terminal domain of TDP-43 has prion-like characteristics. Although knockdown of individual Notch target genes did not rescue the TDP-43 lifespan phenotype, global blockade of Notch signaling, via simultaneous deletion of Delta/Serrate and inversion of the entire E locus, did significantly rescue the lifespan of TDP-43 flies.