Thus, we employed the same GAL4/GAL80 combinations described above, using effectors that have a known and consistent mode of action independent of the type of neuron.
The observed loss of biological activity of 1 and 2 in the presence of a thiol is consistent with a mode of action for these compounds in which covalent modification of cysteine residues in either the p50 or p65 subunit of NF-κB occurs.
This would be consistent with a mode of action in which the native state is only partially stabilized.
In our studies, the activity of TMC207 and PA-824 against replicating M. tuberculosis was consistent with a bacteriostatic mode of action.
These observations are consistent with an estrogenic mode of action for chlordecone, methoxychlor, and o, p′-DDT effects on autoimmunity.
This spectrum of activity is consistent with an antiangiogenic mode of action, mediated through inhibition of VEGFR tyrosine kinase activity in tumour-associated endothelial cells.
Although they were apparently unrelated, these results may be consistent with an antifolate mode of action of metformin, which leads to disturbances in the inter-dependently linked one-carbon and glutathione metabolic processes (Fig. 2A) [ 62- 64].
Choline-transport assays in both transfected cells and monocytes from affected individuals revealed significant reductions in hemicholinium-3-sensitive choline uptake, a finding consistent with a dominant-negative mode of action.
Thirdly, AMPK activators fail to alter Paired Pulse Facilitation, which suggests a post-synaptic mode of action, consistent with the site of mTOR activity [7], [32].
Of note, when VAPwt and VAPP58S were coexpressed, the percentage of rescued males that eclosed was very similar to that observed with VAPP58S alone, suggesting that the ALS8-associated mutation may impair the function of the wild type protein, consistent with a dominant negative mode of action (Figure 2A).
Consistent with a caspase-specific mode of action, concentrations of up to 94 μM failed to protect yeast against Bax-induced lethality.
