These remaining causal relationships depicted in Figure 10 may represent the initial location of the major pathways within the network that underwent plasticity during this experiment, pathways which mediated the changes in plasticity observed elsewhere by the spike rate and PGC measures.
In this set of experiments, one pathway ("Synapse I") received paired stimulation while the second pathway ("Synapse II") received only depolarization (Figure 8A, "LTP group").
In fact, in both cross-dataset experiments, the pathway activity scores computed by the LLR method were much more discriminative than the activity scores computed by other inference methods as well as the expression values of the top gene markers.
In the present experiments, this pathway was found to be newly activated by LIPUS.
PC designed the experiments and pathway ranking strategy, collected the results, and wrote parts of the software.
Simulations reproduced the successional dynamics in the evolution experiments, and pathway activation patterns observed in microarray transcript profiles.
For experiments using pathway specific inhibitors, appropriate concentrations of 10058-F4 or PD98059 were added to the medium as concentrated stock solutions dissolved in dimethyl sulfoxide (DMSO, Wako).
This model prediction of dynamically switching AP-1 dimers captures the experimentally observed overall AP-1 activity, and suggests a resolution to a previously confounding interpretation of experiments using pathway inhibitors.
We are grateful for technical assistance with the microarray experiments and pathway analysis from Conover Talbot (JHMI Microarray Core Facility), for helpful discussions with Wayne Bonlie, and for the gift of the magnetic treatment device from AMRI International (Calgary, AB).
RC conducted the transcriptomic experiments and pathway analysis and analyzed the transcriptomic data together with VJH; JRH, SL, CK, SG conducted and analyzed the phytochemical experiments; JRH performed the multivariate statistical analysis using R; MCC performed the genomic authentication experiments; SG and NJS designed the study; NJS wrote the manuscript with participation of the co-authors.
