30– 33 In this context, it is important to have sensitive biomarkers that correlate with disease severity and are dose-responsive to therapeutic interventions.
In an attempt to connect the modulated transcripts to our candidate HDAC8 substrates, we searched for known biological pathway connections between our high-confidence HDAC8 substrates and the 70 genes dose-responsive to PCI-34051 treatment (Supplementary Table 4) using the Ingenuity IPA Knowledge Base.
Notably, of these 6 compounds that demonstrated dose responsive toxicity to NSCs, selamectin and amiodarone HCL had the most dramatic effect on NSC survival (Fig. 2B, p<0.001 for amiodarone HCL treated NSC versus similarly treated ESC, N = 3 independent replicates).
Analysis reveals that cells transfected with SMAD-binding promoter construct were dose-dependently responsive to both soluble recombinant BMP2 and Tol-BMP-ST with the highest doses significantly different from Tol-ST alone (P < 0.01).
The limits of detection (LOD) calculated as background OD ± 3SD were 188 and 27 pg/mL for EpCAM and CTSL respectively; the dose responsive ranges were from 0 to 2 ng/mL for both CTSL and EpCAM.
The effect was dose responsive, although raising the concentration to 1000 nM caused no further increases; this would concur with the saturation of a receptor-mediated effect, as reported in other tissues (19, 38, 39).
The effects of U0126 on both biological responses were dose responsive.
However, since the female WT +/+ mice did not respond to loading in a significant dose:responsive manner, the effect in Tb.Th is difficult to interpret.
We find that JW480 significantly lowers LPS-induced TNFα secretion from BMDMs in a dose-responsive manner to levels comparable to those observed with WWL115, indicating that KIAA1363 was largely responsible for the TNFα-lowering effects of this compound.
Is it a switch and a mere whiff of bacteria turns on the response or is it dose responsive?
