Figure 8 - Effect of treatment on SOD maturity. Dashed line separate different structural series. The PhMe series delivers more Cu to SOD compared to the CuATSM series. Structural elements x, y, z did a, b, c. We did not generate mass spectrometry data for every treatment group.
Some compounds got more copper in than CuATSM. Some were about as effective as rescuing the early phenotype. Some do so while addressing the limitations of CuATSM:
1) CuATSM take weeks to replenish copper-deficient enzymes in the CNS
2) ATSM binds other metals, such as Zinc (McAllum et al., 2013)
3) CuATSM is quickly metabolized within hours, preventing entry into the CNS.
4) CuATSM has a high affinity for binding human serum albumin, which will limit entry into the CNS
5) CuATSM forms stable crystals quickly, which causes problems for synthesis and formulation (dimers result)
Discussion
[JM2]Should talk about copy number, expression levels, Graffmo vs Gurney
[JM3]How long do SODWTxCCS mice treated continuously live?
[JM4]How long did SODWTxCCS mice treated until weaning, then stopped, live?
[JM5]Labeling errors. Would like raw data to remake.
[JM6]Sam: SODWT mice have diminished COX activity
Jared: SODWT mice are indistinguishable from Ntg
I included Sam’s data here (in this comment) in table format. He runs each homogenate 2-3 times and averages the output. Here, reps mean different homogenates of the same tissue. So, the averages on the far right of the table are the averages of 4 to 9 spec readings.
Sam’s data is consistent. However, these numbers are from only 1 litter each (6d or 21d). It’s possible additional litters would give different results.
Sample | Rep1 (2016.09.19) | Rep2 (2015.09.21) | Avg ± SD |
W847 | 0.0948 | 0.0749 | 0.0849 ± 0.0141 |
W848 | 0.0974 | 0.0886 | 0.0930 ± 0.0062 |
W849 | 0.0726 | 0.0583 | 0.0655 ± 0.0101 |
W850 | 0.0880 | 0.0828 | 0.0854 ± 0.0037 |
W851 | 0.0919 | 0.0930 | 0.0925 ± 0.0008 |
Sample | Rep1 (2015.12.30) | Rep2 (2015.12.30) | Rep3 (2016.02.03) | Avg ± SD |
W831 | 0.0275 | 0.0254 | 0.0271 | 0.0267 ± 0.0011 |
W832 | 0.0236 | 0.0274 | 0.0247 | 0.0252 ± 0.0020 |
W835 | 0.0250 | 0.0230 | 0.0257 | 0.0246 ± 0.0014 |
W837 | 0.0236 | 0.0265 | 0.0232 | 0.0244 ± 0.0018 |
W838 | 0.0287 | 0.0220 | 0.0257 | 0.0255 ± 0.0034 |
W839 | 0.0226 | 0.0285 | 0.0258 | 0.0256 ± 0.0030 |
[JM7]There are no statistical outliers (points above or below 1.5 IQR) for SODWTxCCS+CuATSM. Removing the “eyeballed” outliers @ 15d and 21d doesn’t change the inflection much – most notably increased 21d SODWTxCCS CuATSM.
[JM11]should show in figure: SOD maturity from 15d untreated WTxCCS vs G93AxCCS
[JM12]Include representative mass spectra, deconvolution scheme. Do statistics to compare maturity. Include age-matched G93AxCCS
[JM14]Need advice on reporting statistics
[JM15]Mention the blinding and rigor
Maybe go with either the line or the box-and-whiskerrs. Obviously don’t include full ANOVA table
Work on caption
Replace “DMSO” with “Control” or “Untreated” to be consistent with the other figures. Can explain in Methods.
[JM17]Placeholder. Will probably have a redox tower (no structures), then a separate structure diagram with substitution labels.
[JM18]Planning on removing individual data points.
Maybe color the “important” groups?
Maybe color the controls individually and use legend to differentiate, label as untreated.
15-day-old data are currently represented with diagonal line pattern.
X labels don’t need to be so lengthy.
Remove age.
Straighten labels to 90 deg.
Possibly replace compound labels with key?
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