PREreview of "Frequent lack of repressive capacity of promoter DNA methylation identified through genome-wide epigenomic manipulation"
Journal Club EcoEvol #02 - 06.07.2018
and 2 collaborators
UIUC preprint journal club : 2018-07-30
- Keywords: Consider revisiting, as many of the keywords are already on the title. Additionally, it would be helpful to include terms rather than acronyms which are not familiar to non-experts.
- Introduction: Would be good to include examples of some of the limitations to automated confocal microscopy approaches to orientate readers.
- Line 143: (Atwell et al., 2010). This citation doesn't seem to be right. If the author is referring to genomic heritability it could cite de los Campos et al. (2015).
- Methods: Would like to see further information on the methodology used for carbon isotope discrimination in the main text
- Results: Might consider using the term ‘genetic-heritability’ rather than ‘pseudo-heritability’
- Results: Direct comparison with previously reported dC13 values for accessions that have been demonstrated to differing WUE would be helpful.
- Figure 4: the text on the figure is likely to be too small to see properly
- Line 505: “soil composition...” This is a really interesting point about the complexity of environmental effects on plant physiology. It might be helpful to provide some explanation for readers less familiar with soil content. (e.g. water holding content and effect on root structure - e.g.https://doi.org/10.1073/pnas.1721749115)
- Line 499-500. Repetition of text on 498-499
- Results: It would be helpful to share where the functional annotation for genes come from. This gene appears to be involved in mRNA decapping. There is only one publication, which found it is involved in PAMP triggered immunity, plants were dwarf in stature. TAIR does not annotate a role in cell differentiation (10.15252/embj.201488645)
- Discussion: It is interesting to see a comparison with a related species and how the observed pattern is consistent between the two.
- Data accessibility: This is excellent. Great to see that all data and code will be made available and deposited in a permanent repository!
Preprint Journal Club Review of: "Diurnal active photolocation enhances predator detection in a marine fish"
and 4 collaborators
Diurnal active photolocation enhances predator detection in a marine fish
- For the lab experiment:
a. What kind of glass was used for the partition between the triplet and the predator? This is explicitly stated for the field experiment (spectrally neutral Evotron Plexiglas), but we were wondering if the same glass was used in the laboratory experiments?b. What is the purpose of the “sub-optimal substrate” strip of gravel along the long side of the tank and why is it not included in the schematic drawing of the setup?c. In lines 200-201, the authors state, “Both stimuli were simultaneously present in the tank, but only one was visible to the triplefins.” Here we would like to know how they prevented visibility of one stimulus and suggest that the spatial relationship be stated or illustrated more clearly.
PrePrint Journal Club Review: Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia
and 8 collaborators
- Can chemical inhibition of Musashi2’s RNA-binding function be used to selectively target myeloid leukemia cells?
- How does Ro 08-2750 inhibit MSI RNA-binding activity?
- The structure-activity-relationship was clearly described considering a lack of a co-crystal structure.
- Given that residues F66, F97 and R100 of MSI2 are also conserved in MSI1, it would have been interesting to see how Ro 08-2750 compares between both proteins.
- It would be interesting to see measurements of compound binding to MSI2, for example ITC or thermal shift assays.
- The assays used appeared to be well thought out and provided good evidence for target engagement and therapeutic potential in cellular models of AML. However, given the genetic diversity of AML, it would be informative to include a sentence to describe why MOLM13 and K562 cells were selected for these studies.
- In the discussion the authors state that Ro 08-2750 is the first “selective MSI inhibitor”. MSI2 was compared to SYNCRIP for selectivity; however, given the extensive repertoire of RNA binding domains found in the human genome, we feel that a more extensive characterization is warranted to make a definitive statement. This could be accomplished by either utilizing a biotinylated compound for pulldowns and MS-id or by measuring binding to a panel of RRMs.
- It would be interesting to see KD/KO studies alongside compound treatment to evaluate to what degree this compound may phenocopy genetic perturbation of MSI2 in AML. In addition, it would also be cool to see how the mutants deficient in Ro binding are functional in cells, which may hint at potential mechanisms of resistance.
- For the mouse data presented it would be informative to the reader to include both survival and tumour volume data. Additionally, have the authors done any experiments to test the suitability of this compound for in vivo use (ex. What is the PK of Ro?).
- Additional biophysical assay to measure direct binding of the compound to MSI2’s RRM domain would be informative, ex. ITC or thermal shift assay.
- We found that the molecular dynamics analysis greatly complemented the structural data and enabled a thorough description of the potential binding mechanism for the Ro compounds. It would be useful to note whether co-crystallization of MSI2 and Ro was attempted, though the mutagenesis experiments provided evidence of the importance of interactions with F66, R100, and F97. It is unclear why YANK was selected to perform alchemical analysis given that the program has not yet been extensively validated and carries a “Use at your own risk!” warning. It would have been reassuring to see these calculations carried out with a more validated software.
- Extended figure 7 appears to be mislabeled in text and extended figure 8 is missing.
- For figure 3d, we felt it would be easier to interpret if annexin V + cells were normalized to the DMSO control.
- For the RNA-IP experiments, we would suggest that this data be presented as % input, akin to a ChIP experiment. This would account for any changes in gene expression that may confound the interpretation of this result as well as allow the authors to probe RNAs that should not change in response to compound (ie. negative control)
- On line 216: what does “proximal” mean here?
- Classically, the term inhibitor would be reserved for a compound disrupting an enzymatic activity. Here, antagonist may be a more appropriate term.
- Any supplementary tables listed in the text should be included for readers/reviewers.
OIST E&E PREreview Journal Club, "Frequency of disturbance alters diversity, function, and underlying assembly mechanisms of complex bacterial communities"
and 9 collaborators
ITQB Preprint Journal Club: 3 July 2018
and 2 collaborators
ITQB Preprint Journal Club: 9 Nov 2017
Metabolic Interactions Between Dynamic Bacterial Subpopulations
Adam Z Rosenthal, Yutao Qi, Sahand Hormoz, Jin Park, Sophia Hsin-Jung Li, Michael Elowitz
PREreview Journal Club: "Links between environment, diet, and the hunter-gatherer microbiome"
and 6 collaborators