- Can we trust these measured stem cell replications rate to be relatable to stem cell replication rates in the human tissue environment? Could a difference in measured and actual replication rates matter for interpretation of this metadata analysis?
- Specific tissues have very different cellular and chemical environments in the human body. It’s feasible that these factors may contribute to cancer rates. Are such factors adequately covered by the E factor discussed in the paper? If these factors may mediate stem-cell replication rate are they meaningfully separate from the R factor?
- Specifically why would the hypothesized introduction of the R variable for cancer risk require such strong measures as a direct response from WHO? How might a lay person who peripheral came into contact with this paper view it differently than those with a scientific background? Is such a strong response reasonable or disproportionate (or somewhere in-between)?
- What are ways to build on this basic relationship between divisions and cancer risk into a more encompassing theory for real cancer behavior? What additional variables are needed?
- Due to the potential for link rot utterly disrupting the connectivity between information sources in among publications, how might we further organize older work for future accessibility? In addition to the well known DOI number, what other methods are effective?
- Currently Journals have been trending more and more towards electronic media than physical media. Due to the intrinsic non-permanence of electronic media, what may happen when smaller, predominantly electronic journals go online in the future? How will this data be accessible?
- What different challenges are there in maintaining proper data identification for a bioinformatics analysis with a very large data set compared to a traditional basic science project?
- Who (or what organization) can be charged in enforcing proper data labeling and use? Presumably individual researchers will not be perfect at data stewardship despite that being the ideal outcome.
Maureen 13:09, 10 October 2017 (PDT)great Qs. Looking forward to discussion
- TZAP appears to be correlated to telomere shortening, and the presence of TZAP is confirmed in cell lines with shorter telomeres. Is it likely that TZAP itself contains catalytic properties for directing shortening the telomere loops? Or would it aid in the recruitment or activation of other enzymes?
- On Figure 2C, mutations are made in TRF2 to identify if the TZAP binding region recognizes the same telomeric repeat and can be used to restore function in TRF2 missing its binding domain. Why does chromosomal fusion occur when TRF2 fails to bind? Is there a different phenotype between TRF2 and TRF-Zinc chimera? - Potential answer, the open 3'prime strand in telomere loop formation bind could bind to nonspecific regions of other chromosomes in the absence of TRF2 DNA binding proteins. Phenotypes to me do look different in terms of chromosomal packing, however there is sufficient function to result in fairly normal looking chromosomes
- If we assume that TZAP is directly implicated in shortening telomere length, what process would result in the longer telomeres sometimes found in older (higher replication number) cells? Would TZAP be expressed to a similar amount along a cell’s life time? Is there a “sweet spot”, as seen in the 5 KB and 20Kb celllines, where TZAP will not contribute to shortening?