alexholehouse

Seeing this happen in real cells in realtime would be – I would have thought – technically almost impossible. We're at the cusp of viewing the formation/loss of clusters of RNA POL or mediator clusters with the most advanced super-res (see Ibrahim Cissé's work) but these are comparatively massive protein clusters, so the idea of being able to view DNA structural transitions at [effectively] single-molecule resolution where that transition involves a few nucleotides in a non-perturbative way seems like a reach.

Seems like the obvious next step is to break 'em with synonymous mutations and ask if there's any detectable phenotype.

Edit: For clarity - all the in cell work is cultured cell lines and not cells taken from an animal model or in situ imaging.

Literally my only point was that 'this might not matter for biology because we've not even seen it in cells' is no longer true. It still might not matter for biology though!

1) There are different levels/numbers of i-motifs identified depending on the cell cycle position (highest at G1/S boundary, although this is only comparing cells synchronized to G1, G1/S and early S so maybe more at different points?), suggesting these structures don't just stably form and then just sit happily around for the entire lifetime of the cell.

2) In vitro these motifs are less stable than (say) G-quadruplexes so presumably there is a suggestion they may be transient over short timescales, but this is not actually examined in the paper. No idea how you'd actually test this without inherently perturbing the equilibrium being examined in vivo. Even if you could avoid fixing the cells antibodies would be out of the question because of the inherent linkage (if you bind the i-motif with a 500 pM Kd [high affinity] you're gonna HUGELY stabilize that conformation).

Ah - this is very good point, thanks for following up on this!

I did feel awkward writing it - in this case it was actually meant sincerely. I really wasn't sure if I'd misunderstood. It seemed too ironic in a discussion on open minded-ness to basically say "I immediately stopped listening after I heard something I didn't like" (although maybe this is a reasonable approach? I'd strongly argue it's not, but that's certainly a discussion we can have). I'll do my best to catch myself in the future. I should say that I did read your comment as a touch condescending, just FYI.

WRT to Dunning-Kruger for open-mindedness (which is a very interesting idea) some quick searches didn't reveal anything obvious, but I may be using the wrong keywords - social psychology isn't exactly my strong suit! Sort of intuitively you'd think a similar kind of relationship might exist ("Of course I'm open minded, but I _know_ that X is X and Y is Y, but those are truths not debatable ideas!") - although maybe now I'm conflating open mindedness with the ability to think critically...

If the fact that you disagrees with the first clause in an argument is enough for you to conclude the rest of the discussion is unable to make you change your opinion, I'd argue that is a much more significant barrier to open dialogue.

And why we see fields like law being dominated by women, right?

EDIT: I, and I suspect most other scientists wouldn't disagree that there are [edit - had this as aren't previously, woops!] physiological differences between men and women, but as I read the memo, that was not what was being argued. What was being argued was that those differences were the reason for the gender imbalance in tech (i.e. women are predisposition to be less interested/capable in STEM fields), in other words, the effect size associated with biological sex is larger (and indeed must be significantly larger) than any/all combined societal/'nurture' effects.