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Being mindful of confirmation bias and limitations of this study, I just realized that IRF2BPL is in the same family as IRF2BP2, through which malate/malic acid has been found to downregulate IL-1B response in macrophages under certain pH and ER stress conditions…like you’d also expect to find...

If the proteasome is non-functional (or even severely dysfunctional), absolutely. Though you'd probably also present with much more serious and immediate health issues as well. However, at a milder scale, accumulation of misfolded proteins happens in all sort of situations and activating...

Same first name, different last name it looks like

Not if the problem is over fitting, which would be the most likely issue. Sure, what you’re saying is theoretically possible, it always is, but in all honesty it seems vanishingly so here [Edit: just to make it explicit, in my experience a small test cohort tends to stack the deck against you...

I’d also keep in mind that they did lose a lot of accuracy in the test set using their original HEAL model. If it was simply a case where the training models were overfit and the test cohort happened to really resemble the training cohort by chance, you would expect the HEAL model to also do...

I may have already gotten to a similar conclusion as you via different means. Interested to read your paper, there might be a bit that already aligns with what I am trying to investigate with tissue samples

I think I see @chillier ’s point though of starting at the time frame of PEM and working backwards. You’re probably right that the neuron doesn’t necessarily need to translate new proteins in order to react to some stimulus, but if there is an important modulatory process where this occurs, it...

You may be right! It seems not to be the case for e.g. the peptides in the paper I linked (nor for most that I’m familiar with, which granted isn’t that many neuronal proteins), but in theory it seems possible. [edit: though the time differential gained by translating later wouldn’t be that...

I may not be 100% correct about this in the specific neuronal context, but in most cells the translation happens either within the ER or in nearby free-floating ribosomes in the cytosol and would be in close proximity to the nucleus either way. It’s typically folded proteins that traffic along...

And even if they could somehow definitively prove it for themselves, there’s absolutely no basis for claiming it cures anyone other than themselves. Even well-tested biomedical treatments can’t make that claim full stop—there’s always going to be the percentage of people who are non-responders...

I think for similar big data-driven methods, such as ATAC-seq and RNA-seq, it is possible to get worthwhile results even from such a small cohort. Information at an individual gene level is almost certainly going to be highly variable and frankly is not expected to generalize even from larger...

I wouldn’t give up hope, you could still make an entire career off the vegetable theory

Alternatively, the vast amount of ideas get ignored after being determined inconsequential, but some shining bits raise the alarm so that the problem gets attacked head-on!

Would the corollary, then, be that it tends to look temporally consistent as well? Or would there be room for fluctuation triggered by activity

Very astute @Sasha! Certainly more astute than my brain’s attempts to do the same thing. When I recently learned about the malate-aspartate shuttle, I ended up on a bus that crosses a highway overpass with no pedestrian sidewalks. “It’s just like the MAS crossing the impermeable mitochondrial...

Many of my family members say so, and I will also occasionally crave a fruit or vegetable. But I also sometimes crave capers straight out of the jar, so my hypothalamus is doing some funky things anyways

The other last author is the BSS analysis expert Tate referenced in the email to @Hutan. It seems like they achieved their PhD more recently, and probably directed/advised the first authors on the analysis. Even if the first authors saw the logic in Hutan’s point, ultimately issues like this...

Agreed with Jonathan, though I think there are still additional missing pieces/contradictions with literature (which, to be clear, is to be expected from any theory so I am not disregarding it out of hand on those reasons). If this theory is correct, you would assume it leads to accumulation of...

I have to agree, vast majority of comments at a conference are “okay, enough about what you just said, how does this relate to [my niche area of interest]?” I’ve been trying to chase down various researchers at my own institution just to share bits of my ideas and get feedback/criticism on...

[edit: sorry, hit post too soon] Yes if you pulled more of the red dots into the middle and pushed the green and blue further apart, it wouldn’t look too far off. It’s a weak signal, so probably would come down to ANOVA between groups on PC2 scores. Definitely would like to see replication on a...