For what it’s worth, the full PCA does actually tell an interesting story along PC2—the fact that there are distinct “Neapolitan stripes” between the three groups, despite some messy outliers, is impressive since it is actually taking into consideration all 70K sites (even despite the fact that...
The methods mention that they used the WHO's 2021 case definition, which says this:
So the described features are ME/CFS-like, certainly, if you do not take into account degree of severity or post exertional malaise (considered to be the hallmark characteristic of ME/CFS, if you are...
I have been able to view the PCA on the 70K sites. I don't have permission to share the image itself, but I do have permission to describe it.
As expected, much much less clean separation between groups, all the points are quite dispersed through the 2D space. PC2 gives hints of separation by...
I think it’s more than likely that brain tissue is involved in someway but the issue I’m toying with would not be exclusive to the brain or nerves. Again, sorry to be so vague, even for my idle speculations I prefer to have a couple pieces of evidence to back it up before I put it out there...
I just got a response from the corresponding author, he confirmed that figure 2 is only on significant sites. I've asked if he would mind sharing the PCA on all sites with me. He said that it was more blurry (as you'd expect) but there was still separation between groups.
Thanks! That's really interesting. More specific to the proteasome, or rather, failure to (adequately) degrade particular proteins post viral infection. I still have several details that need to be ironed out, so apologies for being vague.
It may not be the proteasome itself--I was initially...
I briefly saw something about this when I was trying to find the corresponding author's email--from the first news article that came up, it looks like his family member has ME/CFS and he also has trainees with mild ME in his lab.
It is, but from my prior work in macrophages I have never seen it being stimulated by IFNAR or IFNGR activation alone. In macrophages, this is induced via co-stimulation of interferons and LPS, or another TLR activator [edit: leading to both Nf-kB and STAT TF binding to facilitate ACOD1...
Thank you, I am quite aware of all of this, local interferon signaling is my research focus at the moment and exactly what I was referencing in my previous post. My point re: itaconate and SDH was towards local metabolic dysregulation in neighboring cells in response to viral infection [edit...
Thank you, yes I fully understand that, my point was mainly to address the issue of “infected cells and neighboring cells” per your previous post. All the evidence I’ve seen of viral infection leading to altered metabolic environment in nearby cells is mediated through locally activated immune...
Are you at liberty to give more details on exactly what you're finding? I was initially inclined to believe that proteasome findings would be the result of general homeostatic stress like you mentioned, but recently I have more reason to believe they might be directly involved. It's just a hunch...
Thanks for the further info. I am happy to say that the signal is more likely some oligomer attached to nerves, though like @chillier, I just don't see what the story would be with that signal increasing at 24 hours post-exercise. Hence why I was interested in mtDNA, as that would be much more...
This certainly fits with other threads that I have been running down in my own research. However, the main concern would be whether non-myeloid cells actually upregulate IRG1 to a sufficient extent to cause the level of TCA cycle dysregulation you hypothesize.
Tomas noted that other findings...
I haven’t done a DNA methylation analysis like this paper but I do have comparable experience from ATAC-seq which looks at open chromatin (another epigenetic modification that uses similar protocols for sequencing). That study used 3 replicates on old vs. young mice. Even using genetically...
I think there is a discrepancy between what the text says and what the figure legend says. I initially had the same concern as you that they might be pre-selecting the features that would make the findings look best, so I checked the text and saw this:
This certainly suggested to me that all...
It just refers to all the signaling that happens as a result of the NOTCH protein binding to one of its ligands, which is a pretty broad category. It’s involved in a lot of biological processes, most notably in early embryonic development and growth, which is why mutations in it are highly...
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