Several experiments were only n=1, but the 2023 PNAS paper includes muscle biopsies from a small cohort validating the levels of a few of the identified proteins
Thanks a lot, that’s really helpful. I think I finally figured out something really critical that ive been circling around for months without realizing it. I was focusing on one way to get to “flu-like” symptoms, when there is at least one different pathway that would end up being described...
Oh my goodness I made a critical mistake while reading this paper and it may have been a clue this whole time. I must have mixed it up because I had a ton of interferon-related papers open at the same time as I was typing up the summary of this one.
Malate does not inhibit interferon beta...
Sorry, would you actually mind sharing what you mean specifically here? I think it could be an extremely important detail viewed in light of one other detail you shared
Thanks for sharing! Sorry for the confusing wording, mostly just trying to account for the difference between symptoms that someone almost never experiences outside of viral infection and symptoms that overlap with what normally worsens/appears for them during PEM
Just to chase down a potential lead, if anyone has a recent infection in memory that coincided with a brief improvement, I'd appreciate getting a better sense of the timeline.
Specifically I'd be interested in knowing the approximate start and end of:
1) the improvement in ME/CFS symptoms
2)...
Thanks for explaining more. I think I get where you're coming from, there's just residual confusion from us understanding the same term to mean different things. For understanding the illness itself I think it comes down to understanding what is the feedback loop driving the chronic disease...
Interesting tidbit: the cluster of hits surrounding the most significant SNP in this region (the upper left "cluster" in the top plot, highlighted by the blue in the lower plot) sits right in the middle of an identified long non-coding RNA and overlaps a transcription factor binding site. I will...
Thanks for sharing--yeah, the latter link is something I have been thinking about a lot lately in terms of how to interpret hits in intergenic or intronic regions. That link in particular is an example of a non-coding RNA that is right in proximity of ZNFX1 on the opposite strand, but plenty of...
Hi @KNBaldwin, I’m sorry your loved one is suffering and you’re feeling the frustration of not having answers for her.
I can provide some context as a grad student who has worked on several projects involving cytokine measurement (in studies about acute infection, long covid, etc.). They can...
Blood, most likely. Wouldnt prove the theory but would be strong evidence toward or against its viability. Sorry to be vague on details, it’s early stages of planning so logistics and feasibility might change
Thanks :) I am trying to be mindful of just always seeing connections to the thing I'm interested in whether it's real or not, but as far as hypotheses go this is the best one could hope for in terms of something strongly hinted at by the genetics data. I should note that TRIM38, another tier 1...
Explain like I'm brain-foggy:
ZNFX1 is a gene that was known to be important in the response of tissue cells to viral infection, but we didn't know exactly what it does in that context.
By knocking out the gene in a cell type, it was confirmed that cells without ZNFX1 produce much less...
Potentially interesting connection to some other thoughts about how cells could maintain a portion of the interferon response long term:
STAT1+STAT2+IRF9 form the ISGF3 complex, which has been found to be transcriptionally active and upregulated long term in several cell lines and tissue...
Upon reading this paper, ZNFX1 seems to be more of a chaperone protein that suppresses NLPR3 under normal conditions until other cascades "free" NLRP3 from ZNFX1. So I'm not sure that increased expression of ZNFX1 would itself have much effect on NLRP3 activation if all other parts of the...
Reason for posting:
An alternative way that ZNFX1 could be directly relevant to immune signaling in the brain, one that might make more sense with potentially increased expression in DecodeME pwME with that SNP
[Edit: realizing belatedly that this is a connection that was already made by...
Mitochondria-localised ZNFX1 functions as a dsRNA sensor to initiate antiviral responses through MAVS
Abstract
In the past two decades, emerging studies have suggested that DExD/H box helicases belonging to helicase superfamily 2 (SF2) play essential roles in antiviral innate immunity...
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