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congrats @chillier @audrey_ryback

I am not sure what to make of it. It isn’t clear to me why the endpoint phenotype being checked is mitochondrial. Upstream signalling responses to the igg fragments seem like they would be more interesting to investigate in the first instance. Or an omics approach to narrow things down for...

Possibly claims of mechanism in the abstract, when there are currently none that can be made in specific terms with reliable evidence behind them.

we have an efferocytosis lab or two next door, i will have to chat with them

Just looking at the slopes as a whole from group to group is what I'd meant

To me it looks like, for the metabolites where there are appreciable differences, that the HC seem to change after exercise but the ME/CFS don't. Scanning over the gradients of the lines, that is. Having looked at this for a few minutes my primary conclusion would be "ME/CFS are not changing in...

Well done. Many (not all, but many) times I try to encourage this within the existing field I am met with resistance. Too much ego. Broadening horizons has proven productive.

This would depend on whether differences in activity levels between the cohorts are sufficient to elicit an effect on this in muscle.

in muscle it certainly would

On attributing the differences seen to bioenergetics and not the other possibilities raised in the thread, Todd told me "We did not see differences in ventilation and hemodynamic responses between patients and controls, so they wouldn't explain the submaximal VO2 and workload findings."

What other explanations might there be for these CPET differences than the proposed "bioenergetic" ones? Cardiovascular delivery, pulmonary gas exchange? I don't know enough about CPET to interpret without spending a lot of time learning about it. I can't find whether the controls were...

Good to find that these results are now available for us to see. I am very curious to know what the people who understand these imaging methods think of this.

Yes, samples from intramural. No, not mice. That's a separate result. The point is that the Hwang paper presents a methodical and cohesive story. The sequential combination of results is the important part. Wallitt being on the Hwang paper doesn't mean it should be discarded. (Figure 5 in the...

As someone who peer reviews 15+ papers a year I can promise you that s4me discussion is more effectively critically and detail-oriented than 9/10 peer reviews. I got 7 reviews back total on my last paper. It was eventually clear to me that 2/7 of them read the paper properly. I initially thought...

Thanks Jess, this is what I had in mind. And perhaps more importantly the demonstration of a putative mechanism by inductive experiments in models in addition to the patient measurements (which is almost never done in the field). I will take a small cohort of rigorously selected samples...

Not be harsh but to just be honest about the area that I understand to the assay level of detail, the papers cited in the impaired mitochondrial function section don't make a case for mitochondrial problems in ME/CFS. The Tomas work (in spite of having become the de facto mitochondrial...

I have thought this for years. IMO there are two key foundations for this line of investigation without which I would be pivoting my research direction much harder than I am. One is the WASF3 paper and one is the FBXL4 hit in DecodeME. I am not convinced about respiration but I think mitophagy...

Hi Liz, I'm Daniel Missailidis, a postdoc cell biologist who has worked on ME/CFS going on 11 years now. I wrote one of the papers you linked (my PhD training was as a mitochondrial person). We have several different omics datasets and a lot of data from cell lines from people with ME/CFS using...

I don't anticipate that anything like this would be a problem, mass spec data is rigorously QCed edit: Sorry, I'm struggling to keep up with everything due to motion sickness this fine Saturday morning, I'll come back when I can

So this is a less than ideal clinical measure, but this is actually fairly old data from samples largely from a CFS clinic from before we improved things. Our current and future studies use FUNCAP. WST can be confounded by a few factors so I don't personally like to use it to relate to lab...