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  1. jnmaciuch

    Review Fluid transport in the brain, 2022, Rasmussen, Mestre, Nedergaard

    Changes is cell volume correspond to changes in water content which correspond to changes in osmolarity [Edit: if passage through astrocytes is the main way through which any solutes actually enter and exit the brain parenchyma then it would be pretty consequential]
  2. jnmaciuch

    Review Fluid transport in the brain, 2022, Rasmussen, Mestre, Nedergaard

    Flow through aquaporins is usually bidirectional and dictated by osmotic gradient. Aquaporins on astrocytes make up a large proportion of the membrane surface area so it seems that it really is a matter of free flow for water itself, but not other solutes that don’t have a comparable selective...
  3. jnmaciuch

    Review Fluid transport in the brain, 2022, Rasmussen, Mestre, Nedergaard

    So then the argument re: the glympathic system and waste clearance is that some (but likely not all) waste products don’t pass back through the endothelial right junction of the blood vessel endothelium into the circulation, they just pass through astrocytes into the “brain lymph” and get...
  4. jnmaciuch

    Review Fluid transport in the brain, 2022, Rasmussen, Mestre, Nedergaard

    Aquaporins are channels in cell membranes that can open to allow selective passage to water and other solutes. Present on nearly all cells, but especially on endothelial/epithelial cells of blood vessels and astrocytes. What's being described is: blood vessels project into the brain parenchyma...
  5. jnmaciuch

    Review Fluid transport in the brain, 2022, Rasmussen, Mestre, Nedergaard

    It’s primarily through aquaporins if I’m remembering correctly. Passive diffusion is also possible depending on various factors contributing to permeability but accounts for a much lower percentage of total water influx [Edit: cross-posted with @Kitty ]
  6. jnmaciuch

    Comparison of Diagnostic Criteria - discussion thread

    It doesn’t, it’s just a diagnostic code for billing purposes. @hallmarkOvME if you are the in US, you can get an ICD code for chronic fatigue syndrome or idiopathic chronic fatigue on your chart. Many physicians will use them interchangeably, unaware of any specific diagnostic criteria for (ME)/CFS
  7. jnmaciuch

    Low Vasopressin In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, 2025, Huhmar/Bragée/Polo

    Could be an interesting connection! cAMP is part of many very central signaling pathways and its effects tend to be highly context-specific.
  8. jnmaciuch

    Low Vasopressin In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, 2025, Huhmar/Bragée/Polo

    I spoke too soon, apparently those same transcription factors also directly regulate vasopressin transcription in the hypothalamus, so it doesnt have to be a downstream problem review: https://pmc.ncbi.nlm.nih.gov/articles/PMC2733102/ [Edit: looks like we now have two pieces of evidence in...
  9. jnmaciuch

    Low Vasopressin In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, 2025, Huhmar/Bragée/Polo

    Might not be a relevant connection, but this preprint links the actual downstream changes induced by vasopressin on collecting duct cells to CREB-family transcription factors, the same ones that control CRH transcription (discussed in this thread)...
  10. jnmaciuch

    Heightened innate immunity may trigger chronic inflammation, fatigue and [PEM]…, 2025, Che, Hornig, Bateman, Klimas, Komaroff, Lipkin+

    Theoretically possible but unlikely to explain results like this. Chronic exposure to a particular pathogen can often have the opposite effect—blunted responses instead of enhanced (and potentially variable between different immune subsets). It would have to be chronic exposure because the...
  11. jnmaciuch

    Preprint Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis, 2025, Zhang+

    Agreed. I suspect this was just viewed as an easier solution than having every bioinformatician change their workflow when reading excel files into and out of their scripts (which we’re often forced to use no matter how many times we introduce lab mates and PIs to the concept of saving as CSV).
  12. jnmaciuch

    Heightened innate immunity may trigger chronic inflammation, fatigue and [PEM]…, 2025, Che, Hornig, Bateman, Klimas, Komaroff, Lipkin+

    The data isn't really consistent with a T cell story, though. SEB is supposed to crosslink MHCII and the TCR to stimulate cytokine production by T cells, but the strongest cytokine induction was much more attributable to myeloids rather than T cells (IL-1B, CXCL5). Plus no difference in the ones...
  13. jnmaciuch

    Heightened innate immunity may trigger chronic inflammation, fatigue and [PEM]…, 2025, Che, Hornig, Bateman, Klimas, Komaroff, Lipkin+

    There are a lot of different sensor proteins on innate and innate-like immune cells, which each have specificity to structures from bacteria, viruses, fungi, etc. But ultimately those different sensors all trigger cascades that end up at similar places: activating a handful of transcription...
  14. jnmaciuch

    Lactic acid, lactate in ME/CFS

    No, that’s been disproven pretty comprehensively. What we know is that lactic acid tends to correlate with the burning feeling during exercise in healthy subjects but does not appear to be the cause (though it likely has a modifying effect on peripheral nerves mediating muscle fatigue more...
  15. jnmaciuch

    Lactic acid, lactate in ME/CFS

    Sure, but my point is that it’s possible to get lactate spikes from various causes, and macrophages have been identified as one such source
  16. jnmaciuch

    Loss of CRH neurons and other neural changes in ME/CFS autopsy study - University of Amsterdam

    I think it’s unlikely to be such a simple mechanism around “cellular energy” when other neuron populations in the same hypothalamic region are having no issues producing other hormones
  17. jnmaciuch

    Loss of CRH neurons and other neural changes in ME/CFS autopsy study - University of Amsterdam

    Good find! This paper you linked shows that the strongest methylation differences in the CRH promoter are in a CREB-binding region, which is consistent this review I also posted earlier in the thread: https://www.sciencedirect.com/science/article/pii/S0091302211000707) There are still a lot of...
  18. jnmaciuch

    Hypotheses and Research Directions for ME/CFS

    No, certainly not claiming every scientist is perfect on this front—just that we can’t chalk up lack of productive science in certain domains to a complete failure to challenge assumptions once scientists get to a certain level of seniority. I think that trend, where it exists, does play a part...
  19. jnmaciuch

    Uncovering the genetic architecture of ME/CFS: a precision approach reveals impact of rare monogenic variation, 2025, Birch, Younger et al

    I don't think we can really answer any of those questions from this data--they were specifically looking for variants that were common between their ME/CFS cases to highlight in the results, not doing an unbiased search. And they're only guessing it's relevant here because it's relevant in some...
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