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I love when this sort of step forward happens in basic science, allowing us to see what is happening in cells at a basic level. I bet some assumptions get overturned! For us, I bet there's many uses. One occurs to me: This may be a way to test the purinergic signalling theory (atp is a...

A clincial trial on glycocalyx repair is starting soon, by Klimas.

Just hooking onto this most recent mention of the glycocalyx. Was watching the Nancy klimas talk from IIMEC 2024, and she discusses the glycocalyx, a structure I'd never before heard of and which is only rarely mentioned in these pages. They are running a clinical trial on a substance that is...

It does seem different although I think technically his finding is bh4 as a % of total biopterin rather than absolute levels. His work is also n=1 and the model patient is who you think. Ron says he gave Whitney some synthetic BH2 which made this ratio even lower and Whitney felt much worse.

Fascinating story. Most people are interested in the power angle, who can shut down an investigation. And that's important. But what I'm interested in is the mention of prion disease. Prions are amino acids that can make other amino acids take on their shape. In essence they are contagious...

This is pretty amazing stuff, and matches my sense, as I go through my early 40s, that everything is going downhill fast!

This. The Hwang paper does not suggest a genetic cause for elevated wasf3. It suggests it is downstream of endoplasmic reticulum (ER) stress. Perhaps there's a genetic reason for the ER stress but I wouldn't expect to find a direct wasf3 genetic issue. Here's a few anonymous samples they...

It's all just in the original paper. They built a transgenic mouse with extra copies of wasf3 and found it was crap at running. tbh my memory was that they used tudca and salubrinal on the mice but actually those drugs were used on patient cells in vitro (as seen in figure below). My guess is...

This looked exciting but I watched the corresponding segment and it seems to be that bh4 is 39% in a single mecfs patient, and Ron implies it's a blood relation of his. So sample size not big yet! The part where teams are genetically engineering zebra fish to overuse the itaconate shunt is...

Just to add a positive note.:nailbiting: I think this study is awesome. It validates, in an enormous cohort, that you can be sick as hell even if all the standard normal blood tests say you're fine. 1. It extinguishes the argument that you must be fine because the blood tests says so. 2. It...

Creating a baseline of data on what healthy and unhealthy bodies do under exercise is going to be really useful. The timeline they have there is maybe not long enough to capture PEM. But that doesn't mean differences won't be present in the early phases. Hanson's data seems to suggest that...

The just world fallacy goes like this: people who get sick are the ones who, at some subconscious level, want to. it's an extremely comforting pattern of thinking for the healthy and it will never go away.

I'm posting this one because I've never seen hypoxia responses linked to circadian issues before. But they are, the paper claims, linked. There's a mystery in mecfs which perhaps this could shed some light on, and that is that people report feeling better at different times of day. The most...

Hepatic BMAL1 and HIF1α regulate a time-dependent hypoxic response and prevent hepatopulmonary-like syndrome Vaishnavi Dandavate 1 , Nityanand Bolshette 1 , Rachel Van Drunen 1 , Gal Manella 1 , Hanna Bueno-Levy 2 , Mirie Zerbib 2 , Ippei Kawano 1 , Marina Golik 1 , Yaarit Adamovich 1...

One of the metabolic pathways we use, right at the start of actvity, is Phosphocreatine. It's used before the body can get normal metabolic pathways up and running, in the first 10 seconds or so. Isometimes wonder if we might rely on that for longer than other people and end up forcing levels...

it's not the sort of ultra cure you might hope for when matching a treatment to a defined subset. And with people whose course of illness is short, you'd expect some spontaneous remissions. Definitely ambiguous to me whether they have something there.

Well, 1. there's a lot of the body outside the mitochondria. most diseases find their cause other parts of the body. e.g. for us maybe the mitochondria are in themselves fine but they aren't getting enough substrate or oxygen or they keep gettign sent signals to fragment, or the cell itself...

Fascinating little paper. TTMV9 is an anellovirus. Wikipedia says: "Their virome has been present in most humans. They enter in the cell early in life and replicate persistently.[8] This happens in the first month of life. It remains debated whether or not the first infection is symptomatic...

I've noticed I react strongly to food made in a slow cooker. Even if the ingredients should be on my fodmap safe list. I now suspect that could be histamine intolerance! I wonder if this also explains why sometimes I can eat a tomato dish the day it's made but if it sits in the fridge overnight...

I've experienced hypoglycaemia related to rapid gastric emptying before. It usually follows a very specific pattern that is quite rare for me now I live a more constrained life. But it used to go like this: 1. eat not very much for hours. 2. eat a massive quantity of carbs. 3. start to do some...