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Among those who think every cell is an (innate) immune cell, the signal from infected cells to neighboring cells is not metabolic, but rather type I IFNs secreted by the infected cell and activating IFNARs on neighboring cells. ACOD1 is the name given to this gene after its function was...

Theory only at this point. Theory says parenchymal cells (afferent or efferent neurons, GI SMCs, any cell type generating symptoms) are burning carbon in the itaconate cycle and therefore are producing insufficient reducing equivalents (and ATP) to carry out their normal physiological work...

Agreed. Could be as many rogue cell populations as there were infected cells during the "trigger" infection.

Certainly, we need evidence of ACOD1 expression in sick cells, but itaconate inhibition of SDH is not the hypothesized mechanism of TCA cycle dysfunction. What matters is not the local concentration of itaconate, but rather the fraction of TCA cycle flux that is diverted to the shunt. If...

Tom and Jonathan, Just a point of clarification: The innate immune response I'm invoking is the response of parenchymal cells to infection, not a response of the myeloid lineage. The itaconate shunt hypothesis is not about professional immune cells. Instead, it is an extension of the idea that...

True. But the evolution of biological feedback control comes at the cost of nonlinearity and nonlinear systems have features that linear systems do not. Prominent among those features is bistability. A simple definition of bistability is that the system can operate in two different steady states...

Hi Jonathan, There is no publication. I'm just obsessed with finding a cure for this damn disease. The hypothesis has two parts: 1) the shunt itself (cis-aconitate-->itaconate-->itaconyl-CoA-->citramalyl-CoA and then a lyase (CLYBL) that brings the C5 pathway to its short circuit end: pyruvate...

Max Artyomov was asked about the other PRDXs during the Q&A of his recent Harvard talk. He said that he believes other PRDXs respond the same as PRDX5.

Even details of stellate ganglion neuroanatomy would be valuable.

It's still a shame that PR and S4ME are not a single forum.

The field of IDO1 inhibitors and cancer has been hot for years now, but as this Frontiers article highlights, most Pharma firms abandoned these programs with the first Phase 3 failure. I was actually glad these drugs did not meet their clinical endpoint goals because I worried that they might...

Lots of people are working hard to prepare for this. I hope you all can join us at least on livestream. If you are physically present, please stop me and say hello.

@Andy That too is a great idea. Thanks!

This is a great idea. I'm on it.

EDIT: @Chris Ponting Reading your post for maybe the fifth time, I infer that the burden of multiple testing does not devolve from how many tests I DID, but rather how many tests I could have done. Is that inference correct?

@Chris Ponting I've struggled with the statistical aspects of this, and I'll follow up on your suggestions. It has always seemed odd to me that the appropriate statistical test depends on how you came upon the observation you want to test for significance. As I've said elsewhere, I'm a classical...

@Keela Too If you have those data on stepcounts vs. date in a spreadsheet or a text file, I would love to have a look. I'm always happiest when time is on the horizontal axis.

@Barry I have no safety engineering background, but I am an engineer first, and a physiologist second. Like you, I've followed the 737 Max debacle pretty closely, and my favorite insight from that reading is this. The big philosophical difference between Boeing and Airbus is that Boeing has long...

Theoretically, you could find a trap by simulation of differential equation models. Experimentally, you might observe the consequences of a trap by finding some of your cells in one state, and other cells in another state when all the external conditions were the same. Of course, you'd have to...

As I've said elsewhere in this thread, IDO2, despite its numbering, is the ancient gene. It's the one in our evolutionary ancestors. If I had to guess, IDO1 evolved in order to yield a higher affinity (lower Km) for Trp. In other words, IDO1 evolved to compete for Trp. You're not the only...