Posts made by NNight

I don't know if it will be useful to you (you've already been there and done that), but TonEBP/NFAT5 activation could help deactivating HO-1:

We found that TonEBP is a potent suppressor of HO-1 in human and mouse macrophages.

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00850/full

The FXR might help too to rebuild heme:

FXR orchestrates the expression of multiple heme biosynthetic enzymes. Finally, human HepG2 cells and primary human hepatocytes treated with obeticholic acid, showed increased expression of several heme biosynthetic genes.

(In the liver...)

https://pubmed.ncbi.nlm.nih.gov/37695073/

@Razvan
Manganese is interesting as it's part of the SOD2 enzyme which is particularly needed in case of "dehydration".

Empirically, I've also found it to gave me what (the energy) you described. But I don't believe it stayed that way very long, I don't remember well.

Also, manganese is interesting as it seems to do positive things regarding the AQP4 aquaporin, which is involved in the glymphatic system (cleansing system of the brain).

In brain, astrocytes predominantly take up and accumulate manganese and are thus vulnerable to its toxicity. Manganese was shown to induce cell swelling in cultured astrocytes, and oxidative/nitrosative stress (ONS) mediates such swelling. As aquaporin-4 (AQP4) is important in the mechanism of astrocyte swelling, we examined the effect of manganese on AQP4 protein levels in cultured astrocytes. Treatment of cultures with manganese increased AQP4 protein in the plasma membrane (PM), whereas total cellular AQP4 protein and mRNA levels were unchanged, suggesting that increased AQP4 levels is due to its increased stability and/or increased trafficking to the PM and not to its neosynthesis.

Aquaporin-4 in manganese-treated cultured astrocytes

They talk about AQP4 in negative terms here but it really seems to be fundamental for the glymphatic system, for example:

CSF transport is facilitated by the expression of aquaporin-4 (AQP4) water channels on the perivascular endfeet of astrocytes. Mice with genetic deletion of AQP4 (AQP4 KO) exhibit abnormalities in the brain structure and molecular water transport.

Loss of aquaporin-4 results in glymphatic system dysfunction via brain-wide interstitial fluid stagnation

@thibaud
Ok, maybe all starches are not equivalent in your situation (rice is often said to be more easily digestible for example).
Personally I find some lettuce to be well digested too, but it's something personal and you know better than us what works for you

Anyways, welcome to the forum!

Ps: I should have seen that your english was too perfect to be a product of the french education system lol.

@thibaud

The standard answer would be that your diet might be healthier than what you used to eat but is not necessarily optimal as is.

Absolutely no starches nor greens? This seems like a typical "Ray Peat diet".

Don't fall in the "the more atypical my diet is, the more it will be healthy" mentality (I can be a victim of it, I was at least).

You didn't ask that I judge your diet sorry, but adapting your diet and making it more "normal" seems like the only solution. And I am not talking about eating fried PUFA

Are you french?

@thibaud

What do you eat?

@Ecstatic_Hamster said in Low salt diet and water restriction:

Travis told me several times that the process of making oxytocin creates one molecule of vasopressin in addition to the oxytocin, so you have both.

I didn't know their production was necessarily simultaneous, interesting! I believe their degradation might not be though.

I've made a rapid comparison of oxytocin and copper quantities (with help of ChatGPT @sharko ) and they don't match. Copper seems to outnumber oxytocin by a 10^6 factor so this hypothesis seems completely wrong at first sight (except if you consider that it's possible that oxytocin and copper concentrations could be vastly different a the cell's compartment where copper disturbs nuclear receptors activation).

Could oxytocin be helpful as it can bind free copper ions in the cells?

Copper and silver ions seem to impair LXR and FXR activation. This is not necessarily a good thing and could be a cause of symptoms seen in copper overload situations (e.g. Wilson's disease):

Together, these data demonstrate that copper-mediated nuclear receptor dysfunction disrupts liver function in WD and potentially in other disorders associated with increased hepatic copper levels.
Elevated copper impairs hepatic nuclear receptor function in Wilson’s disease

Is this still true when copper is bound to oxytocin?

In this work, we focus on characterizing copper and zinc bound forms of oxytocin and related analogs through far-UV circular dichroism. We report that Cu(II) and Zn(II) bind uniquely to oxytocin and all analogs investigated. Furthermore, we investigate how these metal bound forms may affect downstream signaling of MAPK activation upon receptor binding. We find that both Cu(II) and Zn(II) bound oxytocin attenuates the activation of the MAPK pathway upon receptor binding relative to oxytocin alone.

Metal-induced structural changes to a peptide hormone may have a number of effects on storage, secretion, stability, and/or signaling. In this case, it is possible that both Zn(II) and Cu(II) lend different structural integrities to oxOT at different points in oxOT lifetime. Physiologically, it is possible that Cu(II) is bound to oxOT in serum but, because the concentrations of metal ions surrounding specific tissues are believed to fluctuate, Zn(II) may be able to displace Cu(II) under specific concentrations. It still remains to be seen how Cu(II) would affect oxOT in serum, however, metal binding may be a key player in prevention of degradation; further studies in our lab are underway to test this hypothesis. The binding of metal ions to peptide hormones, particularly oxOT, may provide an additional source for regulation, and this study provides the foundation for future studies.

Investigation of metal modulation of oxytocin structure receptor-mediated signaling

It would be interesting to determine if such an effect (oxytocin binding to copper thus avoiding free copper to disturb FXR and LXR, or other nuclear receptors, activation) could be "significant" in terms of the number of moles of oxytocin with respect to the quantity of copper ions in a cell.

You could do a search on this website with some word you recall was in the thread, or having a look at your browser's history.

@DavidPS thanks!
This Peatbot is quite good for an AI.
That's the impression I've got from reading articles about oxytocin too (and what I've read from Haidut was less "balanced" than these conclusions, but he can have differing opinions from Ray Peat). However, the interpretation of oxytocin effects might be "biased" by how research is done, e.g. supplementing oxytocin with a nasal spray, when oxytocin levels are associated with vasopressin levels, potential other hormones (like secretin) or physiological parameters, and "side effects" could happen if you "de-correlate" them (for example hypo-osmolarity).

@Razvan
Interesting, I've never tried inosine nor P5P.
Last time I took zinc, I had a very strong metallic/strange taste (it was a sort of colloidal solution) and had to spit it out. Made me wondered if I had too much zinc (while I was not even supplementing chronically at the time).

Another person who isn't able to write "Genereux" properly.

Caffeine inhibits hypothalamic A1R to excite oxytocin neuron and ameliorate dietary obesity in mice

We also show that caffeine excites oxytocin expressing neurons, and blockade of the action of oxytocin significantly attenuates the effect of caffeine on energy balance.

Was Ray Peat "against" oxytocin?

@sharko said in Bioenergetic AI Labs: The future of Ray Peat's legacy is already set:

@NNight said in Bioenergetic AI Labs: The future of Ray Peat's legacy is already set:

@sharko
I'm not a naysayer, more like a realist about capabilities of AI.
I agree with T-3, you don't seem to really understand how these models work (your prompt are a bit "fanciful"). And I'm not saying that to be mean.

Ps: I think LLM can be useful for translation, summarization, categorization.

This is a fairly common attitude among Ray fans, many of us like to skip information in order to continue to stick to our faith. You ignored the response I wrote to him. Anyway, I'm really not interested in trying to convince anyone. I enjoy technology that helps me help myself and others.

I'm not really a "Ray fan" and I've always despised the cultish behavior that I had observed on the RPF.

My goal was to give you an honest feedback on your business model (and to criticize some of your "idealism").

I don't want to appear as someone who want to discourage you, this is not my goal. I think it's very good that you want to develop such a project and I'm not of those who are afraid of AI. Again, good Luck!

@sharko
I'm not a naysayer, more like a realist about capabilities of AI.
I agree with T-3, you don't seem to really understand how these models work (your prompt are a bit "fanciful"). And I'm not saying that to be mean.

Ps: I think LLM can be useful for translation, summarization, categorization.

I've been looking at this nightmarish "diagram" for far too long.

@ThinPicking
This is good science fiction.

My latest fad is molybdenum (that's not my first time).

It could be helpful to increase uric acid which seems to be needed during "dehydration" (or dry fasting at least):

Also, it is thought to be able to chelate unbound copper while copper could be impairing transcription factors:

Nevertheless, what is the link between a selective LXR activation and copper homeostasis?
First, copper may bind with high affinity to the DNA‐binding domain of several nuclear receptors, including LXRs, inducing a conformational change that prevents DNA binding and, in turn, their transcriptional activity.
Liver X receptors and copper metabolism: New frontiers for the oxysterol receptors

Ps:

Another theory, first proposed in the 1950s, suggests that uric acid is structural homolog of caffeine (which in turn is a structural homolog of adenosine), and that high uric acid levels promoted mental alertness for primates and contributed to the development of human intelligence [8]. This hypothesis has been increasingly supported by experimental observations, although its role in evolution remains to be confirmed.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093438/

@ThinPicking

Haven't you heard what OpenAI CTO is claiming:

GPT-3 had the intelligence level of a toddler, while GPT-4 was equivalent to that of a high-schooler. The next generation of the model will have the intelligence of someone with a PhD for specific tasks.

Is it viable?
I doubt people would spend so much money for long.
If it works to help their health, it might be worth it, but then they don't need it anymore.
If it doesn't work, then they won't pay more than a few months.

Good luck!

For me salt drives my thirst.

@izkrov

Aldosterone effects are mediated by the mineralocorticoid receptor (MR), a transcription factor highly expressed in the distal nephron. Given that MR expression level constitutes a key element controlling hormone responsiveness, there is much interest in elucidating the molecular mechanisms governing MR expression.

This means that the mineralocorticoid receptor (which mediates the effects of aldosterone) expression might be reduced in conditions of water restriction ("osmotic stress").

Thus, you might (this is an in vitro study) want to restrict water consumption when you limit your salt intake, and vice versa.