Ape Dev

Since the current narative du-jour is bridges & bridge hacks, I wanted to do some digging on the harmony bridge on Ethereum which secures ~$330m worth of tokens.

@cremieuxrecueil Now do how to get recombinant proteins, I want me some myostatin inhibitors with nicer safety profiles and better data than follistatin.

The prices of GLP-1s and amylin analogues keep falling Some subscribers just bulk purchased five years of retatrutide (4mg/wk) and cagrilintide (1mg/wk) and the per-person price per week came out to $5.31 including purity testing (99.5/99.8% pure) Skinny's never been cheaper!

@RegenRandy Nice language model.

This is too absolute. MOTS-c isn’t just an antioxidant, it’s a metabolic signal. When you push mitochondrial respiration, you often get a transient rise in ROS. That signal helps drive AMPK and NRF2 adaptation. Some studies show lower oxidative damage over time. Others show higher ROS in specific conditions. As I say to my 6 year old- two things can be true. The real story is timing and context. Early signaling, then improved redox balance. Not ‘never increases ROS.’ That’s not how mitochondrial biology works.

MOTS-c pushes mitochondria to work harder and burn fuel more efficiently. That’s great for metabolic health. But higher metabolic flux also means more reactive oxygen species. (Think of it like exhaust from your car’s tailpipe) Glutathione is the cell’s primary antioxidant defense. Run the engine harder. Upgrade the cooling system too. (And never run your car with your garage door closed) I've started doing 4mg+ MOTS-c dosing a few times a week, and I always pair it with 100mg of Glutathione to handle the increased exhaust.

@zagreusrevival @amaticahealth I’m thinking of having the test done myself and I’m particularly interested in neuromuscular symptoms because that’s what I experience myself.

@_apedev @amaticahealth Yes, sometimes. Why?

Just showed the @amaticahealth graphs to my mom and she was visibly disturbed. I mean, just look at this mess, my brain is not supposed to be that spiky! I think this type of data will do a lot to help incredulous people to understand the seriousness & urgency of this disease.

@zagreusrevival @amaticahealth Do you have fasciculations / neuromuscular symptoms?

@amaticahealth That huge spike in the upper left is my brain's inability to clear glutamate, which matches my symptoms exactly. I suspected this mechanism, and it's great to see it confirmed in the data. I'm very pleased with RNAseq so far.

@jonjazzpics @SBakerMD @mimikmorgan Look into Dr. Matthew Phillips and his various case reports & studies. This kind of phenomenon, for a certain subset of neurodegeneration, is starting to look more and more common. Also KETO-ALS at Ulm, Bloom Science & effects of ketones on NLRP3.

@SBakerMD @mimikmorgan Remarkable story, but N=1 isn't evidence. We need systematic research before suggesting dietary intervention replaces standard Parkinson's care.

Just finished a great interview with @mimikmorgan She had Parkinson’s disease with tremors, cogwheel rigidity, bradykinesis, could barely walk, was on 1200 mg of L-dopa daily, 330 pills a month -also rheumatoid arthritis on biologics-went keto and now carnivore- off ALL medications, currently deadlifting 135lbs at 72 years of age and getting ready to do a 500 mile walking pilgrimage across Spain! Carnivore can be an awesome healing tool!

@joe_fenrir Low pLDDT isn't really relevant. Neoantigen mRNA vaccine pipeline is sequence > find mutations > predict MHC-binding peptides > encode in mRNA. T cells recognize presented peptides, not the folded protein. Low pLDDT just means the structure model is unreliable.

Structure from the paper. Terrible pLDDT. Enough to say this is as useful as having no structure at all

@JackHadfield14 Dang, I just wish ELISA was a little more standardized across different studies, I nearly pulled the trigger on the protein test just now. Would love to pick your brain a bit on Monday if possible!

@_apedev ELISA in the protein test, RNA Seq in the RNA test

Signing off for Sunday, but will answer any new questions regarding the RNA release on Monday!

@DrSamuelBHume Helpful summary, though it omits a lot of the field... Ephrin? ROCK? Nf-Kb modulation? MAPK? There are at least 4 other NLRP3 inhibitors in trials not listed there.

Who's targeting neuroinflammation in clinical trials?

@fittoberight @paulsaladinomd Now try GLP1s + the myostatin inhibitors that will be flooding the market in 1-2 years.

@paulsaladinomd Preach! GLP-1s = shortcut to sarcopenia and nowhere good. Eat real food, move like you mean it, build muscle the natural way. That's how you win long-term. Ozempic can't touch that. 👊

"Ozempic bod" is not attractive or healthy. GLP-1s are a shortcut to nowhere good. Eat like a human (single ingredient foods and foods with ingredients your great grandmother would recognize) and move like a human. This is the way.

@maggiemoda Yeah, a year or two until everyone's on apitegromab, bimagrumab, trevogrumab or their next-gen successors with even fewer sides and you'll need to find a new status symbol.

Muscle is going to be the new status symbol now that everyone’s on Ozempic. You better hit the gym!!

what @_apedev and I have been cooking in the kitchen

@Elijahkrings @biohacker Plasmalogens are bullshit quackery from Dayan Goodenowe. Stay away.

Would highly encourage you to look into plasmalogens Seem to be very beneficial in restructuring membranes, especially surrounding synapse metabolism & vesicle trafficking Its less about mitochondrial membrane in this context, but overall membrane fluidity & makeup of the CNS which then conserves energy & makes the machinery efficient

They don't want you to know that when you keep mitochondrial health/membrane flexibility optimal during calorie deficits You can have extremely high output With little to no crashes in hormones or energy This is because mitochondrial membrane composition Particularly the ratio of omega-3 to omega-6 phospholipids and cardiolipin integrity directly affects electron transport chain efficiency When your membranes are fluid and well-structured, ATP yield per unit substrate is higher Meaning you extract more energy from less food...

@CharlesMBrenner You'd want to know your NMNAT2 phenotype before taking NR. At least unless you'd like to activate SARM1 and end up with motor neuropathy.

ppl have been asking for head to head comparisons of NR v NMN in humans the data show that at 1.2 g/day, NR had 2.3x the blood NAD-boosting activity versus NMN the paper and the details in this 🧵 doi.org/10.1016/j.isci…

Claiming you die every night because sleep changes your brain chemistry is like saying you die every time you sneeze. Consciousness isn't a static pattern that gets deleted; it's a continuous biological process that persists through change. Compelling writing, but ultimately hogwash dressed up in half-remembered neuroscience.

@BasedBiohacker It's not anabolic at all. We have virtually zero reliable human clinical evidence for this. Cell models and animals, sure. Mostly doesn't translate. It also has nasty sides that don't occur with newer PDE5is like mirodenafil.

tadalafil is NOT just for diamond boners. your brain and muscles will thank you. and no - your piece will not become dependent on it.

@DrSamuelBHume Now do apitegromab and look at the longer term effects of myostatin inhibition on smooth muscle & cardiac muscle.

Adding the muscle-preserving antibody, Bimagrumab, to the GLP1 medicine, Semaglutide, led to: — More weight loss — More fat loss — Bigger reductions in inflammation — Less lean mass loss at a cost of muscle cramps, acne, and GI side-effects

@doctormorphh Mirodenafil >>> tadalafil

the health benefits of tadalafil outweigh the simple side effect of a headache and low bloodpressure - lowers estrogen - improves heart health - lower odds of all cause mortality by 44% - increases the amount of mitochondria you have - decreases stroke risk by 34% - promotes bone cell survival - improves cognition - lowers inflammation - anti-cancer effects (PRMT5 inhibitor) its much more than something that just lowers bloodpressure, its a health compound tadalafil US: modafinilxl.com/buy/generic-ci… tadaladil EU + UK: modawhale.to/shop/erectile-…

@doctornisarEMS @DocPriyamMD You might want to look at recent motor neurone disease trials before you make blanket statements like this.

@DocPriyamMD I don't know of any benefit of water soluble vitamins beyond certain threshold

I am genuinely sick of seeing this nonsense. If you didn’t pass basic physiology, please, just shut the f up about optimizing your health. Let’s talk biology: Vitamin C and B-complex vitamins are water-soluble... the second you shove 25 grams of C into your veins, your kidneys start working overtime to flush it out. You aren’t 'loading your system'; you are literally paying to produce the most expensive urine on the planet...! And don’t get me started on the NAD+ IVs. It’s an expensive biochemical fairy tale. NAD+ is a large, fragile molecule. It gets chewed up by enzymes in your bloodstream long before it ever touches a cell membrane, let alone enters the cell to 'recharge' your mitochondria. It makes me so angry because it’s not just a harmless trend, it’s a grift that prays on people who don't know the difference between a real medical intervention and a wellness scam.