Clifford Carnicom
Ana Maria Mihalcea
Dr. Derrick Lonsdale

https://carnicominstitute.substack.com/

https://substack.com/@anamihalceamdphd

https://www.hormonesmatter.com/category/research-commentary/

![th-1839119118.jpg](https://images.hive.blog/DQmNeUUpoqhr7NY9XD4QbpzwStVcW56yyof46W8GsiPx7wa/th-1839119118.jpg)

![Amines-vs-Amides-988624189.jpeg](https://images.hive.blog/DQmPA79aYhJoVqXFeU6oFiuC8ivomFxip7jHBWKbSjVSieW/Amines-vs-Amides-988624189.jpeg)

Polyamide
Amide  
Monomer
Elastomer
Crystalline Microstructure

Prion 
Hydrogel
Silk

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Thiamine
vs
Thioamide

GSD
glycogen storage disease 
glycogenosis

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if the idea is correct, B1-Thiamine is not supposed to be a forever cocktail, after awhile should stop taking it at high dose, whack the microbes to behave nicely, knock out the bad element from the mycoplasma & spike.

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The Way forward for the Origin of Life: Prions and Prion-Like Molecules First Hypothesis

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467930/

The Hunt for Ancient Prions: Archaeal Prion-Like Domains Form Amyloid-Based Epigenetic Elements

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480180/

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Methylation
Alkylation
Amidation

Pyridone
Amide

Methylated Pyridone

4PY
N1-methyl-4-pyridone-3-carboxamide

The Biochemical Pathways of Nicotinamide-Derived Pyridones

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866226/

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Magic Methyl Effect

Researchers finding ways to rapidly access the “magic methyl” effect

https://chemistry.illinois.edu/news/2020-03-24/researchers-finding-ways-rapidly-access-magic-methyl-effect

The Deuterated “Magic Methyl” Group: A Guide to Site‐Selective Trideuteromethyl Incorporation and Labeling by Using CD3 Reagents

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457246/

Installing the “magic methyl” – C–H methylation in synthesis

https://pubs.rsc.org/en/content/articlehtml/2021/cs/d0cs00973c

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Polymerization of Alkenes

https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Basic_Principles_of_Organic_Chemistry_(Roberts_and_Caserio)/10:_Alkenes_and_Alkynes_I_-_Ionic_and_Radical_Addition_Reactions/10.09:_Polymerization_of_Alkenes

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Blood Clot Analysis
Chemical Solubility Testing - Part 3 of 3 - Dr. Ana Mihalcea With Clifford Carnicom

Protein polymers are a rubber like substance. We used the following reagents:

Strong Sulfuric Acid

Strong Sodium Hydroxide ( Lye)

Acetone

Alcohol

Toluene

Methylene Chloride (Stripper)

Petrol

NN-diethyl-meta-toluamide (DEET)

PIB, PEA,PIBA (Fuel Injector Cleaner)

Summary:

All solubility tests except that of Sodium Hydroxide fail completely within a window of 72 hours.

Sodium Hydroxide (Lye) shows the possibility of a slight reaction within the same time window.


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B1 Thiamine
Magnesium
Potassium Citrate

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Urea Cycle
Citrulline

https://en.m.wikipedia.org/wiki/Urea_cycle#Urea_cycle_disorders

Steps of the urea cycle

Carbamoyl phosphate is converted to citrulline. With catalysis by ornithine transcarbamylase, the carbamoyl phosphate group is donated to ornithine and releases a phosphate group.

A condensation reaction occurs between the amino group of aspartate and the carbonyl group of citrulline to form argininosuccinate. This reaction is ATP dependent and is catalyzed by argininosuccinate synthetase.

Argininosuccinate undergoes cleavage by argininosuccinase to form arginine and fumarate.

Arginine is cleaved by arginase to form urea and ornithine. The ornithine is then transported back to the mitochondria to begin the urea cycle again.

1 L-ornithine
2 carbamoyl phosphate
3 L-citrulline
4 argininosuccinate
5 fumarate
6 L-arginine
7 urea

L-Asp L-aspartate
CPS-1 carbamoyl phosphate synthetase I
OTC Ornithine transcarbamoylase
ASS argininosuccinate synthetase
ASL argininosuccinate lyase
ARG1 arginase 1


Zinc 
Biotin
Ornithine (OTC)
Carbamoyl Phosphate Synthetase

Thiamine
Metalloenzyme

Triphosphate Tunnel Metalloenzyme Function in Senescence Highlights a Biological Diversification of This Protein Superfamily 

https://academic.oup.com/plphys/article/175/1/473/6117054?login=false

The triphosphate tunnel metalloenzyme (TTM) superfamily comprises a group of enzymes that hydrolyze organophosphate substrates. They exist in all domains of life, yet the biological role of most family members is unclear.

AtTTM2 displays pyrophosphatase activity and is involved in pathogen resistance.

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Thiamine triphosphatase and the CYTH superfamily of proteins

https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.12498

Members of this superfamily of proteins exist in all organisms, including bacteria, archaeons, fungi, plants, and animals (except birds), and can be traced back to the last universal common ancestor. Their sequences include several charged residues involved in divalent cation and triphosphate binding.

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Phase separation of a yeast prion protein promotes cellular fitness

https://www.science.org/doi/10.1126/science.aao5654

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Polyphosphate

TTPase
Thiamin Triphosphatase 

GTPase
Guanosine Triphosphatase

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Prion propagation and inositol polyphosphates

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949079/

The first report of genetic variations in the chicken prion protein gene

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277184/

To date, spontaneous prion disease in birds has not been reported, and parenteral and oral challenge of prion agent has failed to infected chickens. Thus, several studies have attempted to find the feature of the chicken prion protein that leads to prion disease resistance.

Octapeptide repeat sequence was found only in mammals. Chicken has a significantly different form of tandem repeat, called Hexapeptide repeat (amino acids, peptide, protein).

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Hexapeptide
Acetyl Hexapeptide-8 Amide
Botulinum
[Birds]

https://en.m.wikipedia.org/wiki/Acetyl_hexapeptide-3

Octapeptide
Ace
Angiotensin II
[Mammals]

Angiotensin-converting enzyme, or ACE, is a central component of the renin–angiotensin system (RAS).

https://en.m.wikipedia.org/wiki/Angiotensin-converting_enzyme

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both Hexapeptide & Octapeptide are used in skin products as botulinum Botox?

the location that defines Piron resistance or pathogenic, is a botox pathway?

its interesting that the Prion pathway went straight to Octapeptide = ACE, precursor to ACE II.

HIV has ACE II inserts? why is Prion in the same pathways?

this is an incomplete story, specially regarding protein metabolite disfunction & and thiamine for carbon metabolite disfunction.

Urea Cycle
Steps of Urea Cycle
Citrulline
Urea Cycle Disorders

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Octapeptide 
Angiotensin-Converting Enzyme ACE
Prion

The Effect of Octapeptide Repeats on Prion Folding and Misfolding

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918816/

The Number of Octapeptide Repeats Affects the Structure and the Thermal Stability of Prion Proteins

The Expansion Rather Than the Deletion of Octapeptides Enhances the Kinetics of Fibril Conversion

The Number of Octapeptide Repeats Affects the Structures of Fibrils

The Number of Octapeptide Repeats Affects the Cytotoxicity of the Amyloid Fibrils

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Thiamine Triphosphate

https://en.m.wikipedia.org/wiki/Thiamine_triphosphate

In E. coli, ThTP is accumulated in the presence of glucose during amino acid starvation. On the other hand, suppression of the carbon source leads to the accumulation, of adenosine thiamine triphosphate (AThTP).

Adenosine Thiamine Triphosphate

https://en.m.wikipedia.org/wiki/Adenosine_thiamine_triphosphate

The molecule is made up of thiamine and adenosine joined together with phosphate groups. It is similar in structure to NAD+. The function of AThTP is not currently known but it has been shown to inhibit the activity of PARP-1.

PARP1

https://en.m.wikipedia.org/wiki/PARP1

Following severe DNA damage, excessive activation of PARP1 can lead to cell death. Initially, overactivation of the enzyme was linked to apoptotic cell death but later, PARP1-mediated cell death turned out to show characteristics of necrotic cell death (i.e. early plasma membrane disruption, structural and functional mitochondrial alterations).

Thiamine Mononitrate (X2)
Potassium Citrate (X2)
Magnesium Chloride (X1)
Sodium Bicarbonate (X1)

X=Tablespoon
12 Ounce of Water

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sipped about a shot glass over the night, well that was intense.

and it is still doing things, not very good for sleeping.

this is the most effective hodgepodge combination tried so far.

its break down the acids from my legs to head, effective almost instantly, and it lasts for hours.

tested megadose of Thiamine for months, to get a good idea what it does, mixing it with buffered alkaline minerals seems to multiply the binding properties.

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https://www.reddit.com/r/LongCovid/comments/yl3a8b/thiamine_my_favorite_b_vitamin/

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Cytosine-Guanine Dinucleotides (CpGs) 

Methylated Cytosine (5mC)

5-Carbon Cytosine
5-Methylcytosine

HLA-DR (gene)

https://en.m.wikipedia.org/wiki/HLA-DR

Gene expression and epigenetic markers of prion diseases

https://link.springer.com/article/10.1007/s00441-022-03603-2

Methylation predominantly occurs at the 5’-carbon of cytosine in cytosine-guanine dinucleotides (CpGs) which are unevenly distributed across the genome being concentrated in “islands” near to gene regulatory regions. Methylated cytosine (5mC) is sometimes referred to as the 5th base of DNA.

DNA Methylation:

X-Chromosome 
DNMT3A / DNMT3B 
DNMT (MTase domain)
Carboxy Terminus 
Chromatin Reading Domains

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"Methylation predominantly occurs at the 5’-carbon"

Thiamine: Thiazole

is that the exact location of Prion misfolding & what Thiamine interacts with?

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Thiazole
Aminothiazole

Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268695/

Though free thiazole cannot be spotted in nature, the ring of thiazole is detected in several natural compounds, such as peptide alkaloids, metabolites, cyclopeptides (and Thiamine).

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Sodium and Potassium Ions in Proteins and Enzyme Catalysis

https://pubmed.ncbi.nlm.nih.gov/26860304/

Na(+) and K(+) play important roles other than being nonspecific ionic buffering agents or mediators of solute exchange and transport. Molecular evolution and regulated high intracellular and extracellular M(+) concentrations led to incorporation of selective Na(+) and K(+) binding sites into enzymes to stabilize catalytic intermediates or to provide optimal positioning of substrates. The mechanism of M(+) activation, as derived from kinetic studies along with structural analysis, has led to the classification of cofactor-like (type I) or allosteric effector (type II) activated enzymes.

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pH-Dependent
Thiazole

Effect of pH and concentration on the chemical stability and reaction kinetics of thiamine mononitrate and thiamine chloride hydrochloride in solution

https://bmcchem.biomedcentral.com/articles/10.1186/s13065-021-00773-y

Thiamine Assays—Advances, Challenges, and Caveats

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390807/

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Thiazole 
Thiazolium Salts (Cation) Alkaline

Thiazolium Salts as Chalcogen Bond Donors

https://pubs.acs.org/doi/10.1021/acs.cgd.2c00510

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https://en.m.wikipedia.org/wiki/Benzothiazole

https://en.m.wikipedia.org/wiki/2-Aminothiophenol

https://en.m.wikipedia.org/wiki/Benzoxazole

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Tafamidis

https://en.m.wikipedia.org/wiki/Tafamidis

Tafamidis, sold under the brand names Vyndaqel and Vyndamax, is a medication used to delay disease progression in adults with certain forms of transthyretin amyloidosis. It can be used to treat both hereditary forms, familial amyloid cardiomyopathy and familial amyloid polyneuropathy, as well as wild-type transthyretin amyloidosis, which formerly was called senile systemic amyloidosis. It works by stabilizing the quaternary structure of the protein transthyretin. In people with transthyretin amyloidosis, transthyretin falls apart and forms clumps called (amyloid) that harm tissues including nerves and the heart.

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Colchicine

https://en.m.wikipedia.org/wiki/Colchicine

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apparently alkaline Ph alters the structure of Thiamin & Thiazole, into an oxidative state, making something more like Tafamidis.

if my Alkaline Thiamine brew is anything like Tafamidis, this paper is talking about 20 mg, and im taking more like 2000+ mg.

high dose gives a hint of a headache, but my joints seem to be way more flexible, a bit of ear ringing, but goes away after a few days of stopping.

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Long-Term Survival With Tafamidis in Patients With Transthyretin Amyloid Cardiomyopathy

https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.120.008193

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https://en.m.wikipedia.org/wiki/Transthyretin

Transthyretin:
Role in disease:
Tafamidis

this link talks about Tafamidis as well, my interest is regarding it having the Thiazole identical to Thiamine.

found information regarding high dose of Nician (B3) may have a negative Methylation binding effect, and Thiamine (B3) actually reverses it.

in my many experiments, lt was bringing down Ph with Citric Acid that converted Thiamine into a completely different compound with a strong Sulfur smell, yet the one paper says its Alkaline high Ph that makes Thiamine unstable.

so my experience is the complete opposite, but its better to just use Buffered minerals with a balanced Ph, to act as coenzyme activators.

all im doing is taking regular B1 with baking soda (alkaline), potassium citrate (for kidney stones), magnesium chloride (constipation).

the most basic & inexpensive forms of each nutritional supplement, nothing fancy, its just when combined with B1 triggers enzymes in mitochondria.

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Thiazole 
Enzyme 
THI1 
2-Ring Octamer
Histone H2A

https://en.m.wikipedia.org/wiki/Histone_H2A

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Histone H5 is a potent Antimicrobial Agent and a template for novel Antimicrobial Peptides

https://www.nature.com/articles/s41598-018-20912-1

trick is this 5-Carbon, and looking at Histone H2A found this one being used as a full spectrum antibiotic.

Histone H5

(is it from 5-Carbon metabolite or pathway?)

5-5arbon
Pentose
Deoxyribose
Ribonucleotide Reductase
Thymidylate Kinase

https://en.m.wikipedia.org/wiki/Pentose

https://en.m.wikipedia.org/wiki/Deoxyribose

https://en.m.wikipedia.org/wiki/Ribonucleotide_reductase

https://en.m.wikipedia.org/wiki/Thymidylate_kinase

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Genetic prion disease–related mutation E196K displays a novel amyloid fibril structure revealed by cryo-EM

https://www.science.org/doi/10.1126/sciadv.abg9676

Each subunit forms five β strands stabilized by a disulfide bond and an unusual hydrophilic cavity stabilized by a salt bridge. Four pairs of amino acids from opposing subunits form four salt bridges to stabilize the zigzag interface of the two protofibrils.