Genes - some of mine & F-actin, glyphosate, microtubules & conception.

Life takes some direction, which involves actin and other cellular matrix proteins - our internal scaffolding to help us build ourselves or a new baby.

The 3x4 Genetics report groups (linked in last post) the 146 potential gene allele results into High Impact with a few starred as very high impact… and three other levels of impact, __2nd most important?__, Moderate, and Low.

• My 3x4 Genetics Report - it shows that my life has been uphill climb. (my Dropbox pdf), Scope of practice is a safety circle; Banking meltdown and other financial news. (substack.com)

My High Impact gene alleles include the enzyme to break down histamine, DAO His645Asp C>G GG. It did help my health a lot to learn how the histamines in foods and other histamine trigger foods were making me have bizarre mental symptoms that seemed odd to me but were so intense that normal was no longer present, more of a faint memory that this was not it. While a restricted diet is not fun, having histamine excess is far worse. I share this information because it can really restore ‘rational’ ‘normal’ ‘pre-crazy’ pretty much back to normal - or eventually once all the various histamine triggers are learned - which can include flickering lights from action movies, a night club, or night-time driving, and a few other lifestyle things besides dietary triggers.

A genetic analysis by a reputable company that hasn’t sold out to Pfizer (ancestry.com - looking at you) can be helpful to get to what might help your unique biochemistry, faster than the trial and error method that I have tended to follow.

The genes with stars are considered more important in the 3x4 Genetics report.

• ACTN3 577 R/X RR = F-Actin Cross-Linking Protein anchors actin to various cellular or muscle tissue structures. ACTN3 Gene - GeneCards Associated with bruxism - teeth grinding at night and jaw pain - okay - had the experimental at the time bite splint in college and learned not to do that. *This allele may have beneficial effects combined with athletic training but also negative effects. I need to learn more. From the report: “ACTN3 encodes for alpha-actinin-3, which is a sarcomeric protein expressed exclusively in fast twitch muscle fibers. Individuals with the RR genotype are more likely to achieve greater improvements in strength, speed, and power training compared to XX carriers.”

• DAO His645Asp C>G GG - the enzyme to break down histamine.

★ GSTM1 INS/DEL DEL - “Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911).” GSTM1 Gene - GeneCards

• IL-1 +/– + That would be interleukin-1 but alpha or beta? what does the + mean? I don’t know yet.

• MAOA Arg297Arg G>T TT    match for one in my paper MAO A/ R297R, rs6323 - the anxious or angry easily gene.

★ MTHFR 677 C>T TT also a match I think MTHFR/C677T that is the Neural Tube Defect risk, and the enzyme allele that doesn’t work well at higher temperatures. From my paper: The C677T allele causes the enzyme to not work as well at temperatures above 37’C/98.6’F, 50–60% lower activity and 65% reduced at temperatures above 46’C. (Rozen, 1997, cited by Raghubeer, Matsha, 2021), making exertion or a fever more of a risk of homocysteine buildup and reduced folate availability at a time when extra is needed.

• NOS3 –786 T>C TT - “NOS3 (Nitric Oxide Synthase 3) is a Protein Coding gene. Diseases associated with NOS3 include Stroke, Ischemic and Alzheimer Disease, Familial, 1” NOS3 Gene - GeneCards.

★ PEMT –744 G>C CC “This gene encodes an enzyme which converts phosphatidylethanolamine to phosphatidylcholine by sequential methylation in the liver. Another distinct synthetic pathway in nucleated cells converts intracellular choline to phosphatidylcholine by a three-step process.” < phosphatidylcholine might be a good supplement then. PEMT Gene - GeneCards.

• PPARGC1A Gly482Ser G>A GA - “involved with multiple transcription factors. This protein can interact with, and regulate the activities of, cAMP response element binding protein (CREB) and nuclear respiratory factors (NRFs). It provides a direct link between external physiological stimuli and the regulation of mitochondrial biogenesis, and is a major factor that regulates muscle fiber type determination. This protein may be also involved in controlling blood pressure, regulating cellular cholesterol homoeostasis, and the development of obesity.” PPARGC1A Gene - GeneCards

I was heavy most of my adult life and reading the report felt like a celebration - I had already worked through most of the steps and lost the load of excess weight and am at a victory line - Yeah! And good news, one of the gene alleles has a positive effect with athletic training - I can be an elite athlete!

I can be, I have reached that and am not currently there anymore. CoV changes have occurred, and I am more injury prone and the increased work load leads to the autoimmune like relapses. I have to stick to a moderate pace and not overdo too many hours or days in a row or I will be sick again. Start over again on extra rest, health aids, time, and then have some energy to do things again. It is better to prevent the relapses.

I have also learned since increasing use of diuretic tea on most days, that I have been puffy with edema all my life. I seem to need some diuretics on a daily basis, just not too much, not an excess.

There is a lot of talk of gender dysphoria these days, but when you have major changes in body shape there can be a bit of an odd feeling of what is ‘normal’ - I feel so skinny - is that me? Except I look like I did in college so yes, it is me. The overweight person was me in hiding. Hiding emotional pain in too much food or hiding my sexuality to please someone else - be like a mom figure. There could have been a few reasons that were too troubling to recognize for a long time. And other people can be part of the bad eating habits or emotional stress. Self-care and figuring out what works for your individual body tendencies is the need to reach your own elite athlete status - whatever it is.

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Excerpt from a long post that gets into Retinoid Toxicity, Mast cell activity & Hyperexcitable mood - by Jenny (*my transcendingsquare archives), Nov 20, 2020 (substack.com):

Actin filaments are in the tips of growing axons and may help guide it in the direction it is supposed to grow. Regrowth of a cut nerve is more likely to occur in body parts than within the brain. New connections are more likely to occur between a different pair of cells may be more likely to grow in a case of brain trauma. How do we grow these connections? Practice - the long work of physical rehabilitation after a stroke or major wound may mean having to spend long hours relearning how to walk or do other seemingly simple tasks that you had known how to do all your life. We can also unlearn how to do a nerve pathway, but that is a little different strategy.

To unlearn a nerve superhighway, we need to literally stop using that pathway, stop thinking those thoughts, or doing those actions - which is as easy as saying don't think of white elephants - uh oh, now you're thinking about a herd of white elephants aren't you? The easiest way to unthink thoughts or not do long term habits is to substitute new thoughts and new habits and keep practicing those until the nerve super highways are set in place - and in the process of doing all that thinking, practicing, and building new pathways, the old unused pathways will be unbuilt, retracted by the body and the parts, the chemicals, may be used to rebuild elsewhere, maybe the new pathways.

The benefits of meditation for stress reduction is measurable but takes time, just doing it - thinking about nothing in particular for several minutes or more every day. See: Peace may take practice, for some tips from Jon Kabat-Zinn about mindfulness - meditation can be simply going for a walk or doing dishes with a peaceful relaxed mindset. Our bodies are made to move and be active, for some people sitting meditation may not be the easiest way to start practicing a meditative mindset.

So, while we weren't thinking about hyperexcitability due to mast cell over activation, some of those hyperexcitable pathways may have been left unstimulated and may have been taken up for reuse elsewhere - bonus.

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Glyphosate could be interfering with actin and other microtubule guide proteins within cells or the extracellular matrix. See section C) Microtubule dysfunction, depolymerization - glyphosate? within my very long post: Spike protein risks & aids - summary page - by Jenny, June 28, 2021, (substack.com) Excerpt:

Why is this bad? Because the end of microtubules typically contain a glycine based area that helps control pathogen risks, (47), and glyphosate disrupts that function. (46) So the spike protein may be disruptive to microtubules - or it may be that some people have microtubules made with glyphosate that are more prone to malfunction when they are needed for the immune functions, or it may be a combination of both - spike protein disrupts microtubules, particularly those that contain glyphosate.

Microtubules are the scaffolding and cranes of our extracellular and intracellular matrix - which is gelatin like - watery and fluid but with some solidity too. Microtubules direct activity by connecting things where they need to be. If the hook end of the crane is dysfunctional - then nothing can be moved around, such as a pathogen needing to be sent to a white blood cell for removal perhaps. - overview, not my specialty except they are essential for cellular division and growth of all cells.

Cb) Microtubules helped you at conception - and every day ever since!

Mitosis is the division and replication of the nuclear DNA before cell division occurs. If our microtubules are dysfunctional - then nothing else is going to work well either, certainly not growing a new baby, which is my specialty - prenatal, lactation, and early childhood nutrition counselor and educator.

The rest of the construction crew include connecting ‘hooks’ - CAPs, cytoskeleton-associated proteins, which can bind with other cytoskeleton proteins like α-tubulin:

"Microtubules are involved in mechanical support, cytoplasmic organization, and several cellular processes by interacting with diverse microtubule-associated proteins such as plus-end tracking proteins, motor proteins, and tubulin-folding cofactors. A number of the cytoskeleton-associated proteins (CAPs) contain the CAP-glycine-rich (CAP-Gly) domain, which is evolutionarily conserved and generally considered to bind to α-tubulin to regulate the function of microtubules." (Wang, et al,2018)

If a major regulatory protein needed for cell division is dysfunctional, then new cells are not going to be able to be grown - for wound healing, immune support, or conception of a new life (a baby).

F-actin is interesting - it helps direct actin - like the hook at the end of the crane that can attach to something else.

“F-actin is a key cytoskeletal component both in dendritic filopodia and in spines, and it is implicated in the regulation of [dendritic] spine morphogenesis and synaptic plasticity. F-actin is both physically and functionally associated with [postsynaptic density] PSD components.” E. Kim, 2009, ‘Postsynaptic Development: Neuronal Molecular Scaffolds’, viewable excerpt: (ScienceDirect/F-actin)

*PSD = “The postsynaptic density (PSD) is an EM electron-dense region localized at the postsynaptic sites of excitatory synapses where the two main types of glutamate-receptor channels, N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (NMDARs and AMPARs, respectively) are clustered.” (ScienceDirect/postsynaptic density)

Photo op

“Mitosis, a scanning electron….” Photo by National Cancer Institute on Unsplash

Looks a little like we make our own tethering cords, or spider web silk.

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

Reference list

(Wang, et al., 2018) Wang LL, Lee KT, Jung KW, Lee DG, Bahn YS. The novel microtubule-associated CAP-glycine protein Cgp1 governs growth, differentiation, and virulence of Cryptococcus neoformans. Virulence. 2018 Jan 1;9(1):566-584. doi: 10.1080/21505594.2017.1423189. PMID: 29338542; PMCID: PMC5955475. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955475/