>if any epigenetic chromosomal markings are more associated with one sex or anything like that.

Yes! This is called epigenetic imprinting. Some genes are differentially methylated between the mother's and father's copy. I wrote about this here: https://denovo.substack.com/p/epigenetics-of-the-mammalian-germline

If it's endogenous then the creature is already infected.

Yes. Porcine endogenous retroviruses (PERVs) can infect human cells in cell culture.

https://www.nature.com/articles/nm0397-282

A biotech company made a gene-edited pig a few years ago with all of the PERVs knocked out. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813284/

The goal is to have a safer source of organs for xeno-transplantation. Giving a pig organ with PERVs to an immuno-suppressed patient is a bad idea.

Receptors are proteins, which are made up of amino acids that fold into a particular 3-dimensional shape. Different amino acids can also have different properties such as positive and negative charges, hydrophobic or hydrophilic side chains, etc.

Receptors can also be modified with sugars, lipids, etc. but the ligand binding site is usually just amino acids.

When a ligand (protein or other molecule) binds to the receptor, it will interact with the amino acids in the binding site, based on their 3D shape and physical properties (charge, hydrogen bonding, etc.) The binding affinity of the ligand will depend on how strongly it interacts with the binding site. This is how the receptors establish selectivity for binding some molecules instead of others.

You can think of the binding event like a hand fitting into a glove. The glove will change shape a bit when the hand goes into it. This conformational change in the receptor can cause downstream biological effects, depending on the function of the receptor. Many receptors are kinases which phosphorylate proteins when the ligand is bound.

Also, some inhibitors (called competitive inhibitors) will bind to the receptor and not cause conformational changes like the normal ligand, but still occupy the binding site.

Regarding the question of rigidity/solidity, proteins can be more or less flexible (depending on the protein) but the individual bonds are pretty rigid, and most receptors will have only a few stable conformations.

> prion-strain specific

What is a "prion strain"? Are there different misfolded forms of PRNP?

>Totally forgot about human fetuses starting as female.

This isn't actually correct, it's more like they start off as undifferentiated, and trigger male or female development depending on whether the SRY gene is present.

> The gonads themselves react to the environment temperature epigenetically. This is the theory that is the biggest departure from the others as it doesn't specifically target a separate messenger hormone (even though one may or may not be present).

This has been proven pretty well, at least in one species of turtle: https://pubmed.ncbi.nlm.nih.gov/29748283/

But other species might be different.

Also, you write, "in humans, all babies start off development as females." But this isn't correct. A better way to say it would be that they start off as undifferentiated, and trigger male or female development depending on whether the SRY gene is present.

Yes, it's basically polarizability. See: https://en.wikipedia.org/wiki/HSAB_theory

Interestingly, age of female puberty has been steadily decreasing over the last century. https://pubmed.ncbi.nlm.nih.gov/12319855/ https://vitalrecord.tamhsc.edu/decreasing-age-puberty/

This is probably due to increasing food consumption.

> whatever melted first will start to crystallize first.

wait, don't you mean whatever melted last (i.e. has higher melting temperature) will crystallize first?

> those with the Murine Double Minute 2 gene

Everyone has the MDM2 gene, I think you mean the tumors with a mutation in MDM2.

Laboratory strains of mice are inbred, so their offspring work like this.

No. As /u/die_kuestenwache mentioned this is due to epigenetic problems.

Luckily for you, I just wrote a deep-dive blog post on the topic, see: https://denovo.substack.com/p/epigenetics-of-the-mammalian-germline

Yes.

> they could survive outrageous amounts of acceleration

In the lab I can spin human cells suspended in an aqueous buffer at 300g and they don't die.

This paper is a good review of pyruvate transport into the mitochondria. Basically, pyruvate can flow across the mitochondrial outer membrane using non-selective anion channels such as VDAC1. There are two proteins, MPC1 and MPC2 (named for being mitochondrial pyruvate carriers), that form a complex that transports pyruvate through the inner membrane into the mitochondrial matrix, where the oxidation happens. The MPC complex carries a proton along with pyruvate (which is known as proton symport). Since pyruvate is negatively charged this means the overall transport process is charge-neutral across the inner membrane.

In general, compounds diffuse from regions of high concentration to regions of low concentration. Since pyruvate is consumed in the mitochondrial matrix, the concentration will be lower there, so pyruvate will diffuse inside if the proper transport proteins are present. In absence of oxygen, pyruvate won't be oxidized in the mitochondrial matrix, so this concentration gradient would be much lower (or absent entirely).

> steam turbines have an efficiency going from 60% for small systems all the way ip over 90% for big turbines, the kind you might expect from a huge reactor.

To clarify, this is expressed as a percentage of the Carnot efficiency, it's not 90% overall.

As a biologist studying female reproduction, I think the answer is probably yes, but I'm not aware of any studies that have actually measured this. It would be a good topic for research!

> because the tRNA that are complementary to the stop codons are not charged with amino acids.

This is not correct, stop codons are recognized by release factors not tRNAs.

Otherwise a very good answer though.

I should mention, when I want to express multiple eukaryotic proteins from the same promoter I will use 2A peptides to separate them. For example: https://www.nature.com/articles/s41598-017-02460-2

> If this happens in a gamete (sperm or egg cell) that goes on to be fertilized

Not only gamete, but any germline cell (that eventually develops into a gamete)

> where it is slipped inside a chromosome.

To expand upon this point, the retroviruses also have an enzyme called integrase that inserts their DNA into the host genome. Integrase inhibitors are a class of anti-HIV drugs.

> What I don’t understand is how this would work for an entire body?

Your understanding is correct, because it doesn't work for an entire body, the efficiency per cell is not nearly good enough. If you want a full-body edit you would have to edit stem cells, select the edited cells you want, and then use various embryology techniques to put the stem cells in an embryo and have them develop into a new organism.

Doing it with the cas9 plasmid is cheaper and works nearly as well. There is a greater chance of off-target edits though. But yes, if I was doing it clinically I would use the ribonucleoprotein.

I do this regularly as part of my research. Here's how it works:

I make a bacterial plasmid that contains the DNA that I want to insert. On either side of this DNA, I have an additional 1000 bases of DNA that has the same sequence as my target site. These are known as homology regions. I can assemble this plasmid using a method such as Gibson assembly.

I then introduce this plasmid into the cells, along with another plasmid expressing Cas9 and guide RNA, using electroporation. The Cas9 and guide RNA cut the target site. The cell then tries to repair it.

The usual repair pathway is called non-homologous end joining, which simply sticks the DNA back together. This is not what I want. However, cells can also repair DNA through homology-directed repair (HDR), where they basically look for similar sequences and swap them into the cut site.

When cells perform HDR, they can use my plasmid to perform the repair because it has the homology regions. Once this happens, the DNA sequence becomes inserted into the target site.

For a good intro-level review of this, I recommend: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901406/

(Note that there are other ways being developed to do edits with CRISPR, I'm just explaining HDR)

Leptin is a hormone produced by fat that promotes the onset of puberty. See: https://www.sciencedirect.com/science/article/pii/S0018506X13000330