Learning Update — June 11, 2021

More DNA, RNA, proteins. Ancient Greek oral tradition.

DNA, RNA, proteins, etc.

  • The ribosome is itself an RNA. It is actually a “ribozyme”, an RNA with enzyme-like properties.

  • Antibiotics work because they inhibit the ribosomes of bacteria, without affecting human (eukaryotic) ribosomes. Exactly how, I do not know.

  • DNA is stored “folded” in the cell. Unraveled, the amount of DNA in a human cell would stretch out to 2 meters! Just one cell!

    • When a gene has to be read by the cell’s machinery, the area of the DNA around that gene “unfolds” to allow access to it. Anything that “stiffens” DNA will make it harder to read and for genes to be expressed. Conversely, anything that “loosens” DNA will make it easier to read.1

    • The tightness of how DNA is packaged is important in regulating which genes on the DNA are “tight” and “loose”, and thus which genes are expressed, and therefore which proteins are produced by the cell, and therefore the cell type.2 This means, I think, that cell type is, at least partially, determined by how the DNA is packaged in the cell — different packagings correspond to different cell types.

  • Y chromosomes do not undergo “recombination” in sexual reproduction. Except for degradation, every son receives his father’s Y chromosome as is with no input from his mother’s genetic code.

    • Typically, genes from the mother and father are “shuffled” or "crossed over" to produce a unique genetic code.

    • As a result, Y chromosome genes tend to degenerate as repetitive DNA sequences accumulate in the chromosome.


Homer and Ancient Oral Tradition

  • The Iliad and Odyssey were likely not written by someone named Homer, or any one person at all. The epic tales are likely the product of an oral tradition that heavily relies on improvised story telling.3

    Parry’s research showed that, in an oral-performance tradition, it makes no sense to speak of a poem as having an authentic, original text. He found that, when he asked a guslar to perform the same poem on consecutive days, the transcripts could be dramatically different, with lines and whole episodes appearing or disappearing. With the guslar he considered the most gifted, a man in his sixties named Avdo Međedović, Parry tried an experiment: he had Međedović listen to a tale he’d never heard before, performed by a singer from another village, and then asked him to repeat it. After one hearing, Međedović not only could retell the whole thing but made it three times longer, and, in Lord’s recollection, much better: “The ornamentation and richness accumulated, and the human touches of character imparted a depth of feeling that had been missing.”

    I actually learned about this sometime last year when I attempted to (start to) read the Iliad, but what is new is that you can hear recordings from the 1930’s and 1950’s of an existing tradition of oral poetry in Yugoslavia, which should not be that different from the Ancient Greek oral tradition; it even sounds to me like it follows the hexameter of the Iliad and Odyssey. The sound is wonderfully ancient, especially when there’s music, as if you are sitting by a fire listening to your local orator recite a classic, legendary story. Here’s an example: https://sds.lib.harvard.edu/sds/audio/461823374.

Learning Update — June 4, 2021

More DNA, RNA, proteins, etc.

DNA, RNA, proteins, etc.

  • The BioNTech COVID-19 vaccine works by injecting you with mRNA that tells your cells (ribosome) to produce this spike protein (without the rest of the virus body). Your immune system is then able to learn to recognize the spike protein, and thus the virus, without actually being exposed to the virus.

    • Interestingly, the vaccine uses the molecule ‘pseudouridine’ (Ψ) in place of uridine (U) in its RNA coding. The ribosome reads the Ψ as it would a U, and attaches the appropriate amino acids to create the spike protein.

      The importance of the Ψ in place of U is that it allows the mRNA to sneak past the immune system, which obviously doesn’t like foreign RNA. How it does this, I do not know.

    • The vaccine also uses triplets that are synonymous to ones in the original virus (see table above), and apparently this isn’t random and is for good reason — but I don’t know the reason.

    • For example, the vaccine codes the spike protein as:

      CΨG GAC CCΨ CCΨ GAG GCC GAG GΨG CAG AΨC GAC AGA CUG AΨC ACA GGC

      You can check that, except for the third and fourth triplet, this encodes the same spike protein as the previous sequence above. (The third and fourth triplet “CCΨ CCΨ” apparently allows the spike protein to keep its form and not degrade when it is free standing without the rest of the virus attached to it.2)

    • I know of one retired micro-biologist that is slightly worried that these Ψ’s might do “something” in the body once the mRNA degrades into its component parts. Oh well.

  • A piece of the puzzle to a question I had and still have: Why is one G nucleotide on the mRNA cap sufficient to protect the cap end, while the tail needs 100-200 A’s?

    Well, an mRNA can be reused many times. But each time it’s used, it loses some of the A’s on its tail. Once the A’s run out, the mRNA is no longer functional and gets discarded. The ‘poly-A’ tail is protection from degradation. So the more you have, the better (in this narrow sense).

    But I still have to ask: Why doesn’t the G nucleotide on the cap “fall off” in the same way? Why not have 100-200 G’s?

1

https://biology.stackexchange.com/questions/56939/do-all-proteins-start-with-methionine

2

https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/

Learning Update — May 28, 2021

RNA, mRNA, cancer vaccines, and COVID vaccination rates

Hello!

Long time no see.

A quick update: I will be using this “newsletter” to write about and share what I am learning.

Hopefully it is an ongoing thing that I’m able to keep up with. I am always learning, but writing takes much more time, for me.

Below is what I’ve been learning about this week.

-Sina


  • RNA is downstream from DNA.

    • Both DNA and RNA store genetic information. But DNA is a more “durable” molecule and your body uses RNA to merely transfer information from your DNA (in the nucleus) to other parts of the cell (the ribosome).

    • Your DNA transcribes an RNA, which turns into an mRNA, which is then read by the ribosome to assemble chains of amino acids into particular proteins.

    • Proteins control everything in your body.

  • mRNA is just RNA with a cap and tail.

    • The cap is a guanine (G) nucleotide. It protects the mRNA from being broken down and also helps the ribosome attach to the mRNA and start reading it.

    • The tail is made up of 100 - 200 adenine (A) nucleotides. It makes the mRNA more stable and helps it move from the nucleus to the rest of the cell.

    • Question I have: Both the cap and tail are protecting the main transcription within the mRNA. But why is one G nucleotide on the cap sufficient to protect the cap end, while the tail needs 100-200 A’s?

  • mRNA vaccines can probably be used to treat cancer:

    • Cancer is a mutation in the DNA of certain cells, the “cancer cells”, which cause them to 1) mutate a lot more and 2) multiply a lot more.

    • Your immune system, specifically T-cells, could identify and kill those cells if they knew how to recognize them. In fact, T-cells do do this when they are able identify such cells — and therefore such cells do not proliferate and go on to cause “cancer.” But since T-cells identify “rouge” cells by examining their surface, when the cancer cell mutations affect the inside of the cell and leave the cell surface unchanged, T-cells are not able to recognize them — and therefore you get “cancer.” This might not be exactly right, but is how I think about it right now.

    • However, mRNA might be used to “teach” the immune system to identify cancer cells. This part I don't understand yet, but more or less: You can encode the genetic differences into mRNA, inject it in the lymph nodes where T-cells hang out, and this will teach the T-cells how to identify the mutated cancer cells.

    • Each vaccine would be unique to the patient: In order to identify cancer causing mutations, the patient’s “normal” DNA would be sequenced from non-cancer cells and compared to DNA sequenced from the cancer cells. The treatment would be highly targeted to the mutations in the individual patient’s cancer cells.

    • Such treatments are currently in trials.

Sources: [1], [2], [3]


  • I expect that Canada will soon be the most COVID-vaccinated country in the world, as other countries struggle with vaccine hesitancy.

[Source]

You don’t have to make it back the way you lost it

Investing Mantra

  • Doubling down on a bad idea is a bad idea that is twice as bad.

    • Don't cling to a mistake just because you spent a lot of time making it.

    • Denial is an investing sin. Accept it as soon as it happens.

  • Losers average losers.

    • Before you buy more after a big fall, make sure you stand by your thesis.

    • Average costing a loser asset is a losing strategy.

    • Only the biggest losers buy more of a loser asset.

  • Chasing losses is a sign that you are gambling.

    • Chasing losses is when you keep gambling to win back money you've already lost.

    • Chronic gamblers notoriously chase losses.

    • People chasing losses believe the game must "balance out".

      • But this is a statistical myth: the Law of Large Numbers only guarantees that certain ratios converge — and the contribution of any one ‘anomaly’ converges to 0 at the limit — so no particular event has to balance out at all.

    • People chasing losses will often gravitate towards long-shots which entail even more risk — a dreadful cycle that will not end well.

  • Psychologically, you are likely to cling to bad investments because you cannot bring yourself to crystallize the loss and acknowledge failure.

    • On the other hand, by selling winners, you can pat yourself on the back for being so clever. 

    • This is a costly asymmetry. On balance, you should do the exact opposite.

    • The only way to avoid this mistake is by sheer will.

  • Terrence Odean analyzed 10,000 discount brokerage accounts that stripped out distress sales and focused only on trades where clients bought and sold stocks in the same day.

    • He discovered that the stocks clients sold outperformed those they bought by 3.4 percentage points on average over the subsequent year.


“You don’t have to make it back the way you lost it. In fact, it’s usually a mistake to make it back the way you lost it.”

— Warren Buffett, BRK Shareholder Meeting 1995


“One of the most important things in stocks is that the stock does not know that you own it. You know, you have all these feelings about it — you remember what you paid, you remember who told you about it — all these little things. And it doesn’t give a damn. It just sits there.”

— Warren Buffett, BRK Shareholder Meeting 1995


“I’d like to repeat that business about not having to ‘get it back the way you lost it.’ You know that’s the reason so many people are ruined by gambling. They get behind and then they feel they have to get it back the way they lost it. It’s a deep part of the human nature. And it’s very smart just to lick it — by will — and little phrases like that are very useful.”

— Charlie Munger, BRK Shareholder Meeting 1995


Thanks for reading. Tell your friends.

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