Learning Update — August 4, 2021

Origins of civilization, evolution of writing, and cuneiform script.

The Start of Western Civilization

  • One thing I’ve been learning (or, trying to learn) a lot about recently is, sort of, the “flow” of civilization — from as far back as possible.

    For example, where did all the biblical texts come from? What languages were they written in? How did those languages change? What is a neat and tidy narrative to understand all that?

    And that’s the problem: I’m learning a lot, but I can’t really neatly sum it all up (for myself or for you!) into a neat narrative. So it can feel like I’m learning nothing.

    There’s lots to say, but for now I’ll start with cuneiform, the script used in Mesopotamia for many languages.

Cuneiform and the Evolution of Script

  • An important question I don’t have an answer to is: why did cuneiform die out? Cuneiform has no descendent scripts. What causes such a dominant, universal script to die out? The explanations I’ve come across so far are not compelling enough.


BONUS: Here is a 53 second video showing how cuneiform was written on clay tablets. It’s magical.


Learning Update — July 6, 2021

mRNA caps. Horses, wooden pipelines, iron railroads, and wholesale transfer pricing power.

mRNA Caps

  • The four (known?) types of mRNA caps are:1

    Cap 0:

    • Has no methyl groups (CH₃ or Me) attached. Only a hydrogen (H).

    • An intermediate in the structure of a cap, but not found in mature eukaryotic (animals, plants, fungus) mRNA messages.

    Cap 1:

    • Has a methyl group (CH₃ or Me) where Cap 0 has a hydrogen (H).

    • Found in all eukaryotic (animals, plants, fungus) mRNA.

    Cap 2:

    • Has an extra methyl group (CH₃ or Me) attached.

    • Found in ~50% of eukaryotic mRNA

    • We don’t know much about Cap 2’s because it has only recently been possible to easily generate them in the lab and experiment with.

    m6Am Cap:

    • I don’t know much else about this one except the name.

    • There is “recent evidence” that this cap is found in ~30% of eukaryotic mRNA caps, and that it regulates “translational initiation” and mRNA stability.

  • Interestingly, many viruses have a Cap 1 structure and will even “steal” methyl groups from the caps of target eukaryotic cells they are infecting and attach it to their own RNA to achieve Cap 1 status.

    This is evidence that the caps are doing something important and that Cap 1 is preferred to Cap 0, at least sometimes.


Horses, Wooden Pipelines, Iron Railroads, and Wholesale Transfer Pricing Power

  • The first oil pipeline (Tidewater) was made of wood, started around 1863ish (?), and was developed to:

    1) get around the “teamster monopoly” — the use of wagons and horses — on shipping oil from Pennsylvania’s Oil Region to the Reading Railroad;

    2) bypass Standard Oil’s monopoly on purchasing oil from producers (i.e. monopsony).

    From The Prize:

    From the first discoveries [of oil], teamsters, lashing their horses, had clogged the roads of the Oil Regions with their loads of barrels. They were more than just a physical bottleneck. Holding a monopoly position, they charged exorbitant rates; it cost more to move a barrel over a few miles of muddy road to a railway stop than to transport it by rail from western Pennsylvania all the way to New York. The teamsters’ stranglehold on transportation led to an ingenious effort to develop an alternative—transportation by pipeline. Between 1863 and 1865, despite much scoffing and public ridicule, wooden pipelines proved that they could carry oil much more efficiently and cheaply. The teamsters, seeing their position challenged, responded with threats, armed attacks, arson, and sabotage. But it was too late. By 1866, pipelines were hooked up to most of the wells in the Oil Regions, feeding into a larger pipeline gathering system that connected with the railroads.

    Also:

    Its construction was carried out with both deception and dispatch. Fake surveys were even taken to throw Standard off as to its route. Many doubted right up to the last moment that the pipeline would work. Yet, by May of 1879, oil was flowing in the pipeline.

    Kids, always remember: If you have only one supplier of a necessary input, that supplier controls your profits. And on the demand side, if you have only one potential customer that you can sell to, that customer controls your profits.

    These are the only two maps I could find of the first Tidewater Pipeline, and I’m not sure how accurate they are.

Learning Update — June 18, 2021

Canals, seaways, cities. More DNA, RNA, proteins.

Canals, Great Lakes, and the St. Lawrence Seaway


DNA, RNA, proteins, etc.

  • The relationship between triplets (codons) and amino acids was worked out by adding various known sequences of mRNA into compounds of burst E. coli cells. The burst cells still contain ribosomes, and all the other materials needed for genetic translation, and will therefore react to the mRNA and manufacture the appropriate proteins.

  • Here’s how it went down. First, in 1961, Marshall Nirenberg took an mRNA of just U’s and added it to some burst E. coli cells:1

    U U U U U U U U U U U U . . .

    And he ended up, exclusively, with the amino acid phenylalanine.

    Then he added an mRNA of just C’s into the burst E. coli cells:

    C C C C C C C C C C C C . . .

    And he ended up, again exclusively, with the amino acid proline.

    Then someone else, Har Gobind Khorana, added a chain of UC’s into burst E. coli cells:

    U C U C U C U C U C U C . . .

    And that experiment produced the amino acids serine and leucine.

    Now think about it. A simple explanation for this result is that sequences of three nucleosides correspond to an amino acid. In this case, UUU corresponds to phenylalanine, CCC corresponds to proline, while UCU and CUC correspond to one of serine and leucine (although it’s not yet clear which).

    But you can figure it out by playing a bit more: Separately, submit (and I am now presumptively grouping nucleotides into groups of three) the sequences:

    UCU UUU UCU UUU UCU . . .
    CUC UUU CUC UUU CUC . . .

    And we will find that the first sequence produces the amino acids phenylalanine (which we think corresponds to UUU) and serine. And then the second sequence produces the amino acids phenylalanine (again, we think is UUU) and leucine.

    Thus we can deduce that UCU specifically corresponds to serine and CUC specifically corresponds to leucine. Etc.

    Eventually we get the entire genetic code:


Happy Learning!

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/

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