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Why do B12 and folate deficiencies lead to HUGE red blood cells?

And, if the issue is DNA synthesis, why are red blood cells (which don't have DNA) the key cell line affected?

For answers, we'll have to go back a few billion years.


2/
RNA came first. Then, ~3-4 billion years ago, DNA emerged.

Among their differences:
đŸ”čRNA contains uracil
đŸ”čDNA contains thymine

But why does DNA contains thymine (T) instead of uracil (U)?

https://t.co/XlxT6cLLXg


3/
🔑Cytosine (C) can undergo spontaneous deamination to uracil (U).

In the RNA world, this meant that U could appear intensionally or unintentionally. This is clearly problematic. How can you repair RNA when you can't tell if something is an error?

https://t.co/bIZGviHBUc


4/
DNA's use of T instead of U means that spontaneous C → U deamination can be corrected without worry that an intentional U is being removed.

DNA requires greater stability than RNA so the transition to a thymine-based structure was beneficial.

https://t.co/bIZGviHBUc


5/
Let's return to megaloblastic anemia secondary to B12 or folate deficiency.

When either is severely deficient deoxythymidine monophosphate (dTMP*) production is hindered. With less dTMP, DNA synthesis is abnormal.

[*Note: thymine is the base in dTMP]

https://t.co/AnDUtKkbZh
I think @SamAdlerBell in his quest to be the contrarian on Fauci gets several things wrong here. 1/


First, the failure last year actually was driven by the White House, the #Trump inner circle. Watch what's happening now, the US' scientific and public health infrastructure is creaking back to life. 2/

I think Sam underestimates the decimation of many of our health agencies over the past four years and the establishment of ideological control over them during the pandemic. 3/

I also am puzzled why Tony gets the blame for not speaking up, etc. Robert Redfield, Brett Giroir, Deb Birx, Jerome Adams, Alex Azar all could have done the same. 4/

Several of these people Bob Redfield, Brett Giroir, Alex Azar were led by craven ambition, Jerome Adams by cowardice, but I do think Deb Birx and Tony tried as institutionalists, insiders to make a difference. 5/
Now you know I love to sh-t in Harvard. But I also like accuracy. So I decided to go look at Harvard’s catalog to see its lack of military history that this article describes (they only teach history of pets it claims) and what I found shocked me! Shocked me! A thread: 1/


First off, Harvard students literally have multiple sections of military history that they can take listed. (It appears these ones are taught at MIT, so they might have to walk down the street for these) but... 2/


Say they want to stay on campus...they can only take numerous classes on war and diplomacy...3/


They have an entire class on Yalta. That’s right. An entire class on Yalta. 4/


But wait! There is more! They can take the British Empire, The Fall of the Roman Empire for those wanting traditional topics... 5/