RNA came first. Then, ~3-4 billion years ago, DNA emerged.
Among their differences:
🔹RNA contains uracil
🔹DNA contains thymine
But why does DNA contains thymine (T) instead of uracil (U)?
https://t.co/XlxT6cLLXg
1/16
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.
RNA came first. Then, ~3-4 billion years ago, DNA emerged.
Among their differences:
🔹RNA contains uracil
🔹DNA contains thymine
But why does DNA contains thymine (T) instead of uracil (U)?
https://t.co/XlxT6cLLXg
🔑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
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
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
So one hypothesis is that megaloblastic anemia results from a deficiency in dTMP leading to an issue with DNA elongation (i.e., addition of nucleotides)
Some (#1) but not all (#2) data support this.
There is more to it.
1. https://t.co/vysYKm4Sst
2. https://t.co/PxjmJAsvwj
To add to our explanation for how B12 and folate deficiencies hinder DNA synthesis, look back at the figure in tweet 5.
What would you anticipate increases in concentration in the setting of B12 or folate deficiency?
B12 and/or folate deficiency result in issues with dTMP production. As dUMP is the precursor, the ratio of dUMP/dTMP rises.
Result: dUTP (uracil + deoxyribose triphosphate) is incorporated into DNA where dTTP should be!
https://t.co/54Bir7QA93
But uracil doesn't belong in DNA!
In response to this misincorporation, attempts are made to repair these strands. U is removed but there isn't enough T to fill the gaps. Single and double-stranded breaks form resulting in non-functional DNA.
https://t.co/JXzqUpRyGc
Without functional DNA, cell division is halted. RBC precursors undergo apoptosis.
Result: "ineffective erythropoiesis" and anemia!
To this point we've explained the anemia but haven't yet explained why the resulting RBCs are so large. That's next.
https://t.co/y5DVkAA8vj
Remember that RNA doesn't uses thymine (it uses uracil). And only the thymine containing nucleotide (dTMP) requires B12/folate.
🔑Result: In B12/folate deficiencies, RNA synthesis is relatively unaffected!
https://t.co/lwmGWuOrFC
In the nuclei of B12/folate deficient RBC precursors, DNA synthesis is poor leaving cells stalled and unable to divide.
But, in the cytoplasm, RNA and protein synthesis continues unabated.
Result: "nuclear-cytoplasmic asynchrony"
Precursors with nuclear-cytoplasmic asynchrony are unable to divide into daughter cells. But the cytoplasm continues to expand.
When survivors eventually cast off their nucleus (and its DNA!) and appear in the peripheral blood, they will be huge.
They will be macrocytic!
There are other explanations (see link).
And I admit this doesn't really explain why RBCs are more affected than other cell lines (though all ARE affected).
AND, why are neutrophils hypersegmented?
For these unanswered questions, I seek your help.
https://t.co/huX6xJOBhp
More from Health
No-regret #hydrogen:
Charting early steps for H₂ infrastructure in Europe.
👉Summary of conclusions of a new study by @AgoraEW @AFRY_global @Ma_Deutsch @gnievchenko (1/17)
https://t.co/YA50FA57Em
The idea behind this study is that future hydrogen demand is highly uncertain and we don’t want to spend tens of billions of euros to repurpose a network which won’t be needed. For instance, hydrogen in ground transport is a hotly debated topic https://t.co/RlnqDYVzpr (2/17)
Similar things can be said about heat. 40% of today’s industrial natural gas use in the EU goes to heat below 100°C and therefore is within range of electric heat pumps – whose performance factors far exceed 100%. (3/17)
Even for higher temperatures, a range of power-to-heat (PtH) options can be more energy-efficient than hydrogen and should be considered first. Available PtH technologies can cover all temperature levels needed in industrial production (e.g. electric arc furnace: 3500°C). (4/17)
In our view, hydrogen use for feedstock and chemical reactions is the only inescapable source of industrial hydrogen demand in Europe that does not lend itself to electrification. Examples include ammonia, steel, and petrochemical industries. (5/17)
Charting early steps for H₂ infrastructure in Europe.
👉Summary of conclusions of a new study by @AgoraEW @AFRY_global @Ma_Deutsch @gnievchenko (1/17)
https://t.co/YA50FA57Em
The idea behind this study is that future hydrogen demand is highly uncertain and we don’t want to spend tens of billions of euros to repurpose a network which won’t be needed. For instance, hydrogen in ground transport is a hotly debated topic https://t.co/RlnqDYVzpr (2/17)
Similar things can be said about heat. 40% of today’s industrial natural gas use in the EU goes to heat below 100°C and therefore is within range of electric heat pumps – whose performance factors far exceed 100%. (3/17)
Even for higher temperatures, a range of power-to-heat (PtH) options can be more energy-efficient than hydrogen and should be considered first. Available PtH technologies can cover all temperature levels needed in industrial production (e.g. electric arc furnace: 3500°C). (4/17)
In our view, hydrogen use for feedstock and chemical reactions is the only inescapable source of industrial hydrogen demand in Europe that does not lend itself to electrification. Examples include ammonia, steel, and petrochemical industries. (5/17)
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/
— Matthew Yglesias (@mattyglesias) January 30, 2021
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/
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#ArudraDarisanam
Unique Natarajar made of emerlad is abt 6 feet tall.
It is always covered with sandal paste.Only on Thriuvadhirai Star in month Margazhi-Nataraja can be worshipped without sandal paste.
After removing the sandal paste,day long rituals & various abhishekam will be https://t.co/e1Ye8DrNWb day Maragatha Nataraja sannandhi will be closed after anointing the murthi with fresh sandal paste.Maragatha Natarajar is covered with sandal paste throughout the year
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