A week ago I voluntarily admitted myself to the hospital to get help bc I am losing weight as a result of increased food intolerances, secondary to my very severe #MECFS. A psychiatrist here decided that im mentally ill, 1/
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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:
🔹RNA contains uracil
🔹DNA 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
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:
🔹RNA contains uracil
🔹DNA 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
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@EricTopol @NBA @StephenKissler @yhgrad B.1.1.7 reveals clearly that SARS-CoV-2 is reverting to its original pre-outbreak condition, i.e. adapted to transgenic hACE2 mice (either Baric's BALB/c ones or others used at WIV labs during chimeric bat coronavirus experiments aimed at developing a pan betacoronavirus vaccine)
@NBA @StephenKissler @yhgrad 1. From Day 1, SARS-COV-2 was very well adapted to humans .....and transgenic hACE2 Mice
@NBA @StephenKissler @yhgrad 2. High Probability of serial passaging in Transgenic Mice expressing hACE2 in genesis of SARS-COV-2
@NBA @StephenKissler @yhgrad B.1.1.7 has an unusually large number of genetic changes, ... found to date in mouse-adapted SARS-CoV2 and is also seen in ferret infections.
https://t.co/9Z4oJmkcKj
@NBA @StephenKissler @yhgrad We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the ... Thus, this mouse-adapted strain and associated challenge model should be ... (B) SARS-CoV-2 genomic RNA loads in mouse lung homogenates at P0 to P6.
https://t.co/I90OOCJg7o
@NBA @StephenKissler @yhgrad 1. From Day 1, SARS-COV-2 was very well adapted to humans .....and transgenic hACE2 Mice
1. From Day 1, SARS-COV-2 was very well adapted to humans .....and transgenic hACE2 Mice
— Billy Bostickson \U0001f3f4\U0001f441&\U0001f441 \U0001f193 (@BillyBostickson) January 30, 2021
"we generated a mouse model expressing hACE2 by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young & aged hACE2 mice sustained high viral loads... pic.twitter.com/j94XtSkscj
@NBA @StephenKissler @yhgrad 2. High Probability of serial passaging in Transgenic Mice expressing hACE2 in genesis of SARS-COV-2
1. High Probability of serial passaging in Transgenic Mice expressing hACE2 in genesis of SARS-COV-2!
— Billy Bostickson \U0001f3f4\U0001f441&\U0001f441 \U0001f193 (@BillyBostickson) January 2, 2021
2 papers:
Human\u2013viral molecular mimicryhttps://t.co/irfH0Zgrve
Molecular Mimicryhttps://t.co/yLQoUtfS6s https://t.co/lsCv2iMEQz
@NBA @StephenKissler @yhgrad B.1.1.7 has an unusually large number of genetic changes, ... found to date in mouse-adapted SARS-CoV2 and is also seen in ferret infections.
https://t.co/9Z4oJmkcKj
@NBA @StephenKissler @yhgrad We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the ... Thus, this mouse-adapted strain and associated challenge model should be ... (B) SARS-CoV-2 genomic RNA loads in mouse lung homogenates at P0 to P6.
https://t.co/I90OOCJg7o