https://t.co/DF40S9biYF
Unfortunately the observed ORF8 inactivation or the nsp6 SGF deletion are both indicative of T cell depletion, yet the deletion of HV and Y suggest functional B cell immunity—specifically the HV deletion is not observed in the patient nor the ORF8

@BallouxFrancois Deactivation. The nsp6 SGF is located in an ER exposed loop that is conserved even in long passage within immunocompromised patients. The loop likely interacts with nsp3 and help antagonizing cellular autophagy. And human-like B cell immunity does not cause deletion here.
@BallouxFrancois Cellular autophagy help display peptides on MHC class II molecules, and ORF8 removed MHC class I molecules. The loss of both functions suggest the host cytotoxic T cell immunity is not functional yet the S deletions are consistent with B cell immunity in an altered host
@BallouxFrancois Environment. As the long covid-associated immnocompromisation was not found to cause either SGF deletions (or any deletions) in ORF1ab nor does it inactivate ORF8, Cytotoxic T cells are functional enough in these patients to require both functions to remain intact.
@BallouxFrancois It can not be HIV since that https://t.co/yKJIxeSzlf depletes helper T cells instead of cytotoxic T cells https://t.co/h0aN2vnkLk ,ironically creating a patient condition that is B-cell deficient but not T-cell deficient.
@BallouxFrancois It just happened that CD8 knockout mice are https://t.co/AAz9fV5p4A “deficient in functional cytotoxic T-cells; however, helper T-cell development and function is comparable to normal.” And are models for both vaccination and challenge trials for LAV vaccines due to specific
@BallouxFrancois Serum B-cell immunity associated with these animals. Combined with evidence of accelerated viral dynamics evident of a non-human host, and the observation that P681H, that is not observed in immunodeficient patient passage but mimics the S1-S2 sequence of MHV, removing a heparan
@BallouxFrancois Sulfate binding motif in the S1-S2, https://t.co/nBCMX6RPGD
Which happened to be a requirement for human infection fitness,
https://t.co/Ytdb1hkZdU
Also suggest a mouse host (which hosts non-Heparan sulfate binding MHV A59 and other non-cell passaged MHV strains) being likely.
@BallouxFrancois https://t.co/k1ViIDUHCq
Notice that for this other case the same kind of deletion—multiple AAs in the S position 144 and no deletion at S position 69-70, and a single deletion in the nsp1 removing a single Methionine residue, was found. This indicate functional B and T cell
@BallouxFrancois Immunity during passage, and the nsp6 SGF and ORF8 are likewise kept intact. The S1-S2 continues to bind Heparan Sulfate in this case, confirming it’s importance for fitness of infection in the human host. In this case the N501Y did not occur.
@BallouxFrancois The persistent infected immunocompromised patient scenario simply don’t fit with the UK isolate’s heightened sensitivity to cytotoxic T cell and evasion of B cell immunity. The GTNGTKR glycan loop being affected also suggest CTLR being different jn the passage host than humans.
@BallouxFrancois @threadreaderapp Unroll

More from Science

An interesting thing about carp is that they can go into anoxic hibernation and switch to an anaerobic metabolism based on converting glycogen to ethanol.

The waste ethanol is diffused out the gills

https://t.co/V3D1umHf04

Carp can switch over to an anaerobic metabolism and quietly exhale booze until the situation gets better.

They basically evolved the same metabolic pathway as yeast, independently.

In theory, if you spent a few thousand years breeding carp for it, you could use them to make booze.

They'd be enormous, almost entirely glycogen deposits with a fish added as an afterthought.

The really interesting thing about anaerobic carp, is that they can go 4-5 months without oxygen by relying on liver glycogen.

You, a human, have only about 100 grams of glycogen in your liver, about 400 more grams in your skeletal muscles. Call it 500 grams total.

In humans, glycogen is also burned for energy. This is where the marathon runner's bonk comes from: you only have about 2,000 calories worth, and running a marathon burns those 2,000 calories.
JUST ONE PERSON—UK 🇬🇧 scientists think one immunocompromised person who cleared virus slowly & only partially wiped out an infection, leaving behind genetically-hardier viruses that rebound & learn how to survive better. That’s likely how #B117 started. 🧵 https://t.co/bMMjM8Hiuz


2) The leading hypothesis is that the new variant evolved within just one person, chronically infected with the virus for so long it was able to evolve into a new, more infectious form.

same thing happened in Boston in another immunocompromised person that was sick for 155 days.

3) What happened in Boston with one 45 year old man who was highly infectious for 155 days straight before he died... is exactly what scientists think happened in Kent, England that gave rise to #B117.


4) Doctors were shocked to find virus has evolved many different forms inside of this one immunocompromised man. 20 new mutations in one virus, akin to the #B117. This is possibly how #B1351 in South Africa 🇿🇦 and #P1 in Brazil 🇧🇷 also evolved.


5) “On its own, the appearance of a new variant in genomic databases doesn’t tell us much. “That’s just one genome amongst thousands every week. It wouldn’t necessarily stick out,” says Oliver Pybus, a professor of evolution and infectious disease at Oxford.

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THREAD: 12 Things Everyone Should Know About IQ

1. IQ is one of the most heritable psychological traits – that is, individual differences in IQ are strongly associated with individual differences in genes (at least in fairly typical modern environments). https://t.co/3XxzW9bxLE


2. The heritability of IQ *increases* from childhood to adulthood. Meanwhile, the effect of the shared environment largely fades away. In other words, when it comes to IQ, nature becomes more important as we get older, nurture less.
https://t.co/UqtS1lpw3n


3. IQ scores have been increasing for the last century or so, a phenomenon known as the Flynn effect. https://t.co/sCZvCst3hw (N ≈ 4 million)

(Note that the Flynn effect shows that IQ isn't 100% genetic; it doesn't show that it's 100% environmental.)


4. IQ predicts many important real world outcomes.

For example, though far from perfect, IQ is the single-best predictor of job performance we have – much better than Emotional Intelligence, the Big Five, Grit, etc. https://t.co/rKUgKDAAVx https://t.co/DWbVI8QSU3


5. Higher IQ is associated with a lower risk of death from most causes, including cardiovascular disease, respiratory disease, most forms of cancer, homicide, suicide, and accident. https://t.co/PJjGNyeQRA (N = 728,160)