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Marc Veldhoen

@marcveld.bsky.social

11K followers 1.3K following 17K posts

Professor of Immunology 🇳🇱 🇬🇧 Lisbon, 🇵🇹 #Immunology Time for Science, not silence https://scholar.google.co.uk/citations?user=7vG1jLIAAAAJ&hl=en https://orcid.org/0000-0002-1478-9562 threads.net/@marc_veld mastodon.online/@marc_veld

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Marc Veldhoen @marcveld.bsky.social · Dec 23

Service post:
This account is on anti-science, COVID-19 denial, Long COVID denial, etc., blocklists. All fine, but I'm also running an automated block program. Some unblock me only to find they’re already blocked.

A reminder: be cautious with blocklists.

Unlike X, once blocked = blocked.

Postbox filled with mail, and the forbidden sign behind it.

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Marc Veldhoen @marcveld.bsky.social · 7h

Although this may open suggestions to ageing too, that is a much more complex issue. Many genes and gene-products need to work in harmony to create a healthy organism. Changing one gene may come at (unexpetcted) costs and requires a lot more reasearch.
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Marc Veldhoen @marcveld.bsky.social · 7h

Evolution rewired a classic immune sensor into a genome stabilizer instead of a brake and sensor of cytosolic dsDNA. The four amino acid tweak in cGAS may underlie the naked mole-rat’s extreme longevity and suggest new ways to stabalise/repoair our DNA.
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Marc Veldhoen @marcveld.bsky.social · 7h

Importantly: delivering naked mole-rat cGAS into aged mice reduced frailty, slowed hair greying, lowered IL-6 and IgG levels, and rejuvenated tissues.
All of this depended on those same 4 amino acids.
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Marc Veldhoen @marcveld.bsky.social · 7h

The result is intreguing: naked mole-rat cGAS helps cells to repair their DNA better, and avoid senescence, thereby maintaining tissue function.
When the 4 amino acids were changed back to how they are in humans/mice, the benefits disappeared.
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Marc Veldhoen @marcveld.bsky.social · 7h

Mechanistically, these changes allow cGAS to:
Stay longer on chromatin after DNA damage, allowing recruitment of other factors.
Resist breakdown via TRIM41
Engage the segregase P97 differently

Result: formation of a RAD50–FANCI complex, boosting HR repair efficiency.
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Marc Veldhoen @marcveld.bsky.social · 7h

In naked mole-rats, that brake on DNA repair is gone. Their cGAS has four key amino acid changes in its C-terminal domain that alters its function, from suppressing to enhancing homologous recombinatio-mediated DNA repair.
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Marc Veldhoen @marcveld.bsky.social · 7h

The authors zoomed in on cGAS, an enzyme best known for detecting cytosolic dsDNA and triggering immune responses via STING - IFNs. In humans/mice, nuclear cGAS inhibits DNA repair resulting in genomic instability, it’s a brake.
www.nature.com/artic...
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Nuclear cGAS suppresses DNA repair and promotes tumorigenesis

Nature - DNA damage induces translocation of cyclic GMP–AMP synthase to the nucleus, where it suppresses homologous recombination by interfering with the formation of the PARP1–Timeless...

www.nature.com

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Marc Veldhoen @marcveld.bsky.social · 7h

Very bad. It is a very high overinterporetation of the paper.

Marc Veldhoen @marcveld.bsky.social · 7h

Naked mole-rats can live up to 37 years, incredibly long for a rodent, and show remarkable resistance to aging and developing cancer. But how their cells maintain genomic stability for decades, avoiding classic ageing signs, has been a mystery for decades.
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Marc Veldhoen @marcveld.bsky.social · 7h

A cGAS-mediated mechanism in naked mole-rats potentiates DNA repair and delays aging

Naked mole rats get much older than closely related mamals of a similar size. cGAS mutations may have an important role in this.

www.science.org/doi/...
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A cGAS-mediated mechanism in naked mole-rats potentiates DNA repair and delays aging

Efficient DNA repair might make possible the longevity of naked mole-rats. However, whether they have distinctive mechanisms to optimize functions of DNA repair suppressors is unclear. We find that naked mole-rat cyclic guanosine monophosphate–adenosine ...

www.science.org

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Marc Veldhoen @marcveld.bsky.social · 8h

They use the same arguments, both don´t understand scientific papers, overinterpret them, cherry-pick, advertise bad papers, deny immune memory, and attack experts. Indeed, who can tell the difference!

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Reposted by Marc Veldhoen

Marc Veldhoen @marcveld.bsky.social · 2d

There was no lymphopenia, no superantigen, no immune damage/dysfunction/exhaustion. There are no large outbreaks of infections. Furthermore, there are no increases in cancers due to SARS-CoV-2 infection, no compounded risk of longCovid, etc.

Now it is brain damage 🤦‍♂️

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Reposted by Marc Veldhoen

Marc Veldhoen @marcveld.bsky.social · 15h

No, Harry, you fail again to read and understand. In a subgroup of moderate-severe COVID-19 patients, without any prior immunity (1st wave!), some may take a little longer to fully recover lymphocyte numbers (particularly B cells) in the blood. No prior numbers known, age is different, etc.

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Marc Veldhoen @marcveld.bsky.social · 11h

Still people making this complete and utter nonsense claim. This is ridiculously bad. It has no basis in reality, there is no data for this. All data shows SARS-COV-2 is another coronavirus, without any special abilities.

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Marc Veldhoen @marcveld.bsky.social · 11h

Possibly. But the study had few subjects, the test is expensive, and its use for diagnosis is still being questioned.

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Marc Veldhoen @marcveld.bsky.social · 11h

Important:

old-variant-containing vaccines retain substantial immunogenicity against antigenically divergent variants.

a gradual decline in nAb responses over time, yet responses remained detectable and relatively durable for up to six months
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Marc Veldhoen @marcveld.bsky.social · 11h

This also happens with an additional infection. Infections after vaccination were mostly mild. They are more likely to occure past the peak of the antibody response. Infection response looks like a booster vaccine.

(less robust immune response in older adults)
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Marc Veldhoen @marcveld.bsky.social · 11h

You expect antibody levels to wane. You expect new variants to bind less neutralising antibodies.

And that is what the authors show, in older adults.

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Marc Veldhoen @marcveld.bsky.social · 11h

People were vaccinated against COVID-19 with different vaccines, and their circulating antibodies (not their memory B cells and plasma cells) levels in blood against variants in the vaccine and new ones.

What is expected?
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Marc Veldhoen @marcveld.bsky.social · 11h

Neutralizing antibody durability and SARS-CoV-2 infection in older adults six months after XBB-containing vaccine booster

Again, same rules apply: antibodies wane. Antibodies are not all of immunity, new strains are selected to bind less of them.

www.nature.com/artic...
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Neutralizing antibody durability and SARS-CoV-2 infection in older adults six months after XBB-containing vaccine booster

Signal Transduction and Targeted Therapy - Neutralizing antibody durability and SARS-CoV-2 infection in older adults six months after XBB-containing vaccine booster

www.nature.com

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Marc Veldhoen @marcveld.bsky.social · 12h

De afweer die we opbouwen heeft een maximum. Dat is bereikt. Het virus zal varianten geven geselecteerd om te infecteren. Voor de meesten zal dat asymptomatisch of milde symptomen zijn. Er zullen altijd mensen zijn die gevoeliger zijn voor infecties, zoals ouderen.

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Marc Veldhoen @marcveld.bsky.social · 12h

First proposed blood test for chronic fatigue syndrome: what scientists think

A blood test has achieved 96% accuracy in diagnosing the condition in a small study of individuals. What does the test detect, and is it a biomarker of the condition?

First proposed blood test for chronic fatigue syndrome: what scientists think

Nature - A blood test has achieved 96% accuracy in diagnosing the condition in a small study of individuals. What does the test detect, and is it a biomarker of the condition?

www.nature.com

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Reposted by Marc Veldhoen

Marc Veldhoen @marcveld.bsky.social · 16h

Persistent lymphocytopenia in convalescent patients with COVID-19: dysregulated B cell, CD4+ T cell, and treg compartments in 7–12% of moderate-severe cases

Unvaccinated cohort, 50 days post infection of patients, January 17 and March 20, 2020.

www.frontiersin.org/...
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Frontiers | Persistent lymphocytopenia in convalescent patients with COVID-19: dysregulated B cell, CD4+ T cell, and treg compartments in 7–12% of moderate-severe cases

BackgroundLong COVID manifests with heterogeneous clinical outcomes, potentially linked to immune dysfunction. However, the recovery of immune-cell subsets d...

www.frontiersin.org

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Marc Veldhoen @marcveld.bsky.social · 15h

Dengue is a good example of an increase due to climate change. It is spreading further north in Europe. Once started in Italy, now also Spain, Portugal and the south of France.

Marc Veldhoen @marcveld.bsky.social · 15h

Sure, you look largely at some specifically picked infections. You look at the usual fluctuations. There is an additional element that antibiotic resustance in for many years on the rise, and hence you see those going up. Childhood vaccines are low, hence measles goes up.