RNA repair mechanism discovered in humans
phys.org
phys.org
The article doesn't seem to describe repair work. Did I miss some detail?
> "In order to fulfill their diverse functions in the cell, RNAs often need to be chemically modified after their creation or repaired after damage," explains Andreas Marx, professor of organic and cellular chemistry at the University of Konstanz.
> One chemical reaction that plays a role here is the three-step linking (ligation) of two RNA strands at their respective opposite ends. This reaction is triggered by specialized enzymes called RNA ligases and is present in all forms of life, from viruses to fungi and plants. In vertebrates, including humans, such RNA ligases had yet to be identified.
> An interdisciplinary research team from Konstanz has now discovered the first human RNA ligase of this type, the protein C12orf29."
But it's an inference -- an assumption that human ligases will do what ligases do in other species and that's not what the actual research shows, at least not that the article indicates.
We've just discovered these. They are investigating what they do. Their investigation shows they protect against oxidative stress, which is significant.
I skimmed the paper and there really isn't any direct evidence that it's a "repair mechanism" beyond the apparent effects of knocking out the gene: cells die faster, and degradation of ribosomal RNA is faster.
The presumed mechanism here would be oxidative stress->damage to rRNA->reduced protein production/increased error rate in proteins->cell is not happy, with the RNA ligase playing the role of repairing localized damage caused by stress thus allowing the cell to continue at its normal rate.
There also isn't any strong evidence that this system resembles the ones seen in viruses and bacteria. There are many RNA ligases that have many different roles and the variations aren't shared between all kingdoms of life.
I have lousy eyesight. I sometimes just fail to find what I'm looking for and it's important to me to understand this stuff.
We are in for a series of revelations that will deeply alter the way we understand the microscopic intricacies that hold us upright and posting on internet forums.
Exciting things happening in the field!
https://www.cell.com/cell/fulltext/S0092-8674(21)00293-2
Even the cell membrane is fantastically complex. Keeping out the bad stuff and letting the good stuff in. While keeping the good stuff in and letting the bad stuff out.
You can't just decide the fact society is made of humans is an irrelevant detail and model them with little rational balls, or whatever you came up with. Because the balls wouldn't do what we do. And I completely disagree it doesn't matter what the human body does. The human body matters to society a great deal, actually. Say, pollution in cities is absorbed by your human body, and affects health, even mental health, and how long you live. This affects social dynamics immensely or doesn't it? We've had entire social movements based on our understanding of the human body, how we categorize in various ways the human body, and violence done against the human body, choices about the human body, how we treat it medically and so on and so on. Countless examples.
Of course you can successfully model specific narrow events, do a representative sample and try to approximately guess, say the outcome of elections. Doesn't always work, but in this very simple example, you can abstract things. But you need to still abstract with deep understanding of what is abstractable for that specific point in space and time.
This approach fails miserably if you need to predict how society will evolve over time, and more fine-grained detail. Say, just 2 years ago society was largely ignorant of the AI revolution bubbling up based on work by Google & subsequently OpenAI. This is something society did, irreducibly, based on the people in it, and their bodies and neurons. And no basic statistics model that abstract us away would have predicted this.
Also, abstraction is an activity which often serves to make additional room for new emergent complexities.
Nature solved this problem of radical open-ended exploration through evolution. It takes a lot of time but in a single run evolution created all species and life on earth. Evolutionary methods also created AlphaGo, AlphaTensor and AlphaFold - three AIs that surpass all humans put together in specific fields.
Basically learning from massive search and problem solving outcomes - that's how you solve hard problems. And if you think about it, that's how science works too - so many papers, many contradicting each other or trying completely different approaches adds up to evolution in the space of scientific ideas. Any one human alone can't do it, but all of us over a long enough time can do so much more, diversity and open-endedness are key.
Arguably the totality of all lifeforms on earth, which are all physically connected to each other by their common genealogical graph (and by Earth as their environment), is more complex, because it contains all the brains.
Personally don't see how this follows.
"There is no larger circle than this ball bearing!"
"What about the wheel it's used in?"
"That's tautological!"
Just as one can abstract out the brain from the body and talk about the complexity of the body (less the brain). Such a comparison is fine by me.
But society and the terrestrial ecosystem don't exist without functioning brains in them. And a genealogical relationship doesn't exist at all as a physical object, just as a conceptualized object (such as a graph). And conceptualized objects, such as graphs, typically aren't that complex (though can probably get there if someone dedicates the computational resources to do so).
>But society and the terrestrial ecosystem don't exist without functioning brains in them.
1) Original reply didn't say anything about society, only life an it's physical interactions.
2) Sure it does. Plenty of life forms without brains exist, and their sum is more complex than the human brain. The human brain itself is a composite of brainless life.
>And a genealogical relationship doesn't exist at all as a physical object, just as a conceptualized object (such as a graph). And conceptualized objects, such as graphs, typically aren't that complex (though can probably get there if someone dedicates the computational resources to do so).
That isn't because of what conceptual objects are, it's because of how they are used. The purpose of most conceptual objects is simplification. One can produce arbitrarily complex conceptual objects, we just don't normally because... why?
We can even throw out all of these semantics if you want and go with a much narrower version of the original statement: "The brain is the most complex physical system", and even that isn't necessarily true. The bacterial ecosystems that compose the digestive system have more interacting cells, with less defined interactions, than the brain. Maybe you meant "most complex computational system"? That's potentially true, depending on your definition of complexity.
I'm not interested in discussing complexity, just the foundations of productive (and polite!) discussion and debate. So we'll go our separate ways here. I would probably agree with you with respect to the brain not being the most complex physical system.
Keep in mind the latter contains the former. So, tautological, unanswerable question yes? (No)
If you instead stated that a screw is the most complex tool humans make, then anyone who said "two screws! (in a smartphone)" as a counterpoint is not debating in good faith.
> More complex than the immune system?
Possibly. From 2016: https://www.nature.com/articles/nature17316
text in <> are mine.
> The research group behind the current study previously showed11 that NHEJ <non-homologous end-joining, an error-prone mechanism of double-strand DNA break (DSB) repair> is essential for NSPC <neural stem/progenitor cells> differentiation, which implies a role for NHEJ-mediated DSB repair during normal brain development. It is possible that subpopulations of cells in the brain display the same types of rearrangements, and that some are positively selected. Similar studies in vivo and in other tissues are needed to test this hypothesis.
From 2022: https://www.nature.com/articles/s41597-022-01508-x
> We show that genome-wide maps of endogenous DSBs are highly correlated between experimental replicates up to 10 kilobases (kb) resolution, and that DSBs are non-uniformly distributed along the genome, in all three cell differentiation stages analyzed.
...
> Our datasets and analytical tools represent a valuable resource for exploring genome fragility during human neurogenesis and investigating how this might contribute to the pathogenesis of NDDs. <neurodevelopmental disorders>
https://en.wikipedia.org/wiki/V(D)J_recombination is wild.
My money is on the immune system being more complicated.
this rabbit hole goes deep...
Hope that helps!
You took it as...?
https://sinclair.hms.harvard.edu/people/david-sinclair
Who considers him a quack? Why should I believe them?
A slew of retracted papers from his mentor's lab, and image duplications/fabricated western blots from David's lab:
https://forbetterscience.com/2020/05/14/never-ageing-anti-ag...
https://forbetterscience.com/2023/04/17/the-original-sins-of...
Several blog posts on the resveratrol controversy by Derek Lowe (required reading in pharma/biotech):
https://www.science.org/content/blog-post/resveratrol-srt501...
https://www.science.org/content/blog-post/does-resveratrol-r...
https://www.science.org/content/blog-post/resveratrol-humans...
https://www.science.org/content/blog-post/latest-sirtuin-con...
Also anecdotal, but I personally know several PIs who worked on sirtuins during their PhDs and they all say that David is full of shit.
Dr. Jeffrey Flier: https://twitter.com/jflier/status/1495909501211447305?s=21
Dr. Charles Brenner: https://twitter.com/CharlesMBrenner/status/14966040557993615...
Dr. Brad Stanfield: https://www.youtube.com/watch?v=JAFnD27ffqE
Put it this way: it's more likely cognitive than knitting and toothpicks.
The central dogma concerns mainly the transcription of DNA to mRNA, the reverse transcription of RNA back to DNA, and the translation of mRNA to protein. But over time RNA has turned up in a wide range of other activities. In this case, ribosomal RNA is the functional heart of the ribosome- the machine that translates mRNA to protein.
Ribosomal RNA represents a very significant investment of resources for the cell and so if it gets damaged, the cell won't be able to make proteins as quickly, or the proteins that get made might have errors, both of which have dire effects on the cell.
> Transfers of information not explicitly covered in the theory