RNA repair mechanism discovered in humans(phys.org)
phys.org
RNA repair mechanism discovered in humans
https://phys.org/news/2023-04-hidden-rna-mechanism-humans.html
82 comments
Isn't the repair work that of the RNA ligases, whose particular versions for humans are first mentioned here?
> "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."
> "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."
Ah. Ok. I see why you would infer that.
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.
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 generally agree with your assessment.
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 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.
Agreed on all counts, though it's important to note that this protein has bacterial homologs that almost definitely have the same function (5'-3' RNA ligase activity).
Thank you. That's helpful.
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.
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.
I think you're right that they're just (at this point) making a conjecture, which is incongruent with the title.
I believe that humans have not yet created any system more complicated than our own bodies. In turn, I think the same claim holds for our own brains too.
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!
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!
A single cell is more advanced technology that anything we've developed so far.
Do we have the ability to make single cellular lifeforms using similar building blocks?
Not anywhere near. I’m just an interested observer, but the nearest is ‘synthetic life’ which takes existing cells and removes/reworks/replaces the existing dna.
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.
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.
We build things with factories where the factory is orders of magnitude more complicated than the thing being built. Life build things via self replication at a microscopic level. Seems like a fundamentally different approach
Life also builds one atom/molecule at a time. Another fundamental difference.
Complexity is a bit subjective. Society is ostensibly more complex than us, because it includes us. Of course, so far society is more often less than the sum of our parts, than the other way around. Growth is hard.
I disagree with that. A whole can be less complex then its constituent parts. This is the entire point of abstraction, you can hide irrelevant complexity.
Abstraction is a way to break down a system to fit in our minds & simulations, including for the purpose of designing it, but it's not what a system truly is, and it's not how it behaves. It's a compromise, like for example your calculator has 8 digits, and shows E if you need more, but this doesn't mean math in the universe is limited to 8 digits.
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.
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.
Which is different from saying a whole can't be more complex than its parts...
Also, abstraction is an activity which often serves to make additional room for new emergent complexities.
Also, abstraction is an activity which often serves to make additional room for new emergent complexities.
Depends how we define "system" maybe? If we include all human activity as part of one system then maybe the complexity does approach it. Conversely should we include all the sub-quantum in our assessment of the human body? Where to draw the lines?
i dont a human can create a system this complicated... i dont think we can even map it out. if it's done, it'd be done by AI and it'd be a black box. we couldn't create an autonomous car, we need ai to come up with million rules and parameters. same story here just order of magnitudes more complex.
Can't do it intentionally, but evolution can do it unintentionally.
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.
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.
Ai kinda follows iterative exploration approach too
Don't forget that having a GNN (or perhaps Sheaf NN) model the system can allow decomposition such that an analytical expression can be extracted to explain the dynamics of the model quite well. This was shown via Cranmer et al, and continues to be a good way to find explanatory models that both interpolate as well as the NN and extrapolate past the provided data.
The brain is the most complex object in the known universe.
By what measure of complexity, and what definition of “object”?
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.
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.
Comparing a brain to anything which encompasses a brain, is tautological. In debate ("arguably", as you say), this is the equivalent of "infinity plus 1", which is a fallacy. So obviously the GP could not have been referencing anything which contains a brain as an "object".
Which is why I asked about what qualifies as an "object". The brain itself is a composite, so why does a larger composite not qualify?
A larger composite (which contains a brain) can not qualify by the very nature of the proposition put forth. At least in adult debate (where "infinity plus 1" is seen as fallacious). Larger composites that do not contain a brain are fine by me, though I'm not the person you originally responded to.
> A larger composite (which contains a brain) can not qualify by the very nature of the proposition put forth
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!"
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!"
The wheel does not need to contain the ball bearing in order to still be a circle, or even a wheel. It just can't be a functional part of a wheel-axle system without it.
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).
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).
The totality of all life on earth need not contain the human brain to be a complex object. So I still don't see the difference here.
>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.
>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.
FYI: I am not the OP who originally said that the "human brain is the most complex object in the known universe".
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.
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.
If we take the argument from first principles I'm not so sure it leads to your destination. Are atoms more or less complex than the things they comprise? And is that complexity not encapsulated by the emergent system that forms from that atomic substrate?
What is more complex: a screw, or a smartphone?
Keep in mind the latter contains the former. So, tautological, unanswerable question yes? (No)
Keep in mind the latter contains the former. So, tautological, unanswerable question yes? (No)
What us more complex? A cpu or a cpu inside a box? Adding a less complex object layer on top of an already complex object technically increases it's complexity. However, it is a silly argument to make.
A smartphone is more complex than a screw because it contains screws. This is a fine comparison to make because it is the one you, the stater, stated.
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.
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?
Gonna have to agree that at the very least, the immune system is way up there! After reading Philipp Dettmer's book "Immune" (recommended), I couldn't help but think, "Wow, the API and protocols that this thing has..."
This - the immune system is fiercely complex, and as I understand it there's reason to believe we don't yet know all the types of cell that are in it. I could be wrong about that - I'm not an immunologist - but seem to recall reading such in the last few years.
To address you and the GP.
> 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>
> 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>
If the rules that govern intelligence are simple (and intuition tells me they are), then the immune system is certainly a complicated and prickly beast.
https://en.wikipedia.org/wiki/V(D)J_recombination is wild.
My money is on the immune system being more complicated.
https://en.wikipedia.org/wiki/V(D)J_recombination is wild.
My money is on the immune system being more complicated.
I don't want to double post: https://news.ycombinator.com/item?id=35933061
immune system cells actually share a lot of the same receptor systems as neurons do, and these systems end up influencing each other to significant degree, both ways.
this rabbit hole goes deep...
this rabbit hole goes deep...
This is interesting to what extend is this interaction?
Known by who?
In common parlance, “known universe” refers to the extent of the universe that is observable by human beings on the planet earth.
Hope that helps!
Hope that helps!
I took it as an intelligent way to poise an interesting counterpoint to assumption.
You took it as...?
You took it as...?
Counterpoint to what assumption? To the idea that the brain is complex? Or was it a cryptic way to imply that there might be other sentience with more-advanced “brains”?
I was pointing out the potential limitations or challenges inherent in using one's own cognitive abilities to understand and evaluate the world, including the brain's ability to comprehend itself. But i loved how this open up a discussion
^^ this
Biological systems are unnecessarily complex systems. This why the key to understanding ourselves won’t happen by studying biology, rather by creating AGI.
https://bower.sh/in-love-with-a-ghost
https://bower.sh/in-love-with-a-ghost
Is this relevant for anti-aging research? How significant is this paper in that context?
Larry Ellison, is that you?
I suggest you look into David Sinclair, he's done some interesting research with epigenetics.
David Sinclair is considered to be a quack (bordering on a fraud) by many within the scientific community.
So I guess we're at the point which Harvard Medical School isn't good signal?
https://sinclair.hms.harvard.edu/people/david-sinclair
Who considers him a quack? Why should I believe them?
https://sinclair.hms.harvard.edu/people/david-sinclair
Who considers him a quack? Why should I believe them?
The former dean of Harvard Medical School: https://twitter.com/jflier/status/1495833104510038026
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.
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.
You're gonna need to backup your claim, because a quick google search didn't lead me to anything.
Not the person you're replying to, but this is what I found after a quick google search:
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
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
See the tweets from the other replier, as well as my reply above.
My grandmother just celebrated her 100th birthday. She still lives on her own, drives, does her own cooking, walks unassisted, etc. When I mentioned I was going out of town for her 100th birthday party, people kept saying she must have good genes. Maybe so. Maybe she has some sort of really good RNA repair mechanism.
If she has a good RNA repair mechanism isn't it heritable or do you posit she bought it or made it from wool and toothpicks?
Maybe inherited, maybe a mutation unique to herself.
Your response seems to miss the difference between the terms inherited and heritable (because it could be heritable without being inherited), but your point is valid: whatever she has may be cognitive, biological, or otherwise, and may or may not have heritable aspects.
A cognitive repair mechanism for RNA. That's novel. Intracellular functions are defined by gene expression, I don't think meditation or yoga is going to do it although I suppose suppression of stress hormones might influence cell function.
Put it this way: it's more likely cognitive than knitting and toothpicks.
Put it this way: it's more likely cognitive than knitting and toothpicks.
The science is starting to stack up in favor:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134740/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134740/
Proclivity to mutation is .. sometimes heritable. That's the BRCA gene, no? In the case of RNA repair, If it's not 50/50, there'd be an advantage in repairable RNA.
I'm looking forward to ways we can increase levels of C12orf29 or supplement it somehow in hopes of boosting RNA repair.
Human tissues may be fine tuned to need a specific range of C12orf29 molecule quantities: too many or too few might be big problems. See https://www.proteinatlas.org/search/C12orf29 for the gene expression for various tissues.
How does this fit into the https://en.m.wikipedia.org/wiki/Central_dogma_of_molecular_b... according to which RNA is short-lived?
The central dogma doesn't really cover the form of RNA that is speculated to be repaired here: ribosomal RNA.
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.
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.
RNA is generally short lived. But specific kinds of RNA can have longer lifetimes. It’s accurate to say that RNA lifetime is extremely tightly regulated, and most of the time that means that it is short lived. Its lifetime is also extremely short compared to DNA and a high percentage of proteins.
Even that page acknowledges that this dogma is a simplification of reality:
> Transfers of information not explicitly covered in the theory
> Transfers of information not explicitly covered in the theory
The article doesn't seem to describe repair work. Did I miss some detail?