Amino acid slows nerve damage from diabetes, in mouse study

Host: Nick Petrić Howe

Welcome back to the Nature Podcast. This week: how serine could help with diabetic nerve damage.

Host: Shamini Bundell

And the latest from the Nature Briefing. I’m Shamini Bundell.

Host: Nick Petrić Howe

And I’m Nick Petrić Howe.

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Interviewer: Nick Petrić Howe

Diabetes is a condition which can have some really serious effects. One of these is diabetic neuropathy, which is when the nerves are damaged, leading to things like pain or numbness and even complications requiring limb amputations. And currently, there aren’t good ways to treat this other than managing diet. But this week in Nature, a study reveals a link between these neuropathies in mice and an amino acid called serine.

Interviewee: Christian Metallo

There have been some recurring discoveries that link serine metabolism to neurological dysfunction over the years.

Interviewer: Nick Petrić Howe

This is Christian Metallo, one of the authors of the new paper. Not only does serine seem to have a link to nerve dysfunction, but it also seems that in metabolic diseases, like diabetes, serine levels in particular and serine metabolism get a little bit out of whack. To see how out of whack serine can get, Christian measured serine levels in mice which were obese and insulin resistant – the typical mouse model for diabetes.

Interviewee: Christian Metallo

What we saw was that serine and a related amino acid glycine were both significantly down. And what we found with isotope tracing is that those diabetic animals, when they were fed that serine, they converted much of that to glucose, which is kind of a bad thing for diabetics.

Interviewer: Nick Petrić Howe

Low serine levels and animals converting serine to glucose definitely counts as out of whack. And that wasn’t all. The serine being so out of whack may also explain why it’s been linked to neurological dysfunction. Christian saw that this imbalance seemed to generate compounds which are toxic to neurons. So, that begs the question: could adding serine to the diet help mitigate some of these diabetic neuropathies?

Interviewee: Christian Metallo

So, we could mitigate it if we fed a serine-enriched diet to the diabetic mice as they were getting older. We could mitigate the onset of sensory neuropathy. It's not a cure, but it does show that it's somewhat tractable and by modulating serine levels, we could impact these neurological comorbidities in a diabetic mouse.

Interviewee: Daniela Manichella

This paper is very interesting and also very broad interest not only for the neuropathy but because the serine, it could be a very good intervention for all kinds of complications of diabetes.

Interviewer: Nick Petrić Howe

This is Daniela Manichella, a neurologist and physician who works on neuropathies, and who wasn’t associated with this latest work. Many complications of diabetes are caused by nerve damage and so theoretically serine could have really broad impact and potentially be used without unpleasant side effects.

Interviewee: Daniela Manichella

Because serine is very natural. We have it in our system, so that will avoid the side effects of the medication that are used in general.

Interviewer: Nick Petrić Howe

Of course, it must be said that mice are quite a long way from humans. Here’s Christian again.

Interviewee: Christian Metallo

Humans and mice are very different. And even in our initial studies, we're seeing how widely different serine homeostasis is between a mouse and a human. I think evolution has done this purposely in a way because we're bigger. We have a bigger and more functional nervous system as well, so it does correlate with the neurological function.

Interviewer: Nick Petrić Howe

Daniela too would want more work in humans to better understand the role of serine, but she also pointed out that more work could be done in mice as well. There are a range of neuropathies that occur with diabetes, and not all were completely covered by this paper. Broadly, it looked more at the neuropathies that cause numbness, rather than the ones that cause pain. As these neuropathies manifest differently, it could mean that serine would have a different effect.

Interviewee: Daniela Manichella

That's why the next step I think will be better characterise which kind of neuropathy, even in mice, and which phenotype are then reversed which, again, is very interesting and high impact because it could be a really good intervention for the patient.

Interviewer: Nick Petrić Howe

Even so, Christian thinks that there are potential drug targets that may emerge from this work, and there are clinical trials already underway using serine as a supplement for other conditions that seem to be affected by it being out of whack.

Interviewee: Christian Metallo

I’m really interested in seeing if this holds true, if serine supplementation actually works to improve patient health in humans. So, I think there are also some interesting drug targets to see, can we stop the diabetic livers and kidneys from getting rid of the serine? The supplementation is promising but there's a lot of serine that must be taken, and we're essentially showing that patients who have diabetes don't do as good of a job of absorbing serine anyway. But we also do see that the diabetic animals do show us some improvement in that. And there's a lot worse things that we can put in our bodies than serine, so there is some promise there. But like with anything, you're going to pee most of it out and you need to see that you're not going to hit some upper limit that causes some other issue to arise.

Interviewer: Nick Petrić Howe

That was Christian Metallo from the Salk Institute for Biological Studies in the US. You also heard from Daniela Manichella from Northwestern University, also in the US. For more on this story, head over to the show notes for a link to the paper and an associated News and Views article.

Host: Shamini Bundell

Coming up, we’ll be hearing about a multimillion-dollar trade in paper authorships. Right now, though, it’s time for the Research Highlights, read by Dan Fox.

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Dan Fox

Chickens are polluting the genomes of their undomesticated relatives — and the process seems to be speeding up. Humans domesticated chickens from populations of wild red junglefowl between 4,000 and 10,000 years ago, probably in southeast Asia. And while the two groups are known to interbreed, the extent to which their gene pools have remixed has been unclear. To gauge this intermingling, researchers sequenced the genomes of 45 red junglefowl museum specimens, collected between 1874 and 1939, and compared them with contemporary birds. They found that modern red junglefowl harbour more domestic chicken DNA than the historic samples, with 20-50% showing signs of domestic ancestry. They were also able to identify a number of genes under selection in domestic chickens, including those involved in brain development and vision, that could explain the differences between domestic and wild birds. Why did the podcast listener cross the road? To read that research in PLoS Genetics.

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Dan Fox

A chamber of molten rock has been discovered lurking beneath an underwater volcano off the coast of Greece, suggesting the volcano, named Kolumbo, might be more likely to erupt than previously thought. Kolumbo last erupted in 1650, killing dozens of people on the nearby island of Santorini. Researchers studied the volcano using high-resolution seismic measurements and found a magma chamber 2 kilometres beneath the sea floor, making it shallow enough to erupt easily. With only 500 metres of water lying over Kolumbo, any eruption could create a tsunami and send ash billowing into the sky. The researchers say that this discovery could suggest that similar reservoirs have gone undetected at other active volcanoes, challenging eruption forecasts. Read that research in full in Geochemistry, Geophysics, Geosystems.

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Host: Nick Petrić Howe

Finally on the show, it’s time for the Briefing chat, where we discuss a couple of articles that have been highlighted in the Nature Briefing. Shamini, what have you got for us to discuss this week?

Host: Shamini Bundell

Well, I was very happy to see an article in Nature all about the Hubble Space Telescope. And you might be thinking, ‘Oh, are we still we still talking about that?’ Because obviously the James Webb Space Telescope (JWST) has been taking most of the limelight recently. It's been all over the news. But this article is all about how scientists are still using Hubble and all the important science it is still doing.

Host: Nick Petrić Howe

Well, yeah, I had thought that now that JWST was up there and it's sending out all these wonderful images, what use do we have for the Hubble? But there is some use. Can it do things JWST can't or anything like that?

Host: Shamini Bundell

It can, exactly. So, it does actually have kind of different properties. So, we've seen lots of photos that have been published. In particular, people have shown comparisons showing how JWST can take much more precise, sort of detailed, crisp images of like the same celestial objects than Hubble can. And JWST has a specific ability to look at infrared wavelengths, which is really good for super distant galaxies. So, yeah, it's amazing. It's showing us things we've never seen before. But Hubble is looking at other wavelengths other than these infrared ones, and in particular, high-energy ultraviolet wavelengths, which are sort of particularly of interest for sort of specific astronomical phenomena, and visible wavelengths as well, which is great for stuff that's much closer to Earth.

Host: Nick Petrić Howe

Well, I'm happy to hear that it is getting some use because this was the telescope I sort of grew up with and had fabulous images when I was a kid. But for researchers, there's actually some proper like useful information that they can get that they can't get from JWST.

Host: Shamini Bundell

Yeah, and apparently, it is in quite high demand still. People are trying to get telescope time and there's some examples of things it's particularly good at. So, the kinds of things that have UV emissions, obviously, in particular, or young stars as they're sort of gobbling up gas and dust, exploding stars. The thing about exploding stars obviously being that they're somewhat unexpected. You don't know when a star is going to explode, so you want to get over there and look at it quite quickly, which, apparently, Hubble is sort of particularly suited to. And my favourite sort of thing about that in the article was apparently Hubble has ‘flexible Thursdays’, which is once a month where Thursday is made available for any sort of like last minute-observations.

Host: Nick Petrić Howe

I do really enjoy the idea of ‘flexible Thursdays’ for a telescope. And so, while it seems that Hubble is doing lots of cool stuff, JWST is now there, so what does that mean for the future of Hubble?

Host: Shamini Bundell

Well, the problem is it's not going to last forever. And we don't actually know how long it's going to last. We can't really predict when something is going to break. There have already been things that have sort of gone wrong and been fixed. For example, one of the computer operating systems is currently running off a backup because the original one broke, and they switched to the backup and they haven't got the first one up again yet. And since NASA retired the Space Shuttle, I think it's going to be a lot harder for them to sort of go and service it or replace any parts to sort of keep it up to date. So, there's definitely a time limit on Hubble, which I think is one of the reasons people are sort of particularly keen to get as much out of it as they can. Some of the researchers in this article sort of estimated probably into the 2030s, it will probably still be going, and possibly by the 2040s, there might be another UV space telescope, but there's definitely no imminent plans for that. And NASA are, to some extent, planning for its demise. And there is a vague plan that because its orbit is going to be gradually sinking and that puts it at risk from damage from drag from the Earth's atmosphere, there's also an issue of solar storms, so there is a vague plan to maybe work with SpaceX and send something that could sort of boost its orbit, sort of shuffle it up a little bit so it at least doesn't sort of break up into lots of different pieces and maybe NASA could bring it down more safely. But yes, after 33 years, nearly, of incredible observations, we're definitely starting to look at the end and the last things and the last images we're going to get from Hubble over the next several years.

Host: Nick Petrić Howe

So, Hubble is having its sort of last data-heavy hurrah, I guess, then. And speaking of data, data leads to publications, and I've been looking into a story about people trading in authorships for papers. How's that for a link?

Host: Shamini Bundell

That was a link, yes.

Host: Nick Petrić Howe

So, the story I've been reading this week is about this trade that's going on in authorships for papers, so people are literally buying their way onto papers to be an author of a paper in a reputable journal. And yeah, no, this is a really surprising story that I was reading this week in Nature.

Host: Shamini Bundell

Not that I'm planning to do it, but who would I contact to get to buy a paper authorship? Are these like real, real valid papers in real valid journals?

Host: Nick Petrić Howe

That seems to be the case. These are real valid papers in real valid journals. And the way you find it is there are literally adverts on many social media sites, and they'll have like the title of the paper, the journal it's going to be published in, the year of publication and the position that you can be as authors.

Host: Shamini Bundell

So, are these like research groups that are basically like, ‘We need more money. I know, we'll sell some paper authorships to raise extra cash for groups.’ Is this some kind of giant scam or what?

Host: Nick Petrić Howe

Well, a lot of this seems to be coming from a website called International Publisher. This is a Russian-language website, and two people have been working hard – Anna Abalkina and Nick Wise – they've been working to investigate this. And they've uncovered more than 1,000 authorship offers linked to this website and of those, 460 have become actual publications.

Host: Shamini Bundell

How far has this investigation gone then?

Host: Nick Petrić Howe

So, this started in 2019, when a large number of these adverts have come about and recently, an analysis of this investigation has been published as a preprint. So, you can look at that and see sort of the findings of it. But yeah, there seems like there's a huge problem going on here. And it seems to be kind of an evolution of paper mills, which you might be familiar with. These are where people basically send the company some money, and they'll make a falsified paper that looks sort of realistic that you can publish and put on your CV. But this is a more sophisticated version of that because these are actual bits of research in genuine reputable journals, and so it's a bit harder to find this. The only reason that they've been able to link these things to specific things is in the adverts they say which paper you can get onto. They have the title and more details about the paper, and so because of that, you can link it because this is a really hard thing to prove. You can't just say, ‘Oh, this person has bought their way onto that.’ You need some sort of proof. But linking these adverts to it seems to be the way. And now because of this investigation, journals have started to retract the papers that have been associated with this.

Host: Shamini Bundell

Woah, it seems like if people can find out what the papers are and maybe identify you, then that's a huge reputational risk. I wonder if it'll just drive the company to be more sneaky with their sort of setup and advertise more quietly? It sounds, like you said, if it's really hard to prove, it could be really hard to fully stamp out.

Host: Nick Petrić Howe

Well, exactly. And like I said, this is an evolution of paper mills which were just producing falsified data. Now we've got real data, but not real authors, like they're just on the paper. So, it is a bit of an arms race going on. And yeah, there is, as you've sort of alluded to, there is this sort of aspect as well that the system of science does value having lots of publications, and in many countries, people's promotion prospects are linked to the number of articles they publish. So, there is like an incentive there. So, there's maybe a wider look to be had at the whole system.

Host: Shamini Bundell

Yes, I suspect we shall have more conversations on the Nature Podcast about publish or perish and the various incentive systems within science and scientific publishing, so we shall look forward to that. And listeners, if you want to hear more about either of these stories we’ve been chatting about, check out the show notes. We've got links to these two and a link to where you can sign up to the Nature Briefing where you can get more updates on what's going on in the world of science.

Host: Nick Petrić Howe

Well, that's about all we’ve got time for this week. But Shamini, just before we go, I think you’ve got a video that you wanted to plug?

Host: Shamini Bundell

Yes, another fantastic documentary. We'll put a link to it in the show notes. But it's all about the problem of sargassum, which is kind of brown floating seaweed that is kind of taking over a lot of the sea and the beaches in various parts of the world. Huge amounts of it are expanding over the sea and impacting a lot of people, a lot of industries, livelihoods. And this documentary, it looks at some potential ideas people are developing to deal with this problem, so please do check this out.

Host: Nick Petrić Howe

Well, colour me intrigued. It's not a problem I have come across before, but I'm interested to hear more about it. But that's all for the podcast for this week. So, listeners, if you want to keep in touch with us, we're on Twitter. We’re @NaturePodcast. Or you can send an email to podcast@nature.com. I’m Nick Petrić Howe.

Host: Shamini Bundell

And I’m Shamini Bundell. Thanks for listening.