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宇宙是如何变透明的?用表观遗传学控制胆固醇的可行性、如何在肥皂膜上刻凹槽? |
作者:Nature Podcast | 2024/4/1 12:53:44 | 浏览:305 | 评论:0

宇宙是如何变透明的?用表观遗传学控制胆固醇的可行性、如何在肥皂膜上刻凹槽? |


本期Nature Podcast为您带来,宇宙是如何变透明的?古代碑文可能揭示巴斯克语的起源、研究人员是如何在肥皂膜上刻出凹槽的、用表观遗传学控制胆固醇、导致人类失去尾巴的基因突变。

本集精选内容

In this episode

00:49 宇宙是如何变透明的?

大约在130亿年前,宇宙中弥漫着浓密的中性氢“迷雾”,阻挡了某些波长的光。当氢气在一个被称为“再电离”的过程中受到辐射的冲击时,这层“迷雾”就被驱散了,但这种辐射的来源一直存在争议。现在,研究人员利用JWST深入窥探宇宙的过去,发现从矮星系中涌出的带电粒子似乎是再电离的主要驱动力。这一发现有助于了解我们现在看到的宇宙中的一些结构是如何形成的。

Nature

Most of the photons that reionized the Universe came from dwarf galaxies

宇宙是如何变透明的?用表观遗传学控制胆固醇的可行性、如何在肥皂膜上刻凹槽? |
10:55 研究亮点

古代碑文可能揭示巴斯克语的起源

研究人员是如何在肥皂膜上,刻出凹槽的。

Research Highlight

Ancient bronze hand’s inscription points to origins of Basque language

宇宙是如何变透明的?用表观遗传学控制胆固醇的可行性、如何在肥皂膜上刻凹槽? |
Research Highlight

Laser pulses engrave an unlikely surface:soap films

宇宙是如何变透明的?用表观遗传学控制胆固醇的可行性、如何在肥皂膜上刻凹槽? |
11:05 用表观遗传学控制胆固醇

为了对抗高胆固醇,许多人服用他汀类药物,但由于这些药物必须每天服用,研究人员一直在寻找替代品。通过编辑表观基因组来控制胆固醇的方法,在实验室培养的细胞中显示出了前景,但在动物身上的疗效还不清楚。现在,研究人员已经证明这种方法可以在小鼠身上起作用,并沉默了一个与高胆固醇有关的基因,长达一年。小鼠的胆固醇明显降低,研究小组希望这一结果能为人类的表观遗传疗法铺平道路。

Nature

Durable and efficient gene silencing in vivo by hit-and-run epigenome editing

宇宙是如何变透明的?用表观遗传学控制胆固醇的可行性、如何在肥皂膜上刻凹槽? |
18:52 导致人类失去尾巴的基因突变

为什么人类和其他类人猿没有尾巴?据推测,大约在2500万年前,我们的基因组一定发生了变化,导致失去了这种灵活的附属器官。现在,研究人员找到了一种可能的原因:一个名为TBXT的特殊基因的插入。研究小组通过对小鼠基因组进行工程改造,从而发现了该基因所起的关键作用——导致动物失去尾巴。这一发现有助于描述导致人类和其他猿类进化的重要基因突变。

News

How humans lost their tails — and why the discovery took 2.5 years to publish

宇宙是如何变透明的?用表观遗传学控制胆固醇的可行性、如何在肥皂膜上刻凹槽? |
Nature

On the genetic basis of tail-loss evolution in humans and apes

宇宙是如何变透明的?用表观遗传学控制胆固醇的可行性、如何在肥皂膜上刻凹槽? |
News and Views

A mobile DNA sequence could explain tail loss in humans and apes

宇宙是如何变透明的?用表观遗传学控制胆固醇的可行性、如何在肥皂膜上刻凹槽? |
播客文字版TRANSCRIPT


<上下滑动查看本期podcast全部文字内容>

Nick Petrić Howe

Welcome back to the Nature Podcast. This week, how the universe's cosmic fog was cleared, an epigenetic way to control cholesterol, and how humans lost their tails. I'm Nick Petrić Howe.


Astronomers looking at the Universe today can see stars and galaxies from millions of miles away, as light from them floods their telescopes. But in the long history of the Universe this hasn’t always been possible, first because there were no stars, but later because the Universe was filled with a cosmic fog — neutral hydrogen that let through visible light but blocked other wavelengths.

Obviously, that’s no longer the case, but how exactly the Universe emerged from the Cosmic Dark Ages, has been a matter of debate. Around 13 billion years ago, not long after the Big Bang, ionising radiation started to reionise the neutral hydrogen, clearing the fog. But the source of that radiation is unclear.

A new paper in Nature though may clear up this issue, as it has identified a likely culprit of the reionisation. Reporter Lizzie Gibney caught up with one of the paper’s authors, Hakim Atek to chat about the discovery. She started by asking him what the different theories are for reionisation.

Hakim Atek

We had many hypothesis. So one of them was supermassive black holes, that could emit strong radiation that would be able to reanalyse the universe. The problem is that those supermassive black holes are not numerous enough to produce enough radiation. So, the second most plausible explanation of sources would be galaxies that form stars at early epochs and could emit enough radiation to analyse the universe. These were the two main candidates for reionisation.

Lizzie Gibney

And your team has been trying to help shine some light on this debate. What have you been doing? How have you been trying to look back into this period of the universe’s history?

Hakim Atek

So far what we have been doing is getting imaging of this galaxies to try to determine if galaxies are the actual responsible for cosmic reionization. So, our team what we have done here is combined the James Webb Space Telescope with gravitational lenses. So thanks to this combination, we can actually detect and characterise the faintest galaxies ever observed at this epoch of reionisation.

Lizzie Gibney

And what is it that the JWSD telescope can see that others haven't been able to see before?

Hakim Atek

So the James Webb Space Telescope is the most powerful telescope ever built. It's essentially designed to peer into the early universe to uncover the formation of the first galaxies and this famous epoch of reionisation.

Lizzie Gibney

And you're looking at some really faint galaxies that are out there and use a technique called gravitational lensing. Does that–does that boost the light that we're getting from these galaxies?

Hakim Atek

Exactly. So this phenomenon is created by massive structures. So here, we use massive galaxies, its a cluster of massive galaxies that will curve this time, and it will act as a magnifying lens. So we can amplify the light of the distant sources, which would be undetectable even with the JWST without using this gravitational lensing effect.

Lizzie Gibney

So we can finally look at the radiation that's coming off these very faint, very early galaxies. And what did you find?

Hakim Atek

What we found is that despite their size, these tiny faint galaxies are actually very efficient, producing ionising radiation. And the amount of radiation they emit is about four times the value assumed for massive galaxies. And the assumption was that faint galaxies would be like massive galaxies. It turns out, they are not. They are much more efficient at producing ionising radiation than we thought.

Lizzie Gibney

So if we have enough of these faint galaxies, cumulatively we'll be able to produce enough of this ionising radiation to– to dissipate the cosmic fog by themselves.

Hakim Atek

Yeah, so, in this exact study, we also confirmed the number of these faintest galaxies, which is very high. So we combined the number density of these galaxies and their ionising power. So we ended up with enough ionising budget to reionise the universe.

Lizzie Gibney

So it sounds like instead of there being just a few big explosions of radiation clearing out the fog, it's like you've got loads of little candles everywhere and that's doing this ionising job and getting rid of the neutral hydrogen to– to make the universe that we can peer through.

Hakim Atek

Exactly. So it's the little tiny galaxies that by their numbers actually outshine the big galaxies.

Lizzie Gibney

And are you making any assumptions to come to this conclusion?

Hakim Atek

Totally. I think the big assumption here is that the small area we're observing is representative of the large-scale distribution of galaxies in the entire universe. And to do that, we also estimate the uncertainties that come from what we call cosmic variance. So with some simulations, we can extrapolate to the rest of the universe and see how the small variation can affect our results.

Lizzie Gibney

And how does this finding of where the radiation came from that reionise the universe? How does that change our picture of this period and the universe's time? Are we learning anything new about what was going on or what happened afterwards?

Hakim Atek

So in addition to pinpoint the exact sources of reionisation, it also has different implications on galaxy formation. For instance, because low mass galaxies are more evenly distributed as a massive once in the early universe, the exact sources of reionisation also share the global temperature of the gas in the universe, which means the cosmic web of the universe will emerge and form the structures we see today.

Lizzie Gibney

So this reionisation process actually helped shift or form the structures that we still see in the universe.

Hakim Atek

Yes, exactly.

Lizzie Gibney

What's next for you and your team? Is this an area that you're going to keep studying?

Hakim Atek

I think now that we are starting to uncover these ultra-faint galaxies, the question is, how faint we can go and still find galaxies at early times, because there is a theoretical limit of the smallest galaxy that can form stars at cosmic dawn. So we now will have the possibility to directly test our theories. And we have upcoming large programmes to do just that.

Lizzie Gibney

And you mentioned right at the start that some astronomers think that it's actually the matter being drawn into the supermassive black holes isn't it that create radiation? And some people think that it's those that created this ionising radiation? Is this going to be a controversial paper? Or do you think people still stick to their guns and be in the supermassive black hole corner?

Hakim Atek

I think we will have some part of the community that will still advocate for this solution, but if they do, then we will have too much ionising radiation in the early Universe, which will have certain implications also on the growth of structures in the universe, and how the helium reionisation occurs, which is the second most abundant element in the universe. So if you have too much radiation, you will ionise that element too quickly, too early in the universe. And the James Webb Space Telescope is still also telling us about the number of the supermassive black holes in the early Universe. And so far, there are not enough out there to reionise the universe.

Lizzie Gibney

So the evidence is leaning in your favour.

Hakim Atek

We hope so.

Nick Petrić Howe

That was Hakim Atek, from the Astrophysics institute in Paris, in France. For more clarity on this discovery, check out the show notes for a link to the paper. And coming up, we'll be talking about a possible epigenetic way to control cholesterol. Right now, though, it's time for the Research Highlights with Dan Fox.

Dan Fox

Inscriptions carved on a bronze hand over 2000 years old, might be the earliest written example of the language that eventually became modern Basque. Basque is one of the oldest living languages, and is thought to have descended from a language spoken by the Vascones, an Iron-Age people who inhabited parts of northern Spain before the arrival of the Romans. Researchers analysed inscriptions on a hand-shaped bronze plate that was unearthed from an ancient Vasconic village. They found that one of the inscribed words is similar to a Basque word meaning ‘of good fortune’, and the inscriptions and design suggest that the hand was dedicated to a deity of fortune, and used as a good-luck charm. Archaeologists have long thought that the Vascones lacked a writing system other than that used on coins, but the findings show that these ancestors of modern Basque people already knew and used writing in the first century BC. Read more about that research in Antiquity.

Dan Fox

Researchers have used lasers to etch a groove into an unexpected surface – soap film. Soap films are thin layers of liquid sandwiched between walls of detergent molecules, or micelles. When a film is stretched or perturbed, any excess micelles in the liquid layer rush to reinforce the walls of the film, quickly restoring is smooth surface. But now researchers have found that if they increase the moving soap film’s detergent concentration beyond the critical point, they could carve long-lasting grooves into his surface using a laser. That's because the high quantities of micelles reduced the film's elasticity, preventing its surface from recovering. The laser pulses created a series of pits in the film; which elongated as the film flowed, creating etchings that resembled dashed lines each less than a millimetre long. You can read that research in full in Physical Review Fluids.

Nick Petrić Howe

High cholesterol affects millions of people worldwide, increasing their risk of heart disease. To reduce cholesterol many people take statins, but these drugs have to be taken every single day which can be a burden.

But maybe that won’t always be the case. A new paper in Nature shows a step towards making a single treatment which could reduce cholesterol forever, by tweaking epigenetics.

Epigenetics, in general terms, refers to the regulation of gene expression but does not change the DNA sequence itself. Instead epigenetic changes are controlled by things like methyl groups being added to DNA and can increase or decrease the expression of genes. The researchers hope to take advantage of this using a pharmaceutical intervention that contain molecules known as epigenetic effectors which influences genetic expression – in this case – silencing a particular gene that can cause disease.

Now this has been shown to work well in cells in a dish, so in the new paper the team were interested to see if it would work in a full-fledged living organism. Their target was Pcsk9, a gene linked to high cholesterol. I asked one of the authors, Angelo Lombardo and asked him why the team picked this gene.

Angelo Lombardo

Pcsk9 is a modern gene actually it has been used since quite many years, actually. So it’s a well-known gene that needs to be shut off to decrease the level of cholesterol in the blood. So that was a very, let's say, nice and convenient gene to target for this specific group of physical experiments which actually, the biggest question was, is that the genetic technology that we are using sufficient enough now to silence a gene in a living organism for a long period of time.

Nick Petrić Howe

And in this paper, you tried to do this silencing in a mouse model. What was your approach?

Angelo Lombardo

Well the approach is, well, similar to COVID the see so we exploited lipid nanoparticles to encapsulate messenger RNA that qualify for these epigenetic effectors and injected them into mice. So we're not discussing about or talking about vaccination in this specific case, we're talking about transient expression in the liver, which is the organ target, in this specific case, to Pcsk9 transient suppression of these epigenetic effector.

Nick Petrić Howe

As you said, you were trying to see if you could get sort of long-term silencing or less expression of that particular gene, how successful were you in that?

Angelo Lombardo

We were quite successful actually, we can achieve significant level of reduction of Pcsk9. The level of reduction that we achieved, were also linked to the delivery that they use, in this case on the specific lipid nanoparticle that we that we use in our study. We haven't yet reached 100% of repression, we were confident that playing with the delivery with the particles that we use, we can further increase efficiencies.

Nick Petrić Howe

And in the paper, you were able to show that this sort of epigenetic silencing this repression of the genes happened for a whole year for the mice. But you know, I would have thought that as cells divide, maybe they wouldn't have these epigenetic marks on them still. So did you need to like reapply this at any point? Or was this just a case of one and done?

Angelo Lombardo

Well, in this study, not only we follow the mice for one year, but you also perform a surgical procedure which actually activates liver proliferation. You know, liver is a highly regenerative organ when damage and these regeneration implies a significant proliferation of liver petasites And also in that specific experimental context, actually digitally signs in remain stable, indicating really that the epigenetic modification imposed by the technology were, indeed editable. So you hit once it says, memorised that you silence the gene. And these memory remains also to the daughter cells.

Nick Petrić Howe

And so you showed this occurred for a year. But do you suspect that this would last much longer than that?

Angelo Lombardo

That’s the hope, of course, actually, the epigenetic proteins that we use in our editors, they do come from a complex of protein, which is active early during embryogenesis. And these complex of proteins silence endogenous retroelements or retroviruses, which are spread throughout our genome. And the silencing falls early during development in the first same moment of life. Weeks, if not months of life, these epigenetic information are then propagated throughout the entire life of an individual. So I think that's an interesting parallelism, you know, with our technology, and hopefully, also our technology will do the very same, so it wants and then for the entire life of the …..,

Nick Petrić Howe

What do you think that this shows is possible?

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