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Platelets are probably best known for their role in blood clotting, making scabs and related, if less salubrious, contributions to heart attacks and strokes. But these tiny, saucer-shaped blood cells have other physiological duties as well, including surveillance for viral or bacterial infections, the recruitment of immune cells to the site of a suspected incursion and even the direct destruction of pathogens. Now, thanks to the findings of a Ludwig Cancer Research study, we can add to this rich portfolio an additional and critically important function.

Researchers led by Ludwig Oxford’s Bethan Psaila and postdoc Lauren Murphy report in the current issue of Science that platelets may also help suppress systemic inflammation. Better yet, the way they do so can be readily harnessed to significantly improve the early and minimally invasive detection of cancer and the sensitivity of prenatal screening.

While platelets do not have their own nuclei, we discovered that they act like sponges, mopping up the fragments of DNA that are released by dead and dying cells. Our bodies employ multiple mechanisms to clear these bits of DNA from the bloodstream, as they can provoke inflammatory and autoimmune disorders if they accumulate. Our findings suggest platelets play an important role in limiting the abundance of DNA fragments in plasma. Fascinatingly, we also discovered that they then release these pieces of DNA when they are activated, suggesting that platelets can deploy their DNA cargo in a manner that prevents nonspecific inflammation yet elicits targeted inflammatory responses where they’re needed, such as, say, at a site of injury.”

Bethan Psaila, Ludwig Oxford

Cell-free (cf) DNA can also include traces of circulating tumor cell-derived DNA (ctDNA). An increasingly sophisticated suite of technologies now exists to isolate and analyze ctDNA for the noninvasive detection of cancers and monitoring of responses to therapy. But ctDNA levels are very low, especially in the earliest stages of disease, when cancers are best detected. Its rarity reduces the sensitivity of cancer screening by such “liquid biopsies”.

As it happens, the cfDNA collected for these diagnostics is currently isolated from blood plasma after all the blood cells, including platelets, have been discarded. The findings of this study suggest that a substantial proportion of cfDNA, including that derived from tumor cells, is contained within platelets, and this important source of information is therefore being missed.

“We’ve demonstrated that platelets take up DNA fragments that bear the mutational signatures of cancer cells,” said Murphy. “This is true not only in patients with advanced cancer but, remarkably, also in people who have pre-cancerous polyps in their colon, suggesting that platelets may offer an additional and so far untapped reservoir of cfDNA that could significantly improve the sensitivity of liquid biopsies.”

The finding that circulating platelets bear the genetic signatures of cancer has significant implications for cancer prevention.

What prompted the researchers to look for DNA in cells that lack a nucleus?

Platelets have a notable morphological quirk: they’re shot through, like sponges, with a network of membrane-lined channels called the open canalicular system. These channels allow them to release certain biomolecules essential to clotting and tissue repair upon activation and to pick up others, like viral RNA and DNA, as they circulate. Given the latter capability, Psaila hypothesized several years ago at a multi-institutional, cross-disciplinary brainstorming session organized by the philanthropy Cancer Research UK that platelets might also be picking up genomic cfDNA.

In partnership with senior author Chris Gregory at the University of Edinburgh, Psaila prepared a pitch, winning a small award that allowed her to hire a research assistant, Murphy, to validate this hypothesis. A year later, the researchers had exciting data that helped Murphy secure a position in a PhD program and a major early detection project grant from Cancer Research UK.

They and their colleagues, including Ludwig Oxford’s Benjamin Schuster-Böckler, whose lab conducted computational analysis for this study, showed that platelets indeed mop up human cfDNA in lab cultures and clinical samples. To prove that they weren’t just seeing residual DNA from megakaryocytes-nucleated cells from which platelets are derived-the researchers examined DNA from the platelets of pregnant women known to be carrying males. They report that they could predict the sex of the baby in every blood sample they analyzed by detecting fragments of the Y chromosome in the platelets, which could only have come from fetal cfDNA they’d mopped up in their travels.

“Given their abundance, ease of isolation and tissue-wide perfusion, platelets are ideally positioned to serve as biosensors for genetic perturbations across tissues,” said Psaila.

Future work in the lab will seek to clarify the role of platelets in the physiological management of cfDNA and the fate and consequences of DNA fragments released upon platelet activation.

This study was funded by Ludwig Cancer Research, Cancer Research UK, the UK Medical Research Council, Rosetrees Trust, Kidani Memorial Trust and Yosemite.

Bethan Psaila is an associate member of the Oxford Branch of the Ludwig Institute for Cancer Research and an associate professor in hematology at the University of Oxford.

Scientists have been curious for years about what is hidden beneath the surface of Mars. With its freezing temperatures, red dust, and dry valleys, the surface of the planet has received most of the attention. But something big is buried deep inside Mars’ mantle.

Thanks to NASA’s Insight lander, we’re finally getting a clearer look below the surface. And what’s there is surprising: leftover chunks from ancient cosmic crashes are buried deep in the planet’s mantle.

These rocky fragments aren’t small. Some are as wide as 2.5 miles (4 kilometers). They’re scattered across Mars’ interior like forgotten debris from the solar system’s wild early days.

Mars got slammed – hard

Giant space rocks – possibly even protoplanets – crashed into Mars some 4.5 billion years ago. They impacted hard enough to melt enormous chunks of the planet’s crust and mantle, and form vast oceans of molten rock.

When those impacts occurred, they shattered the surface. They blasted rocky debris, including parts of the impactors, deep into the interior of the Red Planet.

Unlike Earth, which constantly reshuffles its crust through plate tectonics, Mars’ crust is made of a single plate that has stayed mostly stable.

That’s why those ancient impact scars haven’t been erased. The fragments are still down there, frozen in place like time capsules.

“We’ve never seen the inside of a planet in such fine detail and clarity before,” said Constantinos Charalambous of Imperial College London, the paper’s lead author.

“What we’re seeing is a mantle studded with ancient fragments. Their survival to this day tells us Mars’ mantle has evolved sluggishly over billions of years. On Earth, features like these may well have been largely erased.”

InSight sees into Mars’ mantle

All of this comes from a mission called InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport. It was run by NASA’s Jet Propulsion Laboratory in Southern California and the lander arrived on Mars in 2018.

InSight was the first lander to place a seismometer on Mars’ surface. That device was incredibly sensitive and recorded 1,319 marsquakes before the mission ended in 2022.

Quakes send out waves that travel through the planet. As those waves move through different materials, they change speed and direction.

Scientists can study how those waves behave to figure out what’s inside the planet, kind of like how doctors use ultrasound to see inside the human body.

“We knew Mars was a time capsule bearing records of its early formation, but we didn’t anticipate just how clearly we’d be able to see with InSight,” said Tom Pike of Imperial College London, coauthor of the paper.

What causes marsquakes?

Marsquakes still happen, usually for two reasons. Some are caused when rocks crack under pressure and heat. Others are caused by meteoroids slamming into the surface.

A study published earlier this year in Geophysical Research Letters showed that meteoroid impacts can create high-frequency seismic waves.

These waves travel deep into the mantle, which is a thick layer of rock beneath the crust. The mantle can be nearly 960 miles (1,545 kilometers) thick, and reach temperatures as high as 2,732 °F (1,500 °C).

Eight of the marsquakes recorded by InSight had strong, high-frequency signals that got noticeably scrambled and delayed.

“When we first saw this in our quake data, we thought the slowdowns were happening in the Martian crust,” Pike said.

“But then we noticed that the farther seismic waves travel through the mantle, the more these high-frequency signals were being delayed.”

Buried lumps in Mars’ mantle

Computer simulations helped scientists figure it out. Those delays only happened when the quake waves passed through small regions of the mantle that had a different composition from everything around them. These were the buried impact fragments.

Some were massive. Others were smaller. All were mixed into the mantle, which Charalambous compared to “shattered glass – a few large shards with many smaller fragments.”

That fits with what we already know: In the early solar system, planets like Mars got hit often and hard.

Charalambous said the fact that these features are still visible “tells us Mars hasn’t undergone the vigorous churning that would have smoothed out these lumps.”

What other planets might be hiding

This discovery doesn’t just help us understand Mars. It also gives clues about other rocky planets – especially ones that don’t have tectonic activity, like Venus and Mercury.

If Mars is holding onto traces of ancient impacts deep in its mantle, maybe those planets are, too.

Mars has always been a quiet planet on the surface. But now we know that, deep inside, it’s holding the scars of an ancient and violent past – and it hasn’t let them go.

The study was published in the journal Science.

Image credit: NASA/JPL-Caltech

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Scientists from Trinity College Dublin have discovered that electrically stimulating “macrophages” – one of the immune systems key players – can “reprogram” them in such a way to reduce inflammation and encourage faster, more effective healing in disease and injury. 

This breakthrough uncovers a potentially powerful new therapeutic option, with further work ongoing to delineate the specifics.

Macrophages are a type of white blood cell with several high-profile roles in our immune system. They patrol around the body, surveying for bugs and viruses, as well as disposing of dead and damaged cells, and stimulating other immune cells – kicking them into gear when and where they are needed.

However, their actions can also drive local inflammation in the body, which can sometimes get out of control and become problematic, causing more damage to the body than repair. This is present in lots of different diseases, highlighting the need to regulate macrophages for improved patient outcomes. 

In the new study, just published in the international journal Cell Reports Physical Science, the Trinity team worked with human macrophages isolated from heathy donor blood samples provided via the Irish Blood Transfusion Board, St James’s Hospital. They stimulated these cells using a custom bioreactor to apply electrical currents and measured what happened.

The scientists discovered that this stimulation caused a shift of macrophages into an anti-inflammatory state that supports faster tissue repair; a decrease in inflammatory marker (signalling) activity; an increase in expression of genes that promote the formation of new blood vessels (associated with tissue repair as new tissues form); and an increase in stem cell recruitment into wounds (also associated with tissue repair).

We have known for a very long time that the immune system is vital for repairing damage in our body and that macrophages play a central role in fighting infection and guiding tissue repair.” 

Dr. Sinead O’Rourke, Research Fellow in Trinity’s School of Biochemistry and Immunology, and first author of the research article

“As a result, many scientists are exploring ways to ‘reprogram’ macrophages to encourage faster, more effective healing in disease and to limit the unwanted side-effects that come with overly aggressive inflammation. And while there is growing evidence that electrical stimulation may help control how different cells behave during wound healing, very little was known about how it affects human macrophages prior to this work.”

“We are really excited by the findings. Not only does this study show for the first time that electrical stimulation can shift human macrophages to suppress inflammation, we have also demonstrated increased ability of macrophages to repair tissue, supporting electrical stimulation as an exciting new therapy to boost the body’s own repair processes in a huge range of different injury and disease situations.”

The findings from the interdisciplinary team led by Trinity investigators, Professor Aisling Dunne (School of Biochemistry and Immunology) and Professor Michael Monaghan (School of Engineering) is especially significant given that this work was performed with human blood cells (showing its effectiveness for real patients), electrical stimulation is relatively safe and easy in the scheme of therapeutic options, and the outcomes should be applicable to a wide range of scenarios.

Corresponding author Prof. Monaghan added: “Among the future steps are to explore more advanced regimes of electrical stimulation to generate more precise and prolonged effects on inflammatory cells and to explore new materials and modalities of delivering electric fields. This concept has yielded compelling effects in vitro and has huge potential in a wide range of inflammatory diseases.”