Problems with iron levels in the blood and the body’s ability to regulate this important nutrient as a result of SARS-CoV-2 infection could be a key trigger for long COVID, new research has discovered.

Iron levels, and the way the body regulates iron, were disrupted early on during SARS-CoV-2 infection, and took a very long time to recover, particularly in those people who went on to report long COVID months laterAimee Hanson

The discovery not only points to possible ways to prevent or treat the condition, but could help explain why symptoms similar to those of long COVID are also commonly seen in a number of post-viral conditions and chronic inflammation.

Although estimates are highly variable, as many as three in 10 people infected with SARS-CoV-2 could go on to develop long COVID, with symptoms including fatigue, shortness of breath, muscle aches and problems with memory and concentration (‘brain fog’). An estimated 1.9 million people in the UK alone were experiencing self-reported long COVID as of March 2023, according to the Office of National Statistics.

Shortly after the start of the COVID-19 pandemic, researchers at the University of Cambridge began recruiting people who had tested positive for the virus to the COVID-19 cohort of the National Institute for Health and Care Research (NIHR) BioResource. These included asymptomatic healthcare staff identified via routine screening through to patients admitted to Cambridge University Hospitals NHS Foundation Trust, some to its intensive care unit.

Over the course of a year, participants provided blood samples, allowing researchers to monitor changes in the blood post-infection. As it became clear that a significant number of patients would go on to have symptoms that persisted – long COVID – researchers were able to track back through these samples to see whether any changes in the blood correlated with their later condition.

In findings published in Nature Immunology, researchers at the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), University of Cambridge, together with colleagues at Oxford, analysed blood samples from 214 individuals. Approximately 45% of those questioned about their recovery reported symptoms of long COVID between three and ten months later.

Professor Ken Smith, who was Director of CITIID at the time of the study and will take up a position as Director of the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne, Australia, in April, said: “Having recruited a group of people with SARS-CoV-2 early in the pandemic, analysis of several blood samples and clinical information collected over a 12 month period after infection has proved invaluable in giving us important and unexpected insights into why, for some unlucky individuals, initial SARS-CoV-2 infection is followed by months of persistent symptoms.”

The team discovered that ongoing inflammation – a natural part of the immune response to infection – and low iron levels in blood, contributing to anaemia and disrupting healthy red blood cell production, could be seen as early as two weeks post COVID-19 in those individuals reporting long COVID many months later.

Early iron dysregulation was detectable in the long COVID group independent of age, sex, or initial COVID-19 severity, suggesting a possible impact on recovery even in those who were at low risk for severe COVID-19, or who did not require hospitalisation or oxygen therapy when sick.

Dr Aimee Hanson, who worked on the study while at the University of Cambridge, and is now at the University of Bristol, said: “Iron levels, and the way the body regulates iron, were disrupted early on during SARS-CoV-2 infection, and took a very long time to recover, particularly in those people who went on to report long COVID months later.

“Although we saw evidence that the body was trying to rectify low iron availability and the resulting anaemia by producing more red blood cells, it was not doing a particularly good job of it in the face of ongoing inflammation.”

Interestingly, although iron dysregulation was more profound during and following severe COVID-19, those who went on to develop long COVID after a milder course of acute COVID-19 showed similar patterns in the blood. The most pronounced association with long COVID was how quickly inflammation, iron levels and regulation returned to normal following SARS-CoV-2 infection – though symptoms tended to continue long after iron levels had recovered.

Co-author Professor Hal Drakesmith, from the MRC Weatherall Institute of Molecular Medicine at the University of Oxford, said iron dysregulation is a common consequence of inflammation and is a natural response to infection.

“When the body has an infection, it responds by removing iron from the bloodstream. This protects us from potentially lethal bacteria that capture the iron in the bloodstream and grow rapidly. It’s an evolutionary response that redistributes iron in the body, and the blood plasma becomes an iron desert.

“However, if this goes on for a long time, there is less iron for red blood cells, so oxygen is transported less efficiently affecting metabolism and energy production, and for white blood cells, which need iron to work properly. The protective mechanism ends up becoming a problem.”

The findings may help explain why symptoms such as fatigue and exercise intolerance are common in long COVID, as well as in several other post-viral syndromes with lasting symptoms.

The researchers say the study points to potential ways of preventing or reducing the impact of long COVID by rectifying iron dysregulation in early COVID-19 to prevent adverse long-term health outcomes.

One approach might be controlling the extreme inflammation as early as possible, before it impacts on iron regulation. Another approach might involve iron supplementation; however as Dr Hanson pointed out, this may not be straightforward.

“It isn’t necessarily the case that individuals don’t have enough iron in their body, it’s just that it’s trapped in the wrong place,” she said. “What we need is a way to remobilise the iron and pull it back into the bloodstream, where it becomes more useful to the red blood cells.”

The research also supports ‘accidental’ findings from other studies, including the IRONMAN study, which was looking at whether iron supplements benefited patients with heart failure – the study was disrupted due to the COVID-19 pandemic, but preliminary findings suggest that trial participants were less likely to develop severe adverse effects from COVID-19. Similar effects have been observed among people living with the blood disorder beta-thalassemia, which can cause individuals to produce too much iron in their blood.

The research was funded by Wellcome, the Medical Research Council, NIHR and European Union Horizon 2020 Programme.

Reference
Hanson, AL et al. Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19. Nat Imm; 1 March 2024; DOI: 10.1038/s41590-024-01754-8

source: cam.ac.uk

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The discovery of an extremely rare astrolabe reveals a complex history of Islamic – Jewish scientific exchange

By Tom Almeroth-Williams

The identification of an eleventh century Islamic astrolabe bearing both Arabic and Hebrew inscriptions makes it one of the oldest examples ever discovered and one of only a handful known in the world.

The astronomical instrument was adapted, translated and corrected for centuries by Muslim, Jewish and Christian users in Spain, North Africa and Italy.

Dr Federica Gigante, from Cambridge’s History Faculty and Christ’s College, made the discoveries in a museum in Verona, Italy, and just published her study in the journal Nuncius.

Dr Gigante first came across a newly-uploaded image of the astrolabe by chance on the website of the Fondazione Museo Miniscalchi-Erizzo. Intrigued, she asked them about it.

“The museum had not yet started an in-depth study of the object,” Dr Gigante said. “It’s now the single most important object in their collection.”

“When I visited the museum and studied the astrolabe up close, I noticed that not only was it covered in beautifully engraved Arabic inscriptions but that I could see faint inscriptions in Hebrew. I could only make them out in the raking light entering from a window. I thought I might be dreaming but I kept seeing more and more. It was very exciting.”

“This isn’t just an incredibly rare object. It’s a powerful record of scientific exchange between Arabs, Jews and Christians over hundreds of years.”

“The Verona astrolabe underwent many modifications, additions, and adaptations as it changed hands. At least three separate users felt the need to add translations and corrections to this object, two using Hebrew and one using a Western language.”

Astrolabes were the world’s first smartphone, a portable computer which could be put to hundreds of uses. They provided a portable two-dimensional model of the universe fitting in their user’s hand, enabling them to calculate time, distances, plot the position of the stars and even forecast the future, by casting a horoscope.

Islamic Spanish origins

Dr Gigante, an expert on Islamic astrolabes and previously a curator of Islamic scientific instruments, dated and located the creation of the ‘Verona astrolabe’ by analysing key scientific, design, construction and calligraphic characteristics.

She identified the object as Andalusian, and – from the style of the engraving, and the arrangement of the scales on the back – matched it to instruments made in Al–Andalus, the Muslim-ruled area of Spain, in the eleventh century.

One side of a plate is inscribed in Arabic “for the latitude of Cordoba, 38° 30′,” لعزض قرطبة لح ل, while the other side “for the latitude of Toledo, 40°,” لعزض طليطلة م. Dr Gigante suggests that the astrolabe might have been made in Toledo at a time when it was a thriving centre of coexistence and cultural exchange between Muslim, Jews and Christians.

The astrolabe features Muslim prayer lines and prayer names, arranged to ensure that its original intended users kept to time to perform their daily prayers.

Translated into English, the signature inscribed on the astrolabe reads “for Isḥāq […]/the work of Yūnus.” This was engraved sometime after the astrolabe was made probably for a later owner.

The two names, Isḥāq and Yūnus, that is Isaac and Jonah in English, could be Jewish names written in the Arabic script, a detail that suggests that the object was at a certain point circulating within a Sephardi Jewish community in Spain, where Arabic was the spoken language.

A second, added plate is inscribed for typical North African latitudes suggesting that another point of the object’s life, it was perhaps used in Morocco, or Egypt.

Hebrew inscriptions

Hebrew inscriptions were added to the astrolabe by more than one hand. One set of additions are carved deeply and neatly, while a different set of translations are very light, uneven, and show an insecure hand.

Dr Gigante said: “These Hebrew additions and translations suggest that at a certain point the object left Spain or North Africa and circulated amongst the Jewish diaspora community in Italy, where Arabic was not understood, and Hebrew was used instead.”

Unusually, one of the Hebrew additions, engraved neatly above the Arabic marking for latitude 35°, reads “34 and a half” rather than “34 ½”, which suggests that the engraver was not an astronomer or astrolabe maker.

Other Hebrew inscriptions are instead translations of the Arabic names for astrological signs, for Scorpio, Sagittarius, Capricorn, Aquarius, Pisces, and Aries.

Dr Gigante points out that these translations reflect the recommendations prescribed by the Spanish Jewish polymath Abraham Ibn Ezra (1089–1167) in the earliest surviving treatise on the astrolabe in the Hebrew language written in 1146 in Verona, exactly where the astrolabe is found today.

 Jewish Verona

Twelfth-century Verona hosted one of the longest-standing and most important Jewish communities in Italy. Ibn Ezra’s treatise assumes pre-existing knowledge of the astrolabe among the Verona Jewish community, showing that the instrument must already have been popular.

Ibn Ezra’s description has a lot in common with the ‘Verona astrolabe’ which would have been in circulation by the time Ibn Ezra was in Verona. He warned his readers that an instrument must be checked before use to verify the accuracy of the values to be calculated.

Dr Gigante suggests that the person who added the Hebrew inscriptions might have been following such recommendations.

This part of the astrolabe features inscriptions in Arabic and Hebrew

Arabic

Hebrew

Incorrect corrections

The astrolabe features corrections inscribed not only in Hebrew but also in Western numerals, the same we use in English today.

All sides of the astrolabe’s plates feature lightly scratched markings in Western numerals, translating and correcting the latitude values, some even multiple times. Dr Gigante thinks it is highly likely that these additions were made in Verona for a Latin or Italian language speaker.

In one case, someone lightly scratched the numbers “42” and “40” near the inscription reading “for the latitude of Medinaceli, 41° 30’”.

Dr Gigante said: “Not only do both numerals differ from the value given in the Arabic, they don’t agree between themselves. It may be that a later user of the instrument thought the original Arabic value was wrong and amended it. But the correct, modern value for the latitude of Medinaceli is 41°15′, indicating that the Arabic value was more accurate than either amendment.”

Elsewhere on the instrument, Gigante found similar conflicting and erroneous amendments relating to the latitudes of Cordoba and Toledo.

Star map

The astrolabe features a ‘rete’ – a pierced disk representing a map of the sky – which is one of the earliest known made in Spain. Remarkably, it features similarities with the rete of the only surviving Byzantine astrolabe made in AD1062 as well as with those of the earliest European astrolabes, made in Spain on the model of Islamic ones.

A calculation of the star position allows a rough timing of the sky for which it was created. Dr Gigante explains that “due to a phenomenon called the precession of the equinoxes, whereby the earth rotates on its axis not in a straight line, but in a “wobbly” manner, like a spinning top about to stop, the stars’ apparent positions above our heads change constantly, about 1 degree every 70 years.”

By analysing the position of the stars on the rete, it is possible to calculate that they were placed in the position that stars had in the late 11^th century, and that they match those of other astrolabes made, for example, in AD 1068.

Later life

The astrolabe is thought to have made its way into the collection of the Veronese nobleman Ludovico Moscardo (1611–81) before passing by marriage to the Miniscalchi family. In 1990, the family founded the Fondazione Museo Miniscalchi-Erizzo to preserve the collections.

“This object is Islamic, Jewish and European, they can’t be separated,” Dr Gigante said.

References

F. Gigante, ‘A Medieval Islamic Astrolabe with Hebrew Inscriptions in Verona: The Seventeenth-Century Collection of Ludovico Moscardo’, Nuncius (2024). DOI : 10.1163/18253911-bja10095

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Published 4th March 2024

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Image credits

_{Astrolabe images: Federica Gigante
Federica Gigante: Federica Candelato}

source: cam.ac.uk

By Ellie Austin and Paul Casciato

Watch the full film and cast your vote

Climate action film “Facing The New Reality” featuring Cambridge Zero Director Professor Emily Shuckburgh is a finalist for the Smiley Charity Film Awards.

Watch and vote for the film
via this link by 12 March 2024

The 7-minute film, Facing The New Reality, premiered at the opening ceremony of the world’s biggest climate event of its kind at Climate Week NYC in September 2023, in front of hundreds of world-leading politicians, business executives and civil society representatives.

Since then, the film has been viewed more than 54,000 times online and has now been shortlisted in the Smiley Charity Film Awards.

The film is the only finalist with a sole focus on climate change, and is up against some of the industry’s biggest names, including a Greenpeace short film with Simon Pegg and Jane Fonda.

In Facing The New Reality, Professor Shuckburgh and fellow climate scientists Harvard’s Naomi Oreskes, World Meteorological Organization’s Petteri Taalas and Energy for Growth Hub’s Rose Mutiso take centre stage to report on the current state of the planet, outline the action needed to tackle climate change and urge global leaders to take the critical decisions today to construct a just and sustainable world.

Professor Shuckburgh offers a glimpse of optimism in the film and urges the assembled world leaders to press on with the critical action needed this decade to address climate change.

“We have all the building blocks in order to do it, we just simply haven’t put them together… yet,” Professor Shuckburgh said.

Climate Week NYC has grown hugely in importance from small panel discussions in 2009 to a weeklong happening of events, networking, dinners and spectacle and was described by New York Times as “Burning Man for Climate Geeks” last year.

Climate Week NYC is a partnership between The Climate Group and the United Nations General Assembly and is run in coordination with the United Nations and the City of New York.

In 2023 it centred around the UN General Assembly, the UN Secretary-General’s Climate Ambition Summit as well as hundreds of national government, business and climate group initiatives, making it a unique opportunity for Cambridge to communicate with the world.

Facing The New Reality was produced by The Climate Group, with the creative agency Nice & Serious, who ask viewers to “let it inspire us, let it challenge us, and let it empower us to act – because the time to make a difference is now.”

Watch the full film and cast your vote via the Smiley Charity Awards page by March 12th 2024.

“There’s still hope if we’re determined.”

Professor Emily Shuckburgh, Director of Cambridge Zero, the University of Cambridge’s ambitious climate change initiative to help to stop climate change and create a resilient and sustainable zero-carbon world.

“We’re thrilled to be a finalist at the Smiley Charity Film Awards, but what we really need is for global leaders to take bold action today to create a sustainable tomorrow.” – Prof Shuckburgh

Professor Shuckburgh also appeared on Climate Week NYC’s main stage for one of the key discussions on the New frontiers of Climate Action alongside the Chief Sustainability Officers of Google and Siemens, a Cambridge alumni event hosted by Cambridge in America Mission Possible: Creating a Better Planetary Future and met with dozens of supporters, policymakers, business, industry and climate leaders.

Across the week she shared Cambridge’s efforts to tackle climate change. She mentioned Cambridge research on materials, batteries, photovoltaics, the Cambridge ecosystem for innovation, including Cambridge research on AI, aviation, the Centre for Landscape Regeneration and the ground-breaking work of the Cambridge Conservation Initiative.

Published 5 March 2024

_{The text in this work is licensed under a Creative Commons Attribution 4.0 International License}

source: cam.ac.uk

A galaxy that suddenly stopped forming new stars more than 13 billion years ago has been observed by astronomers.

Using the James Webb Space Telescope, an international team of astronomers led by the University of Cambridge have spotted a ‘dead’ galaxy when the universe was just 700 million years old, the oldest such galaxy ever observed.

This galaxy appears to have lived fast and died young: star formation happened quickly and stopped almost as quickly, which is unexpected for so early in the universe’s evolution. However, it is unclear whether this galaxy’s ‘quenched’ state is temporary or permanent, and what caused it to stop forming new stars.

The results, reported in the journal Nature, could be important to help astronomers understand how and why galaxies stop forming new stars, and whether the factors affecting star formation have changed over billions of years.

“The first few hundred million years of the universe was a very active phase, with lots of gas clouds collapsing to form new stars,” said Tobias Looser from the Kavli Institute for Cosmology, the paper’s first author. “Galaxies need a rich supply of gas to form new stars, and the early universe was like an all-you-can-eat buffet.”

“It’s only later in the universe that we start to see galaxies stop forming stars, whether that’s due to a black hole or something else,” said co-author Dr Francesco D’Eugenio, also from the Kavli Institute for Cosmology.

Astronomers believe that star formation can be slowed or stopped by different factors, all of which will starve a galaxy of the gas it needs to form new stars. Internal factors, such as a supermassive black hole or feedback from star formation, can push gas out of the galaxy, causing star formation to stop rapidly. Alternatively, gas can be consumed very quickly by star formation, without being promptly replenished by fresh gas from the surroundings of the galaxy, resulting in galaxy starvation.

“We’re not sure if any of those scenarios can explain what we’ve now seen with Webb,” said co-author Professor Roberto Maiolino. “Until now, to understand the early universe, we’ve used models based on the modern universe. But now that we can see so much further back in time, and observe that the star formation was quenched so rapidly in this galaxy, models based on the modern universe may need to be revisited.”

Using data from JADES (JWST Advanced Deep Extragalactic Survey), the astronomers determined that this galaxy experienced a short and intense period of star formation over a period between 30 and 90 million years. But between 10 and 20 million years before the point in time where it was observed with Webb, star formation suddenly stopped.

“Everything seems to happen faster and more dramatically in the early universe, and that might include galaxies moving from a star-forming phase to dormant or quenched,” said Looser.

Astronomers have previously observed dead galaxies in the early universe, but this galaxy is the oldest yet – just 700 million years after the big bang, more than 13 billion years ago. This observation is one of the deepest yet made with Webb.

In addition to the oldest, this galaxy is also relatively low mass – about the same as the Small Magellanic Cloud (SMC), a dwarf galaxy near the Milky Way, although the SMC is still forming new stars. Other quenched galaxies in the early universe have been far more massive, but Webb’s improved sensitivity allows smaller and fainter galaxies to be observed and analysed.

The astronomers say that although it appears dead at the time of observation, it’s possible that in the roughly 13 billion years since, this galaxy may have come back to life and started forming new stars again.

“We’re looking for other galaxies like this one in the early universe, which will help us place some constraints on how and why galaxies stop forming new stars,” said D’Eugenio. “It could be the case that galaxies in the early universe ‘die’ and then burst back to life – we’ll need more observations to help us figure that out.”

The research was supported in part by the European Research Council, the Royal Society, and the Science and Technology Facilities Council (STFC), part of UK Research and Innovation (UKRI).

source: cam.ac.uk

Reference:
Tobias J. Looser et al. ‘A recently quenched galaxy 700 million years after the Big Bang.’ Nature (2024). DOI: 10.1038/s41586-024-07227-0

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The winds that help to form planets in the gaseous discs of early solar systems have been imaged for the first time by the James Webb Space Telescope (JWST) using the noble gases neon and argon.

Planetary systems like our Solar System seem to contain more rocky objects than gas-rich ones. Around our sun, these include the inner planets, the asteroid belt and the Kuiper belt. But scientists have known for a long time that planet-forming discs start with 100 times more mass in gas than in solids, which leads to a pressing question; when and how does most of the gas leave the disc/system?

JWST is helping scientists uncover how planets form, by advancing understanding of their birthplaces, the circumstellar discs surrounding young stars. In a new study published in the Astronomical Journal, a team of scientists including those from the University of Leicester, the University of Cambridge and led by the University of Arizona, image for the first time an old planet-forming disc (still very young relative to the Sun) which is actively dispersing its gas content.

Knowing when the gas disperses is important as it constrains the time that is left for nascent planets to consume the gas from their surroundings.

During the very early stages of planetary system formation, planets coalesce in a spinning disc of gas and tiny dust around the young star. These particles clump together, building up into bigger and bigger chunks called planetesimals. Over time, these planetesimals collide and stick together, eventually forming planets. The type, size, and location of planets that form depend on the amount of material available and how long it remains in the disc. So, the outcome of planet formation depends on the evolution and dispersal of the disc.

At the heart of this discovery is the observation of T Cha, a young star (relative to the Sun) enveloped by an eroding disc notable for its vast dust gap, approximately 30 astronomical units in radius. For the first time, astronomers have imaged the dispersing gas (aka winds) using the four lines of the noble gases neon (Ne) and argon (Ar), one of which is the first detection in a planet-forming disc. The images of [Ne II] show that the wind is coming from an extended region of the disc. The team is also interested in knowing how this process takes place, so they can better understand the history and impact on our solar system.

Scientists have been trying to understand the mechanisms behind the winds in protoplanetary discs for over a decade. The observations by JWST represent a huge step-change in the data they have to work with, compared to previous data from ground-based telescopes.

“We first used neon to study planet-forming discs more than a decade ago, testing our computational simulations against data from Spitzer, and new observations we obtained with the ESO VLT,” said co-author Professor Richard Alexander from the University of Leicester. “We learned a lot, but those observations didn’t allow us to measure how much mass the discs were losing.

“The new JWST data are spectacular, and being able to resolve disc winds in images is something I never thought would be possible.  With more observations like this still to come, JWST will enable us to understand young planetary systems as never before.”

“These winds could be driven either by high-energy stellar photons (the star’s light) or by the magnetic field that weaves the planet-forming disc,” said Naman Bajaj from the University of Arizona, the study’s lead author.

To differentiate between the two, the same group, this time led by Dr Andrew Sellek of Leiden Observatory and previously of the Institute of Astronomy at the University of Cambridge, performed simulations of the dispersal driven by stellar photons. They compare these simulations to the actual observations and find dispersal by high-energy stellar photons can explain the observations, and hence cannot be excluded as a possibility.

“The simultaneous measurement of all four lines by JWST proved crucial to pinning down the properties of the wind and helped us to demonstrate that significant amounts of gas are being dispersed,” said Sellek.

To put it into context, the researchers calculate that the mass dispersing every year is equivalent to that of the moon! These results will be published in a companion paper, currently under review at the Astronomical Journal.

The [Ne II] line was discovered towards several planet-forming discs in 2007 with the Spitzer Space Telescope and soon identified as a tracer of winds by team member Professor Ilaria Pascucci at the University of Arizona; this transformed research efforts focused on understanding disc gas dispersal. Now the discovery of spatially resolved [Ne II] – as well as the first detection of [Ar III] – using the James Webb Space Telescope, could become the next step towards transforming our understanding of this process. 

The implications of these findings offer new insights into the complex interactions that lead to the dispersal of the gas and dust critical for planet formation. By understanding the mechanisms behind disc dispersal, scientists can better predict the timelines and environments conducive to the birth of planets. The team’s work demonstrates the power of JWST and sets a new path for exploring planet formation dynamics and the evolution of circumstellar discs.

source: cam.ac.uk

Reference:
Naman S. Bajaj et al. ‘JWST MIRI MRS Observations of T Cha: Discovery of a Spatially Resolved Disk Wind.’ The Astronomical Journal (2024). DOI: 10.3849/1538-3881/ad22e1

Adapted from a University of Leicester press release.

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The tone and tuning of musical instruments has the power to manipulate our appreciation of harmony, new research shows. The findings challenge centuries of Western music theory and encourage greater experimentation with instruments from different cultures.

There are many more kinds of harmony out therePeter Harrison

According to the Ancient Greek philosopher Pythagoras, ‘consonance’ – a pleasant-sounding combination of notes – is produced by special relationships between simple numbers such as 3 and 4. More recently, scholars have tried to find psychological explanations, but these ‘integer ratios’ are still credited with making a chord sound beautiful, and deviation from them is thought to make music ‘dissonant’, unpleasant sounding. 

But researchers from the University of Cambridge, Princeton and the Max Planck Institute for Empirical Aesthetics, have now discovered two key ways in which Pythagoras was wrong.

Their study, published in Nature Communications, shows that in normal listening contexts, we do not actually prefer chords to be perfectly in these mathematical ratios.

“We prefer slight amounts of deviation. We like a little imperfection because this gives life to the sounds, and that is attractive to us,” said co-author, Dr Peter Harrison, from Cambridge’s Faculty of Music and Director of its Centre for Music and Science.

The researchers also found that the role played by these mathematical relationships disappears when you consider certain musical instruments that are less familiar to Western musicians, audiences and scholars. These instruments tend to be bells, gongs, types of xylophones and other kinds of pitched percussion instruments. In particular, they studied the ‘bonang’, an instrument from the Javanese gamelan built from a collection of small gongs.

“When we use instruments like the bonang, Pythagoras’s special numbers go out the window and we encounter entirely new patterns of consonance and dissonance,” Dr Harrison said.

“The shape of some percussion instruments means that when you hit them, and they resonate, their frequency components don’t respect those traditional mathematical relationships. That’s when we find interesting things happening.”

“Western research has focused so much on familiar orchestral instruments, but other musical cultures use instruments that, because of their shape and physics, are what we would call ‘inharmonic’. 

The researchers created an online laboratory in which over 4,000 people from the US and South Korea participated in 23 behavioural experiments. Participants were played chords and invited to give each a numeric pleasantness rating or to use a slider to adjust particular notes in a chord to make it sound more pleasant. The experiments produced over 235,000 human judgments.

The experiments explored musical chords from different perspectives. Some zoomed in on particular musical intervals and asked participants to judge whether they preferred them perfectly tuned, slightly sharp or slightly flat. The researchers were surprised to find a significant preference for slight imperfection, or ‘inharmonicity’. Other experiments explored harmony perception with Western and non-Western musical instruments, including the bonang.

Instinctive appreciation of new kinds of harmony

The researchers found that the bonang’s consonances mapped neatly onto the particular musical scale used in the Indonesian culture from which it comes. These consonances cannot be replicated on a Western piano, for instance, because they would fall between the cracks of the scale traditionally used. 

“Our findings challenge the traditional idea that harmony can only be one way, that chords have to reflect these mathematical relationships. We show that there are many more kinds of harmony out there, and that there are good reasons why other cultures developed them,” Dr Harrison said.

Importantly, the study suggests that its participants – not trained musicians and unfamiliar with Javanese music – were able to appreciate the new consonances of the bonang’s tones instinctively.

“Music creation is all about exploring the creative possibilities of a given set of qualities, for example, finding out what kinds of melodies can you play on a flute, or what kinds of sounds can you make with your mouth,” Harrison said.

“Our findings suggest that if you use different instruments, you can unlock a whole new harmonic language that people intuitively appreciate, they don’t need to study it to appreciate it. A lot of experimental music in the last 100 years of Western classical music has been quite hard for listeners because it involves highly abstract structures that are hard to enjoy. In contrast, psychological findings like ours can help stimulate new music that listeners intuitively enjoy.”

Exciting opportunities for musicians and producers

Dr Harrison hopes that the research will encourage musicians to try out unfamiliar instruments and see if they offer new harmonies and open up new creative possibilities. 

“Quite a lot of pop music now tries to marry Western harmony with local melodies from the Middle East, India, and other parts of the world. That can be more or less successful, but one problem is that notes can sound dissonant if you play them with Western instruments. 

“Musicians and producers might be able to make that marriage work better if they took account of our findings and considered changing the ‘timbre’, the tone quality, by using specially chosen real or synthesised instruments. Then they really might get the best of both worlds: harmony and local scale systems.”

Harrison and his collaborators are exploring different kinds of instruments and follow-up studies to test a broader range of cultures. In particular, they would like to gain insights from musicians who use ‘inharmonic’ instruments to understand whether they have internalised different concepts of harmony to the Western participants in this study.

Reference

R. Marjieh, P.M.C. Harrison, H. Lee, F. Deligiannaki, & N. Jacoby, ‘Timbral effects on consonance disentangle psychoacoustic mechanisms and suggest perceptual origins for musical scales’, Nature Communications (2024). DOI: 10.1038/s41467-024-45812-z

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Professor Ross King from Cambridge’s Department of Chemical Engineering and Biotechnology, who originated the idea of a ‘Robot Scientist’, discusses why he believes that AI-powered scientists could surpass the best human scientists by the middle of the century, but only if AI for science is developed responsibly and ethically. 

Thanks to the widespread availability of food and medical care, the ability to travel, and many other scientific and technological developments, billions of people today are living better lives than kings of centuries past. It is deeply surprising to me how little appreciated this astonishing fact is.

Of course, despite all the progress we’ve made, the world faces many challenges in the 21st century: climate change, pandemics, poverty and cancer, to name just a few.

If all the countries in the world could join together to share technology and resources, we might be to deal with and overcome these challenges. However, history presents no example of such collaboration, and the current geopolitical situation does not offer much in the way of hope.

Our best hope of dealing with these challenges is to make science and technology more productive. The only feasible way to achieve this is through the integration of Artificial Intelligence (AI) and laboratory automation.

AI systems already possess superhuman scientific powers. They can remember massive volumes of facts and learn from huge datasets. They can execute flawless logical reasoning, and near optimal probabilistic reasoning. They are can read every scientific paper, indeed everything ever written. These powers are complimentary to human scientists.

When the scientific method was developed in the 17th century, one of the core insights was the need to conduct experiments in the physical world, not just to think.

Today, laboratory automation is steadily advancing, and robots can now carry out most of the laboratory tasks that humans can. We are also now seeing the emergence of the ‘Cloud Lab’ concept. The idea is to provide laboratory automation at scale and remotely, with scientists sending their samples to the cloud lab, using a computer interface to design and execute their experiments.

And then there are AI Scientists: AI systems integrated with laboratory automations that are capable of carrying out the closed-loop automation of scientific research (aka ‘Robot Scientists’, ‘Self-driving Labs’). These systems automatically originate hypotheses to explain observations, devise experiments to test these hypotheses, physically run these experiments using laboratory robotics, interpret the results, and then repeat the cycle.

AI Scientists can work cheaper, faster, more accurately, and longer than humans. They can also be easily multiplied. As the experiments are conceived and executed automatically by computer, it’s possible to completely capture and digitally curate all aspects of the scientific process, making the science more reproducible. There are now around 100 AI Scientists around the world, working in areas from quantum mechanics to astronomy, from chemistry to medicine.

Within the last year or so the world has been stunned by the success of Large Language Models (LLMs) such as ChatGPT, which have achieved breakthrough performance on a wide range of conversation-based tasks. LLMs are surprisingly strong absorbers of technical knowledge, such as chemical reactions and logical expressions. LLMs, and more broadly Foundation Models, show great potential for super-charging AI Scientists. They can act both as a source of scientific knowledge, since they have read all the scientific literature, and a source of new scientific hypotheses.

One of the current problems with LLMs is their tendency to hallucinate, that is to output statements that are not true. While this is a serious problem in many applications, it is not necessarily so in science, where physical experiments are the arbiters of truth. Hallucinations are hypotheses.

AI has been used as a tool in the research behind tens of thousands of scientific papers. We believe this only a start. We believe that AI has the potential to transform the very process of science.

We believe that by harnessing the power of AI, we can propel humanity toward a future where groundbreaking achievements in science, even achievements worthy of a Nobel Prize, can be fully automated. Such advances could transform science and technology, and provide hope of dealing with the formidable challenges that face humankind in the 21st century

The Nobel Turing Challenge aims to develop AI Scientists capable of making Nobel-quality scientific discoveries at a level comparable, and possibly superior to the best human scientists by 2050.

As well as being a potential transformative power for good, the application of AI to science has potential for harm. As a step towards preventing this harm, my colleagues and I have prepared the Stockholm Declaration on AI for Science. This commits the signees to the responsible and ethical development of AI for science. A copy of the declaration can be signed at: https://sites.google.com/view/stockholm-declaration. 

We urge all scientists working with AI to sign.

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A new test to help diagnose a condition that can lead to oesophageal cancer – developed by Cambridge researchers and trialled by the NHS – has reduced the need for invasive endoscopy in thousands of low-risk patients.

It is very exciting to see the positive results of the NHS England real-world pilot for our capsule-sponge testRebecca Fitzgerald

The NHS pilot, which has tested over 8,500 patients with the ‘capsule sponge test’, showed almost eight out of 10 patients who completed a test were discharged without the need for further testing, freeing up endoscopy capacity for higher risk patients and those referred for urgent tests for oesophageal cancer.

The test involves patients swallowing a small capsule-shaped device that contains a tiny sponge that collects cell samples for analysis before being extracted via a string thread attached to the sponge. It has been developed by Professor Rebecca Fitzgerald, Director of the Early Cancer Institute at the University of Cambridge.

Professor Fitzgerald said: “It is very exciting to see the positive results of the NHS England real-world pilot for our capsule-sponge test. This is a major step forward to making this simple test more routinely available outside of clinical trials. Timely diagnosis is vital for improving outcomes for patients.”

Barrett’s oesophagus – a condition affecting the food pipe which can go on to cause oesophageal cancer in some patients – is usually diagnosed or ruled out via endoscopy (a camera test of the food pipe) following a GP referral to a gastroenterologist or other specialist practitioner who can carry out the procedure.

The sponge-on-a-string test being trialled by the NHS can instead be carried out quickly in a short appointment, without the need for sedation.

Amanda Pritchard, NHS chief executive, said: “Thousands of people have now benefitted from this incredibly efficient test on the NHS – while the sponge on a string is small in size, it can make a big difference for patients – they can conveniently fit the test into their day and it can often replace the need for an endoscopy while also helping to reduce waiting lists by freeing up staff and resources.

“The NHS is always striving to adopt the latest innovations and new ways of working that help improve patient experience and increase efficiency simple sponge on a string test is just one example of many pioneering tools we’ve trialled in recent years to help diagnose and treat people sooner.”

In a survey of over 350 patients who had the capsule sponge test, patients often said they would recommend the test to a friend or family member, and 94% of patients reported experiencing only mild or no pain at all.

The NHS began piloting the test during the pandemic when there was increased pressure on services and a growing backlog for endoscopy.

Gastro-oesophageal reflux, also known as acid reflux, is a relatively common condition, affecting around one to two in every ten people to some degree, and some of these people may already have or will develop Barrett’s oesophagus, which is a precursor to oesophageal cancer.

There are around 9,300 new oesophageal cancer cases in the UK every year. The key to saving lives is to detect it an earlier stage of Barrett’s oesophagus before it becomes cancerous.

The NHS pilot was launched at 30 hospital sites across 17 areas in England including Manchester, Plymouth, London, Kent and Cumbria. Evaluation of the pilot showed that using capsule sponge was highly cost effective compared to using endoscopy-only for diagnosing patients – saving around £400 per patient.

Patients with positive results from the capsule sponge test who were referred on for an endoscopy had the highest prevalence of Barrett’s oesophagus at 27.2%, compared to zero patients with negative results who completed an endoscopy.

One of the first pilot sites at East and North Hertfordshire NHS Trust has now performed around 1,400 capsule sponge tests – offering to both patients with reflux symptoms via a new consultant led, nurse run early diagnosis service, as well as to patients on an existing Barrett’s surveillance programme.

In the first 1000 patients, the capsule test identified Barrett’s in 6% patients with reflux and found two new cancers and three patients with dysplasia who may have had a longer time to diagnosis otherwise. While 72% reflux patients were discharged back to their GP without the need for an endoscopy.

As of January, 368 patients have had a positive test result of whom about half have confirmed Barrett’s oesophagus.

Dr Danielle Morris, a consultant gastroenterologist at East and North Hertfordshire NHS Trust, said: “Using the capsule sponge test as a diagnosis triage tool has had huge benefits for patients, avoiding the need for unnecessary gastroscopy in almost seven out of 10 patients, and helping to reduce endoscopy waiting lists enabling us to prioritise those who really need endoscopy to have it done quickly.

“The test is performed by a single trained practitioner in an outpatient setting, so it is very resource light compared to gastroscopy, and our patients are very supportive of the service – with almost nine in 10 patients preferring the capsule sponge to a gastroscopy.”

Adapted from a press release from NHS England.

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If all GP practices moved to a model where patients saw the same doctor at each visit, it could significantly reduce doctor workload while improving patient health, a study suggests. 

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How could tiny antennae attached to tiny algae speed up the transition away from fossil fuels? This is one of the questions being studied by Cambridge researchers as they search for new ways to decarbonise our energy supply, and improve the sustainability of harmful materials such as paints and dyes.

Funded by the European Union’s Horizon 2020 research and innovation programme, the Bio-inspired and Bionic materials for Enhanced Photosynthesis (BEEP) project, led by Professor Silvia Vignolini in the Yusuf Hamied Department of Chemistry, studied how marine organisms interact with light.

The four-year sustainable energy project brought together nine research groups from across Europe and drew its inspiration from nature, in particular from the marine world, where organisms including algae, corals and sea slugs have evolved efficient ways to convert sunlight into energy. Harnessing these properties could aid in the development of new artificial and bionic photosynthetic systems.

Some of the brightest and most colourful materials in nature – such as peacock feathers, butterfly wings and opals – get their colour not from pigments or dyes, but from their internal structure alone. The colours our eyes perceive originate from the interaction between light and nanostructures at the surface of the material, which reflect certain wavelengths of light.

As part of the BEEP project, the team studied structural colour in marine species. Some marine algae species have nanostructures in their cell walls that can transmit certain wavelengths of visible light or change their structures to guide the light inside the cell. Little is known about the function of these structures, however: scientists believe they might protect the organisms from UV light or optimise light harvesting capabilities.

The team studied the optical properties and light harvesting efficiency of a range of corals, sea-slugs, microalgae and seaweeds. By understanding the photonic and structural properties of these species, the scientists hope to design new materials for bio-photoreactors and bionic systems.

“We’re fascinated by the optical effects performed by these organisms,” said Maria Murace, a BEEP PhD candidate at Cambridge, who studies structural colour in seaweeds and marine bacteria. “We want to understand what the materials and the structures at the base of these colours are, which could lead to the development of green and sustainable alternatives to the conventional paints and toxic dyes we use today.”

BEEP also studied diatoms: tiny photosynthetic algae that live in almost every aquatic system on Earth and produce as much as half of the oxygen we breathe. The silica shells of these tiny algae form into stunning structures, but they also possess remarkable light-harvesting properties.

The BEEP team engineered tiny light-harvesting antennae and attached them to diatom shells. “These antennae allowed us to gather the light that would otherwise not be harvested by the organism, which is converted and used for photosynthesis,” said Cesar Vicente Garcia, one of the BEEP PhD students, from the University of Bari in Italy. “The result is promising: diatoms grow more! This research could inspire the design of powerful bio-photoreactors, or even better

The scientists engineered a prototype bio-photoreactor, consisting of a fully bio-compatible hydrogel which sustains the growth of microalgae and structural coloured bacteria. The interaction of these organisms is mutually beneficial, enhancing microalgal growth and increasing the volume of biomass produced, which could have applications in the biofuel production industry.

Alongside research, the network has organised several training and outreach activities, including talks and exhibitions for the public at science festivals in Italy, France and the UK.

“Society relies on science to drive growth and progress,” said Floriana Misceo, the BEEP network manager who coordinated outreach efforts. “It’s so important for scientists to share their research and help support informed discussion and debate because without it, misinformation can thrive, which is why training and outreach was an important part of this project.”

“Coordinating this project has been a great experience. I learned immensely from the other groups in BEEP and the young researchers,” said Vignolini. “The opportunity to host researchers from different disciplines in the lab was instrumental in developing new skills and approaching problems from a different perspective.”

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under a Marie Skłodowska-Curie grant.

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Cambridge mathematicians have developed a set of resources for students and teachers that will help them understand how maths can help tackle infectious diseases.

From measles and flu to SARS and COVID, mathematicians help us understand and predict the epidemics that can spread through our communities, and to help us look at strategies that we may be able to use to contain them.

The project, called Contagious Maths, was led by Professor Julia Gog from Cambridge’s Department of Applied Mathematics and Theoretical Physics (DAMTP), and was supported by a Rosalind Franklin Award from the Royal Society.

The curriculum-linked resources will give students between the ages 11 and 14 the opportunity to join researchers on the mathematical frontline to learn more about infectious disease spread, along with interactive tools to try mathematical modelling for themselves. Teachers receive full lesson plans, backed up by Cambridge research.

“I’ve always loved maths. I was lucky enough to have amazing teachers at sixth form who challenged me and were 100% behind me pursuing maths at the highest level, but maths as it’s taught in school can be highly abstract, so students often wonder what the point of maths even is,” said Gog, who is also Director of the Millennium Maths Project. “This is something I’m trying to help with now: to offer a glimpse from school to the research world to see the role mathematics can play in tackling important real-world problems.”

The Contagious Maths project introduces mathematical modelling; explores how mathematicians can model the spread of disease through a population and the type of questions we might think about when looking at models; and gives an insight into what mathematics researchers working on these real-life problems actually do.

“I’ve been engaged in outreach for many years at Cambridge, and the Contagious Maths project grew out of discussions with colleagues who have expertise in reaching school-age children,” said Gog. “The 11-14 age group we are targeting is a real crunch point for retaining girls in maths, and future female mathematicians. What exactly happens is complex and multifaceted, but this is a period when people form their views on how they fit with maths and science.

“Many of them disengage, as it can seem that maths at school is utterly disconnected from the real world. It can also be a time when maths appears very starkly right or wrong, whereas any research mathematician can tell you it’s always so much more subtle that than, and therefore so much more interesting!”

Gog hopes the Contagious Maths resources might be able to help, as they are designed to be used in regular school lessons, and cover a topic with clear real-world importance.

“The maths is never black and white in this field: there are always ways to challenge and develop the models, and some tricky thinking to be done about how the real epidemics and the simulations are really related to each other,” she said. “I suspect some students will find this frustrating, and just want maths to be algorithmic exercises. But some will be intrigued, and they are the ones we are trying to reach and expose to this larger world of applied maths research.”

Contagious Maths also provides teachers with all the ideas and tools they need, so they have at their fingertips all they need to deliver these lessons, even if they have no experience with research mathematics. “We hope this project will help these teachers to bring in the wider view of mathematics, and we hope it inspires them too,” said Gog. “It’s been really fun developing these resources, teaming up with both NRICH and Plus to make the most of our combined expertise.”

Maths teachers can attend a free online event on 20 March to learn more about the project.

In addition to the school resources, Gog and her colleagues have designed another version of Contagious Maths for a more general self-guided audience, which will work for students older than 14 or anyone, of any age, who is interested in learning about mathematical modelling.

“The paradox between the cleanness and precision of mathematics, and the utter hot mess of anything that involves biological dynamics across populations – like an outbreak of an infectious disease, is what intrigued me to stay in mathematics beyond my degree, and to move into research in mathematical biology,” said Gog. “Elegant theoretical ideas can tell us something valuable and universal about mitigating the devastating effects of disease on human and animal populations. Super abstract equations can hold fundamental truths about real-world problems – I don’t think I will ever tire of thinking about that.”

Adapted from a Royal Society interview with Professor Julia Gog.

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School uniform policies could be restricting young people from being active, particularly primary school-aged girls, new research suggests.

Social norms and expectations tend to influence what they feel they can do in these clothes. Unfortunately, when it comes to promoting physical health, that’s a problemEsther van Sluijs

The University of Cambridge study used data about the physical activity participation of more than a million five-to-17-year-olds internationally. It found that in countries where a majority of schools require students to wear uniforms, fewer young people tend to meet the average of 60 minutes of physical activity per day recommended by the World Health Organisation (WHO).

Regardless of uniform policies, across most countries fewer girls than boys reach those recommended exercise levels. Among primary school students, however, the difference in activity between girls and boys was found to be wider in countries where most schools mandated uniforms. The same result was not found in secondary school-aged students.

The authors suggest that this could be explained by the fact that younger children get more incidental exercise throughout the school day than older students; for example, through running, climbing and various other forms of active play at break and lunchtimes. There is already evidence that girls feel less comfortable in participating in active play if they are wearing certain types of clothing, such as skirts or dresses.

Importantly, the results do not definitively prove that school uniforms limit children’s physical activity and the researchers stress that “causation cannot be inferred”. Previous, smaller studies however provide support for these findings, indicating that uniforms could pose a barrier. For the first time, the research examines large-scale statistical evidence to assess that claim.

The study was led by Dr Mairead Ryan, a researcher at the Faculty of Education and Medical Research Council (MRC) Epidemiology Unit, University of Cambridge.

“Schools often prefer to use uniforms for various reasons,” Dr Ryan said. “We are not trying to suggest a blanket ban on them, but to present new evidence to support decision-making. School communities could consider design, and whether specific characteristics of a uniform might either encourage or restrict any opportunities for physical activity across the day.”

The WHO recommends that young people get an average of 60 minutes of at least moderate-intensity physical activity per day during the week. The study confirms previous observations that most children and adolescents are not meeting this recommendation, especially girls. The difference in the percentage of boys and girls meeting physical activity guidelines across all countries was, on average, 7.6 percentage points.

Existing evidence suggests that uniforms could be a factor. Previous concerns have, for example, been raised about girls’ PE uniforms and school sports kits. A 2021 study in England found that the design of girls’ PE uniforms deterred students from participating in certain activities, while the hockey player Tess Howard proposed redesigning gendered sports uniforms for similar reasons, after analysing interview and survey data.

Children often get their exercise away from PE and sports lessons, however.

“Activities like walking or cycling to school, breaktime games, and after-school outdoor play can all help young people incorporate physical activity into their daily routines,” Ryan said. “That’s why we are interested in the extent to which various elements of young people’s environments, including what they wear, encourage such behaviours.”

The study analysed existing data on the physical activity levels of nearly 1.1 million young people aged five to 17 in 135 countries and combined this with newly collected data on how common the use of school uniforms is in these countries.

In over 75% of the countries surveyed, a majority of schools required their students to wear uniforms. The study found that in these countries, physical activity participation was lower. The median proportion of all students meeting the WHO recommendations in countries where uniform-wearing was the norm was 16%; this rose to 19.5% in countries where uniforms were less common.

There was a consistent gender gap between boys’ and girls’ physical activity levels, with boys 1.5 times more likely to meet WHO recommendations across all ages. However, the gap widened from 5.5 percentage points at primary school level in non-uniform countries to a 9.8 percentage point difference in countries where uniforms were required in most schools.

The finding appears to match evidence from other studies suggesting that girls are more self-conscious about engaging in physical activity when wearing uniforms in which they do not feel comfortable.

“Girls might feel less confident about doing things like cartwheels and tumbles in the playground, or riding a bike on a windy day, if they are wearing a skirt or dress,” said senior author Dr Esther van Sluijs, MRC Investigator. “Social norms and expectations tend to influence what they feel they can do in these clothes. Unfortunately, when it comes to promoting physical health, that’s a problem.”

The authors of the study argue that there is now enough evidence to warrant further investigation into whether there is a causal relationship between school uniforms and lower activity levels. They also highlight the importance of regular physical activity for all young people, regardless of their gender.

“Regular physical activity helps support multiple physical, mental, and well-being needs, as well as academic outcomes,” Dr Ryan said. “We now need more information to build on these findings, considering factors like how long students wear their uniforms for after school, whether this varies depending on their background, and how broader gendered clothing norms may impact their activity.”

The findings are reported in the Journal of Sport and Health Science.

Reference
Ryan, M et al. Are school uniforms associated with gender inequalities in physical activity? A pooled analysis of population-level data from 135 countries/regions. Journal of Sport and Health Science; 15 Feb 2024; DOI: doi.org/10.1016/j.jshs.2024.02.003

Cambridge scientists have identified more than one hundred key genes linked to DNA damage through systematic screening of nearly 1,000 genetically modified mouse lines.

Continued exploration on genomic instability is vital to develop tailored treatments that tackle the root genetic causes

Gabriel Balmus

The work, published in Nature, provides insights into cancer progression and neurodegenerative diseases as well as a potential therapeutic avenue in the form of a protein inhibitor.

The genome contains all the genes and genetic material within an organism’s cells. When the genome is stable, cells can accurately replicate and divide, passing on correct genetic information to the next generation of cells. Despite its significance, little is understood about the genetic factors governing genome stability, protection, repair, and the prevention of DNA damage.

In this new study, researchers from the UK Dementia Research Institute, at the University of Cambridge, and the Wellcome Sanger Institute set out to better understand the biology of cellular health and identify genes key to maintaining genome stability.

Using a set of genetically modified mouse lines, the team identified 145 genes that play key roles in either increasing or decreasing the formation of abnormal micronuclei structures. These structures indicate genomic instability and DNA damage, and are common hallmarks of ageing and diseases.

The most dramatic increases in genomic instability were seen when the researchers knocked out the gene DSCC1, increasing abnormal micronuclei formation five-fold. Mice lacking this gene mirrored characteristics akin to human patients with a number of rare genetic disorders, further emphasising the relevance of this research to human health.

Using CRISPR screening, researchers showed this effect triggered by DSCC1 loss could be partially reversed through inhibiting protein SIRT1. This offers a highly promising avenue for the development of new therapies.

The findings help shed light on genetic factors influencing the health of human genomes over a lifespan and disease development.

Professor Gabriel Balmus, senior author of the study at the UK Dementia Research Institute at the University of Cambridge, formerly at the Wellcome Sanger Institute, said: “Continued exploration on genomic instability is vital to develop tailored treatments that tackle the root genetic causes, with the goal of improving outcomes and the overall quality of life for individuals across various conditions.”

Dr David Adams, first author of the study at the Wellcome Sanger Institute, said: “Genomic stability is central to the health of cells, influencing a spectrum of diseases from cancer to neurodegeneration, yet this has been a relatively underexplored area of research. This work, of 15 years in the making, exemplifies what can be learned from large-scale, unbiased genetic screening. The 145 identified genes, especially those tied to human disease, offer promising targets for developing new therapies for genome instability-driven diseases like cancer and neurodevelopmental disorders.”

This research was supported by Wellcome and the UK Dementia Research Institute.

Reference
Adams, DJ et al. Genetic determinants of micronucleus formation in vivo. Nature; 14 Feb 2024; DOI: 10.1038/s41586-023-07009-0

Adapted from a press release from the Wellcome Sanger Institute.

source: cam.ac.uk

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By Stephen Bevan
Published: 15th February 2024

New types of cancer treatment – which use the body’s immune system to fight the disease and are “kinder” to patients than chemotherapy ­– will feature at this year’s Cambridge Festival.

Cambridge researchers will discuss their pioneering work in cancer immunotherapy as part of a package of events focusing on cancer and the University’s work to help end the death and disease it causes.

Klaus Okkenhaug, Professor of Immunology in the Department of Pathology, says immunotherapy is already changing patients’ experience of cancer treatment, and has the potential to transform cancer care and outcomes in the future.

“These are drugs that remove the brakes on the immune system and unleash powerful immune responses, and that’s very effective against cancer,” he said.  “It’s a therapy which is advancing rapidly now, with a large number of immunotherapies approved over recent years. What’s exciting is that many patients have gone into very, very long-term remission, and in fact some of those patients are considered effectively cured. It’s less toxic than chemotherapy, so it’s also kinder on patients.”

In Cancer immunotherapy: Innovation from laboratory bench to bedside (28 March), Professor Okkenhaug, Dr Pippa Corrie and Professor Rahul Roychoudhuri will explain how the current treatments work – among them cancer-killing viruses, tumour vaccines, and adoptive cell therapy – how they help patients, and how they might be improved.

“Cancer immunotherapy has already achieved a lot,” said Prof Okkenhaug. “We’ve had tremendous success with tumour vaccines, particularly those against Human papillomavirus (HPV) which can cause cervical cancer – and which now we could potentially eradicate. And there is also a lot of excitement about adoptive cell therapy, a personalised treatment where cells taken from a patient’s blood are genetically modified and reintroduced to kill the disease. There have been some remarkable results, particularly in blood cancers.

“There are amazing opportunities, and because of Cambridge’s unique ecosystem, where so many scientists are working together, and working in partnerships with industry, you actually see the time it takes for an idea to be translated into patient trials get smaller.”

Get hands-on with cancer research in Cambridge (16 March), also part of the Festival, is a day of interactive science featuring the groundbreaking programmes and institutes of the Cancer Research UK Cambridge Centre.

Alongside exhibits, experiments, informative demonstrations, and plenty of fun activities, scientists and clinicians will help tell the full story of the cancer research happening across Cambridge.

Neuropathologist Dr Mayen Briggs is part of the team running the Minderoo Precision Brain Tumour Programme, which is working to revolutionise treatment and improve survival rates for brain cancer patients with more targeted and effective care.

Patients with the most aggressive and fatal form of brain tumour, glioblastoma, are being offered a detailed diagnosis and tailored treatment plan, based on genomic sequencing.

“The idea is to use more targeted and precision brain chemotherapy by understanding the genetics behind a lot of these tumours,” said Dr Briggs, “and to sequence all of these tumours, understand what is driving them, and to identify instances where other drugs can be used.

“It has a big impact. We’re not just using information on which genes might be mutated, but also how these mutations might be affecting how these genes work. This additional information has the potential to guide treatment. If a patient isn’t responding to a particular therapy, using this information, we can try and work out why.

“It’s information we didn’t have before and it opens up truly personalised treatment options for patients, therapies that wouldn’t normally have been available to them because they’re not part of conventional treatments. It’s an especially significant development for those patients where therapy hasn’t changed a huge amount in terms of what we’re able to offer them.”

So far, the programme – which has enrolled more than 200 patients from Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust – has identified potential drug targets in more than 90 per cent of patients on the trial, recommended precision therapies for 10 per cent, and informed a change in diagnosis and treatment for three per cent.

Dr Briggs – a member of the Brain Cancer Virtual Institute at the Cancer Research UK Cambridge Centre ­– will join colleagues in ‘Jelly brain surgery and neuropathology’ as part of CRUK’s Festival activities. Festival-goers will get the chance to step into the role of a brain surgeon and operate on special jelly ‘brains’, working with neuropathologists to recognise the patterns and identify the features of normal and abnormal brain tissue.

The event – at the Cambridge Academy for Science and Technology – will also include an opportunity to find out more about the new Cambridge Cancer Research Hospital, and contribute ideas. Visitors can also get creative with an activity decorating radiotherapy masks.

Other Cambridge Festival events include:

Researching cancer in Cambridge (23 and 24 March), will hear from Cancer Research UK Cambridge Institute scientists about the work they are doing as part of their mission for 3 in 4 people to survive cancer by 2034. Interactive stalls will focus on two of the fundamental questions that all cancer researchers must ask: How do we identify cancer in the body? And, how do we get rid of it safely and effectively? There will be an opportunity to look inside the body using light, sound, magnets and more, and the chance to hear an MRI orchestra.  

A talk – Urgent call for cancer awareness in francophone Africa (22 March) – by Cambridge post-doctoral Research Associate Dr Yvonne Joko Walburga will take the audience through the epidemiology of cancer in French-speaking Africa. She will speak about the most common cancers, the risk factors, the prevention measures that are in place, and the challenges of cancer treatment and research on the sub-Saharan African continent, with a focus on French-speaking Africa.

Challenging the mysteries of cancer (16 March), features a range of interactive activities: looking at real cancer cells under the microscope, creating DIY 3D cells, finding the right antibody (key) that fits the right antigen (lock), and origami to make 2D miniature lab coats.

Science spotlight: Step into our science (21 March), is an online event which includes a virtual tour of the Babraham Institute’s Biological Support Unit to see how vital work is carried out at the world-leading biosciences research institute. Much of the Institute’s work underpins biomedical treatments for conditions such as cancer, autoimmune conditions and infectious diseases, to name a few.

The Cambridge Festival, which runs 13-28 March, is one of the largest of its kind in the country, featuring more than 360 mostly free events, and showcases cutting edge research across the University of Cambridge and beyond.

How you can support Cambridge’s cancer research.

The text in this work is licensed under a Creative Commons Attribution 4.0 International License.

source: cam.ac.uk

The University of Cambridge is a partner in the new £11m Innovation and Knowledge Centre (IKC) REWIRE, set to deliver pioneering semiconductor technologies and new electronic devices.

Semiconductors, also known as microchips, are a key component in nearly every electrical device from mobile phones and medical equipment to electric vehicles.

They are increasingly being recognised as an area of global strategic significance due to the integral role they play in net zero, AI and quantum technology.

Co-created and delivered with industry, the REWIRE IKC is led by the University of Bristol, in partnership with Cambridge and Warwick Universities.

The IKC will accelerate the UK’s ambition for net zero by transforming the next generation of high-voltage electronic devices using wide/ultra-wide bandgap (WBG/UWBG) compound semiconductors.

The project is being led by Professor Martin Kuball and his team at the University of Bristol. Cambridge members of the IKC team include Professors Rachel Oliver, Florin Udrea and Teng Long.

The centre will advance the next generation of semiconductor power device technologies and enhance the security of the UK’s semiconductor supply chain.

Compound semiconductor WBG/UWBG devices have been recognised in the UK National Semiconductor Strategy as key elements to support the net zero economy through the development of high voltage and low energy-loss power electronic technology.

They are essential building blocks for developing all-electric trains, ships and heavy goods electric vehicles, better charging infrastructure, renewable energy and High Voltage Direct Current grid connections, as well as intelligent power distribution and energy supplies to telecommunication networks and data centres.

“Power devices are at the centre of all power electronic systems and pave the way for more efficient and compact power electronic systems, reducing energy loss,” said Kuball. “The REWIRE IKC will focus on power conversion of wind energy, electric vehicles, smart grids, high-temperature applications, device and packaging, and improving the efficiency of semiconductor device manufacture.”

Our home electrical supply is at 240 Volts, but to handle the power from offshore wind turbines, devices will have to operate at thousands of Volts. These very high voltages can easily damage the materials normally used in power electronics.

“Newly emerging ultra-wide bandgap materials have properties which enable them to handle very large voltages more easily,” said Oliver, who Director of the Cambridge Centre for Gallium Nitride. “The devices based on these materials will waste less energy and be smaller, lighter and cheaper. The same materials can also withstand high temperatures and doses of radiation, which means they can be used to enable other new electricity generation technologies, such as fusion energy.”

“The REWIRE IKC will play a prominent role within the UK’s semiconductor strategy, in cementing the UK’s place as a leader in compound semiconductor research and development, developing IP to be exploited here in the UK, rebuilding the UK semiconductor supply chain, and training the next generation of semiconductor materials scientists and engineers,” said Professor Peter Gammon from the University of Warwick.

Industry partners in the REWIRE IKC include Ampaire, BMW, Bosch, Cambridge GaN Devices (CGD), Element-Six Technologies, General Electric, Hitachi Energy, IQE, Oxford Instruments, Siemens, ST Microelectronics and Toshiba.

REWIRE is one of two new IKCs announced being funded by the Engineering and Physical Sciences Research Council (EPSRC) and Innovate UK, both part of UK Research and Innovation. The second IKC at the University of Southampton will improve development and commercialisation of silicon photonics technologies in the UK.

“This investment marks a crucial step in advancing our ambitions for the semiconductor industry, with these centres helping bring new technologies to market in areas like net zero and AI, rooting them right here in the UK,” said Minister for Tech and the Digital Economy Saqib Bhatti. “Just nine months into delivering on the National Semiconductor Strategy, we’re already making rapid progress towards our goals. This isn’t just about fostering growth and creating high-skilled jobs, it’s about positioning the UK as a hub of global innovation, setting the stage for breakthroughs that have worldwide impact.”

Adapted from a University of Bristol media release.

For more information on energy-related research in Cambridge, please visit the Energy IRC, which brings together Cambridge’s research knowledge and expertise, in collaboration with global partners, to create solutions for a sustainable and resilient energy landscape for generations to come.

source: cam.ac.uk

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Researchers from the University of Cambridge and the British Antarctic Survey have uncovered the first direct evidence that the West Antarctic Ice Sheet shrunk suddenly and dramatically at the end of the Last Ice Age, around 8,000 years ago.

The evidence, contained within an ice core, shows that in one location the ice sheet thinned by 450 metres — that’s more than the height of the Empire State Building — in just under 200 years.

This is the first evidence anywhere in Antarctica for such a fast loss of ice. Scientists are worried that today’s rising temperatures might destabilize parts of the West Antarctic Ice Sheet in the future, potentially passing a tipping point and inducing a runaway collapse. The study, published in Nature Geoscience, sheds light on how quickly Antarctic ice could melt if temperatures continue to soar.

“We now have direct evidence that this ice sheet suffered rapid ice loss in the past,” said Professor Eric Wolff, senior author of the new study from Cambridge’s Department of Earth Sciences. “This scenario isn’t something that exists only in our model predictions and it could happen again if parts of this ice sheet become unstable.”

From west to east, the Antarctic ice sheets contain enough freshwater to raise global sea levels by around 57 metres. The West Antarctic Ice Sheet is considered particularly vulnerable because much of it sits on bedrock below sea level.

Model predictions suggest that a large part of the West Antarctic Ice Sheet could disappear in the next few centuries, causing sea levels to rise. Exactly when and how quickly the ice could be lost is, however, uncertain.

One way to train ice sheet models to make better predictions is to feed them with data on ice loss from periods of warming in Earth’s history. At the peak of the Last Ice Age 20,000 years ago, Antarctic ice covered a larger area than today. As our planet thawed and temperatures slowly climbed, the West Antarctic Ice Sheet contracted to more or less its current extent.

“We wanted to know what happened to the West Antarctic Ice Sheet at the end of the Last Ice Age, when temperatures on Earth were rising, albeit at a slower rate than current anthropogenic warming,” said Dr Isobel Rowell, study co-author from the British Antarctic Survey. “Using ice cores we can go back to that time and estimate the ice sheet’s thickness and extent.”

Ice cores are made up of layers of ice that formed as snow fell and was then buried and compacted into ice crystals over thousands of years. Trapped within each ice layer are bubbles of ancient air and contaminants that mixed with each year’s snowfall — providing clues as to the changing climate and ice extent.

The researchers drilled a 651-metre-long ice core from Skytrain Ice Rise in 2019. This mound of ice sits at the edge of the ice sheet, near the point where grounded ice flows into the floating Ronne Ice Shelf.

After transporting the ice cores to Cambridge at -20C, the researchers analysed them to reconstruct the ice thickness. First, they measured stable water isotopes, which indicate the temperature at the time the snow fell. Temperature decreases at higher altitudes (think of cold mountain air), so they could equate warmer temperatures with lower-lying, thinner ice.

They also measured the pressure of air bubbles trapped in the ice. Like temperature, air pressure also varies systematically with elevation. Lower-lying, thinner ice contains higher-pressure air bubbles.

These measurements told them that ice thinned rapidly 8,000 years ago. “Once the ice thinned, it shrunk really fast,” said Wolff, “this was clearly a tipping point — a runaway process.”

They think this thinning was probably triggered by warm water getting underneath the edge of the West Antarctic Ice Sheet, which normally sits on bedrock. This likely untethered a section of the ice from bedrock, allowing it to float suddenly and forming what is now the Ronne Ice Shelf. This allowed neighbouring Skytrain Ice Rise, no longer restrained by grounded ice, to thin rapidly. 

The researchers also found that the sodium content of the ice (originating from salt in sea spray) increased about 300 years after the ice thinned. This told them that, after the ice thinned, the ice shelf shrunk back so that the sea was hundreds of kilometres nearer to their site.

“We already knew from models that the ice thinned around this time, but the date of this was uncertain,” said Rowell. Ice sheet models placed the retreat anywhere between 12,000 and 5,000 years ago and couldn’t say how quickly it happened. “We now have a very precisely dated observation of that retreat that can be built into improved models,” said Rowell.

Although the West Antarctic Ice Sheet retreated quickly 8,000 years ago, it stabilised when it reached roughly its current extent. “It’s now crucial to find out whether extra warmth could destabilise the ice and cause it to start retreating again,” said Wolff.

Reference

Grieman et al. (2024) Abrupt Holocene ice loss due to thinning and ungrounding in the Weddell Sea Embayment. Nature Geoscience. DOI: 10.1038/s41561-024-01375-8

source: cam.ac.uk

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“Follow your curiosity”

By Ellie Austin

To mark the International Day of Women and Girls in Science , two of our academics speak about their research careers and how they ended up using their STEM interests to tackle climate change. 

Build food security amid changing environments with crop science

Dr Nadia Radzman is a plant biologist. She’s an expert in legume biology, i.e., “anything that’s got to do with beans!…I’m a little bit obsessive about it.” 

“I initially wanted to do something with virology…I didn’t even consider plant biology as something I wanted to pursue,” said Dr Radzman.

However, after finding herself allocated to a plant biology lab during her second summer of undergrad, she wound up falling in love with legumes.

Now she uses her background in chemistry and molecular biology, and her love for beans, to secure a brighter, well-nourished future for people across the planet. 

“Within the context of climate change, [legumes] will become very important in the future,” said Dr Radzman. 

Her work investigates how the important plant nutrient, nitrogen, can be acquired naturally by the plant from the air (“fixed”), without the use of polluting synthetic fertilisers.

She’s also interested in how plants can be used to breathe in the climate-changing greenhouse gas, carbon dioxide, to trap (“sequester”) carbon underground. 

“Legumes can mutually associate with very specific bacteria in the soil through symbiosis and form these structures on the roots called nodules…these nodules fix nitrogen from the air into a form that can be utilised by the plants,” said Dr Radzman.

“Because nitrogen and carbon are very strongly correlated, if you have a higher fixation of nitrogen it also correlates with a higher sequestration of carbon too.”

“When we want to fix nitrogen from the air we have to use the Haber-Bosch process, which is high temperature and a lot of fossil fuels…but plants can do it in just ambient temperature.” 

Dr Radzman’s latest project is applying her findings about these underground roots structures into the aboveground shoots. She’s interested in how a changing environment will influence the shoot, which is the part of the plant that produces the beans.

“I figured out that there are aspects of [nodules] that can be translated into the shoot…and the shoot is important in terms of food security, and when we talk about climate change.” 

Dr Radzman is also one of the first batch of King’s College Research Associates in their entrepreneurship lab. Her start-up idea is to improve the technology available to transfer genetically modified plant tissue into field-ready growing plants, which is one of the most challenging aspects of engineering crops. 

She was inspired to scale-up her science to industry after being approached by a few African NGOs asking how they can adapt their agriculture to the increasingly extreme dry seasons due to climate change.

“Native African legume crops are very drought tolerant, but these crops are usually forgotten or neglected…these crops need to have a higher yield to support the population.”

“Because of climate change, we need to improve our crops faster and cheaper, especially for the Global South. To do that, we will need new technologies,” said Dr Radzman. 

“Having a role model is important. It can be a motivation that someone has made it, so I can do it too.”

Dr Nadia Radzman

Creating safe and sustainable batteries for the energy transition

Dr Svetlana Menkin is interested in battery interfaces. Her research is all about next-generation batteries, which involve using materials such as Sodium and Calcium ions, or Zinc, to store energy.

These batteries are vital for green transition to store the production of renewable energy, so that we can use our captured solar energy from the day well into the night. 

But what is a battery interface? What is a battery? Why does it matter? Dr Menkin explains:

“In batteries we have cathodes and anodes (two electrodes), which are connected by electrolytes, which are absorbed in a separator. This electrolyte allows ions to pass from one side to another, but not the electrons.” 

This transport of electrons and ions creates what’s known as a “charge transport.” The purpose of batteries is to store a charge, i.e. store electrical energy, which can then be “discharged” to power our devices. 

“When you charge a battery, you ‘put in’ electrons from the circuit, which forces the ions from one electrode to the other. When you discharge, you let these ions (this ‘charge’ that you’ve passed) go back [to the other electrode] which then gives up the electrons you stored. You then use these electrons for the device…and this is how you store energy in a battery.” Eureka! 

“Batteries are all about controlling how this charge is transported,” said Menkin. “Between the electrodes, in the electrolyte, the charge should pass…but typically the electrodes develop a layer at the interface [between the electrodes and the electrolytes],” said Menkin, which could happen for example as a product of a chemical reaction of the electrolyte with the anode. 

“This is very critical for the battery because this will determine performance: how fast it can charge, safety of the battery, the degradation/ how many cycles it can do.” 

These next-generation batteries are more sustainable than alternatives such as Lithium-ion batteries. “Calcium is one of the most abundant elements…it is three magnitudes more abundant than lithium. Lithium is only found in particular places, and so it’s more energy intensive to move it about from place to place. The methods to extract Lithium from sources are also not very environmentally friendly,” said Dr Menkin.

The challenge with these next-generation batteries, however, is that this interface becomes very unstable. When unchecked, this instability can lead to short-circuits and battery fires.

Dr Menkin aims to understand these interfaces so she can improve battery safety, and hence the availability of more sustainable batteries to industry.

“Eight years ago calcium-rechargeable batteries were considered impossible…so it’s very new, but we will try.” 

Mentoring Women and Girls in Science

When asked about what first sparked their interest in STEM, Dr Radzman and Dr Menkin both noted female teachers in their early education.

“Towards the end of high school, I had a chemistry teacher. I remember one class where she explained to us the structure of diamonds, and I was fascinated by how diamonds and coal are made of the same carbon atoms but it is the structure that makes them so different…I was inspired by how excited she was. This was when it clicked: I was going to study chemistry,” said Dr Menkin.  

“I had a very good high school teacher…in my high school, there were not a lot of girls who wanted to pursue science. But she was really, really encouraging, and motivated me to pursue [my interests in STEM],” said Dr Radzman.

“Having a role model is important,” said Dr Radzman. It can be a motivation that someone has made it, so I can do it too.”

“Each step that I made, to bring me to where I am now, I had somebody who was there to support me and was there to tell me ‘yes this is possible for you,’” said Dr Menkin. 

Radzman’s final piece of advice? “Follow your curiosity…take up your space, and stand your ground.”

“We see that female candidates, if they see that they are almost hitting the criteria, they don’t apply. Male candidates, [who are] not eligible, [they] apply. I think this is the critical point: you need somebody to tell you that it is possible for you,” said Dr Menkin.  

“If you look at something and you can imagine yourself being happy there, apply. Go for it! …if you wonder whether it’s possible for you, it is,” said Dr Menkin.

The International Day of Women and Girls in Science is a campaign to promote full and equal access and participation of women in Science, Technology, Engineering and Mathematics (STEM).

Applications to join Dr Menkin’s lab as a PhD student are open now until the end of the month. Find out more information about how to apply here.

Published 11 February 2024

^{Images: Nick Saffell}

source: cam.ac.uk

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A team of astronomers, led by the University of Cambridge, has used the NASA/ESA/CSA James Webb Space Telescope to reveal, for the first time, what lies in the local environment of galaxies in the very early Universe.

This has solved one of the most puzzling mysteries in astronomy – why astronomers detect light from hydrogen atoms that should have been entirely blocked by the pristine gas that formed after the Big Bang.

These new observations have found small, faint objects surrounding the galaxies that show the ‘inexplicable’ hydrogen emission. In conjunction with state-of-the-art simulations of galaxies in the early Universe, the observations have shown that the chaotic merging of these neighbouring galaxies is the source of this hydrogen emission. The results are reported in the journal Nature Astronomy.

Light travels at a finite speed (300 000 km a second), which means that the further away a galaxy is, the longer it has taken the light from it to reach our Solar System. As a result, not only do observations of the most distant galaxies probe the far reaches of the Universe, but they also allow us to study the Universe as it was in the past.

To study the early Universe, astronomers require exceptionally powerful telescopes that are capable of observing very distant – and therefore very faint – galaxies. One of Webb’s key capabilities is its ability to observe these galaxies, and probe the early history of the Universe.

The earliest galaxies were sites of vigorous and active star formation, and were rich sources of a type of light emitted by hydrogen atoms called Lyman-α emission. However, during the epoch of reionisation, an immense amount of neutral hydrogen gas surrounded these stellar nurseries. Furthermore, the space between galaxies was filled by more of this neutral gas than is the case today. The gas can effectively absorb and scatter this kind of hydrogen emission, so astronomers have long predicted that the abundant Lyman-α emission released in the early Universe should not be observable today.

This theory has not always stood up to scrutiny, however, as examples of early hydrogen emission have previously been observed by astronomers. This has presented a mystery: how is it that this hydrogen emission – which should have long since been absorbed or scattered – is being observed?

“One of the most puzzling issues that previous observations presented was the detection of light from hydrogen atoms in the very early Universe, which should have been entirely blocked by the pristine neutral gas that was formed after the Big Bang,” said lead author Callum Witten from Cambridge’s Institute of Astronomy. “Many hypotheses have previously been suggested to explain the great escape of this ‘inexplicable’ emission.”

The team’s breakthrough came thanks to Webb’s combination of angular resolution and sensitivity. The observations with Webb’s NIRCam instrument were able to resolve smaller, fainter galaxies that surround the bright galaxies from which the ‘inexplicable’ hydrogen emission had been detected. In other words, the surroundings of these galaxies appear to be a much busier place than we previously thought, filled with small, faint galaxies.

These smaller galaxies were interacting and merging with one another, and Webb has revealed that galaxy mergers play an important role in explaining the mystery emission from the earliest galaxies.

“Where Hubble was seeing only a large galaxy, Webb sees a cluster of smaller interacting galaxies, and this revelation has had a huge impact on our understanding of the unexpected hydrogen emission from some of the first galaxies,” said co-author Sergio Martin-Alvarez from Stanford University.

The team then used computer simulations to explore the physical processes that might explain their results. They found that the rapid build-up of stellar mass through galaxy mergers both drove strong hydrogen emission and facilitated the escape of that radiation via channels cleared of the abundant neutral gas. So, the high merger rate of the previously unobserved smaller galaxies presented a compelling solution to the long-standing puzzle of the ‘inexplicable’ early hydrogen emission.

The team is planning follow-up observations with galaxies at various stages of merging, to continue to develop their understanding of how the hydrogen emission is ejected from these changing systems. Ultimately, this will enable them to improve our understanding of galaxy evolution.

Reference:
Callum Witten et al. ‘Deciphering Lyman-α emission deep into the epoch of reionization.’ Nature Astronomy (2024). DOI: 10.1038/s41550-023-02179-3

Adapted from an ESA press release.

source: cam.ac.uk

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The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Scientists have grown ‘mini-placentas’ in the lab and used them to shed light on how the placenta develops and interacts with the inner lining of the womb – findings that could help scientists better understand and, in future, potentially treat pre-eclampsia.

Most of the major disorders of pregnancy – pre-eclampsia, still birth, growth restriction, for example – depend on failings in the way the placenta develops in the first few weeks. This is a process that is incredibly difficult to study.Ashley Moffett

The study, published today in Cell Stem Cell, shows that it is possible to experiment on a developing human placenta, rather than merely observe specimens, in order to study major disorders of pregnancy.

Successful pregnancy depends on the development of the placenta in the first few weeks of gestation. During this period, the placenta implants itself into the endometrium – the mucosal lining of the mother’s uterus.

Interactions between the cells of the endometrium and the cells of the placenta are critical to whether a pregnancy is successful. In particular, these interactions are essential to increase the maternal blood supply to the placenta, necessary for fetal growth and development.

When these interactions do not work properly, they can lead to complications, such as pre-eclampsia, a condition that causes high blood pressure during pregnancy. Pre-eclampsia occurs in around six in 100 first pregnancies and can put at risk the health of both the mother and the baby.

Professor Ashley Moffett from the Department of Pathology at the University of Cambridge said: “Most of the major disorders of pregnancy – pre-eclampsia, still birth, growth restriction, for example – depend on failings in the way the placenta develops in the first few weeks. This is a process that is incredibly difficult to study – the period after implantation, when the placenta embeds itself into the endometrium, is often described as a ‘black box of human development’.

“Over the past few years, many scientists – including several at Cambridge – have developed embryo-like models to help us understand early pre-implantation development. But further development is impeded because we understand so little about the interactions between the placenta and the uterus.”

Professor Moffett and colleagues at the Friedrich Miescher Institute, Switzerland, and the Wellcome Sanger Institute, Cambridge, have used ‘mini-placentas’ – a cellular model of the early stages of the placenta – to provide a window into early pregnancy and help improve our understanding of reproductive disorders. Known as ‘trophoblast organoids’, these are grown from placenta cells and model the early placenta so closely that they have previously been shown to record a positive response on an over-the-counter pregnancy test.

In previous work, Professor Moffett and colleagues identified genes that increase the risk of or protect against conditions such as pre-eclampsia. These highlighted the important role of immune cells uniquely found in the uterus, known as ‘uterine natural killer cells’, which cluster in the lining of the womb at the site where the placenta implants. These cells mediate the interactions between the endometrium and the cells of the placenta.

In their new study, her team applied proteins secreted by the uterine natural killer cells to the trophoblast organoids so that they could mimic the conditions where the placenta implants itself. They identified particular proteins that were crucial to helping the organoids develop. These proteins will contribute to successful implantation, allowing the placenta to invade the uterus and transform the mother’s arteries.

“This is the only time that we know of where a normal cell invades and transforms an artery, and these cells are coming from another individual, the baby,” said Professor Moffett, who is also a Fellow at King’s College, Cambridge.

“If the cells aren’t able to invade properly, the arteries in the womb don’t open up and so the placenta – and therefore the baby – are starved of nutrients and oxygen. That’s why you get problems later on in pregnancy, when there just isn’t enough blood to feed the baby and it either dies or is very tiny.”

The researchers also found several genes that regulate blood flow and help with this implantation, which Professor Moffett says provide pointers for future research to better understand pre-eclampsia and similar disorders.

Dr Margherita Turco, from the Friedrich Miescher Institute in Switzerland and co-lead of this work, added: “Despite affecting millions of women a year worldwide, we still understand very little about pre-eclampsia. Women usually present with pre-eclampsia at the end of pregnancy, but really to understand it – to predict it and prevent it – we have to look at what’s happening in the first few weeks.

“Using ‘mini-placentas’, we can do just that, providing clues as to how and why pre-eclampsia occurs. This has helped us unpick some of the key processes that we should now focus on far more. It shows the power of basic science in helping us understand our fundamental biology, something that we hope will one day make a major difference to the health of mothers and their babies.”

The research was supported by Wellcome, the Royal Society, European Research Council and Medical Research Council.

Reference
Li, Q et al. Human uterine natural killer cells regulate differentiation of extravillous trophoblast early in pregnancy. Cell Stem Cell; 17 Jan 2024; DOI: doi.org/10.1016/j.stem.2023.12.013

source: cam.ac.uk

Researchers have discovered the oldest black hole ever observed, dating from the dawn of the universe, and found that it is ‘eating’ its host galaxy to death.

It’s a new era: the giant leap in sensitivity, especially in the infrared, is like upgrading from Galileo’s telescope to a modern telescope overnightRoberto Maiolino

The international team, led by the University of Cambridge, used the NASA/ESA/CSA James Webb Space Telescope (JWST) to detect the black hole, which dates from 400 million years after the big bang, more than 13 billion years ago. The results, which lead author Professor Roberto Maiolino says are “a giant leap forward”, are reported in the journal Nature.

That this surprisingly massive black hole – a few million times the mass of our Sun – even exists so early in the universe challenges our assumptions about how black holes form and grow. Astronomers believe that the supermassive black holes found at the centre of galaxies like the Milky Way grew to their current size over billions of years. But the size of this newly-discovered black hole suggests that they might form in other ways: they might be ‘born big’ or they can eat matter at a rate that’s five times higher than had been thought possible.

According to standard models, supermassive black holes form from the remnants of dead stars, which collapse and may form a black hole about a hundred times the mass of the Sun. If it grew in an expected way, this newly-detected black hole would take about a billion years to grow to its observed size. However, the universe was not yet a billion years old when this black hole was detected.

“It’s very early in the universe to see a black hole this massive, so we’ve got to consider other ways they might form,” said Maiolino, from Cambridge’s Cavendish Laboratory and Kavli Institute for Cosmology. “Very early galaxies were extremely gas-rich, so they would have been like a buffet for black holes.”

Like all black holes, this young black hole is devouring material from its host galaxy to fuel its growth. Yet, this ancient black hole is found to gobble matter much more vigorously than its siblings at later epochs.

The young host galaxy, called GN-z11, glows from such an energetic black hole at its centre. Black holes cannot be directly observed, but instead they are detected by the tell-tale glow of a swirling accretion disc, which forms near the edges of a black hole. The gas in the accretion disc becomes extremely hot and starts to glow and radiate energy in the ultraviolet range. This strong glow is how astronomers are able to detect black holes.

GN-z11 is a compact galaxy, about one hundred times smaller than the Milky Way, but the black hole is likely harming its development. When black holes consume too much gas, it pushes the gas away like an ultra-fast wind. This ‘wind’ could stop the process of star formation, slowly killing the galaxy, but it will also kill the black hole itself, as it would also cut off the black hole’s source of ‘food’.

Maiolino says that the gigantic leap forward provided by JWST makes this the most exciting time in his career. “It’s a new era: the giant leap in sensitivity, especially in the infrared, is like upgrading from Galileo’s telescope to a modern telescope overnight,” he said. “Before Webb came online, I thought maybe the universe isn’t so interesting when you go beyond what we could see with the Hubble Space Telescope. But that hasn’t been the case at all: the universe has been quite generous in what it’s showing us, and this is just the beginning.”

Maiolino says that the sensitivity of JWST means that even older black holes may be found in the coming months and years. Maiolino and his team are hoping to use future observations from JWST to try to find smaller ‘seeds’ of black holes, which may help them untangle the different ways that black holes might form: whether they start out large or they grow fast.

The research was supported in part by the European Research Council, the Royal Society, and the Science and Technology Facilities Council (STFC), part of UK Research and Innovation (UKRI).

Reference:
Roberto Maiolino et al. ‘A small and vigorous black hole in the early Universe.’ Nature (2024). DOI: 10.1038/s41586-024-07052-5

source: cam.ac.uk

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Combining three different sources of genetic information has allowed researchers to further understand why only some people with a common mutation go on to develop rare blood cancer.

Our hope is that this information can be incorporated into future disease prediction effortsJyoti Nangalia

Large-scale genetic analysis has helped researchers uncover the interplay between cancer-driving genetic mutations and inherited genetic variants in a rare type of blood cancer.

Researchers from the University of Cambridge, Wellcome Sanger Institute, and collaborators, combined various comprehensive data sets to understand the impact of both cancer-driving spontaneous mutations and inherited genetic variation on the risk of developing myeloproliferative neoplasms (MPN).

The study, published in the journal Nature Genetics, describes how inherited genetic variants can influence whether a spontaneous mutation in a particular gene increases the risk of developing this rare blood cancer.

This analysis has an impact on current clinical predictions of disease development in individuals. Further research is required to understand the biological mechanisms behind how these inherited genetic variants influence the chances of developing rare blood cancer. In the future, this knowledge could aid drug development and interventions that reduce the risk of disease.

Myeloproliferative neoplasms, MPNs, are a group of rare, chronic, blood cancers. There are around 4,000 cases of MPN in the UK each year. These occur when the bone marrow overproduces blood cells, which can result in blood clots and bleeding. MPNs can also progress into other forms of blood cancer, such as leukaemia.

In the population, there is a large amount of natural variation between individuals’ blood cells, which can affect the amount of blood cells a person has and their particular traits. This is because multiple different genes can influence blood cell features in an individual. During routine blood tests, researchers take known information about these genes and analyse the variation to give a genetic risk score, which is how likely that individual is to develop a disease over their lifetime.  

MPNs have been linked to random somatic mutations in certain genes including in a gene called JAK2. However, mutated JAK2 is commonly found in the global population, and the vast majority of these individuals do not have or go on to develop MPN.

Whilst previous studies have identified over a dozen associated inherited genetic variants that increase the risk of MPN, these studies insufficiently explain why most individuals in the population do not go on to develop MPN.

This new study, from the Wellcome Sanger Institute and collaborators, combined information on the known somatic driver mutations in MPN, inherited genetic variants, and genetic risk scores from individuals with MPN.

They found that the inherited variants that cause natural blood cell variation in the population also impact whether a JAK2 somatic mutation will go on to cause MPN.  They also found that individuals with an inherited risk of having a higher blood cell count could display MPN features in the absence of cancer-driving mutations, thus, mimicking disease.

Dr Jing Guo, from the University of Cambridge and the Wellcome Sanger Institute and first author of the study, said: “Our large-scale statistical study has helped fill the knowledge gaps in how variants in DNA, both inherited and somatic, interact to influence complex disease risk. By combining these three different types of datasets we were able to get a more complete picture of how these variants combine to cause blood disorders.”

Professor Nicole Soranzo, co-senior author from the University of Cambridge, the Wellcome Sanger Institute, and Human Technopole, Italy, said: “There has been increasing realisation that human diseases have complex causes involving a combination of common and rare inherited genetic variants with different severity.

“We have previously shown that variation in blood cell parameters and function has complex genetic variability by highlighting thousands of genetic changes that affect different gene functions. Here, we show for the first time that common variants in these genes also affect blood cancers, independent of causative somatic mutations. This confirms a new important contribution of normal variability beyond complex disease, contributing to our understanding of myeloproliferative neoplasms and blood cancer more generally.”

Dr Jyoti Nangalia, co-senior author from the Wellcome-MRC Cambridge Stem Cell Institute at the University of Cambridge, and the Wellcome Sanger Institute, said: “We have a good understanding of the genetic causes of myeloproliferative neoplasms. In fact, many of these genetic mutations are routine diagnostic tests in the clinic. However, these mutations can often be found in healthy individuals without the disease.

“Our study helps us understand how inherited DNA variation from person to person can interact with cancer-causing mutations to determine whether disease occurs in the first place, and how this can alter the type of any subsequent disease that emerges. Our hope is that this information can be incorporated into future disease prediction efforts.”  

This research was funded by Cancer Research UK and Wellcome.

Reference

J Guo, K Walter, P M Quiros, et al. ‘Inherited polygenic effects on common hematological traits influence clonal selection on JAK2V617F and the development of myeloproliferative neoplasms.’ Jan 2024,  Nature Genetics. DOI: 10.1038/s41588-023-01638-x

Adapted from a press release by the Wellcome Sanger Institute

source: cam.ac.uk

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Taking away the largest serving of wine by the glass – in most cases the 250ml option – led to an average reduction in the amount of wine sold at pubs and bars of just under 8%, new research led by a team at the University of Cambridge has discovered.

When the largest serving size of wine by the glass was unavailable, people shifted towards the smaller options, but didn’t then drink the equivalent amount of wineEleni Mantzari

While only modest, the finding could provide one way of nudging customers to drink less alcohol and have an impact at a population level, say the researchers.

Alcohol consumption is the fifth largest contributor to premature death and disease worldwide. In 2016 it was estimated to have caused approximately 3 million deaths worldwide.

There are many factors that influence how much we drink, from advertising to labelling to availability and cost. Previous research from the Behaviour and Health Research Unit at Cambridge has shown that even glass size can influence how much alcohol is consumed.

In research published today in PLOS Medicine, the Cambridge team carried out a study in 21 licensed premises (mainly pubs) in England to see whether removing their largest serving of wine by the glass for four weeks would have an impact on how much wine is consumed. Wine is the most commonly drunk alcoholic drink in the UK and Europe. Twenty of the premises completed the experiment as designed by the researchers and were included in the final analysis.

After adjusting for factors such as day of the week and total revenue, the researchers found that removing the largest wine glass serving led to an average (mean) decrease of 420ml of wine sold per day per venue – equating to a 7.6% decrease.

There was no evidence that sales of beer and cider increased, suggesting that people did not compensate for their reduced wine consumption by drinking more of these alcoholic drinks. There was also no evidence that it affected total daily revenues, implying that participating licensed premises did not lose money as a result of removing the largest serving size for glasses of wine, perhaps due to the higher profit margins of smaller serving sizes of wine. However, it is important to note that the study was not designed to provide statistically meaningful data on these points.

First author Dr Eleni Mantzari, from the University of Cambridge, said: “It looks like when the largest serving size of wine by the glass was unavailable, people shifted towards the smaller options, but didn’t then drink the equivalent amount of wine.

“People tend to consume a specific number of ‘units’ – in this case glasses – regardless of portion size. So, someone might decide at the outset they’ll limit themselves to a couple of glasses of wine, and with less alcohol in each glass they drink less overall.”

Professor Dame Theresa Marteau, the study’s senior author and an Honorary Fellow at Christ’s College Cambridge, added: “It’s worth remembering that no level of alcohol consumption is considered safe for health, with even light consumption contributing to the development of many cancers. Although the reduction in the amount of wine sold at each premise was relatively small, even a small reduction could make a meaningful contribution to population health.”

Evidence suggests that the public prefer information-based interventions, such as health warning labels, to reductions in serving or package sizes. However, in this study, managers at just four of the 21 premises reported receiving complaints from customers.

The researchers note that although the intervention would potentially be acceptable to pub or bar managers, given there was no evidence that it can result in a loss in revenue, a nationwide policy would likely be resisted by the alcohol industry given its potential to reduce sales of targeted drinks. Public support for such a policy would depend on its effectiveness and how clearly this was communicated.

The research was funded by Wellcome.

source: cam.ac.uk

Reference
Mantzari, E et al. Impact on wine sales of removing the largest serving size by the glass: an A-B-A reversal trial in 21 pubs, bars and restaurants in England. PLOS Medicine; DOI: 10.1371/journal.pmed.1004313

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Using X-rays to see inside the human body has revolutionised non-invasive medical diagnostics. However, the dose of X-rays required for imaging is far higher than background levels, due to the poor performance of the detector materials currently available. This can cause harm to patients, and in some cases even cancer.

A team of researchers, jointly led by the Universities of Oxford and Cambridge, have discovered that a solar cell material – bismuth oxyiodide (BiOI) – is capable of detecting X-ray dose rates over 250 times lower than the current best performing detectors used commercially. This has the potential to make medical imaging safer, and open up new opportunities in non-invasive diagnostics, such as X-ray video techniques. Their results are reported in the journal Nature Communications.

“We have developed BiOI single crystals into X-ray detectors that work over 100 times better than the current state-of-the-art for medical imaging,” said Dr Robert Hoye from the University of Oxford, who led the work. “BiOI is nontoxic, stable in air, and can be grown cost-effectively and at scale. We are very excited by the potential BiOI has to make the next generation of non-invasive diagnostics more accessible, safer, and more effective.”

BiOI is a nontoxic semiconductor that absorbs visible light and is stable in air. Owing to these qualities, over the past decade there has been a surge of interest in this material for solar cells (turning sunlight into clean electricity), photoelectrochemical cells (turning sunlight into fuels) and energy harvesting to power smart devices, among many other applications.

BiOI contains two heavy elements – bismuth and iodine – which allows the material to strongly absorb X-rays. However, previous attempts to make BiOI into X-ray detectors were ineffective due to significant energy losses from defects arising from the nanocrystalline nature of the detectors made.

The researchers developed and patented a method to grow high-quality single crystals of BiOI using a scalable vapour-based approach. The low defect density in these crystals led to stable and ultra-low dark currents, which was critical to substantially improve the sensitivity and detection limit of this material to X-rays.

“Showing that these simply-processed, low-temperature grown, stable crystals can give such high sensitivity for X-ray detection is quite remarkable,” said Professor Judith Driscoll from Cambridge’s Department of Materials Science and Metallurgy, who co-led the work. “We began working on this material, BiOI, several years ago, and we find it outshines other rival materials in a range of optoelectronic and sensing applications, when toxicity and performance are considered together.”

The researchers formed an interdisciplinary team to understand why BiOI works so well as an X-ray detector. They used advanced optical techniques to resolve processes taking place over a trillionth of a second, and coupled these with simulations to link these processes with what is happening at the atomic level.

Through this study, the team revealed the unusual way in which electrons couple to vibrations in the lattice. Unlike other bismuth-halide compounds, the electrons in BiOI remain delocalised, meaning that electrons can easily and rapidly move within the lattice of BiOI. At the same time, the unusual electron coupling with lattice vibrations results in an irreversible energy loss channel that would still be present even if the material were defect-free.

The researchers found that these losses can be overcome by cooling down the sample to reduce thermal energy, or by applying an electric field to rip away electrons from the lattice. The latter case is ideally matched with how X-ray detectors operate. By applying a small electric field, electrons can be transported over a millimetre length-scale, allowing the efficient extraction of electrons generated in the single crystals through the absorption of X-rays.

“We have built a microscopic quantum mechanical model of electrons and ions that can fully explain the remarkable optoelectronic properties of BiOI that make it such a good material for X-ray detection,” said Dr Bartomeu Monserrat from Cambridge’s Department of Materials Science and Metallurgy, who co-led the project. “This gives us a roadmap for designing even more materials with similarly advantageous properties.

This work offers important insights into how delocalised charge-carriers can be achieved in bismuth-halide compounds. The researchers are now working on applying these insights to design materials with similarly advantageous properties as BiOI, as well as how to tune the composition of BiOI to improve its transport properties further. They are also working on bringing the unique benefits of BiOI to society by devising routes to increase the size of the BiOI detectors, while preserving the exceptional properties found in single crystals.

The study also involved researchers from Imperial College London, Queen Mary University London, Technical University Munich and CNRS in Toulouse.

Reference:
R A Jagt, I Bravić, et al. ‘Layered BiOI single crystals capable of detecting low dose rates of X-rays.’ Nature Communications (2023). https://doi.org/10.1038/s41467-023-38008-4

Adapted from a story by the University of Oxford

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source: cam.ac.uk

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Seven outstanding Cambridge researchers have been elected as Fellows of the Royal Society, the UK’s national academy of sciences and the oldest science academy in continuous existence.

These individuals have pushed forward the boundaries of their respective fields and had a beneficial influence on the world beyond.Sir Adrian Smith, President of the Royal Society

The Royal Society is a self-governing Fellowship of many of the world’s most distinguished scientists drawn from all areas of science, engineering and medicine.

The Society’s fundamental purpose, as it has been since its foundation in 1660, is to recognise, promote and support excellence in science and to encourage the development and use of science for the benefit of humanity.

This year, a total of 80 researchers, innovators and communicators from around the world have been elected as Fellows of the Royal Society for their substantial contribution to the advancement of science. These include 59 Fellows, 19 Foreign Members and two Honorary Fellows.

Sir Adrian Smith, President of the Royal Society said: “I am delighted to welcome our newest cohort of Fellows. These individuals have pushed forward the boundaries of their respective fields and had a beneficial influence on the world beyond. This year’s intake have already achieved incredible things, and I have no doubt that they will continue to do so. I look forward to meeting them and following their contributions in future.” 

The Fellows and Foreign Members join the ranks of Stephen Hawking, Isaac Newton, Charles Darwin, Albert Einstein, Lise Meitner, Subrahmanyan Chandrasekhar and Dorothy Hodgkin.

The Cambridge Fellows are:

Professor Cathie Clarke FRS

Professor of Theoretical Astrophysics, Institute of Astronomy, and Fellow of Clare College

Clarke studies astrophysical fluid dynamics, including accretion and protoplanetary discs and stellar winds. She was the first to demonstrate how protoplanetary disc formation around low-mass young stars is determined by their radiation field. In 2017 she became the first woman to be awarded the Eddington Medal by the Royal Astronomical Society and in 2022 she became director of the Institute of Astronomy.

She said: “It’s a great honour to join the many Cambridge astrophysicists who have held this title. I would like to particularly pay tribute to the many junior colleagues, PhD students and postdocs who have contributed to my research.”

Professor Christopher Jiggins FRS

Professor of Evolutionary Biology (2014), Department of Zoology, and Fellow of St John’s College

Jiggins studies adaption and speciation in the Lepidoptera (butterflies and moths). In particular he is interested in studying how species converge due to mimicry as a model for understanding the predictability of evolution and the genetic and ecological causes of speciation. He demonstrated the importance of hybridisation and movement of genes between species in generating novel adaptations. He also works on the agricultural pest cotton bollworm and carries out genomic studies of the insect bioconversion species, black soldier fly.

He said: “I am amazed and delighted to receive this honour, and would thank all the amazing students, and postdocs that I have been lucky enough to work with over the years.”

Dr Philip Jones FRS

Senior Group Leader, Wellcome Sanger Institute and Professor of Cancer Development, University of Cambridge, and Fellow of Clare College

Jones studies how normal cell behaviour is altered by mutation in aging and the earliest stages of cancer development. He focuses on normal skin and oesophagus, which become a patchwork of mutant cells by middle age. He has found that different mutations can either promote or inhibit cancer development giving hope of new ways to prevent cancer in the future. He is also a Consultant in Medical Oncology at Addenbrooke’s Hospital in Cambridge.

He said: “I am delighted to be elected to the Fellowship of the Royal Society. This honour is a tribute to the dedication of my research team and collaborators and support of my mentors and scientific colleagues over many years.”

Dr Lori Passmore FRS

Group Leader, Structural Studies Division, MRC Laboratory of Molecular Biology, and Fellow of Clare Hall

Passmore a cryo-electron microscopist and structural biologist who works at the Medical Research Council (MRC) Laboratory of Molecular Biology and at the University of Cambridge. She is known for her work on multiprotein complexes involved in gene expression and the development of new supports for cryo-EM studies. She also studies the molecular mechanisms underlying Fanconi anemia, a rare genetic disease resulting in an impaired response to DNA damage.

She said: “I am so honoured to be recognised alongside such an exceptional group of scientists. I am grateful to all the trainees, collaborators and colleagues whom I have worked with over the past years – science is truly collaborative and this is a recognition of all the courageous work of many people.”

Professor Peter Sewell FRS

Professor of Computer Science, Department of Computer Science and Technology, and Fellow of Wolfson College

Sewell’s research aims to put the engineering of the real-world computer systems that we all depend on onto better foundations, developing techniques to make systems that are better-understood, more robust and more secure. He and his group are best known for their work on the subtle relaxed-memory concurrency behaviour and detailed sequential semantics of processors and programming languages. He co-leads the CHERI cybersecurity project, for which his team have established mathematically-proven security properties of Arm’s Morello industrial prototype architecture.

He said: “This honour is a testament to the work of many excellent colleagues over the years, without whom none of this would have been possible.”

Professor Ivan Smith FRS

Professor of Geometry, Centre for Mathematical Sciences, and Fellow of Caius College

Smith is a mathematician who deals with symplectic manifolds and their interaction with algebraic geometry, low-dimensional topology and dynamics. In 2007, he received the Whitehead Prize for his work in symplectic topology, highlighting the breadth of applied techniques from algebraic geometry and topology, and in 2013 the Adams Prize. 

He said: “I am surprised, delighted and hugely honoured to be elected a Fellow of the Royal Society. I’ve been very fortunate to work in a rapidly advancing field, learning it alongside many inspirational and generous collaborators, who should definitely share this recognition.”

Professor William Sutherland CBE FRS

Miriam Rothschild Chair of Conservation Biology, Department of Zoology and Professorial Fellow of St Catharine’s College

Sutherland is a conservation scientist who is interested in improving the processes by which decisions are made. This has involved horizon scanning to identify future issues to reduce the surprises of future developments. His main work has been the industrial-scale collation of evidence to determine which interventions are effective and which are not and then establishing processes for embedding evidence in decision making. He has developed a free, online resource, Conservation Evidence, summarising evidence for the effectiveness of conservation actions to support anyone making decisions about how to maintain and restore biodiversity and an open access book Transforming Conservation: a practical guide to evidence and decision making.

He said: “I am delighted that our work on the means of improving decision making in conservation and elsewhere has been recognised in this way and thank my numerous collaborators.”

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The protection offered by COVID-19 vaccination declines more rapidly in people with severe obesity than in those with normal weight, scientists at the Universities of Cambridge and Edinburgh have found. The study suggests that people with obesity are likely to need more frequent booster doses to maintain their immunity.

This poses a major challenge for health servicesSadaf Farooqi

Clinical trials have shown that COVID-19 vaccines are highly effective at reducing symptoms, hospitalisation and deaths caused by the virus, including for people with obesity. Previous studies have suggested that antibody levels may be lower in vaccinated people who have obesity and that they may remain at higher risk of severe disease than vaccinated people with normal weight. The reasons for this have, however, remained unclear.

This study, published in the journal Nature Medicine, shows that the ability of antibodies to neutralise the virus declines faster in vaccinated people who have obesity. The findings have important implications for vaccine prioritisation policies around the world.

During the pandemic, people with obesity were more likely to be hospitalised, require ventilators and to die from COVID-19. In this study, supported by the NIHR Bioresource and funded by UKRI, the researchers set out to investigate how far two of the most extensively used vaccines protect people with obesity compared to those with a normal weight, over time.

A team from the University of Edinburgh, led by Prof Sir Aziz Sheikh, looked at real-time data tracking the health of 3.5 million people in the Scottish population as part of the EAVE II study. They looked at hospitalisation and mortality from COVID-19 in adults who received two doses of COVID-19 vaccine (either Pfizer-BioNTech BNT162b2 mRNA or AstraZeneca ChAdOx1).

They found that people with severe obesity (a BMI greater than 40 kg/m2) had a 76% higher risk of severe COVID-19 outcomes, compared to those with a normal BMI. A modest increase in risk was also seen in people with obesity (30-39.9kg/m2), which affects a quarter of the UK population, and those who were underweight. ‘Break-through infections’ after the second vaccine dose also led to hospitalisation and death sooner (from 10 weeks) among people with severe obesity, and among people with obesity (after 15 weeks), than among individuals with normal weight (after 20 weeks).

Prof Sir Aziz Sheikh said: “Our findings demonstrate that protection gained through COVID-19 vaccination drops off faster for people with severe obesity than those with a normal body mass index. Using large-scale data assets such as the EAVE II Platform in Scotland have enabled us to generate important and timely insights that enable improvements to the delivery of COVID-19 vaccine schedules in a post-pandemic UK.”

The University of Cambridge team – jointly led by Dr James Thaventhiran, from the MRC Toxicology Unit and Prof Sadaf Farooqi from the Wellcome-MRC Institute of Metabolic Science – studied people with severe obesity attending the Obesity clinic at Addenbrooke’s Hospital in Cambridge, and compared the number and function of immune cells in their blood to those of people of normal weight.

They studied people six months after their second vaccine dose and then looked at the response to a third ‘booster’ vaccine dose over time. The Cambridge researchers found that six months after a second vaccine dose, people with severe obesity had similar levels of antibodies to the COVID-19 virus as those with a normal weight.

But the ability of those antibodies to work efficiently to fight against the virus (known as ‘neutralisation capacity’) was reduced in people with obesity. 55% of individuals with severe obesity were found to have unquantifiable or undetectable ‘neutralising capacity’ compared to 12% of people with normal BMI.

“This study further emphasises that obesity alters the vaccine response and also impacts on the risk of infection,” said Dr Agatha van der Klaauw from the Wellcome-MRC Institute of Metabolic Science and first author of the paper. “We urgently need to understand how to restore immune function and minimise these health risks.”

The researchers found that antibodies produced by people with severe obesity were less effective at neutralising the SARS-CoV-2 virus, potentially because the antibodies were not able to bind to the virus with the same strength.

When given a third (booster) dose of a COVID-19 vaccine, the ability of the antibodies to neutralise the virus was restored in both the normal weight and severely obese groups. But the researchers found that immunity again declined more rapidly in people with severe obesity, putting them at greater risk of infection with time.

Dr James Thaventhiran, a Group Leader from the MRC Toxicology Unit in Cambridge and co-lead author of the SCORPIO study said: “It is promising to see that booster vaccines restore the effectiveness of antibodies for people with severe obesity, but it is concerning that their levels decrease more quickly, after just 15 weeks. This shows that the vaccines work as well in people with obesity, but the protection doesn’t last as long.”

Prof Sadaf Farooqi from the Wellcome-MRC Institute of Metabolic Science and co-lead author of the SCORPIO study said: “More frequent booster doses are likely to be needed to maintain protection against COVID-19 in people with obesity. Because of the high prevalence of obesity across the globe, this poses a major challenge for health services”.

Reference

A A van der Klaauw et al., ‘Accelerated waning of the humoral response to COVID-19 vaccines in obesity’, Nature Medicine (2023). DOI: 10.1038/s41591-023-02343-2

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