Red-sensitive bistable pigments identified in the eye of the mantis shrimp

Researchers from ULiège and Humboldt University have analyzed 17 visual pigments in the mantis shrimp, one by one. Some detect red and switch reversibly between two states, a property that shows promise for optogenetics

University of Liège

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Mantis shrimp far red vision - Schematic illustration

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Credit: Photo : Amande Franklin / Illustration : Alina Pushkarev

With around thirty visual pigments, compared to just three in humans, mantis shrimp possess a visual system that remains a mystery. Researchers from University of Liège and Humboldt University in Berlin have, for the first time, analysed these pigments one by one and discovered that some detect red light that very few animals can perceive. This breakthrough has potential applications in optogenetics.

Vision is one of the most sophisticated sensory systems; it relies on proteins (opsins) that capture light and convert the signal into an electrical message that the brain can interpret. When combined with retinal, a small, universal molecule derived from vitamin A, opsins form the visual pigments (rhodopsins) that absorb light in the photoreceptors of the retina. In humans, three cone pigments are sufficient for colour perception. In many invertebrates, such as insects and crustaceans, the eye has multiple facets, and different regions may specialise in ultraviolet, blue, or green light. Mantis shrimp take this a step further. Their eye is divided into two hemispheres separated by a central band, known as the median band, dedicated to colour vision, and this band expresses an exceptional number of opsins.

But why does this crustacean possess such powerful vision? This question has puzzled ecologists and biologists for decades. It remained difficult to resolve because all these proteins coexist in the eye, and invertebrate opsins are notoriously difficult to produce and study in the lab. An international team of scientists has merged its expertise by combining an in vitro expression platform developed by Marjorie Lienard, a researcher at ULiège, with the electrophysiological expertise of Peter Hegemann’s laboratory at Humboldt University in Berlin, with the support of biologists, biochemists and theorists from other universities in Germany, the United Kingdom and the United States.

A scientific team led by Camille Brouillon, Alina Pushkarev and Marjorie Liénard has measured the light sensitivity and signal-transmission mechanisms of the seventeen visual opsins found in the mantis shrimp's median band. It turned out that twelve of them were ‘standard’ green opsins, similar to our own green pigment. Three are infrared opsins, including two red-blue bistable opsins that straddle the boundary between the visible and infrared spectrum. The remaining two are blue-orange bistable opsins. “This is the first time such pigments have been described in an animal whilst using the same chromophore as humans,” explains Marjorie Liénard, a molecular biologist at ULiège. “Combined with the coloured filters present in the mantis shrimp’s eye, they enable expand sensitivity to be achieved at 687 nanometres,” explains Alina Pushkarev, a marine biologist at Peter Hegemann’s laboratory.

Four of these pigments have a distinctive property: they are bistable, meaning they can reversibly switch between two stable states when they absorb light, without requiring an external cellular mechanism to regenerate. “Two of them are activated by red light and deactivated by blue light. The other two work the other way round: they are activated by blue light and deactivated by orange light,” explains Peter Hegemann, a professor of biophysics at Humboldt University in Berlin and co-recipient of the 2026 Nobel Prize in Medicine. In humans, when a pigment absorbs a photon of light, retinal changes conformation and eventually detaches from the opsin; it must then be regenerated to function again. This process helps explain why, after looking at an intense light source, spots persist for a while in our field of vision. “Bistable pigments, on the other hand, can be reactivated directly by a second photon of light that restores the retinal, suggesting that the visual system remains continuously operational,” explains Camille Brouillon, author of the study. The team also identified the molecular mechanism behind the shift in sensitivity between red and blue.

These results suggest that the mantis shrimp uses different pigment combinations depending on ambient light levels. “You could compare this to wearing sunglasses during the day and using a torch at dusk,” explains Marjorie Liénard. “In bright light, when the ultraviolet, blue and green pigments are saturated, the red opsins continue to function. At dawn and dusk, the animal can rely on its dozen green opsins and its bistable blue opsins.” However, how the mantis shrimp uses this information to locate prey, avoid predators, or defend its territory remains unconfirmed and will need to be demonstrated through behavioural experiments, which are difficult to carry out with these robust predators.

Beyond biology, these proteins interest optogenetics, a technique that controls cell activity using light. The opsins of the mantis shrimp, unlike channelrhodopsins of the single-celled alga Chlamydomonas reinhardtii, belong to the family of G-protein-coupled receptors (GPCRs), which trigger signalling cascades within cells. G-protein signalling is implicated in numerous diseases, including cardiovascular, neurological and inflammatory conditions, and is the target of a significant proportion of approved medicines. Opsins of this type, which can be activated by red light and deactivated by blue light, could serve as molecular switches to modulate these signalling pathways precisely and reversibly. Red light penetrates deeper into tissues and is less harmful to cells than blue or ultraviolet light.

These applications have not yet been developed. The team is now working to make these opsins' signalling more selective, search for similar proteins in closely related species, and understand what gives some of them their bistable nature. For Marjorie Liénard, this study illustrates the value of studying organisms with unique ecological characteristics: “Nature still harbours many innovations, which can only be uncovered through an approach combining molecular biology, biochemistry, physiology and sensory ecology.”

Mantis shrimp

Credit

Michaël Bok

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Journal

Science Advances

DOI

10.1126/sciadv.aef5666

Article Title

Spectral tuning and signalling of diverse and most red-sensitive animal opsins in mantis shrimp eyes.

Article Publication Date

14-Oct-2026

 

Penn engineers use AI, Reddit to identify potential side effects of unapproved new GLP-1

An AI analysis of nearly 150,000 Reddit posts provides the first systematic look at self-reported side effects of gray-market versions of retatrutide, highlighting how social media could help researchers identify signals for further investigation

University of Pennsylvania School of Engineering and Applied Science

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Neil Sehgal, a doctoral student in CIS, used AI to analyze roughly 150,000 Reddit posts about gray-market versions of retatrutide, a new, unapproved GLP-1.

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Credit: Sylvia Zhang, Penn Engineering

Retatrutide, a next-generation GLP-1 weight-loss drug, is not yet approved for use. Nevertheless, online forums reveal that people are purchasing unapproved versions of the drug, which are not intended for human consumption, and sharing their experiences. 

Now, researchers at the University of Pennsylvania have used AI to take a closer look at these online conversations, analyzing nearly 150,000 posts and comments from roughly 40,000 Reddit users, to provide the first systematic look at the kind of side effects these users claim to be experiencing. 

“Our goal is to identify hypotheses in online conversations that we could test. AI helps us find recurring patterns in people’s self-reports, including experiences that may be missed by conventional drug-safety monitoring,” says Sharath Chandra Guntuku, Research Associate Professor in Computer and Information Science (CIS), Director of Penn’s Computational Social Listening Lab and senior author of a new paper in JAMA Network Open.

Among Reddit users who shared classifiable potential symptoms, the most frequently reported symptom was increased appetite, which differs from retatrutide's Phase 2 clinical trials, where gastrointestinal complaints were identified as the most common side effects.

Because of the Reddit sample’s limitations, the researchers underscore that their findings should be treated with caution. These differences do not establish that retatrutide causes the reported symptoms or that the experiences of the Reddit users reflect those of the clinical trial participants, but rather point to the kinds of patterns that AI-assisted analysis can uncover.

“We can't say that retatrutide is causing these symptoms, or even that Reddit users are actually taking genuine retatrutide, since the drug is not legally available, and gray market formulations vary,” says Lyle Ungar, Professor in CIS and a co-author of the study. 

In other words, rather than being taken as evidence of previously unrecognized side effects, the results should serve as a starting point for other public health researchers. “This is the first glimpse into the experiences of a population that is otherwise outside conventional drug safety monitoring because they are taking unapproved versions of a drug that has yet to finish clinical trials,” says Neil Sehgal, the study’s first author and a doctoral student in CIS.

 

Using AI to Listen at Scale

 

The new study builds on earlier research by the same Penn team, which used large language models (LLMs) to analyze more than 400,000 Reddit posts about semaglutide and tirzepatide, identifying potential side effects — including menstrual irregularities — that may not have been fully captured in clinical trials or regulatory documents. “We wanted to apply the same methodology to gray-market retatrutide,” says Sehgal.

Unlike semaglutide, which activates one hormone receptor involved in regulating appetite and blood sugar, or tirzepatide, which activates two, retatrutide activates three, giving the researchers reason to investigate whether users might experience a different pattern of symptoms.

The researchers used AI to sift through nearly 150,000 Reddit posts and comments, identifying approximately 14,000 users who described personally taking an unapproved version of retatrutide. The AI tools then extracted symptoms those users attributed to the drug and matched their descriptions to standardized medical terminology, winnowing the sample to 7,823 users reporting at least one classifiable symptom beyond expected effects like weight loss or appetite suppression.

“A researcher might be able to examine a few thousand Reddit posts by hand, but looking at nearly 150,000 would be an enormous undertaking,” says Sehgal. “AI makes it possible to analyze these conversations at scale, identifying patterns in what people are sharing that would otherwise be difficult to recognize.”

 

Unexpected Findings

 

The team found that, while nausea and other gastrointestinal symptoms were the most common side effects reported in retatrutide's Phase 2 trials (the drug is currently in Phase 3 trials, the final step before FDA approval), the Reddit users claiming to take unapproved versions of retatrutide more frequently described a different set of symptoms, including increased appetite, an unexpected finding given retatrutide's demonstrated weight-loss effects in Phase 2 clinical trials. 

A similar contrast emerged when the researchers compared their findings with their earlier study of semaglutide and tirzepatide. Reddit posts about gray-market retatrutide featured proportionally more reports of appetite-related symptoms, sleep disturbances, increased heart rate and muscle-related changes, and fewer reports of nausea and other gastrointestinal symptoms.

“Retatrutide works differently from existing GLP-1 drugs, so it's possible that its effects on the body are different, too,” says Jena Shaw Tronieri, Senior Research Investigator at Penn's Center for Weight and Eating Disorders and a co-author of the study. 

“But the people discussing it on Reddit also may be different,” she notes. “Users willing to obtain an unapproved medication on the gray market likely differ from other clinical populations. Some may be taking multiple experimental peptides, and we can't verify exactly what they're taking. We need more research to understand what, if anything, these differences in self-reported symptoms mean.”

 

Spotting Emerging Safety Signals

 

The researchers hope that AI-assisted social media analysis can help identify potential safety concerns earlier, giving clinicians and public health researchers a starting point for further investigation. 

Sehgal points to the team's previous GLP-1 study as an example of how that process can work. 

After the Penn researchers identified reports of menstrual irregularities among semaglutide and tirzepatide users, another research group was inspired to investigate the same symptoms using the FDA's adverse-event database. 

Their subsequent study, published in Obstetrics & Gynecology, also identified disproportionate reports of certain menstrual changes, providing additional evidence that the symptoms merit investigation.

“That's what we hope will happen with this study,” says Sehgal. “Other researchers can take what we find on Reddit and look for the same patterns in other datasets, using entirely different methods. Whether those signals hold up or not, the goal is to build a better understanding of what people are actually experiencing.”

This study was conducted at the University of Pennsylvania School of Engineering and Applied Science and Perelman School of Medicine. Additional co-authors include Benjamin Rader of Boston Children’s Hospital. This project was funded in part by the University of Pennsylvania's Penn Medical Communication Research Institute. Tronieri reports receiving an investigator-initiated grant, on behalf of the University of Pennsylvania, from Novo Nordisk and receiving consulting fees from Currax Pharmaceuticals, LLC. The other authors report no conflicts of interest. 

Sehgal, at right, demonstrates the process used in the research: leverage AI to analyze posts and comments on Reddit about taking an unapproved GLP-1.

Credit

Sylvia Zhang, Penn Engineering

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Journal

JAMA Network Open

Method of Research

Data/statistical analysis

Subject of Research

Not applicable

Article Title

Self-Reported Adverse Effects Among Social Media Users Taking Nonapproved Retatrutide

Article Publication Date

14-Oct-2026

COI Statement

Tronieri reports receiving an investigator-initiated grant, on behalf of the University of Pennsylvania, from Novo Nordisk and receiving consulting fees from Currax Pharmaceuticals, LLC. The other authors report no conflicts of interest.

 

Human papillomavirus: Can we finally predict which infections will progress to cancer?

Most HPV infections clear up on their own, but some can progress to cancer. Researchers at ULiège are analysing the challenges of risk prediction and the potential of artificial intelligence

University of Liège

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Infection with human papillomavirus (HPV) is extremely common and, in the vast majority of cases, clears up on its own. However, in some people, it persists and can develop into precancerous lesions or even cancer. How can these high-risk situations be identified at an early stage? This is the central question of a study led by researchers from the University of Liège.

For several decades, researchers have been attempting to identify biomarkers capable of accurately predicting the progression of infection with high-risk oncogenic HPV. Despite significant progress, no viral, immune or molecular marker currently allows us to reliably predict which infections will resolve spontaneously and which will progress to a more severe disease.

This difficulty stems in particular from the complexity and dynamic nature of carcinogenesis (the biological process by which a healthy cell transforms into a cancer cell) associated with HPV. The course of an infection depends on multiple factors, including viral characteristics, the host’s immune response, genetic and epigenetic factors, the microbiota, hormonal influences and the environment. Added to these interactions are random events, notably the accumulation of mutations linked to virus-induced genomic instability. “Perhaps the main challenge is no longer to discover a new biomarker, but to understand how all the biological mechanisms interact to determine the outcome of an HPV infection,”emphasises Michael Herfs, an oncologist at GIGA-ULiège.

Artificial intelligence as a new hope

Faced with this complexity, Diane Bruyère, Romane Geuzaine and Michael Herfs believe that approaches relying on a single biomarker have probably reached their limits. Recent advances in high-throughput molecular analysis and artificial intelligence are now opening up new avenues.

These technologies make it possible to simultaneously integrate vast amounts of biological data in order to build more comprehensive predictive models. The aim is to better distinguish between the various possible trajectories of an infection or a low-grade precancerous lesion: spontaneous regression, persistence or progression to a more serious lesion, or even invasive cancer. These integrative approaches are now regarded as one of the most promising avenues for improving risk stratification. 

“Artificial intelligence and integrative models could help us better understand the diversity of biological trajectories observed in patients and, ultimately, offer a more personalised risk assessment,” explains Diane Bruyère, a researcher at the Laboratory of Experimental Pathology.

Towards more personalised care

Whilst these new models offer great hope, they have not yet been sufficiently validated for use in routine clinical practice. At present, care still relies on HPV testing, cytology and histopathological analysis, supplemented by monitoring that is not highly personalised.

For researchers, the future lies in a better overall understanding of the biology of HPV infections rather than in the search for a single indicator. Ultimately, a more accurate prediction of individual risk could make it possible to tailor patient follow-up, reduce unnecessary interventions and improve the management of those infected.

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Journal

Trends in Molecular Medicine

DOI

10.1016/j.molmed.2026.09.009

Article Title

Predicting outcome in oncogenic HPV infection: are we there yet ?

Article Publication Date

14-Oct-2026

 

Fatal Neanderthal wound may be earliest evidence of a wooden spear attack on a human ancestor

University of Cambridge

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A video of a 3D rendering of the hole in the scapula and fragments embedded in the sediment underneath the scapula in situ prior to conservation.

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Credit: Dr Emma Pomeroy

• Circular hole in 75,000-year-old scapula suggests lethal conflict involving sharpened wooden spears among Neanderthals in the Middle East.
   
• Remains also show evidence of brutal facial injury at least a year before death, meaning Neanderthal was likely cared for prior to dying violently.

A round hole in the shoulder blade (scapula) of a Neanderthal whose partial remains were unearthed in a cave in Iraqi Kurdistan may be the earliest known example of lethal interpersonal violence with a wooden spear in the hominin fossil record.

The Neanderthal’s scapula – a broad, flat bone so thin in places it becomes almost translucent when held up to light – was preserved almost intact under seven-and-a-half metres of rock and sediment for around 75,000 years.

Intact, that is, apart from the 15mm-wide circular perforation, which Cambridge archaeologists who led the excavation say was made by a spear of sharpened wood, as a spear tip of flint or stone would leave a flat or angular hole.

The spear penetrated the left chest cavity from the front and travelled through the body – including lung and likely major arteries – before punching a hole in the left scapula, causing rapid death. Researchers think the fatal strike may have been an intended “heart shot”.

Bevelling around the hole is typical of an exit wound. The team found tiny shards of bone displaced by the weapon, the position of which suggests a spear entered from above at a downward trajectory. They were even able to piece back part of the hole using these fragments, guided by faint ridges where the bone was marked by muscle.

“It’s extraordinary to have a perfectly preserved scapula from 75,000 years ago. These bones are so thin that you often don’t get complete scapulae from modern burials,” said Dr Emma Pomeroy, study lead author from Cambridge’s Department of Archaeology. “We were able to lift it out in one piece from under almost eight metres of rock and sediment.”

Archaeologists call the remains Shanidar A, named for the famous cave in which they were found, and have published their findings in the journal Scientific Reports.

Due to decomposition, very few wooden objects survive from deep in prehistory. Some waterlogged examples of spears dated to around 200,000 years ago – when early Neanderthals roamed Europe – were found in Schöningen, Germany, in the 1990s.  

These preserved spears – some over two metres long – were manufactured from carefully-selected timber to have weight distribution optimised for throwing, like modern javelins, and were probably used for hunting large game.

The earliest known rounded wooden spear is over 400,000 years old. Just the pointed end survived, pulled from the UK shoreline at Clacton-on-Sea in 1911.

Similar technology may well have caused the death of Shanidar A, argue researchers. They say the wound could be the first evidence for use of sharpened wooden spears in the prehistoric Middle East.

“Holes left by recreations of spears from this time are an excellent fit for the one we found in the Neanderthal scapula,” said Pomeroy, a fellow at Newnham College, Cambridge. “That early technology absolutely works for this wound.”

“What evidence we have suggests that Neanderthals and their ancestors developed woodworking and weapon-making skills many thousands of years before the death of Shanidar A. This package of capabilities could have spanned the full range of Neanderthal homelands, from Wales to Siberia.”

Pomeroy points out that the death might have been a hunting accident. “Animals such as mammoths may have been hunted up close with thrusting spears, so it’s easy to imagine lethal injuries.”

However, she says there are hints of deliberate violence. “The position of the wound and the force required to push it right through the Neanderthal’s body bear the hallmarks of an intended kill shot directed towards the heart.”  

There is no way of knowing the context for the violence, and whether modern humans could have been involved, although archaeologists believe the most straightforward interpretation is interpersonal violence between Neanderthals.

“All we can ever know about the end of this Neanderthal’s life is that it was violent, and came at the end of a wooden spear,” said Prof Graeme Barker, fellow of St. John’s College, Cambridge, who leads the Shanidar Cave excavations.

“Evidence of systematic violence is extremely rare in deep prehistory. The vast majority comes from periods of settled farming communities thousands of years after hunter-gather societies like our Neanderthals.” 

Split tooth and signs of caring

The shoulder blade was excavated alongside a mostly complete right hand, two left ribs plus a right-rib fragment, and seven teeth – all that remains of an adult Neanderthal estimated to have been around 45 years old when they died violently.

One tooth, an incisor from the front of the lower jaw, had been split lengthways, with only half remaining, while surrounding teeth had been rotated inward.

The half-tooth had significant tartar (dental calculus) build-up along the exposed root canal, suggesting it stayed in the mouth for some time after what scientists say must have been major blunt-force trauma to the front of the face.

“Surviving a blow that splits a tooth in this fashion, then continuing to live and eat for a period of at least a year and maybe more, would have required care and support from other Neanderthals,” said Pomeroy.

Shanidar A may have been fed soft food after the initial injury, says Pomeroy. Previous research on sediment in Shanidar Cave shows that plant foods were being soaked before cooking around the same time. “There’s no doubt that Shanidar A would have had difficulty communicating and been in absolute agony for a long period of time.”

“The remains of Shanidar A reflect the dual nature of so much of what we recognise as human. On the one hand, we have evidence of a terribly violent end. On the other, this was clearly an individual who was cared for during their lifetime.”

Prof Barker said: “It is fascinating to have evidence for both compassion and violence amongst Neanderthals, our closest evolutionary cousins, embodied in this one individual.” 

‘Funerary behaviour’

The vast cave in the foothills of Iraqi Kurdistan known as Shanidar is one of the world’s most famous Neanderthal sites. Excavations in the 1950s led by Ralph Solecki found ten individuals, including a “cluster” of four located in the same spot despite dying at different times, suggesting the Neanderthals had returned to inter their dead.

Remains of a Neanderthal from another part of the cave, who lived thousands of years later, showed evidence of a paralysed arm, arthritis, deafness and partial blindness. Yet they had lived a long life, so must have been cared for.

These signs of compassion, social support, and ritual around death, led to a revision of the Victorian view of Neanderthals as brutish and subhuman. Evidence of sophistication has continued to emerge, from cave art to jewellery, along with genetic analysis showing interbreeding between Neanderthals and modern humans.

Shanidar A was unearthed in 2020, and is one of three further Neanderthals found in the burial cluster by the Cambridge-led team since 2015, taking the total to five – four adults and an infant – in an area of the cave just 1.5 metres long by one metre wide, and a metre deep.

The spot is located directly behind a large vertical boulder, a “prominent marker”, and the remains are separated by thin layers of sediment. Shanidar A is the deepest yet found in the cluster, and possibly the first lain to rest in the space, positioned on their back, head facing east, as with the body directly above.

“The best explanation is intentional and symbolic funerary behaviour,” said Pomeroy. “These Neanderthals returned to the same place to lay their dead to rest. Some were deposited before the earlier body had fully decomposed, so this was happening within years or decades.”

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Journal

Scientific Reports

DOI

10.1038/s41598-026-69193-z

Article Title

Evidence for funerary behaviour and lethal trauma in a new Neanderthal individual from Shanidar Cave

Article Publication Date

15-Oct-2026

The ventral (left) and dorsal (right) views of the Shanidar A scapula. Ventral is the front of the scapula, the side that faces the ribs (chest). Dorsal is the back of the scapula.

Credit

Dr Emma Pomeroy

View of the entrance to Shanidar Cave in Iraqi Kurdistan.

Credit

Prof Graeme Barker

Various views of the mandibular left lateral incisor that had been spilt longitudinally. Views of the tooth, from left to right: top (chewing surface), bottom (root end). Middle: toward the front of the dental arch (mesial), toward the lips (labial), toward the back of the dental arch (distal), and toward the tongue (lingual).

 

The hole in the scapula and the fragments found embedded in the sediment below the perforation. Top left: Ventral view of the hole in the scapula, showing two refitting fragments. Top right: The linea muscularis, highlighted by the dashed line, indicates that the fragments are correctly refitted. Bottom: 3D rendering of the hole and fragments embedded in the sediment underneath the scapula in situ prior to conservation.

Credit

Dr Emma Pomeroy

The left scapula of Shanidar A, photographed in the University of Cambridge’s Leverhulme Centre for Human Evolutionary Studies.

Credit

University of Cambridge

B roll of the scapula of Shanidar A [VIDEO]