The researchers found “remarkably large” fossilized teeth belonging to a previously unknown species called Yakamys sirindhornae. This prehistoric rodent lived approximately 34 million years ago, during the middle of the Paleogene period. Its remains, consisting of a lower second molar and a lower incisor, were recovered from the Bang Mark Pit at the Krabi lignite mine in Thailand’s Krabi Province.

Although only two teeth have been identified, they offer valuable clues about rodent gigantism, the evolutionary process through which rodents develop unusually large bodies. The discovery suggests that Southeast Asia played a more significant role in the early evolution of giant rodents than scientists had recognized.

Giant Rodents Have a Much Older History Than Expected

“Today, the largest living rodent is the capybara, but very large rodents are not restricted to recent ecosystems,” said Virginie Millien, a biology professor at McGill University and co-author of the study. “Giant rodents evolved repeatedly during the later history of the group, mostly in South America. This discovery suggests that Southeast Asia also played an important role in the early evolutionary history of large-bodied rodents.”

The newly identified animal’s name reflects both its impressive size and its connection to Thailand. Yakamys combines “yak,” the Thai word for giant, with “mys,” the Greek word for mouse or rat.

The second part of its scientific name recognizes an important supporter of scientific research in Thailand.

“The species name, sirindhornae, honors Princess Maha Chakri Sirindhorn, in recognition of her longstanding support for science and paleontological research in Thailand,” Millien said.

How Big Was This 34-Million-Year-Old Rodent?

To estimate the animal’s size, the research team applied seven established methods that use tooth measurements to calculate body mass. Their results suggest that Yakamys sirindhornae weighed approximately 30 kilograms, making it about twice as heavy as other known rodents from the same period, including Hulgana.

That would have made the newly discovered species exceptionally large compared with its contemporaries. However, the researchers emphasize that determining an extinct animal’s weight from a small number of fossilized teeth involves considerable uncertainty.

“This is only a ballpark figure, as there is substantial uncertainty associated with fossil body-mass estimation,” Millien said.

The limited fossil evidence also makes it difficult to reconstruct how Yakamys evolved or what its life was like. Additional discoveries will be needed to better understand its physical characteristics, ecological role, and evolutionary relationships.

International Research Uncovers Thailand’s Prehistoric Past

The fossils were identified through an ongoing international collaboration investigating ancient mammals in Thailand’s Krabi Basin. The project brings together scientists from McGill University, Thailand’s Department of Mineral Resources, and French research organizations, including CNRS and Université de Poitiers.

By revealing evidence of an unusually large rodent in Southeast Asia 34 million years ago, the discovery expands scientists’ understanding of where and when rodent gigantism emerged. Future fossil finds could help establish how these ancient giants lived and how their evolution relates to the enormous rodents that appeared elsewhere in the world.

The research received support from CNRS, Université de Poitiers, Université de Montpellier, McGill University, and the Department of Mineral Resources of Thailand.

The discovery comes from an international team at the University of California, Davis, Peking University, and the Geological Museum of Guizhou. Their findings, published in Nature Ecology & Evolution, are based on two exceptionally well-preserved skeletons dating back nearly 237 million years to the Late Triassic period.

Both fossils were uncovered in China’s Guizhou Province, in a region that was once submerged beneath an ancient ocean hundreds of miles from major landmasses.

“This area is part of an ecosystem that we’ve been looking at and trying to reconstruct,” said study corresponding author Ryosuke Motani, a professor in the Department of Earth and Planetary Sciences at UC Davis. “We’ve been mostly studying marine reptiles and the fish from this place, but now we also have this amphibian, and it’s a sort of very unusual member of the lineage.”

The finding is especially surprising because amphibians are generally unable to survive in seawater. Among the more than 8,000 amphibian species living today, none are known to spend their entire lives in marine environments, and fewer than 2% have any ability to tolerate salt.

Mammals, reptiles, and birds, by comparison, all include species that can live entirely at sea without relying on land for food or fresh water. Until this discovery, scientists had never identified convincing fossil evidence of an amphibian with the same ability.

A Giant Armored Amphibian Built for the Seafloor

Because the two skeletons are so complete, researchers were able to piece together the animal’s appearance and develop a clearer picture of how it lived.

Gerrothorax maritimus measured nearly three feet long, but its proportions were far different from those of a modern salamander. Rather than having a long, slender body, it was unusually broad and flattened, with a distinctive disc-shaped form.

Its body was also covered in thick bony armor, which may have helped protect it from large marine predators such as ichthyosaurs.

“If you think about today’s amphibians, this animal is unusual because it’s big,” Motani said. “It’s probably, body mass-wise, about the same as the giant salamander, but what’s different is that giant salamanders are elongated whereas this animal is really chunky.”

The structure of its skull, together with its heavy armor, suggests that this ancient amphibian was an ambush predator. Instead of actively chasing its meals, it likely rested on the seafloor until an unsuspecting animal came within reach.

“They would probably just wait at the bottom and then when prey comes around, they would just suck it in,” said Motani, who noted that the hunting strategy resembles that of the wobbegong, a type of carpet shark that lives near the seafloor and captures prey using suction.

How Could an Amphibian Survive in Salt Water?

One of the biggest mysteries surrounding Gerrothorax maritimus is how it managed to survive in an environment that is hostile to nearly all modern amphibians.

The problem comes down largely to amphibian skin. Unlike the relatively waterproof skin of many other animals, amphibian skin allows water and gases to pass through it. This makes it useful for breathing and maintaining hydration, but also leaves amphibians especially vulnerable to the effects of salt water.

“That skin is permeable, and that allows the animals to use it for multiple purposes,” said Motani. “They use it for respiration and water intake, so amphibians don’t drink or breathe through the mouth because they can do both through the skin.”

As a result, modern amphibians generally depend on freshwater habitats or environments close to them. A few species have developed limited salt tolerance, including the crab-eating frog. Even these animals can lose weight when exposed to brackish water and must eventually return to freshwater to recover.

The ancient Gerrothorax maritimus, however, may have evolved a very different solution.

Researchers suggest that its extensive bony armor restricted the movement of water through its skin. This protective covering may have reduced its dependence on absorbing water directly through the skin, allowing the animal to take in seawater through its mouth instead.

Under this proposed mechanism, water would have been absorbed through the digestive tract, while the animal’s gills could have helped eliminate excess salt. Gills are known to have been present in members of the Gerrothorax genus, giving the researchers reason to suspect that this species possessed a more fishlike approach to managing its salt balance.

Together, these adaptations may explain how an amphibian managed to occupy an ecological niche that remains inaccessible to its modern relatives.

Fossil Evidence Points to a Fully Marine Lifestyle

The researchers also examined whether Gerrothorax maritimus truly lived in the ocean or whether its remains might have been transported there after death.

Several clues strongly favor a marine lifestyle.

First, the skeletons were recovered from sediments deposited in a deep marine environment. Their remarkable completeness also provides important evidence about where the animals died.

“Carcasses at sea, unless they sink to the bottom right away, tend to dry out and lose limbs prior to sinking to the bottom,” said Motani. “But these animals had their fingers preserved, so that means they probably died near where they lived.”

The preservation of such delicate skeletal structures suggests that the bodies were not carried long distances before reaching the seafloor.

To investigate further, the team analyzed the fossils’ chemical composition, focusing on the relative abundance of different forms of strontium, known as isotopes.

The results closely matched the strontium isotope signatures expected in ocean water during the Late Triassic, providing another independent line of evidence that the animals inhabited a marine environment.

Taken together, the fossil preservation, geological setting, and chemical findings make a compelling case that Gerrothorax maritimus spent its life entirely at sea.

The discovery reveals an unexpected evolutionary path for amphibians, showing that at least one ancient species appears to have overcome the biological limitations that keep its living relatives largely confined to freshwater environments.

The research received funding from the National Natural Science Foundation of China.

Heart disease remains one of the world’s leading causes of death. According to the World Health Organization (WHO), cardiovascular diseases kill nearly 17.9 million people worldwide each year, with heart attacks and strokes responsible for more than 80% of those deaths. Coronary heart disease develops when fatty deposits containing cholesterol (cholesterol) build up inside the arteries that supply blood to the heart. If left untreated, the condition can eventually cause a heart attack.

Reducing LDL cholesterol, commonly known as “bad cholesterol,” is a proven way to lower the likelihood of a heart attack. However, bringing LDL cholesterol into the recommended range does not eliminate the danger. Some patients continue to develop coronary heart disease despite successful treatment, suggesting that other particles transporting fats through the bloodstream play an important role. Until recently, the biological reasons behind this remaining risk were not well understood.

“For this study, we wanted to understand what happens beyond the accumulation of cholesterol in artery walls, whether different fat-carrying particles can damage the blood vessels differently and why the remaining risk of heart disease still occurs,” says Jakub Morze, lead author and a postdoctoral fellow at Chalmers University of Technology, in Sweden.

What Is Bad Cholesterol?

Cholesterol is a substance similar to fat that circulates in the bloodstream. The body needs it to build cells and manufacture certain vitamins and hormones. Problems can arise when too much cholesterol accumulates in blood vessel walls, creating deposits called plaques.

These plaques can narrow arteries and interfere with blood flow. If a plaque ruptures, a blood clot may form quickly and completely obstruct the affected vessel, potentially triggering a heart attack or stroke.

Because cholesterol and other fats cannot travel through the blood on their own, they are transported by specialized particles known as lipoproteins. Three major classes of these particles contain a surface protein called apolipoprotein B (apoB). When too many of these particles circulate in the blood, they can deliver excess cholesterol into artery walls. The cholesterol they carry is commonly referred to as “bad cholesterol.”

Looking Beyond Bad Cholesterol

To investigate these unanswered questions, the scientists used proteomics analysis to examine how three types of fat-carrying particles (LDL, TRL and Lp(a)) affect the body and may contribute to heart disease. This approach allowed the team to investigate biological changes associated with the particles rather than focusing exclusively on the cholesterol they carry.

All three types can contribute to cholesterol deposits inside artery walls, although LDL, which stands for low-density lipoprotein, is the most common. In a previous study, the same research group found that counting harmful lipoprotein particles was the most effective way to predict future heart disease risk.

The researchers also identified two particularly important contributors beyond LDL: triglyceride-rich lipoproteins, or TRL, and lipoprotein(a), known as Lp(a). Their earlier findings suggested that each of these particles poses a greater risk individually than an LDL particle. As a result, TRL and Lp(a) are considered major contributors to the cardiovascular danger that can persist even after LDL cholesterol has been successfully reduced.

What Is Proteomics Analysis?

Proteomics is the systematic, large-scale examination and measurement of proteins within cells, tissues, or body fluids at a particular point in time.

While genomics investigates a person’s relatively stable DNA, proteomics focuses on proteins, which are constantly responding to changes inside the body. These molecules help construct tissues, process food, transmit hormonal messages, and defend against infections.

Because protein patterns shift in response to factors such as diet, stress, aging, and disease, analyzing them can provide a snapshot of current biological activity. Proteomics can help researchers identify biomarkers, diagnose medical conditions, and track how patients respond to treatment.

Blood Proteins Reveal Hidden Heart Disease Risks

The new investigation focused on proteins, which perform countless essential functions throughout the body. Unlike genetic information, which remains largely unchanged, protein levels and activity can respond to diet, stress, aging, and illness. Studying these changes can therefore provide valuable insights into the body’s current biological condition.

Researchers analyzed measurements of nearly 3,000 proteins found in blood samples and compared the results with genetic information and long-term health records. This combination helped them identify protein patterns associated with different lipoprotein particles and provided clues about how those particles might contribute to damage inside the arteries.

One of the most striking discoveries involved TRL and Lp(a). Although these are distinct types of particles, their associated blood protein patterns showed substantial similarities. Those overlapping patterns also appeared to be linked to the later development of heart disease.

The researchers found that these particles carried proteins capable of attracting immune cells, potentially encouraging inflammation and changes in the structure of blood vessel walls. This suggests that TRL and Lp(a) may contribute to cardiovascular disease through some of the same biological processes, rather than simply depositing cholesterol in the arteries.

LDL showed a different pattern. Its associated proteins were primarily connected to cholesterol accumulation in artery walls, highlighting an important distinction between the ways these three types of particles may contribute to heart disease.

“The overlap for TRL and Lp(a) is one of the most interesting findings,” says Morze. “It suggests that these particles may affect some of the same inflammatory and vascular processes. This could help identify targets for more precisely directed prevention in the future.”

How LDL, TRL, and Lp(a) Affect Heart Health

The three types of lipoproteins examined in the study, LDL, TRL, and Lp(a), transport different amounts of cholesterol and other fats through the bloodstream. Each contains the structural protein apolipoprotein B, or apoB.

All three can contribute to atherosclerosis, a condition in which fatty material accumulates inside blood vessel walls. As these deposits develop, they increase the risk of coronary heart disease.

LDL: Low-density lipoprotein transports most of the cholesterol circulating in the blood. An LDL cholesterol measurement indicates how much cholesterol is contained within these particles.

TRL: Triglyceride-rich lipoproteins transport cholesterol along with triglycerides, which the body uses as an important energy source. As triglycerides are removed from these particles, the remaining fragments can deposit cholesterol inside artery walls. In this study, the TRL measurements primarily reflected liver-produced particles called VLDL and the remnants they leave behind.

Lp(a): Lipoprotein(a) resembles an LDL particle but contains an additional protein known as apolipoprotein(a). Higher levels of Lp(a) are already recognized as an established risk factor for coronary heart disease.

Could the Discovery Lead to Better Heart Disease Prevention?

By identifying biological pathways associated with cardiovascular risk beyond LDL cholesterol, the findings offer researchers new possibilities for developing more personalized prevention strategies. In particular, the shared inflammatory and blood vessel effects linked to TRL and Lp(a) could become promising areas for further investigation.

However, the research did not evaluate a new treatment or establish a blood protein test ready for routine clinical use. Additional studies will be needed to determine whether measuring these biological processes, or developing treatments that target them, can improve protection against heart disease.

“Lowering LDL cholesterol remains a cornerstone of prevention,” says Clemens Wittenbecher, who led the study and is Assistant Professor of Precision Medicine and Diagnostics at Chalmers. “Our findings point to biological processes that may help explain some of the risk that remains beyond LDL. The next step is to establish whether measuring or targeting these processes can improve prevention alongside existing treatments.”

The results reinforce the importance of controlling LDL cholesterol while revealing why cholesterol reduction alone may not address every source of cardiovascular risk. Understanding the additional ways blood particles affect arteries could ultimately help scientists develop more precise approaches to protecting heart health.

Study Details and Research Institutions

The study, “Apolipoprotein B-containing lipoproteins: distinct roles in atherosclerosis revealed by plasma proteomic profiling,” was published in the European Heart Journal.

The research authors are Jakub Morze, Elias Björnson, Michael Y Mi, Martin Adiels, Giorgio E Melloni, Gonçalo Rosas da Silva, Andrzej Rynkiewicz, Nicholas A Marston, Marta Guasch-Ferré, Michael Y Tsai, Jerome I Rotter, Robert E Gerszten, Qi Sun, Frank B Hu, Rikard Landberg, Göran Bergström, Chris J Packard, Jan Borén and Clemens Wittenbecher.

At the time of the research, the authors were affiliated with Chalmers University of Technology and the Institute of Medicine at the University of Gothenburg, Sweden; Harvard Medical School, USA; AstraZeneca, Sweden; Municipal Hospital in Olsztyn, Poland; University of Copenhagen, Denmark; University of Minnesota, USA; The Lundquist Institute at Harbour-UCLA Medical Center in Torrance, USA; Harvard T.H. Chan School of Public Health in Boston, USA; and the University of Glasgow, UK.

Scientists at the University of Central Florida (UCF) have discovered that genetic mutations associated with Alzheimer’s can interfere with the nerves that control muscle movement, even without involvement from the brain or spinal cord. The findings could help explain why some people with Alzheimer’s experience changes in walking, balance, or coordination long before noticeable memory problems emerge.

The discovery raises the possibility that movement difficulties could provide earlier warning signs of the disease and that treatments focused exclusively on the brain may overlook important problems elsewhere in the body.

The research was led by James Hickman, a professor at UCF’s Nanoscience Technology Center, and Research Professor Xiufang “Nadine” Guo, working alongside scientists at the healthcare technology company Hesperos. Funded by the National Institutes of Health’s National Institute on Aging, the study used laboratory systems built from human cells to investigate how inherited Alzheimer’s mutations affect movement. The findings were published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

“Motor deficits may be an earlier indication [of Alzheimer’s],” Guo says. “If we can detect those changes and intervene earlier, that could help delay the onset of central nervous system symptoms.”

Why Alzheimer’s Symptoms May Appear Before Memory Loss

Alzheimer’s is generally associated with progressive memory loss, confusion, and declining cognitive abilities. However, doctors have also observed that some patients develop physical symptoms, including changes in balance, coordination, and gait (manner of walking), years before clear cognitive difficulties become apparent.

These observations have raised an important question: Are such movement problems simply a consequence of damage occurring in the brain, or could Alzheimer’s also interfere directly with nerves elsewhere in the body?

To investigate, the UCF team focused on familial Alzheimer’s, a rare inherited form of the disease that typically develops earlier in life (from 40 to 65 years of age) than the more common form.

Their experiments revealed that motor neurons carrying mutations linked to familial Alzheimer’s could disrupt the connections responsible for controlling muscles, even when the brain and spinal cord were completely absent from the experimental system.

Motor neurons are specialized nerve cells that transmit signals to muscles, telling them when to contract and produce movement. The new findings suggest that Alzheimer’s mutations can interfere with this process directly, rather than affecting movement only through damage to the brain.

“This is the first time it’s been demonstrated that deficits in the peripheral nervous system can arise directly from these mutations,” Hickman says. “It means drugs that target the brain may not fix problems in the rest of the body.”

The peripheral nervous system includes the nerves located outside the brain and spinal cord. These nerves carry signals between the central nervous system and the rest of the body, helping control movement, sensation, and other essential functions.

Guo also points out that preserving the ability to move could have benefits beyond physical health. Regular physical activity is associated with better cognitive well-being, so protecting motor function may also help support brain health.

How a Miniature Human Cell System Revealed the Discovery

To examine the relationship between Alzheimer’s mutations and muscle movement, the scientists used an innovative laboratory platform known as “human-on-a-chip” technology.

Developed and manufactured through Hesperos, a company co-founded by Hickman, these miniature systems bring different types of human cells together under controlled conditions. They allow researchers to recreate specific biological functions and observe how diseases interfere with them.

Unlike conventional laboratory experiments that examine isolated cells, these systems can reproduce important interactions between different tissues. They also provide an alternative to animal models, which do not always accurately reflect how human diseases behave.

For this study, the team created a miniature model of the neuromuscular junction, the connection where a motor neuron communicates with a muscle cell.

The model was deliberately designed without a brain or spinal cord. This was a crucial part of the experiment because it allowed the researchers to investigate whether Alzheimer’s-related changes could cause movement problems independently of the central nervous system.

The scientists combined healthy muscle cells with motor neurons derived from stem cells that carried genetic mutations associated with familial Alzheimer’s disease. Stem cells are cells that can develop into specialized types of cells, making them valuable tools for studying human diseases in the laboratory.

The researchers then examined how effectively the altered nerve cells communicated with otherwise healthy muscle tissue.

The results showed that the Alzheimer’s-associated mutations could interfere with normal nerve-to-muscle function. This suggests that at least some movement difficulties linked to the disease may arise directly in the peripheral nervous system rather than being caused entirely by degeneration in the brain.

Why Damaged Nerve Connections Can Affect Walking and Balance

Every voluntary movement depends on successful communication between the nervous system and the muscles.

At the neuromuscular junction, an electrical signal traveling along a motor neuron triggers chemical communication that causes a muscle to contract. This process makes everyday activities possible, from walking and maintaining posture to lifting objects and performing precise movements.

When the connection becomes impaired, muscles may respond less effectively to nerve signals. Depending on the severity and location of the problem, this can contribute to weakness, reduced coordination, and difficulty sustaining physical activity.

To evaluate these effects, the research team measured how consistently nerve signals produced muscle contractions and how long the muscles could continue contracting before becoming fatigued.

These measurements provided a direct assessment of how well the nerve and muscle cells worked together. They also resemble aspects of the functional testing physicians use when examining patients with movement disorders.

“You can’t move unless the motor circuit works,” Hickman says. “When a doctor taps your knee to check your reflex, they’re testing that exact connection.”

By demonstrating impaired nerve-to-muscle communication in a system containing no brain or spinal cord, the study provides evidence that mutations linked to familial Alzheimer’s can produce effects beyond the central nervous system.

However, the experiments do not establish that these changes necessarily occur before memory loss in patients. Further research will be needed to determine how closely the laboratory findings reflect the progression of Alzheimer’s in people, particularly those with the more common forms of the disease.

Could This Discovery Lead to Earlier Alzheimer’s Detection?

The findings suggest a potentially important new direction for Alzheimer’s research: looking beyond memory and other cognitive symptoms when investigating the disease.

If future studies confirm that changes in motor function are detectable early in certain patients, tests of walking, coordination, or nerve-to-muscle activity might eventually help identify disease-related changes before more obvious neurological symptoms develop.

The results also raise questions about treatment. Many Alzheimer’s therapies are designed to address processes occurring in the brain, but medications that target the central nervous system may not necessarily correct abnormalities affecting peripheral nerves and muscles.

Understanding these separate effects could help researchers investigate treatments that protect physical function alongside cognitive health.

Human-on-a-Chip Technology Could Transform Disease Research

Beyond the implications for Alzheimer’s, the researchers see considerable potential in using human-on-a-chip systems to investigate other diseases and evaluate possible treatments.

Because these platforms contain human cells and reproduce measurable biological activities, they can help scientists observe disease-related changes in conditions that more closely resemble human physiology than some conventional experimental models.

This approach may be particularly useful in drug development, where researchers need to understand not only how a potential treatment affects individual cells but also how it influences interactions between different tissues.

Such systems can also uncover biological effects that may be difficult to detect in animal experiments, potentially helping researchers identify promising therapies and recognize limitations earlier in development.

For Hickman, the progress represents the culmination of three decades of work devoted to understanding disease through more realistic laboratory models.

“These systems let us study disease in a way that’s closer to what actually happens in the human body, and that’s what we need to develop better treatments,” he says.