Penn State researchers have now identified a previously unrecognized structure that may control much of this activity. The structure is a lattice located just beneath the surface of neurons and is known as the membrane-associated periodic skeleton, or MPS.

A Hidden Gatekeeper Inside Neurons

In findings published in Science Advances, the team showed that the MPS acts as a physical gatekeeper for nearly every major type of endocytosis. Built from repeating rings of proteins, the structure was already known to help neurons retain their shape. The new results indicate that it also plays a much more active role by controlling where and when substances enter the cell.

“For many, many years we have been trying to understand this molecular mechanism, what kind of machinery will help to facilitate this process, because it’s connected to neurodegenerative diseases,” said Ruobo Zhou, assistant professor of chemistry, of biochemistry and molecular biology, and of biomedical engineering, at Penn State and corresponding author on the study. “When endocytosis — this nutrient uptake and regulation — goes wrong, then there’s protein aggregation that will build up in the brain, which is the hallmark of neurodegenerative diseases such as Alzheimer’s and Parkinson’s.”

Zhou helped discover the MPS in 2013 while working as a postdoctoral researcher on a Harvard team. At the time, scientists believed the structure mainly served as a passive internal support system. In the new study, Zhou and colleagues used super-resolution imaging on neurons grown in the laboratory and found that the MPS behaves more like a cellular traffic controller, regulating all major forms of endocytosis.

Watching Cellular Uptake at the Nanoscale

The researchers relied on advanced super-resolution microscopy, which can reveal structures at the nanoscale — about 10,000 times smaller than the thickness of a human hair. They studied neurons grown in petri dishes and caused selected proteins to form inside the cells so those proteins could be tracked.

The scientists then exposed the neurons to different molecules and observed how the cells absorbed them while the MPS remained intact. They also altered the structure by damaging or protecting specific sections, allowing them to see how neurons responded when the lattice changed.

When the MPS was disrupted, the neurons began absorbing material much faster. This indicated that the lattice normally slows the process and prevents excessive uptake.

The researchers also discovered that the structure can contribute to its own breakdown. Faster endocytosis weakened the lattice and triggered a positive feedback loop. Increased uptake activated molecular signals that directed proteins inside the neurons to cut apart sections of the skeleton. That opened additional entry points and allowed even more nutrients and proteins to enter.

“We discovered that this membrane skeleton is actively regulating the nutrient uptake process of neurons,” Zhou said. “You can think of it as a gatekeeper, guarding this physical barrier to not allow nutrient uptake to happen. When a neuron needs to take in a specific nutrient, this gatekeeper will open the gates and let it in.”

Zhou explained that this flexibility may allow neurons to increase their activity when they need to respond quickly. However, the same mechanism could become harmful if it is no longer properly controlled.

A Possible Link to Alzheimer’s Disease

To investigate that possibility, the researchers created cellular experiments that resembled the early stages of Alzheimer’s disease. They caused neurons to produce higher levels of amyloid precursor protein (APP), a key marker associated with the disease.

Weakening the MPS caused neurons to take in APP more rapidly. After entering the cells, APP was cut into amyloid-B42, a toxic fragment strongly associated with Alzheimer’s disease. Neurons with a damaged MPS accumulated increasing amounts of this harmful molecule and displayed more markers of cell death.

“We created a model which is very much like Alzheimer’s disease and found that in some aging neurons, or neurons under pathologic conditions, the endocytosis of toxic proteins was enhanced, which caused stressing conditions, ultimately leading to neuron deaths,” said Jinyu Fei, a graduate student in the chemistry department in Penn State’s Eberly College of Science and lead author on the study.

A Potential New Treatment Target

The results suggest that the MPS may act as a protective barrier in neurons by slowing APP uptake and limiting the accumulation of toxic molecules. Because the structure is known to deteriorate during aging and neurodegenerative disease, its breakdown could push neurons into a damaging cycle involving greater amyloid production, further structural weakening, and eventual cell death.

The researchers said that protecting or stabilizing this lattice may offer a new way to slow neurodegeneration.

“We think this could open the door for future therapies such as a protein target for neurodegenerative disease treatment,” Fei said. “Preserving or stabilizing the MPS might offer a way to slow the early, hidden cellular changes that precede Alzheimer’s symptoms.”

Other authors on the paper are Yuanmin Zheng, doctoral candidate in biomedical engineering; Caden LaLonde, fourth-year undergraduate student majoring in biochemistry and molecular biology; and Yuan Tao, graduate student at Penn State’s Huck Institutes of Life Sciences.

The National Institutes of Health funded this work.

Animals consistently show fear when people pose a direct lethal threat, such as through hunting or fishing. Their reactions to non-lethal human activity, however, are much less predictable.

How Wildlife Responds to Human Threats

The meta-analysis, published in Ecology Letters, brought together three decades of research examining how wild animals alter their behavior around humans. The researchers compared changes in feeding, vigilance, and movement across many species and ecosystems to determine whether people are always perceived as an extreme danger.

“The short answer is: no, not always,” says Shawn D’Souza, PhD student at CES and the study’s lead author. “We found strong evidence that lethal humans such as hunters and fishers are indeed perceived as threatening. Animals in areas exposed to lethal humans tend to be more vigilant and spend less time foraging. In contrast, responses to non-lethal humans such as tourists or researchers are weaker and more variable.”

Roads and Settlements Can Feel Safer

One of the more unexpected findings was that human infrastructure, including roads and settlements, sometimes caused animals to become less watchful.

“In certain cases, these areas can function as perceived refuges,” D’Souza explains. “Predators often avoid humans, which can make areas near people feel safer for some prey species.”

Co-author Maria Thaker, Professor at CES, says another factor may be the open vegetation commonly found beside roads. These cleared spaces can provide appealing grazing areas for smaller animals. However, feeding near roads also exposes them to the danger of being struck by vehicles.

The Costs of Staying Alert

The researchers focused on foraging, vigilance, and movement because each behavior reflects the difficult choices animals make when assessing danger.

Every moment spent scanning for threats is time taken away from feeding. Changes in movement can also affect how much energy an animal uses and whether it can reach food, shelter, or other important resources. Because these behaviors influence survival and reproduction, they can reveal how fear of people may shape wildlife populations over time.

Animals Adjust to the Level of Risk

The findings generally support the “risk allocation hypothesis,” which proposes that animals change their behavior according to how severe and predictable a threat appears.

When danger is frequent and intense, animals tend to remain cautious, D’Souza says. When a threat is limited or occurs in a predictable way, wildlife may be more willing to relax and resume normal activities.

These decisions can also have consequences far beyond a single animal. Changes in feeding, movement, and fear can spread through ecosystems, affecting grazing patterns, predator-prey relationships, and broader ecological stability.

Possible Implications for Wildlife Conflict

Co-author Kartik Shanker, Professor at CES, says the behavioral effects of lethal human activity could have implications for managing conflict between people and wildlife. According to Shanker, limited culling may sometimes discourage wild animals from entering human-dominated areas more effectively than several other approaches currently in use.

The researchers say more work is needed to predict how different species will respond in different environments.

“We need more predictive frameworks that link behavioral responses to ecological and evolutionary context. That includes incorporating species traits, past exposure to humans, predator communities, and landscape structure,” says D’Souza.

He adds that long-term and experimental research will be essential for determining whether animals are simply becoming accustomed to human activity or experiencing deeper evolutionary changes.

The discoveries were made by researchers at the University of Warwick and the University of Colorado Boulder. Their findings were published in the Monthly Notices of the Royal Astronomical Society (MNRAS).

White Dwarfs Hidden by Brighter Companions

Each white dwarf orbits alongside a red dwarf star. Because the red dwarfs appear larger and brighter, the systems looked like they contained only a single star when viewed in visible light.

The new observations revealed that all four nearby red dwarfs were concealing white dwarf companions.

First author, Dr. Mairi O’Brien, Research Fellow, University of Warwick said: “Nearby isolated white dwarfs are usually easy to find, but we couldn’t see these four stars directly in visible wavelengths because their red dwarf companions were drowning out their light. It’s a reminder that even in our own cosmic neighborhood, we can still find surprises if we look in the right way, at the right wavelengths.”

Astronomers have spent decades carefully cataloging stars near the Sun, yet white dwarfs in systems like these remain difficult to detect. The four systems attracted attention because their visible stars showed a pronounced radial wobble.

This motion occurs when a star moves slightly toward and away from Earth as an unseen, massive object pulls on it while orbiting. The wobble suggested that each red dwarf had a hidden companion.

Hubble Ultraviolet Data Reveals the Stars

The researchers used ultraviolet spectrograph data from the Hubble Space Telescope to examine the four systems in greater detail.

White dwarfs are generally much easier to recognize in ultraviolet light. Red dwarfs, however, can produce powerful flares that imitate the ultraviolet signal of a white dwarf, making confirmation more difficult.

To separate the true signals from the effects of stellar flaring, the team developed specialized calibration methods. This analysis officially confirmed that all four systems contained white dwarf stars.

A White Dwarf Hidden for 27 Years

One of the systems, G 203-47, was especially puzzling. Although it is located only 25 light-years away, astronomers needed 27 years after first detecting its radial wobble to identify the hidden white dwarf.

The object is now recognized as the ninth closest white dwarf to the Sun.

G 203-47 also behaves differently from similar binary systems. Its red dwarf takes more than 100 days to complete one rotation, even though it circles the white dwarf every 14.9 days.

Under normal circumstances, the gravitational interaction between two closely orbiting stars would be expected to synchronize their motion through tidal locking. The Moon and Earth provide a familiar example, since the same side of the Moon continually faces Earth.

In G 203-47, however, the red dwarf rotates far too slowly to be synchronized with its orbit.

Coauthor Dr. David Wilson, Research Associate, University of Colorado Boulder, said: “What’s fascinating is that G 203-47 shouldn’t be rotating this slowly if it formed the same way as similar systems. This suggests that these binaries have had very different evolutionary histories. Some underwent violent, prolonged interactions early on that locked them tidally. Others, like G 203-47, experienced gentler, briefer encounters that left them in this unusual state.”

Clues About Binary Star Evolution

The unusual rotation of G 203-47 suggests that not all white dwarf and red dwarf pairs developed through the same process.

Some systems may have experienced long and intense interactions early in their histories, causing the stars to become tidally locked. Others may have interacted for a shorter period and with less force, leaving their rotations unsynchronized.

The four discoveries have also allowed astronomers to revise the census of white dwarfs within 20 parsecs (65 light-years).

Previous population models predicted that roughly 4 to 5 closely orbiting white dwarf and red dwarf systems should exist in this region. The researchers identified exactly four, closely matching those theoretical estimates.

More Hidden White Dwarfs May Be Nearby

The discoveries may not complete the picture. Most nearby red dwarfs have not yet been systematically examined for concealed white dwarf companions.

Professor Pier-Emmanuel Tremblay, Astronomy and Astrophysics Group, University of Warwick, said: “Only about 30 percent of red dwarfs within 20 parsecs have been systematically surveyed for hidden white dwarf companions. We think there could be as many as 9 or 10 additional binary systems in our local stellar environment that we haven’t found yet. If we put more targeted effort into observing red dwarfs, perhaps we will find more surprises like this.”