Category: 7. Science

Aging and neurodegeneration are both known to disrupt the production of functional proteins in cells – a process called “proteostasis,” or protein homeostasis. Brain cells in particular fall prey to proteostasis disruptions, which are linked to the accumulation of protein aggregates in neurodegenerative diseases. In a new study published July 30 in Science, Stanford researchers have discovered the cascade of events that leads to declining proteostasis in aging brains.

The findings, based on study of the turquoise killifish, lay the foundation for developing therapies that can combat and prevent neurodegenerative diseases in people – and the gradual decline in mental abilities we will all face one day. 

We know that many processes become more dysfunctional with aging, but we really don’t understand the fundamental molecular principles of why we age. Our new study begins to provide a mechanistic explanation for a phenomenon widely seen during aging, which is increased aggregation and dysfunction in the processes that make proteins.” 

Judith Frydman, study author, the Donald Kennedy Chair in the School of Humanities and Sciences at Stanford

Locating the problem 

The turquoise killifish, Nothobranchius furzeri, is a vibrantly colorful fish that adapted to thrive in the ephemeral freshwater pools of the African savanna. Killifish, the shortest-lived vertebrates bred in captivity, develop many issues as they grow old and provide a great model of accelerated aging. Studying why and how the brain ages would be harder in longer-lived animals, such as mice.

To make their new discovery, the researchers conducted a comprehensive investigation of proteostasis in the brains of aging killifish. The scientists compared young, adult, and old killifish. They looked at various players in protein production, such as amino acid concentrations, levels of transfer RNA, messenger RNA (mRNA), proteins, and more. 

In cells, proteostasis balances protein synthesis and degradation and also prevents protein aggregation – harmful clumps of proteins that can result from errors in protein folding. Proteostasis dysfunction and aggregation are part of a series of molecular and cellular changes classified as aging hallmarks. Proteostasis has received attention as a likely link between brain aging and neurodegenerative diseases tied to protein aggregation, like Alzheimer’s.

Frydman’s lab explores how cells achieve proteostasis and has previously focused on how aging affects proteostasis in the simple models of aging provided by yeast and roundworms. The new study confirms that aging processes observed in those simple organisms reflect those in more complex vertebrates like killifish – and humans. 

“With aging, problems mysteriously emerge at many levels – at the mechanistic, cellular, and organ level – but one commonality is that all those processes are mediated by proteins,” Frydman said. “This study confirms that during aging, the central machinery that makes proteins starts to have quality problems.” 

Ultimately, the team located the disruption at a specific stage of protein synthesis called translation elongation. In this step, the ribosome enacts its role as the cellular machinery responsible for converting mRNA into proteins by moving along the mRNA and adding amino acids one by one. In the aging fish brains, the researchers documented ribosomes colliding and stalling, which both resulted in reduced levels of proteins and protein aggregation. 

“Our results show that changes in the speed of ribosome movement along the mRNA can have a profound impact on protein homeostasis – and highlight the essential nature of ‘regulated’ translation elongation speed of different mRNAs in the context of aging,” said Jae Ho Lee, co-lead author of the paper who worked on this as a postdoctoral scholar in the Frydman lab. He is now an assistant professor at Stony Brook University. 

The finding helped to illuminate another aging mystery. One of the hallmarks of aging in all organisms, including humans, is called “protein-transcript decoupling.” In this phenomenon, changes in levels of some mRNA no longer correlate to changes in protein levels in aged individuals. The new study shows that changes in protein synthesis during aging, including ribosomes, can explain the “protein-transcript decoupling.” Since many of the affected proteins are involved in genome maintenance and integrity, these new observations rationalize why these processes decline during aging.

“Showing that the process of protein production loses fidelity with aging provides a kind of underlying rationale for why all these other processes start to malfunction with age,” said Frydman. “And, of course, the key to solving a problem is to understand why it’s gone wrong. Otherwise, you’re just fumbling in the dark.” 

Future aging research 

As a next step, the researchers will explore directly how ribosome dysfunction – which they identified as a key culprit of declining proteostasis – may contribute to age-related neurodegenerative disorders in people. They also want to know whether targeting translation efficiency or ribosome quality control in treatments can restore proteostasis in brain cells and even delay aging-related cognitive decline. 

“This work provides new insights on protein biogenesis, function, and homeostasis in general, as well as a new potential target for intervention for aging-associated diseases,” said Lee. 

Additionally, the research team is probing what leads to cognitive decline as we age and how modulating such processes may shape longevity in a range of different species.

When male leopard seals dive down into icy Antarctic waters, they sing songs structured like nursery rhymes in performances that can last up to 13 hours, scientists said Thursday.

The Australian-led team of researchers compared the complexity of the songs composed by the big blubbery mammals to those of other animals — as well as human musicians like the Beatles and Mozart.

Lucinda Chambers, a bioacoustics PhD student at Australia’s University of New South Wales, told AFP that people are often surprised when they hear the “otherworldly” hoots and trills sung by leopard seals.

“It kind of sounds like sound effects from an ’80s sci-fi” movie, said the lead author of a new study in the journal Scientific Reports.

During the spring breeding season, male leopard seals dive underwater and perform their songs for two minutes before returning to the surface for air. They then repeat this performance for up to 13 hours a day, according to the study.

The researchers determined that all leopard seals share the same set of five “notes” which are impossible to distinguish between individuals.

However each seal arranges these notes in a unique way to compose their own personal song.

“We theorise that they’re using that structure as a way to broadcast their individual identity, kind of like shouting their name out into the void,” Chambers said.

The researchers believe the males use these songs to woo potential female mates — and ward off rivals.

– ‘Songbirds of the ocean’ –

The team studied recordings of 26 seals captured by study co-author Tracey Rogers off the coast of Eastern Antarctica throughout the 1990s.

“They’re like the songbirds of the Southern Ocean,” Rogers, who is also from the University of New South Wales, said in a statement.

“During the breeding season, if you drop a hydrophone into the water anywhere in the region, you’ll hear them singing.”

The team analysed how random the seals’ sequences of notes were, finding that their songs were less predictable than the calls of humpback whales or the whistles of dolphins.

But they were still more predictable than the more complex music of the Beatles or Mozart.

“They fall into the ballpark of human nursery rhymes,” Chambers said.

This made sense, because the songs need to be simple enough so that each seal can remember their composition to perform it every day, she explained.

She compared it to how “nursery rhymes have to be predictable enough that a child can memorise them”.

But each seal song also needs to be unpredictable enough to stand out from those of the other males.

Leopard seals, which are the apex predator in Antarctic waters, swim alone and cover vast distances. They likely evolved their particular kind of song so that their message travels long distances, the researchers theorised.

Varying pitch or frequency might not travel as far in their environment, Chambers said.

Female seals also sing sometimes, though the scientists do not know why.

Chambers suggested it could be to teach their pups how to sing — exactly how this talent is passed down is also a mystery. But she added that this behaviour has never been observed in the wild.

The females could also just be communicating with each other, she said.

dl/ach

How much energy do your gut microbes really provide? New research finds that what you eat, especially fiber, matters more than your microbiome’s makeup for fueling your body with beneficial fermentation products.

Theory: Quantifying the varying harvest of fermentation products from the human gut microbiota

In a recent study published in the journal Cell, a group of researchers determined, with systems-level precision, how variations in diet and gut microbiota composition alter the quantity and composition of fermentation products absorbed by humans.

However, the authors note that the study’s approach has several limitations, including its reliance on a static microbiome composition, limited explicit modeling of cross-feeding interactions, and a focus on major fermentation metabolites while excluding less abundant compounds.

Background

Imagine colon bacteria paying part of your grocery bill: in fiber-rich diets, they can supply up to one-tenth of daily calories. These anaerobes ferment otherwise indigestible complex carbohydrates into short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate that nourish colonocytes, modulate immunity, and even influence brain signaling. The proportion harvested depends on how much microbiota-available carbohydrates (MACs) reach the large intestine and which bacterial guilds dominate the ecosystem. Yet quantitative estimates of this flux in humans remain contentious, hampered by snapshot stool measurements and limited integration of dietary, physiological, and metagenomic data; therefore, systems-level accounting is needed.

About the study

Researchers first isolated 22 prevalent gut bacterial species from healthy adults and revived them from −80°C glycerol stocks under anaerobic workbench conditions. Seed cultures in four different types of media (YCA, BHIS, γ, and ε) were serially diluted to ensure exponential growth before experimental inoculations at an optical density at 600 nanometers (OD600) of ≈ 0.02. Growth was monitored by spectrophotometry, and four to six culture samples were filtered during the logarithmic phase to measure substrate uptake and metabolite release.

Metabolite concentrations were quantified by isocratic high-performance liquid chromatography (HPLC) with refractive-index detection using an ion-exchange column, 0.4 milliliter-per-minute flow, and 2.5 millimolar sulfuric acid mobile phase. Per-biomass rates of carbohydrate consumption and SCFA excretion were calculated from linear relationships between optical density and chromatogram peak areas. These rates were merged with genus-level relative abundances in 219 metagenomes and with dietary, fecal-mass, and physiological data to compute daily bacterial biomass production and fermentation-product fluxes. Two complementary estimators were applied: one scaled by fecal bacterial loss, the other by MAC supply derived from national food surveys, including the 2017–2018 National Health and Nutrition Examination Survey (NHANES). Error propagation used Gaussian statistical formulas based on the standard deviations of biological replicates.

Study results

The ex vivo fermentations revealed remarkable biochemical consistency across taxa despite metabolic diversity. Regardless of medium complexity or pH, each strain converted more than ninety percent of carbohydrate carbon into fermentation acids, validating the measured per-biomass rates as descriptors of anaerobic growth. Averaged across 22 representative species, glucose or maltose uptake clustered tightly, whereas the blend of secreted products differed: Bacteroides favored succinate, Lachnospiraceae produced butyrate, and Enterobacteriaceae generated formate. Weighting these laboratory rates by genus abundance in 219 healthy metagenomes suggested that about 84% of community biomass at the genus level behaves similarly, enabling ecosystem-scale extrapolation.

Applying the excretion coefficients to a 1970s British diet produced convergent point estimates. A fecal-based calculation started with an average 30-gram daily dry-stool output containing approximately 16 grams of bacterial biomass; multiplying by the composite excretion coefficient yielded roughly 470 millimoles of acids per day. A dietary approach traced 36 grams of MACs escaping upper-gut digestion; the carbon needed to regenerate the corresponding 16 grams of biomass predicted a nearly identical 450 millimole daily acid harvest. Less than 2% of this flux left the host in feces, implying near-complete colonic absorption. Protein and mucin fermentation contributed at most one-fifth of the total, confirming carbohydrates as the principal microbial fuel.

Scaling the framework across diets demonstrated that food, not microbial composition, drives energy capture. Processing NHANES dietary records yielded a median harvest of 286 millimoles, well below the British benchmark. By contrast, seasonal diets of Tanzanian Hadza hunter-gatherers, rich in fibrous tubers, generated up to 1,000 millimoles daily. Variation in bacterial community structure altered the relative amounts of acetate, propionate, butyrate, and lactate but changed total production marginally, producing coefficients of variation below ten percent for total acids yet above 30% for individual metabolites.

Translating the fluxes into energy equivalents showed that gut microbes supply between 1.7 and 12.1% of human daily energy expenditure, but more than 21% in laboratory mice because their higher intake of resistant carbohydrates amplifies microbial fermentation. Notably, laboratory mice were fed autoclaved chow, which may further increase the proportion of energy derived from fermentation. Because butyrate supports colonocyte adenosine triphosphate (ATP) production and acetate modulates hepatic gluconeogenesis, lower acid yields from refined diets could contribute to metabolic disease risk, spotlighting dietary fiber as an important focus for public health strategies worldwide in the coming decade.

Conclusions

To summarize, quantitative integration of microbial physiology, diet, and host digestion reveals that colonic bacteria supply a modest but diet-sensitive slice of human energy, returning most MACs to the body as SCFAs. The total flux, about 2–5% of daily expenditure in Western settings, can triple under fiber-rich diets, whereas shifts in community structure mainly reshape the acid mix rather than the sum.

These findings clarify discrepancies between stool concentrations and metabolic impact, expose limitations of mouse extrapolations, and affirm dietary fiber enrichment as a potentially scalable intervention to amplify beneficial microbial energy transfer and improve cardiometabolic risk profiles.

Future studies incorporating dynamic microbiome changes, explicit modeling of cross-feeding, and broader metabolite profiling will be important to further refine these quantitative insights into host-microbiota metabolic interactions.

WASHINGTON: An international crew of four astronauts had their planned launch to the International Space Station from Florida on Thursday postponed over bad weather, delaying a mission that had been watched by a rare gathering of senior Russian space officials in town for a meeting with Nasa’s acting chief.

The astronaut crew — two Nasa astronauts, a Russian cosmonaut and a Japanese astronaut — boarded SpaceX’s Dragon capsule sitting atop its Falcon 9 rocket at Kennedy Space Centre and were due to lift off at 12:09pm.

But roughly a minute before launch, SpaceX mission controllers called a hold on the countdown because of stormy clouds that had been approaching the launchpad. The start of the astronauts’ mission of at least six months on the ISS will move to Friday, Nasa officials said.

The attempted mission, called Crew-11, includes Nasa astronauts Zena Cardman and Michael Fincke, Russian cosmonaut Oleg Platonov, and Japanese astronaut Kimiya Yui. They will replace the Crew-10 crew on the ISS, which departs on August 6. While US-Russian tensions over the war in Ukraine limited contact between the two space agencies, they have continued to share astronaut flights and cooperate on the ISS, a 25-year-old totem of scientific diplomacy crucial to maintaining the two space powers’ storied human spaceflight capabilities.

Russian space chief says cooperation with Nasa to continue till 2028

While normal long-duration ISS missions are six months, the Crew-11 mission may be the first of many to last eight months, part of a new effort to align US mission schedules with Russia’s.

The mission will be the first spaceflight for Cardman, who was selected as a Nasa astronaut in 2017, and Platonov, an engineer trained in aircraft operations and air traffic management who was selected to be a cosmonaut in 2018.

“We know that he’s in good hands,” Sergei Krikalev, Roscosmos human spaceflight chief and a veteran cosmonaut, said of Platonov during a press conference on Wednesday.

ISS cooperation until 2028

The head of Russia’s space agency Roscosmos said on Thursday that he had agreed with his Nasa counterpart during talks in the United States to extend the International Space Station’s (ISS) operation until 2028.

Space is one of the final areas of US-Russia cooperation amid an almost complete breakdown in relations between Moscow and Washington over the Ukraine conflict.

Roscosmos said earlier this week that its chief, Dmitry Bakanov, arrived in the United States for talks with Nasa’s acting administrator Sean Duffy, the first such meeting since 2018.

“The dialogue went well. We agreed that we will operate the ISS until 2028… And we will work on the issue of de-orbiting it until 2030,” Bakanov was quoted as saying by the TASS news agency.

Bakanov was also due to meet the Nasa’s Crew-11 mission team, including Russian cosmonaut Oleg Platonov, ahead of the launch aboard the SpaceX’s Crew Dragon spacecraft.

Published in Dawn, Aug 1st, 2025

Aging selectively impairs the production of crucial DNA- and RNA-binding proteins, which contributes to hallmarks of aging in the brains of killifish, according to a new study. The findings advance our understanding of the relationship between aging and the risk of pathologies including neurodegenerative disease. “A critical next step will be to determine whether these mechanisms are conserved in mammals, particularly in humans, where translational control is intricately linked to neurodegeneration and other age-associated diseases,” write Olivier Dionne and Benoit Laurent in a related Perspective. “This could inform the development of pharmacological strategies to modify proteostasis with the aim of delaying the onset of age-related pathologies and ultimately extending healthy years of life.”

As organisms age, their ability to maintain protein homeostasis, or proteostasis, deteriorates. Proteostasis plays a crucial role in maintaining protein quality by ensuring proper synthesis, folding, and timely degradation. Disruption to proteostasis can result in the accumulation of harmful protein aggregates, which is a hallmark of both aging and neurodegenerative diseases. Although the age-related breakdown of proteostasis often appears alongside disruptions in other hallmark processes of aging, whether proteostasis impairment actively drives these changes remains unknown.

To address this gap, Domenico Di Fraia and colleagues investigated how aging affects mRNA and protein regulation in the brain of the killifish (Nothobranchius furzeri). The killifish is a model well suited for studying aging due to its rapid life cycle and conserved aging brain hallmarks. The authors developed a method for partially inhibiting the proteasome over time to determine whether this specific impairment triggers aging-related brain changes in living animals. They used ribosome profiling (Ribo-seq) to examine how changes in mRNA translation influence protein production during aging. Di Fraia et al. discovered that as the fish aged, proteins rich in basic amino acids, such as lysine, proline, glutamine, and arginine – which are crucial for RNA- and DNA binding – decline, even though these proteins’ mRNA levels remain unchanged.

The authors linked this decline to ribosomal stalling at basic amino acid codons, which impairs translation, increases protein aggregation risk, and reduces the production of these essential proteins. The findings suggest that aging selectively impairs the synthesis of proteins essential for core gene expression and mitochondrial function, which may position proteostasis decline upstream of other aging hallmarks.

As early humans spread from lush African forests into grasslands, their need for ready sources of energy led them to develop a taste for grassy plants, especially grains and the starchy plant tissue hidden underground.

But a new Dartmouth-led study shows that hominins began feasting on these carbohydrate-rich foods before they had the ideal teeth to do so. The study provides the first evidence from the human fossil record of behavioral drive, wherein behaviors beneficial for survival emerge before the physical adaptations that make it easier, the researchers report in Science.

The study authors analyzed fossilized hominin teeth for carbon and oxygen isotopes left behind from eating plants known as graminoids, which includes grasses and sedges. They found that ancient humans gravitated toward consuming these plants far earlier than their teeth evolved to chew them efficiently. It was not until 700,000 years later that evolution finally caught up in the form of longer molars like those that let modern humans easily chew tough plant fibers.

The findings suggest that the success of early humans stemmed from their ability to adapt to new environments despite their physical limitations, says Luke Fannin, a postdoctoral researcher at Dartmouth and lead author of the study.

We can definitively say that hominins were quite flexible when it came to behavior and this was their advantage. As anthropologists, we talk about behavioral and morphological change as evolving in lockstep. But we found that behavior could be a force of evolution in its own right, with major repercussions for the morphological and dietary trajectory of hominins.”

Luke Fannin, postdoctoral researcher at Dartmouth

Nathaniel Dominy, the Charles Hansen Professor of Anthropology at Dartmouth and senior author of the study, says isotope analysis overcomes the enduring challenge of identifying the factors that caused the emergence of new behaviors-behavior doesn’t fossilize.

“Anthropologists often assume behaviors on the basis of morphological traits, but these traits can take a long time-a half-million years or more––to appear in the fossil record,” Dominy says.

“But these chemical signatures are an unmistakable remnant of grass-eating that is independent of morphology,” he says. “They show a significant lag between this novel feeding behavior and the need for longer molar teeth to meet the physical challenge of chewing and digesting tough plant tissues.”

The team analyzed the teeth of various hominin species, beginning with the distant human relative Australopithecus afarensis, to track how the consumption of different parts of graminoids progressed over millennia. For comparison, they also analyzed the fossilized teeth of two extinct primate species that lived around the same time-giant terrestrial baboon-like monkeys called theropiths and small leaf-eating monkeys called colobines.

All three species veered away from fruits, flowers, and insects toward grasses and sedges between 3.4 million to 4.8 million years ago, the researchers report. This was despite lacking the teeth and digestive systems optimal for eating these tougher plants.

Hominins and the two primates exhibited similar plant diets until 2.3 million years ago when carbon and oxygen isotopes in hominin teeth changed abruptly, the study found. This plummet in both isotope ratios suggests that the human ancestor at the time, Homo rudolfensis, cut back on grasses and consumed more oxygen-depleted water.

The researchers lay out three possible explanations for this spike, including that these hominins drank far more water than other primates and savanna animals, or that they suddenly adopted a hippopotamus-like lifestyle of being submerged in water all day and eating at night.

The explanation most consistent with what’s known about early-human behavior, they report, is that later hominins gained regular access to underground plant organs known as tubers, bulbs, and corms. Oxygen-depleted water also is found in these bulging appendages that many graminoids use for storing large amounts of carbohydrates safely away from plant-eating animals.

The transition from grasses to these high-energy plant tissues would make sense for a species growing in population and physical size, Fannin says. These underground caches were plentiful, less risky than hunting, and provided more nutrients for early humans’ expanding brains. Having already adopted stone tools, ancient humans could dig up tubers, bulbs, and corms while facing little competition from other animals.

“We propose that this shift to underground foods was a signal moment in our evolution,” Fannin says. “It created a glut of carbs that were perennial-our ancestors could access them at any time of year to feed themselves and other people.”

Measurements of hominin teeth showed that while they became consistently smaller-shrinking about 5% every 1,000 years-molars grew longer, the researchers report. Hominins’ dietary shift toward graminoids outpaced that physical change for most of their history.

But the study found that the ratio flipped about 2 million years ago with Homo habilis and Homo ergaster, whose teeth exhibited a spurt of change in shape and size more suited to eating cooked tissues, such as roasted tubers.

Graminoids are ubiquitous across many ecosystems. Wherever they were, hominins would have been able to maximize the nutrients derived from these plants as their teeth became more efficient at breaking them down, Dominy says.

“One of the burning questions in anthropology is what did hominins do differently that other primates didn’t do? This work shows that the ability to exploit grass tissues may be our secret sauce,” Dominy says.

“Even now, our global economy turns on a few species of grass––rice, wheat, corn, and barley,” he says. “Our ancestors did something completely unexpected that changed the game for the history of species on Earth.”

Could clothing monitor a person’s health in real time, because the clothing itself is a self-powered sensor? A new material created through electrospinning, which is a process that draws out fibers using electricity, brings this possibility one step closer.  

A team led by researchers at Penn State developed a new fabrication approach that optimizes the internal structure of electrospun fibers to improve their performance in electronic applications. They published their findings in the Journal of Applied Physics. 

This novel electrospinning approach could open the door to more efficient, flexible and scalable electronics for wearable sensors, health monitoring and sustainable energy harvesting, according to Guanchun Rui, a visiting postdoctoral student in the Department of Electrical Engineering and the Materials Research Institute and co-lead author of the study. 

The material is based on poly(vinylidene fluoride-trifluoroethylene), or PVDF-TrFE, a lightweight, flexible polymer known for its ability to generate an electric charge when pressed or bent. That quality, called piezoelectricity, makes it a strong candidate for use in electronics that convert motion into energy or signals. 

“PVDF-TrFE has strong ferroelectric, piezoelectric and pyroelectric properties,” Rui said, explaining that like piezoelectricity, pyroelectricity can generate electric charges when temperature change and thus influence the material. “It’s thermally stable, lightweight and flexible, which makes it ideal for things like wearable electronics and energy harvesters.” 

Electrospinning is a technique that uses electric force to stretch a polymer solution into extremely thin fibers. As the fibers dry, the way the polymer chains pack together determines their performance. The researchers hypothesized that altering the concentration and molecular weight of the polymer solution could lead to more organized molecular structures. 

“Crystallinity means the molecules are more ordered,” Rui said, noting that the team also theorized the structure could have higher polar phase content. “And when we talk about polar phase content, we mean that the positive and negative charges in the molecules are aligned in specific directions. That alignment is what allows the material to generate electricity from motion.” 

The researchers explained that electrospinning plays a key role in enabling this alignment.  

“The process stretches the fibers in a highly mobile state, which predisposes the polymer chains to crystallize into the form we want,” said Patrick Mather, a co-author of the study and professor of chemical engineering and dean of the Schreyer Honors College. “You start with a liquid, and it dries over a split second as it travels to the collector. All the packing happens during that brief flight.” 

One surprising discovery, Mather said, came from experimenting with unusually high concentrations of polymer in the solution. 

“These were very high concentrations, roughly around 30%, and much higher than we typically use,” Mather said. “My initial thought was that this isn’t going to work. But we were using a low molecular weight polymer, and that turned out to be essential. The chains were still mobile enough to pack well during crystallization. That was the biggest surprise. Sometimes, as scientists, we have doubts even when the theory says it should work. But Rui boldly proceeded, and it worked.” 

The implications are significant, according to Mather. By improving the internal structure of the fibers without requiring high-voltage treatment or complex post-processing, the team created a material that could be both low-cost and scalable. 

Rui noted that the material’s first intended application was actually for face masks, with funding from the National Institutes of Health (NIH).  

“When electrospun into a mask, the material holds a charge that can attract and trap bacteria or viruses,” Rui said. “But it also has broader uses in sensors and energy harvesters. If you press it, it can generate electricity.” 

Qiming Zhang, professor of electric engineering and Harvey F. Brush Chair in the College of Engineering and co-lead author of the study, added that the material’s cloth-like texture could make it more comfortable than traditional plastic-based sensors — it could even be directly incorporated into clothing. 

“If you wear it like clothing, it’s much better,” he said. “You could even incorporate sensors into bandages.” 

Mather pointed out that electrospinning is well suited to producing large sheets, which could be important for energy-harvesting systems. Currently, he notes, most sensors and actuators, material that will change or deform via external stimuli, are small films. 

“Most sensors or actuators are small films,” he said. “But this process could be scaled to wide-area sheets. The equipment exists, but we’d just need to pair it with an electrode manufacturing process.” 

Looking ahead, the researchers said they see opportunities to further improve the material through post-processing. Right now, the electrospun sheets are about 70% porous. Applying heat and pressure could densify them and increase sensitivity and output. 

“We already have ideas about the next steps,” Mather said. “One is densification. We could remove the air between fibers by compacting the sheets after electrospinning, which could boost their performance for certain applications.” 

For broader adoption, the team said industrial partners will be key. 

“We need to find an industrial partner,” Mather said. “Someone in the device space or energy harvesting who’s interested in taking this to the next level. In my experience, if something works early, it will work commercially. If it’s very delicate, it won’t hold up. This is a very robust system.” 

July 31, 2025

New AI tool illuminates “dark side” of the human genome

Salk Institute researchers launch ShortStop, a machine learning framework that explores overlooked DNA regions in search of microproteins that may play roles in disease

July 31, 2025

LA JOLLA—Proteins sustain life as we know it, serving many important structural and functional roles throughout the body. But these large molecules have cast a long shadow over a smaller subclass of proteins called microproteins. Microproteins have been lost in the 99% of DNA disregarded as “noncoding”—hiding in vast, dark stretches of unexplored genetic code. But despite being small and elusive, their impact may be just as big as larger proteins.

Salk Institute scientists are now exploring the mysterious dark side of the genome in search of microproteins. With their new tool ShortStop, researchers can probe genetic databases and identify DNA stretches in the genome that likely code for microproteins. Importantly, ShortStop also predicts which microproteins are most likely to be biologically relevant, saving time and money in the search for microproteins involved in health and disease.

ShortStop shines a new light on existing datasets, spotlighting microproteins formerly impossible to find. In fact, the Salk team has already used the tool to analyze a lung cancer dataset to find 210 entirely new microprotein candidates—with one standout validated microprotein—that may make good therapeutic targets in the future.

The findings were published in BMC Methods on July 31, 2025.

“Most of the proteins in our body are well known, but recent discoveries suggest we’ve been missing thousands of small, hidden proteins—called microproteins—coded by overlooked regions of our genome,” says senior author Alan Saghatelian, professor and holder of the Dr. Frederik Paulsen Chair at Salk. “For a long time, scientists only really studied the regions of DNA that coded for large proteins and dismissed the rest as ‘junk DNA,’ but we’re now learning that these other regions are actually very important, and the microproteins they produce could play critical roles in regulating health and disease.”

More about microproteins

It is difficult to detect and catalog microproteins, owing mostly to their size. Compared to standard proteins that can range from hundreds to thousands of amino acids long, microproteins typically contain fewer than 150 amino acids, making them harder to detect using standard protein analysis methods. Therefore, instead of searching for the microproteins themselves, scientists search large, publicly available datasets for the DNA sequences that make them.

Scientists have now learned that certain stretches of DNA called small open reading frames (smORFs) can contain the instructions for making microproteins. Current experimental methods have already cataloged thousands of smORFs, but these tools remain time-consuming and expensive. Furthermore, their inability to separate potentially functional microproteins from nonfunctional microproteins has stalled their discovery and characterization.

How ShortStop works

Not all smORFs translate to biologically meaningful microproteins. Existing methods can’t discriminate between functional and nonfunctional microprotein-generating smORFs. This means that scientists must independently test each microprotein to determine whether it is functional or not.

ShortStop radically alters this workflow, optimizing smORF discovery by sorting microproteins into functional and nonfunctional categories. The key to ShortStop’s two-class sorting is how it’s trained as a machine learning system. Its training relies on a negative control dataset of computer-generated random smORFs. ShortStop compares found smORFs against these decoys to quickly decide whether a new smORF is likely to be functional or nonfunctional.

ShortStop cannot definitively say whether a smORF will code for a biologically relevant microprotein, but this two-class system narrows down the experimental pool immensely. Now researchers can spend less time manually sorting through datasets and failing at the bench.

When the researchers applied ShortStop to a previously published smORF dataset, they identified 8% as likely functional microproteins, prioritizing them for targeted follow-up. This accelerates microprotein characterization by filtering out sequences unlikely to have biological relevance. ShortStop could also identify microproteins that were overlooked by other methods, including one that was validated by being detected in human cells and tissues.

“What makes ShortStop especially powerful is that it works with common data types, like RNA sequencing datasets, which many labs already use,” says first author Brendan Miller, a postdoctoral researcher in Saghatelian’s lab. “This means we can now search for microproteins across healthy and diseased tissues at scale, which will reveal new insights into human biology and unlock new paths for diagnosing and treating diseases, such as cancer and Alzheimer’s disease.”

ShortStop spots microprotein associated with lung cancer

The researchers have already used ShortStop to identify a microprotein that was upregulated in lung cancer tumors. They analyzed genetic data from human lung tumors and adjacent normal tissue to create a list of potential functional smORFs. Among the smORFs ShortStop found, one stood out—it was expressed more in tumor tissue than normal tissue, suggesting it may serve as a biomarker or functional microprotein for lung cancer.

The identification of this lung cancer-related microprotein demonstrates the value of ShortStop and machine learning to prioritize candidates for future research and therapeutic development.

“There’s so much data that already exists that we can now process with ShortStop to find novel microproteins associated with health and disease, stretching from Alzheimer’s to obesity and beyond,” says Saghatelian. “My team is really good at making methods, and with data from other Salk faculty, we can integrate these methods and accelerate the science.”

Other authors include Eduardo Vieira de Souza, Victor Pai, Joan Vaughan, Calvin Lau, and Jolene Diedrich of Salk, as well as Hosung Kim of UC Los Angeles.

The work was supported by the National Institutes of Health (P30CA014195, R01GM102491) and Clayton Medical Research Foundation.

DOI: 10.1186/s44330-025-00037-4