This ultrasound treatment may help stop arthritis before it starts

Researchers at The University of Alabama in Huntsville (UAH), part of The University of Alabama System, have identified a promising new use for continuous low-intensity ultrasound that could one day help treat joint injuries and reduce the risk of post-traumatic osteoarthritis. Their findings suggest the non-invasive approach may shift the body's immune response away from long-lasting inflammation and toward tissue repair, offering a potential drug-free strategy for improving healing.

The study, published in the Nature journal Scientific Reports, was led by Dr. Anuradha Subramanian, professor of chemical and materials engineering. It combined biological research conducted by Dr. Shahid Khan during his doctoral studies with computational and statistical analysis developed by Dr. Satyaki Roy, professor of mathematical sciences, along with contributions from graduate student Owen Trippany. The research was funded by the National Institutes of Health through an R01 grant awarded to Subramanian.

How Ultrasound Influences Immune Cells

The team focused on macrophages, specialized immune cells that play a key role in both inflammation and tissue repair, to understand how they respond to continuous low-intensity ultrasound.

"Following injury, the body recruits inflammatory 'defender' macrophages (M1) to clear damaged tissue and healer macrophages (M2) to support repair and recovery," Subramanian explains. "Persistent dominance of defender macrophages can create a prolonged inflammatory environment that contributes to post-traumatic osteoarthritis."

The researchers wanted to determine whether ultrasound could encourage these immune cells to transition from an inflammatory state to one that promotes healing.

"In an 'M1' state, microphages promote inflammation to fight damage or infection, but prolonged M1 activity can also harm healthy tissue," Subramanian notes. "In contrast, 'M2-like' macrophages support tissue repair and recovery. Shifting macrophages toward an M2-like state is important, because it may help reduce chronic inflammation while encouraging healing in damaged joints. Our findings suggest that continuous low-intensity ultrasound may help restore this balance by promoting a more reparative macrophage response."

Roy says chronic inflammation is a major factor in the development of post-traumatic osteoarthritis.

"Post-traumatic osteoarthritis is driven in part by persistent inflammation that limits tissue repair and accelerates joint degeneration," Roy adds. "Our team is interested in continuous low-intensity ultrasound because it offers a non-pharmacological, non-invasive approach that may help regulate immune cell behavior and promote a more reparative healing environment in injured joints."

A More Realistic Model of Joint Injury

To better recreate the conditions inside an injured joint, the researchers relied on fibronectin fragments, molecules generated as damaged tissue breaks down, instead of using only conventional laboratory methods to trigger inflammation. This approach produced a model that more closely reflects the biological environment that develops after a joint injury.

The team also combined transcriptomics, the large-scale study of gene activity, with an advanced computational method known as differential clustering. Rather than analyzing genes one by one, this technique identifies groups of genes whose behavior changes together, providing a broader picture of how immune cells respond to ultrasound treatment.

"This allowed us to study not only which genes changed, but also how groups of genes changed their coordinated behavior in response to ultrasound stimulation," Roy says.

Early Results Show Reduced Inflammation

The researchers found that continuous low-intensity ultrasound lowered biological markers linked to inflammation while increasing markers associated with a more reparative, M2-like macrophage state.

Although the research is still limited to laboratory experiments, the findings suggest that non-drug, non-invasive technologies could eventually be used to influence immune cell behavior and improve healing after joint injuries. The researchers believe the technique could become part of future treatments designed to slow the progression of osteoarthritis and improve recovery after joint trauma.

"The next steps will involve validating these findings in animal models of early post-traumatic osteoarthritis and studying how ultrasound-based modulation affects long-term tissue repair in joint injury settings," Subramanian says.

Journal Reference:

1. Shahid Khan, Owen Trippany, Anuradha Subramanian, Satyaki Roy. Continuous low-intensity ultrasound influences the transcriptomic profile in M1 macrophages by downregulating inflammation and promoting M2-like markers. Scientific Reports, 2026; DOI: 10.1038/s41598-026-53228-6

Courtesy:

The University of Alabama in Hunstville. "This ultrasound treatment may help stop arthritis before it starts." ScienceDaily. ScienceDaily, 12 July 2026. <www.sciencedaily.com/releases/2026/07/260710003521.htm>. 

 

 

Scientists finally crack nature's secret for building better cancer drugs

Scientists have uncovered how bacteria naturally manufacture multiple versions of powerful cancer drugs, solving a mystery that has puzzled researchers for decades. The discovery could help speed the development of new treatments for cancers that are still difficult to treat.

For years, scientists have hoped to harness bacterial enzymes to create new drug variants through a process known as combinatorial biosynthesis. However, progress has been limited because researchers did not fully understand how the enzymes coordinate their work.

Published in Nature Communications, the new study reveals how bacterial enzymes communicate with one another to assemble a family of closely related anti-cancer compounds. That family includes Romidepsin (Istodax), an FDA-approved treatment for certain blood cancers. By uncovering this natural "mix and match" system and reproducing its underlying principles in the laboratory, the researchers have established a new strategy for designing future cancer therapies.

"For decades, we've known that bacteria can naturally produce multiple versions of powerful anti-cancer drugs, yet we had no idea how they achieved this," said first author Dr. Munro Passmore, Research Fellow, Department of Chemistry, University of Warwick. "This work finally cracks that code. We've identified how the different enzymes communicate and cooperate to produce these drug variants, something that has eluded researchers because the system is so elegantly economical. It's the breakthrough we needed to actually engineer these drugs ourselves."

Tiny Molecular Connectors Reveal Nature's Drug-Making Strategy

The researchers discovered that small molecular regions known as 'docking domains' serve as connectors between the core drug-building machinery and the enzymes responsible for adding different components. These docking domains share a conserved connection point that allows them to interact with multiple enzyme partners.

This flexible design explains how bacteria can create a variety of related drug molecules while still maintaining the precision needed for the compounds to remain effective.

The study also sheds light on how these natural drug-producing systems evolved. According to the researchers, the newly identified compound most likely developed from a related drug-producing pathway through gene duplication and recombination over time.

Prof. Greg Challis, Monash Warwick Alliance Professor of Sustainable Chemistry, University of Warwick and Monash University concludes: "This research gives us a blueprint to do what nature does, but better and faster. By reverse-engineering nature's evolutionary logic, we can now design synthetic pathways that generate new anti-cancer drug candidates with properties optimized for clinical use, such as superior potency, improved selectivity, fewer side effects. Our immediate goal is to build an expanded library of candidates for various cancers where new treatments are urgently needed. This discovery is moving us from understanding how the systems work to building new ones."

How the Discovery Could Improve Cancer Drug Development

The work focuses on a class of anti-cancer medicines known as HDAC inhibitors. These drugs block histone deacetylases, enzymes that help regulate which genes are switched on or off inside cells. Romidepsin (Istodax) is an FDA-approved HDAC inhibitor used to treat T-cell lymphomas.

A chemically related compound called FR-901375 has been known for decades, but scientists had never identified the biological pathway bacteria use to produce it. This study finally fills in that missing piece.

Like other HDAC inhibitors in its family, FR-901375 belongs to a group of complex cyclic molecules called depsipeptides. These compounds are assembled from amino acid building blocks along with a conserved hydroxy acid pharmacophore, all connected through a combination of peptide and ester bonds.

Inside bacteria, these molecules are built by massive protein complexes called PKS-NRPS hybrids, which combine the activities of polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS). The new research shows that the key to this assembly process is the docking domains, which act like molecular connectors that allow one part of the production line to recognize and pass its product to the next. This mechanism is what enables combinatorial biosynthesis and allows bacteria to naturally generate multiple drug variants.

How the Researchers Solved the Mystery

To uncover how this system works, the team combined structural biology, biochemistry, genetics, and computational modeling.

Their work included:

• Bioinformatic searches of public databases that identified the FR-901375 biosynthetic gene cluster in Pseudomonas chlororaphis subsp. piscium, with the findings confirmed by mass spectrometry analysis of extracted metabolites.
• In vitro reconstitution experiments using purified protein domains that demonstrated productive enzyme-enzyme interactions, verified with intact protein mass spectrometry.
• AlphaFold computational modeling to predict protein complex structures, followed by carbene footprinting mass spectrometry to experimentally map the interaction sites.
• Site-directed mutagenesis experiments that confirmed the importance of the predicted binding residues.
• Gene deletion studies in bacterial strains showing that the docking domains are essential for the system to function in vivo.
• Comparative analysis of biosynthetic gene clusters from multiple HDAC inhibitor-producing bacteria, revealing evolutionarily conserved features shared across these natural drug-making systems.

Journal Reference:

1. Munro Passmore, Xinyun Jian, Xinyi Zhao, Emmanuel L. C. de los Santos, Douglas M. Roberts, Józef R. Lewandowski, Matthew Jenner, Lona M. Alkhalaf, Gregory L. Challis. Molecular basis for depsipeptide HDAC inhibitor combinatorial biosynthesis. Nature Communications, 2026; 17 (1) DOI: 10.1038/s41467-026-74383-4

Courtesy:

University of Warwick. "Scientists finally crack nature's secret for building better cancer drugs." ScienceDaily. ScienceDaily, 8 July 2026. <www.sciencedaily.com/releases/2026/07/260701205001.htm>.

 

 

 

Alzheimer's tau protein has a surprising secret role in memory

New research has revealed that tau, a protein best known for its connection to Alzheimer's disease, is also essential for creating long lasting memories. The discovery provides new insight into how healthy memory works and could help guide future efforts to develop treatments for dementia.

The study, led by Flinders University in partnership with researchers from the University of New South Wales and Macquarie University, was published in Nature Communications. It found that tau helps organize and stabilize memories so they can be retained over time.

The researchers studied "remote memory" in mice, which refers to memories recalled days or weeks after an experience. They discovered that tau is not necessary for learning something new or remembering it shortly afterward. Instead, it plays a crucial role in making those memories durable over the long term.

Because the research was conducted in mice, the findings cannot be directly applied to human memory or Alzheimer's disease. Even so, the results offer valuable clues that could shape future dementia research and treatment strategies.

Tau's Role in Long Lasting Memory

Senior author Associate Professor Arne Ittner, a neuroscientist from Flinders' College of Medicine and Public Health, says the findings help explain why people with dementia may still be able to learn new information initially, yet struggle to retain it.

"Why some memories last while others fade has long puzzled scientists and our study shows that tau plays a key role in how the brain forms long-lasting memories. Without it, memories can still form in the moment, but they are weaker," says Associate Professor Ittner.

The team focused on specialized brain cells called "engram cells," which create the physical record of a memory. When a new experience occurs, only a small number of these cells are selected to store it.

According to the study, tau is active during this critical stage of memory formation, helping determine exactly which engram cells are recruited to preserve the experience.

One of the study's lead authors, Renée Kosonen, says tau acts like an organizer that helps the brain build accurate and lasting memories.

"Our findings show that tau helps determine which cells are selected to store a memory, shaping how an experience forms a lasting memory trace," says Ms Kosonen, a researcher at Flinders' Neuroscience and Dementia Research.

How Tau Organizes Memory

The researchers also found that tau reduces unnecessary or "noise" activity in the brain during memory formation. By limiting this background activity, tau allows only a specific group of cells to become part of a memory, producing clearer and more stable memory traces.

The team identified an important molecular process behind this effect. As learning takes place, tau undergoes a subtle chemical change called phosphorylation, which helps coordinate the activity of engram cells.

Although abnormal tau phosphorylation is a well known feature of Alzheimer's disease, the study shows that controlled, low level phosphorylation is a normal and essential part of healthy brain function.

New Clues About Alzheimer's Disease

The researchers made another surprising discovery. Even in the absence of tau, memory traces still existed and could be recovered by directly stimulating engram cells. This suggests that tau is not required to store memories themselves. Instead, it appears to be needed to connect natural cues, such as sights and sounds, with the ability to recall those memories.

The findings also provide new insight into how Alzheimer's related tau may interfere with memory. When disease associated forms of tau were present in engram cells during learning, they disrupted the creation of new memories. When those abnormal forms appeared after memories had already formed, they interfered with the brain's ability to retrieve them.

These effects were associated with abnormal patterns of brain activity, suggesting that memory problems in dementia may result not only from memories being lost, but also from disruptions in how memories are organized and accessed.

"Knowing how tau supports the formation and recall of memory could help us better understand what goes wrong in memory loss," says Associate Professor Ittner.

"Future research will hopefully be able to confirm concepts developed in our study in human memory and show their implication in dementia."

The researchers conclude that tau should be viewed not only as a protein involved in Alzheimer's disease, but also as a fundamental regulator of how the brain organizes, stores, and retrieves lasting memories. That new perspective could deepen scientists' understanding of both healthy memory and the biological changes that contribute to Alzheimer's disease.

Journal Reference:

1. Renée Kosonen, Kristie Stefanoska, Yijun Lin, Samantha Edwards, Emmanuel Prikas, Josefine Bertz, Anne Poljak, Lars M. Ittner, Arne Ittner. Tau T205 phosphorylation modulates engram cell recruitment and remote memory in mice. Nature Communications, 2026; DOI: 10.1038/s41467-026-73207-9

Courtesy:

Flinders University. "Alzheimer's tau protein has a surprising secret role in memory." ScienceDaily. ScienceDaily, 12 July 2026. <www.sciencedaily.com/releases/2026/07/260710003535.htm>.  

 

 

 

Scientists may have finally found how Alzheimer's kills brain cells

Scientists have identified evidence of a previously unknown process that may explain how brain cells die in Alzheimer's disease and frontotemporal dementia (FTD). The discovery, centered on a mechanism known as karyoptosis, could point researchers toward new ways to slow the progression of these devastating conditions.

Many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and FTD, are marked by the buildup of harmful proteins inside neurons. Over time, these nerve cells die, contributing to memory loss and other symptoms. Although scientists have long known about several forms of cell death, including apoptosis, those mechanisms have never fully explained the extensive neuron loss seen in these disorders.

Now, researchers from King's College London, working with the UK Dementia Research Institute and supported in part by Alzheimer's Research UK, have identified karyoptosis as a potential missing link connecting toxic protein accumulation to the death of brain cells.

Karyoptosis refers to a series of chemical reactions set in motion when toxic proteins accumulate inside a cell. As the process unfolds, the cell's nucleus, which contains its genetic material, gradually shrivels before ultimately breaking apart.

Evidence Found in Alzheimer's and FTD Brains

The findings, published in Nature Communications, are based on an analysis of 3,000 brain cells collected from 28 people with either FTD or end stage Alzheimer's disease. Using computational algorithms, the researchers identified different forms of cell death occurring within the tissue.

They found signs of karyoptosis in 35 percent of cells from the frontal cortex of people with Alzheimer's disease, compared with just 15 percent of cells from healthy older adults.

"This study is the culmination of a 10-year journey at King's, from when we first identified karyoptosis in a relatively rare disease to discovering that it is a common feature of dementias which affect millions of people."

A Possible New Target for Dementia Treatments

The researchers also uncovered a key molecular pathway that appears to control karyoptosis. They found that forcing proteins inside neurons to clump together, a hallmark of many neurodegenerative diseases, can trigger this destructive process.

According to the study, the buildup of toxic proteins destabilizes the outer membrane of the nucleus, causing it to shrink and eventually disintegrate.

The team then investigated proteins known as kinases, which act as molecular switches in this pathway. In laboratory experiments using rat neurons, blocking these switches reduced markers associated with karyoptosis. In particular, the interaction between the kinase p38 MAP kinase and the protein LaminB1 emerged as a promising target for slowing or preventing the breakdown of the nucleus.

The researchers believe this pathway could eventually lead to therapies that reduce brain cell loss in dementia. Their next goal is to develop ways to selectively target the interaction between p38 MAP kinase and LaminB1 in humans.

"By specifically targeting the interaction between p38 MAP kinase and LaminB1 we may slow down the process of cell death, buying time for more pinpointed therapies against specific neurodegenerative diseases," said Dr. Manolis Fanto, Reader in Functional Genomics, Institute of Psychiatry, Psychology and Neuroscience, King's College London.

Building a Road Map for Future Therapies

"The death and loss of cells in the brain drives many symptoms experienced by people living with dementia. Our study uncovers a new series of chemical events which can coordinate cell death in brain cells. We have started to lay out the road map of how karyoptosis works, and I'm excited to see future breakthroughs this may drive in the dementia research community and beyond," said Dr. Rebecca Casterton, Senior Researcher at the UK Dementia Research Institute at King's and first author on the paper.

"For decades, we've known that toxic proteins build up in Alzheimer's disease and frontotemporal dementia, but exactly how they lead to the loss of brain cells has remained unclear.

"The identification of karyoptosis is a crucial step towards finding targets for treatments that could stop or slow cell loss. It could help widen the window for therapies that tackle the underlying causes of disease, bringing us closer to a cure for dementia. This is why Alzheimer's Research UK funds and supports research," said Dr. Sara Rodrigues, Senior Research Manager at Alzheimer's Research UK.

The study, "Karyoptosis mediates cell death and neurodegeneration upon proteotoxic stress," was published in Nature Communications.

The research was primarily funded by Alzheimer's Research UK and the Biotechnology and Biological Sciences Research Council International Partnership. Additional support came from a studentship provided by the UK Medical Research Council and the UK Dementia Research Institute.

Journal Reference:

1. Rebecca Casterton, Aitana Martinez-Cotrina, Jodi Barnard, Eleanor Wycherley, Yanling Hu, Rhys Anderson, Sebastien Janel, Jiin Byun, Olivia Houghton, Daniel A. Solomon, Juan Alcalde, Frank Lafont, Marc-David Ruepp, Frank Hirth, Bart Tummers, Yong-Yeon Cho, Gian De Nicola, Sarah Mizielinska, Manolis Fanto. Karyoptosis mediates cell death and neurodegeneration upon proteotoxic stress. Nature Communications, 2026; 17 (1) DOI: 10.1038/s41467-026-73802-w

Courtesy:

King's College London. "Scientists may have finally found how Alzheimer's kills brain cells." ScienceDaily. ScienceDaily, 5 July 2026. <www.sciencedaily.com/releases/2026/06/260626124701.htm>.

 

 

Streetlights are trapping thousands of pill bugs in giant “death spirals”

 

Researchers have uncovered a surprising side effect of artificial lighting: ordinary streetlights can lure thousands of tiny land dwelling isopods into giant synchronized "death spirals." The newly documented behavior, observed in Israel, is the first of its kind and suggests that human made lighting can dramatically disrupt the instincts of small ground dwelling animals.

The study was led by PhD student Idan Sheizaf under the supervision of Prof. Ariel Chipman at The Hebrew University of Jerusalem. Published in Ecology and Evolution, the research describes how land dwelling isopods, relatives of crabs and shrimp that are better known as woodlice or pill bugs, abandon their normally solitary habits to join enormous circular formations containing more than 5,000 individuals.

A surprising discovery in northern Israel

The unusual behavior first came to light after amateur naturalist Eviatar Itzkovich noticed huge swirling groups of isopods during summer nights in the Golan Heights.

The researchers focused on the species Armadillo sordidus, a little studied isopod that typically spends its time hidden beneath rocks and damp leaf litter, where moisture helps prevent it from drying out.

Although woodlice commonly cluster together to conserve moisture, scientists had never documented coordinated movement on this scale. Before this work, very little was known about A. sordidus. The study also expanded the species' known range. Previously, it had only been recorded in southern Syria and the Golan Heights. Researchers have now documented it in the Jezreel Valley for the first time.

Experiments reveal the role of artificial light

To determine what was causing the strange circular marches, the team tested several possible explanations, including magnetic fields and different types of lighting.

Strong magnets placed near the moving isopods had no effect, even though the Golan Heights is known for unusual magnetic properties. The animals continued circling uninterrupted.

Ultraviolet flashlights attracted only a small number of isopods and never triggered the swirling formations.

White light, however, consistently produced the dramatic behavior. When researchers positioned a white lamp so that its beam shone straight down, the isopods repeatedly gathered into large rotating circles.

The experiments showed that the shape of the illuminated area is what matters most. A vertical beam creates a circular boundary of light on the ground. Drawn toward that edge, the isopods begin walking along its perimeter. As more individuals join, the movement reaches a tipping point and develops into a large, self sustaining circular procession.

Reflecting on the findings, Idan Sheizaf said: "While collective movement is common in the animal kingdom, seeing it in this form in isopods was entirely unexpected. It appears that the geometry of our modern world -- specifically the circular pools of light created by streetlights, is interacting with the natural instincts of these creatures to create a mesmerizing, yet potentially harmful, emergent phenomenon."

Why the "death spirals" may be dangerous

Although the swirling formations are visually striking, researchers believe they represent an unintended trap created by artificial light at night (ALAN), not a natural social behavior.

Most of the participants were female, and many were carrying eggs, making it unlikely that the gatherings were related to mating. Instead, the evidence suggests that artificial lighting is disrupting the animals' normal instincts.

The consequences could be severe. During one observation, a centipede preyed on the distracted isopods while they remained caught in the swirling formation. By pulling these animals out of their sheltered habitats and keeping them moving in circles, streetlights may leave them vulnerable to predators while also wasting energy needed for survival.

The findings highlight how even a simple change to the environment, such as installing a streetlight, can reshape ancient behaviors in small animals that often go unnoticed.

Journal Reference:

1. Idan Sheizaf, Eviatar Itzkovich, Ariel D. Chipman. A Novel Light‐Induced Collective Circular Movement in Armadillo sordidus Isopods. Ecology and Evolution, 2026; 16 (4) DOI: 10.1002/ece3.73487

Courtesy:

 The Hebrew University of Jerusalem. "Streetlights are trapping thousands of pill bugs in giant “death spirals”." ScienceDaily. ScienceDaily, 6 July 2026. <www.sciencedaily.com/releases/2026/06/260626125707.htm>. 

Scientists solve a 30-year rye pollen mystery that could transform cancer research

 

Nearly 30 years ago, researchers discovered two unusual molecules in rye pollen that appeared to slow tumor growth in animal studies. Despite the promising findings, the research reached a dead end because scientists could not determine the molecules' exact three dimensional structures.

Now, chemists at Northwestern University have solved that long standing mystery. By constructing the molecules from scratch in the laboratory, they confirmed the precise structures of secalosides A and B for the first time.

With an accurate molecular blueprint available, researchers can now investigate how these compounds from rye pollen, which comes from a cereal crop widely grown for its grain, interact with the immune system. That knowledge could eventually help guide the development of new approaches to cancer treatment.

The findings were published in the Journal of the American Chemical Society.

"In preliminary studies, other researchers found that rye pollen could help different animal models clear tumors through some unknown, non-toxic mechanism," said Northwestern's Karl A. Scheidt, who led the study. "Now that we confirmed the structure of these molecules, we can find the active ingredient -- or what part of the molecule is doing the work. This is an exciting starting point to make better versions of these molecules that could possibly inform approaches to cancer therapy."

Scheidt is a professor of chemistry at Northwestern's Weinberg College of Arts and Sciences and a professor of pharmacology (by courtesy) at Northwestern University Feinberg School of Medicine. He also is a member of the Chemistry of Life Processes Institute and of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Nature's Role in Drug Discovery

Many important medicines have their roots in nature. Scientists have long studied plants, fungi, and microbes for compounds that can inspire new treatments.

Morphine, a powerful pain medication, comes from the opium poppy. Taxol, an important chemotherapy drug, was first isolated from the Pacific yew tree. Statins, which help lower cholesterol and reduce the risk of heart disease, originated from fungi.

"Natural products aren't necessarily effective drugs on their own, but they are great leads," Scheidt said. "We can find inspiration in natural products and use chemistry to make better versions that are orally available, survive the metabolism and hit the right targets."

Rye pollen could eventually join that list. Rye pollen extract is already sold as a dietary supplement that many people use to support prostate health. However, scientists have not yet developed it into a pharmaceutical treatment. A major obstacle was the lack of a clear picture of the molecules' three dimensional structures.

Solving a Decades Long Molecular Puzzle

Traditional techniques, including advanced nuclear magnetic resonance spectroscopy, could not fully determine how key parts of the molecules were arranged. As a result, scientists spent decades debating between two possible structural models.

Both versions contained the same atoms connected in the same way and shared the same overall shape. The difference was that one critical region existed as a mirror image in each model. Even that subtle variation can dramatically affect how a molecule interacts with biological targets and whether it produces a biological effect.

"It's like your hands," Scheidt said. "They are mirror images of each other, but you need a different glove for each. If you had two left-handed gloves, it wouldn't work because your hands can't be superimposed on top of one another."

Building the Molecules From Scratch

To resolve the uncertainty, the Northwestern team relied on total synthesis, a process in which researchers build a natural molecule step by step in the laboratory.

The work proved exceptionally difficult because secalosides A and B contain an extremely rare, highly strained 10 membered ring at their core. That tightly compressed structure is notoriously challenging to assemble.

The researchers overcame the problem by first creating a larger, more flexible ring. They then triggered a chemical reaction that converted it into the smaller strained ring in a single step.

After producing both proposed versions of the molecules, the team compared them with samples extracted from rye pollen. Only one matched perfectly, allowing the researchers to definitively identify the correct structures.

"We've demonstrated we can make the core of this natural product," Scheidt said. "Now, we're trying to find potential collaborators in immunology who could help us translate this to a possible clinical endpoint."

The study, "Synthesis and structural confirmation of secalosides A and B," was supported by the National Institute of General Medical Science, the Chemistry of Life Processes Institute Lambert Fellowship and the National Science Foundation.

Journal Reference:

1. Yunchan Nam, Anthony T. Tam, Troy E. Reynolds, Diego N. Rojas, Jonathan A. Brekan, Sneha Sil, Karl A. Scheidt. Synthesis and Structural Confirmation of Secalosides A and B. Journal of the American Chemical Society, 2025; 148 (1): 86 DOI: 10.1021/jacs.5c18864

Courtesy:

 Northwestern University. "Scientists solve a 30-year rye pollen mystery that could transform cancer research." ScienceDaily. ScienceDaily, 6 July 2026. <www.sciencedaily.com/releases/2026/06/260625014838.htm>. 

Scientists discover a completely different way to fight viruses

 

Scientists have uncovered a previously unknown way that sea anemones defend themselves against viruses, revealing that the evolution of animal immune systems may be far more diverse than previously believed. The newly identified defense relies on a protein that closely resembles one of the most important antiviral proteins in humans, yet performs the opposite function while still being essential for protecting the animal from infection. The findings suggest that evolution produced more than one successful strategy for fighting viruses across the animal kingdom.

The research, led by PhD candidate Ton Sharoni and Prof. Yehu Moran at the Hebrew University of Jerusalem in collaboration with scientists from the University of North Carolina at Charlotte, was published in Nature Ecology & Evolution. It challenges the long standing idea that animals inherited a single core antiviral system from a common ancestor and instead points to multiple evolutionary solutions for resisting viral infections.

An Ancient Animal Offers New Clues About Immunity

Viruses have threatened living organisms throughout evolutionary history. In humans and other vertebrates, one of the body's key antiviral defenses depends on a protein called MAVS. When a virus is detected, MAVS helps trigger the immune system so it can respond to the infection.

To investigate how old this defense system might be, the researchers studied sea anemones. These ancient marine animals split from the evolutionary line that eventually led to humans more than 600 million years ago. Because they are close relatives of corals and jellyfish, sea anemones provide scientists with a valuable glimpse into the early evolution of animal immunity.

During the study, the team discovered a previously unknown protein they named CARDIB (CARD Inhibitor Binding protein). At first, CARDIB looked remarkably similar to MAVS, leading researchers to believe it might perform the same antiviral role found in humans.

That assumption quickly fell apart.

"Everything about CARDIB suggested it should function like MAVS," said Prof. Yehu Moran, head of the Department of Ecology, Evolution and Behavior at the Hebrew University. "Instead, we discovered that it does the exact opposite. Rather than activating antiviral defenses, CARDIB normally suppresses them."

A Surprising Protein That Protects by Slowing the Immune System

The discovery immediately raised an important question. Why would an animal deliberately suppress its own immune response?

To find out, the researchers used CRISPR gene editing to remove the CARDIB gene from sea anemones before exposing them to viruses.

The results were unexpected. Sea anemones without CARDIB became much more susceptible to infection. Viruses multiplied more rapidly, the animals failed to properly activate their antiviral defenses, and their ability to fight infection dropped dramatically.

"The results were completely counterintuitive," said Sharoni. "Although CARDIB acts as a brake on the immune system under normal conditions, that brake turns out to be essential for mounting an effective antiviral response."

Overall, the experiments showed that sea anemones rely on an antiviral pathway that is fundamentally different from the one used by humans, even though both systems contain molecular components that look strikingly alike.

Natural Environment Confirms the Discovery

The researchers also wanted to determine whether this newly identified immune pathway mattered outside carefully controlled laboratory conditions.

To answer that question, genetically modified sea anemones were moved from laboratory aquaria into outdoor marine mesocosms supplied with natural estuarine water in South Carolina. This exposed the animals to the wide variety of viruses and microorganisms found in their normal environment.

The difference became obvious within days. Sea anemones lacking CARDIB and related antiviral genes accumulated substantially more viruses than unmodified animals. Researchers also found that one immune gene that appeared only moderately important in laboratory tests became clearly important under natural environmental conditions.

"This demonstrated that the pathway we discovered is not simply a laboratory phenomenon," said Moran. "It plays a crucial role in helping these animals cope with the viral challenges they face in nature."

Multiple Evolutionary Solutions to Fighting Viruses

The findings suggest that evolution did not settle on a single universal antiviral strategy. Instead, different groups of animals may have independently developed distinct molecular systems for detecting viruses and preventing them from spreading.

"Humans and sea anemones both need protection from viruses, but this work shows that evolution can organize those defenses in fundamentally different ways," Moran added.

The research also underscores the importance of looking beyond traditional laboratory animals. Ancient organisms such as sea anemones can preserve evolutionary innovations that would remain hidden if scientists focused only on humans, mice, and other commonly studied species.

As researchers continue exploring the remarkable diversity of life, discoveries like this are revealing that evolution has repeatedly found unexpected ways to solve some of biology's most fundamental challenges.

Journal Reference:

1. Ton Sharoni, Adrian Jaimes-Becerra, Sydney Birch, Hee-Jin Kwak, Daria Aleshkina, Magda Lewandowska, Joachim M. Surm, Hannah Justin, Reuven Aharoni, Adam M. Reitzel, Yehu Moran. An ancient anthozoan protein reveals an alternative evolutionary path of antiviral signalling. Nature Ecology, 2026; DOI: 10.1038/s41559-026-03112-3

Courtesy:

The Hebrew University of Jerusalem. "Scientists discover a completely different way to fight viruses." ScienceDaily. ScienceDaily, 30 June 2026. <www.sciencedaily.com/releases/2026/06/260630020534.htm>. 

 

 

Old muscle stem cells can act young again but there’s a catch

 

Growing older often means recovering more slowly from muscle injuries, but scientists may have uncovered an important reason why.

A new study from UCLA, conducted in mice, found that aging muscle stem cells build up high levels of a protein that slows their ability to spring into action and repair damaged tissue. At the same time, that protein appears to help the cells endure the challenging conditions found in aging muscle.

The research, published in the journal Science, suggests that some biological changes linked to aging may not simply be signs of decline. Instead, they may serve as protective adaptations that help cells survive.

"This has led us to a new way of thinking about aging," said Dr. Thomas Rando, senior author of the study and director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

"It's counterintuitive, but the stem cells that make it through aging may actually be the least functional ones. They survive not because they're the best at their job, but because they're the best at surviving. That gives us a completely different lens for understanding why tissues decline with age."

Protein Linked to Slower Muscle Repair

The researchers, led by postdoctoral scholars Jengmin Kang and Daniel Benjamin, compared muscle stem cells taken from young and old mice. They found that levels of a protein known as NDRG1 rose dramatically with age, reaching concentrations 3.5 times higher in older cells.

NDRG1 functions like a brake inside the cell. It suppresses a signaling pathway called mTOR, which normally helps drive cell activation and growth.

To determine whether NDRG1 was contributing to slower muscle recovery, the scientists studied mice that had aged naturally to roughly the equivalent of 75 human years. When they blocked NDRG1 activity, the older muscle stem cells quickly regained youthful behavior, becoming more active and improving muscle repair after injury.

The improvement, however, came with a drawback. Without the protective effects provided by NDRG1, fewer stem cells remained alive over time. As a result, the tissue became less capable of regenerating after repeated injuries.

Survival Versus Performance

"Think of it like a marathon runner versus a sprinter," said Rando, who is also a professor of neurology at the David Geffen School of Medicine at UCLA. "The stem cells in young animals are hyper-functioning -- really good at what they do, namely sprinting, but they're not good for the long term. They can make it through the 100-yard dash, but they can't make it even halfway through the marathon. By contrast, aged stem cells are like marathon runners -- slower to respond, but better equipped for the long haul. However, what makes them so proficient over long distances is exactly what renders them poor at sprinting."

The researchers confirmed their results using several different methods. They examined muscle stem cells from both young and old mice in laboratory cultures as well as in living tissue.

Across these experiments, the pattern remained consistent. Higher levels of NDRG1 reduced the cells' ability to rapidly activate and repair muscle, while also increasing their resilience and long-term survival.

A Cellular Survivorship Bias

According to the researchers, the rise in NDRG1 may be driven by what they describe as a "cellular survivorship bias" -- stem cells with insufficient NDRG1 gradually disappear over time, leaving behind a population that survives better but functions more slowly.

"Some age-related changes that look detrimental -- like slower tissue repair -- may actually be necessary compromises that prevent something worse: the complete depletion of the stem cell pool," Rando said.

The researchers compare this phenomenon to trade-offs seen throughout nature. During difficult conditions such as drought, famine, or extreme cold, animals often shift resources toward survival mechanisms like hibernation rather than reproduction. Muscle stem cells may be doing something similar as they age, directing resources away from their reproductive role (making more cells) and toward survival.

"Species survive because they reproduce, but in times of deprivation, animals turn on their own resilience programs," Rando said. "There are a lot of examples in nature of allocating resources to survival under times of stress. It's exactly aligned with what we're seeing at the cellular level."

Implications for Future Aging Therapies

The findings could help guide future efforts to develop therapies that improve tissue repair while preserving stem cell survival. However, Rando cautions that enhancing one aspect of stem cell function may come with unintended consequences.

"There's no free lunch. We can improve the function of aged cells for a period of time, for certain tissues, but every time we do this, there's going to be a potential cost and a potential downside."

The team plans to continue studying the molecular mechanisms that determine how stem cells balance survival and performance during aging.

"This gene is almost like our doorway that we've opened into understanding what controls these trade-offs that are so critical, not only for evolution of species but also for the aging of tissues within an individual," Rando said.

Funding for the study came from the National Institutes of Health, the NOMIS Foundation, the Milky Way Research Foundation, the Hevolution Foundation, and the National Research Foundation of Korea.

Journal Reference:

1. Jengmin Kang, Daniel I. Benjamin, Qiqi Guo, Chauncey Evangelista, Soochi Kim, Marina Arjona, Pieter Both, Mingyu Chung, Ananya K. Krishnan, Gurkamal Dhaliwal, Richard Lam, Thomas A. Rando. Cellular survivorship bias as a mechanistic driver of muscle stem cell aging. Science, 2026; 391 (6784): 517 DOI: 10.1126/science.ads9175

Courtesy:
University of California - Los Angeles Health Sciences. "Old muscle stem cells can act young again but there’s a catch." ScienceDaily. ScienceDaily, 3 July 2026. <www.sciencedaily.com/releases/2026/06/260622014315.htm>. 

 

 

 

 

Melanoma's secret to cheating death has finally been revealed

 

Scientists at the University of Pittsburgh School of Medicine have identified a crucial missing piece in the long standing mystery of how melanoma tumors avoid death and continue growing.

Writing this week in Science, Jonathan Alder, Ph.D., and colleagues describe a combination of genetic changes that allows melanoma cells to dramatically extend their lifespan while fueling rapid tumor growth. The discovery could reshape how researchers understand melanoma and may point to new treatment strategies.

"We did something that was, in essence, obvious based on previous basic research and connected back to something that is happening in patients," said Alder, assistant professor in the Division of Pulmonary, Allergy and Critical Care Medicine at Pitt's School of Medicine.

Telomeres Help Control a Cell's Lifespan

Telomeres are protective caps located at the ends of chromosomes that help keep DNA from breaking down. Every time a healthy cell divides, its telomeres become a little shorter. Eventually, they shrink to the point where the cell can no longer divide.

Keeping telomeres at the proper length is critical for health. Telomeres that become too short can cause disorders linked to premature aging and early death. On the other hand, unusually long telomeres are often associated with cancer.

Scientists have long known that melanoma tumors contain exceptionally long telomeres, especially compared with many other types of cancer.

"There's some special link between melanoma and telomere maintenance," said Alder. "For a melanocyte to transform into cancer, one of the biggest hurdles is to immortalize itself. Once it can do that, it's well on its way to cancer."

The Missing Genetic Link Behind Melanoma

The enzyme telomerase lengthens telomeres, helping protect chromosomes and preventing cells from dying. In most healthy cells, telomerase remains inactive. Many cancers, however, activate the enzyme through mutations in the telomerase gene known as TERT, allowing cancer cells to keep dividing.

Melanoma is particularly dependent on this strategy. Roughly 75% of melanoma tumors carry TERT mutations that increase telomerase production and activity.

Yet there was a mystery. Even after researchers introduced TERT mutations into melanocytes, they still could not recreate the unusually long telomeres found in melanoma tumors. That suggested another important factor was missing.

Pattra Chun-on, M.D., an internist pursuing her Ph.D. in Alder's lab, set out to uncover that missing link. Drawing on her background in cancer biology and growing interest in telomeres, she investigated why TERT mutations alone were not enough.

The fun part of this story is when Pattra joined my lab," Alder said. "She contacted me and told me that she was interested in studying cancer. I told her that I study short telomeres and not long telomeres. This went on until I realized that Pattra would never take 'no' for an answer."

TPP1 Completes the Puzzle

Earlier work from Alder's laboratory had identified frequent mutations in a telomere binding protein called TPP1 while analyzing cancer mutation databases.

Chun-on discovered that these TPP1 mutations closely resembled the TERT mutations. They occurred in the newly annotated promoter region of TPP1 and boosted production of the protein. That finding immediately caught Alder's attention because scientists had already shown that TPP1 enhances telomerase activity.

"Biochemists more than a decade before us showed that TPP1 increases the activity of telomerase in a test tube, but we never knew that this actually happened clinically," he said.

Chun-on, who is also enrolled in a Ph.D. program in the Department of Environmental and Occupational Health at Pitt's School of Public Health, then introduced the mutated forms of both TERT and TPP1 into cells. Working together, the two proteins produced the exceptionally long telomeres that characterize melanoma tumors.

The results revealed that TPP1 was the long sought missing factor, one that had been hidden in plain sight.

New Target for Future Melanoma Treatments

The findings offer a new explanation for how melanoma develops and survives. They also identify a cancer specific telomere maintenance system that could become a promising target for future therapies.

Additional authors of the study are Angela M. Hinchie, Agustin A. Gil Silva, Ph.D., Elizabeth Rush, Cindy Sander, Brittani K.N. Seynnaeve, M.D., M.S., John M. Kirkwood, M.D., all of Pitt, UPMC or both; Holly C. Beale, Ph.D., and Olena M. Vaske, Ph.D., both of the University of California, Santa Cruz; Carla J. Connelly, of Johns Hopkins University; and Carol W. Greider, Ph.D., of the University of California, Santa Cruz and Johns Hopkins University.

The research was supported by National Institutes of Health grants R35CA209974 and R01HL135062.

Journal Reference:

1. Pattra Chun-on, Angela M. Hinchie, Holly C. Beale, Agustin A Gil Silva, Elizabeth Rush, Cindy Sander, Carla J. Connelly, Brittani K.N. Seynnaeve, John M. Kirkwood, Olena M. Vaske, Carol W. Greider, Jonathan K. Alder. TPP1 promoter mutations cooperate with TERT promoter mutations to lengthen telomeres in melanoma. Science, 2022; 378 (6620): 664 DOI: 10.1126/science.abq0607

Courtesy:

University of Pittsburgh. "Melanoma's secret to cheating death has finally been revealed." ScienceDaily. ScienceDaily, 30 June 2026. <www.sciencedaily.com/releases/2026/06/260625014833.htm>.