A gene mutation may trap the brain in the wrong reality in schizophrenia patients

 A common feature of schizophrenia is difficulty using new information to understand the world. This challenge can make decision-making harder and, over time, may contribute to a disconnect from reality.

Researchers at MIT have identified a gene mutation that may play a key role in this problem. In experiments with mice, they found that the mutation disrupts a brain circuit responsible for updating beliefs when new information is received.The mutation occurs in a gene called grin2a, which had previously been flagged in large genetic studies of schizophrenia. The new findings suggest that targeting this brain circuit could help improve cognitive symptoms associated with the disorder.

"If this circuit doesn't work well, you cannot quickly integrate information," says Guoping Feng, the James W. and Patricia T. Poitras Professor in Brain and Cognitive Sciences at MIT, a member of the Broad Institute of Harvard and MIT, and the associate director of the McGovern Institute for Brain Research at MIT. "We are quite confident this circuit is one of the mechanisms that contributes to the cognitive impairment that is a major part of the pathology of schizophrenia."

Feng and Michael Halassa, an associate professor of psychiatry and neuroscience at Tufts University, are the senior authors of the study, which appears in Nature Neuroscience. Tingting Zhou, a research scientist at the McGovern Institute, and Yi-Yun Ho, a former MIT postdoc, are the lead authors.

Genetic Clues and Schizophrenia Risk

Schizophrenia has a strong genetic component. In the general population, about 1 percent of people develop the condition. That risk increases to 10 percent if a parent or sibling is affected, and rises to 50 percent for identical twins.

Scientists at the Stanley Center for Psychiatric Research at the Broad Institute have identified more than 100 gene variants associated with schizophrenia through genome-wide association studies. However, many of these variants are located in non-coding regions of DNA, making their effects difficult to interpret.

To address this, researchers used whole-exome sequencing, a method that focuses on protein-coding regions of the genome. This approach allowed them to identify mutations directly within genes.

By analyzing around 25,000 sequences from people with schizophrenia and 100,000 from control subjects, the team identified 10 genes where mutations significantly increase the risk of developing the disorder.

How a Gene Mutation Alters Brain Function

In the new study, researchers created mice carrying a mutation in one of those genes, grin2a. This gene produces part of the NMDA receptor, which is activated by the neurotransmitter glutamate and is commonly found on neurons.

Zhou then examined whether these mice showed behaviors similar to those seen in schizophrenia. While symptoms such as hallucinations and delusions (loss of contact with reality) cannot be directly modeled in mice, scientists can study related issues like difficulty interpreting new sensory information.

For years, researchers have proposed that psychosis may result from a reduced ability to update beliefs when new information becomes available.

"Our brain can form a prior belief of reality, and when sensory input comes into the brain, a neurotypical brain can use this new input to update the prior belief. This allows us to generate a new belief that's close to what the reality is," Zhou says. "What happens in schizophrenia patients is that they weigh too heavily on the prior belief. They don't use as much current input to update what they believed before, so the new belief is detached from reality."

Experiment Reveals Slower Decision-Making

To test this idea, Zhou designed a task where mice had to choose between two levers to receive a reward. One lever was low-reward -- mice needed six presses to get one drop of milk. The other offered a higher reward, delivering three drops per press.

At first, all mice preferred the high-reward option. Over time, however, the effort required for that option gradually increased, while the low-reward lever remained unchanged.

Healthy mice adjusted their behavior as conditions shifted. When the effort required for the high-reward option became comparable to the low-reward option, they eventually switched and stayed with the easier choice.

Mice with the grin2a mutation behaved differently. They continued switching back and forth between the options for longer and delayed committing to the more efficient choice.

Source: ScienceDaily

Deafness reversed: One injection restores hearing in just weeks

 A new study shows that gene therapy can significantly improve hearing in people born with congenital deafness or severe hearing loss. Researchers at Karolinska Institutet, working with hospitals and universities in China, treated ten patients and saw hearing improve in every case. The therapy was also well-tolerated. The findings were published in the journal Nature Medicine.

"This is a huge step forward in the genetic treatment of deafness, one that can be life-changing for children and adults," says Maoli Duan, consultant and docent at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Sweden, and one of the study's corresponding authors.

Targeting the OTOF Gene

The trial included ten patients between the ages of 1 and 24 who were treated at five hospitals in China. All had a genetic form of deafness linked to mutations in a gene called OTOF. These mutations prevent the body from producing enough of the protein otoferlin, which is essential for sending sound signals from the inner ear to the brain.

Rapid Results After a Single InjectionTo address this, researchers used a synthetic adeno-associated virus (AAV) to deliver a working version of the OTOF gene directly into the inner ear. The treatment was given as a single injection through a membrane at the base of the cochlea known as the round window.The effects appeared quickly. Most patients began to regain some hearing within one month. After six months, all participants showed clear improvement. On average, the level of sound they could detect improved from 106 decibels to 52.

Strongest Gains Seen in Younger PatientsChildren showed the most dramatic responses, especially those between the ages of five and eight. One seven-year-old girl regained nearly full hearing and was able to have everyday conversations with her mother just four months after treatment. At the same time, the therapy also produced meaningful improvements in adult patients."Smaller studies in China have previously shown positive results in children, but this is the first time that the method has been tested in teenagers and adults, too," says Dr. Duan. "Hearing was greatly improved in many of the participants, which can have a profound effect on their life quality. We will now be following these patients to see how lasting the effect is."

Treatment Found To Be Safe

The therapy was shown to be safe and well-tolerated. The most commonly reported side effect was a decrease in neutrophils, which are a type of white blood cell. No serious adverse reactions were observed during the follow-up period of 6 to 12 months.

Expanding Gene Therapy for Hearing Loss

"OTOF is just the beginning," says Dr. Duan. "We and other researchers are expanding our work to other, more common genes that cause deafness, such as GJB2 and TMC1. These are more complicated to treat, but animal studies have so far returned promising results. We are confident that patients with different kinds of genetic deafness will one day be able to receive treatment."The research involved multiple institutions, including Zhongda Hospital at Southeast University in China. Funding came from several Chinese research programs as well as Otovia Therapeutics Inc., the company that developed the gene therapy and employs many of the researchers involved. A full list of disclosures and conflicts of interest is available in the published paper.

Source: ScienceDaily

This tiny claw in a 500-million-year-old fossil just rewrote the origin of spiders

 After a long day of teaching, Rudy Lerosey-Aubril turned to a familiar task: preparing a Cambrian arthropod fossil for study. At first glance, the specimen looked typical for its age. But as he carefully removed surrounding material, something unusual appeared. Instead of an antenna, there was a claw.

"Claws are never in that location in a Cambrian arthropod," said Lerosey-Aubril, "It took me a few minutes to realize the obvious, I had just exposed the oldest chelicera ever found."

Oldest Known Chelicerate Identified

In a study published in Nature, Research Scientist Rudy Lerosey-Aubril and Associate Professor Javier Ortega-Hernández, Curator of Invertebrate Paleontology in the Museum of Comparative Zoology - both in the Department of Organismic and Evolutionary Biology at Harvard - describe Megachelicerax cousteaui, a 500 million year old marine predator discovered in Utah's West Desert. It is now recognized as the earliest known chelicerate, a group that includes spiders, scorpions, horseshoe crabs, and sea spiders. This finding extends the known history of chelicerates by about 20 million years.

"This fossil documents the Cambrian origin of chelicerates," noted Lerosey-Aubril, "and shows that the anatomical blueprint of spiders and horseshoe crabs was already emerging 500 million years ago."

Detailed Anatomy of an Ancient Predator

Revealing the fossil's structure required patience and precision. Lerosey-Aubril spent more than 50 hours working under a microscope with a fine needle to expose its features. The animal measured just over 8 centimeters long and preserved a dorsal exoskeleton made up of a head shield and nine body segments.

These two regions had different functions. The head shield carried six pairs of appendages used for feeding and sensing. Beneath the body were plate-like respiratory structures that resemble the book gills seen in modern horseshoe crabs.

The First Clear Evidence of a Chelicera

The most striking feature is the chelicera, a pincer-like appendage that defines chelicerates. This structure separates spiders and their relatives from insects, which instead have antennae at the front of their bodies. Chelicerates rely on grasping appendages, often associated with venom delivery.

Despite the abundance of Cambrian fossils, no clear example of a chelicera from that period had been identified before. This discovery fills that gap and provides direct evidence of when these defining features first appeared.

Source: ScienceDaily

Saturn’s magnetic field is twisted and scientists just figured out why

 Saturn's magnetic field does not form a balanced, symmetrical bubble like Earth's. Instead, it is noticeably uneven, according to new research involving scientists from University College London (UCL). The study suggests this distortion is caused by the planet's rapid rotation along with the large amount of material it drags through space.

Planetary magnetic fields (magnetospheres) act as protective shields, blocking streams of highly charged particles from the solar wind. Saturn's magnetosphere is enormous, extending to more than 10 times the planet's diameter.

Cassini Study Pinpoints Saturn's Magnetic Cusp

The findings, published in Nature Communications, are based on six years of observations from NASA's Cassini mission. Researchers focused on identifying the exact position of Saturn's cusp -- a region where magnetic field lines bend back toward the poles and allow charged particles to funnel into the atmosphere.

The analysis showed that this cusp is consistently shifted to one side. When viewed from the Sun, it appears displaced to the right and is most often located between 1:00 and 3:00 (as it might appear on a clockface), rather than at 12:00 as seen on Earth.

Fast Rotation and Plasma Drive the Shift

Scientists believe this offset is linked to two key factors. Saturn spins extremely quickly, completing one rotation in just 10.7 hours. At the same time, it is surrounded by a dense "soup" of plasma (ionized gas), much of which comes from gases released by its moons, especially Enceladus.

Together, the rapid spin and this heavy plasma environment appear to pull the magnetic field lines sideways. Researchers note that further simulations will be needed to fully confirm this explanation.

Enceladus and the Search for Life

Saturn's surroundings are of growing interest because of Enceladus, a moon that ejects icy plumes from a subsurface ocean and may potentially support life. It is also a primary target for a proposed European Space Agency mission planned for the 2040s.

Co-author Professor Andrew Coates (Mullard Space Science Laboratory at UCL) said: "The cusp is the place where the solar wind can slip directly into the magnetosphere. Knowing the location of Saturn's cusp can help us better understand and map the whole magnetic bubble.

"A better understanding of Saturn's environment is especially urgent now as plans for our return to Saturn and its moon Enceladus start to be developed. These results feed into the excitement that we are going back there. This time we will look for evidence of habitability and for potential signs of life.

Source: ScienceDaily

Scientists create “smart” DNA drug that targets cancer cells with extreme precision

 How can doctors destroy cancer cells without harming healthy tissue? That question remains one of the biggest challenges in modern oncology. Researchers at the University of Geneva (UNIGE) have now developed a "smart" system built from synthetic DNA strands that can identify cancer cells with remarkable accuracy and release powerful drugs only where they are needed. In addition to cancer treatment, this approach points toward a future of programmable, responsive medicines. The findings appear in Nature Biotechnology.

Targeted therapies have already reshaped cancer care by directing drugs straight to tumors, helping reduce damage to healthy cells and easing harsh side effects linked to chemotherapy. One of the most successful strategies involves antibody-drug conjugates (ADCs), which use monoclonal antibodies to carry treatments directly to cancer cells.

However, ADCs still have drawbacks. Their relatively large size can limit how well they penetrate tumors, and they can only carry a limited amount of drug. These challenges have pushed scientists to explore new ways to deliver therapies more effectively.

DNA-Based Drug Delivery Offers New Advantages

To overcome these limitations, the UNIGE team designed a system based on short DNA strands. Because these molecules are much smaller than antibodies, they can move more easily through tumor tissue. They can also be engineered to carry multiple components, increasing their potential effectiveness.

A "Two-Key" System for Precision Drug Activation

The new method relies on several separate DNA strands, each carrying a specific function. Some strands include binders that recognize cancer markers, while another carries a toxic drug.

When two distinct cancer markers are present on a cell, the DNA components attach to them and assemble at that exact location. This triggers a chain reaction that builds up more DNA structures at the site, boosting the amount of drug delivered. The process works much like two-factor authentication on a banking website. Both markers must be detected before activation occurs. If one is missing, the reaction does not begin, and the drug remains inactive.

Lab Results Show High Selectivity and Power

In laboratory experiments, the system successfully identified cancer cells with specific combinations of surface proteins and delivered potent drugs directly to them. Nearby healthy cells were not affected.

The researchers also showed that multiple drugs can be delivered together using this approach. This could be important for preventing or overcoming resistance, a common problem in cancer treatment.

"This could mark an important step forward in the evolution of medicine, with the introduction of a self-operating drug system. Until now, computers and AI have helped us design new drugs. What's new here is that the drug itself can, in a simple way, 'compute' and respond intelligently to biological signals," explains Nicolas Winssinger, full professor in the Department of Organic Chemistry of the School of Chemistry and Biochemistry, Faculty of science, UNIGE, and last author of the study.

Source: Sciencedaily

Stroke triggers a hidden brain change that looks like rejuvenation

 A new study in The Lancet Digital Health suggests the brain can respond to stroke in a surprising way. Researchers at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) found that people with severe physical impairments after a stroke may show signs of a "younger" brain structure in areas that were not damaged. This appears to reflect how the brain adapts and reorganizes itself after injury.The research was conducted as part of the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery Working Group. Scientists analyzed brain scans from more than 500 stroke survivors collected across 34 research centers in eight countries. By applying deep learning models trained on tens of thousands of MRI scans, the team estimated the "brain age" of different regions in each hemisphere and examined how stroke affects both structure and recovery."We found that larger strokes accelerate aging in the damaged hemisphere but paradoxically make the opposite side of the brain appear younger," said Hosung Kim, PhD, associate professor of research neurology at the Keck School of Medicine of USC and co-senior author of the study. "This pattern suggests the brain may be reorganizing itself, essentially rejuvenating undamaged networks to compensate for lost function."

AI Reveals Brain Rewiring After Stroke

To carry out the analysis, researchers used a type of artificial intelligence called a graph convolutional network. This system estimated the biological age of 18 brain regions based on MRI data. They then compared this predicted age with each person's actual age, a measure known as the brain-predicted age difference (brain-PAD), which serves as an indicator of brain health.When these brain age measurements were compared with motor function scores, a clear pattern emerged. Stroke survivors with severe movement impairments, even after more than 6 months of rehabilitation, showed younger-than-expected brain age in regions opposite the site of injury. This effect was especially strong in the frontoparietal network, which plays an important role in movement planning, attention, and coordination."These findings suggest that when stroke damage leads to greater movement loss, undamaged regions on the opposite side of the brain may adapt to help compensate," Kim explained. "We saw this in the contralesional frontoparietal network, which showed a more 'youthful' pattern and is known to support motor planning, attention, and coordination. Rather than indicating full recovery of movement, this pattern may reflect the brain's attempt to adjust when the damaged motor system can no longer function normally. This gives us a new way to see neuroplasticity that traditional imaging could not capture."

Large-Scale Data Reveals Hidden Patterns

The study relied on ENIGMA, a global collaboration that combines data from more than 50 countries to better understand the brain across different conditions. By standardizing MRI data and clinical information from many research groups, the team created the largest stroke neuroimaging dataset of its kind."By pooling data from hundreds of stroke survivors worldwide and applying cutting-edge AI, we can detect subtle patterns of brain reorganization that would be invisible in smaller studies. These findings of regionally differential brain aging in chronic stroke could eventually guide personalized rehabilitation strategies," said Arthur W. Toga, PhD, director of the Stevens INI and Provost Professor at USC.

Toward Personalized Stroke Recovery

The researchers plan to continue this work by following patients over time, from the early stages after a stroke through long-term recovery. Tracking how brain aging patterns and structural changes evolve could help doctors tailor treatments to each person's unique recovery process, with the goal of improving outcomes and quality of life.Learn more about associations between contralesional neuroplasticity and motor impairment by viewing this video made by the Stevens INI.The study, "Deep learning prediction of MRI-based regional brain age reveals contralesional neuroplasticity associated with severe motor impairment in chronic stroke: A worldwide ENIGMA study," was funded by the National Institutes of Health (NIH) grant R01 NS115845 and supported by international collaborators from institutions including the University of British Columbia, Monash University, Emory University, and the University of Oslo.

Source: ScienceDaily

Scientists solved the mystery of missing ocean plastic—and the answer is alarming

 Scientists have uncovered something surprising in the Atlantic Ocean. The majority of plastic pollution may no longer be visible at all. Instead, it exists as nanoplastics, particles so small they are measured in billionths of a meter.

"This estimate shows that there is more plastic in the form of nanoparticles floating in this part of the ocean than there is in larger micro- or macroplastics floating in the Atlantic or even all the world's oceans!" said Helge Niemann, researcher at NIOZ and professor of geochemistry at Utrecht University. In mid-June, he received a 3.5 million euro grant to further investigate nanoplastics and what ultimately happens to them.

Ocean Expedition Reveals Tiny Plastic Particles

To gather data, Utrecht master's student Sophie ten Hietbrink spent four weeks aboard the research vessel RV Pelagia. The ship traveled from the Azores to the European continental shelf, where she collected water samples at 12 different locations.

Each sample was carefully filtered to remove anything larger than one micrometer. What remained contained the smallest particles. "By drying and heating the remaining material, we were able to measure the characteristic molecules of different types of plastics in the Utrecht laboratory, using mass spectrometry," Ten Hietbrink explains.

First Real Estimate of Ocean Nanoplastics

Previous studies had confirmed that nanoplastics existed in ocean water, but no one had been able to calculate how much was actually there. This research marks the first time scientists have produced a meaningful estimate.

Niemann notes that this breakthrough was made possible by combining ocean research with expertise from atmospheric science, including contributions from Utrecht University scientist Dusân Materic.

27 Million Tons of Invisible Plastic

When the team scaled their measurements across the North Atlantic, the results were striking. They estimate that about 27 million tons of nanoplastics are floating in this region alone.

"A shocking amount," Ten Hietbrink says. The finding may finally explain a long-standing mystery. Scientists have struggled to account for all the plastic ever produced. Much of it appeared to be missing. This study suggests that a large share has broken down into tiny particles that are now suspended throughout the ocean.

How Nanoplastics Enter the Ocean

These microscopic plastics come from multiple sources. Larger plastic debris can fragment over time due to sunlight. Rivers also carry plastic particles from land into the sea.

Another pathway comes from the atmosphere. Nanoplastics can travel through the air and fall into the ocean with rain or settle directly onto the water's surface through a process known as dry deposition.

Potential Risks to Ecosystems and Human Health

The widespread presence of nanoplastics raises serious concerns. Niemann points out that these particles are small enough to enter living organisms.

"It is already known that nanoplastics can penetrate deep into our bodies. They are even found in brain tissue," he says. Because they are now known to be present throughout the ocean, they likely move through entire food webs, from microorganisms to fish and ultimately to humans. The full impact on ecosystems and health is still unclear and requires further study.

What Scientists Still Don't Know

There are still important gaps in knowledge. Researchers did not detect certain common plastics, such as polyethylene or polypropylene, in the smallest particle range.

"It may well be that those were masked by other molecules in the study," Niemann says. The team also wants to determine whether similar levels of nanoplastics exist in other oceans. Early indications suggest this could be the case, but more research is needed.

Prevention May Be the Only Solution

While this discovery fills a critical gap in understanding ocean pollution, it also presents a difficult reality. These particles are too small and too widespread to remove.

"The nanoplastics that are there can never be cleaned up," Niemann emphasizes. The findings highlight the urgency of preventing further plastic pollution before it breaks down into an even more persistent and invisible problem.

Source: ScienceDaily