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