Not all exercise boosts mental health — it’s the why that matters most

 Research often points to exercise as a good way to boost mental health, but a recent study from the University of Georgia suggests that it's not just physical movement that affects mental health.

It's how, where and why you exercise that makes the difference.

"Historically, physical activity research has focused on how long someone exercises for or how many calories were burned," said Patrick O'Connor, co-author of the study and a professor in the Mary Frances Early College of Education's Department of Kinesiology. "The 'dose' of exercise has been the dominant way researchers have tried to understand how physical activity might influence mental health, while often ignoring whether those minutes were spent exercising with a friend or as part of a game."

While research shows that leisure-time physical activity -- like going for a run, taking a yoga class or biking for fun -- correlates with better mental health outcomes, these benefits may vary significantly depending on the environment and circumstances surrounding the activity, according to the researchers.

To analyze these factors, the researchers reviewed three types of studies. These included large-scale epidemiological studies that examined health patterns in populations, randomized controlled trials where some groups received exercise treatments and others did not, and a much smaller but growing set of investigations into contextual factors.

Exercise and mental health

Multiple studies found that people who engage in regular leisure-time physical activity tend to report lower levels of depression and anxiety. But it's less clear for other forms of activity like cleaning the house or working for a lawn care company. The context may matter as much as the intensity or amount of physical activity.

"For example, if a soccer player runs down the field and kicks the game-winning ball, their mental health is fantastic," O'Connor said. "In contrast, if you do the exact same exercise but miss the goal and people are blaming you, you likely feel very differently. Anecdotes such as these show how context matters even when people are performing a similar exercise dose."

Numerous randomized controlled trials also showed that adopting regular exercise routines boosted mental health, especially for individuals with existing mental health disorders. However, these studies were typically based on small, short-term and homogenous samples, so the results likely aren't generalizable to larger, more diverse groups.

"The average effects on mental health are small across all the randomized controlled studies of exercise, and that's partly because most of the studies focused on people who were not depressed or anxious -- you do get bigger effects in those studies," added O'Connor. "We're communicating to scientists that larger- and longer-term controlled studies are needed to make a compelling case whether exercise does, or does not, truly impact mental health."

Why context matters

Where the evidence is thinnest -- but potentially most important -- is in understanding contextual factors. The same physical activity can feel very different depending on who the activity was done with, as well as where, when and how.

Context can range from peer dynamics and instructor style to external conditions like weather or time of day. "If you're outside and it's hot, and you're having to walk to work, that's part of the context," he added. "Or if you go and take a group exercise class -- some instructors you really like, and some you don't. So, that's also part of the context.

"If we're trying to help people's mental health with exercise, then not only do we need to think about the dose and the mode, we also need to ask: What is the context?" O'Connor said.

For O'Connor, the takeaway is clear. It's not just movement that matters. It's the meaning, the setting and the experience surrounding the activity that determines the impact of exercise on mental health.

Co-authors of the study include Eduardo Bustamante of the University of Illinois Chicago; Angelique Brellenthin of Iowa State University; and David Brown, who recently retired from the Centers for Disease Control and Prevention.

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Can’t sleep, can’t focus, can’t thrive? ADHD and insomnia may be a vicious cycle

 Insomnia could explain why adults with ADHD traits report having a lower quality of life, according to new research led by the University of Southampton and the Netherlands Institute of Neuroscience.

A study published on July 15 in BMJ Mental Health found that having higher ADHD traits was associated with a lower quality of life and that insomnia could be part of the reason why.

At least one in four people with attention deficit hyperactivity disorder (ADHD) report having a sleep disorder, with insomnia being the most common of these.

"Our findings show a link between ADHD traits, insomnia severity, and reduced life satisfaction," says Dr Sarah L. Chellappa, Associate Professor in Psychology at the University of Southampton and senior author on the research paper.

"We know that sleep disruption can impact neurobehavioral and cognitive systems, including attention and emotional regulation. At the same time, sleep disruption may arise from ADHD-related impulsivity and hyperactivity, suggesting a reinforcing cycle between sleep disorders and ADHD."

Researchers from the University of Southampton and the Netherlands Institute for Neuroscience (Prof Eus Van Someren) examined data from the Netherlands Sleep Registry, an online survey with more than ten thousand adult participants.

The team analysed responses from 1,364 participants who had answered questions about ADHD traits, sleep disturbances, circadian factors, depression, and quality of life.

They found ADHD traits were associated with worse depression, more severe insomnia, lower sleep quality, and a preference for going to bed and waking up later.

ADHD and insomnia severity both predicted a lower quality of life, with analysis suggesting insomnia was the potential link in this association.

"Adults with ADHD traits may be more likely to have low sleep quality, insomnia complaints, and low mood levels, all of which lead to reduced life satisfaction," says Professor Samuele Cortese, a co-author on the paper, also from the University of Southampton.

"There needs to be more research to understand this complex interplay. By improving our understanding, we could uncover treatment options that improve the quality of life of people with ADHD. For instance, targeting insomnia complaints in individuals with higher ADHD traits, with Cognitive Behavioural Therapy for Insomnia or Sleep Restriction therapy may help improve their quality of life."

The paper Associations of ADHD symptom severity, sleep/circadian factors, depression, and quality of life is published in BMJ Mental Health and is available online.

The research was supported by the Netherlands Organisation for Scientific Research and the European Research Council.

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Tai chi, yoga, and jogging rival pills for beating insomnia

 Yoga, Tai Chi, walking and jogging may be the best forms of exercise to improve sleep quality and ease insomnia, suggest the findings of a comparative pooled data analysis published in the online journal BMJ Evidence Based Medicine.

The findings back the use of exercise as a primary treatment strategy for poor sleep patterns, say the researchers.

Characterized by difficulties falling and staying asleep, and early morning awakening, the prevalence of insomnia ranges from 4-22%, note the researchers. It is associated with heightened risks of various mental and physical health conditions, including dementia and cardiovascular disease.

Drug treatments for insomnia are not without their side effects, and cognitive behavioral therapy (CBT), while effective, isn't always available due to the shortage of trained therapists, explain the researchers.

An emerging body of research suggests that exercise is helpful, but current guidelines don't specify which types of exercise might be most beneficial. The researchers therefore set out to plug this knowledge gap, with a view to informing clinical practice and helping patients choose the most appropriate exercise for managing their insomnia.

They scoured research databases looking for relevant randomized clinical trials published up to April 2025 and included 22 in a network meta analysis -- a statistical technique used to simultaneously compare multiple interventions.

The trials involved 1348 participants and 13 different treatment approaches to ease insomnia, seven of which were exercise based: yoga; Tai Chi; walking or jogging; aerobic plus strength exercise; strength training alone; aerobic exercise combined with therapy; and mixed aerobic exercises. These programs ranged from 4 up to 26 weeks in length.

The other approaches included CBT; sleep hygiene; Ayurveda; acupuncture/massage; nothing; and existing treatment, such as usual care and/or lifestyle changes, the durations of which ranged from 6 to 26 weeks.

Validated scoring systems for sleep quality and insomnia severity -- PSQI and the ISI45 -- as well as subjective and objective measures of total sleep time, sleep efficiency (percentage of time spent asleep while in bed), number of awakenings after going to sleep, and time taken to fall asleep (sleep latency) were used to assess sleep patterns.

Compared with existing treatment, CBT is likely to result in a large increase in total sleep time based on subjective sleep diary data. It may also improve sleep efficiency, and shorten the amount of time spent awake after falling asleep as well as sleep latency, with sustained improvements, the findings suggest.

But some of the exercise-based interventions also seemed to be effective, when compared with existing treatment.

Yoga likely results in a large increase in total sleep time of nearly 2 hours and may improve sleep efficiency by nearly 15%. It may also reduce the amount of time spent awake after falling asleep by nearly an hour, and shorten sleep latency by around half an hour.

Walking or jogging may result in a large reduction in insomnia severity of nearly 10 points, while Tai Chi may reduce poor sleep quality scores by more than 4 points, increase total sleep time by more than 50 minutes, and reduce time spent awake after falling asleep by over half an hour. It may also shorten sleep latency by around 25 minutes.

Further in-depth analyses revealed that Tai Chi performed significantly better on all subjectively and objectively assessed outcomes than existing treatments for up to 2 years.

There are potentially plausible biological explanations for the findings, say the researchers.

With its focus on body awareness, controlled breathing, and attentional training, yoga may alter brain activity, thereby alleviating anxiety and depressive symptoms which often interfere with a good night's sleep, they suggest.

Tai Chi emphasizes breath control and physical relaxation and has been shown to decrease sympathetic nervous system activity, dampening down hyperarousal, they add. And its combination of meditative movement and mindfulness may promote emotional regulation, deactivate 'mental chatter', and reduce anxiety. It may also help to curb the production of inflammatory chemicals over longer periods, they suggest.

Walking or jogging may improve sleep by increasing energy expenditure, curbing cortisol production, improving emotional regulation, boosting secretion of the sleep hormone melatonin, and enhancing the amount of deep sleep, they continue.

https://www.sciencedaily.com/releases/2025/07/250716000856.htm#:~:text=The%20researchers%20acknowledge,research%20may%20clarify.

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People with eating disorders say cannabis and psychedelics help more than antidepressants

 A pioneering international survey of people living with eating disorders has found that cannabis and psychedelics, such as 'magic mushrooms' or LSD, were best rated as alleviating symptoms by respondents who self-medicated with the non-prescribed drugs.

The worst-rated drugs were alcohol, tobacco, nicotine and cocaine.

Prescribed drugs, such as antidepressants, were generally not well rated for treating eating-disorder symptoms but were positively rated for effects on general mental health.

The research, led by PhD student Sarah-Catherine Rodan at the University of Sydney's Lambert Initiative for Cannabinoid Therapeutics, is published on July 22 in JAMA Network Open.

Ms Rodan said: "Our results provide important insights into the lived experiences of people with eating disorders and their drug use, highlighting promising avenues for future research into treatments.

"The findings suggest more research, including large clinical trials, should be undertaken around the beneficial effects of cannabis and psychedelics for people with eating disorders."

The Lambert Initiative researchers will shortly launch a clinical trial of psilocybin in treating anorexia nervosa in collaboration with the Inside Out Institute at the University of Sydney.

Scope and response of survey

The study analyzed responses from over 7600 self-allocated participants in 83 countries, making it the most comprehensive survey ever conducted on this topic.

The research focused on how people with different types of eating disorders use prescription and non-prescription drugs, and how they perceive these substances' effects on their mental health and eating disorder symptoms.

The major categories of eating disorders were well-represented in the survey: anorexia nervosa (40%); bulimia nervosa (19%); binge-eating disorder (11%); and avoidant/restrictive food intake disorder (ARFID) (9%). About one third of respondents were not formally diagnosed with an eating disorder but self-reported an eating disorder that caused distress.

Co-morbid mental health conditions, which are often found in these populations, were frequently reported including depression (65%), generalised anxiety disorder (55%), ADHD (33%), drug dependence (15%) and alcohol dependence (9%).

Respondents were predominantly female (94%), with most from English-speaking places, like Australia (30%), the UK (21.3%) and the US (18%).

The results revealed patients with eating disorders have high rates of cannabis and psychedelic use relative to the general populations and rate their effects positively in terms of managing symptoms. Notably, cannabis was highly rated by respondents with restrictive eating disorders such as anorexia and ARFID, most likely because it enhances the rewarding value of food, addressing a core issue in these eating disorders.

In contrast, prescription stimulants such as lisdexamfetamine, which have strong appetite suppressing effects and are sometimes prescribed for binge eating disorder (BED), were positively rated by people with BED but poorly rated by those with restrictive type disorders.

Psychedelics, typically only taken once or twice a year by respondents, were reported to have remarkable long-lasting benefits, supporting recent research showing their therapeutic potential in treating conditions such as depression and anxiety. Conversely, commonly prescribed medications - such as antidepressants - which are typically taken daily, were generally rated as relatively ineffective for reducing ED symptoms but were widely acknowledged to help with overall mental health.

The survey also found that drugs like alcohol, nicotine, and cocaine, although quite widely used, led to negative outcomes on eating disorder symptoms and general mental health.

Ms Rodan said: "These findings highlight an important pattern: with traditional medications often falling short in treating eating disorders directly, while many individuals are self-medicating with substances they perceive as helpful. This underlines the urgent need to better investigate these substances in rigorously controlled clinical trials."

Next steps: clinical trials

The insights gained by this study have already prompted further research initiatives. The Lambert Initiative, in collaboration with the Inside Out Institute at the University of Sydney, is preparing to launch a clinical trial of psilocybin in treating anorexia nervosa. Additionally, a pilot study examining the therapeutic potential of the non-intoxicating cannabis component, cannabidiol (CBD), in treating severe anorexia in young people, is nearing completion.

 sources-science daily

Four hidden types of autism revealed — and each tells a different genetic story

 Researchers at Princeton University and the Simons Foundation have identified four clinically and biologically distinct subtypes of autism, marking a transformative step in understanding the condition's genetic underpinnings and potential for personalized care.

Analyzing data from over 5,000 children in SPARK, an autism cohort study funded by the Simons Foundation, the researchers used a computational model to group individuals based on their combinations of traits. The team used a "person-centered" approach that considered a broad range of over 230 traits in each individual, from social interactions to repetitive behaviors to developmental milestones, rather than searching for genetic links to single traits.

This approach enabled the discovery of clinically relevant autism subtypes, which the researchers linked to distinct genetic profiles and developmental trajectories, offering new insights into the biology underlying autism. Their results were published July 9 in Nature Genetics.

"Understanding the genetics of autism is essential for revealing the biological mechanisms that contribute to the condition, enabling earlier and more accurate diagnosis, and guiding personalized care," said senior study author Olga Troyanskaya, director of Princeton Precision Health, the Maduraperuma/Khot Professor of Computer Science and the Lewis-Sigler Institute for Integrative Genomics at Princeton, and deputy director for genomics at the Center for Computational Biology of the Simons Foundation's Flatiron Institute.

The study defines four subtypes of autism -- Social and Behavioral Challenges, Mixed ASD with Developmental Delay, Moderate Challenges, and Broadly Affected. Each subtype exhibits distinct developmental, medical, behavioral and psychiatric traits, and importantly, different patterns of genetic variation.

• Individuals in the Social and Behavioral Challenges group show core autism traits, including social challenges and repetitive behaviors, but generally reach developmental milestones at a pace similar to children without autism. They also often experience co-occurring conditions like ADHD, anxiety, depression or obsessive-compulsive disorder alongside autism. One of the larger groups, this constitutes around 37% of the participants in the study.
• The Mixed ASD with Developmental Delay group tends to reach developmental milestones, such as walking and talking, later than children without autism, but usually does not show signs of anxiety, depression or disruptive behaviors. "Mixed" refers to differences within this group with respect to repetitive behaviors and social challenges. This group represents approximately 19% of the participants.
• Individuals with Moderate Challenges show core autism-related behaviors, but less strongly than those in the other groups, and usually reach developmental milestones on a similar track to those without autism. They generally do not experience co-occurring psychiatric conditions. Roughly 34% of participants fall into this category.
• The Broadly Affected group faces more extreme and wide-ranging challenges, including developmental delays, social and communication difficulties, repetitive behaviors and co-occurring psychiatric conditions like anxiety, depression and mood dysregulation. This is the smallest group, accounting for around 10% of the participants..                                                                                                                         "These findings are powerful because the classes represent different clinical presentations and outcomes, and critically we were able to connect them to distinct underlying biology," said Aviya Litman, a Ph.D. student at Princeton and co-lead author.

• Distinct genetics behind the subtypes

  For decades, autism researchers and clinicians have been seeking robust definitions of autism subtypes to aid in diagnosis and care. Autism is known to be highly heritable, with many implicated genes.

  "While genetic testing is already part of the standard of care for people diagnosed with autism, thus far, this testing reveals variants that explain the autism of only about 20% of patients," said study co-author Jennifer Foss-Feig, a clinical psychologist at the Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai and vice president and senior scientific officer at the Simons Foundation Autism Research Initiative (SFARI). This study takes an approach that differs from classic gene discovery efforts by identifying robust autism subtypes that are linked to distinct types of genetic mutations and affected biological pathways.

  For example, children in the Broadly Affected group showed the highest proportion of damaging de novo mutations -- those not inherited from either parent -- while only the Mixed ASD with Developmental Delay group was more likely to carry rare inherited genetic variants. While children in both of these subtypes share some important traits like developmental delays and intellectual disability, these genetic differences suggest distinct mechanisms behind superficially similar clinical presentations.

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Breakthrough microchip reveals how your body fights viruses—in just 90 minutes

 A new microchip invented by Scripps Research scientists can reveal how a person's antibodies interact with viruses -- using just a drop of blood. The technology offers researchers faster, clearer insights that could help accelerate vaccine development and antibody discovery.

"This lets us take a quick snapshot of antibodies as they are evolving after a vaccine or pathogen exposure," says Andrew Ward, professor in the Department of Integrative Structural and Computational Biology at Scripps Research and senior author of the new paper published in Nature Biomedical Engineeringon June 3, 2025. "We've never been able to do that on this timescale or with such tiny amounts of blood before."When someone is infected with a virus, or receives a vaccine, their immune system creates new antibodies to recognize the foreign invader. Some antibodies work well against the pathogen, while others attach to it only weakly. Figuring out exactly which parts of the virus the best antibodies stick to is key information for scientists trying to optimize vaccines, since they want to design vaccines that elicit strong, reliable immune responses.

"If we know which particular antibodies are leading to the most protective response against a virus, then we can go and engineer new vaccines that elicit those antibodies," says Leigh Sewall, a graduate student at Scripps Research and first author of the new paper.

In 2018, Ward's lab unveiled a technique known as electron microscopy-based polyclonal epitope mapping (EMPEM). This method allowed scientists to visualize how antibodies in blood samples attach to a virus. Although groundbreaking, it had downsides: it took a full week to complete and required relatively large amounts of blood.

"During the COVID-19 pandemic, we began really wanting a way to do this faster," says Alba Torrents de la Peña, a Scripps Research staff scientist who helped lead the work. "We decided to design something from scratch."

With the new system, known as microfluidic EM-based polyclonal epitope mapping (mEM), researchers start with four microliters of blood extracted from a human or animal-about one hundred times less than what's required in original EMPEM. The blood is injected in a tiny, reusable chip where viral proteins are stuck to a special surface. As the blood flow through the chip, antibodies recognize and bind to those. Then, the viral proteins -- with any antibodies attached -- are gently released from the chip and prepared for imaging using standard electron microscopy. The entire process only takes about 90 minutes.

To test the value and effectiveness of mEM, the research team used the system to map antibodies in humans and mice that had either received a vaccination against or been infected with a virus, including influenza, SARS-CoV-2 and HIV. The new technique was not only fast at mapping out the interactions between antibodies and those viruses, but more sensitive than EMPEM; it revealed new antibody binding sites on both influenza and coronavirus proteins that had not been picked up by EMPEM.

To track how antibodies evolved over time in individual mice after they received a vaccination against one of the pathogens, the team took small blood samples from a mouse at different time points.

"That was something that wouldn't have been possible in the past, because of the amount of blood needed for EMPEM," says Sewall. "So to be able to look at an individual over time was really exciting."

The researchers are now working to automate and multiplex the system, which could eventually allow dozens of samples to be processed in parallel. Ultimately, they envision mEM becoming a widely adopted tool to monitor and guide vaccine development in pathogens ranging from coronaviruses to malaria.

"This technology is useful in any situation where you have really limited sample volume, or need initial results quickly," says Torrents de la Peña. "We hope this becomes accessible to more researchers as it is simplified and streamlined."

In addition to Ward, Sewall, and Torrents de la Peña, authors of the study, "Microfluidics Combined with Electron Microscopy for Rapid and High-Throughput Mapping of Antibody-Viral Glycoprotein Complexes," are Rebeca de Paiva Froes Rocha, Grace Gibson, Michelle Louie, Sandhya Bangaru, Andy S. Tran, Gabriel Ozorowski, Blanca Chocarro Ruiz, Nathan Beutler, Thomas F. Rogers, Dennis R. Burton, and Andrew B. Ward of The Scripps Research Institute; Zhenfei Xie and Facundo D. Batista of the Ragon Institute of MGH, MIT and Harvard; and Subhasis Mohanty and Albert C. Shaw of Yale University School of Medicine.

Source: ScienceDaily

This tiny patch could replace biopsies—and revolutionize how we detect cancer

 A patch containing tens of millions of microscopic nanoneedles could soon replace traditional biopsies, scientists have found.

The patch offers a painless and less invasive alternative for millions of patients worldwide who undergo biopsies each year to detect and monitor diseases like cancer and Alzheimer's.Biopsies are among the most common diagnostic procedures worldwide, performed millions of times every year to detect diseases. However, they are invasive, can cause pain and complications, and can deter patients from seeking early diagnosis or follow-up tests. Traditional biopsies also remove small pieces of tissue, limiting how often and how comprehensively doctors can analyse diseased organs like the brain.

Now, scientists at King's College London have developed a nanoneedle patch that painlessly collects molecular information from tissues without removing or damaging them. This could allow healthcare teams to monitor disease in real time and perform multiple, repeatable tests from the same area - something impossible with standard biopsies.

Because the nanoneedles are 1,000 times thinner than a human hair and do not remove tissue, they cause no pain or damage, making the process less painful for patients compared to standard biopsies. For many, this could mean earlier diagnosis and more regular monitoring, transforming how diseases are tracked and treated.

Dr Ciro Chiappini, who led the research published today in Nature Nanotechnology, said: "We have been working on nanoneedles for twelve years, but this is our most exciting development yet. It opens a world of possibilities for people with brain cancer, Alzheimer's, and for advancing personalised medicine. It will allow scientists - and eventually clinicians - to study disease in real time like never before."

The patch is covered in tens of millions of nanoneedles. In preclinical studies, the team applied the patch to brain cancer tissue taken from human biopsies and mouse models. The nanoneedles extracted molecular 'fingerprints' -- including lipids, proteins, and mRNAs -- from cells, without removing or harming the tissue.

The tissue imprint is then analysed using mass spectrometry and artificial intelligence, giving healthcare teams detailed insights into whether a tumour is present, how it is responding to treatment, and how disease is progressing at the cellular level.

Dr Chiappini said: "This approach provides multidimensional molecular information from different types of cells within the same tissue. Traditional biopsies simply cannot do that. And because the process does not destroy the tissue, we can sample the same tissue multiple times, which was previously impossible."

Source: ScienceDaily

Cold sore virus hijacks human genome in 3D--and scientists found its weak spot

 Viruses are entirely dependent on their hosts to reproduce. They ransack living cells for parts and energy and hijack the host's cellular machinery to make new copies of themselves. Herpes simplex virus-1 (HSV-1), it turns out, also redecorates, according to a new study in Nature Communications.

Researchers at the Center for Genomic Regulation (CRG) in Barcelona have discovered the cold sore virus reshapes the human genome's architecture, rearranging its shape in three-dimensional space so that HSV-1 can access host genes most useful for its ability to reproduce."HSV-1 is an opportunistic interior designer, reshaping the human genome with great precision and choosing which bits it comes into contact with. It's a novel mechanism of manipulation we didn't know the virus had to exploit host resources," says Dr. Esther González Almela, first author of the study.

While other herpes viruses have been seen compacting and reshaping host chromosomes, it was unclear whether it was a side effect of the virus invading and setting up its own viral replication factories. The study is the first proof that HSV-1 reshapes the human genome deliberately and within hours of infection.

Crucially, the researchers found that blocking a single host enzyme, topoisomerase I, completely blocked HSV-1's ability to rearrange the human genome during infection, bringing the hostile takeover to a halt. The discovery represents a new potential strategy to control a virus which infects nearly four billion people worldwide.

"In cell culture, inhibiting this enzyme stopped the infection before the virus could make a single new particle," says ICREA Research Professor Pia Cosma, corresponding author of the study at the Center for Genomic Regulation (CRG) in Barcelona. "That gives us a potential new therapeutic target to stop infection."

The researchers made the findings by combining super-resolution microscopy, an imaging technique which can see structures 20 nanometers wide, around 3,500 times thinner than a strand of hair, with Hi-C, a technique that reveals which bits of DNA are touching inside the nucleus. They used both techniques to gain new mechanistic insights into how HSV-1 hijacks human cells.

They found the hostile takeover begins within the first hour, with the virus hijacking the human RNA-polymerase II enzyme to help synthesize its own proteins. Topoisomerase I, an enzyme that snips DNA to release torsional stress, and cohesin, a structural protein, followed human RNA-polymerase II into the newly forming viral replication compartments.

Three hours after infection, most polymerase and a sizeable fraction of the other two factors had abandoned human genes. The wholesale theft causes transcription to collapse across the host genome, which in turn caused chromatin, the human genome's natural state inside cells, to be crushed into a dense shell just 30% of its original volume.This was an unexpected finding, as the structure of chromatin is thought to dictate transcription. "We always thought dense chromatin shut genes down but here we see the opposite: stop enough transcription first and the DNA compacts afterwards. The relationship between activity and structure might be a two-way street," says Dr. Álvaro Castells García, co-first author of the study.

Two in every three people under age 50 live with HSV-1. Once infected, people have the virus for life, though most cases are asymptomatic or manifest as recurrent cold sores. Rarely, the virus can cause blindness or life-threatening disease in newborns and immunocompromised people.

The findings of the study can help address the public health burden of HSV-1, which is considered a global health challenge because of its prevalence and ability to cause recurrent outbreaks. Though treatments are available to manage symptoms, drug-resistant strains are on the rise, and there is no cure.

Source: ScienceDaily

Inside the tumor: AI cracks five hidden cell types to stop cancer’s comeback

 A multinational team of researchers, co-led by the Garvan Institute of Medical Research, has developed and tested a new AI tool to better characterize the diversity of individual cells within tumors, opening doors for more targeted therapies for patients.

Findings on the development and use of the AI tool, called AAnet, have today been published in Cancer Discovery, a journal of the American Association for Cancer Research.

Not all tumor cells the same

Tumors aren't made up of just one cell type - they're a mix of different cells that grow and respond to treatment in different ways. This diversity, or heterogeneity, makes cancer harder to treat and can in turn lead to worse outcomes, especially in triple-negative breast cancer.

"Heterogeneity is a problem because currently we treat tumors as if they are made up of the same cell. This means we give one therapy that kills most cells in the tumor by targeting a particular mechanism. But not all cancer cells may share that mechanism. As a result, while the patient may have an initial response, the remaining cells can grow and the cancer may come back," says Associate Professor Christine Chaffer, co-senior author of the study and Co-Director of the Cancer Plasticity and Dormancy Program at Garvan.

But while heterogeneity is a problem, researchers don't know enough to characterize it: "So far researchers haven't been able to clearly explain how adjacent cells in a tumor differ from each other, and how to classify those differences into meaningful ways to better treat tumors. But this is exactly what we need to know so we can kill all cells within that tumor with the right therapies," Associate Professor Chaffer adds.

A new tool characterizes five new cancer cell groups

To solve this problem, the team developed and trained a powerful new AI tool called AAnet that can detect biological patterns in cells within tumors.

They then used the AI tool to uncover patterns in the level of gene expression of individual cells within tumors, focusing on preclinical models of triple-negative breast cancer and human samples of ER positive, HER2 positive and triple-negative breast cancer. Through this, they identified five different cancer cell groups within a tumor, with distinct gene expression profiles that indicated vast differences in cell behaviour.

"By using our AI tool, we were consistently able to discover five new groups of cell types within single tumors called 'archetypes'. Each group exhibited different biological pathways and propensities for growth, metastasis and markers of poor prognosis. Our next steps are to see how these groups may change over time, for example before and after chemotherapy," says Associate Professor Chaffer.

This is a first for cancer research. Co-lead, Associate Professor Smita Krishnaswamy from Yale University who led the development of the AI tool states: "Thanks to technology advances, the last 20 years have seen an explosion of data at the single-cell level. With this data we have been finding out that not only is each patient's cancer different, but each cancer cell behaves differently from another. Our study is the first time that single-cell data have been able to simplify this continuum of cell states into a handful of meaningful archetypes through which diversity can be analyzed to find meaningful associations with spatial tumor growth and metabolomic signatures. This could be a game changer."

New classification to drive better, targeted treatments

The researchers say the use of AAnet to characterize the different groups of cells in a tumor according to their biology opens doors for a paradigm shift in how we treat cancer.

"Currently the choice of cancer treatment for a patient is largely based on the organ that the cancer came from such as breast, lung or prostate and any molecular markers it may exhibit. But this assumes that all cells in that cancer are the same. Instead, now we have a tool to characterize the heterogeneity of a patient's tumor and really understand what each group of cells is doing at a biological level. With AAnet, we now hope to improve the rational design of combination therapies that we know will target each of those different groups through their biological pathways. This has the potential to vastly improve outcomes for that patient," says Associate Professor Chaffer.

On the application of AAnet, co-senior author of the study and Chief Scientific Officer of Garvan Professor Sarah Kummerfeld states: "We envision a future where doctors combine this AI analysis with traditional cancer diagnoses to develop more personalized treatments that target all cell types within a person's unique tumor. These results represent a true melding of cutting-edge technology and biology that can improve patient care. Our study focused on breast cancer, but it could be applied to other cancers and illnesses such as autoimmune disorders. The technology is already there."

Source: ScienceDaily

This virus infects millions—and we just discovered its secret weapon

 New research from the University of Pittsburgh School of Medicine and La Jolla Institute for Immunology, published today (June 30) in Nature Microbiology, reveals an opportunity for developing a therapy against cytomegalovirus (CMV), the leading infectious cause of birth defects in the United States.

Researchers discovered a previously unappreciated mechanism by which CMV, a herpes virus that infects the majority of the world's adult population, enters cells that line the blood vessels and contributes to vascular disease. In addition to using molecular machinery that is shared by all herpes viruses, CMV employs another molecular "key" that allows the virus to sneak through a side door and evade the body's natural immune defenses.The finding might explain why efforts to develop prophylactic treatments against CMV have, so far, been unsuccessful. This research also highlights a new potential avenue for the development of future antiviral drugs and suggests that other viruses of the herpes family, such as Epstein-Barr and chickenpox, could use similar molecular structures to spread from one infected cell to the next while avoiding immune detection.

"If we don't know what weapons the enemy is using, it is hard to protect against it," said senior author Jeremy Kamil, Ph.D., associate professor of microbiology and molecular genetics at Pitt. "We found a missing puzzle piece that represents one possible reason why immunization efforts against CMV have been unsuccessful."

In the United States, approximately one in every 200 babies is born with congenital CMV infection. Of the babies infected, one in five will have birth defects, such as hearing loss, or go on to have long-term health challenges. For most adults, CMV infections are asymptomatic. But a CMV infection during pregnancy presents significant health risks to the unborn child and could be deadly for people who are immunosuppressed, including organ transplant recipients.

Because of the large size of its genome and its complicated molecular machinery, CMV long evaded attempts to develop prophylactic treatments. Similar to other herpes viruses, CMV relies on a protein called gH to enter cells of the vessel lining. But unlike other herpes viruses, which use a protein partner called gL to facilitate infection, the new study found that CMV replaces gL with another partner called UL116 and recruits a protein called UL141. The resulting complex of gH-UL116-UL141, called GATE by the authors, then becomes an alternative tool for breaking into cells lining the blood vessels and causing internal damage while simultaneously preventing the body's own immune system from recognizing the signs of infection.The newly discovered GATE could become a potential vaccine target for CMV and other herpes viruses.

"Previous attempts to generate a CMV vaccine have failed, but that was before we identified the GATE complex. We hope that new strategies targeting GATE will improve our chances to combat CMV infection, and also perhaps cleanse our bodies of this lifelong infection," said Chris Benedict, Ph.D., associate professor at La Jolla Institute for Immunology and co-senior author of the study with Kamil and LJI professor, president & CEO Erica Ollmann Saphire, Ph.D., MBA. "If we can develop antiviral drugs or vaccines that inhibit CMV entry, this will allow us to combat the many diseases this virus causes in developing babies and immune-compromised people."

Other authors of this research are Michael Norris, Ph.D., of the University of Toronto; Lauren Henderson, Mohammed Siddiquey, Ph.D., both of Louisiana State University Health Shreveport; and Jieyun Yin, Ph.D., Kwangsun Yoo, Ph.D., Simon Brunel, Ph.D., Michael Mor, Ph.D., and Erica Ollmann Saphire, Ph.D., all of La Jolla Institute for Immunology.

Source: ScienceDaily

Sweet-smelling molecule halts therapy-resistant pancreatic cancer

 Cancer cells have the capacity to multiply rapidly. The aggressive cancer cells undergo conversion from their tightly connected epithelial state into a mesenchymal state, which lacks contact restrictions and spreads easily to other parts of the body. Such epithelial-to-mesenchymal plasticity also makes the cancer cells resistant to elimination by anticancer therapies.

The search is ongoing for newer anticancer agents that can overcome this acquired resistance to therapy and destroy the 'rogue' cancer cells. A group of researchers led by Dr. Hideyuki Saya, Director of the Oncology Innovation Center, Fujita Health University, Japan, has uncovered the mechanism of the anticancer activity of benzaldehyde, a compound responsible for the aroma of almonds, apricots, and figs.

Giving insights into their motivation for this study, Dr. Saya explains, "In the 1980s, researchers demonstrated the anticancer activity of benzaldehyde and its derivatives. The first author of our study, Dr. Jun Saito, is the daughter of one of the researchers involved in those early studies, and she was driven by a strong desire to uncover the mechanism behind benzaldehyde's anticancer effects." This study, published online in the British Journal of Cancer on May 02, 2025, shows the impact of benzaldehyde on key signaling protein interactions within the cancer cells and the resulting cytotoxicity.

Early studies reported the ability of benzaldehyde to inhibit the progressive development of mouse embryonic cells, indicating its potential in preventing rapid cell proliferation. Here, the anticancer effects of benzaldehyde were studied by using a mouse model grafted to have a growing pancreatic cancer.

In cell culture studies, benzaldehyde inhibited the growth of cancer cells resistant to radiation therapy and also those resistant to treatment with osimertinib, an agent blocking tyrosine kinases in growth factor signaling. Benzaldehyde synergized with radiation to eliminate previously radiation-resistant cancer cells.

The study findings revealed that benzaldehyde exerted its anticancer effects by preventing interactions of the signaling protein 14-3-3ζ with the Ser28-phosphorylated form of histone H3 (H3S28ph). This interaction, key to cancer cell survival, was also responsible for treatment resistance and the expression of genes related to epithelial-mesenchymal plasticity.

Here, benzaldehyde prevented 14-3-3ζ-dependent phosphorylation of the serine28 amino acid of histone H3. Consequently, benzaldehyde treatment reduced the expression of genes responsible for treatment resistance. Treatment of mice with a benzaldehyde derivative inhibited the growth of pancreatic tumors and suppressed the epithelial-to-mesenchymal plasticity, thus preventing the spread of cancer to distant organs like the lungs.

Source: ScienceDaily

Tirzepatide: The weight-loss drug that also shrinks breast tumors in mice

 The anti-obesity medication tirzepatide, marketed as Mounjaro for diabetes and Zepbound for obesity, reduced obesity-associated breast cancer growth in a mouse model, according to a study being presented at ENDO 2025, the Endocrine Society's annual meeting in San Francisco, Calif.

"Obesity is a significant risk factor for breast cancer, and while it is very preliminary data, our studies in mice suggest that these new anti-obesity drugs may be a way to reduce obesity-associated breast cancer risk or improve outcomes," said study author Amanda Kucinskas, B.S., a Ph.D. candidate in the labs of Drs. Erin Giles and Kanakadurga Singer at the University of Michigan in Ann Arbor, Mich.Existing research has shown that having obesity can lead to worse breast cancer outcomes compared to those who do not have obesity, and weight loss can improve outcomes. However, there are many challenges with traditional weight loss methods.

Kucinskas and colleagues leveraged tirzepatide, one of a new class of effective anti-obesity medications that target GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide) receptors. The researchers sought to learn whether or not tirzepatide would reduce obesity-associated breast cancer growth.

This mouse study included 16 mice. The 9-week-old C57BL/6 mice were fed a 40% high-fat diet and housed in a warm environment to induce obesity. At 32 weeks of age, the mice with obesity were randomly assigned injections of tirzepatide or a placebo every other day for 16 weeks. Tumor volumes were measured twice weekly.

The researchers found that the anti-obesity drug reduced body weight and body fat by approximately 20% in mice, similar to the amount of weight loss achieved by women on this drug. They found this was primarily due to a loss of adipose mass, with a reduction in adipose depot weights compared to controls.

The anti-obesity drug also reduced tumor volume compared to the controls. At the end of the study, the researchers found that tumor volume was significantly correlated with body weight, total adipose mass and the amount of fat stored in the liver.

"While these are very preliminary results, they suggest that this new anti-obesity drug may also have a beneficial impact on breast cancer outcomes," Kucinskas said.

Ongoing studies are underway in collaboration with Dr. Steve Hursting's lab at the University of North Carolina at Chapel Hill to separate the weight loss from the tumor-specific effects of tirzepatide.

Source: ScienceDaily

Immune system discovery reveals potential solution to Alzheimer's

 A new way of thinking about Alzheimer's disease has yielded a discovery that could be the key to stopping the cognitive decline seen in Alzheimer's and other neurodegenerative diseases.

University of Virginia School of Medicine scientists have been investigating the possibility that Alzheimer's is caused, at least in part, by the immune system's wayward attempts to fix DNA damage in the brain. Their research reveals that an immune molecule called STING drives the formation of the harmful plaques and protein tangles thought responsible for Alzheimer's. Blocking the molecule protected lab mice from mental decline, the researchers say.

An important player in the brain's immune system, STING also may be a key contributor to Parkinson's disease, amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), dementia and other memory-robbing conditions. That means that developing treatments to control its activity could have far-reaching benefits for many patients facing now-devastating diagnoses.

"Our findings demonstrate that the DNA damage that naturally accumulates during aging triggers STING-mediated brain inflammation and neuronal damage in Alzheimer's disease," said researcher John Lukens, PhD, director of UVA's Harrison Family Translational Research Center in Alzheimer's and Neurodegenerative Diseases. "These results help to explain why aging is associated with increased Alzheimer's risk and uncover a novel pathway to target in the treatment of neurodegenerative diseases."

Alarming Trends in Alzheimer's

Alzheimer's is a growing problem across the country and around the world: More than 7 million Americans are already living with the condition, and that number could top 13 million by 2050. That has researchers working frantically to find ways to better understand and treat the condition.

The causes of Alzheimer's remain murky, but scientists are increasingly coming to appreciate the role of the immune system in the disease's development. STING is part of that immune response; the molecule helps direct the clearance of viruses and stressed cells harboring DNA damage.

While STING is an important defender of the brain, it can also become hyperactive and cause harmful inflammation and tissue damage. That had Lukens and his team eager to determine what part it could be playing in Alzheimer's. Blocking the molecule's activity in lab mice, they found, helped prevent Alzheimer's plaque formation, altered the activity of immune cells called microglia and redirected the workings of important genes, among other effects.

"We found that removing STING dampened microglial activation around amyloid plaques, protected nearby neurons from damage and improved memory function in Alzheimer's model mice," said researcher Jessica Thanos, part of UVA's Department of Neuroscience and Center for Brain Immunology and Glia (BIG Center). "Together, these findings suggest that STING drives detrimental immune responses in the brain that exacerbate neuronal damage and contribute to cognitive decline in Alzheimer's disease."

Promising Treatment Target

While scientists have been investigating other molecules thought to be important in Alzheimer's, STING makes for a particularly attractive target for developing new treatments, the UVA Health researchers say. That's because blocking STING appears to slow both the buildup of amyloid plaques and the development of tau tangles, the two leading candidates for the cause of Alzheimer's. Other molecules lack that robust involvement, and, further, could be targeted only at very specific -- and very limited -- stages in the disease's progression.

"We are only beginning to understand the complex role of innate immune activation in the brain, and this is especially true in both normal and pathological aging," Thanos said. "If we can pinpoint which cells and signals sustain that activation, we will be in a much better position to intervene effectively in disease."

While Lukens' pioneering research has opened new doors in the fight against Alzheimer's, much more work will need to be done to translate the findings into treatments. For example, scientists will need to better understand STING's roles in the body -- such as in the immune system's response to cancer -- to ensure any new treatment doesn't cause unwanted side effects.

But those are the types of big questions that Lukens and his collaborators at the Harrison Family Translational Research Center are eager to tackle as part of their efforts to fast-track new treatments and, eventually, they hope, cures. (The center is part of UVA's Paul and Diane Manning Institute of Biotechnology, now under construction at Fontaine Research Park.)

"Our hope is that this work moves us close to finding safer and more effective ways to protect the aging brain, as there is an urgent need for treatments that can slow or prevent neuronal damage in Alzheimer's," Lukens said. "Shedding light on how STING contributes to that damage may help us target similar molecules and ultimately develop effective disease-modifying treatments."

Findings Published

The researchers have published their findings in Alzheimer's & Dementia: The Journal of the Alzheimer's Association. The research team consisted of Thanos, Olivia C. Campbell, Maureen N. Cowan, Katherine R. Bruch, Katelyn A. Moore, Hannah E. Ennerfelt, Nick R. Natale, Aman Mangalmurti, Nagaraj Kerur and Lukens. The scientists have no financial interest in the work.

The study was supported by the National Institutes of Health's National Institute of Aging, grants R01AG071996, R01AG087406 and RF1AG078684; the Alzheimer's Association, grant ADSF-21-816651; the Cure Alzheimer's Fund; The Owens Family Foundation; and The Harrison Family Foundation.

sources-science daily

Guardrails, education urged to protect adolescent AI users Report cites benefits and dangers of new technology

 The effects of artificial intelligence on adolescents are nuanced and complex, according to a report from the American Psychological Association that calls on developers to prioritize features that protect young people from exploitation, manipulation and the erosion of real-world relationships.

"AI offers new efficiencies and opportunities, yet its deeper integration into daily life requires careful consideration to ensure that AI tools are safe, especially for adolescents," according to the report, entitled "Artificial Intelligence and Adolescent Well-being: An APA Health Advisory." "We urge all stakeholders to ensure youth safety is considered relatively early in the evolution of AI. It is critical that we do not repeat the same harmful mistakes made with social media."

The report was written by an expert advisory panel and follows on two other APA reports on social media use in adolescence and healthy video content recommendations.

The AI report notes that adolescence -- which it defines as ages 10-25 -- is a long development period and that age is "not a foolproof marker for maturity or psychological competence." It is also a time of critical brain development, which argues for special safeguards aimed at younger users.

"Like social media, AI is neither inherently good nor bad," said APA Chief of Psychology Mitch Prinstein, PhD, who spearheaded the report's development. "But we have already seen instances where adolescents developed unhealthy and even dangerous 'relationships' with chatbots, for example. Some adolescents may not even know they are interacting with AI, which is why it is crucial that developers put guardrails in place now."

The report makes a number of recommendations to make certain that adolescents can use AI safely. These include:

Ensuring there are healthy boundaries with simulated human relationships. Adolescents are less likely than adults to question the accuracy and intent of information offered by a bot, rather than a human.

Creating age-appropriate defaults in privacy settings, interaction limits and content. This will involve transparency, human oversight and support and rigorous testing, according to the report.

Encouraging uses of AI that can promote healthy development. AI can assist in brainstorming, creating, summarizing and synthesizing information -- all of which can make it easier for students to understand and retain key concepts, the report notes. But it is critical for students to be aware of AI's limitations.

Limiting access to and engagement with harmful and inaccurate content. AI developers should build in protections to prevent adolescents' exposure to harmful content.

Protecting adolescents' data privacy and likenesses. This includes limiting the use of adolescents' data for targeted advertising and the sale of their data to third parties.

The report also calls for comprehensive AI literacy education, integrating it into core curricula and developing national and state guidelines for literacy education.

"Many of these changes can be made immediately, by parents, educators and adolescents themselves," Prinstein said. "Others will require more substantial changes by developers, policymakers and other technology professionals."

Report: https://www.apa.org/topics/artificial-intelligence-machine-learning/health-advisory-ai-adolescent-well-being

In addition to the report, further resources and guidance for parents on AI and keeping teens safe and for teens on AI literacy are available at APA.org.

sources-science daily