Researchers at Tel Aviv University have made a groundbreaking discovery that could change our understanding of genetic mutations and their impact on brain development. The study reveals that not all genetic mutations are detrimental; some may protect against developmental conditions.
Under the leadership of Professor Illana Gozes, Director of The Elton Laboratory for Molecular Neuroendocrinology, the research team discovered a protective inherited mutation in the Activity-Dependent Neuroprotective Protein (ADNP) gene. This finding challenges the conventional belief that mutations in the ADNP gene always result in developmental difficulties. .
“I was struck by how this particular mutation enhanced certain protein interactions, potentially offering protection against developmental disorders,” explains Dr. Gozes. “This discovery opens up entirely new perspectives on how we view genetic variations and their impact on brain development.”
The study focused on a unique case where a mother carrying an ADNP mutation showed above-average adaptive behaviour. In contrast, her child, inheriting this protective mutation and a second variant, demonstrated better outcomes than in similar cases.
Key findings include:
• The protective mutation (ADNP_Glu931Glyfs*12) creates an additional protein interaction site
• This enhancement leads to stronger cellular connections and improved protein function
• The discovery suggests potential new therapeutic approaches for neurodevelopmental disorders
This finding is particularly intriguing because it might influence our approach to genetic therapy. Could other seemingly harmful mutations harbour unexpected benefits? How might this knowledge be applied to develop more effective treatments?
Dr Shula Shazman, a study co-author, notes that their computational modelling revealed how this protective mutation strengthens crucial cellular processes. This insight raises interesting questions about the potential for identifying similar protective mutations in other genes associated with neurodevelopmental disorders.
The research has immediate implications for understanding and treating ADNP syndrome, a rare genetic condition affecting brain development. More broadly, it challenges us to reconsider our assumptions about genetic mutations in neurodevelopmental disorders.
The study employed advanced computational modeling alongside clinical observations, led by the psychiatrist, Prof. Joseph Levine. The results demonstrated how modern bioinformatics can reveal unexpected benefits in genetic variations previously considered purely detrimental.
Looking ahead, this research opens several compelling avenues for further investigation: How common are protective mutations in other neurological conditions? Could this discovery lead to new therapeutic strategies for related disorders?
A study from Rutgers Health and other institutions indicates that stress hormones – not impaired cellular insulin signalling – may be the primary driver of obesity-related diabetes.
“We have been interested in the basic mechanisms of how obesity induces diabetes. Given that the cost of the diabetes epidemic in the U.S. alone exceeds $300 billion per year, this is a critically important question,” said Christoph Buettner, chief of endocrinology, metabolism and nutrition at Rutgers Robert Wood Johnson Medical School and the study’s senior author.
Scientists have long thought obesity causes diabetes by impairing insulin signalling within the liver and fat cells. However, new research shows that overeating and obesity increase the body’s sympathetic nervous system—the “fight or flight” response—and that the increased levels of the stress hormones norepinephrine and epinephrine counteract insulin’s effects even though cellular insulin signalling still works.
The authors observed that overeating in normal mice increases the stress hormone norepinephrine within days, indicating how quickly surplus food stimulates the sympathetic nervous system.
To see what effect this excess hormone production has in spurring disease development, the authors then deployed a new type of genetically engineered mice that are normal in every way but one: They cannot produce stress hormones catecholamines outside of their brains and central nervous systems.
The researchers fed these mice the obesity-inducing high-fat and high-sugar diet, but although they ate as many calories and got just as obese as normal mice, they did not develop metabolic disease.
“We were delighted to see that our mice ate as much because it indicates that the differences in insulin sensitivity and their lack of metabolic disease are not due to reduced food intake or reduced obesity but the greatly reduced stress hormones. These mice cannot increase stress hormones that counteract insulin; hence, insulin resistance does not develop during obesity development.”
The new findings may help explain why some obese individuals develop diabetes while others don’t and why stress can worsen diabetes even with little weight gain.
“Many types of stress – financial stress, marital stress, the stress associated with living in dangerous areas or suffering discrimination or even the physical stress that comes from excessive alcohol consumption — all increase diabetes and synergize with the metabolic stress of obesity,” Buettner said.
“Our finding that even obesity principally induces metabolic disease via increased stress hormones provides new insight into the common basis for all these factors that increase the risk of diabetes. Stress and obesity, in essence, work through the same basic mechanism in causing diabetes, through the actions of stress hormones.”
While it is well known that catecholamines can impair insulin action, the new study suggests that this may be the fundamental mechanism underlying insulin resistance in obesity. The dynamic interplay between stress hormones, which work in opposition to insulin, has long been known. Stress hormones increase glucose and lipids in the bloodstream, while insulin lowers these. However, an unexpected finding of the new study is that insulin signaling can remain intact even in insulin-resistant states like obesity. It’s just that the heightened activity of stress hormones effectively “push the gas pedal harder,” resulting in increased blood sugar and fat levels. Even though the level of insulin’s “braking” effect remains the same, the accelerated gas pedal effect of catecholamines overwhelms the brake effect of insulin and results in relatively diminished insulin action.
“Some colleagues are at first surprised that insulin resistance can exist even though cellular insulin signaling is intact. But let’s not forget that the gas pedal effects of stress hormones are exerted through very different signaling pathways than insulin signaling. That explains why the ability of insulin to ‘brake’ and reduce the release of sugar and fat into the bloodstream is impaired even though insulin signaling is intact because stress signaling is predominant.”
The findings suggest that medications that reduce catecholamines, a term for all the stress-related hormones and neurotransmitters produced by the SNS and the adrenal gland, might help prevent or treat diabetes. However, medicines that block catecholamines, as they are currently used to treat high blood pressure, haven’t shown major benefits for diabetes. This may be because current drugs don’t block the relevant receptors or because they affect the brain and body in complex ways, Buettner said.
Buettner and the study’s first author, Kenichi Sakamoto, an assistant professor of endocrinology at Robert Wood Johnson Medical School, are planning human studies to confirm their findings. They’re also examining the role of the sympathetic nervous system and other forms of diabetes, including Type 1 diabetes.
“We would like to study if short-term overfeeding, as some of us experience during the holidays by gaining five to 10 pounds, increases insulin resistance with heightened sympathetic nervous system activation,” Buettner said.
The findings may ultimately lead to new therapeutic approaches to tackle insulin resistance, diabetes and metabolic disease, focused on reducing stress hormones rather than targeting insulin signaling.
“We hope this paper provides a different take on insulin resistance,” Buettner said. “It may also explain why none of the drugs currently used to treat insulin resistance, except insulin itself, directly increases cellular insulin signaling.”
According to a new study, a mid-day walk or household chores may improve cognitive processing speed, equivalent to four years younger.
Exercise has been shown to improve brain health and reduce the risk of cognitive decline and dementia over the long term. However, engaging in everyday physical activity has immediate benefits for brain health, according to a new study by Penn State College of Medicine researchers.
The team found that middle-aged people who participated in everyday movement showed improvement in cognitive processing speed equivalent to being four years younger, regardless of whether the activity was lower intensity, like walking the dog or doing household chores, or higher intensity, like jogging.
“You don’t have to go to the gym to experience all the potential benefits of physical activity,” said Jonathan Hakun, assistant professor of neurology and psychology at Penn State and the Penn State College of Medicine. “All movement is important. Everyday movement is a source of accumulated physical activity that could be credited toward a healthy lifestyle and may directly impact cognitive health.”
Previous research that has examined the relationship between physical activity and cognitive health typically looked at the long-term relationship, for example, over decades for a retrospective study or months to a year for intervention studies. Hakun said he was interested in connecting the dots sooner to understand the potential short-term impact of physical activity on cognitive health.
The research team leveraged smartphone technology to interact with participants multiple times during their daily lives using ecological momentary assessment. Over nine days, participants checked in six times a day, approximately every 3.5 hours.
During each check-in, participants reported if they had been physically active since their last check-in. If they were active, they were asked to rate the intensity of their activity — light, moderate or vigorous. For example, walking and cleaning were considered light intensity while running, fast biking and effortful hiking were considered vigorous. Participants were then prompted to play two “brain games,” one designed to assess cognitive processing speed and the other designed to evaluate working memory, which Hakun said can be a proxy for executive function.
The team found that when participants reported being physically active sometime in the previous 3.5 hours, they showed improvements in processing speed equivalent to being four years younger. While there were no improvements in working memory, the response time during the working memory task mirrored the improvements observed for processing speed.
“We get slower as we age, both physically and cognitively. The idea here is that we can momentarily counteract that through movement. It’s compelling,” Hakun said. “There’s the potential for a brief walk or a little extra movement to give you a boost.”
Additionally, people who reported being active more often experienced more incredible short-term benefits than those who reported less physical activity overall. Hakun said this suggests that regular physical activity may increase cognitive health benefits. However, he explained that more research is needed to understand how much physical activity and the frequency and timing of being active influence cognitive health.
Vowel density maps reveal that distinct vowel spaces for vocalizations of pain, disgust, and joy remain consistent across languages. Credit Ponsonnet et al.
An estimated 7,000 languages are spoken worldwide, each offering unique ways to express human emotion. But do certain emotions show regularities in their vocal expression across languages?
In JASA, published on behalf of the Acoustical Society of America by AIP Publishing, an interdisciplinary team of linguists and bioacousticians led by Maïa Ponsonnet, Katarzyna Pisanski, and Christophe Coupé explored this by comparing expressive interjections (like “wow!”) to nonlinguistic vocalizations (like screams and cries) across the globe.
Pisanski explained how studying cries, screams, and laughter can shed light on the origins of speech.
“Why did humans start to speak, and other primates didn’t? We all produce laughter, and hundreds of species produce playlike vocalizations,” said Ponsonnet. “Yet we are the only species that evolved spoken language. These commonalities across species can help us understand where humans diverged and how.
“Critically, by comparing interjections to vocalizations expressing the same emotions, we can test whether the acoustic patterns we observe in interjections can be traced back to vocalizations.”
The researchers analyzed vowels in interjections from 131 languages, comparing them with nearly 500 vowels from vocalizations produced in joyful, painful, or disgusting contexts.
They predicted that the vocalizations’ acoustic forms reflect their adaptive or social functions. “We believe that many vocal expressions have a function. For example, babies’ cries tend to be loud and harsh, evolving to annoy parents enough to stop the aversive signal. We expect vocal expressions of pain, disgust, and joy to reflect their functions too,” said Pisanski.
The researchers found evidence to support this for vocalizations: Each of the three emotions yielded consistent and distinct vowel signatures across cultures. Pain interjections also featured similar open vowels, such as “a,” and wide falling diphthongs, such as “ai” in “Ay!” and “aw” in “Ouch!” However, for disgusted and joyful emotions, in contrast to vocalizations, the interjections lacked regularities across cultures. The researchers expressed surprise at this latter finding.
The team aims to expand this research across more cultures and emotions to understand better how widespread vocal expressions arise and where they come from.
The work provides novel genetic insights into dietary preferences and opens the possibility of selectively targeting SI to reduce sucrose intake at the population level.
The study was led by Dr. Peter Aldiss, “Excess calories from sugar are an established contributor to obesity and type 2 diabetes. In the UK, we consume 9-12% of our dietary intake from free sugars, such as sucrose, with 79% consuming up to three sugary snacks daily. At the same time, genetic defects in sucrose digestion have been associated with irritable bowel syndrome, a common functional disorder affecting up to 10% of the population.
“Our study suggests that genetic variation in our ability to digest dietary sucrose may impact not only how much sucrose we eat, but how much we like sugary foods.”
The experts began by investigating the dietary behaviours in mice lacking the SI gene. Here, mice developed a rapid reduction in sucrose intake and preference. This was confirmed in two large population-based cohorts involving 6,000 individuals in Greenland and 134,766 in the UK BioBank.
The team took a nutrigenetics approach to understanding how genetic variation in the SI gene impacts sucrose intake and preference in humans. Strikingly, individuals with a complete inability to digest dietary sucrose in Greenland consumed significantly less sucrose-rich foods, while individuals with a defective, partially functional SI gene in the UK liked sucrose-rich foods less.
“These findings suggest that genetic variation in our ability to digest dietary sucrose can influence our intake, and preference, for sucrose-rich foods whilst opening up the possibility of targeting SI to reduce sucrose intake at the population level selectively,” says Dr Aldiss.
“In the future, understanding how defects in the SI gene act to reduce the intake, and preference, of dietary sucrose will facilitate the development of novel therapeutics to help curb population-wide sucrose intake to improve digestive and metabolic health.”
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