Placebos reduce stress, anxiety, depression -- even when people know they are placebos

A study out of Michigan State University found that nondeceptive placebos, or placebos given with people fully knowing they are placebos, effectively manage stress -- even when the placebos are administered remotely.

Researchers recruited participants experiencing prolonged stress from the COVID-19 pandemic for a two-week randomized controlled trial.

Half of the participants were randomly assigned to a nondeceptive placebo group and the other half to the control group that took no pills.

The participants interacted with a researcher online through four virtual sessions on Zoom.

Those in the nondeceptive placebo group received information on the placebo effect and were sent placebo pills in the mail along with and instructions on taking the pills.

The study, published in Applied Psychology: Health and Well-Being, found that the nondeceptive group showed a significant decrease in stress, anxiety and depression in just two weeks compared to the no-treatment control group.

Participants also reported that the nondeceptive placebos were easy to use, not burdensome and appropriate for the situation.

"Exposure to long-term stress can impair a person's ability to manage emotions and cause significant mental health problems long-term, so we're excited to see that an intervention that takes minimal effort can still lead to significant benefits," said Jason Moser, co-author of the study and professor in MSU's Department of Psychology.

"This minimal burden makes nondeceptive placebos an attractive intervention for those with significant stress, anxiety and depression."

The researchers are particularly hopeful in the ability to remotely administer the nondeceptive placebos by health care providers.

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Physical activity reduces stress-related brain activity to lower cardiovascular disease risk

New research indicates that physical activity lowers cardiovascular disease risk in part by reducing stress-related signaling in the brain.

In the study, which was led by investigators at Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham healthcare system and published in the Journal of the American College of Cardiology, people with stress-related conditions such as depression experienced the most cardiovascular benefits from physical activity.

To assess the mechanisms underlying the psychological and cardiovascular disease benefits of physical activity, Ahmed Tawakol, MD, an investigator and cardiologist in the Cardiovascular Imaging Research Center at Massachusetts General Hospital, and his colleagues analyzed medical records and other information of 50,359 participants from the Mass General Brigham Biobank who completed a physical activity survey.

A subset of 774 participants also underwent brain imaging tests and measurements of stress-related brain activity.

Over a median follow-up of 10 years, 12.9% of participants developed cardiovascular disease. Participants who met physical activity recommendations had a 23% lower risk of developing cardiovascular disease compared with those not meeting these recommendations.

Individuals with higher levels of physical activity also tended to have lower stress-related brain activity. Notably, reductions in stress-associated brain activity were driven by gains in function in the prefrontal cortex, a part of the brain involved in executive function (i.e., decision making, impulse control) and is known to restrain stress centers of the brain. Analyses accounted for other lifestyle variables and risk factors for coronary disease.

Moreover, reductions in stress-related brain signaling partially accounted for physical activity's cardiovascular benefit.

As an extension of this finding, the researchers found in a cohort of 50,359 participants that the cardiovascular benefit of exercise was substantially greater among participants who would be expected to have higher stress-related brain activity, such as those with pre-existing depression.

"Physical activity was roughly twice as effective in lowering cardiovascular disease risk among those with depression. Effects on the brain's stress-related activity may explain this novel observation," says Tawakol, who is the senior author of the study.

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How fear unfolds inside our brains

Our nervous systems are naturally wired to sense fear. Whether prompted by the eerie noises we hear alone in the dark or the approaching growl of a threatening animal, our fear response is a survival mechanism that tells us to remain alert and avoid dangerous situations.

But if fear arises in the absence of tangible threats, it can be harmful to our well-being. Those who have suffered episodes of severe or life-threatening stress can later experience intense feelings of fear, even during situations that lack a real threat. Experiencing this generalization of fear is psychologically damaging and can result in debilitating long-term mental health conditions such as post-traumatic stress disorder (PTSD).

The stress-induced mechanisms that cause our brain to produce feelings of fear in the absence of threats have been mostly a mystery. Now, neurobiologists at the University of California San Diego have identified the changes in brain biochemistry and mapped the neural circuitry that cause such a generalized fear experience. Their research, published in the journal Science on March 15, 2024, provides new insights into how fear responses could be prevented.

In their report, former UC San Diego Assistant Project Scientist Hui-quan Li, (now a senior scientist at Neurocrine Biosciences), Atkinson Family Distinguished Professor Nick Spitzer of the School of Biological Sciences and their colleagues describe the research behind their discovery of the neurotransmitters -- the chemical messengers that allow the brain's neurons to communicate with one another -- at the root of stress-induced generalized fear.

Studying the brains of mice in an area known as the dorsal raphe (located in the brainstem), the researchers found that acute stress induced a switch in the chemical signals in the neurons, flipping from excitatory "glutamate" to inhibitory "GABA" neurotransmitters, which led to generalized fear responses.

"Our results provide important insights into the mechanisms involved in fear generalization," said Spitzer, a member of UC San Diego's Department of Neurobiology and Kavli Institute for Brain and Mind. "The benefit of understanding these processes at this level of molecular detail -- what is going on and where it's going on -- allows an intervention that is specific to the mechanism that drives related disorders."

Building upon this new finding of a stress-induced switch in neurotransmitters, considered a form of brain plasticity, the researchers then examined the postmortem human brains of individuals who had suffered from PTSD. A similar glutamate-to-GABA neurotransmitter switch was confirmed in their brains as well.

The researchers next found a way to stop the production of generalized fear. Prior to the experience of acute stress, they injected the dorsal raphe of the mice with an adeno-associated virus (AAV) to suppress the gene responsible for synthesis of GABA. This method prevented the mice from acquiring generalized fear.

Further, when mice were treated with the antidepressant fluoxetine (branded as Prozac) immediately after a stressful event, the transmitter switch and subsequent onset of generalized fear were prevented.

Not only did the researchers identify the location of the neurons that switched their transmitter, but they demonstrated the connections of these neurons to the central amygdala and lateral hypothalamus, brain regions that were previously linked to the generation of other fear responses.

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Evidence from the remains of 1918 flu pandemic victims contradicts long-held belief that healthy young adults were particularly vulnerable

New analysis of the remains of victims of the 1918 influenza pandemic, which killed an estimated 50 million people worldwide, contradicts the widespread belief the flu disproportionately impacted healthy young adults.

Because so many people fell ill so quickly, physicians at the time believed the healthy were as likely to die from the flu as those who had already been sick or frail. Despite numerous historical accounts, though, it turns out there is no concrete scientific evidence to support that belief.

Researchers at McMaster University and the University of Colorado Boulder who analyzed victims' age of death and studied lesions on victims' bones report that the most susceptible to dying of the flu had exhibited signs of previous environmental, social and nutritional stress.

"Our circumstances -- social, cultural and immunological -- are all intertwined and have always shaped the life and death of people, even in the distant past," explains Amanda Wissler, an assistant professor in the Department of Anthropology at McMaster and lead author on the study, published today in the journal PNAS.

"We saw this during COVID-19, where our social backgrounds and our cultural backgrounds influenced who was more likely to die, and who was likely to survive," she says.

Much of the research on the 1918 pandemic relies on historical documentation such as vital statistics, census data and life insurance records, none of which include information on pre-existing conditions, or general environmental, dietary or other chronic stressors which can impact one's overall health over the course of a lifetime.

For the study, researchers examined the skeletal remains of 369 individuals from the Hamman-Todd Documented skeletal collection, which is housed at the Cleveland Museum of Natural History. All had died between 1910 and 1938. The sample was divided into two groups: a control group who had died before the pandemic, and those who died during the pandemic.

A living person's skeletal structure may undergo lasting changes due to poor health, resulting in diminished height, irregular growth, developmental tooth defects and other indicators.

The team searched for lesions, or indicators of stress, on the shinbones of the pandemic victims. New bone formation occurs in response to inflammation caused by physical trauma or infection, for example. Researchers can determine if a lesion had been active, in the midst of healing or had completely healed, all of which provide evidence of underlying conditions.

"By comparing who had lesions, and whether these lesions were active or healing at the time of death, we get a picture of what we call frailty, or who is more likely to die. Our study shows that people with these active lesions are the most frail," says Sharon DeWitte, a biological anthropologist at the University Colorado Boulder and co-author on the study.

Preexisting medical conditions such as asthma or congestive heart failure are common risk factors which can contribute to poor outcomes from infectious diseases such as influenza.

Racism and institutional discrimination can amplify these effects, as evidenced in the COVID-19 pandemic, say researchers. During the Black Death in London, for example, individuals who had previously suffered environmental, nutritional and disease stressors were more likely to die from the plague than their healthier peers.

"The results of our work counter the narrative and the anecdotal accounts of the time," says Wissler. "This paints a very complicated picture of life and death during the 1918 pandemic."

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Exposure to air pollution while in the womb is linked to adverse changes in cell processes in new-born babies

Exposure to air pollution while in the womb is linked to alterations in proteins that can be detected after a baby is born, and which affect cell processes such as autophagy, the "self-eating" of damaged cells that occurs in response to stress.

Dr Olga Gorlanova, a research physician at the University Children's Hospital, University of Basel, Switzerland, told the European Respiratory Society International Congress in Milan, Italy, that her study also showed that healthy, new-born babies had individual and different responses to their mothers' exposure to air pollution during pregnancy. This might mean that some babies were more vulnerable to it than others. This was the case even if they were born into households in areas with relatively low levels of pollution.

Earlier work by Dr Gorlanova and her colleagues had shown that exposure to air pollution during pregnancy could affect lung function and the immune system in new-borns. In the current study, they looked at proteins involved in autophagy, ageing and cell remodelling to see how prenatal exposure to air pollution could affect them.

The researchers measured 11 proteins found in the cord blood of 449 healthy new-born babies from the Bern Basel Infant Lung Development (BILD) cohort study. The BILD study, started in 1999 in Bern, aims to recruit 1000 babies by 2025. It is investigating the effects of genetics and the environment (particularly air pollution) on lung development in babies and children.

Dr Gorlanova and colleagues measured the mothers' exposure to nitrogen dioxide (NO2) and tiny particles called PM10,which areparticulate matter measuring 10 microns or less in diameter. Vehicle emissions, tyre and brake wear, and smoke are some of the sources of these pollutants. They found that NO2 and PM10 were both linked to changes in proteins involved in autophagy. Exposure to NO2 was linked to a decrease in the activity of the proteins SIRT1 and IL-8, and an increase in levels of the Beclin-1 protein.

"Our results indicate that NO2, a pollutant formed mainly from traffic emissions, is associated with increased levels of Beclin-1 protein, which is central to initiating autophagy. Exposure to higher NO2 was also linked to decreased levels of SIRT1, which is a protein that plays a protective role in stress resistance, inflammation and aging. IL-8 is a protein active in certain inflammatory cells," said Dr Gorlanova.

"We grouped the babies into four distinct clusters according to the levels of air pollution they were exposed to while in the womb. The four clusters all had similar concentrations of the proteins being studied but had differences their exposure to NO2 and PM10 air pollution. One cluster had low concentrations of nine proteins, while another cluster, consisting of seven percent of all the babies, had higher levels of proteins that are involved in inflammatory and remodelling processes: IL-8 and IL-1B. Both these groups of new-borns had been exposed to lower, although differing, levels of prenatal air pollution than the other two groups. Our findings suggest that healthy new-borns have an individual response pattern to air pollution. We think that this may be an indication that some babies are more vulnerable to it than others.

"Additionally, our work adds to the growing body of evidence that autophagy-related mechanisms may be involved in how human cells react to air pollution. The findings are consistent with evidence from tissue and animal research. Further exploration of these mechanisms may help to better understand the deleterious effects of pollution on infants."

The researchers plan to examine whether babies with distinct protein response patterns to air pollution will suffer from more breathing problems during infancy and childhood compared to those that do not show the same protein responses.

Professor Marielle Pijnenburg, associate professor of pediatric pulmonology and head of the Department of Pediatric Respiratory Medicine and Allergology at Erasmus Medical Center, Rotterdam, The Netherlands, is head of the ERS group on paediatrics and was not involved with the research. She commented: "This study adds to the growing body of evidence that air pollution can affect the health of children before and after they are born. It contributes to other research showing that autophagy-related mechanisms may be involved in how human cells react to air pollution. We need to know more about how these mechanisms can affect the health of lungs, and we need to understand why some new-borns seem to be more susceptible to air pollution than others.

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Researchers uncover why light-to-moderate drinking is tied to better heart health

A new study led by investigators from Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system, offers an explanation for why light-to-moderate alcohol consumption may be associated with lower risk of heart disease. For the first time, researchers found that alcohol, in light to moderate quantities, was associated with long-term reductions in stress signaling in the brain. This impact on the brain's stress systems appeared to significantly account for the reductions in cardiovascular events seen in light to moderate drinkers participating in the study. Findings are published in the Journal of the American College of Cardiology.

"We are not advocating the use of alcohol to reduce the risk of heart attacks or strokes because of other concerning effects of alcohol on health," says senior author and cardiologist Ahmed Tawakol, MD, co-director of the Cardiovascular Imaging Research Center at Massachusetts General Hospital. "We wanted to understand how light to moderate drinking reduces cardiovascular disease, as demonstrated by multiple other studies. And if we could find the mechanism, the goal would be to find other approaches that could replicate or induce alcohol's protective cardiac effects without the adverse impacts of alcohol."

Previous epidemiological studies have suggested that light to moderate alcohol consumption (1 drink per day for women and 1 to 2 drinks per day for men) is associated with a lower risk of cardiovascular disease. But it was unknown whether alcohol was inducing cardiovascular benefits, or whether light/moderate drinkers' health behaviors, socioeconomic status, or other factors protected their hearts.

The study, led by K Mezue and M Osborne, included more than 50,000 individuals enrolled in the Mass General Brigham Biobank. The first part of the study evaluated the relationship between light/moderate alcohol consumption and major adverse cardiovascular events after adjusting for a range of genetic, clinical, lifestyle, and socioeconomic confounders. The researchers found that light/moderate alcohol consumption was associated with a substantial reduction in the risk of cardiovascular disease events, even after accounting for those other factors.

Next, they studied a subset of 754 individuals who had undergone previous PET/CT brain imaging (primarily for cancer surveillance) to determine the effect of light/moderate alcohol consumption on resting stress-related neural network activity.

The brain imaging showed reduced stress signaling in the amygdala, the brain region associated with stress responses, in individuals who were light to moderate drinkers compared to those who abstained from alcohol or who drank little. And when the investigators looked at these individuals' history of cardiovascular events, they found fewer heart attacks and strokes in light to moderate drinkers. "We found that the brain changes in light to moderate drinkers explained a significant portion of the protective cardiac effects," says Tawakol.

It's long been known that alcohol reduces the amygdala's reactivity to threatening stimuli while individuals are drinking. The current study is the first to indicate that light to moderate alcohol consumption has longer-term neurobiological effects in dampening activity in the amygdala, which may have a significant downstream impact on the cardiovascular system.

"When the amygdala is too alert and vigilant, the sympathetic nervous system is heightened, which drives up blood pressure and increases heart rate, and triggers the release of inflammatory cells," explains Tawakol. "If the stress is chronic, the result is hypertension, increased inflammation, and a substantial risk of obesity, diabetes, and cardiovascular disease."

Finally, the investigators examined whether light/moderate alcohol would be even more effective at reducing heart attacks and strokes in people who are prone to a chronically higher stress response, such as those with a history of significant anxiety. They found that, within the 50,000-patient sample, light to moderate drinking was associated with nearly double the cardiac-protective effect in individuals with a history of anxiety compared with others.

Yet while light/moderate drinkers lowered their risk for cardiovascular disease, the study also showed that any amount of alcohol increases the risk of cancer. And at higher amounts of alcohol consumption -- more than 14 drinks a week -- heart attack risk started to increase while overall brain activity started to decrease (which may be associated with adverse cognitive health).

The authors concluded that research should focus on finding new interventions that reduce the brain's stress activity without the deleterious effects of alcohol. The research team is currently studying the effect of exercise, stress-reduction interventions such as meditation, and pharmacological therapies on stress-associated neural networks and how they might induce cardiovascular benefits.

Read more at Science Daily

How chronic stress drives the brain to crave comfort food

When you're stressed, a high-calorie snack may seem like a comforting go-to. But this combination has an unhealthy downside. According to Sydney scientists, stress combined with calorie-dense 'comfort' food creates changes in the brain that drive more eating, boost cravings for sweet, highly palatable food and lead to excess weight gain.

A team from the Garvan Institute of Medical Research found that stress overrode the brain's natural response to satiety, leading to non-stop reward signals that promote eating more highly palatable food. This occurred in a part of the brain called the lateral habenula, which when activated usually dampens these reward signals.

"Our findings reveal stress can override a natural brain response that diminishes the pleasure gained from eating -- meaning the brain is continuously rewarded to eat," says Professor Herzog, senior author of the study and Visiting Scientist at the Garvan Institute.

"We showed that chronic stress, combined with a high-calorie diet, can drive more and more food intake as well as a preference for sweet, highly palatable food, thereby promoting weight gain and obesity. This research highlights how crucial a healthy diet is during times of stress."

The research was published in the journal Neuron.

From stressed brain to weight gain

While some people eat less during times of stress, most will eat more than usual and choose calorie-rich options high in sugar and fat.

To understand what drives these eating habits, the team investigated in mouse models how different areas in the brain responded to chronic stress under various diets.

"We discovered that an area known as the lateral habenula, which is normally involved in switching off the brain's reward response, was active in mice on a short-term, high-fat diet to protect the animal from overeating. However, when mice were chronically stressed, this part of the brain remained silent -- allowing the reward signals to stay active and encourage feeding for pleasure, no longer responding to satiety regulatory signals," explains first author Dr Kenny Chi Kin Ip from the Garvan Institute.

"We found that stressed mice on a high-fat diet gained twice as much weight as mice on the same diet that were not stressed."

The researchers discovered that at the centre of the weight gain was the molecule NPY, which the brain produces naturally in response to stress. When the researchers blocked NPY from activating brain cells in the lateral habenula in stressed mice on a high-fat diet, the mice consumed less comfort food, resulting in less weight gain.

Driving comfort eating

The researchers next performed a 'sucralose preference test' -- allowing mice to choose to drink either water or water that had been artificially sweetened.

"Stressed mice on a high-fat diet consumed three times more sucralose than mice that were on a high-fat diet alone, suggesting that stress not only activates more reward when eating but specifically drives a craving for sweet, palatable food," says Professor Herzog.

"Crucially, we did not see this preference for sweetened water in stressed mice that were on a regular diet."

Stress overrides healthy energy balance

"In stressful situations it's easy to use a lot of energy and the feeling of reward can calm you down -- this is when a boost of energy through food is useful. But when experienced over long periods of time, stress appears to change the equation, driving eating that is bad for the body long term," says Professor Herzog.

The researchers say their findings identify stress as a critical regulator of eating habits that can override the brain's natural ability to balance energy needs.

Read more at Science Daily

New evidence: Immune system cells in the gut linked to stress-induced depression

In experiments with mice and humans, a team led by Johns Hopkins Medicine researchers says it has identified a particular intestinal immune cell that impacts the gut microbiome, which in turn may affect brain functions linked to stress-induced disorders such as depression. Targeting changes mediated by these immune cells in the gut, with drugs or other therapies, could potentially bring about new ways to treat depression.

The findings of the study were published March 20, 2023 in the journal Nature Immunology.

"The results of our study highlight the previously unrecognized role of intestinal gamma delta T cells (γδ T cells) in modifying psychological stress responses, and the importance of a protein receptor known as dectin-1, found on the surface of immune cells, as a potential therapeutic target for the treatment of stress-induced behaviors," says Atsushi Kamiya, M.D., Ph.D., professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and the study's senior author.

Dectin-1 binds to certain antigens, or proteins, to signal immune cells to activate in specific ways. This receptor, the researchers say, may be involved in the microbiome alteration and immune-inflammatory responses in the colon of mice, which suggests that it may be involved in stress responses via γδ T cells in the intestinal immune system.

On the basis of previous studies suggesting that immune inflammatory responses in the gut are related to depression, Kamiya and his team designed experiments to focus on understanding stress-induced behaviors produced by an imbalance in the gut microbiota -- types of microorganisms found in a specific environment, such as bacteria, fungi and viruses.

To this end, the team examined the effects of chronic social defeat stress (CSDS) on the gut microbiota in mice. CSDS is a standard rodent test to study stress-induced disorders such as depression. In a series of experiments, the researchers simulated potential stress inducing environments that could mimic similar responses in human environments. After each exposure, the mice were assessed and classified as stress-resilient (stress did not diminish social interactions) or stress-susceptible (stress increased social avoidance).

Fecal samples were then collected and put through genetic analysis to identify the diversity of bacteria in the gut microbiota of the mice. The analysis showed that the intestinal organisms were less diverse in stress-susceptible mice than in stress-resilient mice. It specifically revealed that there were less Lactobacillus johnsonii (L. johnsonii) -- a type of probiotic, or "good" bacteria -- in stress-susceptible mice compared to stress-resilient mice.

"We found that stress increased the γδ T cells, which in turn increased social avoidance," says Xiaolei Zhu, M.D., Ph.D., assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and the study's lead author. "However, when the stressed mice were given L. johnsonii, social avoidance decreased and the γδ T cells went to normal levels, suggesting that CSDS-induced social avoidance behavior may be the result of lower levels of the bacteria and γδ T cell changes."

Looking for potential natural approaches for prevention of depression rooted somehow in the gut, the researchers explored how changes in dectin-1 on CSDS-induced elevation of γδ T cells responded to pachyman. A compound extracted from wild mushrooms, pachyman is used as a natural anti-inflammatory agent and for treating depression in Eastern medicine. For this experiment, mice were fed a dose of pachyman, which was shown in previous research to affect immune function. Data from flow cytometry analysis -- a technology used to measure the physical and chemical characteristics of a population of cells -- provided evidence that dectin-1 binds to pachyman, inhibiting CSDS-induced γδ17 T cell activity and easing social avoidance behavior.

To gain insight into how the alterations in the gut microbiota could impact the human brain, the researchers investigated the makeup of gut organisms in people with major depressive disorder (MDD) compared to people without MDD. From June 2017 to September 2020, 66 participants, ages 20 or older, were recruited at Showa University Karasuyama Hospital, Keio University Hospital and Komagino Hospital in Tokyo, Japan. Of the study participants, 32 had MDD (17 women and 15 men). The other 34 participants (18 women and 16 men) who did not have MDD formed the control group.

Stool samples were collected from all study participants, who had comprehensive evaluations including psychiatric history and standard screening assessments for depression and anxiety. In these assessments, higher scores indicate greater depressive symptoms. Genetic analysis of the stool samples showed no difference in the diversity of intestinal bacteria between the subjects with MDD and the control group. However, the relative abundance of Lactobacillus was inversely related to higher depression and anxiety scores in the MDD group, meaning that the more Lactobacillusfound in the gut, the lower the potential for depression and anxiety, the researchers say.

"Despite the differences of intestinal microbiota between mice and humans, the results of our study indicate that the amount of Lactobacillus in the gut may potentially influence stress responses and the onset of depression and anxiety," says Kamiya.

The investigators say more research is needed to further understand how γδ T cells in the intestinal immune system may impact the neurological functions in the brain and the role of dectin-1 in other cell types along the gut-brain connection under stress conditions.

"These early-stage findings show that, in addition to probiotic supplements, targeting drugs to such types of receptors in the gut immune system may potentially yield novel approaches to prevent and treat stress-induced psychiatric symptoms such as depression," says Kamiya.

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Biological network in cells helps body adapt to stresses on health

Every minute of every day, our body adapts to meet the needs of each moment. When we binge on carbs, exercise, or become sick, chemical reactions inside our cells switch on, slow down, or shift strategy so that we have the energy and strength we need.

All this happens without us knowing it, perhaps explaining why so little is understood about how the body senses and responds to these constant demands. Seeking answers to this question, scientists at University of Utah Health led research that opens up a whole new world within our cells. Their study, published in Science, uncovers a vast network of interactions that suggest how cells adjust in real time to withstand stresses on our health.

"We're discovering how nature has evolved to 'drug' its own proteins and pathways," says Jared Rutter, Ph.D., distinguished professor in the Department of Biochemistry at University of Utah and the study's corresponding author. "By following nature's lead, we're learning how to make better therapeutics."

These findings -- and the technology that made them possible -- has become the basis for the biotechnology company Atavistik Bio, co-founded by Rutter. The company is leveraging this new understanding to accelerate drug discovery for metabolic diseases and cancer.

At a more fundamental level, Rutter says, the advance deepens knowledge about how cells and our bodies work.

A New Frontier

The network described in the study represents an underappreciated layer of regulation in cells that comes from an unexpected source. For nearly 20 years, Rutter's lab has researched metabolism, the chemical reactions that produce energy and build essential components to keep cells running smoothly. Their new research finds that intermediate products of those chemical reactions are more than passive building blocks and sources of fuel for cells, as had long been thought.

Instead, these intermediate products, along with other metabolites, make up an expansive web of sentries that monitor the environment and prompt cells to adapt when needed. They do this by interacting with proteins and modifying how they work. Does a big meal pump too many carbs in the body? Or too much fat? Like a railroad switch that guides a train onto a new track, these protein-metabolite interactions shift metabolic operations to break down those nutrients and steady the course.

The study's first author Kevin Hicks, Ph.D., developed a new technology, termed MIDAS, that reveals the enormity of the regulatory network that acts as an interface between environmental cues and cell metabolism, called the protein-metabolite interactome. The highly sensitive technique identified interactions that had never been seen. An analysis of 33 human proteins involved in converting carbohydrates into fuel found 830 interactions with metabolites. Given that there are thousands of proteins in the cell, the full scale of the network is predicted to be much larger.

"It's surprising how little we know about the extent of these interactions," Hicks says. "We are pushing our understanding of the biological network in new directions."

Read more at Science Daily

Just one quality conversation with a friend boosts daily well-being

Conversing with a friend just once during the day to catch up, joke around or tell them you're thinking of them can increase your happiness and lower your stress level by day's end.

These are among the results of a new study co-authored by University of Kansas professor of Communication Studies and friendship expert Jeffrey Hall.

"Quality Conversation Can Increase Daily Well-Being" was published in the journal Communication Research by Hall and co-authors Amanda Holmstrom, Natalie Pennington, Evan Perrault and Daniel Totzkay. The study was informed by and provides further support for Hall's Communicate Bond Belong (CBB) theory of relationships. Hall is the director of KU's Relationships and Technology Lab.

"This paper was an attempt to define quality communication in the context of relationships," Hall said."The types of communication we chose to study were ones shown in past research to make people feel more bonded through conversation."

There were seven:

•    Catching up
•     Meaningful talk
•     Joking around
•     Showing care
•     Listening
•     Valuing others and their opinions
•     Offering sincere compliments

Over 900 study participants from five university campuses -- before, during and after pandemic lockdowns -- were directed to engage in one of the seven communication behaviors on a single day, and then reported back that night about their feelings of stress, connection, anxiety, well-being, loneliness and the quality of their day.

As it turned out, Hall said, it didn't matter which of these quality conversations someone had. The very act of intentionally reaching out to a friend in one of these ways was what mattered most.

"One of the take-home messages of this study is that there are many paths toward the same goal," Hall said.

He said the study was also designed to explore the impact of both the quality and quantity of daily communications.

"There's a lot of good research that says the number of interactions you have as well as the quality of interactions are both associated with being a less lonely, happier and more connected person," said Hall. This study found that once is enough, but more is better. Participants who chose to have more quality conversations had better days.

"This means the more that you listened to your friends, the more that you showed care, the more that you took time to value others' opinions, the better you felt at the end of the day," he said.

"The experimental design means that it's not just people who are already having fulfilling lives who have higher-quality conversations," Hall said. "This study suggests that anyone who makes time for high-quality conversation can improve their well-being. We can change how we feel on any given day through communication. Just once is all it takes."

The study also brought in Hall's past research on different ways to connect in the era of social and mobile media. The study found high quality face-to-face communication was more closely associated with well-being than electronic or social media contact.

"If at least one of their quality conversations was face-to-face, that mattered," Hall said.

The paper also explains why quality communication makes people feel better. CBB theory claims that people use conversations with friends to help get their need to belong met.

"Across these three studies, quality conversation mattered most for connection and stress," Hall said. "This supports the idea that we use communication to get our need to belong met, and, in doing so, it helps us manage our stress."

Read more at Science Daily

New study shows repeated stress accelerates aging of the eye

New research from the University of California, Irvine, suggests aging is an important component of retinal ganglion cell death in glaucoma, and that novel pathways can be targeted when designing new treatments for glaucoma patients.

The study, titled, "Stress induced aging in mouse eye," was published today in Aging Cell. Along with her colleagues, Dorota Skowronska Krawczyk, PhD, assistant professor in the Departments of Physiology & Biophysics and Ophthalmology and the faculty of the Center for Translational Vision Research at the UCI School of Medicine, describes the transcriptional and epigenetic changes happening in aging retina. The team shows how stress, such as intraocular pressure (IOP) elevation in the eye, causes retinal tissue to undergo epigenetic and transcriptional changes similar to natural aging. And, how in young retinal tissue, repetitive stress induces features of accelerated aging including the accelerated epigenetic age.

Aging is a universal process that affects all cells in an organism. In the eye, it is a major risk factor for a group of neuropathies called glaucoma. Because of the increase in aging populations worldwide, current estimates show that the number of people with glaucoma (aged 40-80) will increase to over 110 million in 2040.

"Our work emphasizes the importance of early diagnosis and prevention as well as age-specific management of age-related diseases, including glaucoma," said Skowronska-Krawczyk. "The epigenetic changes we observed suggest that changes on the chromatin level are acquired in an accumulative way, following several instances of stress. This provides us with a window of opportunity for the prevention of vision loss, if and when the disease is recognized early."

In humans, IOP has a circadian rhythm. In healthy individuals, it oscillates typically in the 12-21 mmHg range and tends to be highest in approximately two thirds of individuals during the nocturnal period. Due to IOP fluctuations, a single IOP measurement is often insufficient to characterize the real pathology and risk of disease progression in glaucoma patients. Long-term IOP fluctuation has been reported to be a strong predictor for glaucoma progression. This new study suggests that the cumulative impact of the fluctuations of IOP is directly responsible for the aging of the tissue.

"Our work shows that even moderate hydrostatic IOP elevation results in retinal ganglion cell loss and corresponding visual defects when performed on aged animals," said Skowronska-Krawczyk. "We are continuing to work to understand the mechanism of accumulative changes in aging in order to find potential targets for therapeutics. We are also testing different approaches to prevent the accelerated aging process resulting from stress."

Researchers now have a new tool to estimate the impact of stress and treatment on the aging status of retinal tissue, which has made these new discoveries possible. In collaboration with the Clock Foundation and Steve Horvath, PhD, from Altos Labs, who pioneered the development of epigenetic clocks that can measure age based on methylation changes in the DNA of tissues, it was possible for researchers to show that repetitive, mild IOP elevation can accelerate epigenetic age of the tissues.

"In addition to measuring vision decline and some structural changes due to stress and potential treatment, we can now measure the epigenetic age of retinal tissue and use it to find the optimal strategy to prevent vision loss in aging," said Skowronska-Krawczyk.

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Petting dogs engages the social brain, according to neuroimaging

Researchers led by Rahel Marti at the University of Basel in Switzerland report that viewing, feeling, and touching real dogs leads to increasingly higher levels of activity in the prefrontal cortex of the brain. Published in PLOS ONE on October 5, the study shows that this effect persists after the dogs are no longer present, but is reduced when real dogs are replaced with stuffed animals. The findings have implications for animal-assisted clinical therapy.

Because interacting with animals, particularly dogs, is known to help people cope with stress and depression, researchers think that a better understanding of the associated brain activity could help clinicians design improved systems for animal-assisted therapy. The prefrontal cortex might be particularly relevant because it helps regulate and process social and emotional interactions.

In the study, activity in the prefrontal cortex of the brain was non-invasively measured with infrared neuroimaging technology as 19 men and women each viewed a dog, reclined with the same dog against their legs, or petted the dog. Each of these conditions was also performed with Leo, a stuffed lion with fur that was filled with a water bottle to match the temperature and weight of the dogs.

Results showed that prefrontal brain activity was greater when participants interacted with the real dogs, and that this difference was largest for petting, which was the most interactive condition. Another key difference was that prefrontal brain activity increased each time people interacted with the real dog. This was not observed with successive interactions with the stuffed lion, indicating that the response might be related to familiarity or social bonding.

Future studies will be needed to examine the issue of familiarity in detail and whether petting animals can trigger a similar boost of prefrontal brain activity in patients with socioemotional deficits.

The authors add: "The present study demonstrates that prefrontal brain activity in healthy subjects increased with a rise in interactional closeness with a dog or a plush animal, but especially in contact with the dog the activation is stronger. This indicates that interactions with a dog might activate more attentional processes and elicit stronger emotional arousal than comparable nonliving stimuli."

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Some types of stress could be good for brain functioning

It may feel like an anvil hanging over your head, but that looming deadline stressing you out at work may actually be beneficial for your brain, according to new research from the Youth Development Institute at the University of Georgia.

Published in Psychiatry Research, the study found that low to moderate levels of stress can help individuals develop resilience and reduce the risk of developing mental health disorders, like depression and antisocial behaviors. Low to moderate stress can also help individuals to cope with future stressful encounters.

"If you're in an environment where you have some level of stress, you may develop coping mechanisms that will allow you to become a more efficient and effective worker and organize yourself in a way that will help you perform," said Assaf Oshri, lead author of the study and an associate professor in the College of Family and Consumer Sciences.

The stress that comes from studying for an exam, preparing for a big meeting at work or pulling longer hours to close the deal can all potentially lead to personal growth. Being rejected by a publisher, for example, may lead a writer to rethink their style. And being fired could prompt someone to reconsider their strengths and whether they should stay in their field or branch out to something new.

But the line between the right amount of stress and too much stress is a thin one.

"It's like when you keep doing something hard and get a little callous on your skin," continued Oshri, who also directs the UGA Youth Development Institute. "You trigger your skin to adapt to this pressure you are applying to it. But if you do too much, you're going to cut your skin."

Good stress can act as a vaccine against the effect of future adversity

The researchers relied on data from the Human Connectome Project, a national project funded by the National Institutes of Health that aims to provide insight into how the human brain functions. For the present study, the researchers analyzed the project's data from more than 1,200 young adults who reported their perceived stress levels using a questionnaire commonly used in research to measure how uncontrollable and stressful people find their lives.

Participants answered questions about how frequently they experienced certain thoughts or feelings, such as "in the last month, how often have you been upset because of something that happened unexpectedly?" and "in the last month, how often have you found that you could not cope with all the things that you had to do?"

Their neurocognitive abilities were then assessed using tests that measured attention and ability to suppress automatic responses to visual stimuli; cognitive flexibility, or ability to switch between tasks; picture sequence memory, which involves remembering an increasingly long series of objects; working memory and processing speed.

The researchers compared those findings with the participants' answers from multiple measures of anxious feelings, attention problems and aggression, among other behavioral and emotional problems.

The analysis found that low to moderate levels of stress were psychologically beneficial, potentially acting as a kind of inoculation against developing mental health symptoms.

"Most of us have some adverse experiences that actually make us stronger," Oshri said. "There are specific experiences that can help you evolve or develop skills that will prepare you for the future."

But the ability to tolerate stress and adversity varies greatly according to the individual.

Things like age, genetic predispositions and having a supportive community to fall back on in times of need all play a part in how well individuals handle challenges. While a little stress can be good for cognition, Oshri warns that continued levels of high stress can be incredibly damaging, both physically and mentally.

"At a certain point, stress becomes toxic," he said. "Chronic stress, like the stress that comes from living in abject poverty or being abused, can have very bad health and psychological consequences. It affects everything from your immune system, to emotional regulation, to brain functioning. Not all stress is good stress."

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Healthy development thanks to older siblings

In a new study, a Leipzig-based team of researchers including scientists from the Helmholtz Centre for Environmental Research (UFZ), Leipzig University (UL), the MPI for Evolutionary Anthropology (MPI EVA) and the German Centre for Integrative Biodiversity Research (iDiv) used longitudinal data from the LINA (Lifestyle and environmental factors and their Influence on the Newborn Allergy risk) cohort to test 373 German mother-child pairs, from pregnancy until 10 years of age.

Mothers were asked to fill in three validated questionnaires, to assess their stress levels and their child's behavioural problems. First, the researchers assessed which social and environmental factors were linked to an increase in maternal stress levels during pregnancy, and the long-term consequences of maternal stress on the occurrence of child behavioural problems. Second, the researchers assessed whether the presence of siblings had a positive effect on the occurrence of child behavioural problems, by directly reducing stress levels and increasing children's psychological well-being, or by indirectly buffering the negative consequences of maternal stress.

Prenatal stress can cause behavioural problems in the child

The results of the study demonstrated that socio-environmental stressors, like the lack of sufficient social areas in the neighbourhood, were clearly linked to an increase in maternal stress levels during pregnancy. Moreover, mothers who had experienced high stress levels, like worries, loss of joy or tension, during pregnancy were also more likely to report the occurrence of behavioural problems when their children were 7, 8 or 10 years old. "These results confirm previous findings about the negative impact that even mild forms of prenatal stress might have on child behaviour, even after several years, and highlight the importance of early intervention policies that increase maternal wellbeing and reduce the risks of maternal stress already during pregnancy," explains Federica Amici (UL, MPI-EVA), one of the researchers involved in the project.

On a more positive note, the study also found a lower occurrence of behavioural problems in children with older siblings. "Children who have older brothers or sisters in their households are less likely to develop problems, which suggests that siblings are crucial to promote a healthy child development," explains Gunda Herberth (UFZ), coordinator of the LINA study.

Higher social competence thanks to older siblings?

This study further suggests that the presence of older siblings directly reduced the likelihood of developing behavioral problems, but did not modulate the negative effects of maternal stress on child behaviour. How could older siblings reduce the occurrence of behavioural problems in children? By interacting with their older siblings, children may develop better emotional, perspective taking and problem solving skills, which are linked to higher social competence and emotional understanding. Moreover, the presence of older siblings may provide learning opportunities for parents, who might thus develop different expectations and better parental skills.

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Ecotourism is having a negative effect on primate's behavior

New research shows that the increase in primate ecotourism is having a negative effect on monkey's behaviour.

The study, led by the University of Portsmouth, found that this fast-growing tourism sector where tourists can conveniently reach primates via motor boats is causing stress-related behaviours in monkeys.

The research looked at the impact of a single engine motor boat approaching a community of proboscis monkeys, an endangered species living in a remote riparian area (strips of vegetation that border rivers, streams and lakes) in Sabah, Malaysia. Proboscis monkeys are unusual looking with their very long noses, which adds to making them appealing to tourists.

Many of these boats, carrying multiple tourists, approach the primates quickly and loudly, often reaching the river banks just a few metres away from the wildlife.

The researchers found that frequent visits by such groups, which often involve an unusually high level of noise, caused stress-related behaviours in the primates such as self-scratching, an increased vigilant state, increased levels of aggression and reduced feeding.

Lead author of the study, Dr Marina Davila-Ross, Reader in Comparative Psychology at the University of Portsmouth, said: "Our evidence shows that even a single motor boat moving slowly, with humans behaving calmly, can negatively affect the primate's behaviour and induce stress -- an impact that is likely to be larger with tourist boats.

"The riparian area is an important habitat that has become increasingly popular to primate ecotourism, because it enables tourists to conveniently reach primates via motor boats."

The researchers conducted the experiment by approaching the monkeys in a motor boat with different speeds and travel distances -- fast-close (approaching the monkeys for 10 seconds when 40 metres away at a speed of 14.4 km/hr), slow-close (approaching the monkey for 40 seconds when 40 metres away at a speed of 3.6 km/hr), and slow-far conditions (approaching the monkeys for 20 seconds when 100 metres away, at a speed of 3.6 km/hr). For each condition, they compared stress-related behaviours before the boat approached with after the boat started its approach.

The results showed that the monkeys displayed stress-related behaviours for longer in the fast-close and slow-close conditions and also reduced feeding as a result of the boat approaching in the fast-close condition. They also found that male proboscis monkeys displayed more vigilant behaviour than females.

Once the boat started to approach, the proboscis monkeys gazed at the boat for longer than before the boat approached, showed repeated scratching, and often moved quickly backwards to hide in the trees. This could potentially cause the monkeys to leave their safe sleeping sites and to retreat deep into the forest as it gets dark, where they could face a higher risk of predation.

Dr Davila-Ross said: "Collectively, our findings suggest that the approach of a single motor boat induces stress in proboscis monkeys when approaching them as closely as 60 metres from the other side of the river, regardless of the speed of approach. The findings match those obtained in studies on sea mammals and birds, suggesting that stress is a universal response across animals when a boat approaches -- a large, loud, and artificial object moving toward them is likely to be threatening."

The researchers propose that guidelines for primate tourism in the riparian areas, which are largely unregulated, should include an approach speed of no more than 4 km/hr within 100 metres of the proboscis monkeys. They suggest it is also important to keep a distance, preferably no closer than 60 metres away, from the monkeys.

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Heat stress for cattle may cost billions by century's end, study finds

Climate change poses a potentially devastating economic threat to low-income cattle farmers in poor countries due to increasing heat stress on the animals. Globally, by the end of this century those producers may face financial loss between $15 and $40 billion annually.

Farmers in tropical regions -- including large parts of South America, Asia and Africa -- are likely to suffer significantly, particularly when compared with producers in the world's wealthier temperate zones, according to a study by an international team of scientists and economists published in the Lancet Planetary Health.

The researchers, including Mario Herrero, professor of sustainable food systems at Cornell University, and lead author Philip Thornton, of the International Livestock Research Institute and CGIAR; published "Impacts of Heat Stress on Global Cattle Production During the 21st Century."

Escalating demand for livestock products in low- and middle-income countries, along with steadily increasing global average temperatures, is an uncomfortable mix, the researchers said. If livestock are to adapt to new thermal environments and increase their productivity, infrastructural investments or adjustments -- such as switching to more heat-tolerant cattle breeds, and improving shade, ventilation and cooling systems -- will be required.

In the paper's high greenhouse-gas emission scenario, cattle production losses from heat stress are estimated to be $39.94 billion annually, or 9.8% of the value of production of meat and milk from cattle in 2005 -- the scientists' baseline year. The low-emission scenario projects production losses at $14.9 billion annually, or 3.7% of the 2005 value.

By the end of the century, dairy and beef production in the United States is projected to decline by 6.8%, while India -- a major dairy production country -- is projected to lose more than 45% of its dairy farming due to heat stress increases.

"Resource-poor farmers in low-income countries depend heavily on their livestock for their livelihoods," Thornton said. "The adaptation needs are even higher in these countries, and those farmers are the ones where the hit is even more severe."

With climate change, farming and sustainability, Herrero suggested there is a need to create equitable adaptation practices "by design and to think intentionally on reaching the vulnerable sectors of global society," he said. "We cannot just hope that the poor will not be affected."

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Monkeys, like people, can 'choke under pressure'

Being stressed about doing well on a test might not be limited to humans, according to a new study led by researchers at Georgia State University.

Researchers say the study, which involved tufted capuchin monkeys living in groups at Georgia State's Language Research Center, is the first to specifically explore whether other species experience pressure to perform.

The monkeys were given a computerized matching task. Some trials were cued to be harder, with a higher possible reward and a timeout consequence for wrong answers, while other trials were typical in difficulty to their usual computer tasks.

The team found that there was significant variation in how individual monkeys responded to these trials when the difference in difficulty was removed, suggesting that for some monkeys the cues of high stakes were enough to impact performance.

"There are several different explanations for why humans might 'choke' or 'thrive' under pressure, but all of these explanations have traditionally considered this sensitivity to pressure to be a human-specific trait," said the study's lead author, Georgia State Ph.D. candidate Meg Sosnowski.

"Our new results provide the first evidence that other species also might be susceptible to this influence of pressure, and that our responses to that pressure are, in part, the result of individual variation in an evolutionarily common stress response."

The researchers also found that higher levels of a naturally occurring biomarker of stress, cortisol, were related to the monkeys' performance. Higher levels of cortisol were associated with a lower ability to successfully complete the high-pressure trials, providing evidence that an individual's long-term stress state might be related to cognitive performance.

"This opens the door not just to explore how responses to pressure might have impacted the evolution of cognition, but also provides clues pointing us to potential avenues that might mitigate performance deficits, both in humans and in other species," Sosnowski said.

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Modern humans developed a more effective protection against oxidative stress

Very few proteins in the body have a change that makes them unique compared to the corresponding proteins in Neanderthals and apes. Researchers at the Max Planck Institute for Evolutionary Anthropology in Germany and Karolinska Institutet in Sweden have now studied one such protein, glutathione reductase, which protects against oxidative stress. They show that the risk for inflammatory bowel disease and vascular disease is increased several times in people carrying the Neanderthal variant.

What makes modern humans unique is a question that has eluded researchers for a long time. One way to approach this question is to study the proteins, or building blocks, in the body that have changes that are carried by almost all living people today and occurred after we separated from the ancestors we shared with Neanderthals about 500,000 years ago. There are around 100 proteins that have such a unique change. One of these proteins is glutathione reductase which is part of the body's defense against oxidative stress.

The study, which is published in the journal Science Advances, examines the change in glutathione reductase in detail and was led by Hugo Zeberg at Karolinska Institutet and the Max Planck Institute for Evolutionary Anthropologyand Svante Pääbo at the Max Planck Institute. They show that the Neanderthal protein created more reactive oxygen radicals which are the cause of oxidative stress. It is the third protein change unique to present-day humans that has been studied so far.

The study also shows that the Neanderthal protein has passed over to present-day humans in low frequency when our ancestors mixed with them about 60,000 years ago. Today, it occurs mainly on the Indian subcontinent at an estimated frequency of 1 to 2 per cent of the population. The researchers found that people who carry the Neanderthal protein have a higher risk of developing vascular disease and inflammatory bowel disease, both diseases that are linked to oxidative stress.

"The risk increases we see are large; several times increased risk of inflammatory bowel disease and vascular disease," says Hugo Zeberg.

The researchers can only speculate about why this particular change came to be one of the unique changes that almost all modern humans carry.

"Stopping oxidative stress is a bit like preventing something from rusting. Perhaps the fact that we are living longer has driven these changes," says Svante Pääbo.

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'Broken heart' syndrome is on the rise in women

The study, published in the Journal of the American Heart Association (JAHA), suggests middle-aged and older women are being diagnosed with broken heart syndrome more frequently -- up to 10 times more often -- than younger women or men of any age.

The research also suggests that the rare condition has become more common, and the incidence has been rising steadily since well before the COVID-19 pandemic.

"Although the global COVID-19 pandemic has posed many challenges and stressors for women, our research suggests the increase in Takotsubo diagnoses was rising well before the public health outbreak," said Susan Cheng, MD, MPH, MMSc, director of the Institute for Research on Healthy Aging in the Department of Cardiology at the Smidt Heart Institute and senior author of the study. "This study further validates the vital role the heart-brain connection plays in overall health, especially for women."

What the Data Shows

Cheng and her research team used national hospital data collected from more than 135,000 women and men who were diagnosed with Takotsubo syndrome between 2006 and 2017. While confirming that women are diagnosed more frequently than men, the results also revealed that diagnoses have been increasing at least six to 10 times more rapidly for women ages 50 to 74 than for any other demographic.

Additional findings include:
 

• Of the 135,463 documented cases of Takotsubo cardiomyopathy, the annual incidence increased steadily in both sexes, with women contributing most cases (83.3%), especially those over 50.
• In particular, researchers observed a significantly greater increase in incidence among middle-aged women and older women, compared to younger women. For every additional diagnosis of Takotsubo in younger women -- or men of all age groups -- there were 10 additional cases diagnosed for middle-aged women and six additional diagnoses for older women.

Prior to this study, researchers only knew that women are more prone than men to developing Takotsubo syndrome. This latest study is the first to ask whether there are age-based sex differences and if case rates may be changing over time.

The Brain and Heart Connection

As Cheng, who also serves as professor of cardiology and the Erika J. Glazer Chair in Women's Cardiovascular Health and Population Science, explains, the way the brain and nervous system respond to different types of stressors is something that changes as women age.

"There is likely a tipping point, just beyond midlife, where an excess response to stress can impact the heart," said Cheng, director of Cardiovascular Population Sciences in the Barbra Streisand Women's Heart Center. "Women in this situation are at especially affected, and the risk seems to be increasing."

The researchers are next investigating the longer-term implications of a Takotsubo diagnosis, molecular markers of risk, and the factors that may be contributing to rising case rates.

The Smidt Heart Institute has played a leading role in identifying female-pattern heart disease and conditions, developing new diagnostic tools and advancing specialized care for women.

Although medical professionals understand the connection between stress and heart disease risk are critically important, there is still a lot to discern.

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Stress on mothers can influence biology of future generations

A mother's response to stress can even influence her grandchildren.

Biologists at the University of Iowa found that roundworm mothers subjected to heat stress passed, under certain conditions and through modifications to their genes, the legacy of that stress exposure not only to their offspring but even to their offspring's children.

The researchers, led by Veena Prahlad, associate professor in the Department of Biology and the Aging Mind and Brain Initiative, looked at how a mother roundworm reacts when she senses danger, such as a change in temperature, which can be harmful or even fatal to the animal. In a study published last year, the biologists discovered the mother roundworm releases serotonin when she senses danger. The serotonin travels from her central nervous system to warn her unfertilized eggs, where the warning is stored, so to speak, and then passed to offspring after conception.

Examples of such genetic cascades abound, even in humans. Studies have shown that pregnant women affected by famine in the Netherlands from 1944 to 1945, known as the Dutch Hunger Winter, gave birth to children who were influenced by that episode as adults -- with higher rates than average of obesity, diabetes, and schizophrenia.

In this study, the biologists wanted to find out how the memory of stress exposure was stored in the egg cell.

"Genes have 'memories' of past environmental conditions that, in turn, affect their expression even after these conditions have changed," Prahlad explains. "How this 'memory' is established and how it persists past fertilization, embryogenesis, and after the embryo develops into adults is not clear. "This is because during embryogenesis, most organisms typically reset any changes that have been made to genes because of the genes' past activity."

Prahlad and her teams turned to the roundworm, a creature regularly studied by scientists, for clues. They exposed mother roundworms to unexpected stresses and found the stress memory was ingrained in the mother's eggs through the actions of a protein called the heat shock transcription factor, or HSF1. The HSF1 protein is present in all plants and animals and is activated by changes in temperature, salinity, and other stressors.

The team found that HSF1 recruits another protein, an enzyme called a histone 3 lysine 9 (H3K9) methyltransferase. The latter normally acts during embryogenesis to silence genes and erase the memory of their prior activity.

However, Prahald's team observed something else entirely.

"We found that HSF1 collaborates with the mechanisms that normally act to 'reset' the memory of gene expression during embryogenesis to, instead, establish this stress memory," Prahlad says.

One of these newly silenced genes encodes the insulin receptor, which is central to metabolic changes with diabetes in humans, and which, when silenced, alters an animal's physiology, metabolism, and stress resilience. Because these silencing marks persisted in offspring, their stress-response strategy was switched from one that depended on the ability to be highly responsive to stress, to relying instead on mechanisms that decreased stress responsiveness but provided long-term protection from stressful environments.

"What we found all the more remarkable was that if the mother was exposed to stress for a short period of time, only progeny that developed from her germ cells that were subjected to this stress in utero had this memory," Prahlad says. "The progeny of these progeny (the mother's grandchildren) had lost this memory. However, if the mother was subjected to a longer period of stress, the grandchildren generation retained this memory. Somehow the 'dose' of maternal stress exposure is recorded in the population."

The researchers plan to investigate these changes further. HSF1 is not only required for stress resistance but also increased levels of both HSF1 and the silencing mark are associated with cancer and metastasis. Because HSF1 exists in many organisms, its newly discovered interaction with H3K9 methyltransferase to drive gene silencing is likely to have larger repercussions.

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