'Good cholesterol' may protect liver

Study in mice, human blood samples, suggests HDL from the intestine may prevent liver inflammation

July 22, 2021

Science Daily/Washington University School of Medicine

The body's so-called good cholesterol may be even better than we realize. New research from Washington University School of Medicine in St. Louis suggests that one type of high-density lipoprotein (HDL) has a previously unknown role in protecting the liver from injury. This HDL protects the liver by blocking inflammatory signals produced by common gut bacteria.

The study is published July 23 in the journal Science.

HDL is mostly known for mopping up cholesterol in the body and delivering it to the liver for disposal. But in the new study, the researchers identified a special type of HDL called HDL3 that, when produced by the intestine, blocks gut bacterial signals that cause liver inflammation. If not blocked, these bacterial signals travel from the intestine to the liver, where they activate immune cells that trigger an inflammatory state, which leads to liver damage.

"Even though HDL has been considered 'good cholesterol,' drugs that increase overall HDL levels have fallen out of favor in recent years because of clinical trials that showed no benefit in cardiovascular disease," said senior author Gwendalyn J. Randolph, PhD, the Emil R. Unanue Distinguished Professor of Immunology. "But our study suggests that raising levels of this specific type of HDL, and specifically raising it in the intestine, may hold promise for protecting against liver disease, which, like heart disease, also is a major chronic health problem." In the study, the researchers showed that HDL3 from the intestine protects the liver from inflammation in mice.

Any sort of intestinal damage can impact how a group of microbes called Gram-negative bacteria can affect the body. Such microbes produce an inflammatory molecule called lipopolysaccharide that can travel to the liver via the portal vein. The portal vein is the major vessel that supplies blood to the liver, and it carries most nutrients to the liver after food is absorbed in the intestine. Substances from gut microbes may travel along with nutrients from food to activate immune cells that trigger inflammation. In this way, elements of the gut microbiome may drive liver disease, including fatty liver disease and liver fibrosis, in which the liver develops scar tissue.

Randolph became interested in this topic through a collaboration with two Washington University surgeons, Emily J. Onufer, MD, a surgical resident, and Brad W. Warner, MD, the Jessie L. Ternberg PhD, MD, Distinguished Professor of Pediatric Surgery and chief surgeon at St. Louis Children's Hospital, both co-authors on the study. Some premature infants develop a life-threatening condition called necrotizing enterocolitis, an inflammation of the intestine that can require a portion of the intestine to be surgically removed. Even after a successful bowel surgery, such babies often develop liver disease, and Onufer and Warner wanted to understand why.

"They were studying this problem in a mouse model of the condition: They remove a portion of the small intestine in mice and study the liver fibrosis that results," Randolph said. "There were hints in the literature that HDL might interfere with lipopolysaccharide's detection by immune cells and that the receptor for lipopolysaccharide might be linked to liver disease following the bowel surgery.

"However, no one thought that HDL would directly move from the intestine to the liver, which requires that it enter the portal vein," she said. "In other tissues, HDL travels out through a different type of vessel called a lymphatic vessel that, in the intestine, does not link up to the liver. We have a very nice tool in our lab that lets us shine light on different organs and track the HDL from that organ. So, we wanted to shine light on the intestine and see how the HDL leaves and where it goes from there. That's how we showed that HDL3 leaves only through the portal vein to go directly to the liver."

As the HDL3 makes this short journey down the portal vein, it binds to a protein called LBP -- lipopolysaccharide binding protein -- which binds to the harmful lipopolysaccharide. When the harmful lipopolysaccharide is bound to this complex, it is blocked from activating immune cells called Kupffer cells. These are macrophages that reside in the liver and, when activated by lipopolysaccharide, can drive liver inflammation.

As a complex of proteins and fats, HDL3 uses its partnership with LBP to bind to lipopolysaccharide. When LBP is part of the HDL3 complex, it prevents the harmful bacterial molecule from activating the liver Kupffer cells and inducing inflammation, according to experiments conducted by first author Yong-Hyun Han, PhD, when he was a postdoctoral researcher in Randolph's lab. Han is now on the faculty of Kangwon National University in South Korea.

"We think that LBP, only when bound to HDL3, is physically standing in the way, so lipopolysaccharide can't activate the inflammatory immune cells," Han said. "HDL3 is essentially hiding the harmful molecule. However, if LBP is binding to lipopolysaccharide and HDL3 is not present, LBP is not able to stand in the way. Without HDL3, LBP is going to trigger stronger inflammation."

The researchers showed that liver injury is worse when HDL3 from the intestine is reduced, such as from surgical removal of a portion of the intestine.

"The surgery seems to cause two problems," Randolph said. "A shorter intestine means it's making less HDL3, and the surgery itself leads to an injurious state in the gut, which allows more lipopolysaccharide to spill over into the portal blood. When you remove the part of the intestine that makes the most HDL3, you get the worst liver outcome. When you have a mouse that cannot genetically make HDL3, liver inflammation is also worse. We also wanted to see if this dynamic was present in other forms of intestinal injury, so we looked at mouse models of a high-fat diet and alcoholic liver disease."

In all of these models of intestinal injury, the researchers found that HDL3 was protective, binding to the additional lipopolysaccharide released from the injured intestine and blocking its downstream inflammatory effects in the liver.

The researchers further showed that the same protective molecular complexes were present in human blood samples, suggesting a similar mechanism is present in people. They also used a drug compound to increase HDL3 in the intestines of mice and found it to be protective against different types of liver injury. While the drug is only available for animal research, the study reveals new possibilities for treating or preventing liver disease, whether it stems from damage to the intestine caused by high-fat diets, alcohol overuse or physical injury, such as from surgery.

"We are hopeful that HDL3 can serve as a target in future therapies for liver disease," Randolph said. "We are continuing our research to better understand the details of this unique process."

https://www.sciencedaily.com/releases/2021/07/210722171210.htm

Study reveals new aspects of gingivitis and body's response

Links to other health issues suggested

July 14, 2021

Science Daily/University of Washington School of Dentistry

A team led by University of Washington researchers has, for the first time, identified and classified how different people respond to the accumulation of dental plaque, the sticky biofilm that gathers on teeth. Their work, recently published in the journal Proceedings of the National Academy of Sciences(PNAS), sheds important new light on why some people may be more prone to serious conditions that lead to tooth loss and other problems.

Left unchecked, plaque buildup can induce gingivitis, or gum inflammation. Gingivitis, in turn, can lead to periodontitis, a serious gum infection that damages the soft tissue and can destroy the bone that supports teeth. Not only can this result in tooth loss, but chronic inflammation can also spur other serious health consequences, including heart disease, diabetes, cancer, arthritis, and bowel diseases.

The researchers also found a previously unidentified range of inflammatory responses to bacterial accumulation in the mouth. When bacteria build up on tooth surfaces, it generates inflammation, a tool the body uses to tamp down the buildup. Previously, there were two known major oral inflammation phenotypes, or individual traits: a high or strong clinical response and a low clinical response. The team identified a third phenotype, which they called "slow": a delayed strong inflammatory response in the wake of the bacterial buildup.

The study revealed for the first time that subjects with low clinical response also demonstrated a low inflammatory response for a wide variety of inflammation signals. "Indeed, this study has revealed a heterogeneity in the inflammatory response to bacterial accumulation that has not been described previously," said Dr. Richard Darveau of the UW School of Dentistry, one of the study's authors.

His School of Dentistry colleague and study co-author Dr. Jeffrey McLean said, "We found a particular group of people that have a slower development of plaque as well as a distinct microbial community makeup prior to the start of the study." The study authors wrote that understanding the variations in gum inflammation could help better identify people at elevated risk of periodontitis. In addition, it is possible that this variation in the inflammatory response among the human population may be related to susceptibility to other chronic bacterial-associated inflammatory conditions such as inflammatory bowel disease.

In addition, the researchers found a novel protective response by the body, triggered by plaque accumulation, that can save tissue and bone during inflammation. This mechanism, which was apparent among all three phenotypes, utilizes white blood cells known as neutrophils. In the mouth, they act something like cops on the beat, patrolling and regulating the bacterial population to maintain a stable condition known as healthy homeostasis.

In this instance, plaque is not a villain. To the contrary, the researchers said that the proper amount and makeup of plaque supports normal tissue function. Studies in mice have also shown that plaque also provides a pathway for neutrophils to migrate from the bloodstream through the gum tissue and into the crevice between the teeth and gums.

When healthy homeostasis exists and everything is working right, the neutrophils promote colonization resistance, a low-level protective inflammatory response that helps the mouth fend off an excess of unhealthy bacteria and resist infection. At the same time, the neutrophils help ensure the proper microbial composition for normal periodontal bone and tissue function.

The researchers' findings underscore why dentists preach the virtues of regular brushing and flossing, which prevent too much plaque buildup. "The idea of oral hygiene is to in fact recolonize the tooth surface with appropriate bacteria that participate with the host inflammatory response to keep unwanted bacteria out," Dr. Darveau said. The bacteria start repopulating the mouth's surfaces spontaneously and almost immediately afterward, he said.

https://www.sciencedaily.com/releases/2021/07/210714110501.htm

'Springing forward' affects early birds less than night owls

July 20, 2021

Science Daily/Michigan Medicine - University of Michigan

Every spring, the Daylight Saving Time shift robs people of an hour of sleep -- and a new study shows that DNA plays a role in how much the "spring forward" time change affects individuals.

People whose genetic profile makes them more likely to be "early birds" the rest of the year can adjust to the time change in a few days, the study shows. But those who tend to be "night owls" could take more than a week to get back on track with sleep schedule, according to new data published in Scientific Reportsby a team from the University of Michigan.

The study uses data from continuous sleep tracking of 831 doctors in the first year of post-medical school training when the time shift occurred in spring 2019. All were first-year residents or "interns" in medical parlance, and taking part in the Intern Health Study based at the Michigan Neuroscience Institute.

From the large UK Biobank dataset, the researchers calculated genomic "chronotype" predisposition information, also known as the Objective Sleep Midpoint polygenic score. People with low scores were genomically predisposed to be "early birds" and those with high scores were genomically "night owls."

The team then applied these genomic scores in the intern sample and focused on the two groups of about 130 physicians each that had the strongest tendencies to be "early birds" and "night owls" based on their scores. The researchers looked at how their sleep patterns changed from the week before DST to the weekend after it.

In general, the difference in post-DST weekday wakeup times between the two groups was not large -- probably because first-year medical residents have very strict work schedules.

In fact, the stressful duties and demanding schedules that interns endure is what made this population such an interesting one to study, and the larger Intern Health Study that the data come from has yielded important findings about the relationship between stress, sleep, genetics, mood and mental health.

But the time they got to sleep on the nights before workdays, and both sleep and wake times on the weekend, varied significantly between the two groups. The DST change made the differences even more pronounced.

Early birds had adjusted their sleep times by Tuesday, but night owls were still off track on the following Saturday.

Margit Burmeister, Ph.D., the U-M neuroscientist and geneticist who is the paper's senior and corresponding author, says the study gives one more strong reason for abolishing Daylight Saving Time.

"It's already known that DST has effects on rates of heart attacks, motor vehicle accidents, and other incidents, but what we know about these impacts mostly comes from looking for associations in large data pools after the fact," she says. "These data from direct monitoring and genetic testing allows us to directly see the effect, and to see the differences between people with different circadian rhythm tendencies that are influenced by both genes and environment. To put it plainly, DST makes everything worse for no good reason."

The study's first author is Jonathan Tyler, Ph.D., a postdoctoral assistant professor of mathematics at U-M.

Sleep schedules depend on a combination of many factors -- but the fact that people can react so differently to the same abrupt change in time makes it important to study further. The researchers also looked at the "fall back" time change in autumn and found no significant differences between early birds and night owls in how they reacted to the abrupt addition of an hour of sleep.

The findings have implications not just for the annual spring time change, but also for shift workers, travelers across time zones and even people deciding which profession to choose, the researchers note. Burmeister says she hopes to look further at differences between people in different professions in future studies.

Co-author Srijan Sen, M.D., Ph.D. who leads the Intern Health Study and directs the Frances and Kenneth Eisenberg and Family Depression Center at U-M, continues to lead other studies of how each year's crop of interns at over 100 hospitals react to the stresses of their training. The interns in the newly published study, like all interns, are in general chronically sleep-deprived because of the number of hours they need to be on duty or preparing for duty.

"This study is a demonstration of how we much we vary in our response to even relatively minor challenges to our daily routines, like DST," he said. "Discovering the mechanisms underlying this variation can help us understand our individual strengths and vulnerabilities better."

https://www.sciencedaily.com/releases/2021/07/210720135216.htm

Spending time outdoors has positive effect on our brains

July 15, 2021

Science Daily/Max Planck Institute for Human Development

If you're regularly out in the fresh air, you're doing something good for both your brain and your well-being. This is the conclusion reached by researchers at the Max Planck Institute for Human Development and the Medical Center Hamburg-Eppendorf (UKE). The longitudinal study recently appeared in The World Journal of Biological Psychiatry.

During the Corona pandemic, walks became a popular and regular pastime. A neuroscientific study suggests that this habit has a good effect not only on our general well-being but also on our brain structure. It shows that the human brain benefits from even short stays outdoors. Until now, it was assumed that environments affect us only over longer periods of time.

The researchers regularly examined six healthy, middle-aged city dwellers for six months. In total, more than 280 scans were taken of their brains using magnetic resonance imaging (MRI). The focus of the study was on self-reported behavior during the last 24 hours and in particular on the hours that participants spent outdoors prior to imaging. In addition, they were asked about their fluid intake, consumption of caffeinated beverages, the amount of time spent outside, and physical activity, in order to see if these factors altered the association between time spent outside and the brain. In order to be able to include seasonal differences, the duration of sunshine in the study period was also taken into account.

Brain scans show that the time spent outdoors by the participants was positively related to gray matter in the right dorsolateral-prefrontal cortex, which is the superior (dorsal) and lateral part of the frontal lobe in the cerebral cortex. This part of the cortex is involved in the planning and regulation of actions as well as what is referred to as cognitive control. In addition, many psychiatric disorders are known to be associated with a reduction in gray matter in the prefrontal area of the brain.

The results persisted even when the other factors that could also explain the relationship between time spent outdoors and brain structure were kept constant. The researchers performed statistical calculations in order to examine the influence of sunshine duration, number of hours of free time, physical activity, and fluid intake on the results. The calculations revealed that time spent outdoors had a positive effect on the brain regardless of the other influencing factors.

"Our results show that our brain structure and mood improve when we spend time outdoors. This most likely also affects concentration, working memory, and the psyche as a whole. We are investigating this in an ongoing study. The subjects are asked to also solve cognitively challenging tasks and wear numerous sensors that measure the amount of light they are exposed to during the day, among other environmental indicators," says Simone Kühn, head of the Lise Meitner Group for Environmental Neuroscience at the Max Planck Institute for Human Development and lead author of the study.

The results therefore, support the previously assumed positive effects of walking on health and extend them by the concrete positive effects on the brain. Because most psychiatric disorders are associated with deficits in the prefrontal cortex, this is of particular importance to the field of psychiatry.

"These findings provide neuroscientific support for the treatment of mental disorders. Doctors could prescribe a walk in the fresh air as part of the therapy -- similar to what is customary for health cures," says Anna Mascherek, post-doctoral fellow in the Department of Psychiatry and Psychotherapy of the Medical Center Hamburg-Eppendorf (UKE) and co-author of the study.

In the ongoing studies, the researchers also want to directly compare the effects of green environments vs urban spaces on the brain. In order to understand where exactly the study participants spend their time outdoors, the researchers plan to use GPS (Global Positioning System) data and include other factors that may play a role such as traffic noise and air pollution.

https://www.sciencedaily.com/releases/2021/07/210715103025.htm

No link between moderate coffee consumption and increased risk of cardiac arrhythmia

July 20, 2021

Science Daily/University of California - San Francisco

In the largest study of its kind, an investigation by UC San Francisco has found no evidence that moderate coffee consumption leads to a greater risk of cardiac arrhythmia.

In fact, each additional daily cup of coffee consumed among several hundred thousand individuals was associated with a 3 percent lower risk of any arrhythmia occurring, including atrial fibrillation, premature ventricular contractions, or other common heart conditions, the researchers report. The study included a four-year follow up.

The paper is published July 19, 2021, in JAMA Internal Medicine.

"Coffee is the primary source of caffeine for most people, and it has a reputation for causing or exacerbating arrhythmias," said senior and corresponding author Gregory Marcus, MD, professor of medicine in the Division of Cardiology at UCSF.

"But we found no evidence that caffeine consumption leads to a greater risk of arrhythmias," said Marcus, who specializes in the treatment of arrhythmias. "Our population-based study provides reassurance that common prohibitions against caffeine to reduce arrhythmia risk are likely unwarranted."

While some professional societies suggest avoiding caffeinated products to lower the risk for arrhythmia, this connection has not been consistently demonstrated -- indeed, coffee consumption may have anti-inflammatory benefits and is associated with reduced risks of some illnesses including cancer, diabetes, and Parkinson disease.

In the new study, UCSF scientists explored whether habitual coffee intake was associated with a risk of arrhythmia, and whether genetic variants that affect caffeine metabolism could modify that association. Their investigation was conducted via the community-based UK Biobank, a prospective study of participants in England's National Health Services.

Some 386,258 coffee drinkers took part in the coffee research, with an average mean age of 56 years; slightly more than half were female. It was an unprecedented sample size for this type of inquiry.

In addition to a conventional analysis examining self-reported coffee consumption as a predictor of future arrhythmias, the investigators employed a technique called "Mendelian Randomization," leveraging genetic data to infer causal relationships. As those with the genetic variants associated with faster caffeine metabolism drank more coffee, this analysis provided a method to test the caffeine-arrhythmia relationship in a way that did not rely on participant self-report and should have been immune to much of the confounding inherent to most observational studies.

With a mean four-year follow up, data were adjusted for demographic characteristics, health and lifestyle habits.

Ultimately, approximately 4 percent of the sample developed an arrhythmia. No evidence of a heightened risk of arrhythmias was observed among those genetically predisposed to metabolize caffeine differently. The researchers said that higher amounts of coffee were actually associated with a 3 percent reduced risk of developing an arrhythmia.

The authors noted limitations including the self-reporting nature of the study, and that detailed information on the type of coffee -- such as espresso or not -- was unavailable.

"Only a randomized clinical trial can definitively demonstrate clear effects of coffee or caffeine consumption," said Marcus. "But our study found no evidence that consuming caffeinated beverages increased the risk of arrhythmia. Coffee's antioxidant and anti-inflammatory properties may play a role, and some properties of caffeine could be protective against some arrhythmias."

https://www.sciencedaily.com/releases/2021/07/210720114336.htm

New study suggests benefit-to-harm balance of statins for healthy adults 'generally favorable'

Findings should reassure patients and should not deter their use, say researchers

July 14, 2021

Science Daily/BMJ

Statins are associated with a small increased risk of side effects in patients without a history of heart disease, but these effects are mild compared with the potential benefits of treatment in preventing major cardiovascular events, say researchers in The BMJtoday.

They say their findings suggest that the benefit-to-harm balance of statins for adults without heart disease is generally favourable.

Statins are widely used to prevent heart disease, and severe side effects are rare, but many people are reluctant to take them because of the potential for milder effects such as muscle weakness and stiffness.

For people with existing heart disease, the benefits of statins far outweigh the risk of these effects, but when statins are used by people without a history of heart disease (known as primary prevention) the benefit-to-harm balance of treatment might be less favourable.

Yet recent guidelines have recommended wider use of statins for primary prevention.

So, a team of UK and US researchers set out to examine the associations between statins and adverse events in adults without a history of heart disease, and how they vary by type and dose of statins.

They analysed the results of 62 randomised controlled trials with 120,456 participants (average age 61; 40% women) followed up for an average of 3.9 years. The trials were designed differently, and were of varying quality, but the researchers were able to allow for that in their analysis.

Statins were associated with a slightly increased risk of self-reported muscle pain, liver and kidney problems, and certain eye conditions such as cataracts, but were not associated with clinically confirmed muscle disorders or diabetes.

These risks equated to 15 more instances of muscle symptoms, eight more liver events, 12 more kidney events, and 14 more eye conditions per 10,000 patients treated for a year.

However, these increased risks did not outweigh the reduction in the risk of major cardiovascular events. For example, statins were estimated to prevent 19 heart attacks, nine strokes, and eight deaths from cardiovascular disease per 10,000 patients treated for a year.

This suggests that the benefit-to-harm balance of statins for primary prevention of cardiovascular disease is favourable, say the researchers.

Analyses by type of statin showed that atorvastatin, lovastatin, and rosuvastatin were associated with some adverse events, but few significant differences were seen between the statins.

A possible modest dose-response relationship was identified for the effect of atorvastatin on liver dysfunction, but the dose-response relationships for the other types of statins and adverse effects were inconclusive.

This suggests that tailoring statin doses to deal with safety concerns when starting treatment is not currently needed, the researchers add.

This was a large study that was able to accurately assess the adverse effects of treatment with statins. But the researchers point to some limitations in trial design that may have led to events being underestimated or more severe long term events being missed.

However, they say the low risk of adverse events caused by statins reported in this review "should reassure patients and physicians that the potential harms of statins are small and should not deter their use for primary prevention of cardiovascular disease."

They agree that routine monitoring of liver function during treatment is probably warranted in primary prevention, and say further studies are needed to help improve adherence to treatment and achieve more efficient monitoring.

https://www.sciencedaily.com/releases/2021/07/210714183428.htm

Compound derived from turmeric essential oil has neuroprotective properties

July 14, 2021

Science Daily/Kumamoto University

Researchers from Kumamoto University, Japan have found that a component derived from turmeric essential oil, aromatic turmerone (ar-turmerone), and its derivatives act directly on dopaminergic nerves to create a neuroprotective effect on tissue cultures of a Parkinson's disease model. This appears to be due to enhanced cellular antioxidant potency from the activation of Nrf2. The researchers believe that the ar-turmerone derivatives identified in this study can be used as new therapeutic agents for Parkinson's disease.

Parkinson's disease is a neurodegenerative disease caused by the selective death of dopaminergic neurons that transmit information from the substantia nigra of the midbrain to the striatum which results in decreased dopamine production. Symptoms include limb tremors, immobility, muscle rigidity, and other movement disorders. Treatments, such as dopamine supplements, are currently available but there still no way to inhibit dopaminergic neurodegeneration.

Previous studies have reported that the inflammatory response caused by the activation of microglia (cells responsible for immune function in the brain) is observed in the substantia nigra of the midbrain of Parkinson's disease patients. Further experiments designed to mimic the in vivo state of the midbrain (midbrain slice culture) revealed that microglial activation triggers the selective degeneration of dopaminergic neurons in the substantia nigra, and that nitric oxide (NO) derived from activated microglia was involved in the neurodegeneration. These findings suggest that compounds with anti-inflammatory effects on microglia may suppress dopaminergic degeneration.

Thus, researchers analyzed aromatic tumerone (ar-turmerone), a major component of turmeric essential oil that has been reported to exhibit anti-tumor and anti-inflammatory effects on microglia. They used the BV2 microglial cell line and midbrain slice cultures to 1) determine if ar-turmerone suppresses dopaminergic neurodegeneration through its anti-inflammatory effects, and 2) identify structurally similar compounds (derivatives) that might have stronger anti-inflammatory and neuroprotective effects.

Ar-turmerone has an asymmetric carbon (S-Tur) so researchers prepared eight analogues and attempted to identify those with stronger anti-inflammatory effects. They used the inhibitory effects on the inflammatory response as induced by lipopolysaccharide (LPS)-stimulated activation of BV2 cells as an indicator. The analogues with stronger anti-inflammatory effects than S-Tur were (R)-ar-turmerone (R-Tur), ar-atlantone (Atl), and analog 2 (A2).

To examine whether these compounds, including S-Tur, have an inhibitory effect on dopaminergic degeneration, researchers then observed midbrain slice cultures in which microglial activation was induced by interferon-γ and LPS stimulation (IFN-γ/LPS). All four compounds significantly suppressed a decrease in the number of dopaminergic neurons as induced by IFN-γ/LPS. However, the production of NO, which is released from activated microglia and is involved in dopaminergic neurodegeneration, was not inhibited at all. In addition, three compounds, S-Tur, Atl and A2, inhibited dopaminergic degeneration that is induced by MPP+, a toxin that selectively damages dopaminergic neurons independent of microglial activity. These results indicate that S-Tur and its derivatives, Atl and A2, have a direct effect on dopaminergic neurons and exhibit neuroprotective effects. Furthermore, analysis using dopaminergic progenitor cell lines and midbrain slice cultures revealed that the neuroprotective effects of Atl and A2 are mediated by activation of Nrf2, a transcription factor that enhances the antioxidant potency of cells.

"Our study elucidated a new mechanism by which ar-turmerone and its derivatives directly protect mesencephalic slice dopaminergic neurons, independent of their previously reported anti-inflammatory effects on microglia," said Associate Professor Takahiro Seki, who led the study. "We showed that two derivatives, Atl and A2, exhibit neuroprotective effects by increasing the expression of antioxidant proteins through the activation of Nrf2. In particular, the analog A2 identified in this study is a potent activator of Nrf2 and is assumed to have a strong antioxidant effect. We think it is possible that this compound may be a new dopaminergic neuroprotective agent for Parkinson's disease treatment, and it could also be used to treat other diseases caused by oxidative stress, such as liver and kidney diseases."

https://www.sciencedaily.com/releases/2021/07/210714110452.htm

Exposure to light with less blue before sleep is better for energy metabolism

July 9, 2021

Science Daily/University of Tsukuba

Researchers have found that exposure to specific types of light before sleep can have variable effects on energy metabolism during sleep. Specifically, participants who went to sleep after exposure to organic light-emitting diodes (OLEDs), which emit polychromatic white light that contains less blue light than light-emitting diodes (LEDs), exhibited significantly decreased energy expenditure, core body temperature, and increased fat oxidation, indicating fewer negative health consequences compared with after nighttime exposure to LEDs.

Extended exposure to light during nighttime can have negative consequences for human health. But now, researchers from Japan have identified a new type of light with reduced consequences for physiological changes during sleep.

In a study published in June 2021 in Scientific Reports, researchers from University of Tsukuba compared the effects of light-emitting diodes (LEDs), which have been widely adopted for their energy-saving properties, with organic light-emitting diodes (OLEDs) on physical processes that occur during sleep.

Polychromatic white LEDs emit a large amount of blue light, which has been linked with many negative health effects, including metabolic health. In contrast, OLEDs emit polychromatic white light that contains less blue light. However, the impact of LED and OLED exposure at night has not been compared in terms of changes in energy metabolism during sleep, something the researchers at University of Tsukuba aimed to address.

"Energy metabolism is an important physiological process that is altered by light exposure," says senior author of the study Professor Kumpei Tokuyama. "We hypothesized that compared with LEDs, OLED exposure would have a reduced effect on sleep architecture and energy metabolism, similar to that of dim light."

To test this hypothesis, the researchers exposed 10 male participants to LED, OLED, or dim light for 4 hours before they slept in a metabolic chamber. The researchers then measured energy expenditure, core body temperature, fat oxidation, and 6-sulfatoxymelatonin -- which is a measure of melatonin levels -- during sleep. The participants had not recently traveled or participated in shift work.

"The results confirmed part of our hypothesis," explains Professor Tokuyama. "Although no effect on sleep architecture was observed, energy expenditure and core body temperature during sleep were significantly decreased after OLED exposure. Furthermore, fat oxidation during sleep was significantly lower after exposure to LED compared with OLED."

In addition, fat oxidation during sleep was positively correlated with 6-sulfatoxymelatonin levels following exposure to OLED, suggesting that the effect of melatonin activity on energy metabolism varies depending on the type of light exposure.

"Thus, light exposure at night is related to fat oxidation and body temperature during sleep. Our findings suggest that specific types of light exposure may influence weight gain, along with other physiological changes," says Professor Tokuyama.

Many occupations and activities involve exposure to artificial light before sleep. New information about the effects of different kinds of light on physical processes may facilitate the selection of alternative light sources to mitigate the negative consequences of light exposure at night. Furthermore, these findings advance our knowledge regarding the role of light in energy metabolism during sleep.

https://www.sciencedaily.com/releases/2021/07/210709104232.htm

Researchers record brainwaves to measure 'cybersickness'

July 7, 2021

Science Daily/University of Maryland

If a virtual world has ever left you feeling nauseous or disorientated, you're familiar with cybersickness, and you're hardly alone. The intensity of virtual reality (VR) -- whether that's standing on the edge of a waterfall in Yosemite or engaging in tank combat with your friends -- creates a stomach-churning challenge for 30-80% of users.

In a first-of-its kind study, researchers at the University of Maryland recorded VR users' brain activity using electroencephalography (EEG) to better understand and work toward solutions to prevent cybersickness. The research was conducted by Eric Krokos, who received his Ph.D. in computer science in 2018, and Amitabh Varshney, a professor of computer science and dean of UMD's College of Computer, Mathematical, and Natural Sciences.

Their study, "Quantifying VR cybersickness using EEG," was recently published in the journal Virtual Reality.

The term cybersickness derives from motion sickness, but instead of physical movement, it's the perception of movement in a virtual environment that triggers physical symptoms such as nausea and disorientation. While there are several theories about why it occurs, the lack of a systematic, quantified way of studying cybersickness has hampered progress that could help make VR accessible to a broader population.

Krokos and Varshney are among the first to use EEG -- which records brain activity through sensors on the scalp -- to measure and quantify cybersickness for VR users. They were able to establish a correlation between the recorded brain activity and self-reported symptoms of their participants. The work provides a new benchmark -- helping cognitive psychologists, game developers and physicians as they seek to learn more about cybersickness and how to alleviate it.

"Establishing a strong correlation between cybersickness and EEG-measured brain activity is the first step toward interactively characterizing and mitigating cybersickness, and improving the VR experience for all," Varshney said.

EEG headsets have been widely used to measure motion sickness, yet prior research on cybersickness has relied on users to accurately recall their symptoms through questionnaires filled out after users have removed their headsets and left the immersive environment.

The UMD researchers said that such methods provide only qualitative data, making it difficult to assess in real time which movements or attributes of the virtual environment are affecting users.

Another complication is that not all people suffer from the same physical symptoms when experiencing cybersickness, and cybersickness may not be the only cause of these symptoms.

Without the existence of a reliable tool to measure and interactively quantify cybersickness, understanding and mitigating it remains a challenge, said Varshney, a leading researcher in immersive technologies and co-director of the Maryland Blended Reality Center.

For the UMD study, participants were fitted with both a VR headset and an EEG recording device, then experienced a minute-long virtual fly-through of a futuristic spaceport. The simulation included quick drops and gyrating turns designed to evoke a moderate degree of cybersickness.

Participants also self-reported their level of discomfort in real time with a joystick. This helped the researchers identify which segments of the fly-through intensified users' symptoms.

https://www.sciencedaily.com/releases/2021/07/210707160524.htm

Adult ADHD is linked to numerous physical conditions,

July 7, 2021

Science Daily/Karolinska Institutet

Adults with ADHD are at higher risk of a wide range of physical conditions, including nervous system, respiratory, musculoskeletal, and metabolic diseases, according to a large register-based study from Karolinska Institutet in Sweden published in The Lancet Psychiatry.

"Identifying co-occurring physical diseases may have important implications for treating adults with ADHD and for benefiting the long-term health and quality of life of patients," says lead author Ebba Du Rietz, postdoctoral researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.

ADHD is a common neuropsychiatric disorder characterised by inattention, impulsiveness and hyperactivity, and commonly treated with stimulant therapy (methylphenidates or amphetamines).

Previous studies suggest increased risk for a number of physical health conditions in adults with ADHD, but only a limited number of these associations have been thoroughly researched. Moreover, detailed treatment guidelines for adults with ADHD and co-occurring physical disease are largely lacking. Now, researchers at Karolinska Institutet have examined possible associations between ADHD and a wide range of physical diseases in adulthood, and whether genetic or environmental factors are involved.

Over four million individuals (full-sibling and maternal half-sibling pairs) born between 1932-1995 were identified through Swedish registers and followed between 1973-2013. Clinical diagnoses were obtained from the Swedish National Patient Register. The researchers examined the risk of 35 different physical conditions in individuals with ADHD compared to those without, and in siblings of individuals with ADHD compared to siblings of those without.

Individuals with ADHD had a statistically significant increased risk of all studied physical conditions except arthritis. The strongest associations were found for nervous system, respiratory, musculoskeletal, and metabolic diseases. The diagnoses most strongly associated with ADHD were alcohol-related liver disease, sleep disorders, chronic obstructive pulmonary disease (COPD), epilepsy, fatty liver disease and obesity. ADHD was also linked to a slightly increased risk of cardiovascular disease, Parkinson's disease and dementia.

"These results are important because stimulant therapy requires careful monitoring in ADHD patients with co-occurring cardiac disease, hypertension and liver failure," says senior author Henrik Larsson, professor at Örebro University and affiliated researcher at Karolinska Institutet.

The increased risk was largely explained by underlying genetic factors that contributed both to ADHD and the physical disease, with the exception of nervous system disorders and age-related diseases. Full siblings of individuals with ADHD had significantly increased risk for most physical conditions.

The researchers now aim to study the underlying mechanisms and risk factors as well as the impact of ADHD on management and prognosis of physical diseases in adults.

The study was funded by the Swedish Research Council, the Swedish Brain Foundation, the Swedish Research Council for Health, Working Life and Welfare, Region Stockholm, StratNeuro (Karolinska Institutet), the European Union's Horizon 2020 research and innovation programme, and The National Institute of Mental Health. Ebba Du Rietz has served as a speaker for Shire Sweden AB outside the submitted work. Henrik Larsson has served as a speaker for Evolan Pharma and Shire/Takeda and has received research grants from Shire/Takeda. Co-author Marica Leone is an employee of Janssen Pharmaceutical Companies of Johnson & Johnson. See the scientific article for a complete list of potential conflicts of interest.

https://www.sciencedaily.com/releases/2021/07/210706191617.htm

There's a 'man in the moon': Why our brains see human faces everywhere

Our need to quickly judge friend or foe has produced an intriguing evolutionary side-effect

July 6, 2021

Science Daily/University of Sydney

It's so commonplace we barely give it a second thought, but human brains seem hardwired to see human faces where there are none -- in objects as varied as the moon, toys, plastic bottles, tree trunks and vacuum cleaners. Some have even seen an imagined Jesus in cheese on toast.

Until now scientists haven't understood exactly what the brain is doing when it processes visual signals and interprets them as representations of the human face.

Neuroscientists at the University of Sydney now say how our brains identify and analyse real human faces is conducted by the same cognitive processes that identify illusory faces.

"From an evolutionary perspective, it seems that the benefit of never missing a face far outweighs the errors where inanimate objects are seen as faces," said Professor David Alais lead author of the study from the School of Psychology.

"There is a great benefit in detecting faces quickly," he said, "but the system plays 'fast and loose' by applying a crude template of two eyes over a nose and mouth. Lots of things can satisfy that template and thus trigger a face detection response."

This facial recognition response happens lightning fast in the brain: within a few hundred milliseconds.

"We know these objects are not truly faces, yet the perception of a face lingers," Professor Alais said. "We end up with something strange: a parallel experience that it is both a compelling face and an object. Two things at once. The first impression of a face does not give way to the second perception of an object."

This error is known as "face pareidolia." It is such a common occurrence that we accept the notion of detecting faces in objects as 'normal' -- but humans do not experience this cognitive process as strongly for other phenomena.

The brain has evolved specialised neural mechanisms to rapidly detect faces and it exploits the common facial structure as a short-cut for rapid detection.

"Pareidolia faces are not discarded as false detections but undergo facial expression analysis in the same way as real faces," Professor Alais said.

Not only do we imagine faces, we analyse them and give them emotional attributes.

The findings are published today in the Proceedings of the Royal Society B.

The researchers say this expression analysis of inanimate objects is because as deeply social beings, simply detecting a face isn't enough.

"We need to read the identity of the face and discern its expression. Are they a friend or a foe? Are they happy, sad, angry, pained?" Professor Alais said.

What the study examined was whether once a pareidolia face is detected, it is subsequently analysed for facial expression, or discarded from face processing as a false detection.

The research shows that once a false face is retained by the brain it is analysed for its facial expression in the same way that a real face is.

"We showed this by presenting sequences of faces and having participants rate each face's expression on a scale ranging from angry to happy," Professor Alais said.

What was intriguing is that a known bias in judging human faces persisted with analysis of inanimate imagined faces.

A previous study undertaken by Professor Alais showed that in a Tinder-like situation of judging face after face, a bias is observed whereby the assessment of the current face is influenced by our assessment of the previous face.

The scientists tested this by mixing up real faces with pareidolia faces -- and the result was the same.

"This 'cross-over' condition is important as it shows the same underlying facial expression process is involved regardless of image type," Professor Alais said.

"This means that seeing faces in clouds is more than a child's fantasy," he said.

"When objects look compellingly face-like, it is more than an interpretation: they really are driving your brain's face detection network. And that scowl, or smile; that's your brain's facial expression system at work. For the brain, fake or real, faces are all processed the same way."

https://www.sciencedaily.com/releases/2021/07/210706191620.htm

New study uncovers how a series of sleep loss impacts mental and physical wellbeing

July 6, 2021

Science Daily/University of South Florida

All it takes is three consecutive nights of sleep loss to cause your mental and physical well-being to greatly deteriorate. A new study published in Annals of Behavioral Medicine looked at the consequences of sleeping fewer than six hours for eight consecutive nights -- the minimum duration of sleep that experts say is necessary to support optimal health in average adults.

Lead author Soomi Lee, assistant professor in the School of Aging Studies at the University of South Florida, found the biggest jump in symptoms appeared after just one night of sleep loss. The number of mental and physical problems steadily got worse, peaking on day three. At that point, research shows the human body got relatively used to repeated sleep loss. But that all changed on day six, when participants reported that the severity of physical symptoms was at its worst.

"Many of us think that we can pay our sleep debt on weekends and be more productive on weekdays," Lee said. "However, results from this study show that having just one night of sleep loss can significantly impair your daily functioning."

Data provided by the Midlife in the United States study included nearly 2,000 middle-aged adults who were relatively healthy and well-educated. Among them, 42% had at least one night of sleep loss, sleeping 1 ½ fewer hours than their typical routines. They recorded their mental and physical behaviors in a diary for eight consecutive days, allowing researchers to review how sleep loss causes wear and tear on the body.

Participants reported a pile-up of angry, nervous, lonely, irritable and frustrated feelings as a result of sleep loss. They also experienced more physical symptoms, such as upper respiratory issues, aches, gastrointestinal problems and other health concerns. These negative feelings and symptoms were continuously elevated throughout consecutive sleep loss days and didn't return to baseline levels unless they had a night sleep of more than six hours.

About one-third of U.S. adults sleep less than six hours per night. Lee says once that becomes a habit, it's increasingly difficult for your body to fully recover from lack of sleep, continuing the vicious cycle of worsening daily well-being, which could impact one professionally. A previous study led by Lee found losing just 16 minutes of sleep could impact job performance. Her previous findings also show that minor sleep loss can decrease daily mindfulness, which is a critical recourse for managing stress and maintaining healthy routines.

Lee says the best way to maintain a strong daily performance is to set aside more than six hours to sleep every night.

https://www.sciencedaily.com/releases/2021/07/210706133113.htm

Vertical greenery can act as a stress buffer

July 6, 2021

Science Daily/Nanyang Technological University

Vertical greenery 'planted' on the exterior of buildings may help to buffer people against stress, a Nanyang Technological University, Singapore (NTU Singapore) study has found.

The benefits of nature on mental health and for wellbeing have long been recognised, and now a team of NTU Singapore psychologists has used Virtual Reality (VR) to examine whether vertical greenery has a stress buffering effect (ability to moderate the detrimental consequences of stress) in an urban environment.

Using VR headsets, 111 participants were asked to walk down a virtual street for five minutes. Participants were randomly assigned to either a street that featured rows of planted greenery (e.g., on balconies, walls, and pillars of buildings), or one with only buildings that had green painted walls in place of green plants. The virtual environments used in the study was developed by the NTU research team.

To match a real-world experience, heavy traffic noise was played as the participants walked through the virtual street. Heart rate variability, which is a physiological indicator of stress, was continuously monitored using a portable electrocardiogram (ECG) device.

The study found that those who viewed buildings which only had green paint experienced a signi?cant increase in stress as recorded by one measure of heart rate variability, while those who viewed the buildings with the green plants did not experience any change in stress.

Following the experiment, participants answered a questionnaire that assessed their positive (e.g., interested, excited) and negative emotions (e.g., upset, hostile), and the level of anxiety they were feeling.

Participants reported feeling less positive when walking through the street with buildings covered by only green walls, while those walking through the street with buildings covered by plants did not report feeling either more or less positive.

The findings published in the peer-reviewed academic journal Landscape and Urban Planning, have implications for the well-being of people living in urban areas and can guide greening efforts in cities, say the researchers.

Walls of greenery can help lower ambient temperature, which reduces energy consumption from cooling systems. They can also reduce carbon emissions and lessen the effect of 'urban heat island' -- a phenomenon where city centres experience much warmer temperatures than less populated areas because of limited greenery and a high concentration of built structures.

While vertical greenery is often planted for these sustainability benefits, the NTU study is one of the first to explore its contribution to mental health, and the authors say that it provides additional impetus for city planners to adopt a 'biophilic design' concept -- an approach to architecture that seeks to connect people more closely to nature -- which is favoured in cities such as Singapore, Wellington (NZ), and San Francisco.

Principal investigator of the study, Associate Professor Lin Qiu from the Psychology programme at the NTU School of Social Sciences said, "With urbanisation, more people are expected to be living in urban areas globally in future. It is thus important for urban city planners and architects to understand factors that can contribute to healthy living, as urban planning can have a direct impact on quality of life for the population. Our work can guide efforts to green cities, by providing evidence of how vertical greenery can be a viable way to integrate nature into our built environment and promote mental health."

Co-lead author of the research, Sarah Chan, a Ph.D. candidate from the Interdisciplinary Graduate Programme at NTU said, "Our ?ndings have important practical implications for city planning and design, especially for high density urban areas that face land constraints. It provides evidence that vertical greenery systems, which make use of vertical structures above-ground, may help moderate the detrimental consequences of stress.

"While previous studies looked at effects of green vegetation, the fact that the colour green could simply be a primitive visual feature, resulting in positive effects, was not considered. Thanks to emerging technology like VR, we overcame this limitation and were able to use a control condition, matching vertical greenery with the colour green in our study."

Moving forward, the NTU research team plans to use VR to investigate the psychological impact of using nature in architecture, for instance, using natural materials like wood compared to concrete.

https://www.sciencedaily.com/releases/2021/07/210706115307.htm

Psychedelic spurs growth of neural connections lost in depression

July 5, 2021

Science Daily/Yale University

The psychedelic drug psilocybin, a naturally occurring compound found in some mushrooms, has been studied as a potential treatment for depression for years. But exactly how it works in the brain and how long beneficial results might last is still unclear.

In a new study, Yale researchers show that a single dose of psilocybin given to mice prompted an immediate and long-lasting increase in connections between neurons. The findings are published July 5 in the journal Neuron.

"We not only saw a 10% increase in the number of neuronal connections, but also they were on average about 10% larger, so the connections were stronger as well," said Yale's Alex Kwan, associate professor of psychiatry and of neuroscience and senior author of the paper.

Previous laboratory experiments had shown promise that psilocybin, as well as the anesthetic ketamine, can decrease depression. The new Yale research found that these compounds increase the density of dendritic spines, small protrusions found on nerve cells which aid in the transmission of information between neurons. Chronic stress and depression are known to reduce the number of these neuronal connections.

Using a laser-scanning microscope, Kwan and first author Ling-Xiao Shao, a postdoctoral associate in the Yale School of Medicine, imaged dendritic spines in high resolution and tracked them for multiple days in living mice. They found increases in the number of dendritic spines and in their size within 24 hours of administration of psilocybin. These changes were still present a month later. Also, mice subjected to stress showed behavioral improvements and increased neurotransmitter activity after being given psilocybin.

For some people, psilocybin, an active compound in "magic mushrooms," can produce a profound mystical experience. The psychedelic was a staple of religious ceremonies among indigenous populations of the New World and is also a popular recreational drug.

It may be the novel psychological effects of psilocybin itself that spurs the growth of neuronal connections, Kwan said.

"It was a real surprise to see such enduring changes from just one dose of psilocybin," he said. "These new connections may be the structural changes the brain uses to store new experiences."

https://www.sciencedaily.com/releases/2021/07/210705113923.htm

Consuming a diet with more fish fats, less vegetable oils can reduce migraine headaches

Frequency, intensity of monthly migraines declined among those on higher fish oil diet

July 1, 2021

Science Daily/NIH/National Institute on Aging

A diet higher in fatty fish helped frequent migraine sufferers reduce their monthly number of headaches and intensity of pain compared to participants on a diet higher in vegetable-based fats and oils, according to a new study. The findings by a team of researchers from the National Institute on Aging (NIA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), parts of the National Institutes of Health; and the University of North Carolina (UNC) at Chapel Hill, were published in the July 3 issue of The BMJ.

This study of 182 adults with frequent migraines expanded on the team's previous work on the impact of linoleic acid and chronic pain. Linoleic acid is a polyunsaturated fatty acid commonly derived in the American diet from corn, soybean, and other similar oils, as well as some nuts and seeds. The team's previous smaller studies explored if linoleic acid inflamed migraine-related pain processing tissues and pathways in the trigeminal nerve, the largest and most complex of the body's 12 cranial nerves. They found that a diet lower in linoleic acid and higher in levels of omega-3 fatty acids (like those found in fish and shellfish) could soothe this pain pathway inflammation.

In a 16-week dietary intervention, participants were randomly assigned to one of three healthy diet plans. Participants all received meal kits that included fish, vegetables, hummus, salads, and breakfast items. One group received meals that had high levels of fatty fish or oils from fatty fish and lowered linoleic acid. A second group received meals that had high levels of fatty fish and higher linoleic acid. The third group received meals with high linoleic acid and lower levels of fatty fish to mimic average U.S. intakes.

During the intervention period, participants monitored their number of migraine days, duration, and intensity, along with how their headaches affected their abilities to function at work, school, and in their social lives, and how often they needed to take pain medications. When the study began, participants averaged more than 16 headache days per month, over five hours of migraine pain per headache day, and had baseline scores showing a severe impact on quality of life despite using multiple headache medications.

The diet lower in vegetable oil and higher in fatty fish produced between 30% and 40% reductions in total headache hours per day, severe headache hours per day, and overall headache days per month compared to the control group. Blood samples from this group of participants also had lower levels of pain-related lipids. Despite the reduction in headache frequency and pain, these same participants reported only minor improvements in migraine-related overall quality of life compared to other groups in the study.

Migraine, a neurological disease, ranks among the most common causes of chronic pain, lost work time, and lowered quality of life. More than 4 million people worldwide have chronic migraine (at least 15 migraine days per month) and over 90% of sufferers are unable to work or function normally during an attack, which can last anywhere from four hours to three days. Women between the ages of 18 and 44 are especially prone to migraines, and an estimated 18% of all American women are affected. Current medications for migraine usually offer only partial relief and can have negative side effects including sedation, and the possibility of dependence or addiction.

"This research found intriguing evidence that dietary changes have potential for improving a very debilitating chronic pain condition like migraine without the related downsides of often prescribed medications," said Luigi Ferrucci, M.D., Ph.D., scientific director of NIA.

The NIH team was led by Chris Ramsden, a clinical investigator in the NIA and NIAAA intramural research programs, and UNC adjunct faculty member. Ramsden and his team specialize in the study of lipids -- fatty acid compounds found in many natural oils -- and their role in aging, especially chronic pain and neurodegenerative conditions. The UNC team was led by Doug Mann, M.D., of the Department of Neurology, and Kim Faurot, Ph.D., of the Program on Integrative Medicine. Meal plans were designed by Beth MacIntosh, M.P.H., of UNC Healthcare's Department of Nutrition and Food Services.

"Changes in diet could offer some relief for the millions of Americans who suffer from migraine pain," said Ramsden. "It's further evidence that the foods we eat can influence pain pathways."

The researchers noted that these findings serve as validation that diet-based interventions increasing omega-3 fats while reducing linoleic acid sources show better promise for helping people with migraines reduce the number and impact of headache days than fish-oil based supplements, while reducing the need for pain medications. They hope to continue to expand this work to study effects of diet on other chronic pain conditions.

https://www.sciencedaily.com/releases/2021/06/210630213035.htm

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Melatonin in mice: there's more to this hormone than sleep

June 24, 2021

Science Daily/RIKEN

Researchers at the RIKEN Center for Brain Science and the RIKEN BioResource Research Center in Japan, along with collaborators at the State University of New York at Buffalo, have created a mouse model that allows the study of naturally occurring melatonin. Published in the Journal of Pineal Research, these first experiments using the new mice showed that natural melatonin was linked to a pre-hibernation state that allows mice to slow down their metabolism and survive when food is scarce, or temperatures are cold.

Melatonin is called "the hormone of darkness" because it's released by the brain in the dark, which usually means at night. It tells the body when it's dark outside so that the body can switch to 'night mode'. Although other hormones are easily studied in the laboratory, it has been difficult to study how the body reacts to melatonin because laboratory mice don't actually have any. To solve this problem, the researchers crossed laboratory mice with wild mice -- which do produce melatonin -- and bred new lab mice that can produce melatonin innately. This was a lot harder than it sounds and took over 10 mouse generations.

Once they had melatonin-producing lab mice, the researchers were able to study how the hormone affects entrainment -- the alignment of the body clock with the outside world. Mice like to run on wheels regularly, and researchers can use this to measure entrainment after suddenly changing the light/dark cycle, which mimics sudden changes in times zones. Compared with regular lab mice, the mice with innate melatonin adapted their wheel running times faster to darkness starting six hours earlier, similar to 'east-bound jet lag'.

The researchers were also able to resolve a debate about whether life span is affected by melatonin, which has been hard to study because of the missing melatonin in lab mice. "Now we finally have an answer: endogenous melatonin has no life-extending effects," says Takaoka Kasahara, a senior author of the new study.

Despite many similarities, mice with innate melatonin differed from regular lab mice in several ways. The regular lab mice were heavier, had bigger reproductive organs, and were more successful at mating, producing more pups. On the other hand, melatonin-producing female mice were able to enter a state called daily torpor, a kind of low-power mode similar to hibernation that can last for a few hours a day. Daily torpor is a way for mice to deal with food scarcity and cold temperatures by conserving energy.

"There is an evolutionary advantage to producing melatonin, because it protects wild mice from losing weight when they can't find enough food. Lab mice, however, are typically given unlimited food and live in warm cages," Kasahara observes. "Our finding that mice lacking melatonin are more successful at reproducing can explain why lab mice lack melatonin. Over the years, by selecting for mice that reproduce the most pups, we might have also been inadvertently selecting for mice with lower and lower levels of melatonin."

Having shown that melatonin can affect circadian rhythms, the specially bred melatonin-proficient mice will be valuable for studying the detailed molecular and neural mechanisms of melatonin signaling on the circadian clock and sleep, as well as the effects of melatonin on immunity and bone formation. These relationships have been suggested, but have not yet been closely examined.

Further research on melatonin's relationship with daily torpor and hibernation is also important. Melatonin is necessary for seasonal reproduction in several animals, signaling the length of the night, which indicates the season. "This research could very well lead to a better understanding of seasonal affective disorder, or winter depression, in humans," says Kasahara. "Indeed, one of the newest antidepressants, agomelatin, activates melatonin receptors."

https://www.sciencedaily.com/releases/2021/06/210623141703.htm

Stress can turn hair gray -- and it's reversible

June 22, 2021

Science Daily/Columbia University Irving Medical Center

Legend has it that Marie Antoinette's hair turned gray overnight just before her beheading in 1791.

Though the legend is inaccurate -- hair that has already grown out of the follicle does not change color -- a new study from researchers at Columbia University Vagelos College of Physicians and Surgeons is the first to offer quantitative evidence linking psychological stress to graying hair in people.

And while it may seem intuitive that stress can accelerate graying, the researchers were surprised to discover that hair color can be restored when stress is eliminated, a finding that contrasts with a recent study in mice that suggested that stressed-induced gray hairs are permanent.

The study, published June 22 in eLife, has broader significance than confirming age-old speculation about the effects of stress on hair color, says the study's senior author Martin Picard, PhD, associate professor of behavioral medicine (in psychiatry and neurology) at Columbia University Vagelos College of Physicians and Surgeons.

"Understanding the mechanisms that allow 'old' gray hairs to return to their 'young' pigmented states could yield new clues about the malleability of human aging in general and how it is influenced by stress," Picard says.

"Our data add to a growing body of evidence demonstrating that human aging is not a linear, fixed biological process but may, at least in part, be halted or even temporarily reversed."

Studying hair as an avenue to investigate aging 

"Just as the rings in a tree trunk hold information about past decades in the life of a tree, our hair contains information about our biological history," Picard says. "When hairs are still under the skin as follicles, they are subject to the influence of stress hormones and other things happening in our mind and body. Once hairs grow out of the scalp, they harden and permanently crystallize these exposures into a stable form."

Though people have long believed that psychological stress can accelerate gray hair, scientists have debated the connection due to the lack of sensitive methods that can precisely correlate times of stress with hair pigmentation at a single-follicle level.

Splitting hairs to document hair pigmentation Ayelet Rosenberg, first author on the study and a student in Picard's laboratory, developed a new method for capturing highly detailed images of tiny slices of human hairs to quantify the extent of pigment loss (graying) in each of those slices. Each slice, about 1/20th of a millimeter wide, represents about an hour of hair growth.

"If you use your eyes to look at a hair, it will seem like it's the same color throughout unless there is a major transition," Picard says. "Under a high-resolution scanner, you see small, subtle variations in color, and that's what we're measuring."

The researchers analyzed individual hairs from 14 volunteers. The results were compared with each volunteer's stress diary, in which individuals were asked to review their calendars and rate each week's level of stress.

The investigators immediately noticed that some gray hairs naturally regain their original color, which had never been quantitatively documented, Picard says.

When hairs were aligned with stress diaries by Shannon Rausser, second author on the paper and a student in Picard's laboratory, striking associations between stress and hair graying were revealed and, in some cases, a reversal of graying with the lifting of stress.

"There was one individual who went on vacation, and five hairs on that person's head reverted back to dark during the vacation, synchronized in time," Picard says.

Blame the mind-mitochondria connection 

To better understand how stress causes gray hair, the researchers also measured levels of thousands of proteins in the hairs and how protein levels changed over the length of each hair.

Changes in 300 proteins occurred when hair color changed, and the researchers developed a mathematical model that suggests stress-induced changes in mitochondria may explain how stress turns hair gray.

"We often hear that the mitochondria are the powerhouses of the cell, but that's not the only role they play," Picard says. "Mitochondria are actually like little antennas inside the cell that respond to a number of different signals, including psychological stress."

The mitochondria connection between stress and hair color differs from that discovered in a recent study of mice, which found that stress-induced graying was caused by an irreversible loss of stem cells in the hair follicle.

"Our data show that graying is reversible in people, which implicates a different mechanism," says co-author Ralf Paus, PhD, professor of dermatology at the University of Miami Miller School of Medicine. "Mice have very different hair follicle biology, and this may be an instance where findings in mice don't translate well to people."

Hair re-pigmentation only possible for some 

Reducing stress in your life is a good goal, but it won't necessarily turn your hair to a normal color.

"Based on our mathematical modeling, we think hair needs to reach a threshold before it turns gray," Picard says. "In middle age, when the hair is near that threshold because of biological age and other factors, stress will push it over the threshold and it transitions to gray.

"But we don't think that reducing stress in a 70-year-old who's been gray for years will darken their hair or increasing stress in a 10-year-old will be enough to tip their hair over the gray threshold."

https://www.sciencedaily.com/releases/2021/06/210622154339.htm

Personality traits relate to being a morning or evening person

June 22, 2021

Science Daily/University of Warwick

The link between the different hierarchies of personality, sleep patterns and even genetics has been discovered by researchers from the Department of Psychology at the University of Warwick.

A typical example of a morning person is thought to be someone who wakes up naturally at 6am, goes for a jog, showers, has breakfast and is ready for a productive day at work by 9am. Whereas an evening person struggles to get up in the morning and feels more productive in the evening.

Researchers from the University of Warwick with colleagues from the University of Tartu have recently had the paper, 'Personality Traits Relate to Chronotype at Both the Phenotypic and Genetic Level' published in the Journal of Personality, in which they have analysed the relationship between sleep timing (chronotype), preference to the morning/evening, and personality traits at a phenotypic and genetic level.

Ultimately the researchers have found that the relationship between personality and morningness-eveningness is partly due to genetic factors.

Using a large-scale sample of participants form the Estonian Biobank researchers asked them to answer questionnaires about their sleep timings and personality, personality was also assessed by someone who knew the participant well. Once answered researchers were able to identify the phenotypic relationships between the sleep and personality.

However they were also able to calculate the genetic correlations through summary statistics of large genome-wide association studies of personality and sleep preferences.

Personalities can be divided into three hierarchies: personality domains, facets and items, researchers analysed all three, but in particular they found on a domain level that people high in Conscientiousness and low in Openness were associated with being earlier chronotypes (i.e., they went to bed and got out of bed earlier).

On a facet level, researchers found that less straightforward (a facet of Agreeableness) and excitement-seeking (a facet of Extraversion), yet more self-disciplined (a facet of Conscientiousness) people were more likely to have earlier chronotypes. Higher Conscientiousness and lower Openness were also genetically related to preference for morningness.

Postgraduate researcher Dr Anita Lenneis, from the Department of Psychology at the University of Warwick comments:

"Our findings have helped us to come up with two possible pathways of how personality might influence chronotype. Personality traits such as Conscientiousness and C5: Self-discipline in particular may influence chronotype through shaping people's preferences for various social activities and behaviours which in turn, may influence what time people go to and get out of bed, or personality may influence chronotype is through active decisions people make regarding their sleep.

"However, it could also be that chronotype influences personality or that chronotype and personality mutually influence each other. The findings of the genetic correlations support this view but further studies will be necessary to better understand the shared genetic mechanisms between the two constructs as well as the causality of their relationships."

Professor Anu Realo, from the Department of Psychology at the University of Warwick adds:

"Not only have we shown there is a relationship between chronotype, personality and partially your genes, our findings also suggest that it might be possible to change your chronotype or at least train yourself into a different more socially convenient sleep pattern by increasing your self-control. Ideally work hours would be adapted to your chronotype, but if not, evening people who typically experience worse health could learn to go to bed at earlier hours which might also accelerate the release of melatonin. Melatonin is also influenced by artificial light, so regularly turning off the lights at earlier hours might also lead to falling asleep at earlier hours of the evening. However, future studies will need to investigate whether such interventions to enhance self-control would result in a permanent change or would indeed promote better health in later chronotypes."

https://www.sciencedaily.com/releases/2021/06/210622123338.htm

'Urban green space affects citizens' happiness'

Study finds the relationship between green space, the economy, and happiness

June 22, 2021

Science Daily/The Korea Advanced Institute of Science and Technology (KAIST)

A recent study revealed that as a city becomes more economically developed, its citizens' happiness becomes more directly related to the area of urban green space.

A joint research project by Professor Meeyoung Cha of the School of Computing and her collaborators studied the relationship between green space and citizen happiness by analyzing big data from satellite images of 60 different countries.

Urban green space, including parks, gardens, and riversides not only provides aesthetic pleasure, but also positively affects our health by promoting physical activity and social interactions. Most of the previous research attempting to verify the correlation between urban green space and citizen happiness was based on few developed countries. Therefore, it was difficult to identify whether the positive effects of green space are global, or merely phenomena that depended on the economic state of the country. There have also been limitations in data collection, as it is difficult to visit each location or carry out investigations on a large scale based on aerial photographs.

The research team used data collected by Sentinel-2, a high-resolution satellite operated by the European Space Agency (ESA) to investigate 90 green spaces from 60 different countries around the world. The subjects of analysis were cities with the highest population densities (cities that contain at least 10% of the national population), and the images were obtained during the summer of each region for clarity. Images from the northern hemisphere were obtained between June and September of 2018, and those from the southern hemisphere were obtained between December of 2017 and February of 2018.

The areas of urban green space were then quantified and crossed with data from the World Happiness Report and GDP by country reported by the United Nations in 2018. Using these data, the relationships between green space, the economy, and citizen happiness were analyzed.

The results showed that in all cities, citizen happiness was positively correlated with the area of urban green space regardless of the country's economic state. However, out of the 60 countries studied, the happiness index of the bottom 30 by GDP showed a stronger correlation with economic growth. In countries whose gross national income (GDP per capita) was higher than 38,000 USD, the area of green space acted as a more important factor affecting happiness than economic growth. Data from Seoul was analyzed to represent South Korea, and showed an increased happiness index with increased green areas compared to the past.

The authors point out their work has several policy-level implications. First, public green space should be made accessible to urban dwellers to enhance social support. If public safety in urban parks is not guaranteed, its positive role in social support and happiness may diminish. Also, the meaning of public safety may change; for example, ensuring biological safety will be a priority in keeping urban parks accessible during the COVID-19 pandemic.

Second, urban planning for public green space is needed for both developed and developing countries. As it is challenging or nearly impossible to secure land for green space after the area is developed, urban planning for parks and green space should be considered in developing economies where new cities and suburban areas are rapidly expanding.

Third, recent climate changes can present substantial difficulty in sustaining urban green space. Extreme events such as wild?res, ?oods, droughts, and cold waves could endanger urban forests while global warming could conversely accelerate tree growth in cities due to the urban heat island effect. Thus, more attention must be paid to predict climate changes and discovering their impact on the maintenance of urban green space.

"There has recently been an increase in the number of studies using big data from satellite images to solve social conundrums," said Professor Cha. "The tool developed for this investigation can also be used to quantify the area of aquatic environments like lakes and the seaside, and it will now be possible to analyze the relationship between citizen happiness and aquatic environments in future studies," she added.

https://www.sciencedaily.com/releases/2021/06/210622095313.htm

Stress during pandemic linked to poor sleep

June 17, 2021

Science Daily/Washington State University

Many people likely lost sleep over COVID-19. A study of twins led by Washington State University researchers found that stress, anxiety and depression during the first few weeks of the pandemic were associated with less and lower quality sleep.

In a survey of more than 900 twins taken shortly after COVID-19 lockdown measures began, about half of the respondents reported no change in their sleep patterns, but around a third, 32.9%, reported decreased sleep. Another 29.8% reported sleeping more. In the analysis, the researchers found that any change in sleep was connected to self-reported mental health issues, though it was more strongly associated with decreased sleep.

"The results show that deviations from your typical sleep behavior may be associated with depression, anxiety and stress," said Siny Tsang, lead author on the study published in Frontiers in Neuroscience.

Tsang, a staff scientist with the WSU Elson S. Floyd College of Medicine, emphasized that this showed a connection, not a cause, but the study supports previous research that has found a two-way relationship between disrupted sleep patterns and poor mental health. In other words, when people don't sleep well, they are more likely to feel stress, anxiety and depression, and when they are dealing with those same problems, they are more likely to sleep less -- and sometimes more -- than the typical six to nine hours a night.

This study analyzes survey responses collected between March 26 and April 5, 2020 from participants in the Washington State Twin Registry. Since then, the same group has answered three more waves of survey questions. Researchers are particularly interested in studying twins, so they can investigate whether associations are mediated by genetic factors, shared environment, or both. The pandemic also offered an opportunity for a natural experiment to see how a stressful situation affects sleep amount and quality among individuals in the community, Tsang said.

The research relies on the self-reported perception of sleep length and quality, but the researcher said that when it comes to mental health, perception can matter more than the real amount of sleep.

"Even if your cell phone says you consistently sleep eight hours every day, you may feel that you slept less or slept poorly, and that may be linked to stressful or anxious feelings," Tsang said. "It may not matter whether or not the actual number has changed. It's how you are feeling that is associated with your mental health."

WSU researchers have also conducted twin-studies on COVID-19 lockdown effects on alcohol use and pandemic stress and exercise. These have all been initial studies taken at the early stages of the pandemic and associated social distancing measures. The scientists are still analyzing results of later surveys, but they are starting to see a common theme.

"A pattern that is consistent across these three studies is that people who reported change in physical exercise, alcohol use or sleep are more stressed, anxious and depressed than those who had said that they have had no change," Tsang said.

https://www.sciencedaily.com/releases/2021/06/210617082718.htm