Not-so private eyes: Eye movements hold clues to how we make decisions

Peer-Reviewed Publication

UNIVERSITY OF COLORADO AT BOULDER

New research led by scientists at the University of Colorado Boulder suggests that eyes may really be the window to the soul—or, at least, how humans dart their eyes may reveal valuable information about how they make decisions. 

The new findings offer researchers a rare opportunity in neuroscience: the chance to observe the inner workings of the human brain from the outside. Doctors could also potentially use the results to, one day, screen their patients for illnesses like depression or Parkinson’s Disease.

“Eye movements are incredibly interesting to study,” said Colin Korbisch, doctoral student in the Paul M. Rady Department of Mechanical Engineering at CU Boulder and lead author of the study. “Unlike your arms or legs, the speed of eye movements is almost totally involuntary. It’s a much more direct measurement of these unconscious processes happening in your brain.”

He and his colleagues, including researchers at Johns Hopkins University in Baltimore, published their findings in November in the journal Current Biology.

In the study, the team asked 22 human subjects to walk on a treadmill then choose between different settings displayed on a computer screen: a brief walk up a steep grade or a longer walk on flat ground. 

Researchers discovered that the subjects’ eyes gave them away: Even before they made their choices, the treadmill users tended to move their eyes faster when they looked toward the options they ended up choosing. The more vigorously their eyes moved, the more they seemed to prefer their choice. 

“We discovered an accessible measurement that will tell you, in only a few seconds, not just what you prefer but how much you prefer it,” said Alaa Ahmed, senior author of the study and associate professor of mechanical engineering at CU Boulder.

Shifty eyes

Ahmed explained that how or why humans make choices (Tea or coffee? Dogs or cats?) is notoriously difficult to study. Researchers don’t have many tools that will easily allow them to peer inside the brain. Ahmed, however, believes that our eyes could provide a glimpse into some of our thought processes. She’s particularly interested in a type of movement known as a “saccade.”

“The primary way our eyes move is through saccades,” Ahmed said. “That’s when your eyes quickly jump from one fixation point to another.”

Quickly is the key word: Saccades usually take just a few dozen milliseconds to complete, making them faster than an average blink. 

To find out if these darting motions give clues about how humans come to decisions, Ahmed and her colleagues decided to hit the gym.

In the new study, the team set up a treadmill on the CU Boulder campus. Study subjects exercised on various inclines for a period of time then sat down in front of a monitor and a high-speed, camera-based device that tracked their eye movements. While at the screen, they pondered a series of options, getting 4 seconds to pick between two choices represented by icons: Did they want to walk for 2 minutes at a 10% grade or for 6 minutes at a 4% grade? Once done, they returned to the treadmill to feel the burn based on what they chose. 

The team found that subjects’ eyes underwent a marathon of activity in just a short span of time. As they considered their options, the individuals flitted their eyes between the icons, first slowly and then faster. 

“Initially, the saccades to either option were similarly vigorous,” Ahmed said. “Then, as time passed, that vigor increased and it increased even faster for the option they eventually chose.”

The researchers also discovered that people who made the hastiest decisions—the most impulsive members of the group, perhaps—also tended to move their eyes more vigorously. Once the subjects decided on their pick, their eyes slowed again. 

“Real-time read-outs of this decision-making process typically require invasive electrodes placed into the brain. Having this more easily measured variable opens a lot of possibilities,” Korbisch said. 

Diagnosing illness

Flicks of the eye could matter for a lot more than understanding how humans make decisions. Studies in monkeys, for example, have suggested that some of the same pathways in the brain that help primates pick between this or that may also break down in people with Parkinson’s—a neurological illness in which individuals experience tremors, difficulty moving and other issues.

“Slowed movements aren’t just a symptom of Parkinson’s but also appear in a lot of mental health disorders, such as depression and schizophrenia,” Ahmed said. “We think these eye movements could be something that medical professionals track as a diagnostic tool, a way to identify the progress of certain illnesses.”

Eyes, in other words, could be windows to a lot more than just the soul.

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JOURNAL

Current Biology

DOI

10.1016/j.cub.2022.10.053 

ARTICLE TITLE

Saccade vigor reflects the rise of decision variables during deliberation

Effective Prevention

Absolute Risk Reduction Supports More Equitable Vaccine Distribution Policies

Peer-Reviewed Publication

UNIVERSITY OF NEW MEXICO HEALTH SCIENCES CENTER

In a new study, New Mexico researchers using an alternative analysis based on evidence-based medicine found that the effectiveness of COVID vaccines is much greater in areas of the world with higher prevalence of infection – an approach that could lead to more equitable distribution of vaccines.

In a peer-reviewed paper published Dec. 12 in BMJ Open, the investigators calculated and compared absolute risk reduction (ARR) and the number needed to be vaccinated (NNV) in different geographical areas.

“At certain times during the pandemic, the NNV to prevent one hospitalization in some parts of the world was less than 1,000, whereas in other locations, it was more than 10,000,” said corresponding author Howard Waitzkin, MD, PhD, a professor emeritus at The University of New Mexico.

Until now, scientific publications about COVID-19 vaccines have assessed their effectiveness by measuring relative risk reduction, which compares people who receive vaccination with those who don’t.

Absolute risk reduction measures how much a vaccine reduces an individual’s baseline risk in a population. The number needed to be vaccinated indicates the number of people who should be vaccinated to prevent one adverse outcome, such as getting sick or needing hospitalization from COVID-19.

Adopting these alternative measures of vaccine effectiveness could guide better policies about distributing vaccines in COVID-19 and similar epidemics, the researchers contend.

“Vaccine distribution should target subpopulations with higher baseline risks of disease, rather than focusing only on the goal of vaccinating entire populations,” Waitzkin said.

“This approach could alleviate some economic and practical burdens of trying to provide vaccines for everyone, especially in poorer regions that have trouble obtaining enough vaccines due to what’s called vaccine apartheid.”

The research team also clarified other absolute measures to assess harms from vaccines.

“A risk-benefit analysis that compares absolute measures of harms and benefits can help set distribution policies,” said co-author Ella Fassler, a New Mexico-based investigative journalist with the New Mexico-based Allende Program in Social Medicine. “But scientific publications about the vaccines also have not reported these evidence-based medicine comparisons.”

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JOURNAL

BMJ Open

DOI

10.1136/bmjopen-2022-063525 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

How missing evidence-based medicine indicators can inform COVID-19 vaccine distribution policies: a scoping review and calculation of indicators from data in randomised controlled trials

ARTICLE PUBLICATION DATE

12-Dec-2022

Drinking coffee regularly after pregnancy may lower the risk of type 2 diabetes for women who had diabetes during pregnancy

NUS researchers at the Global Centre for Asian Women’s Health (GloW) found that among women who had gestational diabetes mellitus, coffee may potentially be a better substitute for other less healthy beverages in preventing or delaying the subsequent prog

Peer-Reviewed Publication

NATIONAL UNIVERSITY OF SINGAPORE, YONG LOO LIN SCHOOL OF MEDICINE

The prevalence of type 2 diabetes is projected to continue rising and one in three Singaporeans currently has a risk of developing diabetes in their lifetime. Several early-life cardiometabolic complications make identifying high-risk populations and application of diabetes preventive strategies paramount.

Among the high-risk groups are women who experienced diabetes during pregnancy, commonly known as gestational diabetes mellitus or gestational diabetes. Compared to the general healthy female population, these women may face a ten-fold higher risk of developing type 2 diabetes.

Current known research has found that, instead of artificially- and sugar-sweetened drinks, drinking two to five cups of either caffeinated or decaffeinated coffee a day is potentially a healthier substitute in delaying the onset or preventing type 2 diabetes.

This is likely due to the bioactive components in coffee, such as polyphenols, which are naturally-occurring plant micronutrients. Bioactive components are types of chemicals found in small amounts in plants and certain foods, such as fruits, vegetables, nuts, oils, and whole grains, and may promote good health.

This common and popular drink appears to reduce the risk of type 2 diabetes in the general population. However, whether it may also be beneficial among women who had gestational diabetes remained unknown.

To investigate this, Professor Cuilin Zhang, Director of the Global Centre for Asian Women’s Health (GloW) and a professor in the Department of Obstetrics and Gynecology at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), with her team at GloW, in collaboration with the Harvard T.H. Chan School of Public Health and the National Institutes of Health (NIH), examined the roles of long-term coffee consumption after the complicated pregnancy and subsequent risk of type 2 diabetes among women with a history of gestational diabetes.

The team further examined coffee consumption with type 2 diabetes by replacing commonly consumed sugary drinks with coffee. Findings from this study, “Habitual coffee consumption and subsequent risk of type 2 diabetes in individuals with a history of gestational diabetes – a prospective study” was recently published in the American Journal of Clinical Nutrition.

In their study, the researchers followed more than 4,500 predominantly white female participants who had a history of gestational diabetes, for over 25 years, and examined the associations of long-term coffee consumption with subsequent risk of type 2 diabetes.

The consumption of caffeinated coffee among women after their pregnancies, was discovered to have a linear inverse association with the risk of type 2 diabetes. Compared to those who did not drink caffeinated coffee at all, among those who drank one cup of caffeinated coffee or less, two to three cups, and four and more cups a day, the risk of type 2 diabetes was reduced by 10%, 17%, and 53% respectively.

Interestingly, decaffeinated coffee was not associated with the risk of type 2 diabetes in their study. However, this null finding might be due to the relatively small number of women who consumed decaffeinated coffee, so that the study was not able to detect a significant association.

More importantly, replacing artificially sweetened and sugar-sweetened beverages with caffeinated coffee also reduces the risk, by 10% for a cup of artificially sweetened beverage, and 17% for a cup of sugar-sweetened one.

“Thus far, the overall findings suggest that caffeinated coffee, when consumed properly (two to five cups per day, without sugar and whole-fat/high-fat dairy), could be incorporated into a relatively healthy lifestyle for certain population,” noted Professor Zhang.

“The beneficial roles of coffee have been consistently suggested across diverse populations, including Asians. Coffee is a popular beverage choice in Singapore, but local coffee drinking culture and behaviours may vary among individuals, such as brewing methods, drinking frequency, and other condiments contained in the coffee. Thus, more studies are needed to examine the roles of coffee consumption in the local context with major health outcomes,” concluded Professor Zhang.

Adding on to Professor Zhang’s point, Dr Jiaxi Yang, the first author of the study and a postdoctoral research fellow at GloW and the Department of Obstetrics and Gynecology at NUS Medicine, said, “Although coffee presents as a potentially healthier alternative to sweetened beverages, the health benefits of coffee vary and much depend on the type and the amount of condiments, like sugar and milk, that you add into your coffee.” Dr Yang is currently leading the working group of Nutrition and Lifestyle at GloW.

However, concerns should be given when coffee is taken in excessive amounts. It also needs to be emphasised that certain groups should be careful about drinking coffee. Not much is known about the effects of coffee on pregnancies, foetuses and children.

 

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JOURNAL

American Journal of Clinical Nutrition

DOI

10.1093/ajcn/nqac241 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Habitual coffee consumption and subsequent risk of type 2 diabetes in individuals with a history of gestational diabetes – a prospective study

ARTICLE PUBLICATION DATE

Subcutaneous fat emerges as a protector of females’ brains

Peer-Reviewed Publication

MEDICAL COLLEGE OF GEORGIA AT AUGUSTA UNIVERSITY

 

IMAGE: DR. ALEXIS STRANAHAN view more 

CREDIT: MICHAEL HOLAHAN, AUGUSTA UNIVERSITY

AUGUSTA, Ga. (Dec. 13, 2022) – Females’ propensity to deposit more fat in places like their hips, buttocks and the backs of their arms, so-called subcutaneous fat, is protective against brain inflammation, which can result in problems like dementia and stroke, at least until menopause, scientists report.

Males of essentially any age have a greater propensity to deposit fat around the major organs in their abdominal cavity, called visceral adiposity, which is known to be far more inflammatory. And, before females reach menopause, males are considered at much higher risk for inflammation-related problems from heart attack to stroke.

“When people think about protection in women, their first thought is estrogen,” says Alexis M. Stranahan, PhD, neuroscientist in the Department of Neuroscience and Regenerative Medicine at the Medical College of Georgia at Augusta University. “But we need to get beyond the kind of simplistic idea that every sex difference involves hormone differences and hormone exposure. We need to really think more deeply about the underlying mechanisms for sex differences so that we can treat them and acknowledge the role that sex plays in different clinical outcomes.”

Diet and genetics are other likely factors that explain the differences broadly assigned to estrogen, says Stranahan, corresponding author of a study in the American Diabetes Association journal Diabetes.

She acknowledges that the findings are potentially heretical and revolutionary and certainly surprising even to her. “We did these experiments to try and nail down, first of all, what happens first, the hormone perturbation, the inflammation or the brain changes.”

To learn more about how the brain becomes inflamed, they looked at increases in the amount and location of fat tissue as well as levels of sex hormones and brain inflammation in male and female mice at different time intervals as they grew fatter on a high-fat diet.

Since, much like with people, obese female mice tend to have more subcutaneous fat and less visceral fat than male mice, they reasoned that the distinctive fat patterns might be a key reason for the protection from inflammation the females enjoy before menopause.

They found again the distinctive patterns of fat distribution in males and females in response to a high-fat diet. They found no indicators of brain inflammation or insulin resistance, which also increase inflammation and can lead to diabetes, until after the female mice reached menopause. At about 48 weeks, menstruation stops and fat positioning on the females starts to shift somewhat, to become more like males.

They then compared the impact of the high-fat diet, which is known to increase inflammation body wide, in mice of both sexes following surgery, similar to liposuction, to remove subcutaneous fat. They did nothing to directly interfere with normal estrogen levels, like removing the ovaries. 

The subcutaneous fat loss increased brain inflammation in females without moving the dial on levels of their estrogen and other sex hormones.

Bottom line: The females’ brain inflammation looked much more like the males’, including increased levels of classic inflammation promoters like the signaling proteins IL-1β and TNF alpha in the brain, Stranahan and her colleagues report. 

 “When we took subcutaneous fat out of the equation, all of a sudden the females’ brains start to exhibit inflammation the way that male brains do, and the females gained more visceral fat,” Stranahan says. “It kind of shunted everything toward that other storage location.” The transition occurred over about three months, which translates to several years in human time.

By comparison, it was only after menopause, that the females who did not have subcutaneous fat removed but did eat a high-fat diet, showed brain inflammation levels similar to the males, Stranahan says.

When subcutaneous fat was removed from mice on a low-fat diet at an early age, they developed a little more visceral fat and a little more inflammation in the fat. But Stranahan and her colleagues saw no evidence of inflammation in the brain.

One take-home lesson from the work: Don’t get liposuction and then eat a high-fat diet, Stranahan says. Another is: BMI, which simply divides weight by height and is commonly used to indicate overweight, obesity and consequently increased risk of a myriad of diseases, is likely not a very meaningful tool, she says. An also easy and more accurate indicator of both metabolic risk and potentially brain health, is the also easy-to-calculate waist to hip ratio, she adds.

“We can’t just say obesity. We have to start talking about where the fat is. That is the critical element here,” Stranahan says.

She notes that the new study looked specifically in the hippocampus and hypothalamus of the brain. The hypothalamus controls metabolism and exhibits changes with inflammation from obesity that help control conditions that develop bodywide as a result. The hippocampus, a center of learning and memory, is regulated by signals associated with those pathologies but doesn’t control them, Stranahan notes. While these are good places to start such explorations, other regions of the brain could respond very differently, so she is already looking at the impact of loss of subcutaneous fat in others. Also, since her evidence indicates estrogen may not explain the protection females have, Stranahan wants to better define what does. One of her suspects is the clear chromosomal differences between the XX female and the XY male.

Stranahan has been studying the impact of obesity on the brain for several years and is among the first scientists to show that visceral fat promotes brain inflammation in obese male mice, and, conversely, transplanting subcutaneous fat reduces their brain inflammation. Females also have naturally higher levels of proteins that can tamp down inflammation. It’s been shown that in males, but not females, microglia, immune cells in the brain, are activated by a high-fat diet.

She notes that some consider the reason that females have higher stores of subcutaneous fat is to enable sufficient energy stores for reproduction, and she is not challenging the relationship. But many questions remain like how much fat is needed to maintain fertility versus the level that will affect your metabolism, Stranahan says.

The research was supported by the National Institutes of Health.  

Read the study abstract.

VIDEO

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JOURNAL

Diabetes

ARTICLE TITLE

Sex Differences in Adipose Tissue Distribution Determine Susceptibility to Neuroinflammation in Mice With Dietary Obesity

Doctors give ineffective weight loss advice to patients with obesity

Peer-Reviewed Publication

OXFORD UNIVERSITY PRESS USA

A new research study published today in Family Practice, published by Oxford University Press, finds that when doctors tell patients living with obesity to lose weight the guidance they give is generally vague, superficial, and commonly not supported by scientific evidence.

Obesity is a chronic and relapsing condition, but physicians often lack guidance on which information is helpful for patients who would like to lose weight. As a result, the information patients receive can be hard to use and implement. Bad experiences are regularly reported by patients, who often see these conversations about weight as difficult.  

The researchers analyzed 159 audio recordings of consultations between general practitioners and patients living with obesity collected from the United Kingdom between 2013 and 2014. The investigation found that weight-loss advice from doctors to patients with obesity rarely included effective methods and mostly consisted of telling patients merely to eat less and be more physically active. The advice was mostly generic and rarely tailored to patients’ existing knowledge and behaviors, such as what strategies they had tried to lose weight before.  

The advice was mostly (97% of the time in analyzed consultations) abstract or general. Superficial guidance, such as one doctor telling a patient to just “change their lifestyle a bit” was common. Doctors gave patients information on how to carry out their advice in only 20% of the consultations. They mostly offered weight loss guidance without any detail about how to follow it. Doctors frequently (76% of the time in the consultations) told patients to get help somewhere else for support in weight loss, often suggesting that they return for another consultation at their surgery.

The analysis indicated that when doctors did offer specific information it was often scientifically unsupported and unlikely to result in actual weight loss. The notion that small changes in behavior (“take the stairs more often”) can have a large weight loss impact is a common myth and is even prevalent in scientific literature, but it isn’t supported by research. Another common myth was that patients just needed the “right mindset” to lose weight.

“This research demonstrates that doctors need clear guidelines on how to talk opportunistically to patients living with obesity about weight loss,” said one of the paper’s lead authors, Madeleine Tremblett. “This can help them to avoid amplifying stigmatizing stereotypes and give effective help to patients who want to lose weight."

The paper, “What advice do general practitioners give to people living with obesity to lose weight? A qualitative content analysis of recorded interactions,” is available (at midnight on December 13th) at: https://academic.oup.com/fampra/article-lookup/doi/10.1093/fampra/cmac137.

Direct correspondence to: 
Madeleine Tremblett
Nuffield Department of Primary Care Health Sciences
University of Oxford
Radcliffe Primary Care Building, Radcliffe Observatory Quarter
Woodstock Road, Oxford. OX2 6GG UNITED KINGDOM
madeleine.tremblett@phc.ox.ac.uk

To request a copy of the study, please contact:
Daniel Luzer 
daniel.luzer@oup.com

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JOURNAL

Family Practice

DOI

10.1093/fampra/cmac137 

METHOD OF RESEARCH

Content analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

What advice do general practitioners give to people living with obesity to lose weight? A qualitative content analysis of recorded interactions

ARTICLE PUBLICATION DATE

13-Dec-2022

£2.4 million to fund largest-ever trial of ketamine-assisted therapy for alcohol disorder

A new £2.4 million phase III trial delivered across seven NHS sites across the UK will investigate whether ketamine-assisted therapy could help alcoholics stay off alcohol for longer.

Business Announcement

UNIVERSITY OF EXETER

A new £2.4 million phase III trial delivered across seven NHS sites across the UK will investigate whether ketamine-assisted therapy could help alcoholics stay off alcohol for longer.

Led by the University of Exeter, the new trial is being funded by the National Institute for Health and Care Research (NIHR) with additional funding from Awakn Life Sciences, a biotech company who specialise in researching and developing therapeutics to treat addiction.

The latest trial builds on a positive result of an earlier phase II trial, designed to test whether the treatment is safe. It showed ketamine and therapy treatment was safe and tolerable for people with severe alcohol use disorder. The earlier study found that participants who had ketamine combined with therapy stayed completely sober, representing 86 per cent abstinence in the six month follow-up. Now, the Ketamine for Reduction of Alcohol Relapse (KARE) trial will move to the next step of drug development, a phase III trial. It will test this promising finding further, with the aim of rolling it out into the NHS if it proves effective.

The trial will be run in conjunction with the NHS and the treatment will be provided in seven NHS sites across the UK. The trial will recruit 280 people with severe alcohol use disorder and participants will be randomly allocated to two arms. Half will be given ketamine at the dose used in the first clinical trial with psychological therapy. The other half will be given a very low dose of ketamine and a seven-session education package about the harmful effects of alcohol. Researchers will look at whether the ketamine and therapy package reduces harmful drinking.

Trial lead Professor Celia Morgan, from the University of Exeter, said: “More than two million UK adults have serious alcohol problems, yet only one in five of those get treatment. Three out of four people who quit alcohol will be back drinking heavily after a year. Alcohol-related harm is estimated to cost the NHS around £3.5 billion each year, and wider UK society around £40 billion. Alcohol problems affect not only the individual but families, friends and communities, and related deaths have increased still further since the pandemic. We urgently need new treatments. If this trial establishes that ketamine and therapy works, we hope we can begin to see it used in NHS settings.”

Professor Anne Lingford-Hughes, Professor of Addiction Biology at Imperial College London and Consultant Addiction Psychiatrist at Central North West London NHS Foundation Trust, said: “This is the largest trial of its kind in the world and builds on our earlier, smaller positive trial. We currently have few effective treatment options for people with alcoholism, and not all of these work for everyone. We desperately therefore need new treatments using different approaches such as this trial to help people regain control of their life and reduce the immense harms they experience from alcohol.”

Dr Stephen Kaar, one of the study leads of the University of Manchester, and Consultant Addictions Psychiatrist at Greater Manchester Mental Health NHS Foundation Trust, said: “Ketamine assisted psychotherapy for people with alcohol dependence offers the chance for a paradigm shift in how we treat this challenging and frequently re-occurring problem. 

“By bringing together the specific biochemical effects of ketamine and the supportive, structured and change focused space of psychotherapy, this study should finally establish the usefulness of this approach to treating addictions. 

“Ultimately, this study should lead to increased treatment options and improved outcomes for people with alcohol dependence, who at present have very few treatment options, when it comes to helping them stay sober or to develop a healthy relationship with alcohol after a detox.”

Awakn CEO Anthony Tennyson added “For this phase III to have the support and funding from the NIHR and for it to be delivered in the NHS is a great endorsement of this treatment’s potential and a sign of how badly a new more effective treatment is needed to help the millions of people suffering from Alcohol addiction in the UK. We are very proud to be part of this important piece of work.

The new trial will recruit participants across the following partner organisations: Imperial College London; Oxford Health NHS Trust; Greater Manchester Mental Health NHS Trust; Northern, Eastern, and Western Devon CCG; South London and Maudsley NHS Foundation Trust; the Exeter Clinical Trials Unit; Mersey Care NHS Trust; University College London Hospitals NHS Foundation Trust; NHS Forth Valley; Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust. Recruitment will commence mid-way through 2023. To pre register interest in taking part, contact morekare@exeter.ac.uk

ENDS 

For further information:  

Louise Vennells

University of Exeter  

Press Office  

07768 511866

l.vennells@exeter.ac.uk   

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SUBJECT OF RESEARCH

People

EPIGENETICS

Meta-analysis reveals how crowds may change gene expression in some insects

Peer-Reviewed Publication

HIROSHIMA UNIVERSITY

 

IMAGE: THE HORIZONTAL AXIS INDICATES GENE RANKING BASED ON THE METHOD DEVELOPED IN OUR LABORATORY FOR THE META-ANALYSIS OF RNA-SEQUENCING DATA. THE VERTICAL AXIS SHOWS THE VALUES USED TO RANK GENES. HIGH-RANKING AND LOW-RANKING GENES INDICATE UPREGULATED GENES IN RESPONSE TO HIGH AND LOW DENSITIES, RESPECTIVELY. GENE NAMES ARE DESCRIBED NEXT TO PLOTS FOR PREVIOUSLY REPORTED DENSITY-RESPONSE GENES. IN ADDITION, THE GENES THAT HAVE NOT BEEN REPORTED AS DENSITY-RESPONSIVE GENES WERE ALSO INCLUDED IN HIGH-RANKING AND LOW-RANKING GENES. view more 

CREDIT: KOUHEI TOGA, HIROSHIMA UNIVERSITY

A grasshopper hatched in a crowded environment may look and behave differently than a grasshopper hatched in isolation — even if they have the same genes. The mechanism of this density-dependent phenomenon, called polyphenism, is well-documented in both aphids and locusts, but how genes regulate these traits has remained shrouded until now. Researchers from Hiroshima University analyzed datasets collected from prior studies to better understand how genes can influence one another to change their expression depending on environmental conditions. 

They published their results on Sept. 23 in Insects. 

“Aphids exhibit multiple wing types and locusts exhibit different body colors and behaviors,” said corresponding author Hidemasa Bono, professor in Hiroshima University’s Graduate School of Integrated Sciences for Life. “These well-known agricultural pests are representative of insects that exhibit density-dependent plasticity. To reveal the molecules common to all or multiple species that exhibit this same type of plasticity, we collected and reanalyzed publicly available RNA sequencing data of aphids and locusts.” 

The RNA sequencing data, called a transcriptome, is a collection of various expressed genes. It can also help identify new genes involved in producing specific traits. By performing a meta-analysis, researchers combine transcriptome results from multiple studies to see what the data says. In this study, the researchers analyzed 66 public transcriptome datasets from seven species of aphids and locusts.

“Meta-analysis is thought to be effective in providing additional insights into density-dependent polyphenism because it can uncover new information that would not be found with conventional hypothesis-driven research methods,” said first author Kouhei Toga, researcher in Hiroshima University’s Graduate School of Integrated Sciences for Life. “This study is the first meta-analysis conducted on datasets of two evolutionarily distant lineages, and it identified many density-responsive genes, which have scarcely been the focuses of research that aims to elucidate the molecular mechanisms of density-dependent plasticity.”

Specifically, the researchers found that DNA replication, DNA metabolic processes and the mitotic cell cycle were all enriched in response to crowded conditions. According to Toga, their results emphasize the importance of these processes— which have rarely been the focus of research in this area — as regulatory mechanisms in density-dependent polyphenism research. 

They also found discrepancies with some studies, including one that found a gene related to pigmentation in more gregarious locusts was more highly expressed in isolated conditions. When compared with the data from other studies, the researchers found the gene fit in a category of other genes that upregulated their expression when under oxidative stress. According to Bono, oxidative stress is a more likely explanation for the high gene expression in solitary locusts than in crowded conditions. 

“We also found neurological system modifications may play an important role in inducing density-dependent phenotypic changes in two lineages,” Bono said, explaining that several genes functioning in the nervous system, which would lead to density-dependent behavioral changes, increased under isolated conditions.

The findings can be generally applied to other species that exhibit density-dependent polyphenism due to the sheer amount of data from so many studies, which serves as a cross-check of previous hypotheses and results, according to Toga. 

“With increasing public RNA sequencing data, a meta-analysis that combines the data from multiple studies has succeeded in providing novel insights into targeted biological processes,” Toga said. “We hope that functional analysis of the genes identified in this study will lead to the development of methods to control the growth of aphids and locusts. We also hope to clarify how organisms respond and adapt to density by applying meta-analysis to various species.”

###

The Center for Innovation for Bio-Digital Transformation and the Japan Science and Technology Agency supported this research. Computations for this work were performed on the computers at the Hiroshima University Genome Editing Innovation Center.

About Hiroshima University

Since its foundation in 1949, Hiroshima University has striven to become one of the most prominent and comprehensive universities in Japan for the promotion and development of scholarship and education. Consisting of 12 schools for undergraduate level and 4 graduate schools, ranging from natural sciences to humanities and social sciences, the university has grown into one of the most distinguished comprehensive research universities in Japan.
English website: https://www.hiroshima-u.ac.jp/en

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JOURNAL

Insects

DOI

10.3390/insects13100864 

ARTICLE TITLE

Meta-Analysis of Transcriptomes in Insects Showing Density-Dependent Polyphenism

Trouble falling asleep at night? Chase that daytime light, study shows

Peer-Reviewed Publication

UNIVERSITY OF WASHINGTON

 

IMAGE: AN OVERCAST DECEMBER DAY ON THE UNIVERSITY OF WASHINGTON CAMPUS IN SEATTLE. view more 

CREDIT: UNIVERSITY OF WASHINGTON

(Note: researcher contact information at the end)

 

A study measuring the sleep patterns of students at the University of Washington has turned up some surprises about how and when our bodies tell us to sleep — and illustrates the importance of getting outside during the day, even when it’s cloudy.

Published online Dec. 7 in the Journal of Pineal Research, the study found that UW students fell asleep later in the evening and woke up later in the morning during — of all seasons — winter, when daylight hours on the UW’s Seattle campus are limited and the skies are notoriously overcast.

The team behind this study believes it has an explanation: The data showed that in winter students received less light exposure during the day. Other research has indicated that getting insufficient light during the day leads to problems at night, when it’s time for bed.

“Our bodies have a natural circadian clock that tells us when to go to sleep at night,” said senior author Horacio de la Iglesia, a UW professor of biology. “If you do not get enough exposure to light during the day when the sun is out, that ‘delays’ your clock and pushes back the onset of sleep at night.”

The study used wrist monitors to measure sleep patterns and light exposure for 507 UW undergraduate students from 2015 to 2018. Data indicated that students were getting roughly the same amount of sleep each night regardless of season. But, on school days during the winter, students were going to bed on average 35 minutes later and waking up 27 minutes later than summer school days. This finding surprised the team, since Seattle — a high-latitude city — receives nearly 16 hours of sunlight on the summer solstice, with plenty evening light for social life, and just over eight hours of sunlight on the winter solstice.

“We were expecting that in the summer students would be up later due to all the light that’s available during that season,” said de la Iglesia.

Based on student sleep data, the researchers hypothesized that something in winter was “pushing back” the students’ circadian cycles. For most humans, including college students, the innate circadian cycle governing when we’re awake and asleep runs at about 24 hours and 20 minutes — and is “calibrated” daily by input from our environment. For UW students in the study, sleep data indicated that their circadian cycles were running up to 40 minutes later in winter compared to summer.

The team focused on light as a potential explanation for this winter delay. But light has different impacts on circadian rhythms at different times of the day.

“Light during the day — especially in the morning — advances your clock, so you get tired earlier in the evening, but light exposure late in the day or early night will delay your clock, pushing back the time that you will feel tired,” said de la Iglesia. “Ultimately, the time that you fall asleep is a result of the push and pull between these opposite effects of light exposure at different times of the day.”

Data showed that daytime light exposure had a greater impact than evening light exposure in the UW study. Each hour of daytime light “moved up” the students’ circadian phases by 30 minutes. Even outdoor light exposure on cloudy or overcast winter days in Seattle had this effect, since that light is still significantly brighter than artificial indoor lighting, said de la Iglesia. Each hour of evening light — light from indoor sources like lamps and computer screens — delayed circadian phases by an average of 15 minutes.

“It’s that push-and-pull effect,” said de la Iglesia. “And what we found here is that since students weren’t getting enough daytime light exposure in the winter, their circadian clocks were delayed compared to summer.”

The study offers lessons not just for college students. 

“Many of us live in cities and towns with lots of artificial light and lifestyles that keep us indoors during the day,” said de la Iglesia. “What this study shows is that we need to get out — even for a little while and especially in the morning — to get that natural light exposure. In the evening, minimize screen time and artificial lighting to help us fall asleep.”

Lead author on the paper is Gideon Dunster, an associate manager with the Allen Institute for Cell Science, who conducted the study as a UW doctoral student. Co-authors are UW undergraduate alum Isabelle Hua, now a researcher at the National Institute of Neurological Disorders and Stroke; Alex Grahe in the UW Department of Biology; Jason Fleischer and Satchidananda Panda of the Salk Institute; Kenneth Wright and Céline Vetter of the University of Colorado, Boulder; and UW teaching professor of biology Jennifer Doherty. The research was funded by the National Science Foundation. Dunster was supported by the Riddiford-Truman Fellowship and the Hoag Endowed Graduate Fellowship through the UW Department of Biology.

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For more information, contact Horacio de la Iglesia at horaciod@uw.edu.

Grant number: 1743364

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JOURNAL

Journal of Pineal Research

DOI

10.1111/jpi.12843 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Daytime light exposure is a strong predictor of seasonal variation in sleep and circadian timing of university students

ARTICLE PUBLICATION DATE

7-Dec-2022

COI STATEMENT

Co-author Kenneth P. Wright (University of Colorado, Boulder) reports research support/donated materials: DuPont Nutrition & Biosciences, Grain Processing Corporation, and Friesland Campina Innovation Centre and being a consultant to and/or receiving personal fees from Circadian Therapeutics, Inc., Circadian Biotherapies, Inc., Philips, Inc, and U.S. Army Medical Research and Materiel Command - Walter Reed Army Institute of Research, outside the submitted work.

Unravelling the secrets of a good night's sleep

Researchers from the University of Tsukuba identify a signaling pathway within brain cells that regulates how long and how deeply we sleep

Peer-Reviewed Publication

UNIVERSITY OF TSUKUBA

Tsukuba, Japan—A good night's sleep can work wonders for both mind and body. But what is it that determines how much we need to sleep, and what can cause us to sleep more deeply?
In a new study, researchers from the University of Tsukuba have now provided some answers, revealing a signaling pathway within brain cells that regulates the length and depth of sleep.

"We examined genetic mutations in mice and how these affect their patterns of sleep," says senior author of the study, Professor Hiromasa Funato. "We identified a mutation that led to the mice sleeping much longer and more deeply than usual." The researchers found that this was caused by low levels of an enzyme called histone deacetylase 4 (HDAC4), which is known to suppress the expression of target genes.

Previous studies on HDAC4 have shown that it is greatly affected by the attachment of phosphate molecules in a process known as phosphorylation. When this occurs, HDAC4 tends to move away from the cell nucleus, and the suppression of certain proteins is reduced. The researchers were interested in whether this phosphorylation of HDAC4 would affect sleep.

"We focused on a protein called salt-inducible kinase 3, otherwise known as SIK3, which phosphorylates HDAC4," says Professor Funato. "We previously found that this protein has strong effects on sleep." The team found that when there was a lack of SIK3 or when HDAC4 was modified to prevent phosphorylation, the mice slept less. In contrast, when the mice had a more active version of SIK3, which increased the phosphorylation of HDAC4, they slept a lot more. They also identified a further protein, LKB1, which phosphorylates SIK3, and has similar sleep-suppressing effects when deficient.

"Our findings indicate that there is a signaling pathway within brain cells from LKB1 to SIK3 and then to HDAC4," says study co-senior author, Professor Masashi Yanagisawa. "This pathway leads to the phosphorylation of HDAC4, which promotes sleep, most probably because it affects the expression of sleep-promoting genes."

The team carried out further experiments to identify the brain cells in which these pathways regulate sleep. This involved altering the amounts of SIK3 and HDAC4 in different cell types and brain regions. The results indicated that signaling within the cells of the cortex regulates the depth of sleep, while signaling within the hypothalamus regulates the amount of deep sleep. For both brain regions, the excitatory neurons, which can activate other neurons, were identified as playing a key role.

These results provide an important insight into how sleep is regulated, which could potentially lead to a greater understanding of sleep disorders as well as the development of new treatments.

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This work was supported by the World Premier International Research Center Initiative from MEXT, JSPS KAKENHI, JST CREST, AMED, JSPS DC2, University of Tsukuba Basic Research Support Program Type A, Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program).

 

Original Paper

The article, "Kinase signalling in excitatory neurons regulates sleep quantity and depth," was published in Nature at DOI: 10.1038/s41586-022-05450-1

Correspondence

Professor and Director YANAGISAWA Masashi
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba
Professor / Visiting Professor FUNATO Hiromasa
Department of Anatomy, Graduate School of Medicine, Toho University / International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba

Related Link

International Institute for Integrative Sleep Medicine (WPI-IIIS)

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JOURNAL

Nature

DOI

10.1038/s41586-022-05450-1 

ARTICLE TITLE

Kinase signalling in excitatory neurons regulates sleep quantity and depth

ARTICLE PUBLICATION DATE

7-Dec-2022