SOCIOBIOLOGY

A pair of brain regions prompts females to kill or care for their young

Peer-Reviewed Publication

NYU LANGONE HEALTH / NYU GROSSMAN SCHOOL OF MEDICINE

A middle-brain region tied to the control of emotions likely prompts females to kill their young, a new study in mice shows. With the region also present in humans, the study authors say the findings could play a similar role in better understanding infanticide by women.

Before giving birth for the first time, female mice are known to often kill others’ pups. This behavior may have evolved to preserve scarce food supplies for their own future offspring, according to experts. However, most studies have focused on infanticide by adult males, and the brain mechanism behind this behavior in females has until now remained poorly understood.

Led by researchers at NYU Grossman School of Medicine, the study showed that chemically blocking the region, called the principal nucleus of the bed nucleus of stria terminalis (BNSTpr), prevented infanticide nearly 100% of the time. By contrast, when the study team artificially activated the brain region, both mothers and females without offspring killed pups in nearly all trials, attacking within a second of the stimulation. The mice rarely attacked other adults, the authors say, suggesting that the structure specifically controls aggression toward young animals.

The investigation also revealed that the BNSTpr appears to work in opposition to a brain region called the medial preoptic area (MPOA), itself known to promote mothering behavior. According to the findings, mice that had not yet reached motherhood showed high BNSTpr activity, which dampened activity in the MPOA. After the mice gave birth, however, MPOA activity ramped up, likely suppressing the infanticidal system in the process. The new mothers tended to avoid infanticide regardless of whether the pup was theirs.

“Our investigation pinpoints for the first time the brain mechanisms that we believe encourage and discourage infanticide in females,” said study lead author Long Mei, PhD, a Leon Levy Foundation postdoctoral fellow in NYU Langone Health’s Neuroscience Institute.

The new study, publishing online June 7 in the journal Nature, also demonstrates that the switch to maternal behaviors can be reversed by extra pressure to the BNSTpr, notes Mei.

According to the U.S. Centers for Disease Control and Prevention, child abuse is the fourth leading cause of death among preschool children in the United States. Mei notes that while early studies had largely focused on potential problems in the parenting centers of the brain, experts have more recently begun to search for a separate system dedicated to infanticide and aggression against children.

For the investigation, researchers first narrowed down the most likely brain regions behind infanticidal behavior by tracking which structures were connected to the MPOA. Next, they artificially stimulated each of the resulting seven areas in live mice to determine which, if any, caused the animals to attack pups. Then, the team blocked activity in the BNSTpr, the most promising candidate remaining, to see if this would prevent infanticide.

To demonstrate that the BNSTpr and MPOA counteract each other, the study authors prepared brain slices from female rodents and activated one region while at the same time recording cell activity in the other. They also traced how activity in these structures changed as rodents reached motherhood.

“Since these two connecting regions in the middle of the brain can be found in both rodents and humans alike, our findings hint at a possible target for understanding, and perhaps even treating, mothers who abuse their children,” said study senior author and neuroscientist Dayu Lin, PhD. “Maybe these cells normally remain dormant, but stress, postpartum depression, and other known triggers for child abuse may prompt them to become more active,” added Lin, a professor in the Departments of Psychiatry and Neuroscience and Physiology at NYU Langone.

That said, Lin, also a member of NYU Langone’s Neuroscience Institute, cautions that it remains unclear if the two brain regions perform the same roles in humans as they do in rodents.

She adds that the study team next plans to examine the BNSTpr and MPOA in male mice and to explore ways of turning off activity in the former region without invasive surgery.

Funding for the study was provided by National Institutes of Health grants R01HD092596, R21HD090563, R01MH101377, and U19NS107616. Additional funding was provided by the Leon Levy Foundation.

In addition to Mei and Lin, other NYU study investigators involved in the study were Rongzhen Yan, PhD; Luping Yin, PhD; and Regina Sullivan, PhD.

---

JOURNAL

Nature

DOI

10.1038/s41586-023-06147-9 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Antagonistic circuits mediating infanticide and maternal care in female mice

ARTICLE PUBLICATION DATE

7-Jun-2023

Columbia scientists discover that water molecules define the materials around us

A new paper argues that materials like wood, bacteria, and fungi belong to a newly identified class of matter, "hydration solids."

Peer-Reviewed Publication

COLUMBIA UNIVERSITY

 

IMAGE: SPIRIT ISLAND, JASPER NATIONAL PARK, CANADA. “WHEN WE TAKE A WALK IN THE WOODS, WE THINK OF THE TREES AND PLANTS AROUND US AS TYPICAL SOLIDS," PROFESSOR OZGUR SAHIN SAID. "THIS RESEARCH SHOWS THAT WE SHOULD REALLY THINK OF THOSE TREES AND PLANTS AS TOWERS OF WATER HOLDING SUGARS AND PROTEINS IN PLACE." view more 

CREDIT: PHOTO CREDIT: TERRY OTT

For decades, the fields of physics and chemistry have maintained that the atoms and molecules that make up the natural world define the character of solid matter. Salt crystals get their crystalline quality from the ionic bond between sodium and chloride ions, metals like iron or copper get their strength from the metallic bonds between iron or copper atoms, and rubbers get their stretchiness from the flexible bonds within polymers that constitute the rubber. The same principle applies for materials like fungi, bacteria, and wood.

Or so the story goes.

A new paper published today in Nature upends that paradigm, and argues that the character of many biological materials is actually created by the water that permeates these materials. Water gives rise to a solid and goes on to define the properties of that solid, all the while maintaining its liquid characteristics. In their paper, the authors group these and other materials into a new class of matter that they call “hydration solids,” which they say “acquire their structural rigidity, the defining characteristic of the solid state, from the fluid permeating their pores.” The new understanding of biological matter can help answer questions that have dogged scientists for years.

“I think this is a really special moment in science,” Ozgur Sahin, a professor of Biological Sciences and Physics and one of the paper’s authors, said. “It’s unifying something incredibly diverse and complex with a simple explanation. It’s a big surprise, an intellectual delight.”

Steven G. Harrellson, who recently completed doctoral studies in Columbia’s physics department, and is an author on the study, used the metaphor of a building to describe the team’s finding: “If you think of biological materials like a skyscraper, the molecular building blocks are the steel frames that hold them up, and water in between the molecular building blocks is the air inside the steel frames. We discovered that some skyscrapers aren’t supported by their steel frames, but by the air within those frames.”

“This idea may seem hard to believe, but it resolves mysteries and helps predict the existence of exciting phenomena in materials,” Sahin added.

When water is in its liquid form, its molecules strike a fine balance between order and disorder. But when the molecules that form biological materials combine with water, they tip the balance toward order: Water wants to return to its original state. As a result, the water molecules push the biological matter’s molecules away. That pushing force, called the hydration force, was identified in the 1970s, but its impact on biological matter was thought to be limited. This new paper’s argument that the hydration force is what defines the character of biological matter almost entirely, including how soft or hard it is, thus comes as a surprise.

We have long known that biological materials absorb ambient moisture. Think, for example, of a wooden door, that expands during a humid spell. This research, however, shows that that ambient water is much more central to wood, fungi, plants, and other natural materials’ character than we had ever known.

The team found that bringing water to the front and center allowed them to describe the characteristics that familiar organic materials display with very simple math. Previous models of how water interacts with organic matter have required advanced computer simulations to predict the properties of the material. The simplicity of the formulas that the team found can predict these properties suggests that they’re onto something.

To take one example, the team found that the simple equation E=Al/λ neatly describes how a material’s elasticity changes based on factors including humidity, temperature, and molecule size. (E in this equation refers to the elasticity of a material; A is a factor that depends on the temperature and humidity of the environment; l is the approximate size of biological molecules and λ is the distance over which hydration forces lose their strength).

“The more we worked on this project, the simpler the answers became,” Harrellson said, adding that the experience “is very rare in science.”

The new findings emerged from Professor Sahin’s ongoing research into the strange behavior of spores, dormant bacterial cells. For years, Sahin and his students have studied spores to understand why they expand forcefully when water is added to them and contract when water is removed. (Several years ago, Sahin and colleagues garnered media coverage for harnessing that capability to create small engine-like contraptions powered by spores.)

Around 2012, Sahin decided to take a step back to ask why the spores behave the way they do. He was joined by researchers Michael S. DeLay and Xi Chen, authors on the new paper, who were then members of his lab. Their experiments did not provide a resolution to the mysterious behavior of spores. “We ended up with more mysteries than when we started,” Sahin remembers. They were stuck, but the mysteries they encountered were hinting that there was something worth pursuing.

After years of pondering potential explanations, it occurred to Sahin that the mysteries the team continually encountered could be explained if the hydration force governed the way that water moved in spores.

The team had to do more experiments to test the idea. In 2018, Harrellson, who is now a software engineer at the data analytics firm Palantir, joined the project.

“When we initially tackled the project, it seemed impossibly complicated. We were trying to explain several different effects, each with their own unsatisfying formula. Once we started using hydration forces, every one of the old formulas could be stripped away. When only hydration forces were left, it felt like our feet finally hit the ground. It was amazing, and a huge relief; things made sense,” he said.

The results of those experiments led the team and their collaborators to this paper. In addition to Harrellson, DeLay, Chen, and Sahin, the paper’s other authors are Ahmet-Hamdi Cavusoglu, Jonathan Dworkin, and Howard A. Stone. Adam Driks of Loyola University Chicago, who also contributed research, passed away before the completion of the work. Funding for the research was provided by the U.S. Department of Energy’s Office of Science and Basic Energy Sciences; by the Office of Naval Research; by the National Institutes of Health; and by the David and Lucile Packard Fellows Program.

The paper’s findings apply to huge amounts of the world around us: Hygroscopic biological materials–that is, biological materials that allow water in and out of them–potentially make up anywhere from 50% to 90% of the living world around us, including all of the world’s wood, but also other familiar materials like bamboo, cotton, pine cones, wool, hair, fingernails, pollen grains in plants, the outer skin of animals, and bacterial and fungal spores that help these organisms survive and reproduce.

The term coined in the paper, “hydration solids,” applies to any natural material that’s responsive to the ambient humidity around it. With the equations that the team identified, they and other researchers can now predict materials’ mechanical properties from basic physics principles. So far that was true mainly of gases, thanks to the well-known general gas equation, which has been known to scientists since the 19th century.

“When we take a walk in the woods, we think of the trees and plants around us as typical solids. This research shows that we should really think of those trees and plants as towers of water holding sugars and proteins in place,” Sahin said: “It’s really water’s world.”

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JOURNAL

Nature

DOI

10.1038/s41586-023-06144-y 

ARTICLE TITLE

Hydration solids

ARTICLE PUBLICATION DATE

7-Jun-2023

CSHL harnesses biology’s favorite chemical

Peer-Reviewed Publication

COLD SPRING HARBOR LABORATORY

 

IMAGE: SHOUJUN SUN, SEEN HERE, IS A POSTDOCTORAL FELLOW IN COLD SPRING HARBOR LABORATORY PROFESSOR JOHN MOSES’ LAB. SUN LED A NEW MOSES LAB STUDY THAT MARKS A SIGNIFICANT BREAKTHROUGH FOR THE FIELD OF CLICK CHEMISTRY. view more 

CREDIT: MOSES LAB/COLD SPRING HARBOR LABORATORY

For chemists like Cold Spring Harbor Laboratory (CSHL) Professor John Moses, diversity is a gateway to discovery. The more molecules scientists have to explore, the more likely it is they will find something useful. With the latest advancement from Moses’ lab, they can now quickly assemble a vast array of complex molecules. Among those molecules, Moses hopes to find effective new cancer therapeutics.

In collaboration with two-time Nobel laureate K. Barry Sharpless, Moses’ lab has devised a chemical transformation they call phosphorus fluoride exchange, or PFEx. PFEx efficiently snaps together chemical building blocks to form new molecules, in a reliable process known as click chemistry. Click chemistry already offers chemists a powerful set of tools. As the newest addition to that tool kit, PFEx takes a cue from biology and uses phosphorous as a chemical connector.

Inside cells, phosphorous gives structure to DNA and holds together essential energy-storing molecules. It’s a versatile connector. It can readily connect multiple chemical groups. These groups can be arranged around the phosphorous hub to create three-dimensional shapes.

Moses says: “Nature has recognized its importance—it’s a privileged group. If we’re trying to make drugs that interact with biology, we should not ignore that fact.”

Chemists can now use PFEx to click together multiple different chemical components around a single phosphorous hub. By incorporating more phosphorous connectors, they can build even more complex molecules. “We’re now decorating this three-dimensional linkage. And that’s going to allow us to access some new chemical space,” says CSHL Research Investigator Joshua Homer. “When you access new space, you’re accessing new function.”

PFEx reactions might even enable drugs to latch onto their targets inside the body. Moses’ team has already begun exploring PFEx as a source of cancer therapeutics. One benefit to this approach is that researchers can optimize the reactivity of the molecules involved in PFEx reactions. This could ensure potential drugs interact only with their desired targets, reducing the risk of side effects.

The researchers expect their new kind of click chemistry will help create materials with useful properties. For example, PFEx might be used to incorporate flame retardants or antimicrobials into new surfaces. Moses says PFEx materials will have an important advantage over the “forever chemicals” found in many of today’s products. Phosphorous bonds are not excessively stable. This means they can be easily broken down when a product is ready for recycling.

  

The power and potential of PFEx-based chemistry lie in its ability to rapidly and reliably click together complex molecules using sustainable lab science. The illustration above shows how PFEx is compatible with other click chemistry bonds, including the 2022 Nobel prize-winning CuAAC reactions.

CREDIT

Moses lab/Cold Spring Harbor Laboratory

JOURNAL

Chem

DOI

10.1016/j.chempr.2023.05.013 

ARTICLE TITLE

Phosphorus Fluoride Exchange: Multidimensional Catalytic Click Chemistry from Phosphorus Connective Hubs

ARTICLE PUBLICATION DATE

7-Jun-2023

Sweet snacks: Children have very different preferences

Some focus primarily on price, others on taste, according to a study by the University of Bonn

Peer-Reviewed Publication

UNIVERSITY OF BONN

 

IMAGE: FROM THE MARKET RESEARCH OF THE AGRICULTURAL AND FOOD INDUSTRY AT THE UNIVERSITY OF BONN "JUGGLES" SNACKS IN FRONT OF A SCHOOL. view more 

CREDIT: ASSEMBLY: VOLKER LANNERT/UNIVERSITY OF BONN

Would third- and fourth-graders buy fewer unhealthy snacks if they were more expensive? The answer provided by researchers at the University of Bonn is nuanced: Some elementary school students do actually pay attention to the price. Others, however, have such strong preferences that they are willing to pay a little more for them. A third group, in contrast, does not yet seem to have sufficient cognitive skills to be significantly influenced by prices. The study illustrates above all how differently children behave when it comes to their snack purchases - a finding that should also be of interest to policymakers. The results have now been published in the journal Food Quality and Preference.

Should I go for the chocolate cookies or maybe the apple slices? Even elementary school children are faced with this decision: The purchasing power of six- to twelve-year-olds in Germany is estimated at more than two billion euros. Many of them invest much of their pocket money in ice cream and other sweet treats. But frequently reaching for unhealthy snacks can have long-term consequences: One in seven children in Germany is considered overweight. At the same time, the number of those who develop diabetes or suffer from cardiovascular problems at a young age is increasing.

"In countries like Great Britain, a sugar tax is now levied on sweet drinks," explains Stefanie Landwehr, a doctoral student at the Chair for Agricultural and Food Market Research at the University of Bonn. This measure also seems to be successful with teenagers, as studies suggest. But is this also the case with younger children? And in comparison, what influence do certain brands that are popular in the age group have on the purchase decision?

Cookie, fruit pulp or apple slices?

Landwehr investigated these questions together with Prof. Dr. Monika Hartmann, chair of the department, as well as Prof. Sean B. Cash (Tufts University Boston, USA) and Dr. Ching-Hua Yeh (University of Bonn). The researchers were able to recruit around 120 elementary school students between the ages of seven and ten as test subjects. The young participants were first asked to answer a few questions, such as about their favorite snacks and their knowledge of nutrition. They also completed a simple test on their understanding of quantities. Sample question: If there are 50 children at a children's birthday party, is that a lot or a little? "The results allow conclusions to be drawn about how well children can evaluate numbers," Landwehr explains. "Those who have lower skills in this regard are probably less able to assess prices."

After completing this part, the girls and boys received three euros as a reward. They were then able to buy a snack as part of a simple purchase experiment. The assortment included a chocolate chip cookie (the unhealthiest alternative), a squeeze pack with fruit pulp (slightly healthier), and apple slices (the healthiest choice). The products were offered at three different price levels - 60 cents, one euro or 1.40 euros. In addition, each snack came in two varieties: one from McDonald's, a very well-known brand among children, and a second from an unknown manufacturer.

Now the children were shown photos of two different products at different prices, such as a no-name chocolate cookie for one euro and apple slices from McDonald's for 1.40 euros. The girls and boys could state which product they would buy, but also had the option of choosing neither. The choice was noted on a response card. In total, this experiment was repeated ten times with different snack and price combinations. "So we ended up with ten report cards for each child," explains Prof. Monika Hartmann. These were turned over and shuffled, and the respective child was allowed to draw a card. The choice ticked on it was then implemented: For example, if the card was drawn where the child chose a no-name chocolate cookie for the price of one euro, the child paid and received the cookie.

Cookie fans do not look at the price

Analysis of the data shows that elementary school kids varied widely in their purchase decisions. "In general, they could be divided into three groups," Landwehr says. The cookie lovers who could not be dissuaded from buying their favorite snack even if it was more expensive. The price-sensitive shoppers, who made their decision primarily dependent on the purchase price. And those who did not yet have a clear understanding of cheap or expensive - these were mostly the younger ones. They often tended to choose the fruit pulp; the price did not matter much to them.

Somewhat surprising for the researchers was another result: McDonald's snacks were by no means more popular with the children. On the contrary: On average, they were actually less willing to pay for them than for snacks from unknown manufacturers. "It may be because McDonald's is known more for its burgers and fries and less for apple slices or chocolate cookies," Landwehr speculates. It is quite possible that other brands may well have an effect on children's consumption decisions, she says.

Overall, the study shows that younger children are a very heterogeneous target group: Measures aimed at steering their consumption behavior in a certain direction do not work equally for everyone. "For instance, age and understanding of 'cheap' or 'expensive' plays a significant role in the impact of price signals," Landwehr explains. "However, there are children who have such an understanding but are still unlikely to be influenced by higher prices. In the fight against obesity, it therefore makes sense to rely on a variety of strategies to reach as many girls and boys as possible."

Participating institutions and funding:

In addition to the University of Bonn, Tufts University Boston (USA) was also involved in the study. The work was funded by the German Research Foundation (DFG).

Publication: Stefanie C. Landwehr, Monika Hartmann, Sean B. Cash, Ching-Hua Yeh: The kids are not all the same - Heterogeneity in children’s snack purchase behavior. Food Quality and Preference, DOI: https://doi.org/10.1016/j.foodqual.2023.104906

DOI

10.1016/j.foodqual.2023.104906 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

The kids are not all the same - Heterogeneity in children’s snack purchase behavior.

Scientists use seaweed to create new material that can store heat for reuse

Peer-Reviewed Publication

SWANSEA UNIVERSITY

 

IMAGE: BEADS WHICH CAN STORE HEAT, WHICH WOULD OTHERWISE BE WASTED, FROM VARIOUS SOURCES, INCLUDING INDUSTRIAL OPERATIONS AND THE SUMMER SUN. THE NEW MATERIAL HAS BEEN MADE USING ALGINATE, AN INEXPENSIVE, ABUNDANT AND NON-TOXIC SEAWEED DERIVATIVE. view more 

CREDIT: SPECIFIC, SWANSEA UNIVERSITY

Researchers from the SPECIFIC Innovation and Knowledge Centre and COATED M2A programme at Swansea University have collaborated with the University of Bath to make a groundbreaking advancement in thermal storage research, developing a new efficient material that is easily scalable and can be sized and shaped to fit multiple applications.                                                                    

Published in the Journal of Materials Science, the material has been made using alginate, an inexpensive, abundant, and non-toxic seaweed derivative.

The process starts with the dissolving of sodium alginate in water. Following this, expanded graphite is added, and a method of gelation is chosen:

The first method is achieved by transferring the solution into a mould for freezing. After being kept at - 20°C for over two hours, beads are formed and transferred to a saturated calcium chloride solution.

The second uses a drop-cast technique, with the mixture being dropped into thermochemical calcium salt, causing gelation on contact.

Once sufficient salt diffusion has occurred, the synthesised beads are filtered and dried at 120°C.

Compared to SPECIFIC's previous carrier material, vermiculite, the alginate-based beads from both methods offer a remarkable improvement in heat storage capacity.

The new spherical beads boast increased salt capacity, achieving up to four times greater energy density than the vermiculite carrier. This is facilitated by their efficient packing in a fixed bed that maintains good airflow. As a result, the new material can achieve the same heat energy storage capacity in just a quarter of the volume.

Jack Reynolds, who led the research as part of his doctorate at Swansea University, explains: 

"The ability to recover and store otherwise-wasted heat from various sources, including industrial operations and the summer sun, presents an exciting opportunity in the quest for sustainable and affordable energy resources. Our new heat storage material marks a significant step forward in realising this potential."

Dr Jonathon Elvins, Senior Technology Transfer Fellow and co-author, added: 

"SPECIFIC remains committed to driving innovation in thermal storage technology and actively collaborating with industry partners and researchers worldwide to accelerate the transition towards a greener and more sustainable future.”

"To explore new applications for this latest technology, we are preparing for a trial at Tata Steel UK’s Trostre steelworks to investigate ways of capturing waste heat from industrial processes for use elsewhere."

The research at SPECIFIC Innovation and Knowledge Centre and COATED M2A was funded by the European Regional Development Fund through the Welsh Government, the European Social Fund via the Welsh Government, the Engineering and Physical Sciences Research Council (EPSRC), and Tata Steel UK. It was also supported by the Industrial Decarbonisation Research and Innovation Centre.

END

Pictures:

• Researcher Jack Reynolds putting the seaweed-based alginate solution into moulds for freezing into beads
• Close-up of the newly formed alginate beads.
• Jack Reynolds (left) with the alginate solution and Dr Jonathon Elvins (right) with the finished beads

Credit:  SPECIFIC, Swansea University

Jack Reynolds (l) with alginate, which derives from seaweed, with Dr Jonathon Elvins (r) with beads that are produced from the alginate and that can store heat for reuse. Pictured at Swansea University, where they conducted their research.

CREDIT

SPECIFIC, Swansea University

How seaweed can be used to sto [VIDEO] |

Researchers Jack Reynolds and Dr Jonathon Elvins of Swansea University explain the new material they created, based on seaweed, which can store heat that would otherwise be wasted.

Read the paper in full: Development and characterisation of an alginate and expanded graphite based composite for thermochemical heat storage.

 

When reporting this story, please use Swansea University hyperlinks.

Founded in 1920, Swansea University is a research-led, dual campus university located along Swansea Bay in south Wales, UK. Its stunning beachfront campuses and friendly welcome make Swansea University a desirable destination for more than 22,000 students from across the globe. There are three academic faculties, delivering around 450 undergraduate and 350 postgraduate degree programmes.

 

Swansea is a UK top 30 institution, ranked 26th in the 2023 Guardian University Guide. In the 2021 Research Excellence Framework, 86% of Swansea University’s overall research and 91% of its research environment were classed as world-leading and internationally excellent, with 86% of its research impact rated outstanding and very considerable.

 

Swansea University is a registered charity. No. 1138342.  

 

For more information:

Kevin Sullivan, senior press officer, Swansea University k.g.sullivan@swansea.ac.uk;

01792 295050

 

   Follow us on Twitter:  www.twitter.com/SwanseaUni

   Find us on Facebook: www.facebook.com/swanseauniversity

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JOURNAL

Journal of Materials Science

DOI

10.1007/s10853-023-08370-1 

Worm genetics reveal important pathways for sleep regulation

Using an unbiased genetic approach in worms, researchers from the University of Tsukuba find that tissues in the body regulate sleep via pathways that are important for making and disposing of proteins

Peer-Reviewed Publication

UNIVERSITY OF TSUKUBA

Tsukuba, Japan—Although the regulation of sleep—how much, when, and how sleep occurs—is mainly considered to be controlled by the brain, sleep deprivation also affects the body, and signals from the body can affect sleep. However, the ways in which the body regulates sleep are largely unknown. In a recent study published in Cell Reports, Japanese researchers have revealed that sleep in worms is regulated by the body via cellular pathways that maintain proper protein function, from synthesis to degradation.

When exploring the body's regulation of sleep, it can be difficult to know where to start. The researchers from the University of Tsukuba chose to use an unbiased investigative technique known as forward genetic screening. To do this, they first applied a chemical to cause random mutations in about 500 worms, and then used a video-based monitoring system to identify the worms that slept much more or less than average. When they identified such worms, they looked at what mutations they had, how the mutations affected the sleep.

"Using this method, we were able to identify that mutations in the sel-1 and sel-11 genes were associated with longer sleep duration," says senior author of the study Professor Yu Hayashi. "Both genes code for proteins that are part of the endoplasmic-reticulum-associated protein degradation pathway, which helps cells to get rid of proteins that are misfolded."

The researchers also found that mutations in mars-1, which is important for protein synthesis, were associated with prolonged sleep in the worms. Moreover, although sel-1, sel-11, and mars-1 were expressed in a wide range of tissues, when the researchers made the worms express normal versions of some of these genes in skin cells led to normal sleep patterns. These results indicated that protein-regulating pathways in the body are indeed important for controlling sleep.

"We were also able to identify some downstream pathways that are involved in sleep regulation by modifying the expression of proteins in the worms," says Professor Hayashi. "Furthermore, when we tested our results from worms in mice, we found that these pathways also seem to regulate sleep in mammals."

Sleep disturbances are widely considered to influence inflammation and immunity, and may contribute to diseases such as inflammatory bowel disease and arthritis. A better understanding of how sleep is regulated is thus key to disease prevention. The results of this study add to a growing body of literature on sleep regulation and are hoped to improve sleep disturbance therapies in the near future that may prevent inflammatory diseases such as arthritis.

###
This work was supported by AMED under grant numbers JP19gm1110008, JP21wm0425018, and JP21zf0175005; CREST, JST under grant number JPMJCR1655, JSPS KAKENHI under grant numbers JP21H00414 and JP2121H04961; the Astellas Foundation for Research on Metabolic Disorders; the Asahi Glass Foundation (to Y.H.)
 

Original Paper

Title of original paper:
ER proteostasis regulators cell-non-autonomously control sleep

Journal:
Cell Reports

DOI:
10.1016/j.celrep.2023.112267

Correspondence

Visiting Professor HAYASHI, Yu
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba
Professor, Department of Biological Sciences, Graduate School of Science, The University of Tokyo

Related Link

International Institute for Integrative Sleep Medicine (WPI-IIIS)

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JOURNAL

Cell Reports

DOI

10.1016/j.celrep.2023.112267 

ARTICLE TITLE

ER proteostasis regulators cell-non-autonomously control sleep