Kariyat: global study on plant-herbivore interactions ‘opens window of possibilities’

Global data set provides more insight into plant-insect herbivore feeding habits

Peer-Reviewed Publication

UNIVERSITY OF ARKANSAS SYSTEM DIVISION OF AGRICULTURE

 

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INSECT LAB — RUPESH KARIYAT INSPECTS PETRI DISHES WITH RICE LEAVES AND FALL ARMYWORMS AT HIS LAB ON THE UNIVERSITY OF ARKANSAS, FAYETTEVILLE CAMPUS.

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CREDIT: UNIVERSITY OF ARKANSAS SYSTEM DIVISION OF AGRICULTURE PHOTO BY PADEN JOHNSON

FAYETTEVILLE, Ark. — Plant life is a hard life when it comes to fending off insects, and the further one gets from the equator the more difficult it can be, according to a study on plant-insect interactions published last month in the journal Science.

For years to come, generations of entomologists and plant pathologists will look to the study’s global data set that confirms long-held assumptions and “opens a window of possibilities,” says Rupesh Kariyat, associate professor of crop entomology with the Arkansas Agricultural Experiment Station.

Kariyat, who participated in the study with nearly 200 other scientists at 790 sites worldwide, said the data gathered on 503 plant species in 135 families will spawn many new studies on plant-herbivore interactions.

The study, “Plant size, latitude, and phylogeny explain within-population variability in herbivory,” was published last month in Science, the American Association for the Advancement of Science journal. Phylogeny is the study of how related groups of organisms evolve over time, and herbivory is the act of feeding on plants.

Kariyat said the study’s focus was to develop a more complete understanding of insect herbivory, which could eventually lead to integrated pest management recommendations and assist entomologists and plant pathologists studying the impacts of climate change on plant-insect-pathogen interactions.

“The study looks at how insects feed on plants at a global scale,” Kariyat said, describing how researchers studied the variability of feeding rates based on plant type, latitude and insect species. “A long-lasting assumption has been that plant-insect interactions — not pollinators, but insects that feed on plants — are highly variable, and you cannot fit it into one specific box.”

Kariyat said the study confirmed what he calls “a cornerstone in ecology.” Variability in insect eating habits, the study shows, is substantial across different members of the same species of plants. Now, they also have a ton of comparative data to go along with it.

Latitude, which measures the distance from the Earth’s equator, was found to be a significant factor affecting herbivory variability. Farther away from the equator, the growing season is shorter, which results in reduced time for herbivore foraging. So, more kinds of insects feed on the same plant species and its relatives than would be seen closer to the equator, Kariyat explained.

With the volume of data collected during this study, the authors hypothesize that herbivory may maintain plant diversity at latitudes closer to the equator because it is a “more consistent force within plant populations.” In other words, there is less competition for food sources nearer the equator for insect herbivores because of the increased diversity in plant life. This results in less variability of insect feeding on plant populations.

An additional hypothesis is that herbivory is more variable among small plants than large plants, which could explain why trees, for example, invest more of their biomass in defense, the authors noted. Kariyat said some tree defenses from insect herbivores include toxic secondary metabolites such as tannins and tree sap.

Keeping it together

While scientists have looked at various populations of plants on different latitudes for decades to understand how plants create defenses against insect feeding and the variability of herbivory at different latitudes, Kariyat said the studies had yet to be done with the same protocol. That changed when scientists formed the Herbivory Variability Network about four years ago.

The network is led by Will Wetzel with Montana State University’s department of land resources and environmental sciences, Moria Robinson of Michigan State University’s department of entomology, Phil Hahn with the University of Florida’s department of entomology and nematology, Nora Underwood and Brian Inouye with Florida State University’s department of biological science and Susan Whitehead with Virginia Tech’s department of biological sciences.

“They had this beautiful idea of ‘Why don’t we ask people who work in herbivory, across the globe if they can go out and collect data on their plants with a protocol that we set, so that all the data, whether you collected it from Bangladesh or the Democratic Republic of Congo, are exactly the same,” Kariyat said.

When Kariyat was a faculty member at the University of Texas Rio Grande Valley several years ago, he became involved with the Herbivory Variability Network by chance.

It was a fortunate opportunity, Kariyat said, not just because the group was looking for data on plants native to south Texas.

For the study, Kariyat enlisted his graduate student, Mandeep Tayal, to assist in collecting and curating plant specimens when COVID-19 protocols limited access to the lab but not the field. Zoom meetings that became common during the pandemic also facilitated meetings with group members worldwide, Kariyat said.

Tayal, listed as a co-author of the study, is pursuing his entomology doctorate at Clemson University. Kariyat expects the study could open many opportunities for Tayal and provide reams of data for scientists now and in the future.

Prior to this study, Kariyat authored or co-authored 68 published research papers. Although he was a smaller piece of the puzzle on the study published in Science, Kariyat said this one has attracted the most attention from colleagues across the country.

“We think this is going to make a splash in the field and will be cited a lot when they work on this,” Kariyat said of the study. “It opens a window of possibilities for anyone, anywhere, to look at the data and start their own questions and answers. All of the raw data can be requested through the Herbivory Variability Network.”

Kariyat has already begun a spin-off study with Alejandro Vasquez Marcano, a crop entomology Ph.D. student with the Arkansas Agricultural Experiment Station, which is the research arm of the University of Arkansas System Division of Agriculture. This new research evaluates insect herbivory damage to plants, including flowers, fruits, and seeds, during the reproductive stage.

How to use it

With the information gathered from the study, Kariyat said researchers can build collaborations and perform comparison studies on a wide range of plant species and their relatives to understand better how much variation in herbivory there is on those species.

For example, he said, with the information gathered they can see how much variation on herbivory there is on many plants in question and get in touch with people who worked on similar studies. Some examples of questions crop entomologists would ask include: “How much do insects feed on a particular plant? And is there more feeding in the early or late season? Then, Kariyat said, they can question if the behavior is associated with global warming, climate change, or invasive species.

Kariyat mentioned the spotted lanternfly as an invasive species that has established itself in the Northeast United States and is one of growing interest to entomologists because they feed on a wide range of fruit, ornamental and woody trees.

“One thing we really want to do is be proactive,” Kariyat said of invasive species. “Once an insect population is established, then there is no eradication. It is just management. But if we know it will come here, we can devise methods to restrict movement and reduce impact or incidence.”

Kariyat also works with the Cooperative Extension Service, the outreach arm of the Division of Agriculture, and teaches courses through the Dale Bumpers College of Agricultural, Food and Life Sciences.

​To learn more about Division of Agriculture research, visit the Arkansas Agricultural Experiment Station website: https://aaes.uada.edu. Follow us on 𝕏 at @ArkAgResearch and Instagram at @ArkAgResearch. To learn about Extension Programs in Arkansas, contact your local Cooperative Extension Service agent or visit https://uaex.uada.edu/. Follow us on 𝕏 at @AR_Extension. To learn more about the Division of Agriculture, visit https://uada.edu/. Follow us on 𝕏 at @AgInArk.

About the Division of Agriculture

The University of Arkansas System Division of Agriculture’s mission is to strengthen agriculture, communities, and families by connecting trusted research to the adoption of best practices. Through the Agricultural Experiment Station and the Cooperative Extension Service, the Division of Agriculture conducts research and extension work within the nation’s historic land grant education system.

The Division of Agriculture is one of 20 entities within the University of Arkansas System. It has offices in all 75 counties in Arkansas and faculty on five system campuses.

The University of Arkansas System Division of Agriculture offers all its Extension and Research programs and services without regard to race, color, sex, gender identity, sexual orientation, national origin, religion, age, disability, marital or veteran status, genetic information, or any other legally protected status, and is an Affirmative Action/Equal Opportunity Employer.

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JOURNAL

Science

DOI

10.1126/science.adh8830 

ARTICLE TITLE

Plant size, latitude, and phylogeny explain within-population variability in herbivory

 

New insights into Zebra mussel attachment fibers offer potential solutions to combat invasive species, develop sustainable materials

Peer-Reviewed Publication

MCGILL UNIVERSITY

A recent study from researchers in Canada and Germany has revealed that an unlikely event, occurring over 12 million years ago played an important role in shaping one of Canada’s most damaging invasive species.

Zebra and quagga mussels, belonging to the Dreissenid family, are widespread freshwater invasive species throughout North America that present a significant danger to native ecosystems by competing for resources. Using a fibrous anchor called a byssus, Dreissenid mussels contribute to biofouling on surfaces and obstruct intake structures in power stations and water treatment plants.

“This new study, which looks into the way these mussels stick to surfaces, may help improve strategies against biofouling, a problem causing millions in damages in Canada alone” shares co-author and lead McGill Professor, Matthew Harrington.

Surprisingly, researchers discovered that a previously undocumented event contributed to Dreissenid mussel's resilience as a species. University of Göttingen Professor and co-author Daniel J. Jackson explains, "More than 12 million years ago, it is likely that a single bacterium transferred genetic material into a single mussel endowing its descendants with the ability to make these fibers. Given their crucial role in mussel attachment in freshwater habitats, this horizontal gene transfer event supported the harmful global expansion of these mussels.”

This research, marking important progress in the understanding of invasive mussels and their attachment mechanisms, could offer potential solutions to mitigate their environmental and economic impact in Canada.

The study also sheds light on how mussel fibres could inspire the development of sustainable materials.

Sustainable materials inspired by mussel biology

“This research not only advances our understanding of mussel evolution and biofouling, but also presents an exciting opportunity for the development of novel materials,” said Harrington who is also co-director of McGill Institute of Advanced Materials. "Dreissenid byssus fibers, which resemble spider silk structurally, could inspire future development of tough polymer fibers, contributing to more durable and sustainable materials typically used in textiles and technical plastics.”

“We found that the building blocks of the fibres are massive coiled-coil proteins, the largest ever found,” Harrington said. These proteins, structurally similar to those found in human hair, were found to transform into silk-like beta crystallites through simple application of stretching forces during formation. This method of fiber fabrication is much simpler than spider silk formation, potentially offering an easier route toward biotechnological manufacture of sustainable fibers – an industry currently dominated by artificial spider silks.

About this study

“Invasive mussels fashion silk-like byssus via mechanical processing of massive horizontally acquired coiled coils” by Matthew Harrington et al., was published in PNAS.
https://www.pnas.org/doi/full/10.1073/pnas.2311901120

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JOURNAL

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2311901120 

ARTICLE TITLE

Invasive mussels fashion silk-like byssus via mechanical processing of massive horizontally acquired coiled coils

 

Immersive VR goggles for mice unlock new potential for brain science

Goggles enabled researchers to study responses to overhead threats for first time

Peer-Reviewed Publication

NORTHWESTERN UNIVERSITY

 

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THIS ILLUSTRATION SHOWS THE VR SETUP, WITH AN "OVERHEAD THREAT" PROJECTED INTO THE TOP FIELD OF VIEW. 

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CREDIT: DOM PINKE/NORTHWESTERN UNIVERSITY

Northwestern University researchers have developed new virtual reality (VR) goggles for mice.

Besides just being cute, these miniature goggles provide more immersive experiences for mice living in laboratory settings. By more faithfully simulating natural environments, the researchers can more accurately and precisely study the neural circuitry that underlies behavior.

Compared to current state-of-the-art systems, which simply surround mice with computer or projection screens, the new goggles provide a leap in advancement. In current systems, mice can still see the lab environment peeking out from behind the screens, and the screens’ flat nature cannot convey three-dimensional (3D) depth. In another disadvantage, researchers have been unable to easily mount screens above mice’s heads to simulate overhead threats, such as looming birds of prey.

The new VR goggles bypass all those issues. And, as VR grows in popularity, the goggles also could help researchers glean new insights into how the human brain adapts and reacts to repeated VR exposure — an area that is currently little understood.

The research will be published on Friday (Dec. 8) in the journal Neuron. It marks the first time researchers have used a VR system to simulate an overhead threat.

“For the past 15 years, we have been using VR systems for mice,” said Northwestern’s Daniel Dombeck, the study’s senior author. “So far, labs have been using big computer or projection screens to surround an animal. For humans, this is like watching a TV in your living room. You still see your couch and your walls. There are cues around you, telling you that you aren’t inside the scene. Now think about putting on VR goggles, like Oculus Rift, that take up your full vision. You don’t see anything but the projected scene, and a different scene is projected into each eye to create depth information. That’s been missing for mice.”

Dombeck is a professor of neurobiology at Northwestern’s Weinberg College of Arts and Sciences. His laboratory is a leader in developing VR-based systems and high-resolution, laser-based imaging systems for animal research.

The value of VR

Although researchers can observe animals in nature, it is incredibly difficult to image patterns of real-time brain activity while animals engage with the real world. To overcome this challenge, researchers have integrated VR into laboratory settings. In these experimental setups, an animal uses a treadmill to navigate scenes, such as a virtual maze, projected onto surrounding screens. 

By keeping the mouse in place on the treadmill — rather than allowing it to run through a natural environment or physical maze — neurobiologists can use tools to view and map the brain as the mouse traverses a virtual space. Ultimately, this helps researchers grasp general principles of how activated neural circuits encode information during various behaviors.

“VR basically reproduces real environments,” Dombeck said. “We’ve had a lot of success with this VR system, but it’s possible the animals aren’t as immersed as they would be in a real environment. It takes a lot of training just to get the mice to pay attention to the screens and ignore the lab around them.”

Introducing iMRSIV

With recent advances in hardware miniaturization, Dombeck and his team wondered if they could develop VR goggles to more faithfully replicate a real environment. Using custom-designed lenses and miniature organic light-emitting diode (OLED) displays, they created compact goggles.

Called Miniature Rodent Stereo Illumination VR (iMRSIV), the system comprises two lenses and two screens — one for each side of the head to separately illuminate each eye for 3D vision. This provides each eye with a 180-degree field-of-view that fully immerses the mouse and excludes the surrounding environment.

Unlike VR goggles for a human, the iMRSIV (pronounced “immersive”) system does not wrap around the mouse’s head. Instead, the goggles are attached to the experimental setup and closely perch directly in front of the mouse’s face. Because the mouse runs in place on a treadmill, the goggles still cover the mouse’s field of view.

“We designed and built a custom holder for the goggles,” said John Issa, a postdoctoral fellow in Dombeck’s laboratory and study co-first author. “The whole optical display — the screens and the lenses — go all the way around the mouse.”

Reduced training times

By mapping the mice’s brains, Dombeck and his team found that the brains of goggle-wearing mice were activated in very similar ways as in freely moving animals. And, in side-by-side comparisons, the researchers noticed that goggle-wearing mice engaged with the scene much more quickly than mice with traditional VR systems.

“We went through the same kind of training paradigms that we have done in the past, but mice with the goggles learned more quickly,” Dombeck said. “After the first session, they could already complete the task. They knew where to run and looked to the right places for rewards. We think they actually might not need as much training because they can engage with the environment in a more natural way.”

Simulating overhead threats for the first time

Next, the researchers used the goggles to simulate an overhead threat — something that had been previously impossible with current systems. Because hardware for imaging technology already sits above the mouse, there is nowhere to mount a computer screen. The sky above a mouse, however, is an area where animals often look for vital — sometimes life-or-death — information.

“The top of a mouse’s field of view is very sensitive to detect predators from above, like a bird,” said co-first author Dom Pinke, a research specialist in Dombeck’s lab. “It’s not a learned behavior; it’s an imprinted behavior. It’s wired inside the mouse’s brain.”

To create a looming threat, the researchers projected a dark, expanding disk into the top of the goggles — and the top of the mice’s fields of view. In experiments, mice — upon noticing the disk — either ran faster or froze. Both behaviors are common responses to overhead threats. Researchers were able to record neural activity to study these reactions in detail.

“In the future, we’d like to look at situations where the mouse isn’t prey but is the predator,” Issa said. “We could watch brain activity while it chases a fly, for example. That activity involves a lot of depth perception and estimating distances. Those are things that we can start to capture.”

Making neurobiology accessible

In addition to opening the door for more research, Dombeck hopes the goggles open the door to new researchers. Because the goggles are relatively inexpensive and require less intensive laboratory setups, he thinks they could make neurobiology research more accessible.

“Traditional VR systems are pretty complicated,” Dombeck said. “They’re expensive, and they’re big. They require a big lab with a lot of space. And, on top of that, if it takes a long time to train a mouse to do a task, that limits how many experiments you can do. We’re still working on improvements, but our goggles are small, relatively cheap and pretty user friendly as well. This could make VR technology more available to other labs.”

The study, “Full field-of-view virtual reality goggles for mice,” was supported by the National Institutes of Health (award number R01-MH101297), the National Science Foundation (award number ECCS-1835389), the Hartwell Foundation and the Brain and Behavior Research Foundation.

VR goggles (IMAGE)

NORTHWESTERN UNIVERSITY

A view through the new miniature VR goggles. 

CREDIT

Dom Pinke/Northwestern University

An artist's interpretation of a cartoon mouse wearing VR goggles.

CREDIT

@rita

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JOURNAL

Neuron

DOI

10.1016/j.neuron.2023.11.019 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Full field-of-view virtual reality goggles for mice

ARTICLE PUBLICATION DATE

8-Dec-2023

 

MIT engineers design a robotic replica of the heart’s right chamber

The realistic model could aid the development of better heart implants and shed light on understudied heart disorders.

Peer-Reviewed Publication

MASSACHUSETTS INSTITUTE OF TECHNOLOGY

MIT engineers have developed a robotic replica of the heart’s right ventricle, which mimics the beating and blood-pumping action of live hearts. 

The robo-ventricle combines real heart tissue with synthetic, balloon-like artificial muscles that enable scientists to control the ventricle’s contractions while observing how its natural valves and other intricate structures function. 

The artificial ventricle can be tuned to mimic healthy and diseased states. The team manipulated the model to simulate conditions of right ventricular dysfunction, including pulmonary hypertension and myocardial infarction. They also used the model to test cardiac devices. For instance, the team implanted a mechanical valve to repair a natural malfunctioning valve, then observed how the ventricle’s pumping changed in response. 

They say the new robotic right ventricle, or RRV, can be used as a realistic platform to study right ventricle disorders and test devices and therapies aimed at treating those disorders. 

“The right ventricle is particularly susceptible to dysfunction in intensive care unit settings, especially in patients on mechanical ventilation,” says Manisha Singh, a postdoc at MIT’s Institute for Medical Engineering and Science (IMES). “The RRV simulator can be used in the future to study the effects of mechanical ventilation on the right ventricle and to develop strategies to prevent right heart failure in these vulnerable patients.”

Singh and her colleagues report details of the new design in a paper appearing today in Nature Cardiovascular Research. Her co-authors include Associate Professor Ellen Roche, who is a core member of IMES and the associate head for research in the Department of Mechanical Engineering at MIT, along with Jean Bonnemain, Caglar Ozturk, Clara Park, Diego Quevedo-Moreno, Meagan Rowlett, and Yiling Fan of MIT, Brian Ayers of Massachusetts General Hospital,  Christopher Nguyen of Cleveland Clinic, and Mossab Saeed of Boston Children’s Hospital.

A ballet of beats

The right ventricle is one of the heart’s four chambers, along with the left ventricle and the left and right atria. Of the four chambers, the left ventricle is the heavy lifter, as its thick, cone-shaped musculature is built for pumping blood through the entire body. The right ventricle, Roche says, is a “ballerina” in comparison, as it handles a lighter though no-less-crucial load.

“The right ventricle pumps deoxygenated blood to the lungs, so it doesn’t have to pump as hard,” Roche notes. “It’s a thinner muscle, with more complex architecture and motion.”

This anatomical complexity has made it difficult for clinicians to accurately observe and assess right ventricle function in patients with heart disease. 

“Conventional tools often fail to capture the intricate mechanics and dynamics of the right ventricle, leading to potential misdiagnoses and inadequate treatment strategies,” Singh says. 

To improve understanding of the lesser-known chamber and speed the development of cardiac devices to treat its dysfunction, the team designed a realistic, functional model of the right ventricle that both captures its anatomical intricacies and reproduces its pumping function.  

The model includes real heart tissue, which the team chose to incorporate because it retains natural structures that are too complex to reproduce synthetically. 

“There are thin, tiny chordae and valve leaflets with different material properties that are all moving in concert with the ventricle’s muscle.Trying to cast or print these very delicate structures is quite challenging,” Roche explains. 

A heart’s shelf-life

In the new study, the team reports explanting a pig’s right ventricle, which they treated to carefully preserve its internal structures. They then fit a silicone wrapping around it, which acted as a soft, synthetic myocardium, or muscular lining. Within this lining, the team embedded several long, balloon-like tubes, which encircled the real heart tissue, in positions that the team determined through computational modeling to be optimal for reproducing the ventricle’s contractions. The researchers connected each tube to a control system, which they then set to inflate and deflate each tube at rates that mimicked the heart’s real rhythm and motion. 

To test its pumping ability, the team infused the model with a liquid similar in viscosity to blood. This particular liquid was also transparent, allowing the engineers to observe with an internal camera how internal valves and structures responded as the ventricle pumped liquid through. 

They found that the artificial ventricle’s pumping power and the function of its internal structures were similar to what they previously observed in live, healthy animals, demonstrating that the model can realistically simulate the right ventricle’s action and anatomy. The researchers could also tune the frequency and power of the pumping tubes to mimic various cardiac conditions, such as irregular heartbeats, muscle weakening, and hypertension. 

“We’re reanimating the heart, in some sense, and in a way that we can study and potentially treat its dysfunction,” Roche says.

To show that the artificial ventricle can be used to test cardiac devices, the team surgically implanted ring-like medical devices of various sizes to repair the chamber’s tricuspid valve — a leafy, one-way valve that lets blood into the right ventricle. When this valve is leaky, or physically compromised, it can cause right heart failure or atrial fibrillation, and leads to symptoms such as reduced exercise capacity, swelling of the legs and abdomen, and liver enlargement

The researchers surgically manipulated the robo-ventricle’s valve to simulate this condition, then either replaced it by implanting a mechanical valve or repaired it using ring-like devices of different sizes. They observed which device improved the ventricle’s fluid flow as it continued to pump. 

“With its ability to accurately replicate tricuspid valve dysfunction, the RRV serves as an ideal training ground for surgeons and interventional cardiologists,” Singh says. “They can practice new surgical techniques for repairing or replacing the tricuspid valve on our model before performing them on actual patients.”

Currently, the RRV can simulate realistic function over a few months. The team is working to extend that performance and enable the model to run continuously for longer stretches. They are also working with designers of implantable devices to test their prototypes on the artificial ventricle and possibly speed their path to patients. And looking far in the future, Roche plans to pair the RRV with a similar artificial, functional model of the left ventricle, which the group is currently fine-tuning.

“We envision pairing this with the left ventricle to make a fully tunable, artificial heart, that could potentially function in people,” Roche says. “We’re quite a while off, but that’s the overarching vision.”

This research was supported in part by the National Science Foundation.

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Written by Jennifer Chu, MIT News

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JOURNAL

Nature Cardiovascular Research

DOI

10.1038/s44161-023-00387-8 

ARTICLE TITLE

"Robotic Right Ventricle is a Biohybrid Platform that Simulates Right Ventricular function in (patho)physiological conditions and intervention”

 WAIT, WHAT?!

New genes can arise from nothing

Peer-Reviewed Publication

UNIVERSITY OF HELSINKI

 

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RESEARCHERS STUDIED AN ERROR MECHANISM IN DNA REPLICATION, AND NOTICED THAT SOME ERRORS CREATE PALINDROMES THAT CAN FOLD INTO HAIRPIN STRUCTURES.

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CREDIT: ARI LÖYTYNOJA

The complexity of living organisms is encoded within their genes, but where do these genes come from? Researchers at the University of Helsinki resolved outstanding questions around the origin of small regulatory genes, and described a mechanism that creates their DNA palindromes. Under suitable circumstances, these palindromes evolve into microRNA genes.

The human genome contains ca. 20,000 genes that are used for the construction of proteins. Actions of these classical genes are coordinated by thousands of regulatory genes, the smallest of which encode microRNA molecules that are 22 base pairs in length. While the number of genes remains relatively constant, occasionally new genes emerge during evolution. Similar to the genesis of biological life, the origin of new genes has continued to fascinate scientists.

All RNA molecules require palindromic runs of bases that lock the molecule into its functional conformation. Importantly, the chances of random base mutations gradually forming such palindromic runs are extremely small, even for the simple microRNA genes. Hence, the origin of these palindromic sequences has puzzled researchers. Experts at the Institute of Biotechnology, University of Helsinki, Finland resolved this mystery, describing a mechanism that can instantaneously generate complete DNA palindromes and thus create new microRNA genes from previously noncoding DNA sequences.

In a project funded by the Academy of Finland, researchers studied errors in DNA replication. Ari Löytynoja, the project leader, compares DNA replication to typing of text.

“DNA is copied one base at a time, and typically mutations are erroneous single bases, like mis-punches on a laptop keyboard. We studied a mechanism creating larger errors, like copy-pasting text from another context. We were especially interested in cases that copied the text backwards so that it creates a palindrome.”

Researchers recognised that DNA replication errors could sometimes be beneficial. They described these findings to Mikko Frilander, an expert in RNA biology. He immediately saw the connection to the structure of RNA molecules.

“In an RNA molecule, the bases of adjacent palindromes can pair and form structures resembling a hairpin. Such structures are crucial for the function of the RNA molecules,” he explains.

Researchers decided to focus on microRNA genes due to their simple structure: the genes are very short – just a few tens of bases – and they have to fold into a hairpin structure to function correctly.

A central insight was to model the gene history using a custom computer algorithm. According to postdoctoral researcher Heli Mönttinen, this enables the closest inspection of the origin of genes thus far.

“The whole genome of tens of primates and mammals is known. A comparison of their genomes reveals which species have the microRNA palindrome pair, and which lack it. With a detailed modelling of the history, we could see that whole palindromes are created by single mutation events,” says Mönttinen.

By focusing on humans and other primates, researchers in Helsinki demonstrated that the newly found mechanism can explain at least a quarter of the novel microRNA genes. As similar cases were found in other evolutionary lineages, the origin mechanism appears universal.

In principle, the rise of microRNA genes is so easy that novel genes could affect human health. Heli Mönttinen sees the significance of the work more broadly, for example in understanding the basic principles of biological life.

“The emergence of new genes from nothing has fascinated researchers. We now have an elegant model for the evolution of RNA genes,” she highlights.

Although the results are based on small regulatory genes, researchers believe that the findings can be generalised to other RNA genes and molecules. For example, by using the raw materials generated by the newly found mechanism, natural selection may create much more complex RNA structures and functions.

The study was published in PNAS.

A central insight was to model the gene history using information from related species. The modelling demonstrated that the palindromes of microRNA genes are generated by single mutation events.

CREDIT

Ari Löytynoja

JOURNAL

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2310752120 

ARTICLE TITLE

Generation of de novo miRNAs from template switching during DNA replication

 

What happens when the brain loses a hub? 

Rare experiment during brain surgery helps researchers better understand neural networks

Peer-Reviewed Publication

UNIVERSITY OF IOWA HEALTH CARE

A University of Iowa-led team of international neuroscientists have obtained the first direct recordings of the human brain in the minutes before and after a brain hub crucial for language meaning was surgically disconnected. The results reveal the importance of brain hubs in neural networks and the remarkable way in which the human brain attempts to compensate when a hub is lost, with immediacy not previously observed. 

Hubs are critical for connectivity 

Hubs are everywhere. The hub of a bicycle wheel, with spokes shooting out from the center, keeps the wheel from collapsing when the bicycle is ridden. Airport hubs connect cities across the world. And social hubs like coffee shops or online social networks are places people gather for interaction. 

The human brain has hubs, too – the intersection of many neuronal pathways that help coordinate brain activity required for complex functions like understanding and responding to speech. However, whether highly interconnected brain hubs are irreplaceable for certain brain functions has been controversial. By some accounts the brain, as an already highly interconnected neural network, can in principle immediately compensate for the loss of a hub, in the same way that traffic can be redirected around a blocked off city center.  

With a rare experimental opportunity, the UI neurosurgical and research teams led by Matthew Howard III, MD, professor and DEO of neurosurgery, and Christopher Petkov, PhD, professor and vice chair for research in neurosurgery, have achieved a breakthrough in understanding the necessity of a single hub. By obtaining evidence for what happens when a hub required for language meaning is lost, the researchers showed both the intrinsic importance of the hub as well as the remarkable and rapid ability of the brain to adapt and at least partially attempt to immediately compensate for its loss. The findings were reported recently in the journal Nature Communications.  

Evaluating the impact of losing a brain hub 

The study was conducted during surgical treatment of two patients with epilepsy. Both patients were undergoing procedures that required surgical removal of the anterior temporal lobe—a brain hub for language meaning—to allow the neurosurgeons access to a deeper brain area causing the patients’ debilitating epileptic seizures. Before this type of surgery, neurosurgery teams often ask the patients to conduct speech and language tasks in the operating room as the team uses implanted electrodes to record activity from parts of the brain close to and distant from the planned surgery area. These recordings help the clinical team effectively treat the seizures while limiting the impact of the surgery on the patient’s speech and language abilities.  

Typically, the recording electrodes are not needed after the surgical resection procedure and are removed. The innovation in this study was that the neurosurgery team was able to safely complete the procedure with the recording electrodes left in place or replaced to the same location after the procedure. This made it possible to obtain rare pre- and post-operative recordings allowing the researchers to evaluate signals from brain areas far away from the hub, including speech and language areas distant from the surgery site. Analysis of the change in responses to speech sounds before and after the loss of the hub revealed a rapid disruption of signaling and subsequent partial compensation of the broader brain network.  

“The rapid impact on the speech and language processing regions well removed from the surgical treatment site was surprising, but what was even more surprising was how the brain was working to compensate, albeit incompletely within this short timeframe,” says Petkov, who also holds an appointment at Newcastle University Medical School in the UK. 

The findings disprove theories challenging the necessity of specific brain hubs by showing that the hub was important to maintain normal brain processing in language. 

“Neurosurgical treatment and new technologies continue to improve the treatment options provided to patients,” says Howard, who also is a member of the Iowa Neuroscience Institute. “Research such as this underscores the importance of safely obtaining and comparing electrical recordings pre and post operatively, particularly when a brain hub might be affected.”  

According to the researchers, the observation on the nature of the immediate impact on a neural network and its rapid attempt to compensate provides evidence in support of a brain theory proposed by Professor Karl Friston at University College London, which posits that any self-organizing system at equilibrium works towards orderliness by minimizing its free energy, a resistance of the universal tendency towards disorder. These neurobiological results following human brain hub disconnection were consistent with several predictions of this and related neurobiological theories, showing how the brain works to try to regain order after the loss of one of its hubs.  

In addition to Petkov and Howard, the research team included researchers in the UI Departments of Neurosurgery, Radiology, and Psychological and Brain Sciences, as well as colleagues from Newcastle University, UCL, and University of Cambridge in the UK, and from Carnegie Mellon University, University of Wisconsin-Madison, and Gonzaga University in the United States. 

The research was funded in part by grants from National Institutes of Health, the Wellcome Trust. and the European Research Council. 

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JOURNAL

Nature Communications

DOI

10.1038/s41467-023-42088-7 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Immediate neural impact and incomplete compensation after semantic hub disconnection