Even as SARS-CoV-2 mutates, some human antibodies fight back

A 'cocktail' of human antibodies shows promise in fighting severe SARS-CoV-2 infections

Peer-Reviewed Publication

LA JOLLA INSTITUTE FOR IMMUNOLOGY

 

IMAGE: ANTIBODIES 2A10 (YELLOW SHADES), 1H2 (BLUE SHADES), AND 1C3 WERE ISOLATED FROM A VACCINATED RESEARCH VOLUNTEER. THE LJI TEAM FOUND THESE ANTIBODIES CAN NEUTRALIZE MANY SARS-COV-2 VARIANTS BY BINDING TO VULNERABLE SITES ON THE VIRAL STRUCTURE (GREY). IMAGE FROM THE SAPHIRE LAB, LA JOLLA INSTITUTE FOR IMMUNOLOGY view more 

CREDIT: SAPHIRE LAB, LA JOLLA INSTITUTE FOR IMMUNOLOGY

LA JOLLA, CA—An anonymous San Diego resident has become a fascinating example of how the human immune system fights SARS-CoV-2. In a new investigation, scientists from La Jolla Institute for Immunology (LJI) have shown how antibodies, collected from this clinical study volunteer, bind to the SARS-CoV-2 "Spike" protein to neutralize the virus.

Although studies have shown antibodies bound to Spike before, this new research reveals how the original Moderna SARS-CoV-2 vaccine could prompt the body to produce antibodies against the later Omicron variants of SARS-CoV-2. The researchers also capture highly detailed, 3D structures of three promising neutralizing antibodies bound to Spike. 

This important work shows exactly where Spike is vulnerable to human antibodies—and how future vaccines and antibody therapeutics might exploit these weaknesses. In fact, studies in mice suggest some of these antibodies may help prevent severe cases of COVID-19.

“To blunt the next pandemic and protect people from seasonal re-emergence of this one, we need antibodies of the broadest possible capacity—ones that are not escaped," says LJI President and CEO Erica Ollmann Saphire, Ph.D., senior author of the new Cell Reports study. “We found those in a vaccinated San Diegan.”

"Studying that person’s immune response in detail uncovered antibodies that are still effective against many Omicron variants," adds LJI Instructor Kathryn Hastie, Ph.D., co-leader of the study and Director of the LJI Antibody Discovery Center. "We now have to figure out how to boost these antibodies that we want over others that are less effective."

Taking on viral variants

Throughout the pandemic, scientists at LJI have gathered blood samples here in San Diego, and from labs around the world, with the goal of understanding the roles of different immune cells in fighting SARS-CoV-2. [Learn more about LJI leadership of the Coronavirus Immunotherapy Consortium (CoVIC)]

Antibodies are among the immune system's most elite fighters. These molecules are made by B cells and each antibody has a specific structure meant to bind to a specific target on a pathogen. It's as if B cells see a bullseye on a pathogen and then go to work making their arrows.

For the new study, the antibodies came from a clinical studies volunteer who received two doses of the Moderna SARS-CoV-2 vaccine. The Moderna vaccine works by prompting the body to make the Spike protein—glimpses of the viral bullseye—so it can begin work on its antibodies and other weaponry against the real virus. 

The samples from the study volunteer were collected in early 2021—before the emergence of Omicron. That means any antibodies made by the volunteer were a result of vaccination, rather than exposure to Omicron.

The SARS-CoV-2 Omicron variant emerged in late 2021 and spread quickly. Omicron stood out from other variants because it contained mutations that helped it evade immune cell protection. Many antibodies designed to fight earlier SARS-CoV-2 variants couldn't hit their mark on Omicron. 

Finding winning antibodies

Luckily, not everyone produces the same types of antibodies. In fact, the composition of virus-fighting cells and antibodies varies wildly in each person. For the new study, the researchers began with a pool of antibodies from the San Diego volunteer. Like many people who received the first two Moderna vaccine shots, this individual produced a robust pool of antibodies capable of neutralizing the ancestral D614G variant of SARS-CoV-2.

As new viral variants of concern emerged, the researchers tested this pool to see how many antibodies could still bind to the mutated virus. 

”We found that this pool of antibodies could also neutralize other variants, such as Delta and Omicron,” says Hastie.

They found that the subject maintained moderate to high levels of antibodies against Beta, Delta and Omicron lineages BA.1, BA.1.1 and BA.2. Among these surviving antibodies, the researchers uncovered five antibodies that actually decreased the infectivity of BA.1 by more than 85 percent.

The researchers then took these five remaining antibodies through another battery of tests. One antibody, called 1C3, showed promise in blocking part of the infection process (when the virus's receptor binding domain interacts with human protein ACE2) but only against BA.1 and BA.2 lineages. Another antibody, 1H2, could also neutralize some Omicron lineages, but did so in a different way than 1C3. Meanwhile, antibody 2A10 was reactive to all SARS-CoV-2 Omicron lineages tested, including those that are most common now: XBB and BQ1. 

Mapping out antibody targets

The scientists went on to map out these vulnerabilities on Spike using a high-resolution imaging technique called cryo-electron microscopy. "We were really interested to see how these antibodies recognize the Spike protein and structure," says LJI Postdoctoral Fellow Xiaoying Yu, who co-led the new study with Hastie. "This structural work lets us see exactly how the antibodies interact with the protein and how they can neutralize the virus."

The imaging work revealed that two of the promising antibodies bind to the SARS-CoV-2 Spike by latching onto two parts of the protein at once. By capturing Spike in a sort of hug of death, these antibodies lock the viral structure in place to halt infection. This finding is consistent with another recent Cell Reports study from the Saphire Lab showing the importance of bivalent antibodies against SARS-CoV-2 variants.

Could these three promising antibodies be recreated in an antibody therapeutic to treat COVID-19? The results from a mouse model are encouraging. The LJI team found that each antibody by itself could indeed reduce the viral load in the lungs in mice infected with SARS CoV-2 BA.1 and BA.2. 

Going forward, the researchers plan to run more human antibodies through this same pipeline at LJI—from antibody isolation to screening, structural analysis, and animal model experiments. "We can carry out the entire pipeline of antibody discovery now," says Yu. "This research will help us combat the variants we have right now and give us targets for future vaccine development and therapeutics."

Additional authors of the study, "Potent, omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before omicron emergence," were Fernanda A. Sosa Batiz, Dawid Zyla, Stephanie S. Harkins, Chitra Hariharan, Hal Wasserman, Michelle A. Zandonatti, Robyn Miller, Erin Maule, Kenneth Kim, Kristen Valentine, and Sujan Shresta.

This research was supported by the National Institutes of Health (grant NIH U19 AI142790-02S1), the GHR Foundation, the Swiss National Science Foundation Early Postdoc Mobility Fellowship (P2EZP3_195680), a Postdoc Mobility Fellowship (P500PB_210992), and an American Association of Immunologists Career Reentry Fellowship.

DOI: 10.1016/j.celrep.2023.112421

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JOURNAL

Cell Reports

DOI

10.1016/j.celrep.2023.112421 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Potent Omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before Omicron emergence

COI STATEMENT

K.M.H, S.S.H., and E.O.S. have a patent pending for the antibodies described in this study.

Transparent labeling of training data may boost trust in artificial intelligence

Peer-Reviewed Publication

PENN STATE

UNIVERSITY PARK, Pa. — Showing users that visual data fed into artificial intelligence (AI) systems was labeled correctly might make people trust AI more, according to researchers. The findings also may pave the way to help scientists better measure the connection between labeling credibility, AI performance, and trust, the team added.

In a study, the researchers found that high-quality labeling of images led people to perceive that the training data was credible and they trusted the AI system more. However, when the system shows other signs of being biased, some aspects of their trust go down while others remain at a high level.

For AI systems to learn, they first must be trained using information that is often labeled by humans. However, most users never see how the data is labeled, leading to doubts about the accuracy and bias of those labels, according to S. Shyam Sundar, James P. Jimirro Professor of Media Effects in the Donald P. Bellisario College of Communications and co-director of the Media Effects Research Laboratory at Penn State.

“When we talk about trusting AI systems, we are talking about trusting the performance of AI and the AI's ability to reflect reality and truth,” said Sundar, who also is an affiliate of Penn State’s Institute for Computational and Data Sciences. “That can happen if and only if the AI has been trained on a good sample of data. Ultimately, a lot of the concern about trust in AI should really be a concern about us trusting the training data upon which that AI is built. Yet, it has been a challenge to convey the quality of training data to laypersons.”

According to the researchers, one way to convey that trustworthiness is to give users a glimpse of the labeling data.

“Often, the labeling process is not revealed to users, so we wondered what would happen if we disclosed training data information, especially accuracy of labeling,” said Chris (Cheng) Chen, assistant professor in communication and design, Elon University, and first author of the study. “We wanted to see whether that would shape people's perception of training data credibility and further influence their trust in the AI system.”

The researchers recruited a total of 430 participants for the online study. The participants were asked to interact with a prototype Emotion Reader AI website, which was introduced as a system designed to detect facial expressions in social media images. Researchers informed participants that the AI system had been trained on a dataset of almost 10,000 labeled facial images, with each image tagged as one of seven emotions — joy, sadness, anger, fear, surprise, disgust or neutral. The participants were also informed that more than 500 people had participated in data labeling for the dataset. However, the researchers had manipulated the labeling, so in one condition the labels accurately described the emotions, while in the other, half of the facial images were mislabeled.

To study AI system performance, researchers randomly assigned participants to one of three experimental conditions: no performance, biased performance and unbiased performance. In the biased and unbiased conditions, participants were shown examples of AI performance involving the classification of emotions expressed by two Black and two white individuals. In the biased performance condition, the AI system classified all images of white individuals with 100% accuracy and all images of Black individuals with 0% accuracy, demonstrating a strong racial bias in AI performance.

According to the researchers, the participants’ trust fell when they perceived that the system’s performance was biased. However, their emotional connection with the system and desire to use it in the future did not go down after seeing a biased performance.

Training data credibility

The researchers coined the term “training data credibility” to describe whether a user perceives training data as credible, trustworthy, reliable and dependable.

They suggest that developers and designers could measure trust in AI by creating new ways to assess user perception of training data credibility, such as letting users review a sample of the labeled data.

“It’s also ethically important for companies to show the users how the training data has been labeled, so that they can determine if it’s high-quality or low-quality labeling,” said Chen.

Sundar added that AI developers would need to devise creative ways to share training data information with users, but without burdening or misleading them.

“Companies are always concerned about creating an easy flow for the user, so that users continue to engage,” said Sundar, who also is director of the Penn State Center for Socially Responsible Artificial Intelligence, or CSRAI. “In calling for seamless ways to show labeling quality, we want interface designs that inform users and make them think rather than persuade them to blindly trust the AI system.”

The researchers presented their findings today (April 24) at the ACM CHI Conference on Human Factors in Computing Systems, and reported them in its proceedings, the premier publication for research on human-computer interaction.

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DOI

10.1145/3544548.3580805 

ARTICLE TITLE

Is this AI trained on Credible Data? The Effects of Labeling Quality and Performance Bias on User Trust

ARTICLE PUBLICATION DATE

19-Apr-2023

Gene that confers seed tolerance to salinity identified

Biotechnology could help farmers deal with inhospitable soils

Peer-Reviewed Publication

INSTITUTO GULBENKIAN DE CIENCIA

 

IMAGE: EXPRESSION OF THE SCL30A GENE (IN BLUE) IN DEVELOPING ARABIDOPSIS THALIANA SEEDS. view more 

CREDIT: © INÊS BARBOSA, IGC

Seeds only germinate when a series of internal and environmental needs are met. Otherwise, they get stuck in a state of dormancy. Researchers from the Instituto Gulbenkian de Ciência (IGC) led by Paula Duque just revealed a mechanism that allows plants to integrate environmental signals and decide whether they should initiate development. SCL30a is a gene behind this decision system.

The group’s interest in this gene came from gene expression studies in Arabidopsis thaliana, a model plant belonging to the cabbage and turnip family. The increased expression of SCL30a during germination made them suspect that it could define morphological and functional characteristics of seeds in response to stress.

To address this hypothesis, the researchers altered the expression of the SCL30a protein and assessed the seeds’ characteristics in a variety of settings. When they treated seeds lacking this protein with salt, these germinated less and later than normal seeds. By contrast, seeds overexpressing the protein germinated twice as fast, especially under adverse conditions.

The analyses the researchers carried out revealed that these outcomes stemmed from the inhibition of signals sent by abscisic acid (ABA), a hormone that restrains germination in stress conditions. By controlling the expression of genes induced by this hormone, the SCL30a protein reduces the plant’s sensitivity to high salinity, allowing seeds to germinate. “These findings are in line with accumulating evidence showing that regulation of gene expression by this class of proteins is crucial to control plant stress responses”, Tom Laloum, a postdoctoral researcher at the IGC and one of the first authors of the study, explains. The researchers also showed that this protein controls other aspects of plant development mediated by ABA, including seed size, which increased when SCL30a was overexpressed. 

The principal investigator Paula Duque explains that these genetic functions “could be translated into crop species, resulting in larger seeds that germinate better under adverse environments”. This could solve limitations on crop productivity due to soil salinization, a problem that is expanding in different areas of the world, including Portugal.

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JOURNAL

Plant Cell & Environment

DOI

10.1111/pce.14593 

ARTICLE TITLE

The SCL30a SR protein regulates ABA-dependent seed traits and germination under stress

ARTICLE PUBLICATION DATE

25-Apr-2023

Deep impact: New diving suit could increase undersea range of Navy divers

Business Announcement

OFFICE OF NAVAL RESEARCH

 

IMAGE: A U.S. NAVY DIVER (CENTER) TESTS THE OFFICE OF NAVAL RESEARCH-SPONSORED DEEP SEA EXPEDITIONARY WITH NO DECOMPRESSION (DSEND) SYSTEM AT THE NAVY EXPERIMENTAL DIVING UNIT IN FLORIDA. DSEND INCLUDES A HARDENED YET LIGHTWEIGHT ATMOSPHERIC DIVE SUIT FEATURING ROTATING, DETACHABLE JOINTS ALLOWING FOR GREATER DEXTERITY, FLEXIBILITY AND MANEUVERABILITY. view more 

CREDIT: (U.S. NAVY PHOTO BY RONNIE NEWSOME)

ARLINGTON, Va.—The lights above the water’s surface cast a ghostly glow on the bottom of the sprawling tank, as a U.S. Navy diver deftly swam through a sunken aircraft fuselage.

Wearing a special diving suit designed to protect against the crushing pressure of ocean depths, the diver found her target — a mannequin representing a human body. The exercise was part of a simulated crash recovery mission to test the capabilities of the Deep Sea Expeditionary with No Decompression (DSEND) system, which includes a hardened yet lightweight atmospheric dive suit featuring rotating, detachable joints allowing for greater dexterity, flexibility and maneuverability.

Sponsored by the Office of Naval Research (ONR) — in partnership with Naval Sea Systems Command (NAVSEA), Naval Undersea Warfare Center (NUWC) and Naval Surface Warfare Center (NSWC) Panama City — DSEND recently underwent demonstrations at NSWC Carderock Division in Maryland and at the Navy Experimental Diving Unit in Florida.

“DSEND is truly a game-changer because it’s a self-contained environment that keeps internal pressure steady, as a diver descends to depths with increasing external pressure,” said Dr. Sandra Chapman, a program officer in ONR’s Warfighter Performance Department. “It increases diver safety, allows them to expand the operational envelope and would eliminate lengthy decompression times.”

Navy diving missions include deep ocean salvage of vessels and aircraft, underwater rescues, explosive ordnance disposal, ship hull maintenance and recovery of sunken equipment.

The deeper divers descend, however, the greater the danger from increasing water pressure. In deep-water situations, Navy divers use a saturation system, or diving bell, that is pressurized with gas so the pressure inside the bell matches outside pressure.

The drawback is that, when returning to the surface, divers must ascend slowly and stop at intervals so they don’t suffer decompression sickness. This is a potentially lethal condition in which the inert gas dissolved in the blood and tissues by high pressure forms bubbles as pressure decreases. Although the time-consuming ascent safeguards divers, it limits the amount of hours they can spend at a site.

DSEND’s one-atmosphere environment presents a solution to this challenge. Equipped with a self-contained life support system, the DSEND suit encloses a diver in a stabilized pressure cocoon during the entire dive. The diver can work at great depths for many hours and ascend without the drawn-out process of decompression.

“Because DSEND maintains one consistent pressure atmosphere, the diver is never exposed to the negative physiological effects associated with deep diving, such as decompression sickness, cold and wet exposure,” said Paul McMurtrie, NAVSEA diving systems program manager. “A diver can work for long periods of time in deep water and rapidly return to the surface.”

Although constructed from hard, durable material, DSEND is lightweight and enables users to swim and walk on the bottom easily. This improves on atmospheric diving suits traditionally used by the Navy in the past, which were more rigid and powered by attached thrusters, making it difficult to move around.

The suit also is easier to don and remove, and can be adjusted to diver size. In addition, DSEND features joints, grippers and hand attachments made from novel materials that are strong, lightweight and mirror the natural movements of human joints, reducing diver fatigue.

“DSEND will allow divers to conduct harder missions by going deeper, executing faster and operating longer,” said Tom Hansen, a research engineer at NUWC Division Newport, “all while being protected by a sensorized suit of armor. It feels like we’re developing the futuristic smart armor you see in movies.”

During the Maryland and Florida demos, DSEND divers completed various exercises, including pulling a mannequin from an aircraft fuselage, rigging a piece of wreckage for salvage and traversing makeshift tunnels representing sunken vessels.

Within the next year, Chapman hopes to see DSEND undergo additional development, including at-sea demos in realistic operating environments.

Navy Master Chief Jericho Diego, a master diver and the senior enlisted leader at NUWC Division Keyport, said, “This system has the potential to be very advantageous to Navy divers. Eliminating the need for decompression increases safety, and the more flexible arm attachments allow us to retrieve targets and do our jobs more effectively.”

Climate change is already impacting stream flows across the US

DRI researchers examined more than 500 watersheds across the country and found that increased winter temperatures are driving more extreme fluctuations in streamflow

Peer-Reviewed Publication

DESERT RESEARCH INSTITUTE

Climate change is here, and scientists continue to discover new ways that the world around us is changing. In a new study published in the May issue of the Journal of Hydrology, DRI researchers show that altered weather patterns are impacting stream flows across the country, with implications for flooding, drought, and ecosystems.

Led by Abhinav Gupta, Ph.D., a Maki postdoctoral fellow at DRI, the research examined how day to day variations in streamflow changed in more than 500 watersheds in the U.S. between 1980 and 2013. They found that increased winter temperatures have driven the changes, with impacts varying due to local climate and amongst snow and rain-dominated watersheds. This information is important, the researchers say, for helping water managers adapt to climate change’s impacts.

“We wanted to understand how climate change has impacted the hydrological balance across the U.S. based on the observed data,” Gupta says. “Once we understand how climate change has impacted stream flows in the recent past, we can figure out what kind of changes we might see in the future.”

Streams receive water from a variety of sources, including fast, direct input from rainfall, and groundwater that gradually seeps through springs and soil. To understand how climate change is altering stream flows over time, the authors needed to differentiate between normal variability, like seasonal changes, and longer-term trends. To do this, they broke down stream inputs into events that occur at different timescales, like hourly and daily (rainfall), vs monthly and annual (groundwater). Then, they looked at trends for each timescale to see how they changed over time.

“Once we understand how these trends are evolving, we can make educated guesses about what exactly is changing in the watershed – whether it is snowmelt, surface runoff, base flow, or one of many other factors,” says Gupta. “Without studying streamflow in this way (what is called streamflow statistical structure) it's not possible to study all of these components together, at once.”

Their results show that snow-dominated watersheds across the country are receiving more precipitation as rain than historically. This means that streams now have more water coming in short bursts from rainstorms, rather than the slow trickle of melting snow. The shift to short-term stream inputs could also be attributed to faster snowmelt rates due to higher temperatures, the authors say.

“In the past, streamflow changed very slowly over time,” Gupta says. “But now, because of climate change, we have faster fluctuations in streamflow, which means that we can have a lot of water in a very small amount of time and then we can have no water for a long period of time. These extreme swings are occurring more and more.”

Although the researchers found increased temperatures and changes in rainfall in all watersheds, differences in local climate dictate how this influences streamflow. In humid locales like Florida and the Pacific Northwest, storm inputs decreased, as higher temperatures caused more evaporation, leading the soil to absorb more rainwater. In the Great Plains and Mississippi Valley, contributions to streams from slow, long-term inputs like groundwater are very low, likely also due to high evaporation rates. Arid watersheds saw an increase in the number of days each year without rainfall over the study period, as well as a significant increase in winter temperatures, making streamflow more sporadic.

The study didn’t examine other variables that could impact how water moves through watersheds, like changes in forest cover that impact the amount of water used by plants, or soil type, which affects how quickly rainfall permeates into groundwater. Because each watershed is unique, with its own recipe of soil type, climate, and forest cover, “we cannot paint everything with the same brush,” Gupta says. “We need different strategies for different watersheds to adapt to changes in climate. Even within the same region, watershed impacts can vary.”

More research is needed, the study authors say, to understand what is driving changes in streamflow. If streams are increasingly dependent on groundwater, this could impact how water managers regulate groundwater pumping for human use. “That’s the kind of thing we need to know moving forward, in terms of how we manage our water resources,” says Sean McKenna, study co-author and Director of Hydrologic Sciences at DRI. “Can we pump more groundwater, or do we need to be more careful because if we do, we could lose streamflow?”

Gupta says that he plans to build on this research. “Based on this study, we have been able to identify watersheds across the U.S. that have changed. Now that we know which watersheds in our dataset have been affected by climate change, we can look at the future changes in those watersheds.”

 

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More information: Changes in streamflow statistical structure across the United States due to recent climate change is available from the Journal of Hydrology. DOI: https://doi.org/10.1016/j.jhydrol.2023.129474

Study authors include: DRI researchers Abhinav Gupta, Rosemary Carroll, and Sean McKenna

 

About DRI
The Desert Research Institute (DRI) is a recognized world leader in basic and applied environmental research. Committed to scientific excellence and integrity, DRI faculty, students who work alongside them, and staff have developed scientific knowledge and innovative technologies in research projects around the globe. Since 1959, DRI’s research has advanced scientific knowledge on topics ranging from humans’ impact on the environment to the environment’s impact on humans. DRI’s impactful science and inspiring solutions support Nevada’s diverse economy, provide science-based educational opportunities, and inform policymakers, business leaders, and community members. With campuses in Las Vegas and Reno, DRI serves as the non-profit research arm of the Nevada System of Higher Education. For more information, please visit www.dri.edu.

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JOURNAL

Journal of Hydrology

DOI

10.1016/j.jhydrol.2023.129474 

METHOD OF RESEARCH

Observational study

ARTICLE TITLE

Changes in streamflow statistical structure across the United States due to recent climate change

Mixing theory, observation to envision warmer world

Peer-Reviewed Publication

MICHIGAN STATE UNIVERSITY

 

IMAGE: MICHIGAN STATE UNIVERSITY PHD GRAD LAURA TWARDOCHLEB INVESTIGATES THE EFFECTS OF WARMING ON FRESHWATER BIODIVERSITY. view more 

CREDIT: PHOEBE ZARNETSKE, MICHIGAN STATE UNIVERSITY

Climate changes are conjuring a whirlwind ride that seems to present some creatures opportunities to thrive. Scientists scripting supercharged scenarios caution the difference between seasonal coping and long-term adaption is vast – and tricky to predict.

Michigan State University biologists have studied damselflies – which resemble dragonflies and are abundant as both predator and prey in wetlands – to understand what happens throughout their lifecycle from nymph to winged insect, along with what they eat when summers grow warmer and longer.

Their work in this week’s Proceedings of the Royal Society B has a twist – combining seasons of observational and experimental work in the field and lab with input from a theoretical ecologist, a mathematician by training with supersized modeling creds.

The results: A more realistic look at what a hot summer can bring to a nearby pond, and new respect for the blinding speed global warming is bringing.

“We are seeing the pace of climate change is much more rapid than organisms have endured in their evolutionary experience,” said co-author Phoebe Zarnetske, an associate professor of integrative biology

PI of the Spatial and Community Ecology (SpaCE) Lab and director, IBEEM. “That rapid pace is going to be even more of an issue with the increase in extreme events like heat waves.”

The work in “Life-history responses to temperature and seasonality mediate ectotherm consumer–resource dynamics under climate warming” finds that inserting the right level of data gleaned from field experiences, specifically the effects of seasonal changes in temperature on consumer lifecycles, creates a more robust predator-prey simulation model. The work differs from the findings of similar models with less biological realism that predicted warming trends would doom predators. They see Michigan damselflies surviving climate warming by shifting into a lifecycle similar to their southern relatives – squeaking out two lifecycles in a season rather than one.

The work developed from first author Laura Twardochleb’s work as a PhD student in Zarnetske’s lab. She had spent time observing damselflies’ one-year lifecycle in Michigan. They emerge as adults from ponds in the spring. They mate, reproduce and the juveniles grow over a year in the pond by eating zooplankton. They make good study subjects, she said, because they thrive both outside and in the laboratory.

Twardochleb, now with the California State Water Resources Control Board, was part of MSU’s Ecology, Evolution, and Behavior Program and as a part of that took a class by Chris Klausmeier, MSU Foundation Professor of Plant Biology and Integrative Biology.

She saw that early models projecting how warming climates would affect ectothermic predators were significantly simpler than the nature she was observing. For one thing, the models didn’t allow for the north’s change of seasons. The models also weren’t keeping track of a predator’s size and growth rate and changes in their lifecycle with warming.

Meanwhile, Klausmeier, a theoretical ecologist, was recognizing the special sauce an experimentalist brings when creating mathematical models that take assumptions about how organisms behave, grow, birth, die.

“I can make up any model I want unconstrained by reality,” Klausmeier said. “But that’s a little dangerous because of course you want something related to the real world. When you join with an experimentalist you can bring not just the experimental results and parameters, but also bring the deep natural history and knowledge to the system to know the key variables and constraints.”

The work, factoring in a warmer, but still seasonal climate shows how the damselflies can grow and breed more quickly. Creating a model that only allowed the virtual damselflies to live a one-year lifecycle in a warmer world, they burned out and died. Extinction was on the horizon.

But allow the bugs the option of bringing two generations into a season, and thriving was a possibility. “A lot of models said [predators] were going to starve,” Twardochleb said. “That’s what’s exciting – that we can make models more realistic.”

Twardochleb said the work is good groundwork to understand how other species will respond to a warmer world, particularly species like mosquitoes which are both nuisances and potentially carry diseases.

Zarnetske added that the continual challenge will be beyond the idea that different species will be adapting to a new world. Climate change is outpacing that kind of evolution in an unprecedented way. And the weather extremes – heat waves, droughts, floods – are a whole variable.

“That’s our next step,” Zarnetske said. “Unpredictability is hard.”

The work was supported by the National Science Foundation, NASA, the MSU Department of Fisheries and Wildlife and Environmental Science and Policy Program, Kellogg Biological Station and the Society for Freshwater Science.

Damselflies are iconic species whose lifecycles reflect changes to a warming world.

CREDIT

Laura Twardochleb, Michigan State University

JOURNAL

Proceedings of the Royal Society B Biological Sciences

ARTICLE TITLE

Life-history responses to temperature and seasonality mediate ectotherm consumer–resource dynamics under climate warming

ARTICLE PUBLICATION DATE

25-Apr-2023

Almost half of people with concussion still show symptoms of brain injury six months later

Peer-Reviewed Publication

UNIVERSITY OF CAMBRIDGE

Even mild concussion can cause long-lasting effects to the brain, according to researchers at the University of Cambridge. Using data from a Europe-wide study, the team has shown that for almost a half of all people who receive a knock to the head, there are changes in how regions of the brain communicate with each other, potentially causing long term symptoms such as fatigue and cognitive impairment.

Mild traumatic brain injury – concussion – results from a blow or jolt to the head. It can occur as a result of a fall, a sports injury or from a cycling accident or car crash, for example. But despite being labelled ‘mild’, it is commonly linked with persistent symptoms and incomplete recovery. Such symptoms include depression, cognitive impairment, headaches, and fatigue.

While some clinicians in recent studies predict that nine out of 10 individuals who experience concussion will have a full recovery after six months, evidence is emerging that only a half achieve a full recovery. This means that a significant proportion of patients may not receive adequate post-injury care.

Predicting which patients will have a fast recovery and who will take longer to recover is challenging, however. At present, patients with suspected concussion will typically receive a brain scan – either a CT scan or an MRI scan, both of which look for structural problems, such as inflammation or bruising – yet even if these scans show no obvious structural damage, a patient’s symptoms may still persist.

Dr Emmanuel Stamatakis from the Department of Clinical Neurosciences and Division of Anaesthesia at the University of Cambridge said: “Worldwide, we’re seeing an increase in the number of cases of mild traumatic brain injury, particularly from falls in our ageing population and rising numbers of road traffic collisions in low- and middle-income countries.

“At present, we have no clear way of working out which of these patients will have a speedy recovery and which will take longer, and the combination of over-optimistic and imprecise prognoses means that some patients risk not receiving adequate care for their symptoms.”

Dr Stamatakis and colleagues studied fMRI brain scans – that is, functional MRI scans, which look at how different areas of the brain coordinate with each other – taken from 108 patients with mild traumatic brain injury and compared them with scans from 76 healthy volunteers. Patients were also assessed for ongoing symptoms.

The patients and volunteers had been recruited to CENTER-TBI, a large European research project which aims to improve the care for patients with traumatic brain injury, co-chaired by Professor David Menon (head of the division of Anaesthesia) and funded by the European Union.

In results published today in Brain, the team found that just under half (45%) were still showing symptoms resulting from their brain injury, with the most common being fatigue, poor concentration and headaches.

The researchers found that these patients had abnormalities in a region of the brain known as the thalamus, which integrates all sensory information and relays this information around the brain. Counter-intuitively, concussion was associated with increased connectivity between the thalamus and the rest of the brain – in other words, the thalamus was trying to communicate more as a result of the injury – and the greater this connectivity, the poorer the prognosis for the patient.

Rebecca Woodrow, a PhD student in the Department of Clinical Neuroscience and Hughes Hall, Cambridge, said: “Despite there being no obvious structural damage to the brain in routine scans, we saw clear evidence that the thalamus – the brain’s relay system – was hyperconnected. We might interpret this as the thalamus trying to over-compensate for any anticipated damage, and this appears to be at the root of some of the long-lasting symptoms that patients experience.”

By studying additional data from positron emission tomography (PET) scans, which can measure regional chemical composition of body tissues, the researchers were able to make associations with key neurotransmitters depending on which long-term symptoms a patient displayed. For example, patients experiencing cognitive problems such as memory difficulties showed increased connectivity between the thalamus and areas of the brain rich in the neurotransmitter noradrenaline; patients experiencing emotional symptoms, such as depression or irritability, showed greater connectivity with areas of the brain rich in serotonin.

Dr Stamatakis, who is also Stephen Erskine Fellow at Queens' College, Cambridge, added: “We know that there already drugs that target these brain chemicals so our findings offer hope that in future, not only might we be able to predict a patient’s prognosis, but we may also be able to offer a treatment targeting their particular symptoms.”

Reference
Woodrow, RE et al. Acute thalamic connectivity precedes chronic postconcussive symptoms in mild traumatic brain injury. Brain; 26 April 2023; DOI: 10.1093/brain/awad056

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JOURNAL

Brain

DOI

10.1093/brain/awad056 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Acute thalamic connectivity precedes chronic postconcussive symptoms in mild traumatic brain injury

ARTICLE PUBLICATION DATE

26-Apr-2023

Robot fish makes splash with motion breakthrough

Reports and Proceedings

UNIVERSITY OF BRISTOL

 

VIDEO: VIDEO OF ROBOT FISH IN ACTION view more 

CREDIT: TSAM LUNG YOU

A coil-powered robot fish designed by scientists at the University of Bristol could make underwater exploration more accessible.

The robot fish was fitted with a twisted and coiled polymer (TCP) to drive it forward, a light-weight low cost device that relies on temperature change to generate movement, which also limits its speed.

A TCP works by contracting like muscles when heated, converting the energy into mechanical motion . The TCP used in this work is warmed by Joule heating - the pass of current through an electrical conductor produces thermal energy and heats up the conductor. By minimising the distance between the TCP on one side of the robot fish and the spring on the other, this activates the fin at the rear, enabling the robot fish to reach new speeds. The undulating flapping of its rear fin was measured at a frequency of 2Hz, two waves per second. The frequency of the electric current is the same as the frequency of tail flap.  

The findings, published at the 6th IEEE-RAS International Conference on Soft Robotics (RoboSoft 2023), provide a new route to raising the actuation - the action of causing a machine or device to operate - frequency of TCPs through thermomechanical design and shows the possibility of using TCPs at high frequency in aqueous environments.

Lead author Tsam Lung You from Bristol’s Department of Engineering Mathematics said: “Twisted and coiled polymer (TCP) actuator is a promising novel actuator, exhibiting attractive properties of light weight, low-cost high energy density and simple fabrication process.

“They can be made from very easily assessable materials such as a fishing line and they contract and provide linear actuation when heated up. However, because of the time needed for heat dissipation during the relaxation phase, this makes them slow.”

By optimising the structural design of the TCP-spring antagonistic muscle pair and bringing their anchor points closer together, it allowed the posterior fin to swing at a larger angle for the same amount of TCP actuation.

Although this requires greater force, TCP is a strong actuator with high work energy density, and is still able to drive the fin.

Until now, TCPs have been mostly used for applications such as wearable devices and robotic hands. This work opens up more areas of application where TCP can be used, such as marine robots for underwater exploration and monitoring.

Tsam Lung You added: “Our robotic fish swam at the fastest actuation frequency found in a real TCP application and also the highest locomotion speed of a TCP application so far.

“This is really exciting as it opens up more opportunities of TCP application in different areas.”

The team now plan to expand the scale and develop a knifefish-inspired TCP-driven ribbon fin robot that can swim agilely in water.

Antagonistic muscles

Fish sideview

Isometric

CREDIT

Tsam Lung You

 

Paper:

‘Robotic Fish driven by Twisted and Coiled Polymer Actuators at High Frequencies’ by Tsam Lung You et al at the 6th IEEE-RAS International Conference on Soft Robotics (RoboSoft 2023).

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METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Robotic Fish driven by Twisted and Coiled Polymer Actuators at High Frequencies’