Structure of tick-borne virus revealed at atomic resolution for the first time

Rates of the Powassan virus — which can cause seizures and paralysis — are increasing across commonwealth, nation

Penn State

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UNIVERSITY PARK, Pa. — As summer kicks into full gear and people are spending more time outside, there’s one thing on many people’s minds — ticks. Tick season is starting earlier and lasting longer, and ticks are popping up in areas they haven’t been found before, expanding the risk of tick-borne viruses.

One emerging tick-borne virus in North America — including in Pennsylvania — is the Powassan virus (POWV), which can cause encephalitis, seizures, paralysis and coma. Rates of POWV infections have increased in recent years and currently, there are no treatments available, according to Joyce Jose, associate professor of biochemistry and molecular biology at Penn State.

“We don’t know much about the structure of this virus, but we need to know the structure in order to come up with strategies to treat and prevent infection,” Joyce said, explaining that her team, which includes researchers from Penn State, the University of Minnesota and the US Department of Agriculture, has built a high resolution, 3D structure of POWV. They published their findings today (July 9) in the journal Science Advances.

POWV is a member of the Flaviviridae family, which includes West Nile, dengue and yellow fever viruses. It’s transmitted by vectors, which are living organisms that carry the virus and infect other organisms. In this case, the vectors are ticks.

Because POWV can cause serious health problems, it’s been challenging for researchers to study it in its natural form, Joyce said. Typically, they inactivate the virus by modifying it with chemicals or ultraviolet light. However, these processes often damage the virus, making it difficult to determine its structure at a high resolution, she explained.

Instead, the team used a surrogate to study POWV. Using the yellow fever vaccine virus, a weakened strain of the yellow fever virus that’s less infectious, they swapped out two protein genes and replaced them with two genes that encode the structural proteins found on the surface of POWV. These proteins — envelope proteins and membrane proteins — are arranged on the surface of POWV in a herringbone-like pattern. It’s a standard and safe practice that has been used to study the surface structure of other types of viruses, Joyce said.

They then imaged the virus in Penn State’s Cryo-Electron Microscopy (cryo-EM) facility. Cryo-EM is a technique that allows researchers to determine the 3D structure of proteins and viruses at near atomic resolution. With cryo-EM, researchers can see every molecule in the virus, enabling the team to capture every angle and reconstruct it into a 3D structure featuring the details of the surface proteins.

“When I started my research, viruses used to look like blobs because the resolution was so low,” Joyce said. “Now, we know how every molecule sits on the surface, as well as which ones are more exposed and accessible.”

Understanding the structure of the virus is necessary for understanding viral transmission, something Joyce said is not well understood. Interestingly, she noted, the team found that the type of host the virus transmits through isn’t determined by the structural proteins on the surface of the virus but by the virus’s nonstructural proteins.

“One thing we learned is that the viruses that are transmitted by mosquitoes cannot be transmitted by ticks and vice versa, but we don’t understand what prevents them from cross-transmitting,” she said. “Knowing what the virus looks like — what proteins are on the surface — is the first step. It can shed light on virus-host and virus-vector interactions and how to prevent them.”

Vaccines and treatments typically target surface proteins, as well, so this revealing these visual details could potentially inform future therapeutics, Joyce said. Next, the team plans to continue to examine the factors that influence how viruses are transmitted.

Other Penn State authors on the paper include Ibrahim Moustafa, Sung Hyun Cho and Anqi Wang. First author Sayan Das earned a graduate degree at Penn State and senior author Susan Hafenstein was at Penn State at the time of the research; they are now at the University of Minnesota. Dana Mitzel of the U.S. Department of Agriculture also contributed to the paper. A full list of contributors is available here.

Funding from the National Institutes of Health and the U.S. Department of Agriculture supported this work.

At Penn State, researchers are solving real problems that impact the health, safety and quality of life of people across the commonwealth, the nation and around the world.

For decades, federal support for research has fueled innovation that makes our country safer, our industries more competitive and our economy stronger. Recent federal funding cuts threaten this progress.ß

Learn more about the implications of federal funding cuts to our future at Research or Regress.

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Journal

Science Advances

DOI

10.1126/sciadv.adw7700 

Method of Research

Imaging analysis

Subject of Research

Cells

Article Title

Atomic resolution structure of a chimeric Powassan tick-borne flavivirus

Article Publication Date

9-Jul-2025

 

Prenatal and childhood lead exposure linked to faster memory decay in children

Study is among the first to quantify how exposure to lead influences memory in children in a way that can be used in both human and animal models

The Mount Sinai Hospital / Mount Sinai School of Medicine

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New York, NY — July 9, 2025 — A study led by researchers at the Icahn School of Medicine at Mount Sinai shows that exposure to lead during pregnancy and early childhood may accelerate the rate at which children forget information—a critical marker of memory impairment that may have implications for learning and development.

Using delayed matching-to-sample task (DMTS)—a cognitive task that can be used to evaluate underlying neurobehavioral functions, such as attention and working memory, and has been demonstrated to be sensitive to metal neurotoxicants—the study examined how both prenatal and early childhood blood lead levels affect working memory in children ages 6 to 8. In this task, the children were presented a picture, and then had to select that same picture from three choices presented after a brief delay. The study was published in Science Advances on July 9, 2025.

Researchers applied an innovative statistical approach known as a nonlinear modified power function to model memory decay, uncovering a measurable link between higher childhood lead levels and faster forgetting rates.

The findings showed that higher lead exposure at ages 4–6 was significantly associated with a faster rate of forgetting—even at low median blood lead levels (~1.7 µg/dL). Additionally, older children and those whose mother’s IQ was higher were more likely to show better memory retention.

“The nonlinear modified power function has been validated in previous animal and human studies but is now applied in the field of environmental health,” said Katherine Svensson, PhD, MS, a postdoctoral fellow in Environmental Medicine at the Icahn School of Medicine at Mount Sinai and co-first author of the study. “This new usage is important because children are exposed to many environmental chemicals, and this model provides a validated method to further assess the effect of additional environmental exposures, such as heavy metals, air pollution, or endocrine disruptors, on children’s working memory.”

This study also validates a method for assessing neurobehavioral function, paving the way for translational research that can bridge human data with mechanistic insights from laboratory studies.

“Our work advances the current literature by incorporating operant tests—specifically the DMTS—which are commonly used in animal toxicology studies but sparse in human studies. This translational approach is a key innovation of our work,” said Jamil M. Lane, PhD, MPH, Instructor, Environmental Medicine, Icahn School of Medicine at Mount Sinai, and co-first author.

The implications are clear: even low-level lead exposure can undermine key cognitive functions in young children. As memory and attention are foundational for academic and social success, this research underscores the urgent need for continued investment in lead prevention efforts—especially in historically overburdened communities.

“There may be no more important a trait than the ability to form memories. Memories define who we are and how we learn,” said Robert Wright, MD, MPH, Ethel H. Wise Chair of the Department of Environmental Medicine and Co-Director of the Institute for Exposomic Research at the Icahn School of Medicine at Mount Sinai. “This paper breaks new ground by showing how environmental chemicals can interfere with the rate of memory formation. Children with higher levels of blood lead forgot the test stimulus faster than those with low blood lead levels.”

This study opens the door for future work to explore how environmental exposures like lead intersect with other cognitive domains such as attention, executive function, and reward processing. It also strengthens the case for policy interventions that protect children’s developing brains before irreversible harm occurs.

Research funding for this study was provided in part by NIH grants: T32HD049311, R01ES014930, R01ES013744, R24ES028522, P30ES023515, R01ES026033, R01MH122447, R01ES029511, R01ES028927, R03ES033374, and K25HD104918. Read the full study here.  DOI: 10.1126/sciadv.adq4495

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About the Mount Sinai Health System

Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across seven hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2024-2025. 

For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Instagram, LinkedIn, X, and YouTube.

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Journal

Science Advances

DOI

10.1126/sciadv.adq4495 

Subject of Research

People

Article Publication Date

9-Jul-2025

 

Source criticism in school requires more than isolated interventions

Uppsala University

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Thomas Nygren, Professor of History and Civics Education
Department of Education, Uppsala University

 

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Credit: Mikael Wallerstedt

Strengthening school students’ resilience to disinformation requires more than isolated interventions on source criticism. A new study from Uppsala University shows that short teaching interventions on disinformation have no long-term effect on upper secondary school students’ ability to distinguish between credible and misleading news.

The results are now published in the scholarly journal PLOS One and are based on a study of 459 Swedish upper secondary school students.

The study, supported by the Swedish Institute for Educational Research, is one of the first to systematically examine the long-term effects of different teaching models against misinformation and disinformation in ordinary classrooms. Three types of interventions have been compared: a game about propaganda and manipulation on social media (Bad News), a digital workshop on fact-checking (News Evaluator) and subject-specific lesson segments in social sciences, history, psychology, science and art.

Three types of interventions have been compared:

– Bad News, an online game where students in pairs try out spreading disinformation themselves during a lesson. By using strategies such as emotional manipulation, trolling and polarisation, they learn to recognise common propaganda techniques. A concluding class discussion deepens their understanding.

– The News Evaluator, a digital self-test where students individually practise assessing the credibility of news. The test takes about 20 minutes to complete and is followed by a joint class discussion on the challenges of current news feeds.

– Subject-specific lesson segments, spread over three lessons in the subjects of social sciences, history, psychology, science and art. The focus was on integrating source criticism into subject teaching using authentic examples and subject-relevant discussions.

Despite previous research suggesting that such interventions can have short-term effects, the new study shows little improvement in students’ source criticism skills three months after the interventions. The students’ use of digital tools such as reverse image search remained low and most still had difficulty identifying misleading information. On the other hand, the study showed that students who considered it important to have access to credible information, and those who valued democratic ideals highly, were better at identifying true and false information.

“The results show that isolated lessons or games are not enough. Strengthening young people’s resilience to disinformation requires more long-term and integrated teaching strategies. Schools have a central role in equipping young people for life in a public sphere where digital source criticism is crucial for democratic participation. Source-critical exercises need to come up regularly and in different ways in teaching in different subjects,” says Professor Thomas Nygren of Uppsala University, who conducted the study.

Teachers want tried and tested material

Over the years of working on the News Evaluator platform and on how young people develop source criticism, he has repeatedly encountered teachers asking for tried and tested materials to teach complex issues such as disinformation. The News Evaluator provides ready-made lesson plans, slideshows and teacher guides for all five subjects used in the study. Developed in close cooperation between researchers and teachers, the material aims to support the teaching of digital source criticism in a concrete way and to counter misleading information and disinformation.

“Now we have resources that are scientifically tested and easy to use in the classroom. To facilitate this, all teaching materials from the study are freely available to teachers,” says Nygren.

Direct link to teaching material: https://nyhetsvarderaren.se/in-english/ 

Swedish Institute for Educational Research: https://www.skolfi.se/

 

 

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Journal

PLOS One

DOI

10.1371/journal.pone.0326928 

Method of Research

Observational study

Subject of Research

People

Article Title

Investigating the Long-Term Impact of Misinformation Interventions in Upper Secondary Education

Article Publication Date

9-Jul-2025

 

From injury to agony: Scientists discover brain pathway that turns pain into suffering

Salk scientists uncover a key neural circuit in mice that gives pain its emotional punch, opening new doors for treating fibromyalgia, migraine, and PTSD

Salk Institute

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CGRP-expressing neurons (green) in the parvocellular subparafascicular nucleus (SPFp) of the thalamus.

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Credit: Salk Institute

LA JOLLA (July 9, 2025)—Pain isn’t just a physical sensation—it also carries emotional weight. That distress, anguish, and anxiety can turn a fleeting injury into long-term suffering.

Researchers at the Salk Institute have now identified a brain circuit that gives physical pain its emotional tone, revealing a new potential target for treating chronic and affective pain conditions such as fibromyalgia, migraine, and post-traumatic stress disorder (PTSD).

Published on July 9, 2025, in Proceedings of the National Academy of Sciences, the study identifies a group of neurons in a central brain area called the thalamus that appears to mediate the emotional or affective side of pain in mice. This new pathway challenges the textbook understanding of how pain is processed in the brain and body.

“For decades, the prevailing view was that the brain processes sensory and emotional aspects of pain through separate pathways,” says senior author Sung Han, associate professor and holder of the Pioneer Fund Developmental Chair at Salk. “But there’s been debate about whether the sensory pain pathway might also contribute to the emotional side of pain. Our study provides strong evidence that a branch of the sensory pain pathway directly mediates the affective experience of pain.”

The physical sensation of pain is what allows you to immediately detect it, assess its intensity, and identify its source. The affective part of pain is what makes it so unpleasant. This emotional discomfort motivates you to take action and helps you learn to associate negative feelings with the situation so you can avoid it in the future. 

This is a critical distinction. Most people start to perceive pain at the same stimulus intensities, meaning we all process the sensory side of pain fairly similarly. In comparison, our ability to tolerate pain varies greatly. How much we suffer or feel threatened by pain is determined by our affective processing, and if that becomes too sensitive or lasts too long, it can result in a pain disorder. This makes it important to understand which parts of the brain control these different dimensions of pain.

Sensory pain was thought to be mediated by the spinothalamic tract, a pathway that sends pain signals from the spinal cord to the thalamus, which then relays them to sensory processing areas across the brain.

Affective pain was generally thought to be mediated by a second pathway called the spinoparabrachial tract, which sends pain information from the spinal cord into the brainstem.

However, previous studies using older research methods have suggested the circuitry of pain may be more complex. This long-standing debate inspired Han and his team to revisit the question with modern research tools. 

Using advanced techniques to manipulate the activity of specific brain cells, the researchers discovered a new spinothalamic pathway in mice. In this circuit, pain signals are sent from the spinal cord into a different part of the thalamus, which has connections to the amygdala, the brain’s emotional processing center. This particular group of neurons in the thalamus can be identified by their expression of CGRP (calcitonin gene-related peptide), a neuropeptide originally discovered in Professor Ronald Evans’ lab at Salk. 

When the researchers “turned off” (genetically silenced) these CGRP neurons, the mice still reacted to mild pain stimuli, such as heat or pressure, indicating their sensory processing was intact. However, they didn’t seem to associate lasting negative feelings with these situations, failing to show any learned fear or avoidance behaviors in future trials. On the other hand, when these same neurons were “turned on” (optogenetically activated), the mice showed clear signs of distress and learned to avoid that area, even when no pain stimuli had been used.

“Pain processing is not just about nerves detecting pain; it’s about the brain deciding how much that pain matters,” says first author Sukjae Kang, a senior research associate in Han’s lab. “Understanding the biology behind these two distinct processes will help us find treatments for the kinds of pain that don’t respond to traditional drugs.”

Many chronic pain conditions—such as fibromyalgia and migraine—involve long, intense, unpleasant experiences of pain, often without a clear physical source or injury. Some patients also report extreme sensitivity to ordinary stimuli like light, sound, or touch, which others would not perceive as painful. 

Han says overactivation of the CGRP spinothalamic pathway may contribute to these conditions by making the brain misinterpret or overreact to sensory inputs. In fact, transcriptomic analysis of the CGRP neurons showed that they express many of the genes associated with migraine and other pain disorders. 

Notably, several CGRP blockers are already being used to treat migraines. This study may help explain why these medications work and could inspire new nonaddictive treatments for affective pain disorders.

Han also sees potential relevance for psychiatric conditions that involve heightened threat perception, such as PTSD. Growing evidence from his lab suggests that the CGRP affective pain pathway acts as part of the brain’s broader alarm system, detecting and responding to not only pain but a wide range of unpleasant sensations. Quieting this pathway with CGRP blockers could offer a new approach to easing fear, avoidance, and hypervigilance in trauma-related disorders. 

Importantly, the relationship between the CGRP pathway and the psychological pain associated with social experiences like grief, loneliness, and heartbreak remains unclear and requires further study.

“Our discovery of the CGRP affective pain pathway gives us a molecular and circuit-level explanation for the difference between detecting physical pain and suffering from it,” says Han. “We’re excited to continue exploring this pathway and enabling future therapies that can reduce this suffering.”

Other authors include Shijia Liua, Jong-Hyun Kima, Dong-Il Kima, Tae Gyu Oh, Jiahang Penga, Mao Yea, Kuo-Fen Lee, Ronald M. Evans, and Martyn Goulding of Salk.

The work was supported by the National Institutes of Mental Health (BRAINS grant 1R01MH116203) and the Simons Foundation (Bridge to Independence award SFARI #388708).

About the Salk Institute for Biological Studies:

Unlocking the secrets of life itself is the driving force behind the Salk Institute. Our team of world-class, award-winning scientists pushes the boundaries of knowledge in areas such as neuroscience, cancer research, aging, immunobiology, plant biology, computational biology, and more. Founded by Jonas Salk, developer of the first safe and effective polio vaccine, the Institute is an independent, nonprofit research organization and architectural landmark: small by choice, intimate by nature, and fearless in the face of any challenge. Learn more at www.salk.edu.

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Journal

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2505889122 

Subject of Research

Animals

Article Title

Thalamic CGRP neurons define spinothalamic pathway for affective pain

Article Publication Date

9-Jul-2025

 

Molecular simulations show graphite ‘hijacks’ diamond formation through unexpected crystallization pathways

University of California - Davis

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Molten carbon can crystallize into diamond or graphite, but it has been difficult to study this process. New simulations show that graphite can sometimes "hijack" the pathway that would lead to diamond. Image shows simulations of the nucleation pathways of graphite (top row) and diamond (bottom row) from direct molecular dynamics simulations at pressures of 15 and 15.5 GPa and a temperature of 3650 K.

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Credit: Davide Donadio/UC Davis

The graphite found in your favorite pencil could have instead been the diamond your mother always wears. What made the difference? Researchers are finding out.

How molten carbon crystallizes into either graphite or diamond is relevant to planetary science, materials manufacturing and nuclear fusion research. However, this moment of crystallization is difficult to study experimentally because it happens very rapidly and under extreme conditions.

In a new study published July 9 in Nature Communications, researchers from the University of California, Davis and George Washington University use computer simulations to study how molten carbon crystallizes into either graphite or diamond at temperatures and pressures similar to Earth’s interior. The team’s findings challenge conventional understanding of diamond formation and reveal why experimental results studying carbon's phase behavior have been so inconsistent.

Using leading-edge, machine learning-powered molecular simulations, the research team discovered that liquid carbon exhibits far more complex crystallization behavior than previously thought. Most surprisingly, they found that graphite — the soft, pencil-lead form of carbon — can form spontaneously even when diamond should be the stable phase, possibly “hijacking” diamond formation.

“The advantage of simulations is that you can easily realize these extreme conditions without any special machinery,” said study senior author Davide Donadio, a professor in the Department of Chemistry at the College of Letters and Science at UC Davis. “Experimentally, it’s very difficult to obtain such high temperature and high pressure in a controlled manner and to monitor the crystallization process.”

Simulating Earth’s interior

In the study, the team provided an atomistic picture of how this process goes, preparing models at various pressures from 5 to 30 gigapascals (GPa) as the molten carbon cooled from 5000 to 3500 Kelvin (K). Donadio noted that such conditions can be obtained in laser heating experiments.

While the team expected to get glassy carbon from the rapid quench of the liquid, they noticed spontaneous crystallization. At high pressures, the liquid carbon crystallized into diamond, and at lower pressures, it crystallized into graphite.

“This was a nice surprise because normally simulating crystallization is much more complicated than that,” Donadio said. “You usually need to use some tricks to get the molecular dynamics simulations to crystallize. We were even more amazed to observe graphite crystallizing spontaneously at pressures up to 15 GPa — conditions where diamond should be the stable form.”

The unexpected behavior follows a principle known as Ostwald’s step rule, which predicts that crystallization sometimes proceeds through intermediate metastable phases rather than directly to the most stable form. The researchers found that graphite acts as a stepping stone in diamond formation because its structure more closely resembles liquid carbon’s density and bonding patterns.

“The liquid carbon essentially finds it easier to become graphite first, even though diamond is ultimately more stable under these conditions,” said co-author Tianshu Li, a professor of civil and environmental engineering at George Washington University. “It’s nature taking the path of least resistance.”

Differences in crystallization

Through the simulations, the team also revealed the molecular structures of liquid carbon as it crystallized into graphite and then, separately, as liquid carbon crystallized into diamond. Graphite crystallized in column-like patterns that eventually elongated outwards. Diamond crystallized through compact crystallites.

This research accounts for long-standing discrepancies in high-pressure carbon experiments, providing a new framework for interpreting results that seemed contradictory.   

The findings have implications for a variety of areas. They help explain why natural diamond formation is rare and provide new insights into the deep carbon cycle that affects Earth’s climate and geology over geological timescales. In materials manufacturing, understanding these crystallization pathways could improve industrial diamond synthesis, particularly for specialized applications like quantum computing, where precise control over crystal structure is essential.

“Crystallization is so fundamental for technology, and diamonds are extremely useful as materials,” Donadio said. “The work accounts for the presence of graphite where you might not expect it.”   

Additional co-authors include Margaret L. Berrens, Wanyu Zhao and Shunda Chen.

The research was supported by grants from the National Science Foundation.

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Journal

Nature Communications

DOI

10.1038/s41467-025-61674-5 

Method of Research

Computational simulation/modeling

Subject of Research

Not applicable

Article Title

Metastability and Ostwald step rule in the crystallisation of diamond and graphite from molten carbon.

Article Publication Date

9-Jul-2025