The RNA fragments are from viruses that infected the symbionts as long ago as 160 million years. The discovery is described in an open-access study published this week in the Nature journal Communications Biology, and it could help scientists understand how corals and their partners fight off viral infections today. But it was a surprising find because most RNA viruses are not known for embedding themselves in the DNA of organisms they infect.

The research showed that endogenous viral elements, or EVEs, appear widely in the genomes of coral symbionts. Known as dinoflagellates, the single-celled algae live inside corals and provide them with their dramatic colors. The EVE discovery underscores recent observations that viruses other than retroviruses can integrate fragments of their genetic code into their hosts’ genomes.

“So why did it get in there?” asked study co-author Adrienne Correa of Rice University. “It could just be an accident, but people are starting to find that these ‘accidents’ are more frequent than scientists had previously believed, and they’ve been found across all kinds of hosts, from bats to ants to plants to algae.”

That an RNA virus appears at all in coral symbionts was also a surprise.

“This is what made this project so interesting to me,” said study lead author Alex Veglia, a graduate student in Correa’s research group. “There’s really no reason, based on what we know, for this virus to be in the symbionts’ genome.”

The study was supported by the Tara Ocean Foundation and the National Science Foundation and led by Correa, Veglia and two scientists from Oregon State University, postdoctoral scholar Kalia Bistolas and marine ecologist Rebecca Vega Thurber. The research provides clues that can help scientists better understand the ecological and economic impact of viruses on reef health.

The researchers did not find EVEs from RNA viruses in samples of filtered seawater or in the genomes of dinoflagellate-free stony corals, hydrocorals or jellyfish. But EVEs were pervasive in coral symbionts that were collected from dozens of coral reef sites, meaning the pathogenic viruses were — and probably remain — picky about their target hosts.

“There’s a huge diversity of viruses on the planet,” said Correa, an assistant professor of biosciences. “Some we know a lot about, but most viruses haven’t been characterized. We might be able to detect them, but we don’t know who serves as their hosts.”

She said viruses, including retroviruses, have many ways to replicate by infecting hosts. “One reason our study is cool is because this RNA virus is not a retrovirus,” Correa said. “Given that, you wouldn’t expect it to integrate into host DNA.

“For quite a few years, we’ve seen a ton of viruses in coral colonies, but it’s been hard to tell for sure what they were infecting,” Correa said. “So this is likely the best, most concrete information we have for the actual host of a coral colony-associated virus. Now we can start asking why the symbiont keeps that DNA, or part of the genome. Why wasn’t it lost a long time ago?”

The discovery that the EVEs have been conserved for millions of years suggests they may somehow be beneficial to the coral symbionts and that there is some kind of mechanism that drives the genomic integration of the EVEs.

“There are a lot of avenues we can pursue next, like whether these elements are being used for antiviral mechanisms within dinoflagellates, and how they are likely to affect reef health, especially as oceans warm,” Veglia said.

“If we’re dealing with an increase in the temperature of seawater, is it more likely that Symbiodiniaceae species will contain this endogenous viral element? Does having EVEs in their genomes improve their odds of fighting off infections from contemporary RNA viruses?” he said.

“In another paper, we showed there was an increase in RNA viral infections when corals underwent thermal stress. So there are a lot of moving parts. And this is another good piece of that puzzle.”

Correa said, “We can’t assume that this virus has a negative effect. But at the same time, it does look like it’s becoming more productive under these temperature stress conditions.”

Thurber is the Emile F. Pernot Distinguished Professor in Oregon State’s Department of Microbiology.

The study included more than 20 co-authors from the University of Konstanz, Germany; the Institute of Microbiology and Swiss Institute of Bioinformatics, Zürich; the University of Perpignan, France; the Scientific Center of Monaco; the Université Paris-Saclay, Evry, France; the Tara Ocean Foundation, Paris; the University of Maine; Sorbonne University, France; the University of Tsukuba, Japan; Paris Science and Letters University, France; the University of Paris-Saclay; the Weizmann Institute of Science, Rehovot, Israel; Côte d’Azur University, Nice, France; the European Bioinformatics Institute, University of Cambridge, England; Ohio State University; and the National University of Ireland, Galway.

National Science Foundation support was provided by three grants (2145472, 2025457, 1907184).

The three-year study found that a daily drop in each eye of a low dose of atropine, a drug used to dilate pupils, was better than a placebo at limiting eyeglass prescription changes and inhibiting elongation of the eye in nearsighted children aged 6 to 10.

That elongation leads to myopia, or nearsightedness, which starts in young kids and continues to get worse into the teen years before leveling off in most people. In addition to requiring life-long vision correction, nearsightedness increases the risk for retinal detachment, macular degeneration, cataracts and glaucoma later in life — and most corrective lenses don’t do anything to stop myopia progression.

“The idea of keeping eyeballs smaller isn’t just so people’s glasses are thinner — it would also be so that in their 70s they don’t suffer visual impairment,” said lead study author Karla Zadnik, professor and dean of the College of Optometry at The Ohio State University.

“This is exciting work for the myopia research community, which I’ve been part of for 35 years. We’ve talked about treatment and control for decades,” she said. “And it’s exciting to think that there could be options in the future for millions of children we know are going to be myopic.”

The results of the CHAMP (Childhood Atropine for Myopia Progression) trial are published today (June 1, 2023) in JAMA Ophthalmology.

About one in three adults worldwide is nearsighted, and the global prevalence of myopia is predicted to increase to 50% by 2050. Though one federally approved contact lens can slow progression of nearsightedness, no pharmaceutical products are approved in the United States or Europe to treat myopia.

Animal studies years ago hinted at atropine’s ability to slow the growth of the eye, but the full-strength drug’s interference with near vision and concerns about pupil dilation hindered early considerations of its potential as a human therapy for myopia. More recent research has suggested a low dose of atropine might be the ticket.

This new double-masked, randomized phase 3 trial assessed the safety and effectiveness of two low-dose solutions, with atropine concentrations of either .01% or .02%, versus placebo. Treatment for each of the 489 children aged 6 to 10 assessed for the drug’s effectiveness consisted of one daily drop per eye at bedtime, which minimized the disruption of any blurring effects atropine might have on vision.

Researchers were a bit surprised to find that the most significant improvements at all time points compared to placebo resulted from the solution containing .01% of atropine. Though the .02% atropine formulation was also better at slowing progression of myopia than placebo, the results were less consistent.

“The .01% story is clearer and more obvious in terms of significantly slowing both the growth of the eye as well as then resulting in a lower glasses prescription,” Zadnik said.

Including a measure of the eye’s growth was a key component of the study because “the field is actually moving toward axial elongation being as important as, or more important than, the glasses prescription in terms of the most meaningful outcome,” she said. “If we’re trying to slow eye growth to prevent bad outcomes for people in their 80s, measuring the eye growth directly is really important.”

The drugs’ safety was assessed in a larger sample of 573 participants that also included children as young as 3 and up to age 16. Both low-dose formulations were safe and well tolerated. The most common side effects were sensitivity to light, allergic conjunctivitis, eye irritation, dilated pupils and blurred vision, although reports of these side effects were few.

The CHAMP trial was the first study of low-dose atropine to include placebo controls for three years and to involve a large, diverse population recruited from 26 clinical sites in North America and five countries in Europe. In a second section of the trial, researchers are evaluating how the eyes respond when the treatment is over.

The experimental drug is made without preservatives and, if federally approved as a therapy, would be distributed in single-use packaging for convenience and to prevent contamination. Off-label low-dose atropine that can currently be obtained at compounding pharmacies may contain preservatives that can lead to dry eye and corneal irritation, researchers noted.

The experimental product studied in the CHAMP trial is manufactured by Vyluma, a New Jersey development-stage biopharmaceutical company with a focus on pharmaceutical treatments for refractive errors of the eye. A subsidiary of Nevakar Inc., Vyluma sponsored the trial, has submitted a New Drug Application to the FDA to seek approval in the U.S. and has partnered with two companies to commercialize the product outside the United States..

Zadnik led the study as a paid expert consultant to Vyluma. Jennifer Fogt, assistant professor at Ohio State, also worked on the trial. Additional co-authors Erica Schulman of SUNY College of Optometry; Ian Flitcroft of the Center for Eye Research in Dublin, Ireland; Louis Blumenfeld of Eye Physicians of Central Florida; and Tung Fong, Eric Lang, Houman Hemmati and Simon Chandler of Vyluma represented the CHAMP trial group investigators.

A study reporting the researchers’ findings was published April 13 in the journal Accident Analysis and Prevention.

Traffic accidents involving large trucks in the United States have increased 47 percent according to the National Safety Council, and in 2021, these vehicles were responsible for nine percent of all vehicles involved in fatal crashes. Several studies worldwide have highlighted in particular the severity of collisions related to drowsy driving and their substantial risk of fatality.

A major risk here comes from what researchers term “microsleeps.” A microsleep is a brief episode of sleep that lasts for just a few seconds and can occur involuntarily during wakefulness. It can lead to impaired cognitive and motor performance, including slower reaction times, decreased attention, and even complete loss of consciousness. Microsleep episodes can have a significant impact on driving performance and increase the likelihood of dozing off while driving. In 2022, National Police Agency of Japan announced that falling asleep at the wheel was to be included in the same category of “forward inattention” as distraction, which has been the most frequent cause of fatal traffic accidents in the country for over ten years.

A great deal of research into typical microsleep behaviors has investigated one or more aspects of the problem such as eye closure or changes in pupil diameter. No study has yet performed an analysis that takes a more holistic approach considering multiple aspects of the problem, combining the driver’s eye and mouth movements as well as their entire body and vehicle driving behavior. Most such studies have also only considered driver performance during computer simulations. No research has yet looked at actual collisions of large trucks.

“But in recent years, there has been an explosion in the use of dashcam video recorders,” said Hajime Kumagai, lead author of the paper and a specialist in sleep medicine with the Graduate School of Biomedical and Health Sciences at Hiroshima University.

“This means that a great many traffic accidents, and their possible relationship to episodes of microsleeping have been recorded. This inspired us to employ dashcam footage to investigate microsleep-related behaviors immediately prior to real-world truck collisions.”

In total, the researchers reviewed 3,120 seconds of video footage from interior and exterior dashcams across 52 cases from truck collisions in Japan that had actually happened. They analysed the footage from one minute before the crash right up until the crash. In each incident, the person at the wheel had been a professional driver, and all crashes occurred on either urban roads or highways.

The footage was visually analyzed in a second-by-second manner to simultaneously evaluate any eye changes and microsleep-related activity including the driver’s actions to try to prevent falling asleep (anti-sleepiness behaviors), behavioral signs of microsleep, and abnormal vehicle behavior.

The researchers concluded that the key signs of microsleep include behaviors suggesting a creeping sleepiness, such as the absence of body movement, relaxation of antigravity muscles (the muscles such as back and neck muscles, as well as calves and quadriceps used to support ourselves against the force of gravity), eyes being half-closed, and closure of the eyes for one second or more.

“Up to now, technologies used to attempt to detect and counter falling asleep at the wheel have focused mainly on monitoring the driver’s eyes,” said Toshiaki Shiomi, a co-author of the study. “What we found means that it is crucial to monitor not just the eyes but also the driver’s whole body, as well as vehicle behavior in order to reliably detect microsleep-related activity.”

This should also help in avoiding false alarms by ensuring a clear distinction between microsleep-related and non-microsleep-related behaviors.

Developing advanced safety systems that can detect and alert drivers of potential microsleep episodes involving a whole-of-body approach combined with monitoring of the vehicle for typical microsleep-related abnormal vehicle maneuvers could be an effective intervention for reducing accidents in the trucking industry.

The team hopes now to support work developing such advanced safety systems. These might include technologies that monitor both the inside and outside of the truck using cameras or other sensors, as well as deployment of algorithms that can analyze such data in real-time to detect signs of sleepiness or fatigue. These systems could then alert drivers with an alarm when they are at risk of falling asleep at the wheel.

The PCE (Power-conversion efficiency), a measure of the power generated from a given solar irradiation, is considered a significant benchmark for the performance of photovoltaics (PVs), or solar panels, in power generation. The improved efficiency of over 19% that was achieved by the PolyU researchers constitutes a record for binary OSCs, which have one donor and one acceptor in the photo-active layer.

Led by Prof. LI Gang, Chair Professor of Energy Conversion Technology and Sir Sze-Yen Chung Endowed Professor in Renewable Energy at PolyU, the research team invented a novel OSC morphology-regulating technique by using 1,3,5-trichlorobenzene as a crystallisation regulator. This new technique boosts OSC efficiency and stability.

The team developed a non-monotonic intermediated state manipulation (ISM) strategy to manipulate the bulk-heterojunction (BHJ) OSC morphology, which simultaneously optimises crystallisation dynamics and energy loss of non-fullerene OSCs. Unlike the strategy of using traditional solvent additives, which is based on excessive molecular aggregation in films, the ISM strategy promotes the formation of more ordered molecular stacking and favourable molecular aggregation. As a result, the PCE was considerably increased and the undesirable non-radiative recombination loss was reduced. Notably, non-radiative recombination lowers the light generation efficiency and increases the heat loss.

The research team’s findings are described in the study “19.3% Binary Organic Solar Cell and Low Non-Radiative Recombination Enabled by Non-Monotonic Intermediate State Transition” published in Nature Communications . The conversion of solar energy to electricity is an essential technology for achieving a sustainable environment. Although OSCs are promising devices that harness solar energy cost-effectively, their efficiency must be improved if they are to be used widely in practical applications.

Non-fullerene acceptors based organic solar cells represent the frontier of research in the field of organic photovoltaics due to both the materials and morphology manipulation innovations. Nevertheless, non-radiative recombination loss suppress and performance boosting are in the centre of organic cell research.

Prof. Li said, “Challenges in research came from the existing additive-based benchmark morphology control methods, which suffer from non-radiative recombination loss, thus lowering the open-circuit voltage due to excessive aggregation.” The research team took about two years to devise a non-monotonic ISM strategy for increasing the OSC efficiency and lowering the non-radiative recombination loss. The publication of the study promises to galvanise OSC research.

Prof. Li said, “The new finding will make OSC research an exciting field, and this will likely create tremendous opportunities in applications like portable electronics and building-integrated PVs.” The new door will open when low cost single-junction OSCs can achieve a PCE of over 20%, along with more stable performance and other unique advantages such as flexibility, transparency, stretchability, low weight and tuneable colour.

Prof. Li has been recognised as a Highly Cited Researcher 9 years in a row since 2014, which testifies to his significant impact on global research. His pioneering contributions to research on polymer solar cells since 2005 have brought sustainable influence on printable solar energy development with global recognition.

Underpinning the research on OPV field, Prof LI’s study titled, “High-efficiency solution processable polymer photovoltaic cells by self-organization of polymer blends,” was published on Nature Materials in 2005. This represented OPV’s first generation research breakthrough which has fuelled solar technology from this frontier study.

In 2010, Prof LI’s study titled “For the Bright Future — Bulk Heterojunction Polymer Solar Cells with Power Conversion Efficiency of 7.4%” was published on Advanced Materials.

Prof. Li said, “The latest study shows a record low non-radiative recombination loss of 0.168 eV in a binary OSC with a PCE of over 19%. This is a very encouraging result for the long-standing research on OSCs that I have conducted over the past two decades. We have already achieved better OSC efficiency, and this will subsequently help accelerate the applications of solar energy.”

References: Nature Materials 4, 864-868 (2005). High-efficiency solution processable polymer photovoltaic cells by self-organization of polymer blends. Advanced Materials Vol. 22, Issue 20 (2010). For the Bright Future — Bulk Heterojunction Polymer Solar Cells with Power Conversion Efficiency of 7.4%.

Penn State scientists have discovered a new mechanism by which bacteria can select between different rare earth elements, using the ability of a bacterial protein to bind to another unit of itself, or “dimerize,” when it is bound to certain rare earths, but prefer to remain a single unit, or “monomer,” when bound to others.

By figuring out how this molecular handshake works at the atomic level, the researchers have found a way to separate these similar metals from one another quickly, efficiently, and under normal room temperature conditions. This strategy could lead to more efficient, greener mining and recycling practices for the entire tech sector, the researchers state.

“Biology manages to differentiate rare earths from all the other metals out there — and now, we can see how it even differentiates between the rare earths it finds useful and the ones it doesn’t,” said Joseph Cotruvo Jr., associate professor of chemistry at Penn State and lead author on a paper about the discovery published today (May 31) in the journal Nature. “We’re showing how we can adapt these approaches for rare earth recovery and separation.”

Rare earth elements, which include the lanthanide metals, are in fact relatively abundant, Cotruvo explained, but they are what mineralogists call “dispersed,” meaning they’re mostly scattered throughout the planet in low concentrations.

“If you can harvest rare earths from devices that we already have, then we may not be so reliant on mining it in the first place,” Cotruvo said. However, he added that regardless of source, the challenge of separating one rare earth from another to get a pure substance remains.

“Whether you are mining the metals from rock or from devices, you are still going to need to perform the separation. Our method, in theory, is applicable for any way in which rare earths are harvested,” he said.

All the same — and completely different

In simple terms, rare earths are 15 elements on the periodic table — the lanthanides, with atomic numbers 57 to 71 — and two other elements with similar properties that are often grouped with them. The metals behave similarly chemically, have similar sizes, and, for those reasons, they often are found together in the Earth’s crust. However, each one has distinct applications in technologies.

Conventional rare earth separation practices require using large amounts of toxic chemicals like kerosene and phosphonates, similar to chemicals that are commonly used in insecticides, herbicides and flame retardants, Cotruvo explained. The separation process requires dozens or even hundreds of steps, using these highly toxic chemicals, to achieve high-purity individual rare earth oxides.

“There is getting them out of the rock, which is one part of the problem, but one for which many solutions exist,” Cotruvo said. “But you run into a second problem once they are out, because you need to separate multiple rare earths from one another. This is the biggest and most interesting challenge, discriminating between the individual rare earths, because they are so alike. We’ve taken a natural protein, which we call lanmodulin or LanM, and engineered it to do just that.”

Learning from nature

Cotruvo and his lab turned to nature to find an alternative to the conventional solvent-based separation process, because biology has already been harvesting and harnessing the power of rare earths for millennia, especially in a class of bacteria called “methylotrophs” that often are found on plant leaves and in soil and water and play an important role in how carbon moves through the environment.

Six years ago, the lab isolated lanmodulin from one of these bacteria, and showed that it was unmatched — over 100 million times better — in its ability to bind lanthanides over common metals like calcium. Through subsequent work they showed that it was able to purify rare earths as a group from dozens of other metals in mixtures that were too complex for traditional rare earth extraction methods. However, the protein was less good at discriminating between the individual rare earths.

Cotruvo explained that for the new study detailed in Nature, the team identified hundreds of other natural proteins that looked roughly like the first lanmodulin but homed in on one that was different enough — 70% different — that they suspected it would have some distinct properties. This protein is found naturally in a bacterium (Hansschlegelia quercus) isolated from English oak buds.

The researchers found that the lanmodulin from this bacterium exhibited strong capabilities to differentiate between rare earths. Their studies indicated that this differentiation came from an ability of the protein to dimerize and perform a kind of handshake. When the protein binds one of the lighter lanthanides, like neodymium, the handshake (dimer) is strong. By contrast, when the protein binds to a heavier lanthanide, like dysprosium, the handshake is much weaker, such that the protein favors the monomer form.

“This was surprising because these metals are very similar in size,” Cotruvo said. “This protein has the ability to differentiate at a scale that is unimaginable to most of us — a few trillionths of a meter, a difference that is less than a tenth of the diameter of an atom.”

Fine-tuning rare earth separations

To visualize the process at such a small scale, the researchers teamed up with Amie Boal, Penn State professor of chemistry, biochemistry and molecular biology, who is a co-author on the paper. Boal’s lab specializes in a technique called X-ray crystallography, which allows for high-resolution molecular imaging.

The researchers determined that the protein’s ability to dimerize dependent on the lanthanide to which it was bound came down to a single amino acid — 1% of the whole protein — that occupied a different position with lanthanum (which, like neodymium, is a light lanthanide) than with dysprosium.

Because this amino acid is part of a network of interconnected amino acids at the interface with the other monomer, this shift altered how the two protein units interacted. When an amino acid that is a key player in this network was removed, the protein was much less sensitive to rare earth identity and size. The findings revealed a new, natural principle for fine-tuning rare earth separations, based on propagation of miniscule differences at the rare earth binding site to the dimer interface.

Using this knowledge, their collaborators at Lawrence Livermore National Laboratory showed that the protein could be tethered to small beads in a column, and that it could separate the most important components of permanent magnets, neodymium and dysprosium, in a single step, at room temperature and without any organic solvents.

“While we are by no means the first scientists to recognize that metal-sensitive dimerization could be a way of separating very similar metals, mostly with synthetic molecules,” Cotruvo said, “this is the first time that this phenomenon has been observed in nature with the lanthanides. This is basic science with applied outcomes. We’re revealing what nature is doing and it’s teaching us what we can do better as chemists.”

Cotruvo believes that the concept of binding rare earths at a molecular interface, such that dimerization is dependent on the exact size of the metal ion, can be a powerful approach for accomplishing challenging separations.

“This is the tip of the iceberg,” he said. “With further optimization of this phenomenon, the toughest problem of all — efficient separation of rare earths that are right next to each other on the periodic table — may be within reach.”

A patent application was filed by Penn State based on this work and the team is currently scaling up operations, fine-tuning and streamlining the protein with the goal of commercializing the process.

Other Penn State co-authors are Joseph Mattocks, Jonathan Jung, Chi-Yun Lin, Neela Yennawar, Emily Featherston and Timothy Hamilton. Ziye Dong, Christina Kang-Yun and Dan Park of the Lawrence Livermore National Laboratory also co-authored the paper.

The work was funded by the U.S. Department of Energy, the National Science Foundation, the National Institutes of Health, the Jane Coffin Childs Memorial Fund for Medical Research, and the Critical Materials Institute, an Energy Innovation Hub funded by the DOE, Office of Energy Efficiency and Renewable Energy, Advanced Materials and Manufacturing Technologies Office. Part of the work was performed under the auspices of the DOE by Lawrence Livermore National Laboratory.