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Study ties milder COVID-19 symptoms to prior run-ins with other coronaviruses
![Study ties milder COVID-19 symptoms to prior run-ins with other coronaviruses Study ties milder COVID-19 symptoms to prior run-ins with other coronaviruses](https://www.sciencedaily.com/images/scidaily-icon.png)
A study by Stanford University School of Medicine investigators hints that people with COVID-19 may experience milder symptoms if certain cells of their immune systems “remember” previous encounters with seasonal coronaviruses — the ones that cause about a quarter of the common colds kids get.
The findings may help explain why some people, particularly children, seem much more resilient than others to infection by SARS-CoV-2, the coronavirus that causes COVID-19. They also might make it possible to predict which people are likely to develop the most severe symptoms of COVID-19.
The immune cells in question, called killer T cells, roam through the blood and lymph, park in tissues and carry out stop-and-frisk operations on resident cells. The study, published online July 1 in Science Immunology, showed that killer T cells taken from the sickest COVID-19 patients exhibit fewer signs of having had previous run-ins with common-cold-causing coronaviruses.
Discussions about immunity to COVID-19 often center on antibodies — proteins that can latch onto a virus before it’s able to infect a vulnerable cell. But antibodies are easily fooled, said Mark Davis, PhD, a professor of microbiology and immunology; director of Stanford’s Institute for Immunity, Transplantation and Infection; and a Howard Hughes Medical Institute investigator. Davis is the study’s senior author.
“Pathogens evolve quickly and ‘learn’ to hide their critical features from our antibodies,” said Davis, who is also the Burt and Marion Avery Family Professor. But T cells recognize pathogens in a different way, and they’re tough to fool.
Our cells all issue real-time reports on their inner state of affairs by routinely sawing up some samples of each protein they’ve made lately into tiny pieces called peptides and displaying those peptides on their surfaces for inspection by T cells.
When a killer T-cell’s receptor notices a peptide on a cell’s surface that doesn’t belong there — for example, it’s from a protein produced by an invading microorganism — the T cell declares war. It multiplies furiously, and its numerous offspring — whose receptors all target the same peptide sequence — fire up to destroy any cell carrying these telltale-peptide indications of that cell’s invasion by a pathogenic microbe.
Some of the original killer T cell’s myriad daughter cells enter a more placid state, remaining above the fray. These “memory T cells” exhibit heightened sensitivity and exceptional longevity. They persist in the blood and lymph often for decades, ready to spring into action should they ever cross paths with the peptide that generated the wave of T-cell expansion that begat them. That readiness can save valuable time in stifling a previously encountered virus or a close cousin.
As the pandemic progressed, Davis mused: “A lot of people get very sick or die from COVID-19, while others are walking around not knowing they have it. Why?”
To find out, the study’s first author, postdoctoral fellow Vamsee Mallajosyula, PhD, first confirmed that some portions of SARS-CoV-2’s sequence are effectively identical to analogous portions of one or more of the four widespread common-cold-causing coronavirus strains. Then he assembled a panel of 24 different peptide sequences that were either unique to proteins made by SARS-CoV-2 or also found on similar proteins made by one or more (or even all) of the seasonal strains.
The researchers analyzed blood samples taken from healthy donors before the COVID-19 pandemic began, meaning they’d never encountered SARS-CoV-2 — although many presumably had been exposed to common-cold-causing coronavirus strains. The scientists determined the numbers of T cells targeting each peptide represented in the panel.
They found that unexposed individuals’ killer T cells targeting SARS-CoV-2 peptides that were shared with other coronaviruses were more likely to have proliferated than killer T cells targeting peptides found only on SARS-CoV-2. The T cells targeting those shared peptide sequences had probably previously encountered one or another gentler coronavirus strain — and had proliferated in response, Davis said.
Many of these killer T cells were in “memory” mode, he added.
“Memory cells are by far the most active in infectious-disease defense,” Davis said. “They’re what you want to have in order to fight off a recurring pathogen. They’re what vaccines are meant to generate.”
Killer T cells whose receptors target peptide sequences unique to SARS-CoV-2 must proliferate over several days to get up to speed after exposure to the virus, Davis said. “That lost time can spell the difference between never even noticing you have a disease and dying from it,” he said.
To test this hypothesis, Davis and his colleagues turned to blood samples from COVID-19 patients. They found that, sure enough, COVID-19 patients with milder symptoms tended to have lots of killer-T memory cells directed at peptides SARS-CoV-2 shared with other coronavirus strains. Sicker patients’ expanded killer T-cell counts were mainly among those T cells typically targeting peptides unique to SARS-CoV-2 and, thus, probably had started from scratch in their response to the virus.
“It may be that patients with severe COVID-19 hadn’t been infected, at least not recently, by gentler coronavirus strains, so they didn’t retain effective memory killer T cells,” Davis said.
Davis noted that cold-causing seasonal coronavirus strains are rampant among children, who rarely develop severe COVID-19 even though they’re just as likely to get infected as adults are.
“Sniffles and sneezes typify the daycare setting,” he said, “and coronavirus-caused common colds are a big part of the reason. As many as 80% of kids in the United States get exposed within the first couple of years of life.”
Davis and Mallajosyula have filed, through Stanford’s Office of Technology Licensing, for patents on the technology used in this study.
Davis is a member of Stanford Bio-X, the Stanford Cardiovascular Institute, the Stanford Maternal and Child Health Research Institute, the Stanford Cancer Institute and the Stanford Wu Tsai Neurosciences Institute.
Other Stanford study co-authors are former undergraduate student Conner Ganjavi; postdoctoral scholar Saborni Chakraborty, PhD; former life science research professionals Alana McSween and Allison Nau; graduate student Ana Jimena Pavlovitch-Bedzyk; life science research professional Julie Wilhelmy; Monali Manohar, PhD, laboratory director and research scientist at the Sean N. Parker Center for Asthma and Allergy Research; and Kari Nadeau, MD, PhD, professor of pediatrics and director of the Sean N. Parker Center.
The work was funded by the National Institutes of Health (grants AI057229 and U01 AI140498); Stanford’s Institute for Immunity, Transplantation and Infection; the Howard Hughes Medical Institute; the Bill and Melinda Gates Foundation; the Sean N. Parker Center and the Sunshine Foundation.
Stanford’s Department of Microbiology and Immunology also supported the work.
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Early dark energy could resolve cosmology’s two biggest puzzles
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A new study by MIT physicists proposes that a mysterious force known as early dark energy could solve two of the biggest puzzles in cosmology and fill in some major gaps in our understanding of how the early universe evolved.
Now, the MIT team has found that both puzzles could be resolved if the early universe had one extra, fleeting ingredient: early dark energy. Dark energy is an unknown form of energy that physicists suspect is driving the expansion of the universe today. Early dark energy is a similar, hypothetical phenomenon that may have made only a brief appearance, influencing the expansion of the universe in its first moments before disappearing entirely.
Some physicists have suspected that early dark energy could be the key to solving the Hubble tension, as the mysterious force could accelerate the early expansion of the universe by an amount that would resolve the measurement mismatch.
The MIT researchers have now found that early dark energy could also explain the baffling number of bright galaxies that astronomers have observed in the early universe. In their new study, reported in the Monthly Notices of the Royal Astronomical Society, the team modeled the formation of galaxies in the universe’s first few hundred million years. When they incorporated a dark energy component only in that earliest sliver of time, they found the number of galaxies that arose from the primordial environment bloomed to fit astronomers’ observations.
“You have these two looming open-ended puzzles,” says study co-author Rohan Naidu, a postdoc in MIT’s Kavli Institute for Astrophysics and Space Research. “We find that in fact, early dark energy is a very elegant and sparse solution to two of the most pressing problems in cosmology.”
The study’s co-authors include lead author and Kavli postdoc Xuejian (Jacob) Shen, and MIT professor of physics Mark Vogelsberger, along with Michael Boylan-Kolchin at the University of Texas at Austin, and Sandro Tacchella at the University of Cambridge.
Big city lights
Based on standard cosmological and galaxy formation models, the universe should have taken its time spinning up the first galaxies. It would have taken billions of years for primordial gas to coalesce into galaxies as large and bright as the Milky Way.
But in 2023, NASA’s James Webb Space Telescope (JWST) made a startling observation. With an ability to peer farther back in time than any observatory to date, the telescope uncovered a surprising number of bright galaxies as large as the modern Milky Way within the first 500 million years, when the universe was just 3 percent of its current age.
“The bright galaxies that JWST saw would be like seeing a clustering of lights around big cities, whereas theory predicts something like the light around more rural settings like Yellowstone National Park,” Shen says. “And we don’t expect that clustering of light so early on.”
For physicists, the observations imply that there is either something fundamentally wrong with the physics underlying the models or a missing ingredient in the early universe that scientists have not accounted for. The MIT team explored the possibility of the latter, and whether the missing ingredient might be early dark energy.
Physicists have proposed that early dark energy is a sort of antigravitational force that is turned on only at very early times. This force would counteract gravity’s inward pull and accelerate the early expansion of the universe, in a way that would resolve the mismatch in measurements. Early dark energy, therefore, is considered the most likely solution to the Hubble tension.
Galaxy skeleton
The MIT team explored whether early dark energy could also be the key to explaining the unexpected population of large, bright galaxies detected by JWST. In their new study, the physicists considered how early dark energy might affect the early structure of the universe that gave rise to the first galaxies. They focused on the formation of dark matter halos — regions of space where gravity happens to be stronger, and where matter begins to accumulate.
“We believe that dark matter halos are the invisible skeleton of the universe,” Shen explains. “Dark matter structures form first, and then galaxies form within these structures. So, we expect the number of bright galaxies should be proportional to the number of big dark matter halos.”
The team developed an empirical framework for early galaxy formation, which predicts the number, luminosity, and size of galaxies that should form in the early universe, given some measures of “cosmological parameters.” Cosmological parameters are the basic ingredients, or mathematical terms, that describe the evolution of the universe.
Physicists have determined that there are at least six main cosmological parameters, one of which is the Hubble constant — a term that describes the universe’s rate of expansion. Other parameters describe density fluctuations in the primordial soup, immediately after the Big Bang, from which dark matter halos eventually form.
The MIT team reasoned that if early dark energy affects the universe’s early expansion rate, in a way that resolves the Hubble tension, then it could affect the balance of the other cosmological parameters, in a way that might increase the number of bright galaxies that appear at early times. To test their theory, they incorporated a model of early dark energy (the same one that happens to resolve the Hubble tension) into an empirical galaxy formation framework to see how the earliest dark matter structures evolve and give rise to the first galaxies.
“What we show is, the skeletal structure of the early universe is altered in a subtle way where the amplitude of fluctuations goes up, and you get bigger halos, and brighter galaxies that are in place at earlier times, more so than in our more vanilla models,” Naidu says. “It means things were more abundant, and more clustered in the early universe.”
“A priori, I would not have expected the abundance of JWST’s early bright galaxies to have anything to do with early dark energy, but their observation that EDE pushes cosmological parameters in a direction that boosts the early-galaxy abundance is interesting,” says Marc Kamionkowski, professor of theoretical physics at Johns Hopkins University, who was not involved with the study. “I think more work will need to be done to establish a link between early galaxies and EDE, but regardless of how things turn out, it’s a clever — and hopefully ultimately fruitful — thing to try.”
“We demonstrated the potential of early dark energy as a unified solution to the two major issues faced by cosmology. This might be an evidence for its existence if the observational findings of JWST get further consolidated,” Vogelsberger concludes. “In the future, we can incorporate this into large cosmological simulations to see what detailed predictions we get.”
This research was supported, in part, by NASA and the National Science Foundation.
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Plant-derived secondary organic aerosols can act as mediators of plant-plant interactions
![Study ties milder COVID-19 symptoms to prior run-ins with other coronaviruses Study ties milder COVID-19 symptoms to prior run-ins with other coronaviruses](https://www.sciencedaily.com/images/scidaily-icon.png)
A new study published in Science reveals that plant-derived secondary organic aerosols (SOAs) can act as mediators of plant-plant interactions. This research was conducted through the cooperation of chemical ecologists, plant ecophysiologists and atmospheric physicists at the University of Eastern Finland.
The study showed that Scots pine seedlings, when damaged by large pine weevils, release VOCs that activate defences in nearby plants of the same species. Interestingly, the biological activity persisted after VOCs were oxidized to form SOAs. The results indicated that the elemental composition and quantity of SOAs likely determines their biological functions.
“A key novelty of the study is the finding that plants adopt subtly different defence strategies when receiving signals as VOCs or as SOAs, yet they exhibit similar degrees of resistance to herbivore feeding,” said Professor James Blande, head of the Environmental Ecology Research Group. This observation opens up the possibility that plants have sophisticated sensing systems that enable them to tailor their defences to information derived from different types of chemical cue.
“Considering the formation rate of SOAs from their precursor VOCs, their longer lifetime compared to VOCs, and the atmospheric air mass transport, we expect that the ecologically effective distance for interactions mediated by SOAs is longer than that for plant interactions mediated by VOCs,” said Professor Annele Virtanen, head of the Aerosol Physics Research Group. This could be interpreted as plants being able to detect cues representing close versus distant threats from herbivores.
The study is expected to open up a whole new complex research area to environmental ecologists and their collaborators, which could lead to new insights on the chemical cues structuring interactions between plants.
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Folded or cut, this lithium-sulfur battery keeps going
![Study ties milder COVID-19 symptoms to prior run-ins with other coronaviruses Study ties milder COVID-19 symptoms to prior run-ins with other coronaviruses](https://www.sciencedaily.com/images/scidaily-icon.png)
Most rechargeable batteries that power portable devices, such as toys, handheld vacuums and e-bikes, use lithium-ion technology. But these batteries can have short lifetimes and may catch fire when damaged. To address stability and safety issues, researchers reporting in ACS Energy Letters have designed a lithium-sulfur (Li-S) battery that features an improved iron sulfide cathode. One prototype remains highly stable over 300 charge-discharge cycles, and another provides power even after being folded or cut.
The team coated iron sulfide cathodes in different polymers and found in initial electrochemical performance tests that polyacrylic acid (PAA) performed best, retaining the electrode’s discharge capacity after 300 charge-discharge cycles. Next, the researchers incorporated a PAA-coated iron sulfide cathode into a prototype battery design, which also included a carbonate-based electrolyte, a lithium metal foil as an ion source, and a graphite-based anode. They produced and then tested both pouch cell and coin cell battery prototypes.
After more than 100 charge-discharge cycles, Wang and colleagues observed no substantial capacity decay in the pouch cell. Additional experiments showed that the pouch cell still worked after being folded and cut in half. The coin cell retained 72% of its capacity after 300 charge-discharge cycles. They next applied the polymer coating to cathodes made from other metals, creating lithium-molybdenum and lithium-vanadium batteries. These cells also had stable capacity over 300 charge-discharge cycles. Overall, the results indicate that coated cathodes could produce not only safer Li-S batteries with long lifespans, but also efficient batteries with other metal sulfides, according to Wang’s team.
The authors acknowledge funding from the National Natural Science Foundation of China; the Natural Science Foundation of Sichuan, China; and the Beijing National Laboratory for Condensed Matter Physics.
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