The research team, led by Emory University and funded by the National Institute of Health’s (NIH) Rapid Acceleration of Diagnostics (RADx) Tech program, developed a novel method for evaluating how mutations to SARS-CoV-2 can affect recognition by antibodies used in rapid antigen tests. Because most rapid antigen tests detect the SARS-CoV-2 nucleocapsid protein (N protein), the team directly measured how mutations to the N protein impacted diagnostic antibodies’ ability to recognize their target.

“Based on our findings, none of the major past and present SARS-CoV-2 variants of concern contain mutations that would affect the capability of current rapid antigen tests to detect antibodies,” says first study author Filipp Frank, Ph.D., an assistant professor in the department of biochemistry at Emory University. “Further, these data allow us to look one step ahead and predict test performance against almost any variant that may arise.”

The study used a method called deep mutational scanning to evaluate all possible mutations in the N protein in a single, high-throughput experiment. Researchers then measured the impact of the mutations on their interaction with antibodies used in 11 commercially available rapid antigen tests and identified mutations that may allow for antibody escape.

“Accurate and efficient identification of infected individuals remains a critically important strategy for COVID-19 mitigation, and our study provides information about future SARS-CoV-2 mutations that may interfere with detection,” says senior study author Eric Ortlund, Ph.D., a professor in the department of biochemistry at Emory University. “The results outlined here can allow us to quickly adapt to the virus as new variants continue to emerge, representing an immediate clinical and public health impact.”

Findings show that it’s relatively rare for variants to have mutations to the N protein that allow them to evade diagnostic tests, but there are a small proportion of sequences that could impact detection. Researchers, public health officials, and test manufacturers can use these data to determine if a diagnostic test needs to be evaluated for its ability to detect these mutations or to inform future test design.

“Considering the endless cycle of new variants, the data from this study will be useful for years to come,” says Bruce J. Tromberg, Ph.D., director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and lead for the RADx® Tech program at NIH.

While many variants of concern contain multiple mutations to the N protein, the study authors note that their method does not evaluate how multiple mutations could affect diagnostic antibody recognition, representing a limitation of the study.

The project was supported by NIBIB under award numbers 75N92019P00328, U54EB015408, and U54EB027690 as part of the RADx initiative, launched to speed innovation in the development, commercialization and implementation of technologies for COVID-19 testing.

Story Source:

Materials provided by Emory Health Sciences. Note: Content may be edited for style and length.

“This is essential, because inflammation releases free radicals against which nerve fibers cannot protect themselves. Therefore, the inflammation must be cleared quickly, which is precisely what Schwann cells do,” explains Dr. Sabine Taschner-Mandl, who designed the study and heads a research group at St. Anna CCRI. The new results, in which the Medical University of Vienna is also significantly involved, were published in the journal Glia.

Do Schwann cells protect against malignancy?

How are these results related to tumor growth? After nerve injury, Schwann cells adopt a “repair” mode that is also found in benign infantile nerve tumors. There, it causes the tumor cells to mature and thus reach a stage where they lose their aggressive properties and no longer divide unchecked (Weiss T., Taschner-Mandl S., et al., Nat Commun 2021).

“Based on the current results, we now suspect that the immune cell functions of Schwann cells also become effective in childhood nerve tumors. This is because in cancer, there is always a kind of inflammation bubbling away that never comes to a halt. In benign nerve tumors, ganglioneuromas, the accompanying chronic inflammation could be stopped by Schwann cells similar to nerve healing, because unlike malignancies, benign nerve tumors have many Schwann cells in their microenvironment. We also see that a lot of immune cells migrate into these tumors, for which the Schwann cells could also be responsible,” says Sabine Taschner-Mandl.

Healthy Inflammation: First Activate, Then Shut Down

In particular, the current study shows that Schwann cells can influence certain immune cells, so-called T cells, which play an important role in the defense against cancer. Schwann cells — both those in nerve regeneration and those in benign tumors — carry MHC-I and MHC-II molecules on their surface that are important for T-cell regulation. Via these molecules, Schwann cells present recognition features of material they have previously taken up from their environment.

We mimicked an inflammatory response in the laboratory and detected a whole range of additional stimulatory and inhibitory surface molecules that are also necessary for T cell activation,” explains Jakob Berner, MSc, co-first author of the study and interim PhD student in Kaan Boztug’s group at St. Anna CCRI. “Our experiments show that Schwann cells are able to take up large amounts of material via phagocytosis.”

As the first immune response to a nerve cut, Schwann cells secrete substances that attract T cells, macrophages and other immune cells. Now it turned out that not only a reaction between the classical immune cells takes place, but also between Schwann cells and T cells.

While Schwann cells initially fuel the inflammatory response by releasing interferon-gamma, they can later shut it down by up-regulating the T-cell inhibitory PD-L1 molecule.

“First activate, then shut down — that’s the normal process of an inflammatory response. If this were also the case in cancer, then it could curb cancer growth,” comments Sabine Taschner-Mandl. Whether and how these findings can be used for potential cancer therapies is now being researched.

“What’s important about the tuatara is that it represents this enormous evolutionary story that we are lucky enough to catch in what is likely its closing act,” Carrano said. “Even though it looks like a relatively simple lizard, it embodies an entire evolutionary epic going back more than 200 million years.”

The discovery comes from a handful of specimens including an extraordinarily complete and well-preserved fossil skeleton excavated from a site centered around an Allosaurus nest in northern Wyoming’s Morrison Formation. Further study of the find could help reveal why this animal’s ancient order of reptiles were winnowed down from being diverse and numerous in the Jurassic to just New Zealand’s tuatara surviving today.

The tuatara looks a bit like a particularly stout iguana, but the tuatara and its newly discovered relative are in fact not lizards at all. They are actually rhynchocephalians, an order that diverged from lizards at least 230 million years ago, Carrano said.

In their Jurassic heyday, rhynchocephalians were found nearly worldwide, came in sizes large and small, and filled ecological roles ranging from aquatic fish hunters to bulky plant munchers. But for reasons that still are not fully understood, rhynchocephalians all but disappeared as lizards and snakes grew to be the more common and more diverse reptiles across the globe.

This evolutionary chasm between lizards and rhynchocephalians helps explain the tuatara’s odd features such as teeth fused to the jaw bone, a unique chewing motion that slides the lower jaw back and forth like a saw blade, a 100-year-plus lifespan and a tolerance for colder climates.

Following O. gregori‘s formal description, Carrano said the fossil has been added to the museum’s collections where it will remain available for future study, perhaps one day helping researchers figure out why the tuatara is all that remains of the rhynchocephalians, while lizards are now found across the globe.

“These animals may have disappeared partly because of competition from lizards but perhaps also due to global shifts in climate and changing habitats,” Carrano said. “It’s fascinating when you have the dominance of one group giving way to another group over evolutionary time, and we still need more evidence to explain exactly what happened, but fossils like this one are how we will put it together.”

The researchers named the new species after museum volunteer Joseph Gregor who spent hundreds of hours meticulously scraping and chiseling the bones from a block of stone that first caught museum fossil preparator Pete Kroehler’s eye back in 2010.

“Pete is one of those people who has a kind of X-ray vision for this sort of thing,” Carrano said. “He noticed two tiny specks of bone on the side of this block and marked it to be brought back with no real idea what was in it. As it turns out, he hit the jackpot.”

The fossil is almost entirely complete, with the exception of the tail and parts of the hind legs. Carrano said that such a complete skeleton is rare for small prehistoric creatures like this because their frail bones were often destroyed either before they fossilized or as they emerge from an eroding rock formation in the present day. As a result, rhynchocephalians are mostly known to paleontologists from small fragments of their jaws and teeth.

After Kroehler, Gregor and others had freed as much of the tiny fossil from the rock as was practical given its fragility, the team, led by DeMar, set about scanning the fossil with high-resolution computerized tomography (CT), a method that uses multiple X-ray images from different angles to create a 3D representation of the specimen. The team used three separate CT scanning facilities, including one housed at the National Museum of Natural History, to capture everything they possibly could about the fossil.

Once the fossil’s bones had been digitally rendered with accuracy smaller than a millimeter, DeMar set about reassembling the digitized bones of the skull, some of which were crushed, out of place or missing on one side, using software to eventually create a nearly complete 3D reconstruction. The reconstructed 3D skull now provides researchers an unprecedented look at this Jurassic-age reptile’s head.

Given Opisthiamimus‘s diminutive size, tooth shape and rigid skull, it likely ate insects, said DeMar, adding that prey with harder shells such as beetles or water bugs might have also been on the menu. Broadly speaking, the new species looks quite a bit like a miniaturized version of its only surviving relative (tuataras are about five times longer).

“Such a complete specimen has huge potential for making comparisons with fossils collected in the future and for identifying or reclassifying specimens already sitting in a museum drawer somewhere,” DeMar said. “With the 3D models we have, at some point we could also do studies that use software to look at this critter’s jaw mechanics.”

Funding and support for this research were provided by the Smithsonian and the Australian Research Council.

“We tend to use what we can call a ‘moral wiggle room’ to justify selfish decisions. This means that we can act selfishly in certain situations, without feeling that our actions are morally wrong,” says Kajsa Hansson, newly promoted doctor in economics at Linköping University, with a thesis entitled Moral Illusions.

In the thesis, she examines several aspects of what she terms ‘moral illusions’, and compares them to optical illusions. She concludes that we can tweak our morals in some situations to increase self-benefit.

“Fairness is in the eye of the beholder. But I have used a broad definition of morality, and I don’t judge whether a certain type of fairness is good or bad. Instead, I use the idea of whether a person experiences that they are not living up to their own notion of good morality,” says Kajsa Hansson.

Moral illusions mainly arise in competitive situations when many people compete for the same rewards. This is a consequence of psychological mechanisms that cause us to assess fairness differently, depending on whether we are successful or not. This is particularly the case when we lack information about the fairness of the situation. When the brain attempts to fill in missing information, it may create an image that does not match reality — in the same way as occurs for an optical illusion.

One example is how we view losing. If we lose, we tend to blame it on that the playing field was not level, or that the game was rigged. When we win, in contrast, we explain this by our excellent playing skills. This tendency may describe why successful people believe that the world is a meritocracy, and that economic inequalities are thus fair.

Kajsa Hansson has also investigated how we react to decisions when we can avoid information that may encourage unselfish behaviour. In this case, again, our morality can be tweaked, since we are reluctant to seek out more information that risks giving us a bad conscience. Such information may force us to act unselfishly.

There is, however, one situation in which moral illusions do not play a role — when decisions are taken democratically. This may be the case for decisions taken by the national parliament, but it also applies in the committees of clubs, companies, etc., where several people are involved and take decisions collectively. This result contradicts the currently accepted theory, which says that we become less moral when the responsibility for a decision is shared among several people. This phenomenon is known as the “diffusion of responsibility.”

“When decisions are taken democratically, there is always someone else we can blame, and previous studies have shown that we become more selfish when the responsibility for a decision is spread among several people. However, our results do not support the idea that people become less moral when taking such decisions. In fact, quite the opposite,” says Kajsa Hansson.

In the study, Kajsa Hansson and her colleagues carried out three experiments in which the participants must choose whether to donate or claim money. In some experiments, the decision was a democratic one between several participants; in others the participants acted individually. The results showed that it was not possible to see any selfish behaviour. Indeed, they showed that people tend to become more generous in this scenario.

“Our results are actually very good news. They suggest that we possess the insight that we take decisions for others, and we act collectively. We can speculate that people realise that we can contribute more to the common good when everyone contributes,” says Kajsa Hansson.

The thesis considers decision-making in a broad perspective, and looks at how morality affects it. Kajsa Hansson believes that it can help us understand each other better.

“We may not always agree with everyone’s interpretations of reality, but we can understand where they come from.”

The thesis has been funded by the Lars Hierta Memorial Foundation and the Helge Ax:son Johnson Foundation.

Story Source:

Materials provided by Linköping University. Original written by Anders Törneholm. Note: Content may be edited for style and length.

The paper, which published today in The Lancet Global Health, explores the feasibility of eliminating measles and rubella using predominant vaccination strategies in 93 countries with the highest disease burden.

Despite marked reductions in the number of new measles and rubella cases worldwide, gaps remain between current levels of transmission and disease elimination. 

“Measles is one of the most contagious respiratory infections out there, and it moves quickly, so it’s hard to control,” said lead author Amy Winter, an assistant professor of epidemiology and biostatistics at UGA’s College of Public Health. 

The basic reproduction number (R₀) for measles, which represents the number of people that one infected person is likely to transmit that disease to in a fully susceptible population, is roughly 18. By comparison the R₀ for the original SARS-CoV-2 virus is estimated to be around three.

In 2017, the World Health Organization director general requested a report on the feasibility of measles and rubella eradication. One component of this report was to use transmission models to evaluate the theoretical feasibility of eradication of the two viruses given different vaccination strategies.

The assessment was a collaboration with the WHO Strategic Advisory Group of Experts Measles and Rubella Working Group, the World Health Organization, the U.S. Centers for Disease Control and Prevention, and five modeling groups.

Using four national disease transmission models and one sub-national model, the modeling groups projected the annual case rates for measles and rubella for two vaccination scenarios.

Both vaccination scenarios use the two predominant vaccination approaches of routine vaccination as part of childhood immunization schedules and nationwide vaccination campaigns.

The first “business as usual” vaccination scenario continues vaccination coverage and campaigns into the future. The second “intensified investment” vaccination scenario optimally improved vaccination coverage over time. This scenario also included vaccination campaign cessation criteria – a stopping point for when campaigns are no longer deemed necessary because a large enough proportion of the population has been inoculated.

The models show that current vaccine strategies could eliminate rubella and congenital rubella syndrome in all 93 counties, but not measles. 

“The current strategy that we use, which is focused on improving routine vaccination coverage and supplementing it with nationwide vaccination campaigns until routine vaccination is high enough, that alone is not going to be sufficient to reach measles elimination. We need novel approaches,” said Winter. 

The authors evaluated two strategies that could help move a country to elimination faster and reduce the probability of measles outbreaks: One, improve how supplemental vaccine campaigns are delivered to ensure they are reaching children who are not receiving routine vaccinations.

Two, improve vaccine coverage equity by focusing routine and supplemental vaccination on sub-regions with the lowest vaccination coverage first to get them up to par.

“A world that is permanently free of measles and rubella would be an incredible achievement for humanity. Our work suggests that to reach this goal, we need to make vaccine coverage much more equal,” said co-author Mark Jit, professor of vaccine epidemiology at the London School of Hygiene & Tropical Medicine.

“In other words, we need to work even harder to bring measles and rubella vaccination to the most underserved people around the world.”

The final strategy the authors present is a reconsideration of cessation criteria. Currently, most countries stop supplementing routine vaccines with vaccination campaigns once they reach elimination status, said Winter, but the models suggest that outbreaks are still likely to occur if countries rely on routine vaccines alone.

It’s critical, Winter warns, to remain vigilant to surveil for rubella and measles cases and rapidly respond to potential outbreaks even after elimination is achieved.

“We have a globally connected world, so there’s this constant pressure of importations of the viruses in places where it’s already eliminated,” she said. “That’s why keeping vaccination coverage high and continuing to improve surveillance for these diseases is important.”

The researchers report their findings in the Proceedings of the Royal Society B.

If a cowbird ends up in a prothonotary warbler nest with four host chicks, the cowbird either perishes or the number of warbler chicks drops, usually to two, the study found. This suggests that cowbirds engage in what the naturalist Charles Darwin called “niche construction,” modifying their environment to enhance their own survival, the researchers said.

“Brood parasites like brown-headed cowbirds lay their eggs in the nests of so many different species, we wanted to know about one really important aspect of how they make a go of it in a world that, when they hatch, could be any one of 200 different scenarios,” said Nicholas Antonson, a Ph.D. candidate at the University of Illinois Urbana-Champaign who led the study with Mark Hauber, a U. of I. professor of evolution, ecology and behavior. “We focused on what happens when a cowbird hatches into a nest with different numbers of host nestlings.”

Cowbird chicks never eject eggs from host nests or directly kill host young. This differentiates them from another brood parasite, the common cuckoo, which will kill all other chicks in the nest and claim all the food the foster parents can provide, Antonson said. A previous study from Hauber’s own postdoctoral research showed that this strategy does not work for cowbirds in the nests of another host bird: the Eastern phoebe. In that study, cowbirds actually got less food from host parents when there were no nest mates than when there were two host chicks.

“Cowbirds have adapted to live with host nest mates,” Hauber said. “They outcompete them, they raise their heads higher, and they beg more loudly and for longer periods of time, but they do not actively displace the host nest mates.”

To better understand these dynamics, the team deployed nest boxes that were attractive to warblers and cowbirds in a southern Illinois swamp forest. The boxes were designed to exclude ground predators like snakes and raccoons, and aerial predation by hawks and owls. By changing out the bedding in the boxes four days after the eggs hatched, the team also reduced the threat from invertebrate parasites like blowflies.

The team followed nests with and without cowbird parasites and manipulated the number of host chicks in the nests by moving warbler eggs or chicks between nests. All the nests parasitized by cowbirds had either zero, two or four warbler nest mates. Control nests containing only warbler chicks were matched for the total number of young.

Previous studies had quantified the amount of food the host parents brought into the nest and what proportion of the food the cowbird nestling received. In general, cowbirds hatch earlier than their nest mates. They tend to be bigger and more aggressive than warbler chicks and extract more than their fair share of food from the host parents, Antonson said. Cowbirds need more food because they grow two-to-three times larger in the nest than the warbler chicks.

“One of the unique aspects of our study is that we also quantified how many cowbirds survived to fledging in each of these different scenarios,” Antonson said. “We found that cowbirds survive best in the nests where they hatch with two host nestlings. That’s better than when they hatch with four host nestlings or with zero host nestlings. Cowbirds raised with more than that optimal number of two host nestlings appear to reduce the host brood sizes down to two.”

The reduction seen in host nestling numbers when cowbirds are present doesn’t occur in the control warbler nests with no cowbird nestlings, the researchers found.

“We think that the cowbirds are manipulating the host numbers to reduce them to the optimal so that they can grow best,” Hauber said. Stealing food meant for the other nestlings is the likely means by which they do that. Further studies will be needed to confirm that hypothesis.

The Animal Behavior Society, Humboldt Foundation and National Science Foundation supported this research.