Detailed in a new study for the journal Nature, funded by the Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation, and the Royal Society, the results give the first evidence of a process in ferroelectric materials comparable to the Dzyaloshinskii-Moriya interaction in ferromagnets. This particular interaction plays a pivotal role in stabilising topological magnetic structures, such as skyrmions, and it might be crucial for potential new electronic technologies exploiting their electrical analogues.

Bulk ferroelectric crystals have been used for many years in a range of technologies including sonar, audio transducers and actuators. All these technologies exploit the intrinsic electric dipoles and their inter-relationship between the material’s crystal structure and applied fields.

For this study, the scientists created a thin film of the ferroelectric lead titanate sandwiched between layers of the ferromagnet strontium ruthenate, each about 4 nanometres thick — only twice the thickness of a single strand of DNA.

While the atoms of the two materials form a single continuous crystal structure, in the ferroelectric lead titanate layer the electric polarisation would normally form multiple ‘domains’, like a honeycomb. These domains can only be observed using state-of-the-art transmission electron microscopy and x-ray scattering.

But when the University of Warwick team examined the structure of the combined layers, they saw that the domains in the lead titanate were a complex topological structure of lines of vortexes, spinning alternately in different directions.

Almost identical behaviour has also been seen in ferromagnets where it is known to be generated by the Dzyaloshinskii-Moriya interaction (DMi).

Lead author Professor Marin Alexe of the University of Warwick Department of Physics said: “If you look at how these characteristics scale down, the difference between ferromagnetism and ferroelectricity becomes less and less important. It might be that they will merge at some point in one unique material. This could be artificial and combine very small ferromagnets and ferroelectrics to take advantage of these topological features. It’s very clear to me that we are at the tip of the iceberg as far as where this research is going to go.”

Co-author Dorin Rusu, a postgraduate student at the University of Warwick, said: “Realising that in ferroelectrics dipolar textures that mimic their magnetic counterpart to such a degree ensures further research into the fundamental physics that drives such similarities. This result is not a trivial matter when you consider the difference in the origin and strengths of the electric and magnetic fields.”

The existence of these vortexes had previously been theorised, but it took the use of cutting-edge transmission electron microscopes at the University of Warwick, as well as the use of synchrotrons at four other facilities, to accurately observe them. These techniques allowed the scientists to measure the position of every atom to a high degree of certainty.

Co-author Professor Ana Sanchez said: “Electron microscopy is a game-changing technique in understanding these topological structures. It is the key tool in revealing the ins and outs of these novel materials, using a subatomic beam of electrons to generate images of internal structure.”

Co-author Professor Thomas Hase added: “Accessing high end facilities across UK, Europe and US has been critical for this particular research.”

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The research, recently published in the journal Cell, reveals the immune mechanisms and significant benefits of vaccines being delivered directly into the respiratory tract, rather than by traditional injection.

Because inhaled vaccines target the lungs and upper airways where respiratory viruses first enter the body, they are far more effective at inducing a protective immune response, the researchers report.

The reported preclinical study, which was conducted on animal models, has provided the critical proof of concept to enable a Phase 1 clinical trial that is currently under way to evaluate inhaled aerosol vaccines in healthy adults who had already received two doses of a COVID mRNA vaccine.

The tested COVID vaccine strategy was built upon a robust tuberculosis vaccine research program established by Zhou Xing, a co-lead author of the new study and a professor at the McMaster Immunology Research Centre and Department of Medicine.

“What we’ve discovered from many years’ research is that the vaccine delivered into the lung induces all-around protective respiratory mucosal immunity, a property that the injected vaccine is lacking,” Xing says.

Currently authorized COVID vaccines are all injected.

“We wanted, first and foremost, to design a vaccine that would work well against any variant,” explains the study’s co-lead author Matthew Miller, an associate professor at McMaster’s Michael G. DeGroote Institute for Infectious Disease Research.

The McMaster COVID vaccine represents one of only a handful developed in Canada. The urgent work is a critical mission of Canada’s Global Nexus for Pandemics and Biological Threats, which is based at McMaster.

Researchers compared two types of adenovirus platforms for the vaccine. The viruses serve as vectors that can deliver vaccine directly to the lungs without causing illness themselves.

“We can remain ahead of the virus with our vaccine strategy,” says Miller. “Current vaccines are limited because they will need to be updated and will always be chasing the virus.”

Both types of the new McMaster vaccine are effective against highly transmissible variants because they are designed to target three parts of the virus, including two that are highly conserved among coronaviruses and do not mutate as quickly as spike. All COVID vaccines currently approved in Canada target only the spike protein, which has shown a remarkable ability to mutate.

“This vaccine might also provide pre-emptive protection against a future pandemic, and that’s really important because as we’ve seen during this pandemic — and as we saw in 2009 with the swine flu — even when we are able to rapidly make a vaccine for a pandemic virus, it’s already way too late. Millions of people died, even though we were able to make a vaccine in record time,” says Miller.

“We have revealed in our report that besides neutralizing antibodies and T cell immunity, the vaccine delivered into the lungs stimulates a unique form of immunity known as trained innate immunity, which is able to provide very broad protection against many lung pathogens besides SARS-CoV-2,” Xing adds.

In additional to being needle and pain-free, an inhaled vaccine is so efficient at targeting the lungs and upper airways that it can achieve maximum protection with a small fraction of the dose of current vaccines — possibly as little as 1 per cent — meaning a single batch of vaccine could go 100 times further, the researchers say.

“This pandemic has shown us that vaccine supply can be a huge challenge. Demonstrating that this alternative delivery method can significantly extend vaccine supply could be a game changer, particularly in a pandemic setting,” says Brian Lichty, an associate professor in the Department of Medicine who co-led the preclinical study along with Miller, Xing and the senior trainees Sam Afkhami and Michael D’Agostino, who are the joint first authors of the study.

The vaccines were manufactured at the Robert E. Fitzhenry Vector Laboratory at McMaster University.

The research is funded by a CIHR COVID-19 Rapid Response grant.

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Materials provided by McMaster University. Original written by Michelle Donovan. Note: Content may be edited for style and length.

Research into natural products has become a crucial part of drug discovery. Natural products have exhibited promising specificity and efficacy when used against a variety of pathogens, including viruses. For instance, an organic compound called neoechinulin B, isolated from the fungus Eurotium rubrum, has demonstrated antiviral activity against hepatitis C virus (HCV). However, the isolation of such compounds from natural sources can get quite tedious and expensive. Yet, the attempts to synthetically synthesize it seem to be very scarce.

Thus, a group of scientists from across Japan rose to the occasion and embarked on a mission: To discover a simple route for synthesizing neoechinulin B under laboratory conditions. The team included Prof. Kouji Kuramochi and Dr. Koichi Watashi from Tokyo University of Science, along with Dr. Hirofumi Ohashi, Dr. Shusuke Tomoshige, Dr. Kenji Ohgane, and Dr. Shinji Kamisuki from the National Institute of Infectious Diseases, Tohoku University, Ochanomizu University, and Azabu University, respectively. Their findings were recently published in the Journal of Natural Products.

Commenting on their strategy, Prof. Kuramochi, the lead author of the study, says: “We designed a streamlined two-step synthesis strategy to obtain diketopiperazine scaffold of neoechinulin B. The process involved the base-induced coupling of available piperazine-2,5-dione derivative was aldehydes. The coupled products were then treated with a commercial reagent called tetra-n-butylammonium fluoride (TBAF) which gave us neoechinulin B and its 16 other derivatives.”

To ascertain the efficacy of their products, the team tested the antiviral activity of neoechinulin B and its derivatives against different positive-strand RNA viruses, such as HCV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). They found that some derivatives showed anti-HCV activity with minimal cell toxicity, while others showed anti-SARS-CoV-2. Moreover, six derivatives exhibited both strong anti-HCV and SARS-CoV-2.

Further studies by the research team uncovered that neoechinulin B and one derivative can reduced the transcriptional activity of liver X receptors (LXRs). This subsequently disrupts the formation of double-membrane vesicles (DMV), which are the sites where viral RNA replication occur. This process results in reduced viral replication in the infected cells.

Along with the 17 active compounds, the scientists also produced three other compounds which, while structurally related to the others, possessed none of the antiviral properties. Further investigation into their molecular structure revealed that inactive compounds were missing the exomethylene moiety which is the key to the antiviral activities of neoechinulin B and its 16 derivatives against HCV and SARS-CoV-2.

The team believes that the insights from this research could be used as a framework for the development of new broad-spectrum antiviral drugs. The study also solidifies the fact that natural products can act as promising lead compounds for the development of antiviral drugs. “The skeleton of neoechinulin B is simple, but only one chemical synthesis method has been reported in the past. Our research presented a simple and viable method for obtaining promising antiviral compounds bringing us one step closer to its practical application,” concludes Prof. Kuramochi.

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Researchers say the study, which involved tufted capuchin monkeys living in groups at Georgia State’s Language Research Center, is the first to specifically explore whether other species experience pressure to perform.

The monkeys were given a computerized matching task. Some trials were cued to be harder, with a higher possible reward and a timeout consequence for wrong answers, while other trials were typical in difficulty to their usual computer tasks.

The team found that there was significant variation in how individual monkeys responded to these trials when the difference in difficulty was removed, suggesting that for some monkeys the cues of high stakes were enough to impact performance.

“There are several different explanations for why humans might ‘choke’ or ‘thrive’ under pressure, but all of these explanations have traditionally considered this sensitivity to pressure to be a human-specific trait,” said the study’s lead author, Georgia State Ph.D. candidate Meg Sosnowski.

“Our new results provide the first evidence that other species also might be susceptible to this influence of pressure, and that our responses to that pressure are, in part, the result of individual variation in an evolutionarily common stress response.”

The researchers also found that higher levels of a naturally occurring biomarker of stress, cortisol, were related to the monkeys’ performance. Higher levels of cortisol were associated with a lower ability to successfully complete the high-pressure trials, providing evidence that an individual’s long-term stress state might be related to cognitive performance.

“This opens the door not just to explore how responses to pressure might have impacted the evolution of cognition, but also provides clues pointing us to potential avenues that might mitigate performance deficits, both in humans and in other species,” Sosnowski said.

The research team included Marcela Benítez, an assistant professor of anthropology at Emory University, and Sarah Brosnan, who is affiliated with Georgia State’s Department of Psychology and the Center for Behavioral Neuroscience.

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In August 2021, a magnitude 7.5 earthquake hit near the South Sandwich Islands, creating a tsunami that rippled around the globe. The epicenter was 47 kilometers below the Earth’s surface — too deep to initiate a tsunami — and the rupture was nearly 400 kilometers long, which should have generated a much larger earthquake.

Seismologists were puzzled and sought to understand what really happened that day in the remote South Atlantic.

A new study revealed the quake wasn’t a single event, but five, a series of sub-quakes spread out over several minutes. The third sub-quake was a shallower, slower magnitude 8.2 quake that hit just 15 kilometers below the surface. That unusual, “hidden” earthquake was likely the trigger of the worldwide tsunami.

The study was published in the AGU journal Geophysical Research Letters, which publishes short-format, high-impact papers with implications that span the Earth and space sciences.

Because the South Sandwich Islands earthquake was complex, with multiple sub-quakes, its seismic signal was difficult to interpret, according to lead study author Zhe Jia, a seismologist at the California Institute of Technology. The magnitude 8.2 quake was hidden within the tangle of seismic waves, which interfered with each other over the course of the event. The hidden quake’s signal wasn’t clear until Jia filtered the waves using a much longer period, up to 500 seconds. Only then did the 200-second-long quake, which Jia said accounted for over 70% of the energy released during the earthquake, become clear.

“The third event is special because it was huge, and it was silent,” Jia said. “In the data we normally look at [for earthquake monitoring], it was almost invisible.”

Predicting hazards for complex earthquakes can be difficult, as the South Sandwich Islands quake demonstrates. The USGS initially reported the magnitude 7.5 quake and only added the 8.2 event the following day, as the surprise tsunami lapped on shores up to 10,000 kilometers away from its point of origin.

“We need to rethink our way to mitigate earthquake-tsunami hazards. To do that, we need to rapidly and accurately characterize the true size of big earthquakes, as well as their physical processes,” Jia said.

Because this type of earthquake can result in unexpected tsunami, it’s critical to improve our predictions. “With these complex earthquakes, the earthquake happens and we think, ‘Oh, that wasn’t so big, we don’t have to worry.’ And then the tsunami hits and causes a lot of damage,” said Judith Hubbard, a geologist at the Earth Observatory of Singapore who was not involved in the study. “This study is a great example of how we can understand how these events work, and how we can detect them faster so we can have more warning in the future.”

Sneaky seismic signals

When an earthquake hits, it sends waves of vibration through the Earth. The global network of earthquake monitors uses those seismic waves to pinpoint the time, location, depth and magnitude of an earthquake. Common monitoring often focuses on short- and medium-periods of waves, Jia said, and longer periods can be left out. But even incorporating long periods into monitoring, on its own, isn’t enough to catch complex earthquakes with messy seismic signals.

“It’s hard to find the second earthquake because it’s buried in the first one,” Jia said. “It’s very seldom complex earthquakes like this are observed. … And if we don’t use the right dataset, we cannot really see what was hidden inside.”

A simple earthquake can easily be pinpointed and described, Jia said. But a messy one needs to be carefully broken down into its constituent parts, to find out what unique combination of simpler earthquakes built up the complex one.

Jia and his colleagues developed an algorithm to tease apart the seismic signals during those messy earthquakes. By “decomposing” complex earthquake signals into simpler forms, using waves over different periods (varying from 20 to 500 seconds long), the algorithm can identify the location and properties of different sub-earthquakes. It’s akin to someone with perfect pitch hearing five dissonant notes struck at once, yet being able to identify each individual note.

“I think a lot of people are daunted by trying to work on events like this,” said Hubbard. “That somebody was willing to really dig into the data to figure it out is really useful.”

Both Jia and Hubbard noted a long-term goal is to automate the detection of such complex earthquakes, as we can for simple earthquakes. For the 2021 quake, the tsunami was small by the time it reached shores, and most of the permanent residents of the remote, volcanic islands are penguins. But complex earthquakes can pose significant hazards if they generate larger tsunami or strike in a densely populated region.

“Thriving on top of extinct volcanic seamounts of the Langseth Ridge we found massive sponge gardens, but did not know what they were feeding on,” reports Antje Boetius, chief scientist of the expedition, head of the Research Group for Deep Sea Ecology and Technology at the Max Planck Institute for Marine Microbiology and director of the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research. Using samples from the mission, first-author Teresa Morganti, sponge expert from the Max Planck Institute for Marine Microbiology in Bremen was able to identify how sponges adapt to the most nutrient-poor environment. Morganti explains: “Our analysis revealed that the sponges have microbial symbionts that are able to use old organic matter. This allows them to feed on the remnants of former, now extinct inhabitants of the seamounts, such as the tubes of worms composed of protein and chitin and other trapped detritus.”

Living on the leftovers

Sponges are considered to be one of the most basal forms of animal life. They are nevertheless successful and abundant in all oceans, from shallow tropical reefs to the arctic deep-sea. Many sponges accommodate a complex community of microorganisms in a symbiotic relationship, which contributes to the health and nutrition of the sponges by producing antibiotics, transferring nutrients and disposing of excretions. This also goes for Geodia-sponges, which dominated the community on the Arctic seamounts. The unity of sponge and associated microbes is called a sponge holobiont. Teresa Morganti cooperated with Anna de Kluijver, an expert from Utrecht University, and with the lab of Gesine Mollenhauer at the Alfred Wegener Institute to identify the food source, the growth and the age of the sponges. They learned that thousands of years ago, substances seeping from the seabed’s interior were supporting a rich ecosystem, home to a variety of animals. When they died out, their remnants remained. Now these form the base of this unexpected sponge garden.

Microbial analysis of the microorganisms supported the researchers’ hypothesis. “The microbes have just the right toolbox for this habitat,” explains Ute Hentschel from the GEOMAR Helmholtz Centre for Ocean Research in Kiel, who carried out the microbiological analyses with her team. “The microbes have the genes to digest refractory particulate and dissolved organic matter and use it as a carbon and nitrogen source, as well as a number of chemical energy sources available there.”

The scientists also showed that the sponges act as ecosystem engineers: They produce spicules that form a mat on which they crawl. This may further facilitate the local settling of particles and biogenic materials. The sponge holobionts can tap into this detrital matter, thus creating their own food trap.

Protecting requires understanding

Langseth Ridge is an underwater mountain range not far from the North Pole that sits beneath the permanently ice-covered water’s surface. There, sponge biomass was comparable to that of shallower sponge grounds with much higher nutrient input. “This is a unique ecosystem. We have never seen anything like it before in the high Central Arctic. In the study area, primary productivity in the overlying water provides less than one percent of the sponges’ carbon demand. Thus, this sponge garden may be a transient ecosystem, but it is rich in species, including soft corals,” says Antje Boetius.

The Arctic is one of the most affected regions by climate change. “Prior to our study, no similar sponge ground has been identified in the high Central Arctic, an area of the ice-covered ocean which remains understudied given the difficulties associated with observing and sampling such ice- covered deep-sea ecosystems,” Morganti stresses. The close cooperation of scientists from different institutions, including the Max Planck Institute for Marine Microbiology, the Alfred Wegener Institute and GEOMAR, enabled a comprehensive understanding of this surprising hotspot of life in the cold deep. “With sea-ice cover rapidly declining and the ocean environment changing, a better knowledge of hotspot ecosystems is essential for protecting and managing the unique diversity of these Arctic seas under pressure,” concludes Boetius.