Culture

Humans are not the only species facing a potential threat from SARS-CoV-2, the novel coronavirus that causes COVID-19, according to a new study from the University of California, Davis.

An international team of scientists used genomic analysis to compare the main cellular receptor for the virus in humans -- angiotensin converting enzyme-2, or ACE2 -- in 410 different species of vertebrates, including birds, fish, amphibians, reptiles and mammals.

ACE2 is normally found on many different types of cells and tissues, including epithelial cells in the nose, mouth and lungs. In humans, 25 amino acids of the ACE2 protein are important for the virus to bind and gain entry into cells.

The researchers used these 25 amino acid sequences of the ACE2 protein, and modeling of its predicted protein structure together with the SARS-CoV-2 spike protein, to evaluate how many of these amino acids are found in the ACE2 protein of the different species.

"Animals with all 25 amino acid residues matching the human protein are predicted to be at the highest risk for contracting SARS-CoV-2 via ACE2," said Joana Damas, first author for the paper and a postdoctoral research associate at UC Davis. "The risk is predicted to decrease the more the species' ACE2 binding residues differ from humans."

About 40 percent of the species potentially susceptible to SARS-CoV-2 are classified as "threatened" by the International Union for Conservation of Nature and may be especially vulnerable to human-to-animal transmission. The study was published Aug. 21 in the Proceedings of the National Academy of Sciences.

"The data provide an important starting point for identifying vulnerable and threatened animal populations at risk of SARS-CoV-2 infection," said Harris Lewin, lead author for the study and a distinguished professor of evolution and ecology at UC Davis. "We hope it inspires practices that protect both animal and human health during the pandemic."

Endangered species predicted to be at risk

Several critically endangered primate species, such as the Western lowland gorilla, Sumatran orangutan and Northern white-cheeked gibbon, are predicted to be at very high risk of infection by SARS-CoV-2 via their ACE2 receptor.

Other animals flagged as high risk include marine mammals such as gray whales and bottlenose dolphins, as well as Chinese hamsters.

Domestic animals such as cats, cattle and sheep were found to have a medium risk, and dogs, horses and pigs were found to have low risk for ACE2 binding. How this relates to infection and disease risk needs to be determined by future studies, but for those species that have known infectivity data, the correlation is high.

In documented cases of SARS-COV-2 infection in mink, cats, dogs, hamsters, lions and tigers, the virus may be using ACE2 receptors or they may use receptors other than ACE2 to gain access to host cells. Lower propensity for binding could translate to lower propensity for infection, or lower ability for the infection to spread in an animal or between animals once established.

Because of the potential for animals to contract the novel coronavirus from humans, and vice versa, institutions including the National Zoo and the San Diego Zoo, which both contributed genomic material to the study, have strengthened programs to protect both animals and humans.

"Zoonotic diseases and how to prevent human to animal transmission is not a new challenge to zoos and animal care professionals," said co-author Klaus-Peter Koepfli, senior research scientist at Smithsonian-Mason School of Conservation and former conservation biologist with the Smithsonian Conservation Biology Institute's Center for Species Survival and Center for Conservation Genomics. "This new information allows us to focus our efforts and plan accordingly to keep animals and humans safe."

The authors urge caution against overinterpreting the predicted animal risks based on the computational results, noting the actual risks can only be confirmed with additional experimental data. The list of animals can be found here.

Research has shown that the immediate ancestor of SARS-CoV-2 likely originated in a species of bat. Bats were found to be at very low risk of contracting the novel coronavirus via their ACE2 receptor, which is consistent with actual experimental data.

Whether bats directly transmitted the novel coronavirus directly to humans, or whether it went through an intermediate host, is not yet known, but the study supports the idea that one or more intermediate hosts was involved. The data allow researchers to zero in on which species might have served as an intermediate host in the wild, assisting efforts to control a future outbreak of SARS-CoV-2 infection in human and animal populations.

America’s power grid system is not only large but dynamic, which makes it especially challenging to manage. Human operators know how to maintain systems when conditions are static. But when conditions change quickly, due to sudden faults for example, operators lack a clear way of anticipating how the system should best adapt to meet system security and safety requirements.

At the U.S. Department of Energy’s (DOE) Argonne National Laboratory a research team has developed a novel approach to help system operators understand how to better control power systems with the help of artificial intelligence. Their new approach could help operators control power systems in a more effective way, which could enhance the resilience of America’s power grid, according to a recent article in IEEE Transactions on Power Systems.

Converging dynamic and static calculations

The new approach allows operators to make decisions considering both static and dynamic features of a power system in a single decision-making model with better accuracy — a historically tough challenge.

“The decision to turn a generator off or on and determine its power output level is an example of a static decision, an action that does not change within a certain amount of time. Electrical frequency, though — which is related to the speed of a generator — is an example of a dynamic feature, because it could fluctuate over time in case of a disruption (e.g., a load tripped) or an operation (e.g., a switch closed),” said Argonne computational scientist Feng Qiu, who co-authored the study. “If you put dynamic and static formulations together in the same model, it’s essentially impossible to solve.”

In power systems, operators must hold frequency within a certain range of values to meet safety limits. Static conditions, such as the number of generators online, affect system ability of holding frequency and other dynamic features.

Most analysts calculate static and dynamic features separately, but the results fall short. Meanwhile, others have tried to develop simple models that can bridge both types of calculations, but these models are limited in their scalability and accuracy, particularly as systems become more complex.

Artificial neural networks connect the dots between static and dynamic features

Rather than trying to fit existing static and dynamic formulas together, Qiu and his peers developed an approach for creating new formulas that could bridge the two. Their approach centers on using an artificial intelligence tool known as a neural network.

“A neural network can create a map between a specific input and a specific output,” said Yichen Zhang, Argonne postdoctoral appointee and lead author of the study. “If I know the conditions we start with and those we end with, I can use neural networks to figure out how those conditions map to each other.”

While their neural network approach can apply to bulk-power systems, the team tested it on a microgrid system, a controllable network of distributed energy resources, such as diesel generators and solar photovoltaic panels.

The team used the neural network to track how a set of static conditions within the microgrid system mapped to a set of dynamic conditions or values. More specifically, researchers used it to optimize the static resources within their microgrid so the electrical frequency stayed within a safe range.

Simulation data served as the inputs and outputs for training their neural network. The inputs were static data and outputs were dynamic responses, specifically the range of frequencies that are safe. When the researchers passed both sets of data into the neural network, it “learned” to map estimated dynamic responses for a set of static conditions.

“The neural network transformed the complex dynamic equations that we typically cannot combine with static equations into a new form that we can solve together,” Qui said.

Opening doors for new types of analyses

Researchers, analysts and operators can use the Argonne scientists’ approach as a starting point. For example, operators could potentially use it to anticipate when they can turn on and off generation resources, while at the same time ensuring that all the resources that are online are able to withstand certain disruptions.

“This is the kind of scenario that system operators have always wanted to analyze, but were unable before to because of the challenges of calculating static and dynamic features together,” said Argonne postdoctoral appointee and co-author Tianqi Hong. “Now we think this work makes this type of analysis possible.”

“We’re excited by the potential for this type of analytical approach,” said Mark Petri, Argonne’s Electric Power Grid Program director. “For instance, this could provide a better way for operators to quickly and safely restore power after an outage, a problem challenged by complex operational decisions entangled with system dynamics, making the electric grid more resilient to external hazards.”

From schools of fish, to herds of antelope and even human societies, one of the group's many advantages is its inherent safety. Surrounded by their peers, individuals can lower their vigilance and calmly engage in other activities, such as foraging, or watching youtube videos.

But the Safety in Numbers rule has more to it than just being together. In many cases, communication also plays a big role. Social cues of danger are fairly well known. Just think about the different ways animals use to convey the presence of a threat. Shrieks, yelps and barks immediately come to mind.

Now, how about naming a few examples of social cues of safety? After all, knowing that the danger has passed is important for lowering one's defences and resuming other activities. The reason this task is more challenging is because it's actually a trick question - no social safety cues have been identified until now.

Remarkably, the discovery of the first social safety cue was made thanks to a tiny insect: the fruit fly. These results, published today (August 21st) in the scientific journal Nature Communications, mark a new phase in our understanding of how social communication works.

A silent sign of danger

"When people think about social communication of danger, they normally think about alarm calls", says Marta Moita, a principal investigator at the Champalimaud Centre for the Unknown in Portugal. "But we are interested in a different type of threat cue, the expression of the defensive behaviours themselves."

Freezing is one of the three universal defence responses, together with fight and flight. This response is the best course of action in situations where escape is either impossible or less advantageous than just staying still with the hope of remaining unnoticed.

"Freezing may actually be a safer way of conveying the existence of danger to others", Moita points out. "This manner of social communication does not require the active production of a signal that may result in drawing unwelcome attention. Also, freezing may constitute a public cue that can be used by any surrounding animal regardless of species", she explains.

Moita's team has recently demonstrated that individual fruit flies freeze in response to an inescapable threat. This finding triggered their curiosity, would this behaviour change if there other flies were around?

Safety in (exactly how many) numbers

To answer this question, Clara Ferreira, the lead author of the study, proceeded with a systematic set of experiments, beginning with one fly, then two, three, and so forth, up to groups of ten.

"We placed the flies in a transparent closed chamber and repeatedly exposed them to an expanding dark disc, which mimics an object on a collision course. Just imagine the visual effect of an approaching open palm", Ferreira explains. "Many visual animals that are exposed to such a stimulus respond defensively, including humans. If they freeze, they often stay motionless for quite some time, even after the threat is gone."

Their results revealed that group size matters. "All groups - from two to ten - froze less than individual flies. However, we were surprised to find a complex effect of group size on the flies' behaviour", says Ferreira.

In groups of six and more, the flies froze transiently when the threat appeared and then resumed movement once it was gone. On the other hand, the flies' response pattern in groups of five or less was more similar to that of individual flies.

"Flies in those groups still froze less than single flies. However, their freezing time increased as the experiment progressed. The more repetitions of the threatening stimulus they experienced, the longer they would remain motionless when it reappeared", Ferreira explains. "These results were very intriguing", she adds. "This was the first time the effect of group size on freezing was systematically characterised in any species and it revealed a fascinating and intricate relation."

Should I stay or should I go?

These findings clearly demonstrated that flies change their defensive responses when others are present. This novel observation raised a pressing question - what social cues were the flies responding to? To find the answer, Ferreira and Moita meticulously analysed their previous results and conducted additional experiments using blind flies and controllable magnetic "dummy flies".

The results revealed a two-part answer. "The first part describes the flies' response to the appearance of the threat", Ferreira recounts. "We learned that an individual fly was more likely to enter freezing if its peers (magnetic or otherwise) froze in response to the threat. We were somewhat expecting to see this. Previous studies in the lab showed that in specific situations, freezing is a social cue of danger in rats. Here, we witnessed a similar behaviour in flies."

The second part of the answer, however, caught the researchers by surprise: flies were more likely to exit freezing if others began to move. "This means that flies were using the resumption of movement as a social cue of safety!", Ferreira points out.

"This is a completely novel phenomenon", Moita adds. "There are many types of recorded social alarm cues, but this is the first social safety cue to be identified in any animal species. It also pins down movement as the social cue we were searching for. In a sense, this cue 'kills two birds with one stone': the sudden cessation of movement signifies danger, whereas its resumption signifies safety."

Next stop - the brain

Moita and Ferreira's series of striking discoveries opens a unique opportunity to learn how the brain perceives and responds to social cues. "The fruit fly is one of the most powerful animal models used in scientific research nowadays", says Ferreira. "It offers specialised tools to study neurobiology in a very specific and targeted manner."

Indeed, the authors have already begun unraveling the neural basis of this behaviour. "In this project, we identified a set of visual neurons that are crucial for perceiving the movement of others as a safety cue", Ferreira explains. "And we are planning to continue investigating the neural circuits involved."

As Moita points out, even though flies and humans are different, there are parallels across these and other species that may make findings in the fly relevant for revealing general principles. "Since we are studying a fundamental behaviour spanning almost all of animal life - the tendency to seek safety in numbers - we believe that our work paves the way for understanding conserved mechanisms in other animals", she concludes.

CHAMPAIGN, Ill. -- Some birds lay their eggs in the nests of other bird species and let the host parents raise their young. A new study finds that in times of environmental flux, these brood parasites "diversify their portfolios," minimizing the risks of their unorthodox lifestyle by increasing the number and variety of hosts they select as adoptive parents.

"We found that, in unstable environments, brood parasites choose to not put all their eggs in one basket," said study lead author Nicholas Antonson, a Ph.D. student at the University of Illinois, Urbana Champaign. "Our results are consistent with the idea that brood parasites diversify their reproductive risk in areas that are ecologically, behaviorally or environmentally unpredictable."

Antonson led the study with Mark Hauber, a U. of I. professor of evolution, ecology and behavior; Dustin Rubenstein, a professor of environmental biology at Columbia University; and Carlos Botero, a professor of biology at Washington University in St. Louis. They report their findings in the journal Nature Communications.

"This research begins to answer a longstanding question about how species first interact and then coevolve in environments that are also changing," Hauber said. "Theory suggests that in unpredictable environments, predators and parasites should rely on a greater number and variety of prey hosts. But with so many variables in flux, this is a challenging thing to study."

Brood parasite success depends on the host's acceptance of the outsider's eggs and its ability to raise the young. Some birds learn to recognize that the foreign eggs are different and eject them or build new nests. Others seem not to notice. They incubate, hatch and care for the parasitic offspring as if they were their own.

Several other factors could influence how many hosts and which host species a brood parasite targets. The host must be in egg-laying mode when the interloper comes to call. If only one foster parent is involved in taking care of the young, its nest might not succeed as well as one with two parents present. But having two parents around makes it more difficult for parasites to get into the nest to lay their eggs.

"Similarly, if the host returns from a long migratory trip and begins to nest right away, the parasite might have fewer chances to locate its nest for sneaking in the extra egg," Hauber said. "Variability in temperature and precipitation during the breeding season is another potential influence."

To account for these factors, the researchers aggregated published and publicly available data on 81 of the nearly 100 species of avian brood parasites, including cowbirds, cuckoos, black-headed ducks, indigobirds and honeyguides. They used records from the Field Museum of Natural History in Chicago to determine the number and diversity of hosts each brood parasite used in different contexts. The team also accounted for the relative abundance of published research on different species, "as a number of brood parasites closer to the equator remain poorly studied," Antonson said.

They found that in unpredictable environments, brood parasites target more - and more diverse - hosts. The parasites take advantage of as many host species as possible when opportunity allows. The team found a particularly pronounced relationship between temperature variability and bet-hedging.

"In areas where temperatures are stable, brood parasites tend to specialize on fewer and less diverse host species. Those hosts also tend to build more complex and potentially safer nests," Antonson said. "But as the thermal environment becomes more uncertain, the evolutionary pattern that we see is that they spread around the risk of offspring survival by drawing from a larger and more diverse pool of host species."

The new findings offer insight into the evolution of specialization and generalization, Hauber said. They also suggest that "ecological risks and environmental unpredictability favor the evolution of bet-hedging."

In uncertain times, it makes sense to manage risk in your endeavors -- whether it's investing in money-making opportunities or deciding where to lay your eggs.

Brood parasites are birds that are known to lay their eggs in other birds' nests. Cowbirds and cuckoos are among the most famous examples of this group.

New research from Washington University in St. Louis finds that brood parasites living in more variable and unpredictable habitats tend to parasitize -- or squat and drop their eggs in -- the nests of a greater variety and number of hosts. The study is published Aug. 21 in Nature Communications.

"When brood parasites face increased ecological risks -- for example, greater climatic uncertainty in their environment, or greater uncertainty with regards to the availability or behavior of their hosts -- they turn to bet-hedging," said Carlos Botero, assistant professor of biology in Arts & Sciences and the study's senior author.

"In other words, when it is difficult to predict the ideal host, parasites literally lay their few precious eggs in more than one basket," he said. "This means increasing not just the number of different host species they use, but also expanding the diversity of taxonomic families that they choose as hosts."

A birder himself, Botero says that he is fascinated by things animals do that fall outside the boundaries of what some think of as "typical" -- like brood parasitism.

"Parasite mothers can't really do much about the behaviors that their hosts will display as surrogate parents," Botero said. "With bet-hedging in the choice of hosts, parasites are at least able to increase the chances that one -- or a few -- of the surrogate parents they choose will end up behaving in the optimal way.

Botero and his colleagues at the University of Illinois Urbana-Champaign and Columbia University observed a pattern that they considered striking.

The researchers aggregated environmental, parasite and host species data associated with 84 species of obligate avian brood parasites from 19 genera and five different bird families. Their list covered approximately 86% of all known brood parasitic species.

For all of these birds, host behavior is critical when it comes to countering environmental threats. Even small differences in the nest architecture, habitat selection, breeding timing or incubation behavior of the chosen surrogate parents can have life or death implications for young parasitic chicks.

A brood parasite's properly "hedged" portfolio must include a reasonable diversity of host types to ensure that at least some reproductive success is achieved -- no matter what environmental conditions are experienced in any given year.

But bet-hedging does come at a cost, the researchers said.

"A bet-hedging strategy involves making some or sometimes even many 'wrong' choices," Botero said. "For example, for years in which the behaviors, timing and nest type of a given host clearly work better than those of other species, it would be clearly ideal to stick with that option and avoid wasting eggs on others."

The problem is, parasites that live in variable and unpredictable environments cannot know at the onset which option will work best that year.

"Parasitic mothers that diversify their egg-laying choices may not contribute as many offspring to any given generation as they would have if they had chosen the best host type that year," Botero said. "But, over time, they will end up contributing a much larger total number of offspring to future generations by fledging some offspring every year."

"It is this long-term vision that allows bet-hedging lineages to prevail and to steer the course of evolution so that in the end, everyone in their species bet-hedges."

Irvine, Calif., - Physical evidence found in caves in Laos helps tell a story about a connection between the end of the Green Sahara - when once heavily vegetated Northern Africa became a hyper-arid landscape - and a previously unknown megadrought that crippled Southeast Asia 4,000 to 5,000 years ago.

In a paper published today in Nature Communications, scientists at the University of California, Irvine, the University of Pennsylvania, William Paterson University of New Jersey and other international institutions explain how this major climate transformation led to a shift in human settlement patterns in Southeast Asia, which is now inhabited by more than 600 million people.

"In this study, we provide the first proof for a strong link between the end of the Green Sahara and Southeast Asian monsoon failure during the mid- to late Holocene period," said co-author Kathleen Johnson, UCI associate professor of Earth system science. "Our high-resolution and well-dated record suggests a strong connection between Northern Africa and mainland Southeast Asia during this time."

To create a paleoclimate record for the study, Johnson and other researchers gathered stalagmite samples from caves in Northern Laos. In her UCI laboratory, they measured the geochemical properties of the oxygen and carbon isotopes, carbon-14, and trace metals found in the specimens. This helped them verify the occurrence of the drought and extrapolate its impacts on the region.

Johnson said they combined data from the analysis of these stalagmite-derived proxies with a series of idealized climate model simulations - conducted by co-author Francesco Pausata of the University of Quebec in Montreal - in which Saharan vegetation and dust concentrations were altered in a way that permitted them to investigate the ocean-atmosphere feedbacks and teleconnections associated with such an abrupt shift in precipitation.

The modeling experiments suggested that reduced plant growth in the Sahara led to increased airborne dust that acted to cool the Indian Ocean and shift the Walker circulation pattern eastward, causing it to behave in ways similar to modern-day El Niño events. This, ultimately, led to a large reduction in monsoon moisture across Southeast Asia that lasted more than 1,000 years, according to Johnson.

Anthropologists and archaeologists have previously studied the effects of the demise of the Green Sahara, also known as the African humid period, on population centers closer to Western Asia and North Africa, noting the collapse of the Akkadian Empire of Mesopotamia, the de-urbanization of the Indus Civilization (near present-day Pakistan and India) and the spread of pastoralism along the Nile River.

But the link to the origin of the Southeast Asia megadrought and lifestyle pattern shifts in the region had not been previously investigated, according to lead author Michael Griffiths, professor of environmental science at William Paterson University of New Jersey.

"Archaeologists and anthropologists have been studying this event for decades now, in terms of societal adaptations and upheavals, but its exact cause has eluded the scientific community," said Griffiths, who was a National Oceanic and Atmospheric Administration-supported postdoctoral scholar in Johnson's lab and has collaborated with her on this research topic for more than 10 years.

"Results from this work provide a novel and convincing explanation for the origin of the Southeast Asia megadrought and could help us better understand, to varying degrees, the observed societal shifts across many parts of the tropics and extra-tropics," he said.

The researchers suggest that the centuries-long megadrought corresponds to the "missing millennia" in Southeast Asia between 4,000 and 6,000 years ago, a time characterized by a noticeable lack of archaeological evidence in interior Southeast Asia compared to earlier and later portions of the Holocene.

They propose that the mid-Holocene megadrought may have been an impetus for mass population movements and the adoption of new, more resilient subsistence strategies - and that it should now be considered as a possible driver for the inception of Neolithic farming in mainland Southeast Asia.

"This is outstanding evidence for the type of climate change that must have affected society, what plants were available, what animals were available," said co-author Joyce White, adjunct professor of anthropology at the University of Pennsylvania. "All of life had to adjust to this very different climate. From an archaeological point of view, this really is a game changer in how we try to understand or reconstruct the middle Holocene period."

Physical evidence found in caves in Laos helps tell a story about a connection between the end of the Green Sahara, when once heavily vegetated Northern Africa became a hyper-arid landscape, and a previously unknown megadrought that crippled Southeast Asia 4,000 to 5,000 years ago.

In a paper published in Nature Communications, scientists at the University of California, Irvine, University of Pennsylvania, William Paterson University of New Jersey, and other international institutions explain how this major climate transformation led to a shift in human settlement patterns in Southeast Asia, which is now inhabited by more than 600 million people.

"In this study, we provide the first proof for a strong link between the end of the Green Sahara and Southeast Asian monsoon failure during the mid- to late Holocene period," said co-author Kathleen Johnson, UCI associate professor of Earth system science. "Our high-resolution and well-dated record suggests a strong connection between Northern Africa and mainland Southeast Asia during this time."

To create a paleoclimate record for the study, Johnson and other researchers gathered stalagmite samples from caves in Northern Laos. In her UCI laboratory, they measured the geochemical properties of the oxygen and carbon isotopes, carbon-14, and trace metals found in the specimens. This helped them verify the occurrence of the drought and extrapolate its impacts on the region.

Johnson said they combined data from the analysis of these stalagmite-derived proxies with a series of idealized climate model simulations--conducted by co-author Francesco Pausata of the University of Quebec in Montreal--in which Saharan vegetation and dust concentrations were altered in a way that permitted them to investigate the ocean-atmosphere feedbacks and teleconnections associated with such an abrupt shift in precipitation.

The modeling experiments suggested that reduced plant growth in the Sahara led to increased airborne dust that acted to cool the Indian Ocean and shift the Walker circulation pattern eastward, causing it to behave in ways similar to modern-day El Niño events. This, ultimately, led to a large reduction in monsoon moisture across Southeast Asia that lasted more than 1,000 years, according to Johnson.

Anthropologists and archaeologists have previously studied the effects of the demise of the Green Sahara, also known as the African humid period, on population centers closer to Western Asia and North Africa, noting the collapse of the Akkadian Empire of Mesopotamia, the de-urbanization of the Indus Civilization (near present-day Pakistan and India) and the spread of pastoralism along the Nile River.

But the link to the origin of the Southeast Asia megadrought and lifestyle pattern shifts in the region had not been previously investigated, according to lead author Michael Griffiths, professor of environmental science at William Paterson University of New Jersey.

"Archaeologists and anthropologists have been studying this event for decades now, in terms of societal adaptations and upheavals, but its exact cause has eluded the scientific community," said Griffiths, who was a National Oceanic and Atmospheric Administration-supported postdoctoral scholar in Johnson's lab and has collaborated with her on this research topic for more than 10 years.

"Results from this work provide a novel and convincing explanation for the origin of the Southeast Asia megadrought and could help us better understand, to varying degrees, the observed societal shifts across many parts of the tropics and extra-tropics," he said.

The researchers suggest that the centuries-long megadrought corresponds to the "missing millennia" in Southeast Asia between 4,000 and 6,000 years ago, a time characterized by a noticeable lack of archaeological evidence in interior Southeast Asia compared to earlier and later portions of the Holocene.

They propose that the mid-Holocene megadrought may have been an impetus for mass population movements and the adoption of new, more resilient subsistence strategies, and that it should now be considered as a possible driver for the inception of Neolithic farming in mainland Southeast Asia.

"This is outstanding evidence for the type of climate change that must have affected society, what plants were available, what animals were available," said co-author Joyce White, adjunct professor of anthropology at the University of Pennsylvania. "All of life had to adjust to this very different climate. From an archaeological point of view, this really is a game changer in how we try to understand or reconstruct the middle Holocene period."

A team of scientists at the Nagoya University Institute of Transformative Bio-Molecules (WPI-ITbM) have developed a method for visualizing microtubule dynamics and cell membrane protein endocytosis in living plant cells, an important step forward in plant cell biology.

SNAP-tag visualization of in vivo protein dynamics, a method which binds dyes to proteins to allow fluorescent imaging, has made a wide range of contributions to medical and biological study, for example in cancer research. However, live cell imaging using SNAP-tag with synthetic dyes in plant science has been impossible, as synthetic dyes are unable to reach the target proteins due to the presence of the cell wall in plant cells.

In this study, the research team demonstrated that it was possible to perform live cell imaging using SNAP-tag even in plants, using three types of synthetic dyes which bond to the SNAP-tag to mark microtubules, part of the cytoskeleton. They were able to use a particular dye that does not permeate the cell membrane and fluoresces only when it bonds with SNAP-tag to exclusively mark the auxin transporters in the cell membrane, visualizing the process of membrane proteins being taken into the cell (endocytosis) after they had been marked. Thus, they were able to clearly differentiate between transporter proteins which had been newly synthesized inside the cell and those taken into the cell by endocytosis.
They then used tobacco cells to find out which of 31 different dyes were able to enter the cell. Interestingly, it was found that 23 out of these 31 were taken into the tobacco cells, that the majority of them could be used with SNAP-tag to mark cytosolic components in plant cells, and that those which could not permeate the cell membrane could be used to mark membrane proteins outside the cell.

This study provides a new technique for the fluorescent marking of proteins in plant cells, and represent an important step forward in plant cell biology research. It is expected to find use in superresolution imaging using extremely light stable markers, and techniques for determining place- and time-specific pH and Ca2+ levels.

Women are underrepresented in the field of academic surgery, but women surgeons are earning a disproportionate share of research grants from the National Institutes of Health, a new study has found.

Women make up 19% of surgery faculty at academic health systems but held 26.4% of prestigious "R01" grants in place at surgery departments as of October 2018, the researchers found.

"Female surgeon-scientists are underrepresented within academic surgery, but hold a greater than anticipated proportion of NIH funding," said researcher Shayna L. Showalter, MD, a breast surgical oncologist at UVA Health and the UVA Cancer Center. "This means that female surgeon-scientists are a crucial component of future surgical research."

Women in Surgery

Showalter and colleagues queried the number of grants from surgery departments throughout the country to determine the percentage of R01 grants held by women. They identified 212 grants held by 159 principal investigators. Of those 159 investigators, 42 were women, holding a total of 49 R01 grants. "Female surgeon scientists are doing impressive work and have been able to succeed in a very competitive research environment," Showalter said.

Diving deeper, the researchers determined that women were more likely than men to be first-time grant recipients. More than 73% of women were first-time recipients, compared with 54.8% of men. "Within the research community, we are potentially moving away from the tradition of awarding funding to longstanding, proven researchers," Showalter said. "Females in this study were twice as likely to be first-time grant recipients. I hope that the focus continues to be on awarding funding to a diverse group of surgeon-scientists."

Women who held R01 grants were more likely to be part of a department with a female chair or that is more than 30 percent female, the researchers determined. They also found that women had fewer research articles published in scientific journals than did their male colleagues. "This finding may be related to the number of first-time grants and is consistent with previous studies that have demonstrated that women in academic surgery have fewer publication in general than men,' Showalter said.

The researchers encouraged surgery departments to nurture and promote female faculty, and to advocate for women in leadership positions. Strong mentorship programs are important, Showalter said.

"Currently, there are a number of accomplished female surgeon-scientists, and I am confident that many more will play crucial roles in the future of surgical research," she said. "As a community within academia, we need to support and promote a diverse faculty."

Solar flares emit sudden, strong bursts of electromagnetic radiation from the Sun's surface and its atmosphere, and eject plasma and energetic particles into inter-planetary space. Since large solar flares can cause severe space weather disturbances affecting Earth, to mitigate their impact their occurrence needs to be predicted. However, as the onset mechanism of solar flares is unclear, most flare prediction methods so far have relied on empirical methods.

The research team led by Professor Kanya Kusano (Director of the Institute for Space-Earth Environmental Research, Nagoya University) recently succeeded in developing the first physics-based model that can accurately predict imminent large solar flares. The work was published in the journal Science on July 31, 2020.

The new method of flare prediction, called the kappa scheme, is based on the theory of "double-arc instability," that is a magnetohydrodynamic (MHD) instability triggered by magnetic reconnection. The researchers assumed that a small-scale reconnection of magnetic field lines can form a double-arc (m-shape) magnetic field and trigger the onset of a solar flare. The kappa -scheme can predict how a small magnetic reconnection triggers a large flare and how a large solar flare can occur.

The predictive model was tested on about 200 active regions during solar cycle 24 from 2008 to 2019 using data obtained by NASA's Solar Dynamics Observatory (SDO) satellite. It was demonstrated that with few exceptions, the kappa-scheme predicts most imminent solar flares, as well as the precise location they will emerge from. The researchers also discovered that a new parameter - the "magnetic twist flux density" close to a magnetic polarity inversion line on the solar surface - determines when and where solar flares probably occur and how large they are likely to be.

Previous flare prediction methods have relied on empirical relations in which the predictions of the previous day tend to continue into the next day even if flare activity changes. In contrast, the kappa-scheme predicts large solar flares through a physics-based approach regardless of previous flare activity. While it takes a lot more work to implement the scheme in real-time operational forecasting, this study shows that the physics-based approach may open a new direction for flare prediction research.

Editor's Note: The paper, Asymmetric remote C–H borylation of aliphatic amides and esters with a modular iridium catalyst, was published in the journal Science, and will be withdrawn at 14.00 EDT on 28 April 2022. The retraction is under embargo until that time.

A new catalyst design enables unprecedented control over the modification of fatty acid derivatives that opens the door to creating useful substances in a green and efficient manner.

Hokkaido University WPI-ICReDD researchers developed a modular catalyst that can accurately modify fatty acid derivatives in a hitherto inaccessible position. This enables the efficient production of valuable compounds from a renewable bioresource, whereas before we had to either rely on petroleum-derived resources or use complicated and costly methods.

Many pharmaceuticals and plastics consist of a backbone that is essentially a chain of carbon atoms with modifications within their hydrocarbon framework. For their production, fatty acids are attractive raw material because they are easily accessible, renewable natural resources that consist of a chain of carbon atoms attached to a functional group called "carboxyl group." However, our ability to modify these chains has so far been limited to carbon atoms only one or two atoms away from the carboxyl group. Professor Masaya Sawamura of Hokkaido University's Institute for Chemical Reaction Design and Discovery (WPI-ICReDD) explains, "The chemical materials obtained in this way are limited to those with fairly simple structures, and in order to synthesize useful compounds, multi-step processes are necessary."

Building upon previous studies, Sawamura's group constructed a catalyst that consists of an iridium atom at its core and various modules that ensure that a fatty acid derivative -- fatty acid amide or ester in this case -- is precisely positioned in such a way that the C-H bond located three carbons away from the carboxyl group is modified. Moreover, while every C-H bond in a fatty acid derivative can be modified in two ways, giving compounds that are mirror images of one another, the catalyst developed by the team produces only one of the two possible products, which is an important attribute especially for drug development. To increase the breadth of possible modifications further, the researchers try to use different modules in their catalyst to change the way the substrate is positioned in the catalyst to allow different modifications.

In their article published in Science, the team demonstrated that their approach works with various substrates and can produce a large range of useful derivatives. In addition, they used quantum chemical calculations to investigate the precise structure and function of their catalyst driving the observed reactivity and selectivity. The results confirmed that the catalyst has a deep pocket that binds the substrate through interactions between one of its subunits and the carbonyl group of the substrate, and keeps it in place to facilitate the specific reaction -- a feature analogous to natural enzymes.

"The modular catalyst allowed the site-selective modification of fatty acid amides and esters, some of which are bioactive compounds. This simple, modular, and broadly applicable catalytic system allows the introduction of structural and chemical complexity to the hydrocarbon chain of readily available feedstock chemicals," says Ronald Reyes of the research team. Central to the success of these endeavors is a combination of experiments and computation. Sawamura says, "The accumulation of experimental knowledge is a source of great inspiration, but with the support of computer chemistry we can bring this to fruition in the near future."

In a pair of studies, researchers report the discovery and molecular pharmacology of stable, synthetic STING (stimulator of interferon genes) agonists that induce anticancer immune responses in mice. Combined, both studies' results represent progress towards clinically viable STING agonists for future cancer drugs and immunotherapeutic strategies. Activation of the innate STING immune pathway by natural agonists has been demonstrated to play an important role in antitumor immunity, which has made them an attractive target for use in cancer therapies. It's suggested that the administration of synthetic agonists of the STING pathway could be used to trigger de novo anticancer immune responses that can control tumor growth or enhance the outcome of cancer treatments like PD-1 blockade immunotherapy. However, the development of STING agonists for drug development has been challenging and largely limited by the inherent instability of the molecules involved. Here, Emily Chin and colleagues and Bo-Sheng Pan and colleagues, respectively, report on the discovery of stable STING agonists that show antitumor activity in preclinical cancer models. Chin et al. describe SR-717 - a stable, non-nucleotide small molecule STING agonist that functions similarly to the natural STING ligand cGAMP. According to these authors, SR-717 demonstrated robust anti-tumor activities in a mouse model of melanoma. Building on these findings, Pan et al. developed an agonist capable of pharmacologically activating the STING immune pathway through an orally administered drug. When tested in mouse models, the authors found that it was able to induce tumor regression and improve checkpoint blockade therapy. "Non-nucleotide small-molecule STING agonists that can be administered systemically may represent an attractive approach for targeting this pathway and have the potential to transform the therapeutic landscape once optimized," write Thomas Gajewski and Emily Higgs in a related Perspective.

Published in the highly prestigious journal Science, a new study has shed light on a cellular process that occurs in the retinas of people with diabetic retinopathy. This discovery could lead to the development of a treatment for this serious complication of diabetes. The research was led by Dr. Przemyslaw (Mike) Sapieha and Dr. François Binet in collaboration with Dr. Frédérick Antoine Mallette and Dr. Flavio Rezende of the Centre de recherche de l'Hôpital Maisonneuve-Rosemont (CR-HMR), which is part of the Centre intégré universitaire de santé et de services sociaux de l'Est-de-l'Île-de-Montréal, and Dr. Jean-Sébastien Joyal of the CHU Sainte-Justine Research Centre, affiliated with Université de Montréal and also with Dr. Jean-François Côté of the Montreal Clinical Research Institute (IRCM).

Diabetic retinopathy is characterized by vascular degeneration and later the formation of abnormal blood vessels in the retina. This vascular proliferation compromises the nerve cells that carry information from the eyes to the brain.

The study demonstrates that to stop abnormal vascular proliferation, blood vessels apply a series of molecular "brakes" that become activated in a way similar to an accelerated version of natural cellular aging. Collectively, these mechanisms culminate in a process called cellular senescence, which eventually causes tissue scarring in the retina.

When in senescence mode, blood vessels produce inflammatory molecules that become targets of immune cells called neutrophils. Although thought to be the immune system's first responders, the study shows that neutrophils arrive in the retina later on to help clean and remodel damaged blood vessels. They do this through an unconventional cellular mechanism of releasing neutrophil extracellular traps (or NETS) made up of their own DNA onto diseased blood vessels.

More broadly, the results of this study imply that the destruction of senescent blood vessels leads to beneficial vascular remodeling. The study therefore provides insight into the general function of endothelial cells and how they predispose older populations to complications such as myocardial infarction, atherosclerosis and strokes.

Ten post-mortem examinations performed on patients with confirmed COVID-19 found that all patients had lung injuries and early scarring of the lungs as a result of the virus, as well as injury to their kidneys.  Nine patients also had thrombosis - a blood clot- in at least one major organ (heart, lung or kidney). The team were unable to investigate thrombosis in the tenth patient.  

The research team behind the study believe that the findings could help guide clinicians on treating complications as a result of COVID-19, such as using blood thinners to prevent blood clots from developing.  They also hope that better understanding of the key complications in severe cases could help clinicians develop new ways to monitor and treat the disease. 

The study, published in The Lancet Microbe, was led by researchers at Imperial College London and Imperial College Healthcare NHS Trust.  Although the numbers of patients examined is small, this is the largest study to date of post-mortem examinations on COVID-19 patients in England.

Dr Michael Osborn, Honorary Clinical Senior Lecturer at Imperial College London, Consultant Pathologist at Imperial College Healthcare NHS Trust and co-author of the study, said:
"COVID-19 is a new disease and we have only had limited opportunities to comprehensively analyse tissues from patients at autopsy, to better understand what caused a patient's illness and death for research purposes.  Our study is the first of its kind in the country to support existing theories from researchers and doctors on the wards that lung injuries, thrombosis and immune cell depletion are the most prominent features in severe cases of COVID-19.  In the patients we looked at, we also saw evidence of kidney injuries and in some cases pancreatitis and these with our other findings will help clinicians develop new strategies to manage patients.  ??"Autopsy based analysis of COVID-19 for research is vital to learn more of this disease as the pandemic develops. We are extremely grateful to those who consented to this research and appreciate the advancement of medical science their generosity will bring.  

As a result of our work, we have worked with colleagues at the Royal College of Pathologists to produce national guidelines for autopsies in COVID-19 patients and in anticipation of a possible second wave of cases we have put systems in place to rapidly facilitate further studies in the future and so further our understanding on the nature and cause of the disease, which we hope would lead to more effective treatments and fewer deaths."

Dr Brian Hanley, from the Department of Cellular Pathology at Imperial College Healthcare NHS Trust and co-author of the study, added:

"The UK has sadly had a large number of deaths related to COVID-19. The search for effective treatments will rely on an understanding of how the disease affects the body. The post-mortem examination is vital in this respect. The findings in this study support research from other autopsy groups worldwide and in the UK that describe the structural damage to organs caused by COVID-19. It also documents several unexpected complications.  This increased understanding of COVID-19 can help clinical teams with the management of severe cases and also to monitor and treat further complications as a result of the disease."

During the lockdown period researchers nationally had very limited opportunities to carry out post mortem examinations for research purposes on patients who died from the disease.  The team wanted to see whether they can glean new insights on how the virus infects the cells of the body by studying tissue samples from patients who died as a result of severe COVID-19.

The team performed full post-mortem examinations and biopsies on ten patients aged 22-97 at Imperial College Healthcare NHS Trust hospitals during March-June. Full consent for post mortem with widespread tissue sampling and use of the tissue for research was sought from the relatives and friends of the deceased in line with national protocols. Seven of the patients were men and four were women.  Six of the patients were from a BAME background and four patients were white.

In the patients studied, high blood pressure and chronic obstructive pulmonary disease - the name for a group of lung conditions that cause breathing difficulties - were the most common contributing factors to death.  All patients developed a fever and had at least two respiratory symptoms such as cough and shortness of breath during the early stages of the disease.  Most patients died within three weeks of presenting with symptoms and treatments varied across the cohort.

The study team also reported six main findings:

All patients had diffuse alveolar damage (DAD).  DAD is a term used to describe a pattern of lung injury which can be seen as a result of viral infection.  This type of lung injury can affect both gas exchange (oxygen and carbon dioxide) and blood flood in the lungs. 
 

All patients fully assessed Nine of the ten patients had some form of thrombosis- blood clot - in at least one major organ (it was not possible to investigate thrombosis in the tenth patient).  Thrombosis prevents blood from flowing normally through the circulatory system and can lead to strokes and heart attacks.  The researchers found thrombi in the lungs of eight patients, the heart of five patients and the kidneys of four patients. They believe that this supports the theory that COVID-19 causes circulatory complications and that patient treatment could be augmented with blood thinning medication to prevent blood clots
 

All patients had evidence of acute renal tubular injury - a kidney injury that can lead to kidney failure or damage.  The main causes are low blood flow to the kidneys and severe infections.  It often affects patients who are in hospital and intensive care units
 

T-Lymphocyte Depletion (TLD) in the spleen and the lymph nodes was another consistent finding.  T-lymphocytes (white blood cells) are a major component of the immune system and play a role in destroying infections.  TLD is a reduction in T-lymphocytes, which alters the immune system and its response.  Haemophagocytosis is another consistent finding in this group, which occurs when the immune system overreacts to an infection and destroys some of its own cells
 

The researchers found evidence of acute pancreatitis in two of the patients.  Acute pancreatitis is a condition where the pancreas becomes inflamed.  It can be treated with fluids into the veins but in some cases can develop into serious complications and cause organ failure.  Damage to the pancreas in COVID-19 patients has not been reported before but it is not clear in this study whether the pancreatitis was related to COVID-19 infection or other causes
 

The researchers also found evidence of a rare fungal infection, in one of the patients, called Mucormycosis. Mucormycosis is an infection that may spread through the bloodstream to affect another part of the body. Severe infections can involve the lungs, brain and other organs including the kidneys, spleen and heart.

The team is working with a range of research groups both nationally and internationally to perform more detailed analyses of these tissues and is hoping that this research will expand to include a wider range of patients. 

Air pollution is the world’s leading environmental risk factor, and causes more than nine million deaths per year. New research published in the Journal of Clinical Investigation shows air pollution may play a role in the development of cardiometabolic diseases, such as diabetes. Importantly, the effects were reversible with cessation of exposure.

Researchers found that air pollution was a “risk factor for a risk factor” that contributed to the common soil of other fatal problems like heart attack and stroke. Similar to how an unhealthy diet and lack of exercise can lead to disease, exposure to air pollution could be added to this risk factor list as well.  

“In this study, we created an environment that mimicked a polluted day in New Delhi or Beijing,” said Sanjay Rajagopalan, MD, first author on the study, Chief of Cardiovascular Medicine at University Hospitals Harrington Heart and Vascular Institute, and Director of the Case Western Reserve University Cardiovascular Research Institute. “We concentrated fine particles of air pollution, called PM2.5 (particulate matter component < 2.5 microns). Concentrated particles like this develop from human impact on the environment, such as automobile exhaust, power generation and other fossil fuels.”

These particles have been strongly connected to risk factors for disease. For example, cardiovascular effects of air pollution can lead to heart attack and stroke. The research team has shown exposure to air pollution can increase the likelihood of the same risk factors that lead to heart disease, such as insulin resistance and type 2 diabetes.

In the mouse model study, three groups were observed: a control group receiving clean filtered air, a group exposed to polluted air for 24 weeks, and a group fed a high-fat diet. Interestingly, the researchers found that being exposed to air pollution was comparable to eating a high-fat diet. Both the air pollution and high-fat diet groups showed insulin resistance and abnormal metabolism – just like one would see in a pre-diabetic state.  

These changes were associated with changes in the epigenome, a layer of control that can masterfully turn on and turn off thousands of genes, representing a critical buffer in response to environmental factors. This study is the first-of-its-kind to compare genome-wide epigenetic changes in response to air pollution, compare and contrast these changes with that of eating an unhealthy diet, and examine the impact of air pollution cessation on these changes.

“The good news is that these effects were reversible, at least in our experiments” added Dr. Rajagopalan. “Once the air pollution was removed from the environment, the mice appeared healthier and the pre-diabetic state seemed to reverse.”

Dr. Rajagopalan explains that if you live in a densely polluted environment, taking actions such as wearing an N95 mask, using portable indoor air cleaners, utilizing air conditioning, closing car windows while commuting, and changing car air filters frequently could all be helpful in staying healthy and limiting air pollution exposure.

Next steps in this research involve meeting with a panel of experts, as well as the National Institutes of Health, to discuss conducting clinical trials that compare heart health and the level of air pollution in the environment. For example, if someone has a heart attack, should they be wearing an N95 mask or using a portable air filter at home during recovery? 

Dr. Rajagopalan and his team believe that it is important to address the environment as a population health risk factor and continue to diligently research these issues. The authors also note that these findings should encourage policymakers to enact measures aimed at reducing air pollution.