“We’ve known that the virus SARS-CoV-2 enters the body through the respiratory tract, with the nose being a key entry point. What’s new — and surprising — is that bacteria in our noses can influence the levels of proteins that the virus uses to infect cells,” said Cindy Liu, associate professor of environmental and occupational health at the GW Milken Institute School of Public Health.

Higher Gene Expression of Viral Entry Proteins Increases COVID-19 Infection Risk

In the study, Liu and her team analyzed nasal swab samples from over 450 people, including some who later tested positive for COVID-19. They found that those who became infected had higher levels of gene expression for two key proteins — ACE2 and TMPRSS2. ACE2 allows the virus to enter nasal cells, while TMPRSS2 helps activate the virus by cleaving its spike protein.

Those with high expression for these proteins were more than three times as likely to test positive for COVID-19, while those with moderate levels had double the risk. The study also found that people who became infected had more unstable levels of gene expression, with the sharpest increases just days before testing positive, suggesting rising expression levels may signal increased vulnerability to the virus.

Notably, while women generally had higher gene expression levels of these proteins — consistent with previous studies showing higher COVID-19 infection rates in women — men with higher levels were more likely to get infected, indicating elevated protein levels may present a greater risk for men.

Nasal Bacteria May Play a Role in COVID-19 Risk

To understand what could impact the expression levels of these viral entry proteins, the researchers turned to the nasal microbiome — the diverse community of bacteria that naturally reside in the nose. They found that certain nasal bacteria may affect the expression levels of ACE2 and TMPRSS2, influencing the respiratory tract’s susceptibility to COVID-19.

The study identified three common nasal bacteria — Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis/nonliquefaciens — that were linked to higher expression levels of ACE2 and TMPRSS2 and increased COVID-19 risk. On the other hand, Dolosigranulum pigrum, another common type of nasal bacteria, was connected to lower levels of these key proteins and may offer some protection against the virus.

“Some bacteria in your nose may be setting the stage — or even holding the door open — for viruses like SARS-CoV-2 to get in,” said Daniel. Park, a senior research scientist at GW and the first author of the study.

While some of the high-risk bacteria were less common, 20% of participants carried enough S. aureus to nearly double their risk for having elevated ACE2 and TMPRSS2 expression, making it a major nasal microbiome risk factor for increasing individuals’ risk for COVID-19 infection.

Why This Matters

The findings offer new potential ways to predict and prevent COVID-19 infection. The study suggests that monitoring ACE2 and TMPRSS2 gene expression could help identify individuals at higher risk for infection. The research also highlights the potential of targeting the nasal microbiome to help prevent viral infections.

“We’re only beginning to understand the complex relationship between the nasal microbiome and our health,” said Liu. “This study suggests that the bacteria in our nose — and how they interact with the cells and immune system in our nasal cavity — could play an important role in determining our risk for respiratory infections like COVID-19.”

The team plans to explore whether modifying the nasal microbiome, such as through nasal sprays or live biotherapeutics, could reduce the risk of infection — potentially paving the way for new ways to prevent respiratory viral infections in future pandemics.

The study, “The Nasal Microbiome Modulates Risk for SARS-CoV-2 Infection,” was published April 9 in the journal EBioMedicine. The research was supported by the GW Milken Institute School of Public Health and by the National Institutes of Health.

The digital twin was trained on large datasets of brain activity collected from the visual cortex of real mice as they watched movie clips. It could then predict the response of tens of thousands of neurons to new videos and images.

Digital twins could make studying the inner workings of the brain easier and more efficient.

“If you build a model of the brain and it’s very accurate, that means you can do a lot more experiments,” said Andreas Tolias, PhD, Stanford Medicine professor of ophthalmology and senior author of the study published April 10 in Nature. “The ones that are the most promising you can then test in the real brain.”

The lead author of the study is Eric Wang, PhD, a medical student at Baylor College of Medicine.

Beyond the training distribution

Unlike previous AI models of the visual cortex, which could simulate the brain’s response to only the type of stimuli they saw in the training data, the new model can predict the brain’s response to a wide range of new visual input. It can even surmise anatomical features of each neuron.

The new model is an example of a foundation model, a relatively new class of AI models capable of learning from large datasets, then applying that knowledge to new tasks and new types of data — or what researchers call “generalizing outside the training distribution.”

(ChatGPT is a familiar example of a foundation model that can learn from vast amounts of text to then understand and generate new text.)

“In many ways, the seed of intelligence is the ability to generalize robustly,” Tolias said. “The ultimate goal — the holy grail — is to generalize to scenarios outside your training distribution.”

Mouse movies

To train the new AI model, the researchers first recorded the brain activity of real mice as they watched movies — made-for-people movies. The films ideally would approximate what the mice might see in natural settings.

“It’s very hard to sample a realistic movie for mice, because nobody makes Hollywood movies for mice,” Tolias said. But action movies came close enough.

Mice have low-resolution vision — similar to our peripheral vision — meaning they mainly see movement rather than details or color. “Mice like movement, which strongly activates their visual system, so we showed them movies that have a lot of action,” Tolias said.

Over many short viewing sessions, the researchers recorded more than 900 minutes of brain activity from eight mice watching clips of action-packed movies, such as Mad Max. Cameras monitored their eye movements and behavior.

The researchers used the aggregated data to train a core model, which could then be customized into a digital twin of any individual mouse with a bit of additional training.

Accurate predictions

These digital twins were able to closely simulate the neural activity of their biological counterparts in response to a variety of new visual stimuli, including videos and static images. The large quantity of aggregated training data was key to the digital twins’ success, Tolias said. “They were impressively accurate because they were trained on such large datasets.”

Though trained only on neural activity, the new models could generalize to other types of data.

The digital twin of one particular mouse was able to predict the anatomical locations and cell type of thousands of neurons in the visual cortex as well as the connections between these neurons.

The researchers verified these predictions against high-resolution, electron microscope imaging of that mouse’s visual cortex, which was part of a larger project to map the structure and function of the mouse visual cortex in unprecedented detail. The results of that project, known as MICrONS, was published simultaneously in Nature.

Opening the black box

Because a digital twin can function long past the lifespan of a mouse, scientists could perform a virtually unlimited number of experiments on essentially the same animal. Experiments that would take years could be completed in hours, and millions of experiments could run simultaneously, speeding up research into how the brain processes information and the principles of intelligence.

“We’re trying to open the black box, so to speak, to understand the brain at the level of individual neurons or populations of neurons and how they work together to encode information,” Tolias said.

In fact, the new models are already yielding new insights. In another related study, also simultaneously published in Nature, researchers used a digital twin to discover how neurons in the visual cortex choose other neurons with which to form connections.

Scientists had known that similar neurons tend to form connections, like people forming friendships. The digital twin revealed which similarities mattered the most. Neurons prefer to connect with neurons that respond to the same stimulus — the color blue, for example — over neurons that respond to the same area of visual space.

“It’s like someone selecting friends based on what they like and not where they are,” Tolias said. “We learned this more precise rule of how the brain is organized.”

The researchers plan to extend their modeling into other brain areas and to animals, including primates, with more advanced cognitive capabilities.

“Eventually, I believe it will be possible to build digital twins of at least parts of the human brain,” Tolias said. “This is just the tip of the iceberg.”

Researchers from the University Göttingen and the Allen Institute for Brain Science contributed to the work.

The study received funding from the Intelligence Advanced Research Projects Activity, a National Science Foundation NeuroNex grant, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke (grant U19MH114830), the National Eye Institute (grant R01 EY026927 and Core Grant for Vision Research T32-EY-002520-37), the European Research Council and the Deutsche Forschungsgemeinschaft.

Hyaline arteriolosclerosis is a condition that causes the small blood vessels to narrow, becoming thick and stiff. This makes it harder for blood to flow, which can damage the brain over time. It appears as lesions, areas of damaged tissue in the brain.

“Heavy alcohol consumption is a major global health concern linked to increased health problems and death,” said study author Alberto Fernando Oliveira Justo, PhD, of University of Sao Paulo Medical School in Brazil. “We looked at how alcohol affects the brain as people get older. Our research shows that heavy alcohol consumption is damaging to the brain, which can lead to memory and thinking problems.”

The study included 1,781 people who had an average age of 75 at death. All had brain autopsies.

Researchers examined brain tissue to look for signs of brain injury including tau tangles and hyaline arteriolosclerosis. They also measured brain weight and the height of each participant.

Family members answered questions about participants’ alcohol consumption.

Researchers then divided the participants into four groups: 965 people who never drank, 319 moderate drinkers who had seven or fewer drinks per week; 129 heavy drinkers who had eight or more drinks per week; and 368 former heavy drinkers. Researchers defined one drink as having 14 grams of alcohol, which is about 350 milliliters (ml) of beer, 150 ml of wine or 45 ml of distilled spirits.

Of those who never drank, 40% had vascular brain lesions. Of the moderate drinkers, 45% had vascular brain lesions. Of the heavy drinkers, 44% had vascular brain lesions. Of the former heavy drinkers, 50% had vascular brain lesions.

After adjusting for factors that could affect brain health such as age at death, smoking and physical activity, heavy drinkers had 133% higher odds of having vascular brain lesions compared to those who never drank, former heavy drinkers had 89% higher odds and moderate drinkers, 60%.

Researchers also found heavy and former heavy drinkers had higher odds of developing tau tangles, a biomarker associated with Alzheimer’s disease, with 41% and 31% higher odds, respectively.

Former heavy drinking was associated with a lower brain mass ratio, a smaller proportion of brain mass compared to body mass, and worse cognitive abilities. No link was found between moderate or heavy drinking and brain mass ratio or cognitive abilities.

Justo noted that, in addition to brain injuries, impaired cognitive abilities were observed only in former drinkers.

Researchers also found that heavy drinkers died an average of 13 years earlier than those who never drank.

“We found heavy drinking is directly linked to signs of injury in the brain, and this can cause long-term effects on brain health, which may impact memory and thinking abilities,” said Justo. “Understanding these effects is crucial for public health awareness and continuing to implement preventive measures to reduce heavy drinking.”

A limitation of the study was that it did not look at participants before death and did not have information on the duration of alcohol consumption and cognitive abilities.

The study was supported by The São Paulo Research Foundation.

University of Nebraska-Lincoln researchers made major contributions to the study, published online April 8 in the journal Nature Food.

“We are in a race to feed the world and to try to feed the population with the available agricultural land that we have,” said Patricio Grassini, Sunkist Distinguished Professor of Agronomy and one of the paper’s authors.

To do so requires estimates that predict both yield potential, as determined by weather and soil properties, and yield gaps, which is the difference between yield potential and current farm yields, which indicates the room that exists to increase food production on existing cropland. Those estimates are essential in making investments in agricultural research and development, both from public and private sources.

At issue is how best to compile those estimates.

In the Nature Food paper, a team that includes scientists from Nebraska and three other institutions calls into question the statistical methods now widely used. In addition to Grassini, Husker authors of the study included Fatima Tenorio, Fernando Aramburu Merlos and Juan Rattalino Edreira, research assistant professors of agronomy.

In the United States, for example, current statistical models tend to rely too heavily on best-case scenarios — the most productive counties with the most fertile soils in a year with the most favorable weather, Grassini said. The methods also extrapolate a single yield potential across large regions with a wide diversity of climates and soils that likely would produce a similarly wide range in yield potential.

“Therefore, if you use that year as a reference, you are going to be overestimating your production potential because the best county with the best soils in the best year doesn’t really represent your average climate or your most typical soil across the state,” Grassini said.

But in other parts of the world — Africa, for example — these models might underestimate crop yield. There, farmers may have limited access to inputs compared to producers in other areas, thus attaining yields far below what the climate can support.

This statistical approach also leads to conflicting results, with production potential estimates almost doubling from one method to another. Grassini said this approach — driven mostly by geographers and statisticians, not agronomists — has been largely accepted, and more rigorous analysis is needed.

The research team’s conclusions are explained in the paper, titled “Statistical approaches are inadequate for accurate estimation of yield potential and gaps at regional level.”

The study compared estimates of yield potential and yield gaps of major U.S. rainfed crops — corn, soybeans and wheat — derived from four statistical models against those derived from a “bottom-up” spatial scaling approach based on robust crop modeling and local weather and soil data, such as the Global Yield Gap and Water Productivity Atlas developed at Nebraska.

Process-based crop models used in this study have been rigorously validated for their capacity to estimate yield potential based on experimental data from well-managed crops grown across a wide range of environments. This bottom-up approach, which better incorporates long-term data and regional variations, is clearly superior, the team found.

“I expect some controversy,” Grassini said of the team’s conclusions challenging the conventional wisdom.

The approach recommended by the team should better capture yield gaps, which “can help identify regions with largest room to increase crop production, which, in turn provides a basis to orient agricultural research and development programs.”

“This is a call to set the record straight because if we are going to use this information to inform policy and our investments, we better make sure that the information is sound and has been validated,” Grassini said.

Additional team members included Romulo Lollato, associate professor of agronomy, Kansas State University; Sotirios Archontoulis, professor of agronomy, Iowa State University; and Antoine Couëdel, who completed his postdoctoral research at Nebraska and is a researcher at the French Agricultural Research Centre for International Development, France.

But the crater it left behind in the Gulf of Mexico was a literal hotbed for life enriching the overlying ocean for at least 700,000 years, according to research published today in Nature Communications.

Scientists have discovered that a hydrothermal system created by the asteroid impact may have helped marine life flourish at the impact site by generating and circulating nutrients in the crater environment.

“After the asteroid impact, the Gulf of Mexico records an ecological recovery process that is quite different from that of the global ocean, as continuous hydrothermal activity has created a unique marine environment,” said the study’s lead author Honami Sato, an assistant professor at Japan’s Kyushu University.

Sean Gulick, a research professor at The University of Texas at Austin’s Jackson School of Geosciences, is a co-author on the study. In 2016, he co-led a scientific drilling expedition to the impact site, which is called Chicxulub, that recovered core samples from the crater.

The study is the latest discovery to come from research on the 829 meters of core retrieved by the international team of researchers.

Previous research already determined that life returned to the site of the crater within a matter of years. The new study presents evidence that a hydrothermal system created by the asteroid impact and its melt sheet buried beneath the seafloor likely played a role in its recovery and sustenance for hundreds of thousands of years.

“We are increasingly learning about the importance of impact-generated hydrothermal systems for life,” Gulick said. “This paper is a step forward in showing the potential of an impact event to affect the overlying ocean for hundreds of thousands of years.”

The research hinges on a chemical element called osmium. A particular ratio of osmium is associated with asteroid materials. The researchers found evidence that osmium from the asteroid buried kilometers beneath the impact crater was continuously released in the Gulf of Mexico due to submarine hydrothermal activity.

In other words, as hot water moved beneath the seafloor and up toward the surface, so did traces of the asteroid. As the hydrothermal fluid cooled over time, the asteroid traces exited the water and precipitated into sediment. The researchers analyzed the sediment, which was brought to the surface in the core samples, and used it to determine the extent of the hydrothermal system and how long the enrichment of osmium lasted.

The researchers also found that as the hydrothermal system ceased releasing osmium from the asteroid, the types of marine life living at the crater site changed. They found that when the hydrothermal system was releasing this osmium, the type of plankton found living in the environment were associated with high-nutrient environments. When the osmium returned to pre-impact levels, the plankton were associated with low-nutrient environments.

This finding indicates that the ecosystem was no longer being sustained by the nutrients from the hydrothermal system being released into the overlying ocean. However, beneath the seafloor the hydrothermal system continued to persist for many millions of years; it just became ever more deeply buried by millions of years of sedimentation.

“This study reveals that impact cratering events, while primarily destructive, can in some cases also lead to significant hydrothermal activity,” said co-author Steven Goderis, a research professor at the Vrije Universiteit Brussel, in Belgium. “In the case of Chicxulub, this process played a vital role in the rapid recovery of marine ecosystems.”

With the demise of the dinosaurs, the Chicxulub impact is well known for its link to causing mass extinction. Gulick said that this research is important because it shows that this impact can be a catalyst for life, too. At the UT Center for Planetary Systems Habitability, Gulick is leading research on whether large impacts elsewhere in the solar system could help generate conditions that could sustain life on other planets or moons.

The science team included researchers from Kyushu University; the University of Texas at Austin’s Jackson School of Geosciences’ Department of Earth and Planetary Sciences and Institute for Geophysics; the Japan Agency for Marine-Earth Science and Technology; Vrije Universiteit Brussel, Belgium; Institute of Science Tokyo; Universidad de Zaragoza, Zaragoza, Spain; Universitat de Barcelona, Barcelona, Spain; and Imperial College London.

Co-undergrounding is the practice of burying both electric and broadband internet lines together. “One main benefit from undergrounding both electric and broadband together for us was cost saving that we can have from co-deployment of those utility lines,” says Mahsa Arabi, lead study author and an ELEVATE research fellow in the UMass Amherst Energy Transition Institute (ETI). This cost savings makes it feasible for even smaller towns in Massachusetts to make undergrounding upgrades. Using computational modeling across a variety of infrastructure upgrade scenarios, the researchers found that co-undergrounding is 39% more cost-effective than separately burying electrical and broadband wires.

One of the study authors, Erin Baker, faculty director of ETI and distinguished professor in the College of Engineering at UMass Amherst, explains that co-undergrounding wires is becoming more salient to decision makers who are focusing on the efficiency of infrastructure. “Instead of tearing up the road to do this and then a year later tear it up to do that, let’s think about doing it together,” she says.

The researchers also asked: how aggressively should towns pivot to putting lines underground? Should they wait until lines have reached the end of their lifespan and then replace as needed, or proactively move forward?

To answer this, the researchers defined three overarching considerations: the cost of converting lines from above ground to underground, the cost of outages and the hours of outages that can be avoided if lines are underground.

To quantify these factors, the researchers created a nuanced computational model. “A big driver of this whole thing is the cost,” adds Jimi Oke, director of NARS Lab, assistant professor of civil and environmental engineering and principal investigator of the study. “In previous studies, people just used estimates based on average values, but we essentially try to model the dependency of the cost on things like the soil composition, the network type or the other land use variables,” he says.

Using the town of Shrewsbury, Massachusetts as a case study, the team found that the most cost-effective solution is to be aggressively proactive in co-undergrounding and replacing existing infrastructure, as long as it can be confirmed that undergrounding wires reduces outages by at least 50%.

Over 40 years, the cost of an aggressive co-undergrounding strategy in Shrewsbury would be $45.4 million, but the benefit from avoiding outages is $55.1 million. This considers factors like spoiled food, damaged home appliances, missed remote work hours and increased use of backup power sources. For a power outage, the costs are estimated to be $10 per person per hour, $205 per business per hour and $15,000 per industrial customer per hour. In Massachusetts, the average outage duration per customer per year, for both broadband and electricity, is estimated to be 1.38 hours. The researchers also took into consideration an additional benefit of $1.5 million in increased property values from the aesthetic improvement of eliminating overhead lines.

Altogether, this created a net benefit of $11.3 million.

The strategy with the second-highest net benefit was to aggressively convert just the electrical wires from above ground to underground. While this is a less expensive strategy, the savings were notably diminished, for a net benefit that was five times lower than the co-undergrounding strategy. All other strategies, including moderately paced conversions, had a negative net benefit.

One of the biggest remaining question marks is determining exactly how many outages will be prevented by undergrounding. “There’s kind of an intuitive thing [that undergrounding will reduce outages], but there is kind of mixed information about exactly how much because there are outages for a lot of different reasons,” explains Baker. “It means for [undergrounding to be worthwhile] half the outages have to be caused by basically something weather induced. If more than half of your outages are caused by the plant breaking down, then you shouldn’t underground anything. But the moment it flips over and it becomes good enough to do something, it means you want to be fully aggressive.”

Storms aren’t the only causes of outages, says Oke, pointing to California wildfires. California utilities will institute planned outages in order to prevent additional fires, but putting wires underground could prevent the initial fire (and therefore the outage). Consider the 2018 Camp Fire in Northern California — the most destructive wildfire in the state’s history. This fire was caused when a worn-out metal hook on a transmission tower failed, allowing a live line to fall and hit a transmission tower.

“We need to have a framework and a set of regulations that encourages utilities and towns to think strategically,” says Baker. She hopes that their findings can help decision makers do just this.

The team hopes that future research will quantify the impacts of co-undergrounding across a variety of geographic locations and scenarios. Other relevant future directions include investigating alternative underground routing options, and other potential outage mitigation strategies.