Author: Futurity (National Geo)

In a new trial, more than half of patients with persistent smell loss due to COVID-19 saw improvement with injections of platelet-rich plasma.

Early in the pandemic, when people with COVID-19 began reporting that they lost their sense of smell, Zara Patel figured as much. A professor of otolaryngology at Stanford Medicine, Patel has, for years, studied loss of smell as a symptom of viral infections.

“Many viruses can cause smell loss, so it wasn’t surprising to us as rhinologists when we found out that COVID-19 causes loss of smell and taste. It was almost expected,” she says. Patel also knew that the condition could last a while and that few effective treatments were available.

According to a 2022 survey by Patel and colleagues, about 15% of people who experienced smell loss from COVID-19 continued to have problems six months later. That’s roughly 9 million people in the US, and the number is growing. Many who report loss of smell also report loss of taste because smell is such a major component of how we experience food.

Now Patel’s team has tested a new treatment for long-term, COVID-19-related smell loss using injections of platelet-rich plasma derived from a patient’s own blood. In a trial of 26 participants, those who received the treatment were 12.5 times more likely to improve than patients who received placebo injections.

What is platelet-rich plasma?

Platelet-rich plasma is a concentrated form of plasma, the liquid portion of blood, with blood cells and other blood components removed. It’s rich in platelets and, most importantly, growth factors—compounds known to help regenerate tissue. Platelet-rich plasma has been purported to treat mild arthritis when injected into joints, reduce wrinkles when used on the face, and even regrow hair when injected into the scalp.

Patel was skeptical of such a cure-all but was intrigued by a study showing that platelet-rich plasma injections were as effective as surgery in treating carpal tunnel syndrome, which is caused by compressing and injuring a nerve in the wrist. She knew that COVID-19-related smell loss also was a neurological problem, in which long-term effects of the virus prevent nerves deep in the nasal cavity from regenerating correctly. These nerves connect to the brain and normally regenerate every three to four months.

“It’s a nerve damage and nerve regeneration issue that we’re dealing with,” she says.

How SARS-CoV-2 damages nerves

The SARS-CoV-2 virus doesn’t target nerve cells directly; it attacks supporting cells known as sustentacular cells, which have the ACE-2 receptor the virus uses to infect cells. These cells play a role in correct nerve regeneration, so persistent inflammation and damage to these cells may lead to long-term loss of function.

Patel had already completed a small pilot study demonstrating the safety of platelet-rich plasma injections in the nasal cavity when the pandemic hit, so she pivoted her plans for a larger trial to focus specifically on COVID-19-associated smell loss.

All participants had confirmed past COVID-19 infections and persistent smell loss lasting between 6 and 12 months. They also had to have already tried other treatments such as olfactory training and steroid rinses.

“I wanted to make sure that whatever intervention I was going to study was not just in place of or equivalent to the treatments we’re already doing, but a benefit above and beyond,” Patel says.

Half the participants received platelet-rich plasma injections into the tissue deep inside their nasal cavity every two weeks for six weeks, while the other half received placebo injections (of saline) on the same schedule. Neither the participants nor the researchers knew who received what.

Sniff, sniff

The researchers assessed smell ability using a standard olfactory test known as Sniffin’ Sticks. The test includes a range of odors, both pleasant (flowers) and terrible (rotten eggs), and participants are scored on their ability to identify the odors, tell odors apart, and determine their strength, for a possible score of 48.

When the researchers checked in with the participants three months after their first injection, those in the platelet-rich plasma group scored on average 6.25 points higher than they did before treatment, which was 3.67 points greater than the placebo group. They gained most in their ability to tell different odors apart, known as smell discrimination. At three months, 57.1% of the platelet-rich plasma group had shown a clinically significant improvement, compared with just 8.3% in the placebo group.

Interestingly, when the participants rated their own smell ability, both groups reported similar improvement. Patel says that prior studies have found that subjective improvement doesn’t always match up with objective improvement.

The improvements in the placebo group could in part be due to a placebo effect, Patel says, but they could also suggest that some spontaneous recovery can happen even after six months.

COVID-19 has brought attention to post-viral smell loss, and perhaps more appreciation of the role smell plays in our daily lives, Patel says. Though this study did not evaluate taste loss, the recovery of smell likely also would help with recovery of taste.

“People tell me all the time that they never realized how important their sense of smell and taste was to them and their quality of life until they lost it,” she says. “People say, ‘My life has gone gray.’”

Patel is now offering platelet-rich plasma injections to patients outside the trial.

“Our olfactory systems can be resilient,” Patel says. “But the sooner you perform some sort of definitive intervention, probably the better chance you have of improvement.”

The study appears in the International Forum of Allergy and Rhinology. Researchers from UC San Diego contributed to the study.

Source: Stanford University

Researchers report that the amount of emissions from gas-fired power could be cut by as much as 71% if a variety of mitigation options were used around the world.

About a quarter of the world’s electricity currently comes from power plants fired by natural gas. These contribute significantly to global greenhouse gas emissions (amounting to 10% of energy-related emissions according to the most recent figures from 2017) and climate change.

By gathering data from 108 countries around the world and quantifying the emissions by country, the new study estimates that total global carbon dioxide (CO2) emissions from the life cycle of gas-fired power is 39.68 billion tons each year.

“We were astonished by how large the potential reduction in greenhouse gases could be by 2050, and even by 2030,” says Sarah Jordaan, an associate professor in the civil engineering department and the Trottier Institute in Sustainability in Engineering and Design at McGill University and the first author of the paper.

“If natural gas is going to play a role in a low carbon future, even for a transitional period, there will be a need to improve efficiency in power plants and to cut methane emissions from natural gas production as well as to capture and store CO2.”

“We found that the most effective way to reduce greenhouse gas emissions was with carbon capture and storage, followed by making power plants more efficient,” adds Andrew Ruttinger, a PhD student in chemical and biomolecular engineering at Cornell University who participated in the research. “But the mitigation options that will be most successful in any given country will vary depending on the regional context and the existing infrastructure.”

The team calculated that the largest mitigation potential (39%) lies with five biggest emitters, the United States, Russia, Iran, Saudi Arabia, and Japan, all of whom, apart from Japan, are among the largest gas producers and consumers around the world.

“Climate change is a global challenge and achieving a low-carbon energy system points to the need for reducing emissions across the supply chain from gas extraction through end use,” says Arvind Ravikumar, a research associate professor in the petroleum and geosystems engineering department of Petroleum and Geosystems at the University of Texas at Austin.

“Our analysis demonstrates that significant efforts are needed to transition from current emissions levels, but also that by identifying the drivers of emissions in the gas supply chain, governments can take strategic, nationally-determined action to reduce their emissions.”

The research appears in Nature Climate Change.

Additional researchers from Carnegie Mellon, Johns Hopkins, the University of Texas at Austin, and the University of Maryland contributed to the work.

Source: McGill University

A new analysis of data from a yearlong weight-loss study identifies behaviors and biomarkers that contribute to short- and long-term weight loss.

Strictly following a diet—either healthy low-carb or healthy low-fat—was what mattered for short-term weight loss during the first six months. But people who maintained long-term weight loss for a year ate the same number of calories as those who regained weight or who did not lose weight during the second six months.

So what explains this difference?

According to the study, the bacteria living in your gut and the amounts of certain proteins your body makes can affect your ability to sustain weight loss. And some people, it turns out, shed more pounds on low-fat diets while others did better on low-carb diets.

The researchers have identified several biomarkers that predict how successful an individual will be at losing weight and keeping it off long-term. These biomarkers include signatures from the gut microbiome, proteins made by the human body, and levels of exhaled carbon dioxide. The researchers report their findings in the journal Cell Reports Medicine.

“Weight loss is enigmatic and complicated, but we can predict from the outset with microbiome and metabolic biomarkers who will lose the most weight and who will keep it off,” says Michael Snyder, professor and chair of genetics at the Stanford School of Medicine and co-senior author of the paper.

It’s not about your willpower

The data came from 609 participants who logged everything they ate for a year while following either a low-fat or low-carb diet made up of mostly high-quality, minimally processed foods. The researchers tracked participant exercise, how well they followed their diet, and the number of calories they took in.

“Your mindset should be on what you can include in your diet instead of what you should exclude.”

The study shows that just cutting calories or exercising was not enough to sustain weight loss over a year. To try and understand why, the team turned their focus to biomarkers of metabolism.

“We found specific microbiome ecologies and amounts of proteins and enzymes at the beginning of the study period—before people started following the diet—that indicated whether they would be successful at losing weight and keeping it off,” says Dalia Perelman, research dietician and co-lead author of the paper.

Throughout the study, the researchers measured the ratio of inhaled oxygen to exhaled carbon dioxide, known as a respiratory quotient, which serves as a proxy for whether carbohydrates or fats are the body’s primary fuel. A lower ratio means the body burns more fat, while a higher ratio means it burns more carbohydrates. So, those who started the diet with a higher respiratory quotient lost more weight on a low-carb diet.

“There are people who can be eating very few calories but still sustain their weight because of how their bodies metabolize fuels. It is not for lack of will: It is just how their bodies work,” Perelman says.

In other words, if your body prefers carbs and you’re predominately eating fat, it will be much harder to metabolize and burn off those calories.

“If you are following a diet that worked for someone you know and it is not working for you, it might be that that specific diet is not as suited for you,” adds Xiao Li, co-lead author of the paper and a former postdoctoral fellow at Stanford Medicine who is now at Case Western University.

Before biomarkers for weight loss are available

The predictive information gleaned from the gut microbiome, proteomic analysis, and respiratory quotient signatures lays the foundation for personalized diets. Snyder says he thinks tracking amounts of certain gut microbe strains will be a way for people to determine which diets are best for weight loss.

We’re not there yet, so until then, according to the researchers, the focus should be on eating high-quality foods that are unprocessed and low in refined flours and sugar.

The research team identified specific nutrients that were correlated with weight loss during the first six months. Low-carb diets should be based on monounsaturated fats—such as those that come from avocados, rather than from bacon—and high in vitamins K, C, and E. These vitamins are in vegetables, nuts, olives, and avocados. Low-fat diets should be high in fiber, such as is in whole grains and beans, and avoid added sugars.

“Your mindset should be on what you can include in your diet instead of what you should exclude,” Perelman says. “Figure out how to eat more fiber, whether it is from beans, whole grains, nuts, or vegetables, instead of thinking you shouldn’t eat ice cream. Learn to cook and rely less on processed foods. If you pay attention to the quality of food in your diet, then you can forget about counting calories.”

Source: Kimberlee D’Ardenne for Stanford University

A new gene expression-based diagnostic blood test can separate bacterial and viral infections with 90% accuracy, the first to meet standards set by the World Health Organization.

In developing countries, most antibiotic prescriptions are not only pointless—an estimated 70% to 80% of them are given for viral infections, which the medications don’t treat—they’re also harmful, as overuse of antibiotics accelerates antibiotic resistance.

“Accurately diagnosing whether a patient has a bacterial or viral infection is one of the biggest global health challenges.”

A similar problem exists in the United States, where an estimated 30% to 50% of antibiotic prescriptions are given for viral infections.

The new test could allow doctors around the world to quickly and accurately distinguish between bacterial and viral infections, thereby cutting down on antibiotic overuse. The test is based on how the patient’s immune system responds to an infection.

It is the first such diagnostic test validated in diverse global populations—accounting for a wider range of bacterial infections—and the only one to meet the accuracy targets set by the World Health Organization and the Foundation for Innovative New Diagnostics to address antibiotic resistance.

Those targets include at least 90% sensitivity (correctly identifying true positives) and 80% specificity (correctly identifying true negatives) to distinguish bacterial and viral infections.

The new test is described in a paper in Cell Reports Medicine.

“Antimicrobial resistance is continuously rising, so there has been a lot of effort to reduce inappropriate antibiotic usage,” says senior author Purvesh Khatri, associate professor of medicine and biomedical data science at Stanford University. “Accurately diagnosing whether a patient has a bacterial or viral infection is one of the biggest global health challenges.”

Existing methods include growing the pathogen in a Petri dish, which takes several days, or polymerase chain reaction (PCR) testing, which requires knowing the specific pathogen to look for.

That’s why in many cases, “Doctors prescribe antibiotics empirically,” Khatri says. “They say, ‘We’re going to give you an antibiotic and if you get better, you had a bacterial infection. If you don’t, you have a viral infection, and we’ll stop the antibiotic.’”

Immune system reaction

The test is one of a new crop of diagnostic tests that look at the host response—that is, how the patient’s immune system is reacting—to identify the type of infection. They measure the expression of certain genes involved in the host’s immune response.

“The immune system has been doing this for millions of years, constantly learning what is bacteria, what is virus and how to respond to it,” Khatri says. “Instead of looking for the bug itself, we can ask the immune system.”

However, because these host-response tests have been designed using data from Western Europe and North America, they fail to account for the types of infections that are prevalent in low- and middle-income countries. In particular, they have trouble distinguishing the more subtle differences between intracellular bacterial infections and viral infections.

“Epidemiologically, bacterial infections in developed countries are usually from bacteria that replicate outside the human cell,” Khatri says. These extracellular bacteria include E. coli and those that cause strep throat. In developing countries, common bacterial infections like typhus and tuberculosis are caused by intracellular bacteria, which replicate inside human cells, as do viruses.

“The immune system has a different response based on whether it’s an extracellular or intracellular bacterial infection,” Khatri says. “The reason it gets tricky is because once the bacteria are inside the cell, the pathways overlap with the viral infection response.”

Current host-response tests can distinguish extracellular bacterial infections from viral infections with more than 80% accuracy, but they can identify only 40% to 70% of intracellular infections.

Point-of-care test next?

To develop a diagnostic test that can separate both types of bacterial infections from viral infections, Khatri’s team used publicly available gene expression data from 35 countries. These included 4,754 samples from people of various ages, sexes, and races with known infections. The diversity of patients, infections and types of data is more representative of the real world, Khatri says.

Using machine learning and half of these samples, they identified eight genes that are expressed differently in bacterial versus viral infections. They validated their eight-gene test on the remaining samples and more than 300 new samples collected from Nepal and Laos.

They found that these eight genes could distinguish intracellular and extracellular bacterial infections from viral infections with high accuracy, achieving 90% sensitivity and 90% specificity. It is the first diagnostic test to meet (and exceed) the standards proposed by the World Health Organization and the Foundation for Innovative New Diagnostics.

“We’ve shown that this eight-gene signature has higher accuracy and more generalizability for distinguishing bacterial and viral infections, irrespective of whether they are intracellular or extracellular, whether a patient is in a developed or developing country, a man or a woman, an infant or an 80-year-old,” Khatri says.

He hopes the new diagnostic test can eventually be translated into a point-of-care test and adopted by doctors in both developed and developing countries, as it requires only a blood sample and can be performed in 30 to 45 minutes. His team has applied for a patent on the test.

Additional researchers from Mahosot Hospital and the University of Health Sciences in Lao People’s Democratic Republic, Dhulikhel Hospital in Nepal, the University of Oxford, and the University of Toronto contributed to the study.

The Bill and Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases, the Department of Defense, the Ralph & Marian Falk Medical Research Trust, the Thomas C. and Joan M. Merigan Endowment at Stanford University, the Wellcome Trust of Great Britain, the National Science Foundation Graduate Research Fellowship, and the Stanford Graduate Fellowship funded the work.

Source: Stanford University

New research suggests that chemistry in late-stage planet development is fueled by ultraviolet rays, rather than cosmic rays or X-rays.

The chemistry of planet formation has fascinated researchers for decades because the chemical reservoir in protoplanetary discs—the dust and gas from which planets form—directly affects planet composition and potential for life.

The new finding provides a chemical signature that helps researchers trace exoplanets back to their cosmic nurseries in the planet-forming disks.

Jenny Calahan, a doctoral student in astronomy at the University of Michigan and first author of the paper in Nature Astronomy, says the discovery was part happy accident, part building on previous work.

“It has been shown that there are bright, complex organic molecules present in the coldest and densest parts of planet-forming disks,” Calahan says. “This bright emission has been puzzling because we expect these molecules to be frozen out at these temperatures, not in the gas where we can observe them.”

These molecules are emitting from regions that are minus-400 degrees Fahrenheit, and at these temperatures they’re thought to be frozen onto tiny solids that astronomers label as dust grains, or for the later millimeter-to-centimeter-sized solids as pebbles. These molecules should add to an icy coating on the grains, so they cannot be observed in the gas.

The planet-forming disk has three main components, a pebble-rich dusty midplane, a gas atmosphere, and a small dust population coupled to the gas. As the planet-forming disk evolves over time, the changing environment affects the chemistry within. To account for the observed brightness, Calahan adjusted her model to decrease the mass of the small dust population—which typically blocks UV photons—to allow more UV photons to penetrate deep into these coldest regions of the disc. This reproduced the observed brightness.

“If we have a carbon-rich environment paired with a UV-rich environment due to the evolution of the small solids in planet forming regions, we can produce complex organics in the gas and reproduce these observations,” she says.

This represents the evolution of small dust over time.

About 20 years ago, researchers realized that the chemistry of the gaseous disk is governed by chemistry operating on shorter timescales and powered by sources such as cosmic rays and X-rays, says principal investigator Edwin Bergin, professor and chair of astronomy.

“Our new work suggests that what really matters is the ultraviolet radiation field generated by the star accreting matter from the disk,” he says. “The initial steps in making planets, forming larger and larger solids, shifts the chemistry from cosmic rays and X-ray-driven early, to UV-driven during the phase where giant planets are thought to be born.

“Jenny’s work tells us for terrestrial worlds, if you wonder how they get things like water, the key part of the evolution is the early phases before this shift occurs. That is when the volatile molecules that comprise life—carbon, hydrogen, nitrogen—are implanted in solids that make Earth-like worlds. These planets are not born in this phase but rather the composition of solids becomes fixed. The later stages of this model tells us how to determine the composition of material that makes giant planets.”

Source: University of Michigan

In a new book, Joseph Silk explores what the moon can offer humans over the next half century.

As our nearest celestial neighbor, the moon has forever captured the awe of human beings. Some ancient cultures worshipped it as a deity or believed its eclipses to be omens. It was Galileo peering through an early telescope in 1609 who discovered the moon’s rocky surface, and NASA’s Apollo 11 mission in 1969 that sent the first humans to walk upon it.

A half-century has now passed since humans last made direct contact with the moon, with Apollo 17 in 1972. But a new era of exploration has begun with zeal, as a number of space agencies and commercial ventures worldwide launch ambitious lunar projects.

Look forward another half-century or so, says Silk, a Johns Hopkins University astrophysicist, and the moon could be teeming with activity: hotels and villages, lunar mining, ports into deeper space, and giant telescopes that could make the James Webb technology look amateur.

“We will build on the moon. We will colonize the moon. We will exploit the moon. We will do science on the moon,” Silk writes in his new book, Back to the Moon: The Next Giant Leap for Humankind (Princeton University Press, 2022). “Lunar science will open up new vistas on the most profound questions we have ever posed.”

As Back to the Moon hits shelves, there is tangible progress on this front. The Japanese company ispace intends to become the first private venture to make a cargo delivery to the moon, aboard a SpaceX rocket. At the same time, NASA is commencing the first test phase of its $93 billion Artemis program, which will send four astronauts to the moon in 2025 and establish a permanent base there, with the grand ambition to use the moon as a launchpad for the first-ever crewed mission to Mars.

A professor of physics and astronomy, Silk has penned previous books on the big bang, infinity, and other weighty cosmological topics. In Back to the Moon, he posits that the moon in fact offers our only pathway to surpassing the current limits of astronomy. “We’re running out of resources on Earth for it,” he says, “but the moon provides a site for achieving much more.”

The low gravity on the moon, for instance, could allow for easier manufacturing of megatelescopes 10 times larger than what’s possible on Earth, and the lack of lunar atmosphere can allow those telescopes to peer farther afield with exquisite precision, Silk says. These features will be crucial for studying far larger samples of Earth-like planets beyond our own solar system—and in turn for tackling one of humanity’s most probing mysteries: Are we alone in this universe?

In searching for exoplanets that could feasibly host life, astronomers know what to look for, as Silk writes: “the reflected glints of oceans, the green glows of forests, the presence of oxygen in the atmospheres, and even more advanced but subtle signs of intelligent life such as… industrial pollution of planetary atmospheres.” The megatelescopes, Silk says, could also help us understand the very origins of the cosmos, the dark ages before the first stars appeared.

A quarter of a million miles and three days from Earth, the moon can also serve as an improved launch site for deeper travels into space—in part because of the prohibitive payload required for rocket fuel to achieve interplanetary transport from Earth. On the moon, we’ll be able to produce that fuel directly from liquefying oxygen and hydrogen found in abundant lunar ice in the depths of permanently shadowed polar craters.

To pursue these endeavors, human settlement on the moon is necessary, Silk says. NASA already intends to build its Artemis base camp on the lunar south pole, where China, too, has plans for an international research station.

Silk also envisions denser habitats, villages or even cities, constructed within the vast lava tubes beneath the moon’s surface, protected from meteorites and other harms. But within the next 15 or 20 years, he says, moon resorts may be the first civilian projects we’ll see—”a very sophisticated tourism that opens up the moon to many more people than astronauts and engineers.” He can imagine lunar golfing and rover rides over lunar terrain. “At first, this will be accessible only to the very wealthy,” Silk says, likening it to the early days of airplane travel. “But just wait a decade or two.”

Silk acknowledges that humans are likely to carry their earthly failings onto the moon, and that intense international competition could erupt over commercial, military, and mining interests. An Outer Space Treaty, signed by the United Nations in 1967, does prohibit any nation from claiming sovereignty over any part of outer space, but Silk says we need something more detailed and enforceable. “We have to get our act together in the next decade to sort out how different countries can collaborate when they do… anything that involves territorial claims,” he says.

The most pressing argument Silk raises for our investment in the moon is chillingly existential: Ultimately, it may present humankind its best chance of longer-term survival. Silk points to extinction-level threats—global warming, pandemics, and wars, among them—that could force us to seek shelter elsewhere. The moon’s barren landscape and extreme temperatures make it not ideal for large or permanent populations, but it can serve as a steppingstone toward distant planets that humans could potentially colonize. It’s the stuff of sci-fi.

“Whether through cryogenic preservation of humans or genetic rebirth, the centurylong travel times to the nearest stars will not deter future generations of astronauts,” he writes, adding that the limitless potential of robotics and artificial intelligence will also open more doors than we can possibly imagine.

“There’s so much to learn,” Silk says. “Humanity has always been interested in discovering distant realms, in solving difficult questions that haven’t been answered. The moon offers us that vista.”

Source: Katie Pearce for Johns Hopkins University

Researchers have analyzed how light breaks down polystyrene, a nonbiodegradable plastic that packing peanuts, DVD cases, and disposable utensils are made of.

The researchers find that nanoplastic particles can play active roles in environmental systems.

Plastics are ubiquitous in our society, found in packaging and bottles as well as making up more than 18% of solid waste in landfills. Many of these plastics also make their way into the oceans, where they take up to hundreds of years to break down into pieces that can harm wildlife and the aquatic ecosystem.

In particular, when exposed to light, the nanoplastics derived from polystyrene unexpectedly facilitated the oxidation of aqueous manganese ions and formation of manganese oxide solids that can affect the fate and transport of organic contaminants in natural and engineering water systems.

The research shows how the photochemical reaction of nanoplastics through light absorption generates peroxyl and superoxide radicals on nanoplastic surfaces, and initiates oxidation of manganese into manganese oxide solids.

“As more plastic debris accumulates in the natural environment, there are increasing concerns about its adverse effects,” says research team leader Young-Shin Jun, professor of energy, environmental, and chemical engineering in the McKelvey School of Engineering at Washington University in St. Louis, who leads the Environmental Nanochemistry Laboratory.

“However, in most cases, we have been concerned about the roles of the physical presence of nanoplastics rather than their active roles as reactants. We found that such small plastic particles that can more easily interact with neighboring substances, such as heavy metals and organic contaminants, and can be more reactive than we previously thought.”

Jun and her former student, Zhenwei Gao, a postdoctoral scholar at the University of Chicago, experimentally demonstrated that the different surface functional groups on polystyrene nanoplastics affected manganese oxidation rates by influencing the generation of the highly reactive radicals, peroxyl, and superoxide radicals.

The production of these reactive oxygen species from nanoplastics can endanger marine life and human health and potentially affects the mobility of the nanoplastics in the environment via redox reactions, which in turn might negatively affect their environmental remediation.

The team also looked at the size effects of polystyrene nanoplastics on manganese oxidation, using 30 nanometer, 100 nanometer, and 500 nanometer particles. The two larger-sized nanoparticles took longer to oxidize manganese than the smaller particles. Eventually, the nanoplastics will be surrounded by newly formed manganese oxide fibers, which can make them easily aggregated and can change their reactivities and transport.

“The smaller particle size of the polystyrene nanoplastics may more easily decompose and release organic matter because of their larger surface area,” Jun says. “This dissolved organic matter may quickly produce reactive oxygen species in light and facilitate manganese oxidation.”

“This experimental work also provides useful insights into the heterogeneous nucleation and growth of manganese oxide solids on such organic substrates, which benefits our understanding of manganese oxide occurrences in the environment and engineered materials syntheses,” Jun says. “These manganese solids are excellent scavengers of redox-active species and heavy metals, further affecting geochemical element redox cycling, carbon mineralization, and biological metabolisms in nature.”

Jun’s team plans to study the breakdown of diverse common plastic sources that can release nanoplastics and reactive oxidizing species and to investigate their active roles in the oxidation of transition and heavy metal ions in the future.

The research appears in ACS Nano. Partial funding for this research came from the National Science Foundation and the McDonnell International Scholars Academy at Washington University in St. Louis.

Source: Washington University in St. Louis

Researchers are studying elite free divers to understand the limits of human physiology.

The insights could lead to better treatments for lung disease.

The world’s top free divers can hold their breath for minutes at a time, embarking on extended underwater adventures without the aid of scuba equipment.

People with chronic obstructive pulmonary disease often struggle to get enough oxygen. In response, arterioles—tiny branches of the arteries—bringing blood to the lungs constrict. That leads to high pulmonary blood pressure and strains the heart.

“It’s mostly thought of as a beneficial adaptation; if you inhale something blocking an airway, blood vessels going to that area will constrict and send blood elsewhere where it can pick up oxygen,” says Andy Lovering of the University of Oregon. “But the problem is that if you deplete the oxygen from the entire lung, the pressure inside increases, causing pulmonary hypertension.”

Free divers, on the other hand, intentionally put themselves into an oxygen-deprived state. During long dives, their blood oxygen levels sink to extreme lows. That could cause organ damage in some people. But trained divers can quickly bounce back, ready for another dive.

In studies of Croatian divers, Lovering’s team has identified a few distinctive adaptations, described in two recent papers. Together, those adaptations might help divers keep their heart and lungs working effectively under extremely low oxygen conditions.

In a study in Experimental Physiology, the researchers placed both trained divers and healthy nondivers into a low-oxygen environment for 20 to 30 minutes.

“The normal response to low oxygen is for arterioles in lungs to constrict,” raising pulmonary blood pressure, says Tyler Kelly, a graduate student in Lovering’s lab who led the work. “But we found that these athlete divers had a minimal response, if any.”

The arterioles in their lungs didn’t constrict as much in response to low oxygen, reducing the strain on the heart that diminished oxygen usually causes.

“It’s a really unique adaptation,” Lovering says.

In a study in the Journal of Science and Medicine in Sport, the researchers found that the divers were also more likely than nondivers to have a patent foramen ovale, a hole that creates a passageway between the left and right sides of the upper chambers of the heart. This hole is present in all babies in utero, allowing blood to circumvent the developing lungs. It usually closes soon after birth once the lungs kick into action. But in a small number of people, it remains partially open.

In divers, this hole could act like a relief valve, helping to reduce pressure on the right side of the heart under low-oxygen conditions, Lovering suggests.

Lovering’s team isn’t sure yet whether these are adaptations that arise due to extensive training or whether people who have the differences from birth are simply more likely to succeed as divers.

Divers often build their stamina via dryland training, essentially practicing holding their breath for increasingly long time periods while out of the water. In follow-up work, Lovering wants to test whether sending ordinary people through a breath-holding diving training program can induce the same physiological changes in regular people as is seen in the divers.

If so, structured breath-holding exercises could be a treatment for people with chronic lung disease, dampening their body’s response to low oxygen and minimizing the strain on the heart and lungs.

Source: Laurel Hamers for University of Oregon

Just days after the second anniversary of the January 6 attack on the United States Capitol, a new podcast episode reflects on some daunting questions.

Is democracy on the brink of the collapse? Why are US politics so polarized? And are we headed for another civil war? William Howell, a University of Chicago professor and director of the Center for Effective Government, has been thinking about these questions, along with political scientists across the country.

In this episode of the Big Brains podcast, Howell explains why claims of another civil war are overexaggerated, and instead, offers some correctives:

Subscribe to Big Brains on Apple Podcasts, Stitcher, and Spotify.

Source: University of Chicago

A new study reveals how a viral toxin the SARS-CoV-2 virus produces may contribute to severe COVID-19 infections.

The study shows how a portion of the SARS-CoV-2 “spike” protein can damage cell barriers that line the inside of blood vessels within organs of the body, such as the lungs, contributing to what is known as vascular leak.

Blocking the activity of this protein may help prevent some of COVID-19’s deadliest symptoms, including pulmonary edema, which contributes to acute respiratory distress syndrome (ARDS).

“People are aware of the role of bacterial toxins, but the concept of a viral toxin is still a really new idea,”

“In theory, by specifically targeting this pathway, we could block pathogenesis that leads to vascular disorder and acute respiratory distress syndrome without needing to target the virus itself,” says lead author Scott Biering, a postdoctoral scholar at the University of California, Berkeley.

“In light of all the different variants that are emerging and the difficulty in preventing infection from each one individually, it might be beneficial to focus on these triggers of pathogenesis in addition to blocking infection altogether.”

The spike protein and vascular leak

While many vaccine skeptics have stoked fears about potential dangers of the SARS-CoV-2 spike protein—which is the target of COVID-19 mRNA vaccines—the researchers say that their work provides no evidence that the spike protein can cause symptoms in the absence of viral infection. Instead, their study suggests that the spike protein may work in tandem with the virus and the body’s own immune response to trigger life-threatening symptoms.

In addition, the amount of spike protein circulating in the body after vaccination is far less concentrated than the amounts that have been observed in patients with severe COVID-19 and that were used in the study.

“The amount of spike protein that you would have in a vaccine would never be able to cause leak,” says senior author Eva Harris, a professor of infectious diseases and vaccinology. “In addition, there’s no evidence that [the spike protein] is pathogenic by itself. The idea is that it’s able to aid and abet an ongoing infection.”

By examining the impact of the SARS-CoV-2 spike protein on human lung and vascular cells, and on the lungs of mice, the research team was able to uncover the molecular pathways that allow the spike protein to disrupt critical internal barriers in the body. In addition to opening new avenues for the treatment of severe COVID-19, understanding how the spike protein contributes to vascular leak could shed light on the pathology behind other emerging infectious diseases.

“We think that a lot of viruses that cause severe disease may encode a viral toxin,” Biering says. “These proteins, independent of viral infection, interact with barrier cells, and cause these barriers to malfunction. This allows the virus to disseminate, and that amplification of virus and vascular leak is what triggers severe disease. I’m hoping that we can use the principles that we’ve learned from the SARS-CoV-2 virus to find ways to block this pathogenesis so that we are more prepared when the next pandemic happens.”

Vascular leak occurs when the cells that line blood vessels and capillaries are disrupted, allowing plasma and other fluids to leak out of the bloodstream. In addition to causing the lung and heart damage observed in severe COVID-19, vascular leak can also lead to hypovolemic shock, the primary cause of death from dengue.

Dengue and SARS-CoV-2

Before the COVID-19 pandemic, Biering and other members of the Harris Research Program were studying the role of dengue virus protein NS1 in triggering vascular leak and contributing to hypovolemic shock. When the pandemic hit, the team wondered if a similar viral toxin in SARS-CoV-2 could also be contributing to the acute respiratory distress syndrome that was killing COVID-19 patients.

“People are aware of the role of bacterial toxins, but the concept of a viral toxin is still a really new idea,” Harris says. “We had identified this protein secreted from dengue virus-infected cells that, even in the absence of the virus, is able to cause endothelial permeability and disrupt internal barriers. So, we wondered if a SARS-CoV-2 protein, like spike, might be able to do similar things.”

“COVID-19 is not gone. We have better vaccines now, but we don’t know how the virus is going to mutate in the future.”

Spike proteins coat the outer surface of SARS-CoV-2, giving the virus its knobby appearance. They play a critical role in helping the virus infect its hosts: The spike protein binds to a receptor called ACE2 on human and other mammalian cells, which—like a key turning a lock—allows the virus to enter the cell and hijack cellular function. The SARS-CoV-2 virus sheds a large portion of the spike protein containing the receptor-binding domain (RBD) when it infects a cell.

“What’s really interesting is that circulating spike protein correlates with severe COVID-19 cases in the clinic,” Biering says. “We wanted to ask if this protein was also contributing to any vascular leak we saw in the context of SARS-CoV-2.”

Currently, scientists attribute the heart and lung damage associated with severe COVID-19 to an overactive immune response called a cytokine storm. To test the theory that the spike protein might also play a role, Biering and other team members used thin layers of human endothelial and epithelial cells to mimic the linings of blood vessels in the body. They found that exposing these cellular layers to the spike protein increased their permeability, a hallmark of vascular leak.

Using CRISPR-Cas9 gene editing technology, the team showed that this increased permeability occurred even in cells that did not express the ACE2 receptor, indicating that it could occur independently of viral infection. In addition, they found that mice that were exposed to the spike protein also exhibited vascular leak, even though mice do not express the human ACE2 receptor and cannot be infected with SARS-CoV-2.

Finally, with the help of RNA sequencing, the researchers found that the spike protein triggers vascular leak through a molecular signaling pathway that involves glycans, integrins, and transforming growth factor beta (TGF-beta). By blocking the activity of integrins, the team was able to reverse the vascular leak in mice.

“We identified a new pathogenic mechanism of SARS-CoV-2 in which the spike protein can break down the barriers lining our vasculature. The resulting increase in permeability can lead to vascular leak, as is commonly observed in severe COVID-19 cases, and we could recapitulate those disease manifestations in our mouse models,” says coauthor Felix Pahmeier, a graduate student in the Harris lab. “It was interesting to see the similarities and differences between spike and dengue virus protein NS1. Both are able to disrupt endothelial barriers, but the timelines and host pathways involved seem to differ between the two.”

Looking ahead

While blocking the activity of integrins may be a promising target for treating severe COVID-19, Harris says more work needs to be done to understand the exact role of this pathway in disease progression. While increased vascular permeability can accelerate infection and lead to internal bleeding, it can also help the body fight off the virus by giving immune machinery better access to infected cells.

“SARS-CoV-2 evolved to have a spike surface protein with increased capacity of interacting with host cell membrane factors, such as integrins, by acquiring an RGD motif. This motif is a common integrin-binding factor exploited by many pathogens, including bacteria and other viruses, to infect host cells,” says Francielle Tramontini Gomes de Sousa, former assistant project scientist in Harris’s lab and co-first author of the study.

“Our study shows how spike RGD interacts with integrins, resulting in TGF-beta release and activation of TGF-beta signaling. Using in vitro and in vivo models of epithelial, endothelial, and vascular permeability, we were able to improve understanding of the cellular mechanisms of increased levels of TGF-beta in COVID-19 patients and how spike-host cell interactions could contribute to disease.”

The team is continuing to study the molecular mechanisms that lead to vascular leak and is also investigating possible viral toxins in other viruses that cause severe disease in humans.

“COVID-19 is not gone. We have better vaccines now, but we don’t know how the virus is going to mutate in the future,” Biering says.

“Studying this process may be able to help us develop a new arsenal of drugs so that if someone is experiencing vascular leak, we can just target that. Maybe it doesn’t stop the virus from replicating, but it could stop that person from dying.”

The research appears in Nature Communications. Additional coauthors are from UC Berkeley; the Chan Zuckerberg Biohub; the University of California, San Francisco; the University of California, San Diego; Cornell University; and the University of North Carolina at Chapel Hill.

Support for the work came from the National Institute of Allergy and Infectious Diseases (NIAID); a Fast Grant from Emergent Ventures; the National Science Foundation; the National Heart, Lung, and Blood Institute; the National Institutes of Health; the Innovative Genomics Institute; and the Life Sciences Research Foundation.

Source: UC Berkeley