Respiratory viruses, typically causing mild illness, can have more serious consequences, as shown during the Covid-19 pandemic, including severe cases requiring hospitalization and the chronic sequelae of “long Covid.” These conditions often result in the destruction of large areas of the lungs, particularly the alveoli responsible for gas exchanges. Ineffective repair of these structures can lead to ARDS or a permanent reduction in the lungs’ ability to oxygenate blood, causing chronic fatigue and exercise intolerance.

While the role of macrophages during the acute phase of respiratory viral infections is well known, their function in the post-inflammatory period has been largely unexplored. A study by the GIGA Institute at the University of Liège reveals that atypical macrophages, characterized by specific markers and transiently recruited during the early recovery phase, play a beneficial role in regenerating pulmonary alveoli.

Led by Dr. Coraline Radermecker and Prof. Thomas Marichal from the Immunophysiology Laboratory, the study was conducted by Dr. Cecilia Ruscitti and benefited from the ULiège’s advanced technological platforms, including flow cytometry, fluorescence microscopy, and single-cell RNA sequencing. “Our findings provide a novel and crucial mechanism for alveolar repair by these atypical macrophages,” explains Coraline Radermecker. “We have detailed their characteristics, origin, location in the damaged lung, the signals they require to function, and their role in tissue regeneration, specifically acting on type 2 alveolar epithelial cells, the progenitors of alveolar cells.” The scientific community had overlooked these macrophages because they express a marker previously thought to be specific for another immune cell population, the neutrophils, and because they appear only briefly during the repair phase before disappearing.

“Our study highlights the reparative role of these macrophages, countering the prevailing idea that macrophages following respiratory viral infections are pathogenic,” adds Thomas Marichal. “By targeting the amplification of these macrophages or stimulating their repair functions, we could develop therapies to improve alveolar regeneration and reduce complications from serious respiratory infections and ARDS.”

To illustrate, consider the lungs as a garden damaged by a storm (viral infection). These newly discovered macrophages act like specialized gardeners who clear debris and plant new seeds, enabling the garden to regrow and regain its vitality.

This scientific breakthrough underscores the importance of research at the University of Liège and opens new avenues for treating respiratory diseases.

Now, scientists at MIT and the University of Chicago say they have identified the main process that formed the moon’s atmosphere and continues to sustain it today. In a study appearing in Science Advances, the team reports that the lunar atmosphere is primarily a product of “impact vaporization.”

In their study, the researchers analyzed samples of lunar soil collected by astronauts during NASA’s Apollo missions. Their analysis suggests that over the moon’s 4.5-billion-year history its surface has been continuously bombarded, first by massive meteorites, then more recently, by smaller, dust-sized “micrometeoroids.” These constant impacts have kicked up the lunar soil, vaporizing certain atoms on contact and lofting the particles into the air. Some atoms are ejected into space, while others remain suspended over the moon, forming a tenuous atmosphere that is constantly replenished as meteorites continue to pelt the surface.

The researchers found that impact vaporization is the main process by which the moon has generated and sustained its extremely thin atmosphere over billions of years.

“We give a definitive answer that meteorite impact vaporization is the dominant process that creates the lunar atmosphere,” says the study’s lead author, Nicole Nie, an assistant professor in MIT’s Department of Earth, Atmospheric, and Planetary Sciences. “The moon is close to 4.5 billion years old, and through that time the surface has been continuously bombarded by meteorites. We show that eventually, a thin atmosphere reaches a steady state because it’s being continuously replenished by small impacts all over the moon.”

Nie’s co-authors are Nicolas Dauphas, Zhe Zhang, and Timo Hopp at the University of Chicago, and Menelaos Sarantos at NASA Goddard Space Flight Center.

Weathering’s roles

In 2013, NASA sent an orbiter around the moon to do some detailed atmospheric reconnaissance. The Lunar Atmosphere and Dust Environment Explorer (LADEE, pronounced “laddie”) was tasked with remotely gathering information about the moon’s thin atmosphere, surface conditions, and any environmental influences on the lunar dust.

LADEE’s mission was designed to determine the origins of the moon’s atmosphere. Scientists hoped that the probe’s remote measurements of soil and atmospheric composition might correlate with certain space weathering processes that could then explain how the moon’s atmosphere came to be.

Researchers suspect that two space weathering processes play a role in shaping the lunar atmosphere: impact vaporization and “ion sputtering” — a phenomenon involving solar wind, which carries energetic charged particles from the sun through space. When these particles hit the moon’s surface, they can transfer their energy to the atoms in the soil and send those atoms sputtering and flying into the air.

“Based on LADEE’s data, it seemed both processes are playing a role,” Nie says. “For instance, it showed that during meteorite showers, you see more atoms in the atmosphere, meaning impacts have an effect. But it also showed that when the moon is shielded from the sun, such as during an eclipse, there are also changes in the atmosphere’s atoms, meaning the sun also has an impact. So, the results were not clear or quantitative.”

Answers in the soil

To more precisely pin down the lunar atmosphere’s origins, Nie looked to samples of lunar soil collected by astronauts throughout NASA’s Apollo missions. She and her colleagues at the University of Chicago acquired 10 samples of lunar soil, each measuring about 100 milligrams — a tiny amount that she estimates would fit into a single raindrop.

Nie sought to first isolate two elements from each sample: potassium and rubidium. Both elements are “volatile,” meaning that they are easily vaporized by impacts and ion sputtering. Each element exists in the form of several isotopes. An isotope is a variation of the same element, that consists of the same number of protons but a slightly different number of neutrons. For instance, potassium can exist as one of three isotopes, each one having one more neutron, and there being slightly heavier than the last. Similarly, there are two isotopes of rubidium.

The team reasoned that if the moon’s atmosphere consists of atoms that have been vaporized and suspended in the air, lighter isotopes of those atoms should be more easily lofted, while heavier isotopes would be more likely to settle back in the soil. Furthermore, scientists predict that impact vaporization, and ion sputtering, should result in very different isotopic proportions in the soil. The specific ratio of light to heavy isotopes that remain in the soil, for both potassium and rubidium, should then reveal the main process contributing to the lunar atmosphere’s origins.

With all that in mind, Nie analyzed the Apollo samples by first crushing the soils into a fine powder, then dissolving the powders in acids to purify and isolate solutions containing potassium and rubidium. She then passed these solutions through a mass spectrometer to measure the various isotopes of both potassium and rubidium in each sample.

In the end, the team found that the soils contained mostly heavy isotopes of both potassium and rubidium. The researchers were able to quantify the ratio of heavy to light isotopes of both potassium and rubidium, and by comparing both elements, they found that impact vaporization was most likely the dominant process by which atoms are vaporized and lofted to form the moon’s atmosphere.

“With impact vaporization, most of the atoms would stay in the lunar atmosphere, whereas with ion sputtering, a lot of atoms would be ejected into space,” Nie says. “From our study, we now can quantify the role of both processes, to say that the relative contribution of impact vaporization versus ion sputtering is about 70:30 or larger.” In other words, 70 percent or more of the moon’s atmosphere is a product of meteorite impacts, whereas the remaining 30 percent is a consequence of the solar wind.

“The discovery of such a subtle effect is remarkable, thanks to the innovative idea of combining potassium and rubidium isotope measurements along with careful, quantitative modeling,” says Justin Hu, a postdoc who studies lunar soils at Cambridge University, who was not involved in the study. “This discovery goes beyond understanding the moon’s history, as such processes could occur and might be more significant on other moons and asteroids, which are the focus of many planned return missions.”

“Without these Apollo samples, we would not be able to get precise data and measure quantitatively to understand things in more detail,” Nie says. “It’s important for us to bring samples back from the moon and other planetary bodies, so we can draw clearer pictures of the solar system’s formation and evolution.”

This work was supported, in part, by NASA and the National Science Foundation.

The research is published Aug. 2 in Science Advances.

The compound targets gram-positive bacteria, which can cause drug-resistant staph infections, toxic shock syndrome and other illnesses that can turn deadly. It was developed through a collaboration between the labs of Scott Hultgren, PhD, the Helen L. Stoever Professor of Molecular Microbiology, and Michael Caparon, PhD, a professor of molecular microbiology, and Fredrik Almqvist, a professor of chemistry at the University of Umeå in Sweden.

A new type of antimicrobial would be good news for clinicians seeking effective treatments against pathogens that are becoming more resistant to currently available drugs, and thus much more dangerous.

“All of the gram-positive bacteria that we’ve tested have been susceptible to that compound. That includes enterococci, staphylococci, streptococci, C. difficile, which are the major pathogenic bacteria types,” said Caparon, the co-senior author. “The compounds have broad-spectrum activity against numerous bacteria.”

It’s based on a type of molecule called ring-fused 2-pyridone. Initially, Caparon and Hultgren had asked Almqvist to develop a compound that might prevent bacterial films from attaching to the surface of urethral catheters, a common cause of hospital-associated urinary tract infections. Discovering that the resulting compound had infection-fighting properties against multiple types of bacteria was a happy accident.

The team named their new family of compounds GmPcides (for gram-positive-icide). In past work, the authors showed that GmPcides can wipe out bacteria strains in petri dish experiments. In this latest study, they decided to test it on necrotizing soft-tissue infections, which are fast-spreading infections usually involving multiple types of gram-positive bacteria, for which Caparon already had a working mouse model. The best known of these, necrotizing fasciitis or “flesh-eating disease,” can quickly damage tissue severely enough to require limb amputation to control its spread. About 20% of patients with flesh-eating disease die.

This study focused on one pathogen, Streptococcus pyogenes, which is responsible for 500,000 deaths every year globally, including flesh-eating disease. Mice infected with S. pyogenes and treated with a GmPcide fared better than did untreated animals in almost every metric. They had less weight loss, the ulcers characteristic of the infection were smaller, and they fought off the infection faster.

The compound appeared to reduce the virulence of the bacteria and, remarkably, speed up post-infection healing of the damaged areas of the skin.

It is not clear how GmPcides accomplish all of this, but microscopic examination revealed that the treatment appears to have a significant effect on bacterial cell membranes, which are the outer wrapping of the microbes.

“One of the jobs of a membrane is to exclude material from the outside,” Caparon said. “We know that within five to ten minutes of treatment with GmPcide, the membranes start to become permeable and allow things that normally should be excluded to enter into the bacteria, which suggests that those membranes have been damaged.”

This can disrupt the bacteria’s own functions, including those that cause damage to their host, and make the bacteria less effective at combating the host’s immune response to infections.

In addition to their antibacterial effectiveness, GmPcides appear to be less likely to lead to drug-resistant strains. Experiments designed to create resistant bacteria found very few cells able to withstand treatment and thus pass on their advantages to the next generation of bacteria.

Caparon explained that there is a long way to go before GmPcides are likely to find their way into local pharmacies. Caparon, Hultgren and Almqvist have patented the compound used in the study and licensed it to a company, QureTech Bio, in which they have an ownership stake, with the expectation that they will be able to collaborate with a company that has the capacity to manage the pharmaceutical development and clinical trials to potentially bring GmPcides to market.

Hultgren said that the kind of collaborative science that created GmPcides is what is needed to treat intractable problems like antimicrobial resistance.

“Bacterial infections of every type are an important health problem, and they are increasingly becoming multi-drug resistant and thus harder to treat,” he said. “Interdisciplinary science facilitates the integration of different fields of study that can lead to synergistic new ideas that have the potential to help patients.”