A blueprint for building the future: Eco-friendly 3D concrete printing

A research team led by engineers at the University of Virginia School of Engineering and Applied Science is the first to explore how an emerging plant-based material, cellulose nanofibrils, could amplify the benefits of 3D-printed concrete technology.

“The improvements we saw on both printability and mechanical measures suggest that incorporating cellulose nanofibrils in commercial printable materials could lead to more resilient and eco-friendly construction practices sooner rather than later,” said Osman E. Ozbulut, a professor in the Department of Civil and Environmental Engineering.

His team’s findings will be published in the September 2024 issue of Cement and Concrete Composites.

Buildings made of 3D-printed concrete are an exciting trend in housing, and they offer a slew of benefits: Quick, precise construction, possibly from recycled materials, reduced labor costs and less waste, all while enabling intricate designs that traditional builders would struggle to deliver.

The process uses a specialized printer that dispenses a cement-like mixture in layers to build the structure using computer-aided design software. But so far, printable material options are limited and questions about their sustainability and durability remain.

“We’re dealing with contradictory objectives,” Ozbulut said. “The mixture has to flow well for smooth fabrication, but harden into a stable material with critical properties, such as good mechanical strength, interlayer bonding and low thermal conductivity.”

Cellulose nanofibrils are made from wood pulp, creating a material that’s renewable and low impact. Like other plant-fiber derivatives, CNF, as the material is known in industry, shows strong potential as an additive to improve the rheology — the scientific term for flow properties — and mechanical strength of these composites.

However, until the UVA-led team’s meticulous study in Ozbulut’s Resilient and Advanced Infrastructure Lab, the influence of CNF on conventional 3D-printed composites wasn’t clear, Ozbulut said.

“Today, a lot of trial and error goes into designing mixtures,” he said. “We’re addressing the need for more good science to better understand the effects of different additives to improve the performance of 3D-printed structures.”

Experimenting with varying amounts of CNF additive, the team, led by Ozbulut and Ugur Kilic, now a Ph.D. alumnus of UVA, found that adding at least 0.3% CNF significantly improved flow performance. Microscopic analysis of the hardened samples revealed better material bonding and structural integrity.

In further testing in Ozbulut’s lab, CNF-enhanced 3D-printed components also stood up to pulling, bending and compression.

Share Button

Link between global warming and rising sea levels

A McGill-led study suggests that Earth’s natural forces could substantially reduce Antarctica’s impact on rising sea levels, but only if carbon emissions are swiftly reduced in the coming decades. By the same token, if emissions continue on the current trajectory, Antarctic ice loss could lead to more future sea level rise than previously thought.

The finding is significant because the Antarctic Ice Sheet is the largest ice mass on Earth, and the biggest uncertainty in predicting future sea levels is how this ice will respond to climate change.

“With nearly 700 million people living in coastal areas and the potential cost of sea-level rise reaching trillions of dollars by the end of the century, understanding the domino effect of Antarctic ice melt is crucial,” said lead author Natalya Gomez, an Associate Professor in McGill’s Department of Earth and Planetary Sciences and Canada Research Chair in Ice sheet — Sea level interactions.

The study focuses on how the ice sheet interacts with the earth beneath, and how that dynamic is influenced by carbon-emission levels. This relationship has not been thoroughly explored in previous studies, the researchers said.

“Our findings show that while some sea level rise is inevitable, swift and substantive action to lower emissions could prevent some of the most destructive impacts of climate change, particularly for coastal communities,” Gomez said.

Rising seas and nature’s double-edged sword

As ice melts, its weight decreases, causing the land beneath it to rise like an expanding sponge. The researchers say this process, called post-glacial uplift, can be a double-edged sword.

If emissions drop quickly, limiting global warming, post-glacial uplift can act as a natural brake on ice-mass loss. It lifts the ice up, slowing the flow of ice from land to ocean. The study found this dynamic can reduce Antarctica’s contribution to sea- level rise by up to 40 per cent.

However, if carbon outputs keep pace and the planet heats up quickly, the rebounding land will not be enough to slow the rapidly melting ice, and instead pushes more ocean water away from Antarctica, accelerating sea-level rise along populated coastlines.

To reach their findings, Gomez and collaborating scholars from Canada and the United States developed a 3-D model of Earth’s interior. Their model used geophysical field measurements from the U.S. ANET-POLENET project, which had pioneered large-scale deployments of sensitive instruments to record the bedrock uplift and seismic signals across large expanses of Antarctica. These extensive field measurements were essential for characterizing the three-dimensional variations of the Antarctic mantle incorporated in the study.

“Our 3-D model peels back Earth’s layers like an onion, revealing dramatic variations in thickness and consistency of the mantle below. This knowledge helps us better predict how different areas will respond to melting,” said co-author Maryam Yousefi, a geodesist at Natural Resources Canada and previously a Postdoctoral Fellow at McGill and Penn State universities.

It’s the first model to capture the relationship between Antarctica’s ice and underlying earth in such detail, she added.

Notes Rob DeConto, a co-author and glaciologist at the University of Massachusetts, “This study marks a breakthrough in our ability to better predict the impacts of climate change on rising seas and to inform effective environmental policy.”

Global impacts

The findings, published in Science Advances, highlight the inequalities of climate change, the scholars noted. Island nations, which contribute the least to global emissions, are likely to bear the brunt of their consequences, they said.

The study is a collaboration between researchers at McGill, Pennsylvania State, Cambridge, Columbia, Colorado State, Ohio State, the University of Massachusetts Amherst, the University of Washington and the Union of Concerned Scientists. It was funded by the Canadian Natural Sciences and Engineering Research Council, the U.S. National Science Foundation and the Canada Research Chairs program.

Share Button

Improving cat food flavors with the help of feline taste-testers

Cats are notoriously picky eaters. But what if we could design their foods around flavors that they’re scientifically proven to enjoy? Researchers publishing in ACS’ Journal of Agricultural and Food Chemistry used a panel of feline taste-testers to identify favored flavor compounds in a series of chicken-liver-based sprays. The cats particularly enjoyed the sprays that contained more free amino acids, which gave their kibble more savory and fatty flavors.

Cats have a more acute sense of smell than humans, and the aroma of their food plays a big role in whether they’ll eat or snub what their owner serves for dinner. Feline palates are also more sensitive to umami (savory) flavors than humans, and they can’t taste sweetness. While meat-flavored food attractant sprays can help improve the scent and tastiness of dry kibble, the exact correlation between volatile flavor compounds and palatability is not well understood. Additionally, previous studies in this area lack input from a very important focus group: actual cats! So, Shiqing Song and colleagues relied on the expertise of a panel of 10 hungry adult cats to evaluate a series of food sprays containing different volatile flavor compounds.

To prepare their fragrant sprays, the researchers homogenized and heat-treated chicken livers. Then, they broke down proteins in the liver paste to various degrees using enzymes to produce four different food attractants. Song’s team identified over 50 different flavor compounds across the sprays, ranging from tropical and floral to sweaty and rubbery. For the taste test, the researchers coated commercially available cat food with chicken fat and then sprayed it with one of the four chicken liver attractants. The samples were presented to the cats alongside a control food treated with a different, commercially available attractant. The team observed which bowl the cats chose first and how much food they ate throughout the day.

The researchers found that most cats preferred and ate more of the foods sprayed with their attractants, particularly the sprays with proteins that were further broken-down by the enzymes and contained more free amino acids. These compounds are important flavor precursors that can undergo the Maillard reaction, which likely produced many different aroma-enhancing compounds during the heat treatment step. The favored foods contained more mushroom and fatty flavors as well, while the less-enjoyed foods featured acidic- and sweet-tasting compounds, possibly because fewer Maillard reactions occurred. This work could help inform future cat food formulations and increase your chances of choosing a kibble your finicky feline might enjoy.

The authors acknowledge funding from the Natural Science Foundation of Shanghai and thank their feline volunteers for their participation.

Share Button

Discovery of a new population of macrophages promoting lung repair after viral infections

Researchers at the University of Liège (Belgium) have discovered a new population of macrophages, important innate immune cells that populate the lungs after injury caused by respiratory viruses. These macrophages are instrumental in repairing the pulmonary alveoli. This groundbreaking discovery promises to revolutionize our understanding of the post-infectious immune response and opens the door to new regenerative therapies.

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.

Share Button

Scientists pin down the origins of the moon’s tenuous atmosphere

While the moon lacks any breathable air, it does host a barely-there atmosphere. Since the 1980s, astronomers have observed a very thin layer of atoms bouncing over the moon’s surface. This delicate atmosphere — technically known as an “exosphere” — is likely a product of some kind of space weathering. But exactly what those processes might be has been difficult to pin down with any certainty.

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.

Share Button

New compound effective against flesh-eating bacteria

Researchers at Washington University School of Medicine in St. Louis have developed a novel compound that effectively clears bacterial infections in mice, including those that can result in rare but potentially fatal “flesh-eating” illnesses. The compound could be the first of an entirely new class of antibiotics, and a gift to clinicians seeking more effective treatments against bacteria that can’t be tamed easily with current antibiotics.

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.”

Share Button

The junior doctors’ strikes may be over. But is trouble ahead?

The end of the pay dispute sounded too good to be true. And now some are wondering if it might be.

Share Button

Trying to limit calories? Skip the dip, researchers advise

Snacks provide, on average, about one-fourth of most people’s daily calories. With nearly one in three adults in the United States overweight and more than two in five with obesity, according to the National Institutes of Health, researchers in the Penn State Sensory Evaluation Center are investigating how Americans can snack smarter.

The latest study conducted in the center, housed in the College of Agricultural Sciences, investigated how eating behavior changes when consumers are served a dip with a salty snack. The findings, available online now and to be published in the November issue of Food Quality and Preference, suggest that they eat more — a lot more. The chips and dip together yielded a 77% greater caloric intake, and a faster total eating rate compared to the just chips, no-dip control.

However, there was no difference in chip intake, pointed out study corresponding author John Hayes, professor of food science and director of the Penn State Sensory Evaluation Center.

“The most striking findings of our study is that people didn’t eat fewer chips when dip was available — they ate the same amount of chips, plus the dip,” he said. “This lack of compensation means that adding dip to chips can substantially increase overall energy intake without people realizing it.”

Intuitively, many people would guess that if we add something extra to a snack, like dip, people will compensate, and eat less of the main item, Hayes explained.

“But our research shows this is not the case with chips and dip,” he said. “Our participants consumed the same amount of chips regardless of whether dip was present, leading to much greater energy intake when dip was available.”

The study, which was led by research assistant Madeline Harper, who recently graduated from Penn State with a master’s degree in food science, assessed 46 adult participants. In two visits to the Sensory Evaluation Center, they were served 70 grams of ranch-flavored chips, or about 2.5 servings, with or without about a third of a cup of ranch dip. Participants ate as much as they wanted.

Their intake was measured, and all eating sessions were video recorded and annotated for number of bites and active eating time. Researchers used that information to calculate measures of “eating microstructure,” including eating rate and bite size.

Harper suggested that the greater intake of the chips and dip snack was facilitated by a larger bite size resulting from dip inclusion. On average per eating session, participants consumed 345 calories of chips and dip compared to 195 calories of chips alone.

The study was novel, Harper noted, because little research has been conducted on the effect of external sources of oral lubrication like dips on oral processing of salty snacks.

“Clearly, it has an influence on food intake, especially while snacking,” she said. “However, in this chips-and-dip snack, the greater intake resulting from dip inclusion may have been facilitated by a larger total snack bite size, as opposed to faster chip eating rate.”

Even though snacking is a major source of energy in the typical American diet, it remains understudied, Hayes said, adding that understanding eating behavior around snacking is crucial to address issues of overeating and obesity.

“This research opens up new avenues for exploring how the physical properties of foods can influence our eating behaviors and ultimately, our energy intake,” he said. “If we can slow people down, we can influence energy consumption without giving up the pleasure from food.”

Paige Cunningham, postdoctoral scholar in the Department of Food Science and the Department of Nutritional Sciences at Penn State, contributed to the research.

The U.S. Department of Agriculture’s National Institute of Food and Agriculture supported this research.

Share Button

Drug developed for pancreatic cancer shows promise against most aggressive form of medulloblastoma

A drug that was developed to treat pancreatic cancer has now been shown to increase symptom-free survival in preclinical medulloblastoma models — all without showing signs of toxicity.

Medulloblastoma is the most common malignant brain tumor in children. Survival rates vary according to which one of the four subtypes a patient has, but the worst survival rates, historically at about 40%, are for Group 3, which this research focused on.

Jezabel Rodriguez Blanco, Ph.D., an assistant professor who holds dual appointments at MUSC Hollings Cancer Center and the Darby Children’s Research Institute at MUSC, led the research, published in the Journal of Clinical Investigation.

Her research focused on the drug triptolide, which is extracted from a vine used in traditional Chinese medicine, and its water-soluble prodrug version, Minnelide. A prodrug is an inactive medication that the body converts into an active drug through enzymatic or chemical reactions.

MYC is an oncogene, or gene that has the potential to cause cancer. MYC is dysregulated, or out of control, in about 70% of human cancers, and it shows up in much higher levels in Group 3 medulloblastoma than in the other medulloblastoma subgroups. Despite its well-known role in cancer, this oncogene historically has been considered impossible to target with drugs.

Despite its poor druggability, previous research in other cancers had shown that triptolide and its derivatives had the ability to target MYC. When Blanco was still a postdoctoral fellow at the University of Miami, her mentor, David Robbins, Ph.D., attended a presentation by the research team that showed that the more copies of MYC that a tumor has, the better that triptolide works.

“He came to me, and he told me, ‘You know, as Group 3 medulloblastoma has many MYC copies, you should get some research models and try the drug,” Blanco recalled. She started the project from scratch. “I started talking to people, getting cell lines and animal models, learning how to propagate them, getting the drug, using it.”

Blanco received a three-month grant intended for cancer center trainees to develop ideas. Then her lab at the time was awarded a one-year grant from the Southeastern Brain Tumor Foundation in 2018. Since then, she’s received no additional funding specific to this project. Even as she started her faculty position at MUSC and began to focus most of her research on the Sonic Hedgehog subgroup of medulloblastoma, she continued to work on the Group 3 research as a side project. She knew how well triptolide was working in these hard-to-treat tumors, and she did not want her initial results to fall through the cracks.

Determining the mechanism of action has been the most challenging part of the project, she noted, due to the drug’s multiple effects, and there could still be additional mechanisms beyond those that Blanco identified.

“It was affecting MYC gene expression by affecting the RNA pol II activity, and then it was affecting how long the protein lasts. So, the fact that it’s working through two different mechanisms on this oncogene may explain why it’s so effective in tumors that have extra copies of MYC,” she said, explaining that RNA polymerase II is a protein that helps to make copies of DNA instructions, which are used to produce proteins in the cell.

Despite the challenges of narrowing down the mechanism of action specific to the cancer, it was quite clear that however it worked, it did work, she said.

The efficacy was 100 times higher in the Group 3 tumors with extra MYC copies than in the Sonic Hedgehog tumors with normal levels of MYC, she said. She found that Minnelide reduced tumor growth and the spread of cancer cells to the thin tissues that cover the brain and spinal cord, called leptomeninges. It also increased the efficacy of the chemotherapy drug cyclophosphamide, which is currently used in treatment.

Blanco decided to move forward with publication rather than waiting to write a manuscript that answered all possible questions. Knowing that most parents whose children receive a Group 3 medulloblastoma diagnosis will lose their child in less than two years was the incentive she needed to push this work out.

“There was a point at which I could not hold these data anymore because it was working so well that it needed to go out,” she said. “The preclinical models were showing such a nice efficacy that it was like, ‘OK, I cannot keep on holding this work, digging deeper into the mechanism of action because the kids that have Group 3 medulloblastoma are dying while we are doing those experiments.”

Minnelide has been tested or is currently in testing in phase I and phase II clinical trials of adults with different types of cancer, including pancreatic cancer, where it showed some efficacy.

Blanco is hopeful that, with this new research on Group 3 medulloblastoma, a clinical trial for children with this disease can be launched.

Share Button

Retreat of tropical glaciers foreshadows changing climate’s effect on the global ice

As they are in many places around the globe, glaciers perched high in the Andes Mountains are shrinking. Now, researchers at the University of Wisconsin-Madison and their collaborators have uncovered evidence that the high-altitude tropical ice fields are likely smaller than they’ve been at any time since the last ice age ended 11,700 years ago.

That would make the tropical Andes the first region in the world known to pass that threshold as a result of the steadily warming global climate. It also makes them possible harbingers of what’s to come for glaciers globally.

“We think these are the canary in the coal mine. The tropics would probably be the first place you’d expect ice to disappear, and that’s what we’re seeing,” says Shaun Marcott, a professor of geoscience at UW-Madison. Marcott guided the research with colleagues at Boston College and Tulane University. Andrew Gorin, a former Boston College graduate student who is now at University of California, Berkeley, led the study, which appears in the Aug. 2, 2024, issue of the journal Science.

Glaciers grow slowly over time in regions where summer weather isn’t warm enough to melt all of the previous winter’s snowfall. Over time, unmelted snow collects and gets compacted and begins to move under its own weight, resulting in the year-round ice that defines a glacier.

Satellite imagery and on-the-ground observations have provided conclusive evidence for decades that high-altitude glaciers in the Andes are steadily shrinking as warmer temperatures cause them to melt more quickly than falling snow can replenish them.

What has remained unclear, though, is whether the glaciers’ dwindling footprints are anomalously small compared to the rest of the period that began at the end of the last ice age, known as the Holocene. Meanwhile, glaciers in other parts of the world were smaller at some points in the early Holocene, when the global climate was warmer and drier than recent millennia.

“We knew that glaciers ebbed and flowed in the past, so we wanted to learn how the behavior of glaciers today — melting due to human-caused climate change — stacks up against their long-term fluctuations,” says Andy Jones, a UW-Madison doctoral student and study co-author.

To answer this question, the team of scientists analyzed the geochemistry of bedrock from areas near the edges of four glaciers in the high tropical Andes, choosing sites that satellite imagery showed were exposed by melting ice in only the last two or three decades.

The team specifically looked for evidence of two unique isotopes — basically chemical flavors — of a pair of elements with the bedrock’s quartz crystals: beryllium-10 and carbon-14. These isotopes are only present in rock that has spent time at or near the Earth’s surface as they result from interactions between the rock and cosmic rays, which are high-energy particles that constantly rain down on the planet from outer space.

Bedrock accumulates beryllium-10 and carbon-14 once it’s exposed to the surface, so measuring the isotopes’ concentrations in rock crystals near glaciers can be useful for understanding the previous extent of ice coverage. The team found “remarkably low” concentrations of both isotopes in nearly all samples, suggesting that melting ice has exposed bedrock near the glaciers for the first time only recently in most of the sampled locations.

Additional analyses — and the fact that the extremely low concentrations were consistent across sample sites — made the researchers confident that melting ice, rather than erosion, exposed the bedrock.

“It’s highly unlikely this is from erosion,” says Marcott. “Because the multiple locations we went to all show the same thing.”

This consistency points to a single likely conclusion, according to Marcott: The world’s tropical glaciers, more than 99% of which are located in the Andes, are the first to shrink beyond what’s been seen in the recent geologic past.

“Glaciers are very sensitive to the climate system that they live in,” says Marcott. “They really are the place you would look to see some of the first big changes resulting from a warming climate. You can look to these glaciers and imagine what we might be looking at going into the future in other places like the Western United States, which is a no-ice scenario.”

This research was supported by the National Science Foundation (EAR-1805620; EAR-1805133; EAR-1805892).

Share Button