The researchers, whose results were published Feb. 8 in Science, discovered that during the transition from lung adenocarcinoma to small cell lung cancer (SCLC), the mutated cells appeared to undergo a change in cell identity through an intermediate, stem cell-like state, which facilitated the transformation.

“It is very difficult to study this process in human patients. So my aim was to uncover the mechanism underlying the transformation of lung adenocarcinoma to small cell lung cancer in a mouse model,” said study lead Dr. Eric Gardner, a postdoctoral fellow in the laboratory of Dr. Harold Varmus, the Lewis Thomas University Professor of Medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. The complex mouse model took several years to develop and characterize but has allowed the researchers to crack this difficult problem.

This study was in collaboration with Dr. Ashley Laughney, assistant professor of physiology and biophysics and a member of the Meyer Cancer Center at Weill Cornell Medicine and Ethan Earlie, a graduate student in the Laughney lab and part of the Tri-Institutional Computational Biology and Medicine program.

“It is well known that cancer cells continue to evolve, especially to escape the pressure of effective treatments,” said Dr. Varmus. “This study shows how new technologies — including the detection of molecular features of single cancer cells, combined with computer-based analysis of the data — can portray dramatic, complex events in the evolution of lethal cancers, exposing new targets for therapeutic attack.”

Catching Transformation in the Act

SCLC most commonly occurs in heavy smokers, but this type of tumor also develops in a significant number of patients with lung adenocarcinomas, particularly after treatment with therapies that target a protein called Epidermal Growth Factor Receptor (EGFR), which promotes tumor growth. The new SCLC-type tumors are resistant to anti-EGFR therapy because their growth is fueled by a new cancer driver, high levels of Myc protein.

To unravel the interplay of these cancer pathways, the researchers engineered mice to develop a common form of lung adenocarcinoma, in which lung epithelial cells are driven by a mutated version of the EGFR gene. They then turned the adenocarcinoma tumors into SCLC-type tumors, which generally arise from neuroendocrine cells. They did this by shutting off EGFR in the presence of several other changes including losses of the tumor suppressor genes Rb1 and Trp53 as well as turning up the production of Myc,a known driver of SCLC.

Oncogenes, such as EGFR and Myc, are mutated forms of genes that normally control cell growth. They are known for their roles in driving the growth and spread of cancer. Tumor suppressor genes, on the other hand, normally inhibit cell proliferation and tumor development.

Context Matters

Surprisingly, this study showed that oncogenes act in a context-dependent manner. While most lung cells are resistant to becoming cancerous by Myc, neuroendocrine cells, are very sensitive to the oncogenic effects of Myc. Conversely, epithelial cells, which line the air sacs of the lungs and are the precursors to lung adenocarcinomas, grow excessively in response to mutated EGFR.

“This shows that an ‘oncogene’ in the wrong cell type doesn’t act like an oncogene anymore,” Dr. Laughney said. “So, it fundamentally changes how we think about oncogenes.”

The researchers also discovered a stem cell-like intermediate that was neither adenocarcinoma nor SCLC. Cells in this transitional state became neuroendocrine in nature only when mutations in the tumor suppressor genes RB1 and TP53 were present. They observed that loss of another tumor suppressor called Pten accelerated this process. At that stage, oncogenic Myc could drive these intermediate stem-like cells to form SCLC-type tumors.

This study further supports efforts seeking therapeutics that target Myc proteins, which are implicated in many types of cancers. The researchers now plan to use their new mouse model to further explore the adenocarcinoma-SCLC transition, detailing, for example, how the immune system normally responds to this transition.

A new study published in Science suggests that closing the knowledge gap between what treatments health care providers think patients want and what treatments patients really want could help save half a million lives a year and reduce unnecessary use of antibiotics.

“Even when children seek care from a health care provider for their diarrhea, as most do, they often do not receive ORS, which costs only a few cents and has been recommended by the World Health Organization for decades,” said Neeraj Sood, senior author of the study, senior fellow at the USC Schaeffer Center for Health Policy & Economics and a professor at the USC Price School of Public Policy.

“This issue has puzzled experts for decades, and we wanted to get to the bottom of it,” said Sood, who also holds joint appointments at the Keck School of Medicine of USC and the USC Marshall School of Business.

A closer look at childhood illness in India

There are several popular explanations for the underprescription of ORS in India, which accounts for the most cases of child diarrhea of any country in the world:

• Physicians assume their patients do not want oral rehydration salts, which come in a small packet and dissolve in water, because they taste bad or they aren’t “real” medicine like antibiotics.
• The salts are out of stock because they aren’t as profitable as other treatments.
• Physicians make more money prescribing antibiotics, even though they are ineffective against viral diarrhea.

To test these three hypotheses, Sood and his colleagues enrolled over 2,000 health care providers across 253 medium-size towns in the Indian states of Karnataka and Bihar. The researchers selected states with vastly different socioeconomic demographics and varied access to health care to ensure the results were representative of a broad population. Bihar is one of the poorest states in India with below-average ORS use, while Karnataka has above-average per capita income and above-average ORS use.

The researchers then hired staff who were trained to act as patients or caretakers. These “standardized patients” were given scripts to use in unannounced visits to doctors’ offices where they would present a case of viral diarrhea — for which antibiotics are not appropriate — in their 2-year-old child. (For ethical considerations, children did not attend these visits.) The standardized patients made approximately 2,000 visits in total.

Providers were randomly assigned to patient visits where patients expressed a preference for ORS, a preference for antibiotics or no treatment preference. During the visits, patients indicated their preference by showing the health care provider a photo of an ORS packet or antibiotics. The set of patients with no treatment preference simply asked the physician for a recommendation.

To control for profit-motivated prescribing, some of the standardized patients assigned as having no treatment preference informed the provider that they would purchase medicine elsewhere. Additionally, to estimate the effect of stockouts, the researchers randomly assigned all providers in half of the 253 towns to receive a six-week supply of ORS.

Provider misperceptions matter most when it comes to ORS underprescribing

Researchers found that provider perceptions of patient preferences are the biggest barrier to ORS prescribing — not because caretakers do not want ORS, but rather because providers assume most patients do not want the treatment. Health care providers’ perception that patients do not want ORS accounted for roughly 42% of underprescribing, while stockouts and financial incentives explained only 6% and 5%, respectively.

Patients expressing a preference for ORS increased prescribing of the treatment by 27 percentage points — a more effective intervention than eliminating stockouts (which increased ORS prescribing by 7 percentage points) or removing financial incentives (which only increased ORS prescribing at pharmacies).

“Despite decades of widespread knowledge that ORS is a lifesaving intervention that can save lives of children suffering from diarrhea, the rates of ORS use remain stubbornly low in many countries such as India,” said Manoj Mohanan, co-author of the study and professor of public policy, economics, and global health at the Sanford School of Public Policy at Duke University. “Changing provider behavior about ORS prescription remains a huge challenge.”

Study authors said these results can be used to design interventions that encourage patients and caretakers to express an ORS preference when seeking care, as well as efforts to raise awareness among providers about patients’ preferences.

“We need to find ways to change providers’ perceptions of patient preferences to increase ORS use and combat antibiotic resistance, which is a huge problem globally,” said Zachary Wagner, the study’s corresponding author, an economist at RAND Corporation and professor of policy analysis at Pardee RAND Graduate School. “How to reduce overprescribing of antibiotics and address antimicrobial resistance is a major global health question, and our study shows that changing provider perceptions of patient preferences is one way to work toward a solution.”

This research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (Grant 5R01DK126049).

The findings from a large survey study, co-authored by Kyle Hull, Kevin Smith and Clarisse Warren, demonstrate the willingness of people to bend their morals — even behave unethically — when engaging in the political realm.

Results also suggest that hostility toward outgroups (i.e., opposing party) is the driving factor for the moral ambiguity exercised when respondents switch from the personal to the political arena.

And there is not just one guilty party.

“People, regardless of age or ideology, were more willing to engage in immoral behaviors and judgments if the behaviors were in the political realm,” said Hull, a visiting assistant professor in political science. “And a lot of it was just driven by genuine internal dislike of the ‘other’ side.”

The researchers developed a survey and engaged four different samples of adults, totaling 2,472 respondents. The survey included nonpolitical and political moral behavior scales and political and nonpolitical moral tolerance scales.

“Basically, we were taking the same person and asking them virtually the same questions,” said Smith, Leland J. and Dorothy H. Olson Professor of Political Science. “The only difference in the items is we changed ‘person’ to ‘politician.’ And that was enough to shift people’s moral judgment. It changes in a way that induces more flexibility in our moral assessments.”

That includes assessments of politicians’ bad behavior, as the co-authors found people are more morally tolerant of politicians they liked, similar to the behavior they were willing to tolerate from a friend.

In an increasingly polarized — and often toxic — political environment, the researchers said the results highlight the harm of outrage politics.

“I think there’s some reason for concern,” Hull said. “As long as there is some internalized dislike of the outgroup, there’s certainly a risk of behaviors that may be involved when people are willing to act less morally. Politics makes us do things that we just normally wouldn’t do and tolerate things we wouldn’t normally tolerate. It brings out, sometimes, the worst in us.

“The way some politicians and media speak about the other party fuels that fire in a way. The more we engage in pitting one party or the other as the bad guys, and the more you feel that way, the more you are willing to set your morals aside.”

The research builds on Smith’s work exploring how political engagement and ideology drive moral values and choices, not the other way around.

“If that’s true, then people will probably be using different standards for moral behavior or moral choices in their personal lives than they are in the political world,” Smith said. “And that’s what we found. It’s not like politics makes bastards of the left or the right, or the young or the old, or the rich or the poor. Politics seems to make bastards of us all.”

By feeding worms with plastics and cultivating microbes found in their guts, researchers from NTU’s School of Civil and Environmental Engineering (CEE) and Singapore Centre for Environmental Life Sciences Engineering (SCELSE) have demonstrated a new method to accelerate plastic biodegradation.

Previous studies have shown that Zophobas atratus worms — the larvae of the darkling beetle commonly sold as pet food and known as ‘superworms’ for their nutritional value — can survive on a diet of plastic because its gut contains bacteria capable of breaking down common types of plastic. However, their use in plastics processing has been impractical due to the slow rate of feeding and worm maintenance.

NTU scientists have now demonstrated a way to overcome these challenges by isolating the worm’s gut bacteria and using them to do the job without the need for large scale worm breeding.

NTU Associate Professor Cao Bin at the School of CEE and Principal Investigator at SCELSE said, “A single worm can only consume about a couple of milligrams of plastic in its lifetime, so imagine the number of worms that would be needed if we were to rely on them to process our plastic waste. Our method eliminates this need by removing the worm from the equation. We focus on boosting the useful microbes in the worm gut and building an artificial ‘worm gut’ that can efficiently break down plastics.”

The study, published in Environment International in January, is aligned with the University’s commitment to fostering innovation and translating research into practical solutions that benefit society under its NTU2025 five-year strategic plan.

Developing an artificial worm gut

To develop their method, the NTU scientists fed three groups of superworms different plastic diets — High-density polyethylene (HDPE), Polypropylene (PP) and Polystyrene (PS) — over 30 days. The control group was fed a diet of oatmeal.

The NTU scientists selected the plastics as they are among the most common plastics in the world, used in everyday items like food boxes and detergent bottles. HDPE is a type of plastic known for its high-impact resistance, making it difficult to break down.

After feeding the worms plastic, scientists extracted the microbiomes from their gut and incubated them in flasks containing synthetic nutrients and different types of plastics, forming an artificial ‘worm gut’. Over six weeks, the microbiomes were left to grow in the flasks at room temperature.

Increase in plastic-degrading bacteria

The scientists found that compared to the control group, the flasks which contained the gut microbiomes from the plastic-fed worms showed a significant increase in plastic-degrading bacteria.

Furthermore, the microbial communities colonising the plastics in the flasks were simpler and more tailored to the specific type of plastic than the microbes found on plastics that had been fed directly to the worms . When the microbial communities are simpler and targeted to a specific type of plastic, this translates to potential for more efficient plastic degradation when used in real-life applications.

First author of the study Dr Liu Yinan, Research Fellow at the School of CEE and SCELSE, said, “Our study represents the first reported successful attempt to develop plastic-associated bacterial communities from gut microbiomes of plastic-fed worms. Through exposing the gut microbiomes to specific conditions, we were able to boost the abundance of plastic-degrading bacteria present in our artificial ‘worm gut,’ suggesting that our method is stable and replicable at scale.”

The researchers say their proof-of-concept lays the foundation for developing biotechnological approaches that use worms’ gut microbiomes to process plastic waste.

For their next steps, the researchers want to understand how the bacteria in the superworm’s gut break down the plastics at the molecular level. Understanding the mechanism will help scientists engineer plastic-degrading bacterial communities to break down plastics efficiently in the future.

The evidence, contained within an ice core, shows that in one location the ice sheet thinned by 450 metres — that’s more than the height of the Empire State Building — in just under 200 years.

This is the first evidence anywhere in Antarctica for such a fast loss of ice. Scientists are worried that today’s rising temperatures might destabilize parts of the West Antarctic Ice Sheet in the future, potentially passing a tipping point and inducing a runaway collapse. The new study, published in Nature Geoscience, sheds light on how quickly Antarctic ice could melt if temperatures continue to soar.

“We now have direct evidence that this ice sheet suffered rapid ice loss in the past,” said Professor Eric Wolff, senior author of the new study from Cambridge’s Department of Earth Sciences. “This scenario isn’t something that exists only in our model predictions and it could happen again if parts of this ice sheet becomes unstable.”

The Antarctic ice sheets, from west to east, contain enough freshwater to raise global sea levels by around 57 metres. The West Antarctic Ice Sheet is considered particularly vulnerable because much of it sits on bedrock that lies below sea level.

Model predictions suggest that a large part of the West Antarctic Ice Sheet could disappear in the next few centuries, causing sea levels to rise. Exactly when and how quickly the ice could be lost is, however, uncertain.

One way to train ice sheet models to make better predictions is to feed them with data on ice loss from periods of warming in Earth’s history. At the peak of Last Ice Age 20,000 years ago, Antarctic ice covered a larger area than today. As our planet thawed and temperatures slowly climbed, the West Antarctic Ice Sheet contracted to more or less its current extent.

“We wanted to know what happened to the West Antarctic Ice Sheet at the end of the Last Ice Age, when temperatures on Earth were rising, albeit at a slower rate than current anthropogenic warming,” said Dr Isobel Rowell, study co-author from the British Antarctic Survey. “Using ice cores we can go back to that time and estimate the ice sheet’s thickness and extent.”

Ice cores are made up of layers of ice that formed as snow fell and was then buried and compacted into ice crystals over thousands of years. Trapped within each ice layer are bubbles of ancient air and contaminants that mixed with each year’s snowfall — providing clues as to the changing climate and ice extent.

The researchers drilled a 651-metre-long ice core from Skytrain Ice Rise in 2019. This mound of ice sits at the edge of the ice sheet, near the point where grounded ice flows into the floating Ronne Ice Shelf.

After transporting the ice cores back to Cambridge at -20^oC, the researchers analysed them to reconstruct the ice thickness. First, they measured stable water isotopes, which indicate the temperature at the time the snow fell. Temperature decreases at higher altitudes (think of cold mountain air), so they were able to equate warmer temperatures with lower-lying, thinner ice.

They also measured the pressure of air bubbles trapped in the ice. Like temperature, air pressure also varies systematically with elevation. Lower-lying, thinner ice contains higher pressure air bubbles.

These measurements told them that ice thinned rapidly 8,000 years ago. “Once the ice thinned, it shrunk really fast,” said Wolff, “this was clearly a tipping point — a runaway process.”

They think this thinning was probably triggered by warm water getting underneath the edge of the West Antarctic Ice Sheet, which normally sits on bedrock. This likely untethered a section of the ice from bedrock, allowing it to float suddenly and forming what is now the Ronne Ice Shelf. This then allowed neighbouring Skytrain Ice Rise, no longer restrained by grounded ice, to thin rapidly.

The researchers also found that the sodium content of the ice (originating from salt in sea spray) increased about 300 years after the ice thinned. This told them that, after the ice thinned, the ice shelf shrunk back so that the sea was hundreds of kilometres nearer to their site.

“We already knew from models that the ice thinned at around this time, but the date of this was uncertain,” said Rowell. Ice sheet models placed the retreat anywhere between 12,000 and 5,000 years ago and couldn’t say how quickly it happened. “We now have a very precisely dated observation of that retreat which can be built into improved models,” said Rowell.

Although the West Antarctic Ice Sheet retreated quickly 8,000 years ago, it stabilized when it reached roughly its current extent. “It’s now crucial to find out whether extra warmth could destabilize the ice and cause it to start retreating again,” said Wolff.