Author: Futurity (National Geo)

Competition over love and real estate drives two extreme behaviors in green-rumped parrotlets, a new study finds—either caring for or killing one another’s babies.

Infanticide and adoption in the animal kingdom have long puzzled scientists. While both males and females of many species are known to kill the babies of their rivals to secure sexual or social advantage, other animals have been observed caring for the young of dead or missing comrades.

In a new study, published in the Proceedings of the National Academy of Sciences, researchers present nearly 30 years of observations revealing why both of these extreme behaviors are surprisingly common among the small South American birds.

“In parrotlets, infanticide and adoption revolve around real estate and love,” says study senior author Steven Beissinger, a professor of environmental science, policy, and management at the University of California, Berkeley.

“Most of the infanticide attacks happened when a breeding pair was attacked by another pair that was trying to take over a coveted nest site. It also occurred when males wanted to breed with a widow who already had offspring—but we were surprised to find that these new males were just as likely to adopt the offspring as attack them.”

Since 1988, Beissinger has led a team of biologists observing a community of green-rumped parrotlets residing on a cattle ranch in Guárico, Venezuela. While most wild parrots live in the forest canopy—making them very difficult to track and study—green-rumped parrotlets prefer to nest in hollowed-out trees and fence posts in grasslands.

To observe the family dynamics of these birds, Beissinger crafted artificial nesting sites out of large PVC pipes and installed them throughout the ranch. He also began color-banding the parrotlets to track individuals and their relationships.

Early in the study, Beissinger and his former graduate student Scott Stoleson were surprised to find dead babies in a nest, with no clear indication of what had killed them.

“At low population levels, it’s all love and peace, right? But then when you get to high population densities, it’s a bloodbath.”

“We couldn’t tell if something had attacked them, or if they had died from disease, or something else,” Beissinger says. “But when we were watching some of the nests, all of a sudden in went a male who didn’t belong—who wasn’t a parent at that nest—and out he came with a little bit of blood on his beak.”

The sight gave Beissinger the first clue that infanticide might be happening among the parrotlets, and he began tracking instances of the behavior. The study includes observations of more than 2,700 nests between 1988 and 2015.

While infanticide in mammals and birds is still poorly understood, it often appears to be motivated by sexual selection, or the drive to reproduce. For instance, a male may kill the offspring of a widowed female so that he can mate with her more quickly.

However, among parrotlets, competition over nesting sites appears to be the primary motivation for attacks. Parrotlets killed or wounded nestlings and eggs at 256 of the nests that the biologists monitored. In most cases, the attacks were carried out by a single parrotlet or a breeding pair that later claimed the nesting site for themselves.

These attacks occurred more often when the parrotlet population was high and competition for good nesting sites was fierce.

“At low population levels, it’s all love and peace, right? But then when you get to high population densities, it’s a bloodbath,” says coauthor Karl Berg, an associate professor in the School of Integrative Biological and Chemical Sciences at the University of Texas Rio Grande Valley in Brownsville who has worked with Beissinger on the project for more than 20 years.

“It’s not that everybody’s born a killer, but the urge to breed is very strong. When the resources provided by the environment aren’t enough for all individuals to breed, they seek out alternative strategies. Unfortunately, that involves killing innocent little offspring.”

Infanticide also occurred in nests where one parent had died and the surviving parent had found a new mate. However, these new mates were just as likely to adopt the unrelated offspring as kill them—and choosing to become a stepparent ultimately did not hurt the parrotlet’s reproductive success.

“Adoption may be a lot easier to accept than infanticide, but it’s actually more difficult to understand because it challenges Darwin’s ideas about natural selection,” Berg says. “It was very interesting to see that the reproductive fitness outcomes were about even between adoption and infanticide and suggests that they have an alternative strategy—adoption may be a nonviolent means of getting genes into the next generation.”

The study also found that males who adopted unrelated offspring went on to nest with widowed females and started breeding at younger ages than their competitors.

“Stepfathers scored love—a new mate—and real estate—a nest site!” says Beissinger.

The National Science Foundation, the Smithsonian Institution, and the National Geographic Society, funded the work, with additional support from the A. Starker Leopold Chair in Wildlife Biology and the Maxwell-Hanrahan Foundation.

Source: UC Berkeley

When people are presented with two answers to an ethical question, most will think the answer from artificial intelligence is better than the response from another person.

The explosion of ChatGPT and similar AI large language models (LLMs) which came onto the scene last March inspired the research.

“I was already interested in moral decision-making in the legal system, but I wondered if ChatGPT and other LLMs could have something to say about that,” says Eyal Aharoni, an associate professor in Georgia State’s psychology department.

“People will interact with these tools in ways that have moral implications, like the environmental implications of asking for a list of recommendations for a new car. Some lawyers have already begun consulting these technologies for their cases, for better or for worse. So, if we want to use these tools, we should understand how they operate, their limitations, and that they’re not necessarily operating in the way we think when we’re interacting with them.”

To test how AI handles issues of morality, Aharoni designed a form of a Turing test.

“Alan Turing, one of the creators of the computer, predicted that by the year 2000 computers might pass a test where you present an ordinary human with two interactants, one human and the other a computer, but they’re both hidden and their only way of communicating is through text,” Aharoni says.

“Then the human is free to ask whatever questions they want to in order to try to get the information they need to decide which of the two interactants is human and which is the computer. If the human can’t tell the difference, then, by all intents and purposes, the computer should be called intelligent, in Turing’s view.”

For his Turing test, Aharoni asked undergraduate students and AI the same ethical questions and then presented their written answers to participants in the study. They were then asked to rate the answers for various traits, including virtuousness, intelligence, and trustworthiness.

“Instead of asking the participants to guess if the source was human or AI, we just presented the two sets of evaluations side by side, and we just let people assume that they were both from people,” Aharoni says. “Under that false assumption, they judged the answers’ attributes like ‘How much do you agree with this response, which response is more virtuous?’”

Overwhelmingly, the ChatGPT-generated responses were rated more highly than the human-generated ones.

“After we got those results, we did the big reveal and told the participants that one of the answers was generated by a human and the other by a computer, and asked them to guess which was which,” Aharoni says.

For an AI to pass the Turing test, humans must not be able to tell the difference between AI responses and human ones. In this case, people could tell the difference, but not for an obvious reason.

“The twist is that the reason people could tell the difference appears to be because they rated ChatGPT‘s responses as superior,” Aharoni says. “If we had done this study five to 10 years ago, then we might have predicted that people could identify the AI because of how inferior its responses were. But we found the opposite—that the AI, in a sense, performed too well.”

According to Aharoni, this finding has interesting implications for the future of humans and AI.

“Our findings lead us to believe that a computer could technically pass a moral Turing test—that it could fool us in its moral reasoning. Because of this, we need to try to understand its role in our society because there will be times when people don’t know that they’re interacting with a computer and there will be times when they do know and they will consult the computer for information because they trust it more than other people,” Aharoni says.

“People are going to rely on this technology more and more, and the more we rely on it, the greater the risk becomes over time.”

The study appears in the journal Scientific Reports.

Source: Georgia State

The implications of high prices for new diabetes and obesity therapies are alarming, according to researchers.

For years, Kasia Lipska, associate professor of medicine (endocrinology) at Yale School of Medicine (YSM), has been advocating for affordable pricing of insulin, an essential—and sometimes lifesaving—drug for many individuals with diabetes.

Now, she is turning her attention to a similar trend of soaring prices among new diabetes and obesity medications.

The implications of exorbitant prices for these therapies are alarming, according to Lipska, who first became aware of the drug pricing issue in 2016 when one of her patients couldn’t afford to increase the dose of insulin she was taking. In subsequent research, Lipska discovered that 1.1 million Americans, or 14% of those who filled insulin prescriptions, reached catastrophic spending, defined as spending more than 40% of post-subsistence income on insulin alone.

The same insulin and other medications for diabetes and obesity are frequently priced 10 times higher in the US than in peer countries, Lipska says.

In a new paper in Diabetes Care, Lipska, Reshma Ramachandran, assistant professor of medicine (general medicine) at YSM, and first author Kathryn Nagel, former YSM internal medicine department resident, used findings from previous research on insulin pricing to look at the issues underlying drug affordability.

“As with insulin, our patients are facing parallel challenges in accessing other new non-insulin diabetes and anti-obesity medications,” Ramachandran says.

In their research and analysis, Lipska, Ramachandran, and Nagel gathered evidence about the changes needed to achieve fair pricing of new diabetes and obesity drugs, creating a blueprint that policymakers can use for potential action.

“Writing the article helped us map out the different pieces that go into the drug pricing process in the US,” Lipska says. “We learned more about the complex chain of events that leads from drug development and patent law to how much patients pay when the medicine gets to them.”

“Our paper highlights where along the drug development and delivery value chain there is more work yet to be done by policymakers to enable more equitable and affordable access to these medications,” Ramachandran adds.

Ramachandran notes a key lesson learned from efforts to improve access to insulin is that there is no single silver bullet. “Our paper shows that a range of upstream and downstream policies are necessary,” she says.

But there are challenges to policy reform, the researchers observe.

“While the recent Inflation Reduction Act includes several policies to lower prescription drug prices, including for those used in diabetes treatment, the legislation also has serious limitations in providing relief for patients, particularly for novel, transformative treatments,” Ramachandran says.

Lipska points to the power of US corporations as another obstacle to drug affordability.

“Many patient advocacy groups, educational events, and even professional societies that clinicians are a part of are in some way influenced or supported by the pharmaceutical industry,” she says.

Still, the issue is gaining traction, Lipska says. She notes a growing awareness of the need to address the drug pricing crisis through state and federal intervention and of the role clinicians can play in advocating on behalf of their patients.

“There are a lot of policies targeting drug affordability that have recently been proposed or enacted into law,” she says. “Clinicians can give feedback about how certain solutions are playing out in practice and bring an important perspective to this conversation.”

Source: Serena Crawford for Yale University

Chemists and pharmacists should be key players in species conservation efforts, researchers urge.

Their new paper comes as the world faces the loss of a staggering number of species of animals and plants to endangerment and extinction.

“Medicinal chemistry expertise is desperately needed on the front lines of extinction,” says Timothy Cernak, assistant professor of medicinal chemistry at the University of Michigan College of Pharmacy. “Animals are dying at staggering rates, but they don’t have to. Modern bioscience has achieved enormous breakthroughs in treating disease in humans, and the same medications, and the science behind them, can be applied in the wild.”

Local and global efforts to reduce environmental damage are underway, but they are too slow to save the many ailing populations in the wild, he says.

“We are in the middle of a mass extinction. We are chasing mass die-offs around the world. Lowland gorillas, Argentinian penguins, the akikiki bird in Hawaii, loggerhead turtles in Florida. The list goes on, and many precious plants are also hanging by a thread,” he says. “So it’s critical to bring the power of modern pharmaceuticals and the dosing expertise of medicinal chemistry into conservation efforts.”

‘Hard-core science’

Cernak and a team of young scientists, including a local high school student, make the case for establishing and nurturing the emerging field of conservation medicine in a research article published in the Journal of Medicinal Chemistry.

“It’s hard-core science. It’s bringing the lens of medicinal chemistry and modern pharmaceuticals into the conversation to save other species,” Cernak says. “Drivers of the current mass extinction include habitat loss, global warming, and overharvesting, but one specific root cause—wildlife disease—seems ripe for intervention. Medicinal chemistry is that intervention.”

Cernak, in one of many roles and research projects, receives samples of dead and ailing species from around the world. Using the same methods and models used to find compounds that work against human disease, his lab, which recently brought a veterinarian on board, tests chemical compounds on samples to see which ones respond to disease-causing organisms. A major focus is fungus, the single-largest killer of amphibians.

In their paper, the authors propose a new role for chemistry and pharmacy on the front lines of preventing extinction: “A long-term solution to mass extinction is to fix climate change and habitat loss using new technologies and new policies. As a bandage for the short term, chemistry in service of endangered species is needed.

“Medicinal chemists interested in preventing extinction are encouraged to talk to zookeepers, foresters, veterinarians, entomologists, wildlife rehabilitators, and conservationists to learn about the challenges and solutions where conservation medicine could make an impact, and to share their wisdom from the frontlines of drug discovery.”

Conservation medicine challenges

“At the higher level, my mission is to have pharmaceutical companies be involved in this space and young scientists view this as the field they want to go into—a field that doesn’t really exist at this point,” Cernak says. “A more immediate goal is fundraising and more research as the field and the value of the field is established.”

From deadly fungus decimating Panamanian golden frogs, cancerous tumors killing loggerhead turtles, and the numerous pests and illnesses sickening plants such as the hemlock tree, there is no shortage of challenges for conservation medicine to tackle.

One of those challenges may be preventing a disease from threatening public health.

“In January, 96% of sea lion pups in Argentina died from avian flu. If it reaches humans, what are we going to do?” Cernak says. “There may be just five akikiki songbirds left in the wild. They are dying from malaria and pox, diseases that can be treated in humans.”

Studying wildlife diseases could also provide critical insights to medicinal chemists focused on human health, he says, and possibly a new paradigm where drug development and dosing prediction models, which are currently trained heavily on pharmacokinetics in rodents, could be diversified.

“The problem is that too often, conservationists who are trying desperately to treat and save dwindling populations aren’t equipped with the latest pharmaceutical science and tools,” he says. “Given current knowledge gaps, they may not know which drug will work best or what the right dosage might be for an endangered species.”

Hope for endangered species

Bringing chemists and pharmacists into the conservation fold isn’t meant to diminish veterinarians and conservation groups, but to blend their experience and expertise and achieve the same goals of saving lives—and the ecosystem, Cernak says.

“Modern medicine could prevent the extinction of endangered species. Wildlife disease is a major driver of the current mass extinction yet therapeutic intervention in nonhuman species remains poorly understood,” he says. “In zoos, botanical gardens, and animal rehabilitation centers, many diseases are treatable, but the understanding of medicine for endangered species lags far behind our current understanding of human medicine.”

At this moment, Cernak’s lab is not only researching faster, safer pharmaceutical development for humans but also testing the Panamanian golden frogs afflicted with a fungus that threatens their existence.

Cernak supports the Centers for Disease Control and Prevention’s concept of One Health, which recognizes the connection between the health of people, animals and the environment.

“We look at plants and animals the same,” he says. “The concept of One Health Pharmacy—plants, humans, and animals—is we treat any that are sick or in need.”

Cernak’s lab has advanced the use of artificial intelligence and other technology in speeding up the process of drug discovery. He says that only increases the opportunities to help animals and plants sooner than later.

“Streamlining drug and agrochemical discovery with automation and artificial intelligence is likely to usher in a future era of accelerated medicinal invention tailored to specific patient populations,” Cernak and colleagues write in their paper.

“While it may still be decades away, one can imagine a future where it is possible to feed a chatbot prompts like, ‘Invent a single-dose antiviral for elephant endotheliotropic herpesvirus with optimal pharmacokinetic properties for Asian elephants.’ Exciting applications of medicinal chemistry on threatened and endangered species are beginning to offer hope.”

Additional coauthors include Chun-Yi Tsai, a graduate student in chemistry department; Yu-Pu Juang, a postdoctoral researcher in the Cernak Lab; Mohamed Abdelalim, a visiting research investigator, and Tesko Chaganti, a student at Canton High School in Canton, Michigan.

Source: University of Michigan

Researchers have created a new device for taking blood samples that works like a leech.

The new device is less invasive than taking blood from the arm with a needle. It is also easy to handle and can be used by people without medical training.

Many people are afraid of needles, and having a doctor take a blood sample from their arm makes them uncomfortable. There is an alternative: a prick to the fingertip or earlobe. But for many laboratory tests, the drop of blood that can be obtained from these places is not enough.

Above all, however, tests done with them are often inaccurate: laboratory values fluctuate from measurement to measurement.

Although the new device cannot collect as much blood as a needle, it can collect significantly more than a finger prick. This makes diagnostic measurements more reliable.

Inspiration from leeches

The researchers came up with the idea for the new device while previously developing something else: a suction cup that transports medication into the blood via the mucous membrane lining the inside of the mouth.

“For this earlier project, we had already studied leeches, which attach to their host with a sucker. We realized that we could develop a similar system to collect blood,” says David Klein, a doctoral student in the group led by Jean-Christophe Leroux, professor of drug formulation and delivery at ETH Zurich.

After leeches have attached themselves, they penetrate the host’s skin with their teeth. To suck blood from the wound, they create negative pressure by swallowing.

The new device works in a very similar way: A suction cup measuring about two and a half centimeters is attached to the patient’s upper arm or back. Within the cup are a dozen microneedles that puncture the skin when pressed against it. Within a few minutes, the negative pressure in the suction cup has ensured that sufficient blood has been collected to be used for diagnostic tests.

Looking ahead: Biodegradable version

The new device is very cost-effective to produce, says Nicole Zoratto, a postdoc in Leroux’s group. She led the work on this development and is lead author of the study published in the journal Advanced Science. Zoratto also sees a future application for the new device in low-income regions such as sub-Saharan Africa, where it could play a major part in the fight against tropical diseases such as malaria. Diagnosing malaria involves taking blood from the patients.

Another advantage of the new device is that the microneedles are located within the suction cup. This minimizes the risk of injury during the application and after disposal compared to blood sampling with conventional needles.

In the current version of the leech-like device, the suction cup is made of silicone and the microneedles concealed within are made of steel. However, the researchers are in the process of developing a new version made using fully biodegradable materials to create a sustainable product.

The researchers have tested their new device on pigs, and they have made comprehensive manufacturing information.

Before the device can be widely used on humans—in malaria regions and elsewhere—the material composition still needs to be optimized. And above all, safe use must be tested with a small group of test subjects. As such studies are complex and expensive, the research group is still looking for a partner for further funding, for example a charitable foundation. They hope that their new leech devices will soon be able to play a part in the health of children and anyone else who is afraid of needles.

Fondation Botnar via the Basel Research Centre for Child Health funded the work.

Source: ETH Zurich

A first-ever stretchy electronic skin could equip robots and other devices with the same softness and touch sensitivity as human skin, researchers report.

The e-skin opens up new possibilities to perform tasks that require a great deal of precision and control of force and solves a major bottleneck in the emerging technology. Existing e-skin technology loses sensing accuracy as the material stretches, but that is not the case with this new version.

“Much like human skin has to stretch and bend to accommodate our movements, so too does e-skin,” says Nanshu Lu, a professor in the Cockrell School of Engineering’s aerospace engineering and engineering mechanics department and lead author of the paper published in the journal Matter.

Lu envisions the stretchable e-skin as a critical component to a robot hand capable of the same level of softness and sensitivity in touch as a human hand. This could be applied to medical care, where robots could check a patient’s pulse, wipe the body, or massage a body part.

Why is a robot nurse or physical therapist necessary? Around the world, millions of people are aging and in need of care, more than the global medical system can provide.

“In the future, if we have more elderly than available caregivers, it’s going to be a crisis worldwide,” Lu says. “We need to find new ways to take care of people efficiently and also gently, and robots are an important piece of that puzzle.”

Beyond medicine, human-caring robots could be deployed in disasters. They could search for injured and trapped people in an earthquake or a collapsed building, for example, and apply on-the-spot care, such as administering CPR.

E-skin technology senses pressure from contact, letting the attached machine know how much force to use to, for example, grab a cup or touch a person. But, when conventional e-skin is stretched, it also senses that deformation. That reading creates additional noise that skews the sensors’ ability to sense the pressure. That could lead to a robot using too much force to grab something.

In demonstrations, the stretchability allowed the researchers to create inflatable probes and grippers that could change shape to perform a variety of sensitive, touch-based tasks. The inflated skin-wrapped probe was used on human subjects to capture their pulse and pulse waves accurately. The deflated grippers can conformably hold on to a tumbler without dropping it, even when a coin is dropped inside. The device also pressed on a crispy taco shell without breaking it.

The key to this discovery is an innovative hybrid response pressure sensor that Lu and collaborators have been working on for years. While conventional e-skins are either capacitive or resistive, the hybrid response e-skin employs both responses to pressure. Perfecting these sensors, and combining them with stretchable insulating and electrode materials, enabled this e-skin innovation.

Lu and her team are now working toward the potential applications. They are collaborating with Roberto Martin-Martin, assistant professor at the College of Natural Sciences’ computer science department, to build a robotic arm equipped with the e-skin.

The researchers and UT have filed a provisional patent application for the e-skin technology, and Lu is open to collaborating with robotics companies to bring it to market.

Source: UT Austin

Researchers have opened a new avenue in the attack against influenza viruses by creating a vaccine that encourages the immune system to target a portion of the flu virus surface that is less variable.

Their approach worked well in experiments with mice and ferrets and may lead to more broadly-protective influenza vaccines and less reliance on an annual shot tailored to that year’s versions of the virus. Even with vaccines, influenza kills about a half-million people each year around the world.

This new vaccine approach, described in the journal Science Translational Medicine, is part of a five-year-old effort to develop a longer-lasting universal flu vaccine that would be able to foil all versions of the virus.

Influenza strains are referred to by a shorthand code, H5N1 for example, that describes which flavors of two particular surface proteins it carries. The H (sometimes HA), is hemagglutinin, a lollipop-shaped protein that binds to a receptor on a human cell, the first step toward getting the virus inside the cell. The N is neuraminidase, a second protein that enables a newly made virus to escape the host cell and go on to infect other cells.

“On the virus particle, there’s five to 10 times more hemagglutinin than neuraminidase,” says Nicholas Heaton, an associate professor of molecular genetics and microbiology at Duke University who led the research.

“If we took your blood to see if are you likely to be protected from a strain of flu, we’d be measuring what your antibodies do to hemagglutinin as the best metric of what’s likely to happen to you. The strongest correlates of protection have to do with hemagglutinin-directed immunity.”

Vaccines teach the immune system to react to pieces of the virus that have been specifically tailored to the versions of influenza that are expected to be the most threatening in the coming flu season. The reason we need a new flu shot every fall isn’t because the vaccine wears out; it’s because the influenza virus is constantly changing the surface proteins that vaccines target.

Flu shots—and immune systems—tend to target the bulb-like “head” of hemagglutinin rather than the stalk. But the details of that head region also change constantly, creating an arms race between vaccine design and viruses. The stalk, by comparison, changes much less.

“A number of groups have gone through and experimentally mutagenized the whole hemagglutinin and asked ‘which areas can change and still allow the hemagglutinin to function?’” Heaton says. “And the answer is, you can’t really change the stalk and expect it to continue to function.”

So the Duke team sought to design proteins that elicit an immune response more focused on the stalk rather than the head.

“The virus has evolved to have the immune system recognize these (features on the head region). But these are the shapes the virus can change. That is an insidious strategy,” Heaton says.

Using gene-editing, they created more than 80,000 variations of the hemagglutinin protein with changes in one portion right on the top of the head domain and then tested a vaccine filled with a mixture of these variations on mice and ferrets.

Because of the broad variety of head conformations being presented to the immune system and the relative consistency of the stalks, these vaccines produced more antibodies to the stalk portion of hemagglutinin in response.

“The opportunity for the immune system to see that (head portion) over and over and over, like it needs to, is compromised because there’s diversity there,” Heaton says.

In lab tests and animals, the experimental vaccine caused the immune system to respond more strongly to stalk regions because they stayed consistent. This boosted the immune response to the vaccine overall, and in some cases, even improved antibody responses to the head region of the protein as well.

“Antibodies against the stalk work differently,” Heaton says. “Their mechanism of protection is not necessarily to block the first step of infection. So then our idea was, ‘What if we can come up with a vaccine that gives us both? What if we can get good head antibodies and at the same time also get stalk antibodies in case the vaccine selection was wrong, or if there’s a pandemic?’”

“Essentially, the paper says, Yes, we can accomplish that,” Heaton says.

After a shot of the highly variant vaccine was administered in some experiments, 100% of the mice avoided illness or death from what should have been a lethal dose of flu viruses.

The next steps of the research will attempt to understand whether the same level of immunity can be achieved by presenting fewer than 80,000 hemagglutinin variants.

The NIH/National Institute of Allergy and Infectious Diseases funded the work. The study involved the use of the Duke Regional Biocontainment Laboratory, which received partial support for construction from the NIH/NIAID.

Nicholas Heaton and coauthor Zhaochen Luo have a patent on the methods used to create large antigen libraries for this study.

Source: Duke University

Working with human breast and lung cells, scientists say they have charted a molecular pathway that can lure cells down a hazardous path of duplicating their genome too many times, a hallmark of cancer cells.

The findings, published in Science, reveal what goes wrong when a group of molecules and enzymes trigger and regulate what’s known as the “cell cycle,” the repetitive process of making new cells out of the cells’ genetic material.

The findings could be used to develop therapies that interrupt snags in the cell cycle, and have the potential to stop the growth of cancers, the researchers suggest.

To replicate, cells follow an orderly routine that begins with making a copy of their entire genome, followed by separating the genome copies, and finally, dividing the replicated DNA evenly into two “daughter” cells.

Human cells have 23 pairs of each chromosome—half from the mother and half from the father, including the sex chromosomes X and Y—or 46 total, but cancer cells are known to go through an intermediate state that has double that number—92 chromosomes. How this happens was a mystery.

“An enduring question among scientists in the cancer field is: How do cancer cell genomes get so bad?” says Sergi Regot, associate professor of molecular biology and genetics at the Johns Hopkins University School of Medicine.

“Our study challenges the fundamental knowledge of the cell cycle and makes us reevaluate our ideas about how the cycle is regulated.”

Regot says cells that are stressed after copying the genome can enter a dormant, or senescent stage, and mistakenly run the risk of copying their genome again.

Generally and eventually, these dormant cells are swept away by the immune system after they are “recognized” as faulty. However, there are times, especially as humans age, when the immune system can’t clear the cells. Left alone to meander in the body, the abnormal cells can replicate their genome again, shuffle the chromosomes at the next division, and a growing cancer begins.

In an effort to pin down details of the molecular pathway that goes awry in the cell cycle, Regot and graduate research assistant Connor McKenney, who led the Johns Hopkins team, focused on human cells that line breast ducts and lung tissue. The reason: These cells generally divide at a more rapid pace than other cells in the body, increasing the opportunities to visualize the cell cycle.

Regot’s lab specializes in imaging individual cells, making it especially suited to spot the very small percentage of cells that don’t enter the dormant stage and continue replicating their genome.

For this new study, the team scrutinized thousands of images of single cells as they went through cell division. The researchers developed glowing biosensors to tag cellular enzymes called cyclin dependent kinases (CDKs), known for their role in regulating the cell cycle.

They saw that a variety of CDKs activated at different times during the cell cycle. After the cells were exposed to an environmental stressor, such as a drug that disrupts protein production, UV radiation or so-called osmotic stress (a sudden change in water pressure around cells), the researchers saw that CDK 4 and CDK 6 activity decreased.

Then, five to six hours later, when the cells started preparations to divide, CDK 2 was also inhibited. At that point, a protein complex called the anaphase promoting complex (APC) was activated during the phase just before the cell pulls apart and divides, a step called mitosis.

“In the stressed environment in the study, APC activation occurred before mitosis, when it’s usually been known to activate only during mitosis,” says Regot.

About 90% of breast and lung cells leave the cell cycle and enter a quiet state when exposed to any environmental stressors.

In their experimental cells, not all of the cells went quiet.

The research team watched as about 5% to 10% of the breast and lung cells returned to the cell cycle, dividing their chromosomes again.

Through another series of experiments, the team linked an increase in activity of so-called stress activated protein kinases to the small percentage of cells that skirt the quiet stage and continue to double their genome.

Regot says there are ongoing clinical trials testing DNA-damaging agents with drugs that block CDK. “It’s possible that the combination of drugs may spur some cancer cells to duplicate their genome twice and generate the heterogeneity that ultimately confers drug resistance.”

“There may be drugs that can block APC from activating before mitosis to prevent cancer cells from replicating their genome twice and prevent tumor stage progression,” he says.

Funding for the study came from the National Institutes of Health National Institute of General Medical Sciences and National Cancer Institute, the National Science Foundation, and the American Cancer Society.

Source: Johns Hopkins University

“Forever chemicals” have made the news recently, with new EPA rules limiting the amount of some types that can be in drinking water.

Here, Carla Ng, an associate professor of civil and environmental engineering at the University of Pittsburgh Swanson School of Engineering, explains what these chemicals are, where they’re found, and what’s being done to limit their impact.

What exactly are forever chemicals?

When scientists created a chemical compound capable of repelling both water and oil in the 1940s, they believed it was a revolution in materials sciences. They weren’t wrong.

That class of chemical compounds, called per- and polyfluorinated alkyl substances (PFAS), were quickly used to create useful domestic products like Teflon and dental floss, along with industrial agents like firefighting foam. They even found use in parts of the Manhattan Project.

Decades later, PFAS are still around. Because of their impressive surface density, these “forever chemicals” don’t naturally break down in either the human body or nature, causing health concerns like cancer, thyroid disease, and reproductive impairment.

Ng has devoted much of her career to studying common sources of PFAS contamination, and collaborating to create road maps that reduce nonessential uses of PFAS, stop human and environmental exposure from getting worse, and more equitably distribute the associated costs.

Where are they found?

Pretty much everywhere.

Ng explains that while society is more aware of the risks PFAS pose than we were in the 1940s, the chemicals are still being widely used today for specialized firefighting foams, personal care products, and food packaging, just to name a few applications.

“It’s hard to escape them,” Ng says.

The Environmental Protection Agency (EPA) reports that most people in the United States have been exposed to PFAS in some capacity. Exposure happens when touching, eating, drinking, or breathing in materials containing PFAS, commonly from drinking water, waste sites, consumer products like nonstick repellants, or fire extinguishing foam.

Ng recommends using the Environmental Working Group’s interactive map, which tracks PFAS contamination throughout the United States. She notes that states with higher levels typically have the most research completed behind them.

“Scientists still do not know how much PFAS have been produced globally, which means major ‘hotspots’ of PFAS contamination are probably being missed,” Ng says.

How do scientists test for contamination in drinking water?

Until this month, there was no national standard for PFAS maximum contaminant level, so individual states set their own. Pennsylvania, for example, set its maximum level for PFOA and PFOS—both fall under the PFAS umbrella—at 14 parts per trillion for PFOA and 18 parts per trillion for PFOS on January 14, 2023.

The EPA has its own approved method for testing drinking water and utilizes a certified lab. Ng’s lab used a method called 1633—which is still in development by the EPA—when trying to understand how much contamination occurred when a small Pittsburgh community faced its own ecological disaster. While it requires double the volume of water compared to the EPA method, it’s capable of detecting a wide range of PFAS compounds.

Can they be eradicated?

There was a time before PFAS was used for everything and found everywhere. We won’t be going back to that anytime soon.

“Even if we are able to immediately stop the use of these PFAS chemicals, the problem lies with the forever chemical properties that they have,” Ng says. “It’s going to be a really long time before the environment is clean again.”

One question that sits between us and a future with fewer forever chemicals is whether PFAS is necessary. Ng and other researchers have been trying to determine if there are ethical, non-harmful alternatives that will allow us to stop using PFAS in some applications. It’s possible to find a suitable replacement for nonstick pans and dental floss, but what about green technology, safety suits or medical devices?

“The importance is that this shouldn’t be permanent, and we need to have innovation to drive the creation of replacements of these compounds,” Ng says.

There’s still a gray area when it comes to disposing household items that contain these chemicals as they just typically end up in landfills, creating a cyclical problem as regulations of PFAS are still coming to light.

At home, at least, there are ways to limit one’s risk of contamination. Both granular activated carbon and reverse osmosis filters can reduce PFAS levels in drinking water.