Competing cells: Cleaning up after yourself brings benefits

When different cell types compete in a confined space, those which remove debris faster have a better chance to dominate their environment. Researchers from the Max Planck Institute for Dynamics and Self-Organization (MPI-DS) showed in their model that not only a higher net proliferation rate, but also the swift removal of dead cells provides a competitive advantage. They mixed two cell populations only differing in debris removal rate and showed that already after a few generations the population with the higher removal rate starts to dominate the confined space.

Biological organisms and tissues exhibit a constant turnover of cellular material; for instance, to maintain tissue integrity, in case of tumor growth, or for survival of bacterial communities. Intuitively, cell types which are able to proliferate the fastest or die less frequently in a given environment will dominate the confined space within an organism or compartment. “However, these traditional factors do not remain the only ones determining competitive fitness, when taking into account also the debris left behind by dying cells,” Ramin Golestanian, managing director at the MPI-DS says. In their study, the researchers from the department of Living Matter Physics showed that cell types being cleared out faster after death have an advantage that can make them the dominant species.

The scientists created a model to simulate growing cells filling a limited amount of space until mechanical pressure builds up and they reach a state in which division and cell death balance each other. “We wanted to find out what effect dead matter has on the growth of a living system. For this, we designed a simple model that is one of the first to explicitly consider the mechanical effects of dead cells,” Yoav Pollack, first author of the study, describes the approach. “We then analyzed two cell types differing exclusively in the dead-matter removal rate and tracked the proportion of both populations over time. To our excitement, we observed a clear impact on the overall fitness, leading to an advantage for the cell type whose dead cells are removed more quickly,” he explains.

Making room for new cells

At first sight, the removal of dead material might seem disconnected from the formation of new cells — or even counterproductive as it opens up space for other species to invade. But the model shows that by clearing out debris faster, the amount of alive compared to dead cells increases. Overall, this results in a more responsive growth when a species is presented with opportunities for expansion. While this is of little consequence in a homogeneous cell population of the same type, it makes a difference at the interface where different cell types are competing for space. The population with the higher clear-out rate is more likely to have a living cell in the vicinity available to fill vacated space through proliferation. In this way, the higher proportion of living cells gives a competitive advantage.

“In simplified terms, one could say that clearing out and occupying new space is more advantageous than holding on to already occupied space,” comments group leader Philip Bittihn. “In certain cases, this new contribution to competition might also explain why biological tissues and organisms evolved to use specific cell removal mechanisms; ones that are more efficient compared to the alternatives,” he concludes.

As this effect has now been described for the first time, it opens up several new lines of investigation, such as analyzing the extent to which it contributes to the overall fitness in relation to other fitness factors. Yet, the model demonstrates that cleaning up after yourself does indeed pay off for cells.

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Materials provided by Max Planck Institute for Dynamics and Self-Organization. Note: Content may be edited for style and length.

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‘I thought being black meant I couldn’t get skin cancer’

One woman warns others to learn from her mistakes and use sunscreen.

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Experts don’t always give better advice — they just give more

New research finds that people given advice by top performers thought that it helped them more, even though it usually didn’t.

When you want advice to achieve something, whom would you rather ask: the top performer in that area or someone barely scraping by? Most people would choose the top performer. That person’s advice, however, may not be any more helpful.

“Skillful performance and skillful teaching are not always the same thing, so we shouldn’t expect the best performers to necessarily be the best teachers as well,” said David Levari (Harvard Business School), lead author of a recent Psychological Science article.

Across four studies, he and coauthors APS Fellows Daniel T. Gilbert (Harvard University) and Timothy D. Wilson (University of Virginia) found that top performers don’t give better advice than other performers, at least in some domains. Rather, they just give more of it.

“People seem to mistake quantity for quality,” the researchers wrote. “Our studies suggest that in at least in some instances, people may overvalue advice from top performers.”

In the first study, Levari and colleagues set out to determine whether people believe an advisor’s performance is a robust indicator of the quality of their advice.

More than 1,100 participants, sourced through Amazon Mechanical Turk, were told they would be playing a game called Word Scramble and then answering questions about it. Shown a board of letters, participants were given 60 seconds to form as many words as possible. Participants played three rounds, each time with a different board of letters.

The researchers then asked participants to choose which advisors they would prefer to receive advice from to get better at the task. Participants showed a strong preference for the best performers, regardless of how the question was asked (i.e., in a free-choice or forced-choice format).

In the second study, the researchers explored whether the best performers did indeed give the best advice. They asked 100 “advisors” to play six rounds of Word Scramble, write advice for future players, and rate the quality of their own advice. The best performers believed they had given the best advice.

In the same study, another 2,085 participants were randomly assigned to either an advice or a no-advice condition. After playing one round of Word Scramble, participants in the advice condition received direction from a random advisor, then played five more rounds. The no-advice participants played six rounds without feedback. Advisees performed better after receiving advice, and they tended to perform better with each subsequent round. But the advice from the best performers was no more helpful, on average, than the advice from the other performers. The researchers conducted a similar study with darts, showing a similar pattern of results.

“In our experiments, people given advice by top performers thought that it helped them more, even though it usually didn’t. Surprisingly, they thought this even though they didn’t know anything about the people who wrote their advice,” said Levari.

The researchers conducted two more studies to understand why the advice from better performers seemed better. Two undergraduate research assistants who were blind to the study’s purposes and hypotheses coded the advice for seven properties: authoritativeness, actionability, articulateness, obviousness, number of suggestions, “should” suggestions, and “should not” suggestions. Each property was analyzed for its perceived helpfulness and perceived improvement.

Only one property — number of suggestions — consistently predicted both the perceived helpfulness and the perceived improvement of the advice. However, there was no correlation between the number of suggestions and the efficacy of the advice.

“Top performers didn’t write more helpful advice, but they did write more of it, and people in our experiments mistook quantity for quality,” Levari told APS.

So, why wasn’t the advice more helpful? Levari and colleagues have a few ideas.

First, skilled performers may overlook fundamental advice because “natural talent and extensive practice have made conscious thought unnecessary. … A natural-born slugger who has played baseball every day since childhood may not think to tell a rookie about something they find utterly intuitive, such as balance and grip,” they wrote.

Second, top performers may not be skilled communicators. “Even when an excellent performer does have explicit information to share, they may not be especially adept at sharing it,” the researchers wrote. Finally, a large quantity of advice may be more than what can realistically be implemented.

“We spend a lot of time and money looking for good advice, whether from coworkers and coaches, teachers and tutors, or friends and family,” said Levari. “The next time you get advice, you may want to think less about how much of it there was, and more about how much of it you could actually use.”

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Deformable pump gives soft robots a heart

The Tin Man didn’t have one. The Grinch’s was three sizes too small. And for soft robots, the electronically powered pumps that function as their “hearts” are so bulky and rigid, they must be decoupled from the robot’s body — a separation that can leak energy and render the bots less efficient.

Now, a collaboration between Cornell researchers and the U.S. Army Research Laboratory has leveraged hydrodynamic and magnetic forces to drive a rubbery, deformable pump that can provide soft robots with a circulatory system, in effect mimicking the biology of animals.

“These distributed soft pumps operate much more like human hearts and the arteries from which the blood is delivered,” said Rob Shepherd, associate professor of mechanical and aerospace engineering in the College of Engineering, who led the Cornell team. “We’ve had robot blood that we published from our group, and now we have robot hearts. The combination of the two will make more lifelike machines.”

The group’s paper, “Magnetohydrodynamic Levitation for High-Performance Flexible Pumps,” published July 11 in Proceedings of the National Academy of Sciences. The paper’s lead author was postdoctoral researcher Yoav Matia.

Shepherd’s Organic Robotics Lab has previously used soft material composites to design everything from stretchable sensor “skin” to combustion-driven braille displays and clothing that monitors athletic performance — plus a menagerie of soft robots that can walk and crawl and swim and sweat. Many of the lab’s creations could have practical applications in the fields of patient care and rehabilitation.

Like animals, soft robots need a circulatory system to store energy and power their appendages and movements to complete complex tasks.

The new elastomeric pump consists of a soft silicone tube fitted with coils of wire — known as solenoids — that are spaced around its exterior. Gaps between the coils allow the tube to bend and stretch. Inside the tube is a solid core magnet surrounded by magnetorheological fluid — a fluid that stiffens when exposed to a magnetic field, which keeps the core centered and creates a crucial seal. Depending on how the magnetic field is applied, the core magnet can be moved back and forth, much like a floating piston, to push fluids — such as water and low-viscosity oils — forward with continuous force and without jamming.

“We’re operating at pressures and flow rates that are 100 times what has been done in other soft pumps,” said Shepherd, who served as the paper’s co-senior author with Nathan Lazarus of the U.S. Army Research Laboratory. “Compared to hard pumps, we’re still about 10 times lower in performance. So that means we can’t push really viscous oils at very high flow rates.”

The researchers conducted an experiment to demonstrate that the pump system can maintain a continuous performance under large deformations, and they tracked the performance parameters so future iterations can be custom-tailored for different types of robots.

“We thought it was important to have scaling relationships for all the different parameters of the pump, so that when we design something new, with different tube diameters and different lengths, we would know how we should tune the pump for the performance we want,” Shepherd said.

Postdoctoral researcher Hyeon Seok An contributed to the paper.

The research was supported by the U.S. Army Research Laboratory.

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Materials provided by Cornell University. Original written by David Nutt, courtesy of the Cornell Chronicle. Note: Content may be edited for style and length.

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Best available therapy for AIDS-associated Kaposi sarcoma is cost effective in Africa

Although antiretroviral therapy has markedly improved survival in people with AIDS-associated Kaposi sarcoma (a type of cancer caused by a virus), the condition is still a life-threatening problem in low- and middle-income countries.

New research led by researchers at Massachusetts General Hospital (MGH) with Ugandan and Kenyan colleagues published in The Lancet Global Health indicates that the best available chemotherapy for Kaposi sarcoma, which is infrequently used in Africa, would improve clinical outcomes and be cost-effective at its current price compared with therapies that are most frequently provided in the region.

For treating Kaposi sarcoma, different chemotherapy regimens vary in effectiveness, toxicity, and cost. Paclitaxel and pegylated liposomal doxorubicin (PLD) are the most effective and least toxic therapies, but they are more expensive than other options.

“Despite clinical guidelines that endorse the more effective and better tolerated chemotherapy regimens for Kaposi sarcoma, too many people with HIV are still treated with less effective chemotherapy because of logistics and cost,” says senior author Emily P. Hyle, MD, a physician-investigator at the Medical Practice Evaluation Center at Mass General and Assistant Professor of Medicine at Harvard Medical School.

Hyle and first author Esther Freeman, MD, PhD, Director of Clinical Innovation & Education for the Center for Global Health at Mass General and Associate Professor of Dermatology at Harvard Medical School, led an international collaboration to perform a cost-effectiveness analysis of different chemotherapy regimens for treating advanced Kaposi sarcoma in people with HIV on antiretroviral therapy in Kenya.

They found that paclitaxel would improve clinical outcomes and be very cost-effective at its current price compared with bleiomycin-vincristine, which is the most frequently used treatment for advanced Kaposi sarcoma in East Africa.

Over five years, using paclitaxel instead of bleomycin-vincristine to treat 19,150 people with HIV and advanced Kaposi sarcoma in Kenya would save 6,400 years-of-life and would increase cumulative healthcare expenditures by approximately $3.7 million, mostly from HIV-related costs due to a prolonged life expectancy among patients.

At current estimates, PLD would further extend life expectancy but would not be cost-effective compared with paclitaxel; however, this could be addressed if its price was reduced. “PLD is even better tolerated than paclitaxel, and our analysis showed that it would be cost-effective compared with paclitaxel if a 44% price reduction was achieved,” says Hyle.

At an individual level, paclitaxel would improve life expectancy by 4.2 years compared with bleomycin-vincristine, and PLD would improve life expectancy by an additional 0.6 years compared with paclitaxel.

“By encouraging hospitals, health systems, and others to reach for paclitaxel as first line treatment for HIV-associated Kaposi’s sarcoma, we can save lives. The majority of deaths from cancer in the world are in low and middle income countries, and it is our duty to advocate for the highest quality of care, which in this case, is also the most cost-effective,” says Freeman. “We also need to advocate for drug companies to reduce the price of effective chemotherapies in sub-Saharan Africa, similarly to what has been done for antiretroviral therapy pricing in the past, so that more people can have access to life-saving treatment.”

Additional study co-authors include, Nicole C. McCann, BA, Aggrey Semeere, MBChB, MMed, Krishna P. Reddy, MD, Miriam Laker-Oketta, MBChB, Helen Byakwaga, MBChB, PhD, Pamela P. Pei, PhD, Maya E. Hajny Fernandez, BA, Samson Kiprono, MBChB, MMed, Naftali Busakhala, MBChB, Jeffery N. Martin, MD, Toby Maurer, MD, Ingrid V. Bassett, MD, and Kenneth A. Freedberg, MD.

This work was supported by the National Institutes of Health, the Jerome and Celia Reich Endowed Scholar Award, and the Weissman Family MGH Research Scholar Award.

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Weather warning: Sunburn threat as Wales prepares for extreme heat

Mother warns of severe sunburn risk as weather warning extends to all of Wales for Monday and Tuesday.

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Covid booster: Will be offered to all over 50s this autumn

More people than originally planned will be offered the jab in the UK ahead of the coming winter.

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Archie Battersbee: Court rules life-support can end

A judge says continuing treatment for the 12-year-old is “futile”, but his family plans to appeal again.

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Rocking shadows in protoplanetary discs

Astronomers from the University of Warwick reveal a new phenomenon dubbed the “rocking shadow” effect that describes how discs in forming planetary systems are oriented, and how they move around their host star. The effect also gives clues as to how they might evolve with time. Dr Rebecca Nealon presented the new work this week at the 2022 National Astronomy Meeting at the University of Warwick.

Stars are born when a large cloud of gas and dust collapses in on itself. The leftover material that doesn’t make it into the star ends up circling around it, not unlike how water swirls around the drain before falling in. This swirling mass of gas and dust is called a protoplanetary disc, and it’s where planets like the Earth are born.

Protoplanetary discs are often thought to be shaped like dinner plates — thin, round and flat. However, recent telescope images from the Atacama Large Millimeter/Submillimeter Array (ALMA) show that this is not always the case. Some of the discs seen by ALMA have shadows on them, where the part of the disc closest to the star blocks some of the stellar light and casts a shadow onto the outer part of the disc. From this shadow pattern, it can be inferred that the inner part of the disc is oriented completely differently to the outer part, in what is called a broken disc.

In this research, the team used high performance computers to run three-dimensional simulations of a broken disc. The team then produced a mock observation, modelling what such a disc would look like if it were to be observed through a telescope, and how it would change over time.

As the inner disc moved through the gravitational pull of the central star, the shadow it cast moved across the outer disc. But instead of the shadow pattern moving around the disc like a clock-hand as expected, it rocked back and forth with a see-saw-like motion. So although the inside disc kept turning in the same direction, its shadow looked like it was rocking forwards and backwards. The team suggest this is caused by a geometric projection effect, which is likely to occur in all broken discs.

Our research is important because it bridges the gap between theory and observations. In the light of new observations from telescopes like JWST, our cutting-edge numerical techniques mean we have a variety of tools to interpret these data and to learn more about how planets are born.

Rebecca says: “JWST promises to give us a look at embryonic planetary systems in unprecedented detail, and with our new models we’ll be able to find out a lot more about the birth of planets.”

Video: https://youtu.be/jGYLuEx-I78

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Materials provided by Royal Astronomical Society. Note: Content may be edited for style and length.

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Deep dive into the dusty Milky Way

An animated dive into the dusty Milky Way reveals the outlines of our galaxy taking shape as we look out further and further from Earth.

Based on new data from an interactive tool that exploits data from the European Space Agency’s Gaia mission and other space science data sets, astronomers have created an animation to model dust in the Milky Way. The work was presented this week at the National Astronomy Meeting (NAM 2022) at the University of Warwick.

The animation shows the cumulative build-up of dust looking from Earth’s local neighbourhood to ~13000 lightyears towards the galactic centre — around 10% of the overall distance across the Milky Way. Close by, dust swirls all around but, further out, the concentration of dust along the galactic plane becomes clear. Two ‘windows’, one above and one below the galactic plane, are also revealed.

“Dust clouds are related to the formation and death of stars, so their distribution tells a story of how structures formed in the galaxy and how the galaxy evolves,” said Nick Cox, coordinator of the EXPLORE project which is developing the tools. “The maps are also important for cosmologists in revealing regions where there is no dust and we can have a clear, unobstructed view out of the Milky Way to study the Universe beyond, such as to make Deep Field observations with Hubble or the new James Webb Space Telescope.”

The tools used to create the animation combine data from the Gaia mission and the 2MASS All Sky Survey. The tools are part of a suite of applications designed to support studies of stars and galaxies, as well as lunar exploration, and have been developed through funding from the European Union’s Horizon 2020 Programme.

“State-of-the-art machine learning and visual analytics have the power to greatly enhance scientific return and discovery for space science missions, but their use is still relatively novel in the field of astronomy,” said Albert Zijlstra, of the University of Manchester and the EXPLORE project. “With a constant stream of new data, such as the recent third release of Gaia data in June 2022, we have an increasing wealth of information to mine — beyond the scope of what humans could process in a lifetime. We need tools like the ones we are developing for EXPLORE to support scientific discovery, such as by helping us to characterise properties within the data, or to pick out the most interesting or unusual features and structures.”

Video: https://youtu.be/K2hwjD5D7L0

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Materials provided by Royal Astronomical Society. Note: Content may be edited for style and length.

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