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Study finds widespread ‘cell cannibalism,’ related phenomena across tree of life

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Study finds widespread ‘cell cannibalism,’ related phenomena across tree of life


In a new review paper, Carlo Maley and Arizona State University colleagues describe cell-in-cell phenomena in which one cell engulfs and sometimes consumes another. The study shows that cases of this behavior, including cell cannibalism, are widespread across the tree of life.

The findings challenge the common perception that cell-in-cell events are largely restricted to cancer cells. Rather, these events appear to be common across diverse organisms, from single-celled amoebas to complex multicellular animals.

The widespread occurrence of such interactions in non-cancer cells suggests that these events are not inherently “selfish” or “cancerous” behaviors. Rather, the researchers propose that cell-in-cell phenomena may play crucial roles in normal development, homeostasis and stress response across a wide range of organisms.

The study argues that targeting cell-in-cell events as an approach to treating cancer should be abandoned, as these phenomena are not unique to malignancy.

By demonstrating that occurrences span a wide array of life forms and are deeply rooted in our genetic makeup, the research invites us to reconsider fundamental concepts of cellular cooperation, competition and the intricate nature of multicellularity. The study opens new avenues for research in evolutionary biology, oncology and regenerative medicine.

The new research, published in the Nature journal Scientific Reports, is the first to systematically investigate cell-in-cell phenomena across the tree of life. The group’s findings could help redefine the understanding of cellular behavior and its implications for multicellularity, cancer and the evolutionary journey of life itself.

“We first got into this work because we learned that cells don’t just compete for resources — they actively kill and eat each other,” Maley says. “That’s a fascinating aspect of the ecology of cancer cells. But further exploration revealed that these phenomena happen in normal cells, and sometimes neither cell dies, resulting in an entirely new type of hybrid cell.”

Maley is a researcher with the Biodesign Center for Biocomputing, Security and Society; professor in the School of Life Sciences at ASU; and director of the Arizona Cancer Evolution Center.

The study was conducted in collaboration with first author Stefania E. Kapsetaki, formerly with ASU and now a researcher at Tufts University, and Luis Cisneros, formerly with ASU and currently a researcher at Mayo Clinic.

From selfish to cooperative cell interactions

Cell-in-cell events have long been observed but remain poorly understood, especially outside the context of immune responses or cancer. The earliest genes responsible for cell-in-cell behavior date back over 2 billion years, suggesting the phenomena play an important, though yet-to-be-determined, role in living organisms. Understanding the diverse functions of cell-in-cell events, both in normal physiology and disease, is important for developing more effective cancer therapies.

The review delves into the occurrence, genetic underpinnings and evolutionary history of cell-in-cell phenomena, shedding light on a behavior once thought to be an anomaly. The researchers reviewed more than 500 articles to catalog the various forms of cell-in-cell phenomena observed across the tree of life.

The study describes 16 different taxonomic groups in which cell-in-cell behavior is found to occur. The cell-in-cell events were classified into six distinct categories based on the degree of relatedness between the host and prey cells, as well as the outcome of the interaction (whether one or both cells survived).

A spectrum of cell-in-cell behaviors are highlighted in the study, ranging from completely selfish acts, where one cell kills and consumes another, to more cooperative interactions, where both cells remain alive. For example, the researchers found evidence of “heterospecific killing,” where a cell engulfs and kills a cell of a different species, across a wide range of unicellular, facultatively multicellular, and obligate multicellular organisms. In contrast, “conspecific killing,” where a cell consumes another cell of the same species, was less common, observed in only three of the seven major taxonomic groups examined.

Obligate multicellular organisms are those that must exist in a multicellular form throughout their life cycle. They cannot survive or function as single cells. Examples include most animals and plants. Facultative multicellular organisms are organisms that can exist either as single cells or in a multicellular form depending on environmental conditions. For example, certain types of algae may live as single cells in some conditions but form multicellular colonies in others.

The team also documented cases of cell-in-cell phenomena where both the host and prey cells remained alive after the interaction, suggesting these events may serve important biological functions beyond just killing competitors.

“Our categorization of cell-in-cell phenomena across the tree of life is important for better understanding the evolution and mechanism of these phenomena,” Kapsetaki says. “Why and how exactly do they happen? This is a question that requires further investigation across millions of living organisms, including organisms where cell-in-cell phenomena may not yet have been searched for.”

Ancient genes

In addition to cataloging the diverse cell-in-cell behaviors, the researchers also investigated the evolutionary origins of the genes involved in these processes. Surprisingly, they found that many of the key cell-in-cell genes emerged long before the evolution of obligate multicellularity.

“When we look at genes associated with known cell-in-cell mechanisms in species that diverged from the human lineage a very long time ago, it turns out that the human orthologs (genes that evolved from a common ancestral gene) are typically associated with normal functions of multicellularity, like immune surveillance,” Cisneros says.

In total, 38 genes associated with cell-in-cell phenomena were identified, and 14 of these originated over 2.2 billion years ago, predating the common ancestor of some facultatively multicellular organisms. This suggests that the molecular machinery for cell cannibalism evolved before the major transitions to complex multicellularity.

The ancient cell-in-cell genes identified in the study are involved in a variety of cellular processes, including cell-cell adhesion, phagocytosis (engulfment), intracellular killing of pathogens and regulation of energy metabolism. This diversity of functions indicates that cell-in-cell events likely served important roles even in single-celled and simple multicellular organisms well before the emergence of complex multicellular life.



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Paleontology: New fossil fish genus discovered

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Paleontology: New fossil fish genus discovered


Gobies or Gobioidei are one of the most species-rich groups of marine and freshwater fish in Europe. Spending most of their lives on the bottom of shallow waterbodies, they make substantial contributions to the functioning of many ecosystems. With the identification of a new genus of a fossil freshwater goby, students of the international master program ‘Geobiology and Paleobiology’ at LMU and paleontologist Bettina Reichenbacher, professor at the Department of Earth and Environmental Sciences at LMU, have made a discovery that provides critical insights into the evolutionary history of these fish.

Measuring up to 34 mm, the small fish of the new genus †Simpsonigobius were discovered in 18-million-year-old rocks in Turkey and are marked by a distinct combination of morphological features, including otoliths (hearing stones) with a unique shape.

Modern research techniques elucidate position in family tree

To determine the relationships of †Simpsonigobius within the gobioid phylogenetic tree, the researchers utilized a “total-evidence” phylogenetic dataset, which they enhanced in order to combine a total of 48 morphological characters and genetic data from five genes for 48 living and 10 fossil species. In addition, the team employed “tip-dating” for fossil gobioid species for the first time. This is a phylogenetic method in which the age of the fossils (= tips) included in the phylogenetic tree is used to infer the timing of the evolutionary history of the entire group.

The results show that the new genus is the oldest skeleton-based member of the family Oxudercidae — which is classified among the “modern” gobies (families Gobiidae and Oxudercidae) — and the oldest freshwater goby within this modern group. The tip-dating analysis estimated the emergence of the Gobiidae at 34.1 million years ago and that of the Oxudercidae at 34.8 million years ago, which is consistent with previous dating studies using other methods. Moreover, stochastic habitat mapping, in which the researchers incorporated fossil gobies for the first time, revealed that the gobies probably possessed broad salinity tolerance at the beginning of their evolutionary history, which challenges previous assumptions.

“The discovery of †Simpsonigobius not only adds a new genus to the Gobioidei, but also provides vital clues about the evolutionary timeline and habitat adaptations of these diverse fishes. Our research highlights the importance of analyzing fossil records using modern methods to achieve a more accurate picture of evolutionary processes,” says Reichenbacher. First author Moritz Dirnberger, currently a doctoral candidate at the University of Montpellier, adds: “The findings are expected to pave the way for further studies on gobioid evolution and the role of environmental factors in shaping their diversity.”



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Ancient ocean slowdown warns of future climate chaos

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Ancient ocean slowdown warns of future climate chaos


When it comes to the ocean’s response to global warming, we’re not in entirely uncharted waters. A UC Riverside study shows that episodes of extreme heat in Earth’s past caused the exchange of waters from the surface to the deep ocean to decline.

This system has been described as the “global conveyer belt,” because it redistributes heat around the globe through the movement of the ocean waters, making large portions of the planet habitable.

Using tiny, fossilized shells recovered from ancient deep-sea sediments, the study in the Proceedings of the National Academy of Sciences demonstrates how the conveyor belt responded around 50 million years ago. At that time, Earth’s climate resembled conditions predicted by the end of this century, if significant action is not taken to reduce carbon emissions.

Oceans play a crucial role in regulating Earth’s climate. They move warm water from the equator toward the north and south poles, balancing the planet’s temperatures. Without this circulation system, the tropics would be much hotter and the poles much colder. Changes in this system are linked to significant and abrupt climate change.

Furthermore, the oceans serve a critical role in removing anthropogenic carbon dioxide from the atmosphere. “The oceans are by far the largest standing pool of carbon on Earth’s surface today,” said Sandra Kirtland Turner, vice-chair of UCR’s Department of Earth and Planetary Sciences and first author of the study.

“Today, the oceans contain nearly 40,000 billion tons of carbon — more than 40 times the amount of carbon in the atmosphere. Oceans also take up about a quarter of anthropogenic CO2 emissions,” Kirtland Turner said. “If ocean circulation slows, absorption of carbon into the ocean may also slow, amplifying the amount of CO2 that stays in the atmosphere.”

Previous studies have measured changes in ocean circulation in Earth’s more recent geologic past, such as coming out of the last ice age; however, those do not approximate the levels of atmospheric CO2 or warming happening to the planet today. Other studies provide the first evidence that deep ocean circulation, particularly in the North Atlantic, is already starting to slow.

To better predict how ocean circulation responds to greenhouse gas-driven global warming, the research team looked to the early Eocene epoch, between roughly 49 and 53 million years ago. Earth then was much warmer than today, and that high-heat baseline was punctuated by spikes in CO2 and temperature called hyperthermals.

During that period, the deep ocean was up to 12 degrees Celsius warmer than it is today. During the hyperthermals, the oceans warmed an additional 3 degrees Celsius.

“Though the exact cause of the hyperthermal events is debated, and they occurred long before the existence of humans, these hyperthermals are the best analogs we have for future climate change,” Kirtland Turner said.

By analyzing tiny fossil shells from different sea floor locations around the globe, the researchers reconstructed patterns of deep ocean circulation during these hyperthermal events. The shells are from microorganisms called foraminifera, which can be found living throughout the world’s oceans, both on the surface and on the sea floor. They are about the size of a period at the end of a sentence.

“As the creatures are building their shells, they incorporate elements from the oceans, and we can measure the differences in the chemistry of these shells to broadly reconstruct information about ancient ocean temperatures and circulation patterns,” Kirtland Turner said.

The shells themselves are made of calcium carbonate. Oxygen isotopes in the calcium carbonate are indicators of temperatures in the water the organisms grew in, and the amount of ice on the planet at the time.

The researchers also examined carbon isotopes in the shells, which reflect the age of the water where the shells were collected, or how long water has been isolated from the ocean surface. In this way, they can reconstruct patterns of deep ocean water movement.

Foraminifera can’t photosynthesize, but their shells indicate the impact of photosynthesis of other organisms nearby, like phytoplankton. “Photosynthesis occurs in the surface ocean only, so water that has recently been at the surface has a carbon-13 rich signal that is reflected in the shells when that water sinks to the deep ocean,” Kirtland Turner said.

“Conversely, water that has been isolated from the surface for a long time has built up relatively more carbon-12 as the remains of photosynthetic organisms sink and decay. So, older water has relatively more carbon-12 compared to ‘young’ water.”

Scientists often make predictions about ocean circulation today using computer climate models. They use these models to answer the question: ‘how is the ocean going to change as the planet keeps warming?’ This team similarly used models to simulate the ancient ocean’s response to warming. They then used the foraminifera shell analysis to help test results from their climate models.

During the Eocene, there were about 1,000 parts per million (ppm) of carbon dioxide in the atmosphere, which contributed to that era’s high temperatures. Today, the atmosphere holds about 425 ppm.

However, humans emit nearly 37 billion tons of CO2 into the atmosphere each year; if these emission levels continue, similar conditions to the Early Eocene could occur by the end of this century.

Therefore, Kirtland Turner argues it is imperative to make every effort to reduce emissions.

“It’s not an all-or-nothing situation,” she said. “Every incremental bit of change is important when it comes to carbon emissions. Even small reductions of CO2 correlate to less impacts, less loss of life, and less change to the natural world.”



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Pacific coast gray whales have gotten 13% shorter in the past 20-30 years, Oregon State study finds

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Pacific coast gray whales have gotten 13% shorter in the past 20-30 years, Oregon State study finds


Gray whales that spend their summers feeding in the shallow waters off the Pacific Northwest coast have undergone a significant decline in body length since around the year 2000, a new Oregon State University study found.

The smaller size could have major consequences for the health and reproductive success of the affected whales, and also raises alarm bells about the state of the food web in which they coexist, researchers say.

“This could be an early warning sign that the abundance of this population is starting to decline, or is not healthy,” said K.C. Bierlich, co-author on the study and an assistant professor at OSU’s Marine Mammal Institute in Newport. “And whales are considered ecosystem sentinels, so if the whale population isn’t doing well, that might say a lot about the environment itself.”

The study, published in Global Change Biology, looked at the Pacific Coast Feeding Group (PCFG), a small subset of about 200 gray whales within the larger Eastern North Pacific (ENP) population of around 14,500. This subgroup stays closer to shore along the Oregon coast, feeding in shallower, warmer waters than the Arctic seas where the bulk of the gray whale population spends most of the year.

Recent studies from OSU have shown that whales in this subgroup are smaller and in overall worse body condition than their ENP counterparts. The current study reveals that they’ve been getting smaller in recent decades.

The Marine Mammal Institute’s Geospatial Ecology of Marine Megafauna (GEMM) Lab has been studying this subgroup of gray whales since 2016, including flying drones over the whales to measure their size. Using images from 2016-2022 of 130 individual whales with known or estimated age, researchers determined that a full-grown gray whale born in 2020 is expected to reach an adult body length that is 1.65 meters (about 5 feet, 5 inches) shorter than a gray whale born prior to 2000. For PCFG gray whales that grow to be 38-41 feet long at full maturity, that accounts for a loss of more than 13% of their total length.

If the same trend were to happen in humans, that would be like the height of the average American woman shrinking from 5 feet, 4 inches to 4 feet, 8 inches tall over the course of 20 years.

“In general, size is critical for animals,” said Enrico Pirotta, lead author on the study and a researcher at the University of St. Andrews in Scotland. “It affects their behavior, their physiology, their life history, and it has cascading effects for the animals and for the community they’re a part of.”

Whale calves that are smaller at weaning age may be unable to cope with the uncertainty that comes with being newly independent, which can affect survival rates, Pirotta said.

For adult gray whales, one of the biggest concerns is reproductive success.

“With them being smaller, there are questions of how effectively these PCFG gray whales can store and allocate energy toward growing and maintaining their health. Importantly, are they able to put enough energy toward reproduction and keep the population growing?” Bierlich said.

Scarring on PCFG whales from boat strikes and fishing gear entanglement also makes the team concerned that smaller body size with lower energy reserves may make the whales less resilient to injuries.

The study also examined the patterns of the ocean environment that likely regulate food availability for these gray whales off the Pacific coast by tracking cycles of “upwelling” and “relaxation” in the ocean. Upwelling sweeps nutrients from deeper to shallower regions, while relaxation periods then allow those nutrients to remain in shallower areas where light allows for growth of plankton and other tiny organisms, including the prey of gray whales.

“Without a balance between upwelling and relaxation, the ecosystem may not be able to produce enough prey to support the large size of these gray whales,” said co-author Leigh Torres, associate professor and director of the GEMM Lab at OSU.

The data show that whale size declined concurrently with changes in the balance between upwelling and relaxation, Pirotta said.

“We haven’t looked specifically at how climate change is affecting these patterns, but in general we know that climate change is affecting the oceanography of the Northeast Pacific through changes in wind patterns and water temperature,” he said. “And these factors and others affect the dynamics of upwelling and relaxation in the area.”

Now that they know the PCFG gray whales’ body size is declining, researchers say they have a lot of new questions about downstream consequences of that decline and the factors that could be contributing to it.

“We’re heading into our ninth field season studying this PCFG subgroup,” Bierlich said. “This is a powerful dataset that allows us to detect changes in body condition each year, so now we’re examining the environmental drivers of those changes.”

The other co-authors on the paper were Lisa Hildebrand, Clara Bird and Alejandro Ajó at OSU and Leslie New at Ursinus College in Pennsylvania.



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