From single cells to complex creatures: New study points to origins of animal multicellularity

Researchers at UChicago analyze genetic data and protein sequences to find key innovations that allowed modern, multicellular animals to emerge

University of Chicago

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Animals, from worms and sponges to jellyfish and whales, contain anywhere from a few thousand to tens of trillions of nearly genetically identical cells. Depending on the organism, these cells arrange themselves into a variety of tissues and organs, such as a gut, muscles, and sensory systems. While not all animals have each of these tissues, they do all have one tissue, the germline, that produces sperm or eggs to propagate the species.

Scientists don’t completely understand how this kind of multicellularity evolved in animals. Cell-cell adhesion, or the ability for individual cells to stick to each other, certainly plays a role, but scientists already know that the proteins that serve these functions evolved in single-celled organisms, well before animal life emerged.

Now, research from the University of Chicago provides a new view into key innovations that allowed modern, multicellular animals to emerge. By analyzing the proteins predicted from the genomes of many animals (and close relatives to the animal kingdom), researchers found that animals evolved a more sophisticated mechanism for cell division that also contributes to developing multicellular tissues and the germline.

“This work strongly suggests that one of the early steps in the evolution of animals was the formation of the germline through the ability of cells to stay connected by incomplete cytokinesis,” said Michael Glotzer, PhD, Professor of Molecular Genetics and Cell Biology at UChicago and author of the new study. “The evolution of these three proteins allowed both multicellularity and the ability to form a germline: two of the key features of animals.”

Positioning the dividing line

Cell division, or cytokinesis, is the process by which a cell divides into two distinct daughter cells. Many of the proteins involved with cytokinesis are ancient, present long before the first Metazoa arose about 800 million years ago.

Glotzer has been studying animal cell division for several decades, focusing on how cells determine where to divide. In animal cells, a structure called the mitotic spindle segregates the chromosomes before the cells divide; it also dictates the position where cell division occurs. Glotzer and his team homed in on a set of three proteins—Kif23, Cyk4, and Ect2—that bind to each other and the spindle, and which are directly involved in establishing the division plane. Close relatives of these proteins had only been found previously in animals.

Two of these proteins, Kif23 and Cyk4, form a stable protein complex called centralspindlin that Glotzer and his colleagues discovered more than 20 years ago. Not only does centralspindlin contribute to division plane positioning, but it also generates a bridge between the two incipient daughter cells.

The cells that make up non-germline tissues and organs are called somatic cells, which are not passed on to the next generation. Germline cells are special because they can become any cell type. During the development of sperm and eggs, these cells also recombine the chromosomes they inherited from their parents, generating genetic diversity. While centralspindlin-dependent bridges are generally severed in somatic cells, the germlines of most animals have cells that remain connected by stable bridges.

Tracking down the proteins

Given the recent explosion in genome sequence data now available for a wide range of animals, Glotzer first wanted to determine if the two proteins that make up the centralspindlin complex, as well as Ect2, the regulatory protein that binds to it, were present and well conserved in all animals. During his analysis for this study, which was published in Current Biology, he found that all branches of animals have all three of these proteins.

Studies of these proteins in species commonly used in the lab discovered conserved sequence motifs that are linked to their known functions. Using Google DeepMind’s AlphaFold AI platform (developed by UChicago alum and recent Nobel Laureate John Jumper), he was able to predict the interactions among these different proteins and found that every interaction is likely conserved across all animals. This suggests that these proteins were all in place at the beginning of the animal kingdom more than 800 million years ago and have not undergone any dramatic changes since that time.

Next, Glotzer wondered whether any related proteins could be found in single-celled organisms. He identified somewhat related proteins in choanoflagellates, the group of single-celled creatures most closely related to animals. Alphafold predicted that some of them can form a complex somewhat like centralspindlin. Though related, these complexes are clearly distinct from centralspindlin, and they lack the sequences that allow Ect2 to bind to the structure. Remarkably, some choanoflagellate species that have this complex can form colonies via incomplete cytokinesis too.

“Pre-metazoan cells have mechanisms of dividing and separating, probably with some themes and variations. Then this protein complex allowed cells to stop at the stage just before separation,” Glotzer said. “Maybe multicellular life evolved because of a genetic change that prevented cells from fully separating.”

“A mutation that disrupted the assembly of centralspindlin is what allowed my colleagues and me to find these proteins in the first place, more than 25 years ago,” he continued. “And it appears that the evolution of this exact same region contributed to the evolution of animal life on the planet, which is mind blowing.”

The study, “A key role for centralspindlin and Ect2 in the development of multicellularity and the emergence of Metazoa” was supported by the National Institutes of Health.

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Journal

Current Biology

Method of Research

Computational simulation/modeling

Subject of Research

Cells

Article Title

A key role for centralspindlin and Ect2 in the development of multicellularity and the emergence of Metazoa

Article Publication Date

17-Jun-2025

 

Doctors need better guidance on AI

To avoid burnout and medical mistakes, health care organizations should train physicians in AI-assisted decision-making

University of Texas at Austin

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Artificial intelligence is everywhere — whether you know it or not. In many fields, AI is being touted as a way to help workers at all levels accomplish tasks, from routine to complicated. Not even physicians are immune.

But AI puts doctors in a bind, says Shefali Patil, associate professor of management at Texas McCombs, in a recent article. Health care organizations are increasingly pushing them to rely on assistive AI to minimize medical errors. But they lack direct support for how to use it.

The result, Patil says, is that physicians risk burnout, as society decides whom to hold accountable when AI is involved in medical decisions. Paradoxically, they also face greater chances of making medical mistakes. This interview has been edited for length and clarity.

Your article discusses the phenomenon of superhumanization. Unlike the rest of us, doctors are thought to have extraordinary mental, physical, and moral capacities, and they may be held to unrealistic standards. What pressures does this place on medical professionals?

AI is generally meant to aid and enhance clinical decisions. When an adverse patient outcome arises, who gets the blame? It’s up to the physician now to decide whether to take the machine’s recommendation and to anticipate what will happen if there’s an adverse patient result.

There are two possible types of errors — false positives and false negatives. The doctor has to determine if the illness is really bad and to do treatments that are potentially unnecessary, if it turns out to be a false positive. The other is a false negative, where the patient is super sick and the doctor doesn’t catch it.

The doctor has to figure out how to use AI software systems but has no control over the systems that the hospital buys. It all has to do with liability. There are no tight regulations around AI.

AI diagnoses, which are supposed to make doctors’ lives easier and reduce medical errors, are potentially having an opposite effect. Why?

The promise for AI is to alleviate some of the decision-making pressures on physicians. The promise is to make their jobs easier and lead to less burnout.

But these come with liability issues. AI vendors do not reveal the way the algorithms actually work. There’s limited transparency on how the algorithms are making a decision, so it’s difficult to calibrate when to use AI and when not to.

If you don’t use it, and there’s a mistake, you’ll be asked why you did not take the AI recommendation. Or, if AI makes a mistake, you’re held responsible, because it’s not a human being. That’s the tension.

What risks does this situation pose to patient care?

People want a physician who’s competent and decisive without feeling a sense of analysis paralysis because of information overload. Decision-making uncertainty and anxiety cause physicians to second-guess themselves. That leads to poor decision-making and, subsequently, poor patient care.

You predict that medical liability will depend on who people believe is at fault for a mistake. How could that expectation increase the risk of doctor burnout and mistakes?

Decision-making research suggests that people who suffer from performance anxiety and constantly second-guess themselves are not thinking logically through decisions. They’re questioning their own judgments.

That’s a very strong, accepted finding in the field of organizational behavior. It’s not specific to doctors, but we’re extrapolating to them.

What strategies can health care organizations use to alleviate those pressures and support physicians in using AI?

One of the big things that needs to be implemented with medical education is simulation training. It can be done as part of continuing education. It’s going to be very significant, because this is the future of medicine. There’s no turning back.

Learning how these systems actually work and understanding how they update and make a recommendation based on medical literature and past case outcomes is important in effective decision-making.

What do you mean when you write about a “regulatory gap?”

We mean that legal regulations always lag behind technological advances. You’re never going to be able to get fair and effective regulations that meet everybody’s interests. The liability risk always happens. The perception of blame is always after the fact. That’s why we’re trying to say the onus should be on administrators to help physicians deal with this issue.

Can you offer some practical advice for doctors, suggesting some do’s and don’ts for using AI assistance?

Right now, there is very little assistance from hospital administrators in teaching physicians how to calibrate the use of AI. More needs to be done.

Administrators need to implement more practical support that heavily relies on feedback from clinicians. At the moment, administrators don’t get that feedback. Performance outcomes, such as what was useful and what was not, need to be tracked.

“Calibrating AI Reliance – A Physician’s Superhuman Dilemma,” co-authored with Christopher Myers of Johns Hopkins University and Yemeng Lu-Myers of Johns Hopkins Medicine, is published in JAMA Health Forum.

 

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Journal

JAMA Health Forum

DOI

10.1001/jamahealthforum.2025.0106 

Article Title

Calibrating AI Reliance—A Physician’s Superhuman Dilemma

CARNIVORE STUDIES

Study identifies molecular markers related to meat quality in Nelore cattle

By combining different techniques, researchers at São Paulo State University in Brazil have revealed biological pathways related to tenderness, fat deposition, and other relevant characteristics of the meat of the predominant cattle breed in Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo

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Researchers at São Paulo State University (UNESP) in Brazil have identified a robust set of genetic markers associated with meat quality in the Nelore cattle breed (Bos taurus indicus) genome. The results pave the way for substantial progress in the genetic enhancement of the Zebu breed, which accounts for about 80% of the Brazilian beef herd. The research has direct implications for the productivity and quality of Brazilian beef, reinforcing the country’s standing as a major beef exporter. The results were published in the journal Scientific Reports.

In previous studies, the group had identified genes and proteins by studying meat and carcass characteristics separately using different techniques. For the current study, however, the researchers integrated these techniques and examined multiple characteristics using data from 6,910 young Nelore bulls from four commercial genetic improvement programs.

Because the biological material was collected immediately after slaughter, a comprehensive and detailed assessment of characteristics directly influencing meat quality was possible.

“The group had already made significant progress using different ‘omics’ [genomics, transcriptomics, and proteomics] approaches, but it became increasingly clear that no single technique is sufficient to understand the complexity of the biological systems that control variation in meat and carcass quality,” says Gabriela Frezarim, first author of the study. She conducted the study during her PhD at the Faculty of Agricultural and Veterinary Sciences (FCAV) at UNESP in Jaboticabal.

“By integrating these omics techniques, we were able to elucidate not only the isolated genes but also the biological networks involved in the variation of certain animal phenotypes,” adds the researcher, who was supervised by Lucia Galvão de Albuquerque, a professor at FCAV-UNESP. 

Albuquerque is coordinating the project “Genetic aspects of quality, efficiency, and sustainability of meat production in Nelore cattle”, which is supported by FAPESP. Some of the work was conducted during a previous project, which was also funded by the Foundation (read more at: agencia.fapesp.br/28157).

Largest exporter in the world

The results of the current study provide researchers with a series of accurate molecular data that can be used by the productive sector in the future to select animals that produce higher-quality meat and carcasses with a higher commercial yield.

Brazil leads the world in meat exports with 2.89 million tons in 2024. However, the Nelore zebu is known for having meat that is less tender than that of taurine breeds, such as the European Angus (Bos taurus taurus).

In recent years, other research groups have made progress in developing chips that can identify genetic variations associated with characteristics that are of interest for selecting Nelore cattle (read more at: revistapesquisa.fapesp.br/en/cattle-genes/). 

The present study goes further by investigating not only isolated genes, but also complex molecular networks related to extreme performance (high and low) in meat quality traits. The study emphasizes genes and metabolic pathways that explain the differences between individuals. These findings expand the possibilities for genetic selection.

“When working at the DNA level, there’s no guarantee that a particular variation in the genome will necessarily result in the production of a specific RNA or protein because there are complex biological processes involved in these stages that aren’t yet fully understood. Our study seeks to understand these pathways and identify the molecular basis of meat and carcass characteristic expression,” explains Larissa Fonseca, co-supervisor of the study. She is a postdoctoral researcher at FCAV-UNESP and a FAPESP scholarship recipient.

From muscle to meat

“Understanding the molecular mechanisms that influence meat and carcass quality is essential to explaining the phenotypic variability observed in Nelore cattle. The study offers an integrated view of the biological pathways involved in these characteristics and identifies genes and proteins that directly affect tenderness, marbling, and subcutaneous fat thickness,” says Lúcio Mota, another co-author of the study who is conducting postdoctoral research at FCAV-UNESP with a scholarship from FAPESP.

The researcher explains that this approach provides clear molecular bases for the phenotypic differences observed between animals, allowing for more precise selection strategies in genetic improvement.

For example, the researchers found that genes associated with growth, cell cycle regulation, and heat shock proteins are directly linked to meat tenderness.

These proteins maintain muscle structure and control fiber degradation after slaughter, which directly impacts meat tenderness. The expression levels of these genes and proteins differ between cattle, which helps explain why some Nelore cattle have more tender meat, as they favor a more efficient breakdown of muscle fibers after slaughter.

Another conclusion was that genes, transcripts, and proteins involved in organizing the cytoskeleton (the structure that maintains cell shape) and in programmed cell death (apoptosis) directly influence muscle development and consequently the loin eye area (LEA). LEA is an international measure that indicates muscle mass and carcass yield.

Regarding marbling, the intramuscular fat responsible for the flavor and juiciness of meat, proteins related to fatty acid synthesis and composition were identified, along with proteins involved in actin binding and microtubule formation, which are essential for various cellular functions. These findings suggest that the regulation of these proteins may directly impact intramuscular fat deposition, thereby influencing the sensory quality of meat.

Finally, genes associated with the regulation of energy metabolism and muscle tissue remodeling were identified as important for subcutaneous fat thickness, which is a relevant measure of carcass quality.

“This is an initial study, but it provides important guidelines for genetic improvement programs and the development of more effective selection strategies in Nelore cattle for meat and carcass traits,” says Albuquerque.

The researchers now plan to expand their analyses to achieve an even higher level of accuracy. This could allow them to more accurately select animals that will directly improve the quality of Brazilian beef.

About São Paulo Research Foundation (FAPESP)
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.
 

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Journal

Scientific Reports

DOI

10.1038/s41598-025-93714-x 

Article Title

Multi-omics integration identifies molecular markers and biological pathways for carcass and meat quality traits in Nellore cattle

Chronic pain hits US rural residents hardest

Pain may explain higher opioid use in rural areas, UTA study finds

University of Texas at Arlington

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A new study from The University of Texas at Arlington reveals that people who live in rural areas are more likely to have chronic pain than those in urban settings. They’re also more likely to go from having no pain or occasional pain to chronic pain. The findings may help explain higher opioid prescription rates in rural communities and could guide future research into the root causes of this disparity.

“We already know about the rural-urban gap in mortality and life expectancy,” said Feinuo Sun, UT Arlington assistant professor of kinesiology and lead author of the study in The Journal of Rural Health. “But when you look at pain, especially chronic pain, it becomes clear that rural residents face additional burdens.”

Chronic pain has been previously linked to higher risks of disability and mortality and contributes to increased health care costs—an estimated $261 billion and $300 billion annually in the U.S. One key takeaway from Dr. Sun’s study is the importance of timely intervention for middle-aged adults in rural communities as they are among the most vulnerable to developing chronic pain.

“Without early intervention, it can have serious long-term consequences, including premature mortality,” Sun said. “That’s why targeted outreach and early pain management strategies are so important.”

In her research, Sun, who has expertise in demography and population health, uses national data and a spatial analysis approach—a way of mapping how factors like health care services, job types and regional economic conditions shape health outcomes depending on where people live. In a 2024 study she authored, she found that rural residents expect to live more years with chronic pain than suburban and urban residents.

Sun’s latest findings suggest the chronic pain disparities are not solely due to limited access to health care in rural communities. Rural residents are more likely to work physically demanding jobs and experience higher poverty rates, both of which contribute to chronic pain. Elevated pain levels, along with fewer treatment options, may help explain the heavier reliance on opioids in these communities.

Sun’s research seeks to distinguish the root causes for higher opioid demand in rural areas.

“The goal for future research is to understand the causes of these disparities and to examine how differences in pain treatment between rural and urban areas contribute to the overall pain gap,” she said.

About The University of Texas at Arlington (UTA)

Celebrating its 130th anniversary in 2025, The University of Texas at Arlington is a growing public research university in the heart of the thriving Dallas-Fort Worth metroplex. With a student body of over 41,000, UTA is the second-largest institution in the University of Texas System, offering more than 180 undergraduate and graduate degree programs. Recognized as a Carnegie R-1 university, UTA stands among the nation’s top 5% of institutions for research activity. UTA and its 280,000 alumni generate an annual economic impact of $28.8 billion for the state. The University has received the Innovation and Economic Prosperity designation from the Association of Public and Land Grant Universities and has earned recognition for its focus on student access and success, considered key drivers to economic growth and social progress for North Texas and beyond.

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Journal

The Journal of Rural Health

DOI

10.1111/jrh.70036 

Method of Research

News article

Subject of Research

People

Article Title

Development of chronic pain and high-impact chronic pain across the US rural–urban continuum, 2019–2020

Aquatic therapy can heal the muscles and minds of people with chronic low back pain

A Concordia study finds a link between spinal muscle morphology and pain-related fears, anxiety and sleep quality

Concordia University

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image: 

Maryse Fortin: “Aquatic therapy is an interesting medium to study people who have pain-related fear like kinesiophobia and pain catastrophizing, and how those relate to spinal musculature.”

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Credit: Concordia University

A new Concordia study suggests that aquatic therapy for individuals with chronic low back pain can do more than strengthen the muscles around the spine. It can also have a beneficial impact on the negative psychological factors that are often associated with the disabling disease.

The study used a randomized controlled trial involving two groups of chronic low back pain patients. It found that participants who took part in aquatic therapy reported improvements in pain-related fear and sleep disturbance compared to those who followed standard care programs.

The authors believe that this study shows preliminary evidence that links aquatic therapy with improved psychological outcomes for individuals with low back pain. Their findings were published in the Nature journal Scientific Reports.

“Getting into water makes people feel better right away, because it takes away loading on the spine,” says corresponding author Maryse Fortin, an associate professor in the Department of Health, Kinesiology and Applied Physiology.

“This made aquatic therapy an interesting medium to study people who have pain-related fear like kinesiophobia (the fear of movement stemming from a fear of pain or injury) and pain catastrophizing, and how those relate to spinal musculature.”

Stronger backs and healthier lives

The study looked at two groups of 17 participants (34 total) with chronic low back pain. They were randomly assigned to either an aquatic exercise program or to a standard treatment program for low back pain. Both were supervised by graduate students who are also certified athletic therapists, at Concordia’s SwimEx pool or the School of Health Athletic Therapy Centre.

Participants attended two sessions weekly for 10 weeks where they engaged either in a standard treatment (which included land-based exercises) or in a standardized aquatic therapy strengthening program focusing on exercises targeting the torso and hips. They also completed questionnaires about pain, disability, quality of life, pain-related fears, depression, anxiety and sleep quality.

All participants completed their questionnaires and underwent strength tests and MRI scanning before their first session and again after the last one following the 10-week program.

The aquatic therapy group showed significant increase in muscle size in the multifidus and the erector spinae in the upper spine, two sets of spinal muscles that are crucial to spinal stabilization. However, the increases were not noted in the lower lumbar spine, which is most subject to muscle fatty intrusions and degradation and is considered the most problematic area for people with low back pain.

Both the aquatic and standard care groups showed marked improvements in mean and maximum lumbar strength.

“Combined with the reduction in anxiety, pain-based fears and sleep disturbances, these make for really interesting findings, and we definitely need to look at that relationship more closely,” Fortin says. “The changes were clinically significant, not just statistically significant, meaning they have a true impact on how the participants feel.”

The study’s lead author is Brent Rosenstein, PhD 25. Co-authors include Chanelle Montpetit, Nicolas Vaillancourt, Geoffrey Dover, Christina Weiss, Lee Ann Papula and Antonys Melek.

The study received support from the Fonds de recherche du Québec - Santé and from the R. Howard Webster Foundation.

Read the cited paper: “Aquatic exercise versus standard care on paraspinal muscle morphology and function in chronic low back pain patients: a randomized controlled trial.”

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Journal

Scientific Reports

DOI

10.1038/s41598-025-00210-3 

Method of Research

Randomized controlled/clinical trial

Subject of Research

People

Article Title

Aquatic exercise versus standard care on paraspinal muscle morphology and function in chronic low back pain patients: a randomized controlled trial