Research on this ancient ancestor shows that many features seen in modern life were already in place at that time. Cells already had membranes, and genetic information was stored in DNA. Because these essential traits were already established, scientists seeking to understand how life first took shape must look even further back in time, to evolutionary events that occurred before this shared ancestor existed.

Studying Life Before the First Common Ancestor

In a study published in the journal Cell Genomics, researchers Aaron Goldman (Oberlin College), Greg Fournier (MIT), and Betül Kaçar (University of Wisconsin-Madison) describe a way to explore that earlier period of evolution. “While the last universal common ancestor is the most ancient organism we can study with evolutionary methods,” said Goldman, “some of the genes in its genome were much older.” The team focuses on a special group of genes called “universal paralogs,” which preserve evidence of biological changes that took place before the last universal common ancestor.

A paralog is a group of related genes that appear multiple times within a single genome. Humans provide a clear example. Our DNA contains eight different hemoglobin genes, all of which produce proteins that carry oxygen through the blood. These genes all originated from a single ancestral globin gene that existed around 800 million years ago. Over long periods of time, repeated copying errors produced extra versions of the gene, and each copy gradually developed its own specialized role.

What Makes Universal Paralogs Unique

Universal paralogs are much rarer. These gene families appear in at least two copies in the genomes of nearly all living organisms. Their widespread presence suggests that the original gene duplication occurred before the last universal common ancestor emerged. Those duplicated genes were then passed down through countless generations and remain present in life today.

Because of this deep evolutionary reach, the authors argue that universal paralogs are a critical yet often overlooked resource for studying the earliest history of life on Earth. This approach is becoming more practical as new AI-based techniques and AI-optimized hardware make it easier to analyze ancient genetic patterns in detail.

“While there are precious few universal paralogs that we know,” says Goldman, “they can give us a lot of information about what life was like before the time of the last universal common ancestor.” Fournier adds, “The history of these universal paralogs is the only information we will ever have about these earliest cellular lineages, and so we need to carefully extract as much knowledge as we can from them.”

Clues to the First Cellular Functions

In their analysis, Goldman, Fournier, and Kaçar reviewed all known universal paralogs. Every one of these genes plays a role in either building proteins or moving molecules across cell membranes. This finding suggests that protein production and membrane transport were among the first biological functions to evolve.

The researchers also emphasize the importance of reconstructing the ancient forms of these genes. In one study from Goldman’s lab at Oberlin, scientists examined a universal paralog family involved in inserting enzymes and other proteins into cell membranes. Using standard methods from evolutionary biology and computational biology, they reconstructed the protein produced by the original ancestral gene.

Their results showed that this simpler, ancient protein could still attach to cell membranes and interact with the machinery that makes proteins. It likely helped early proteins embed themselves into primitive membranes, offering insight into how the earliest cells may have operated.

A New Window Into Life’s Earliest History

The authors hope that continued advances in computational tools will allow scientists to identify additional universal paralog families and study their ancient ancestors in greater detail. “By following universal paralogs,” says Kaçar, “we can connect the earliest steps of life on Earth to the tools of modern science. They provide us a chance to transform the deepest unknowns of evolution and biology into discoveries we can actually test.” Their goal is to build a clearer picture of evolution before the last universal common ancestor, shedding light on how life as we know it first emerged.

Nanopores are extremely small openings that allow single strands of DNA to pass through while producing electrical signals. These signals help researchers analyze genetic material in detail. Until now, important features of those signals had been misunderstood.

Why Scientists Thought DNA Was Forming Knots

For many years, researchers believed that complex electrical patterns seen during nanopore experiments were caused by DNA forming knots. The idea was easy to picture. Pulling a shoelace through a narrow hole becomes uneven if the lace tangles, and scientists assumed DNA behaved in the same way. Any irregular signal was thought to mean the strand had knotted as it moved through the pore.

That explanation shaped how nanopore data was interpreted for decades.

Twists, Not Knots, Explain the Signals

The new study, published in Physical Review X, shows that this long-standing assumption was often wrong. Instead of forming true knots, DNA frequently twists around itself during nanopore translocation. These twisted structures, known as plectonemes, resemble a coiled phone cord rather than a tied knot.

This distinction matters because twists and knots affect electrical signals in very different ways.

“Our experiments showed that as DNA is pulled through the nanopore, the ionic flow inside twists the strand, accumulating torque and winding it into plectonemes, not just knots. This ‘hidden’ twisting structure has a distinctive, long-lasting fingerprint in the electrical signal, unlike the more transient signature of knots,” explained lead author Dr Fei Zheng from the Cavendish Laboratory.

Experiments Point to a Missing Mechanism

To reach this conclusion, the researchers tested DNA using both glass and silicon nitride nanopores across a wide range of voltages and conditions. They noticed that so-called “tangled” events, when more than one section of DNA occupied the pore at the same time, occurred far more often than knot theory could explain.

These events became even more frequent as voltage increased and as DNA strands grew longer. This pattern suggested that another force was at work.

How Flowing Water Twists DNA

The team found that the twisting comes from electroosmotic flow, the movement of water driven by electric fields inside the nanopore. As water flows past the DNA, it applies a spinning force to the helical molecule. This torque travels along the strand, causing sections outside the pore to coil into plectonemes.

Unlike knots, which tighten under pulling forces and typically disappear quickly, plectonemes can grow larger and remain present throughout the entire translocation process. Computer simulations that applied realistic forces and torques confirmed this behavior and showed that plectoneme formation depends on DNA’s ability to transmit twist along its length.

Blocking Twists Confirms the Discovery

To test the idea further, the researchers created “nicked” DNA, strands that were interrupted at specific points. These interruptions prevented twist from spreading along the molecule and sharply reduced the formation of plectonemes during experiments.

This result confirmed that twist propagation is essential to the process. It also hints at new ways nanopores could be used to detect DNA damage, since breaks in the strand interfere with twisting behavior.

Reading DNA Signals With New Precision

“What’s really powerful here is that we can now tell apart knots and plectonemes in the nanopore signal based on how long they last,” says Prof Ulrich F. Keyser, also from the Cavendish Laboratory and a co-author of the study.

“Knots pass through quickly, just like a quick bump, whereas plectonemes linger and create extended signals. This offers a path to richer, more nuanced readouts of DNA organization, genomic integrity, and possibly damage.”

Broader Implications for Biology and Technology

The findings extend beyond nanopore sensing. In living cells, DNA regularly twists and tangles as enzymes act on it, and both knots and plectonemes play important roles in genome organization and stability. Understanding how these structures form could improve models of cellular DNA behavior.

For diagnostics and biosensing, the ability to detect or control DNA twisting could lead to more sensitive tools capable of identifying subtle genetic changes and early signs of DNA damage linked to disease.

“From the perspective of nanotechnology, the research highlights the power of nanopores, not only as sophisticated sensors but also as tools for manipulating biopolymers in novel ways,” concluded Keyser.

Researchers observed lower rates of stroke overall among women who most closely followed the Mediterranean diet. This included both ischemic strokes and hemorrhagic strokes. Ischemic strokes occur when blood flow to part of the brain is blocked and are the most common form of stroke. Hemorrhagic strokes happen when a blood vessel ruptures and causes bleeding in the brain.

What Defines the Mediterranean Diet

The Mediterranean diet centers on eating plenty of vegetables, fruits, legumes, and fish, along with healthy fats such as olive oil. It limits foods like dairy products, meat, and items high in saturated fatty acids.

“Our findings support the mounting evidence that a healthy diet is critical to stroke prevention,” said study author Sophia S. Wang, PhD, of City of Hope Comprehensive Cancer Center in Duarte, California. “We were especially interested to see that this finding applies to hemorrhagic stroke, as few large studies have looked at this type of stroke.”

How the Study Followed More Than 100,000 Women

The study included 105,614 women who had no history of stroke at the beginning of the research and an average age of 53. Each participant completed a detailed diet questionnaire at the start of the study. Researchers then assigned a score ranging from zero to nine based on how closely each person’s diet matched Mediterranean diet guidelines.

Participants earned one point for consuming more than the population average of whole grain cereals, fruits, vegetables, legumes, olive oil, and fish, as well as for drinking a moderate amount of alcohol. They also earned a point for eating less red meat and dairy than average. About 30% of participants scored between six and nine — the highest group. Another 13% scored between zero and two, placing them in the lowest group.

Stroke Outcomes Over 21 Years

Participants were monitored for an average of 21 years. During that period, researchers recorded 4,083 strokes, including 3,358 ischemic strokes and 725 hemorrhagic strokes. Among women in the highest diet score group, 1,058 ischemic strokes occurred, compared with 395 cases in the lowest group. For hemorrhagic stroke, 211 cases were reported in the highest group and 91 in the lowest group.

After accounting for other stroke risk factors such as smoking, physical activity, and high blood pressure, the differences remained significant. Women with the highest Mediterranean diet scores were 18% less likely to experience any stroke than those with the lowest scores. Their risk of ischemic stroke was 16% lower, and their risk of hemorrhagic stroke was 25% lower.

Why the Findings Matter and Study Limitations

“Stroke is a leading cause of death and disability, so it’s exciting to think that improving our diets could lessen our risk for this devastating disease,” said Wang. “Further studies are needed to confirm these findings and to help us understand the mechanisms behind them so we could identify new ways to prevent stroke.”

One limitation of the study is that dietary information was self reported, which means some participants may not have recalled their eating habits accurately.

The research was funded by the National Institute of Neurological Diseases and Stroke.

A new study led by Nagoya University now sheds light on this long-standing mystery. The research, published in Science Advances, shows that ovarian cancer cells do not act alone. Instead, they enlist help from mesothelial cells, which normally serve as a protective lining inside the abdominal cavity. These mesothelial cells move ahead of the cancer cells, creating pathways that cancer cells then follow. Together, they form hybrid cell clusters that are more resistant to chemotherapy than cancer cells by themselves.

Cancer Cells Form Hybrid Clusters in Abdominal Fluid

To understand how this happens, researchers analyzed abdominal fluid from patients with ovarian cancer. What they found challenged previous assumptions. Cancer cells were rarely drifting freely on their own. Instead, they frequently attached themselves to mesothelial cells, forming compact, mixed cell spheres.

The researchers estimated that roughly 60% of these cancer spheres included recruited mesothelial cells. The cancer cells release a signaling molecule known as TGF-β1, which alters the mesothelial cells. In response, the mesothelial cells develop sharp, spike-like protrusions capable of cutting through surrounding tissue.

How Ovarian Cancer Moves Through the Abdomen

As ovarian cancer grows, some cells detach from the main tumor and enter the fluid-filled space within the abdomen. This fluid is constantly in motion due to normal breathing and body movement. As a result, cancer cells are carried to many different areas of the abdominal cavity.

This method of spread differs sharply from that of many other cancers. In diseases such as breast or lung cancer, tumor cells enter blood vessels and travel through the bloodstream to distant organs. Because blood flows through defined pathways, doctors can sometimes monitor these cancers using blood tests.

Ovarian cancer cells largely bypass blood vessels. Instead, they drift through abdominal fluid that lacks a predictable route. This floating phase occurs before the cells attach to new organs. Until now, scientists did not fully understand what occurred during this stage or how cancer cells coordinated their spread so efficiently.

Invadopodia Drive Tissue Invasion

The research team found that during this floating stage, ovarian cancer cells actively recruit mesothelial cells that have naturally shed from the abdominal lining. Once joined together, the two cell types form hybrid spheres. The mesothelial cells then produce invadopodia, which are spike-like structures that drill into nearby tissue.

These hybrid spheres pose a particular threat. When they reach an organ, they invade tissue more rapidly and withstand chemotherapy drugs more effectively than cancer cells alone.

Watching Cancer Spread in Real Time

Using advanced microscopy, the scientists were able to observe this process directly in abdominal fluid samples from patients. They validated their observations with experiments in mouse models and by analyzing gene activity at the single-cell level.

Lead author Dr. Kaname Uno, a former PhD student and current Visiting Researcher at Nagoya University’s Graduate School of Medicine, explained that the cancer cells themselves remain relatively unchanged. “They manipulate mesothelial cells to do the tissue invasion work. They undergo minimal genetic and molecular changes and just migrate through the openings that mesothelial cells create.”

Before entering research, Dr. Uno spent eight years working as a gynecologist. One patient profoundly shaped his decision to pursue this line of study. She had received normal screening results just three months before doctors diagnosed her with advanced ovarian cancer. Existing diagnostic tools failed to detect the disease early enough to save her life. That experience motivated Dr. Uno to investigate why ovarian cancer spreads so quickly and escapes early detection.

New Opportunities for Treatment and Monitoring

The findings point to potential new approaches for treating ovarian cancer. Current chemotherapy drugs focus on destroying cancer cells but do not target the mesothelial cells that assist in invasion. Future therapies could aim to block the TGF-β1 signal or prevent the formation of these harmful cell partnerships.

The study also suggests a possible new way to track the disease. Monitoring these hybrid cell clusters in abdominal fluid could help doctors better predict how ovarian cancer will progress and how patients respond to treatment.

Ovarian cancer kills more women than any other gynecological cancer. Most patients receive their diagnosis only after the disease spreads throughout the abdomen. Until now, scientists have never fully understood why this cancer advances so fast.

A new study led by Nagoya University explains why. Published in Science Advances, the study shows that cancer cells recruit help from protective mesothelial cells that normally line the abdominal cavity. Mesothelial cells lead the invasion and cancer cells follow the pathways they create. These hybrid cell clusters resist chemotherapy better than cancer alone.

Researchers examined abdominal fluid from ovarian cancer patients and found something unexpected. Cancer cells do not float alone in the abdominal cavity. Instead, they often grab onto mesothelial cells and form hybrid spheres. About 60% of all cancer spheres contain these recruited mesothelial cells. The cancer cells release a protein called TGF-β1 that transforms the mesothelial cells and causes them to develop spike-like structures that cut through tissue.

Invadopodia, spike structures that do the digging for cancer

When ovarian cancer develops, cancer cells break off from the tumor. These cells enter the abdominal fluid and float freely. The fluid moves around as you breathe and move your body. This movement carries the cancer cells to different spots in the abdomen.

Most other cancers spread differently. Breast cancer or lung cancer cells enter blood vessels. They travel through the bloodstream to reach distant organs. Doctors can sometimes track these cancers through blood tests because blood moves in predictable paths through vessels.

Ovarian cancer cells avoid blood vessels entirely. They float in fluid that has no fixed path. This floating stage happens before the cancer cells attach to new organs. Scientists did not fully understand what happened during the floating period or how cells worked together to spread cancer so quickly.

The research team discovered that cancer cells recruit protective mesothelial cells that have shed from the abdominal cavity lining during this floating stage. The two cell types stick together and form hybrid spheres. The mesothelial cells then grow invadopodia, spike-like structures that drill into surrounding tissue. The hybrid spheres resist chemotherapy drugs more effectively and invade tissues faster when they land on organs.

Outsourcing the hard work of cell invasion

The researchers examined abdominal fluid from ovarian cancer patients using advanced microscopy to watch this process in real time. They confirmed their findings with mouse models and single-cell genetic analysis.

Lead author Dr. Kaname Uno, a former PhD student and current Visiting Researcher at Nagoya University’s Graduate School of Medicine, explained that the cancer cells do not need to become more invasive themselves. “They manipulate mesothelial cells to do the tissue invasion work. They undergo minimal genetic and molecular changes and just migrate through the openings that mesothelial cells create.”

Dr. Uno worked as a gynecologist for eight years before he pursued research. One of his patients changed his career path. She had clear screening results just three months before doctors found advanced ovarian cancer. Current medical tools failed to detect the cancer early enough to save her life. This motivated Dr. Uno to investigate why ovarian cancer spreads so rapidly.

This discovery opens new treatment possibilities. Current chemotherapy targets cancer cells but ignores the mesothelial accomplices. Future drugs could block the TGF-β1 signal or prevent the formation of these dangerous partnerships. The research also suggests that doctors could monitor these cell clusters in abdominal fluid to predict disease progression and treatment response.

The researchers found that Mic-628 works by attaching to CRY1, a protein that normally suppresses clock gene activity. This interaction encourages the formation of a larger molecular complex known as CLOCK-BMAL1-CRY1-Mic-628. Once formed, this complex switches on Per1 by acting at a specific DNA site called a “dual E-box.” Through this mechanism, Mic-628 shifts the timing of both the brain’s master clock located in the suprachiasmatic nucleus (SCN) and clocks in other organs, including the lungs. Notably, these clock shifts occurred together and did not depend on when the compound was given.

Faster Recovery From Jet Lag in Animal Tests

To test real-world relevance, the team used a mouse model designed to mimic jet lag by advancing the light-dark cycle by six hours (6-hour light-dark phase advance). Mice that received a single oral dose of Mic-628 adjusted to the new schedule much faster, taking four days instead of seven. Further mathematical analysis showed that this steady, one-direction shift forward is driven by a built-in feedback loop involving the PER1 protein, which helps stabilize the clock change.

Why Advancing the Clock Is So Difficult

Adjusting to earlier schedules, such as traveling east across time zones or working night shifts, requires the body clock to move forward. This type of adjustment is typically slower and more stressful for the body than delaying the clock. Common approaches like light exposure or melatonin depend heavily on precise timing and often produce uneven results. Because Mic-628 consistently advances the clock regardless of dosing time, it offers a fundamentally different drug-based approach to circadian reset.

What Comes Next for Mic-628

The researchers plan to continue studying Mic-628 to better understand its safety and effectiveness in additional animal studies and in humans. Since the compound reliably moves the body clock forward through a clearly defined biological pathway, it could become a model “smart drug” for addressing jet lag, sleep problems linked to shift work, and other disorders caused by circadian misalignment.

The findings were published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS).