“This is a fish that grew legs using the same genes that contribute to the development of our limbs and then repurposed these legs to find prey using the same genes our tongues use to taste food — pretty wild,” says Nicholas Bellono of Harvard University in Cambridge, MA.

Bellono, along with David Kingsley of Stanford University and their colleagues, didn’t set out to study sea robins at all. They came across these creatures on a trip to the Marine Biological Laboratory in Woods Hole, MA. After learning that other fish follow the sea robins around, apparently due to their skills in uncovering buried prey, the researchers became intrigued and took some sea robins back to the lab to find out more. They confirmed that the sea robins could indeed detect and uncover ground-up and filtered mussel extract and even single amino acids.

As reported in one of the two new studies, they found that sea robins’ legs are covered in sensory papillae, each receiving dense innervation from touch-sensitive neurons. The papillae also have taste receptors and show chemical sensitivity that drives the sea robins to dig.

“We were originally struck by the legs that are shared by all sea robins and make them different from most other fish,” Kingsley says. “We were surprised to see how much sea robins differ from each other in sensory structures found on the legs. The system thus displays multiple levels of evolutionary innovation from differences between sea robins and most other fish, differences between sea robin species, and differences in everything from structure and sensory organs to behavior.”

Through further developmental studies, the researchers confirmed that the papillae represent a key evolutionary innovation that has allowed the sea robins to succeed on the seafloor in ways other animals can’t. In the second study, they looked deeper into the genetic basis of the fish’s unique legs. They used genome sequencing, transcriptional profiling, and study of hybrid species to understand the molecular and developmental basis for leg formation.

Their analyses identified an ancient and conserved transcription factor, called tbx3a, as a major determinant of the sea robins’ sensory leg development. Genome editing confirmed that they depend on this regulatory gene to develop their legs normally. The same gene also plays a critical role in the formation of sea robins’ sensory papillae and their digging behavior.

“Although many traits look new, they are usually built from genes and modules that have existed for a long time,” Kingsley said. “That’s how evolution works: by tinkering with old pieces to build new things.”

The findings show that it’s now possible to expand our detailed understanding of complex traits and their evolution in wild organisms, not just in well-established model organisms, according to the researchers. They are now curious to learn more about the specific genetic and genomic changes that led to sea robins’ evolution.

In some mammals, the timing of the normally continuous embryonic development can be altered to improve the chances of survival for both the embryo and the mother. This mechanism to temporarily slow development, called embryonic diapause, often happens at the blastocyst stage, just before the embryo implants in the uterus. During diapause, the embryo remains free-floating and pregnancy is extended. This dormant state can be maintained for weeks or months before development is resumed, when conditions are favorable. Although not all mammals use this reproductive strategy, the ability to pause development can be triggered experimentally. Whether human cells can respond to diapause triggers remained an open question.

Now, a study by the labs of Aydan Bulut-Karslioğlu at the Max Planck Institute for Molecular Genetics in Berlin and Nicolas Rivron at the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences in Vienna, an ERC grantee, has identified that the molecular mechanisms that control embryonic diapause also seem to be actionable in human cells. Their results were published on September 26th in the journal Cell.

Stem cell-derived models to study embryonic diapause in humans

In their research, the scientists did not carry out experiments on human embryos and instead used human stem cells and stem cell-based blastocyst models called blastoids. These blastoids are a scientific and ethical alternative to using embryos for research. The researchers discovered that modulation of a specific molecular cascade, the mTOR signaling pathway, in these stem cell models induces a dormant state remarkably akin to diapause. “The mTOR pathway is a major regulator of growth and developmental progression in mouse embryos,” says Aydan Bulut-Karslioğlu. “When we treated human stem cells and blastoids with an mTOR inhibitor we observed a developmental delay, which means that human cells can deploy the molecular machinery to elicit a diapause-like response.”

This dormant state is characterized by reduced cell division, slower development and a decreased ability to attach to the uterine lining. Importantly, the capacity to enter this dormant stage seems to be restricted to a brief developmental period. “The developmental timing of blastoids can be stretched around the blastocyst stage, which is exactly the stage where diapause works in most mammals,” says shared first author Dhanur P. Iyer. Moreover, this dormancy is reversible, and blastoids resume normal development when the mTOR pathway is reactivated.

The ability to alter the timing of embryonic development has implications for IVF

The authors concluded that humans, like other mammals, might possess an inherent mechanism to temporarily slow down their development, even though this mechanism may not be used during pregnancy. “This potential may be a vestige of the evolutionary process that we no longer make use of,” says Nicolas Rivron. “Although we have lost the ability to naturally enter dormancy, these experiments suggest that we have nevertheless retained this inner ability and could eventually unleash it.” For basic research, the question arises as to whether human and other mammalian cells enter the dormant state via similar or alternative pathways and use it for the same purposes, for example either pausing or timing their development and implantation.

The team’s discoveries could have implications for reproductive medicine: “On the one hand, undergoing faster development is known to increase the success rate of in vitro fertilization (IVF), and enhancing mTOR activity could achieve this,” Nicolas Rivron explains. “On the other hand, triggering a dormant state during an IVF procedure could provide a larger time window to assess embryo health and to synchronize it with the mother for better implantation inside the uterus.”

Overall, the new findings provide unforeseen insights into the processes governing our earliest development, which might open new avenues for enhancing reproductive health. “This exciting collaboration is a testimony to how complex biological questions can be tackled by bringing together respective expertise,” says Heidar Heidari Khoei, postdoctoral fellow in the lab of Nicolas Rivron and the study’s co-first author. “I believe this work not only underscores the importance of collaboration in advancing science but also opens up further possibilities for understanding how various signals are perceived by cells as they prepare for their developmental journey.”

Nicolas Rivron is a group leader at IMBA and funded by an ERC Consolidator Grant.

Genomic research led by the University of California, Davis, reveals clues about montane red foxes’ distant past that may prove critical to their future survival. The study, published in the journal Molecular Biology and Evolution, examines the potential for genetic rescue to help restore populations of these mountain-dwelling red foxes. The research is especially relevant for the estimated 30 or fewer native red foxes living in the Lassen Peak region of California.

The study found that inbreeding is impacting the Lassen red fox population. Thousands of years ago — long before unregulated trapping and poison knocked back their populations in the 1890s and early 1900s — red foxes were not only abundant in these mountains, they were also more connected to neighboring foxes in Oregon, the Rocky Mountains and Washington Cascades than they are today. This positions them well for genetic rescue should managers decide to pursue it and reconnect the populations.

“Nothing we found disqualifies red foxes from genetic rescue,” said lead author Cate Quinn, who conducted the research as a UC Davis postdoctoral researcher with the Mammalian Ecology and Conservation Unit within the School of Veterinary Medicine. She is now a research biologist with the USDA Forest Service Rocky Mountain Research Station. “The study suggests that genetic rescue could be a viable option for the Lassen population.”

Rescue workers

Genetic rescue is a conservation tool to reverse the effects of inbreeding depression, which is when inbreeding reduces an animal’s fitness and ability to reproduce. Genetic rescue involves bringing new individuals to a population to introduce genetic variation and spur growth.

The tool is not considered lightly, and managers first must understand the severity of inbreeding, the historical baseline genetic rescue seeks to restore, and the deeper evolutionary relationships the foxes share with each other.

To fill those knowledge gaps, the scientists sequenced 28 whole genomes from the four subspecies of montane red foxes. These include small, isolated populations in the Pacific mountains, Oregon Cascades, Lassen Cascades and the Sierra Nevada, as well as a larger population in the Rocky Mountains and a subspecies in the Sacramento Valley. Using genomic technology, the authors could peer back in time to see if a population was always isolated, to what extent, and when that began to change.

Abundant, connected and diverse

The study found high levels of recent inbreeding in Lassen and Sierra Nevada red fox populations, with the Lassen red foxes a high priority for intervention. Only one montane red fox is known to have entered the Lassen population in more than 20 years of monitoring, the study said.

The data also revealed that 10,000 to 12,000 years ago, montane red foxes in the Western United States were abundant, connected and genetically diverse. The Lassen population was likely connected to the Oregon red foxes within the last century, breaking from each other relatively recently, Quinn said.

A hopeful way forward

Combined, these findings point to a hopeful way forward for Lassen’s red foxes, and for other red foxes facing similar challenges.

“We think trapping drove their population down, but we didn’t know what was keeping them small,” said senior author Ben Sacks, director of the Mammalian and Ecology Conservation Unit at the UC Davis School of Veterinary Medicine. “Now we see that what kept them small appears to be inbreeding depression. If what drove their decline is gone, can we bring them back? There is hope here.”

Quinn agrees: “Not too long ago, this was an abundant, connected, diverse population. That diversity still exists. If we were to restore them as a group, these foxes may still have a lot of adaptive potential.”

She cautions, however, that true genetic “rescue” requires reconnecting the whole subspecies — not just growing one population.

“If we only consider each small pocket individually, they’re in trouble, but if we look at the whole montane system, restoration is still possible,” Quinn said.

Additional coauthors include Sophie Preckler-Quisquater of UC Davis and Michael Buchalski of the California Department of Fish and Wildlife.

The study was funded by the U.S. Fish and Wildlife Service, California Department of Fish and Wildlife, and UC Davis.

Researchers working at reefs in Moorea, French Polynesia found that the network of dead coral skeletons left in place by bleaching events caused critical processes to break down, ultimately preventing reefs from recovering. The complex landscape protects seaweed from herbivores, enabling it to quickly colonize the reef and outgrow young coral. The results appear in the journal Global Change Biology.

Dynamic ecosystems

Coral reefs are busy ecosystems undergoing constant change. Every now and again, a larger disturbance will rock the reef, like a storm, an influx of coral predators, or a bleaching event. While all of these can deal a blow to the ecosystem, small nuances can drastically affect the reef’s recovery.

Historically, tropical storms and cyclones have been the biggest disruptors to Moorea’s reefs. “They tend to scrape all the coral off the reef and leave behind a flat surface,” said lead author Kai Kopecky, a former doctoral student in UCSB’s Department of Ecology, Evolution, and Marine Biology. But bleaching and predation are on the rise, and these events kill coral, but leave the reef’s structure intact.

Bleaching occurs when stress — usually heat — causes corals to expel the symbiotic algae that provide them with food. Coral can recover from this if conditions quickly return to their liking, but often the colony simply dies, especially in the presence of other stressors like pollution.

A cyclone walloped Moorea’s reefs in 2010. “It removed basically every single coral colony off the fore reef,” Kopecky said. “But within about five years, it recovered back to the amount of coral it had before the storm had hit.”

The reef experienced a big bleaching event in 2019, a year after Kopecky began working on the island. “It basically just cooked and killed about half the corals on the reef,” he recalled. But unlike the storm, this disturbance left all the dead coral structure in place.

Kopecky and his colleagues at the NSF-funded Long Term Ecological Research (LTER) site at Moorea Coral Reef noticed that the reef didn’t experience the same remarkable recovery in the following years. Instead, coral continued to die, and macroalgae, commonly known as seaweed, began to proliferate. Kopecky was curious how the differences between the two events affected reef recovery processes. In 2023, he and his coauthors published a mathematical model of the system, and this new field study focuses on describing the mechanisms at work.

“This combination of time series data on long term responses of ecosystems, mathematical modeling and field experimentation greatly enriches our scientific understanding and ability to devise practical solutions,” said co-author Professor Russ Schmitt, lead principal investigator at the Moorea Coral Reef LTER site.

“The multi-decadal, site-based research focus makes the LTER network both unique and of immense value in our rapidly changing world,” said LTER co-principal investigator Professor Sally Holbrook, who is also one of the study’s authors.

“The current project was led by Kai, a Ph.D. student at the time, and involved UCSB undergraduate researchers who made important contributions in addition to those of senior ecologists. It is a prime example of how the Moorea Coral Reef project fosters and trains the next generation of environmental scientists,” Schmitt added.

Investigating the reefscape

The team prepared small patches of the reef to create a blank slate for their experiment. They then cemented a controlled number of dead coral skeletons in each patch and plugged healthy young coral into the reef in a way that each could be periodically removed and measured as they grew. They also added trays of macroalgae to compare herbivory within the bleached skeletons to consumption out in the open.

“We found that dead coral skeletons prevent herbivores from being able to remove macroalgae, enabling growth and preventing new corals from being able to settle and survive on the reef,” Kopecky said.

Protection by dead coral skeletons could theoretically help young coral, if new recruits settle on the reef shortly after a bleaching event. Unfortunately, corals tend to spawn only once a year, while many algae reproduce continually, giving the seaweeds the advantage in colonizing the newly available substrate.

Macroalgae compete with coral for space, light and resources. Algae grow faster than coral, so without the balancing effect of herbivory they can easily overrun a reef, preventing new corals from settling and shading out those colonies that do. Young coral recruits are particularly vulnerable to this competition, and once a reef flips from being covered by coral to algae, it can be hard to reverse the change, as the team showed in previous research.

Considering long-term shifts

The authors compared the results in their small-scale experiments to the long-term data from the site, and they’ve seen dramatically different trajectories after the different kinds of disturbances. “Coral cover shot up on the reefs after the cyclone, while macroalgae cover went down,” Kopecky said. “After the bleaching event, it was just the opposite.”

The results find context in the concept of ecological memory, which considers how past events can influence the trajectory of an ecosystem. These shifts can produce misalignments between what an ecosystem is used to and what it’s currently experiencing. “As these disturbance regimes change, ecological memory is also changing,” Kopecky explained. Unfortunately, the ecosystem might not be as adapted to cope with the new regime, where vast stands of dead coral skeletons are left behind after a disturbance. This can alter long-standing relationships, such as those between herbivores, algae and coral.

Kopecky wants to know if removing dead skeletons from the reef could stimulate coral recovery, or at least mitigate the impacts of bleaching. “In coral reefs this is a novel idea and strategy,” he said. “But if you look to other ecosystems — like prescribed burns in forests to remove dead wood — people have been increasingly thinking about manipulating dead stuff in ecosystems for management purposes.”

The finding is confounding researchers searching for an explanation. “We don’t know what’s going on, but it’s just a very exciting finding,” said lead author Alec Lessing of Stanford University. “This means there’s something missing from our understanding of how black hole jets interact with their surroundings.”

A nova erupts in a double-star system where an aging, swelled-up, normal star spills hydrogen onto a burned-out white dwarf companion star. When the dwarf has tanked up a mile-deep surface layer of hydrogen that layer explodes like a giant nuclear bomb. The white dwarf isn’t destroyed by the nova eruption, which ejects its surface layer and then goes back to siphoning fuel from its companion, and the nova-outburst cycle starts over again.

Hubble found twice as many novae going off near the jet as elsewhere in the giant galaxy during the surveyed time period. The jet is launched by a 6.5-billion-solar-mass central black hole surrounded by a disk of swirling matter. The black hole, engorged with infalling matter, launches a 3,000-light-year-long jet of plasma blazing through space at nearly the speed of light. Anything caught in the energetic beam would be sizzled. But being near its blistering outflow is apparently also risky, according to the new Hubble findings.

The finding of twice as many novae near the jet implies that there are twice as many nova-forming double-star systems near the jet or that these systems erupt twice as often as similar systems elsewhere in the galaxy.

“There’s something that the jet is doing to the star systems that wander into the surrounding neighborhood. Maybe the jet somehow snowplows hydrogen fuel onto the white dwarfs, causing them to erupt more frequently,” said Lessing. “But it’s not clear that it’s a physical pushing. It could be the effect of the pressure of the light emanating from the jet. When you deliver hydrogen faster, you get eruptions faster. Something might be doubling the mass transfer rate onto the white dwarfs near the jet.” Another idea the researchers considered is that the jet is heating the dwarf’s companion star, causing it to overflow further and dump more hydrogen onto the dwarf. However, the researchers calculated that this heating is not nearly large enough to have this effect.

“We’re not the first people who’ve said that it looks like there’s more activity going on around the M87 jet,” said co-investigator Michael Shara of the American Museum of Natural History in New York City. “But Hubble has shown this enhanced activity with far more examples and statistical significance than we ever had before.”

Shortly after Hubble’s launch in 1990, astronomers used its first-generation Faint Object Camera (FOC) to peer into the center of M87 where the monster black hole lurks. They noted that unusual things were happening around the black hole. Almost every time Hubble looked, astronomers saw bluish “transient events” that could be evidence for novae popping off like camera flashes from nearby paparazzi. But the FOC’s view was so narrow that Hubble astronomers couldn’t look away from the jet to compare with the near-jet region. For over two decades, the results remained mysteriously tantalizing.

Compelling evidence for the jet’s influence on the stars of the host galaxy was collected over a nine-month interval of Hubble observing with newer, wider-view cameras to count the erupting novae. This was a challenge for the telescope’s observing schedule because it required revisiting M87 precisely every five days for another snapshot. Adding up all of the M87 images led to the deepest images of M87 that have ever been taken.

Hubble found 94 novae in the one-third of M87 that its camera can encompass. “The jet was not the only thing that we were looking at — we were looking at the entire inner galaxy. Once you plotted all known novae on top of M87 you didn’t need statistics to convince yourself that there is an excess of novae along the jet. This is not rocket science. We made the discovery simply by looking at the images. And while we were really surprised, our statistical analyses of the data confirmed what we clearly saw,” said Shara.

This accomplishment is entirely due to Hubble’s unique capabilities. Ground-based telescope images do not have the clarity to see novae deep inside M87. They cannot resolve stars or stellar eruptions close to the galaxy’s core because the black hole’s surroundings are far too bright. Only Hubble can detect novae against the bright M87 background.

Novae are remarkably common in the universe. One nova erupts somewhere in M87 every day. But since there are at least 100 billion galaxies throughout the visible universe, around 1 million novae erupt every second somewhere out there.

With MS, the body’s immune system attacks myelin, the fatty, white substance that insulates and protects the nerves. People with primary progressive MS experience a steady decline in symptoms. About 10 to 15% of people with the disease have this type of MS.

The study looked at rituximab and ocrelizumab, anti-CD20 infusion therapies that target a protein called CD20 found on some white blood cells called B-cells. Removing these cells from the bloodstream is believed to reduce inflammation and damage that can occur to the myelin. Ocrelizumab is approved by the U.S. Food and Drug Administration (FDA) for primary progressive MS and for people with relapses, but rituximab is not. Rituximab is FDA approved for other diseases like rheumatoid arthritis and prescribed off label for MS.

“MS is a disabling disease, so treatments that slow the progression to worse disability are sorely needed,” said study author Laure Michel, MD, PhD, of Rennes University in France. “Anti-CD20 therapies are widely prescribed, in part because there are few alternate treatments. However, our study suggests they may not slow disability from worsening for people with primary progressive MS.”

The study involved 1,184 people with primary progressive MS who had an average age of 56. They did not take MS medications in the two years prior to the study. For the study, 295 people were treated with rituximab, 131 were treated with ocrelizumab and 728 were untreated. They were followed for an average of four years.

Participants’ level of disability was measured on a scale with scores ranging from zero, meaning no symptoms, to 10 points, meaning death due to MS. At the start of the study, all participants had a score of 6.5 or less.

Researchers then measured how long it took for people to advance to their first confirmed disability progression. For those whose score was less than 5.5 at the start of the study, advancing one point on the scale was considered progressing in disability. If their score was 5.5 or more, advancing 0.5 points on the scale was disability progression.

After adjusting for possible differences between the treated and untreated groups, researchers found there was no difference in the time it took to progress to the next level of disability between those taking a medication and those taking no medication.

“Medications for MS can be expensive and come with risks of side effects,” said Michel. “Our results indicate that there should be a constant evaluation of MS therapies to determine if the benefits outweigh the risks for people with primary progressive MS.”

A limitation of the study is that it was a look back in time and did not follow people in real time. Also, among those taking medications, most were taking rituximab with fewer people taking ocrelizumab. More research is needed in larger groups of people to confirm the findings.

The study was supported by the France National Research Agency, the French MS registry and the Eugène Devic EDMUS Foundation.

The Rocahepevirus ratti strain is called “rat HEV” because rats are the primary reservoir of the virus. Since the first human case was reported in a person with a suppressed immune system in Hong Kong in 2018, at least 20 total human cases have been reported — including in people with normal immune function.

People infected with rat HEV did not report exposure to rats, leaving the cause of infection undefined. The suspected cause during other human HEV infections, in many cases, is consumption of raw pork — making it a potential route for rat HEV as well.

Researchers at The Ohio State University found that a strain of rat HEV isolated from humans could infect pigs and was transmitted among co-housed animals in farm-like conditions. Rats are common pests in swine barns — suggesting that the pork production industry may be a setting in which rat HEV could make its way to humans.

“We always want to know which viruses might be up and coming, so we need to know the genetics behind this virus in the unlikely event something happens in the United States that would enable rat HEV to expand,” said senior author Scott Kenney, an associate professor of veterinary preventive medicine at Ohio State based in the Center for Food Animal Health at the College of Food, Agricultural, and Environmental Sciences’ Wooster campus.

The study was published recently in PNAS Nexus.

Hepatitis E is the leading cause of the acute viral liver infection in humans worldwide, mostly in developing regions where sanitation is poor. The virus is also endemic in pigs in the United States — though it is present mostly in liver rather than muscle, and is killed when the meat is cooked.

Past studies testing the cross-species infectiousness of rat HEV showed the strain used in experiments did not infect non-human primates.

“It dropped off the radar for six or seven years because it was thought not to be a human pathogen. And now it’s infecting humans, so we need to figure out why,” Kenney said.

One strain linked to human disease is known as LCK-3110. First author Kush Yadav, who completed this work as a PhD student in the Center for Food Animal Health, used the viral genomic sequence to construct an infectious clone of LCK-3110.

The team first showed the cloned virus could replicate in multiple types of human and mammal cell cultures and in pigs. Researchers then injected pigs with an infectious solution containing the LCK-3110 strain or another HEV strain present in pigs in the U.S., as well as saline as a control condition.

Viral particles in the blood and feces were detected one week later in both groups receiving HEV strains, but levels were higher in pigs infected with rat HEV. Two weeks later, co-housed pigs that received no inoculations also began to shed rat HEV virus in their feces — an indication the virus had spread through the fecal-oral route.

Though infected pigs’ organs and bodily fluids were also positive for viral RNA, the animals did not show signs of feeling sick. Previous research suggests rats don’t have clinical symptoms, either.

Even so, the rat HEV virus was detected in cerebrospinal fluid of infected pigs — a finding that aligns with growing concern that various strains of HEV that infect humans can harm the brain. One human death linked to rat HEV was caused by meningoencephalitis.

“HEV is gaining importance for neurological disorders, and a lot of the research now points toward how neuropathology is caused by the hepatitis E virus,” Yadav said. “And even though we have a small number of known human cases, a high percentage of them are immunosuppressed. That means transplant recipients in the United States could be at risk of infection by general HEV as well as rat HEV.

“Research could now focus on whether pork liver products contain rat HEV and explore food safety procedures to block the disease.”

Yadav is now a postdoctoral researcher in the Virginia-Maryland College of Veterinary Medicine at Virginia Tech. Co-authors of the study, all from Ohio State, were Patricia Boley, Carolyn Lee, Saroj Khatiwada, Kwonil Jung, Thamonpan Laocharoensuk, Jake Hofstetter, Ronna Wood and Juliette Hanson.