A research team based in Japan has revealed that stem-like proliferative cells — which are actively growing and dividing but not yet differentiating into specific cell types — appear at the site of injury and help form the blastema.

The findings were published in the scientific journal PLOS Biology.

“Importantly, these stem-like proliferative cells in blastema are different from the resident stem cells localized in the tentacle,” said corresponding author Yuichiro Nakajima, lecturer in the Graduate School of Pharmaceutical Sciences at the University of Tokyo. “Repair-specific proliferative cells mainly contribute to the epithelium — the thin outer layer — of the newly formed tentacle.”

The resident stem cells that exist in and near the tentacle are responsible for generating all cellular lineages during homeostasis and regeneration, meaning they maintain and repair whatever cells are needed during the jellyfish’s lifetime, according to Nakajima. Repair-specific proliferative cells only appear at the time of injury.

“Together, resident stem cells and repair-specific proliferative cells allow rapid regeneration of the functional tentacle within a few days,” Nakajima said, noting that jellyfish use their tentacles to hunt and feed.

This finding informs how researchers understand how blastema formation differs among different animal groups, according to first author Sosuke Fujita, a postdoctoral researcher in the same lab as Nakajima in the Graduate School of Pharmaceutical Sciences.

“In this study, our aim was to address the mechanism of blastema formation, using the tentacle of cnidarian jellyfish Cladonema as a regenerative model in non-bilaterians, or animals that do not form bilaterally — or left-right — during embryonic development,” Fujita said, explaining that the work may provide insight from an evolutionary perspective.

Salamanders, for example, are bilaterian animals capable of regenerating limbs. Their limbs contain stem cells restricted to specific cell-type needs, a process that appears to operate similarly to the repair-specific proliferative cells observed in the jellyfish.

“Given that repair-specific proliferative cells are analogues to the restricted stem cells in bilaterian salamander limbs, we can surmise that blastema formation by repair-specific proliferative cells is a common feature independently acquired for complex organ and appendage regeneration during animal evolution,” Fujita said.

The cellular origins of the repair-specific proliferative cells observed in the blastema remain unclear, though, and the researchers say the currently available tools to investigate the origins are too limited to elucidate the source of those cells or to identify other, different stem-like cells.

“It would be essential to introduce genetic tools that allow the tracing of specific cell lineages and the manipulation in Cladonema,” Nakajima said. “Ultimately, understanding blastema formation mechanisms in regenerative animals, including jellyfish, may help us identify cellular and molecular components that improve our own regenerative abilities.”

About 200,000 people in Sweden currently live with fibromyalgia, a long-term pain syndrome that causes great suffering for patients through widespread pain, fatigue, and stiffness in the body. There is no cure for fibromyalgia. Existing drugs often have insufficient effect, raising the need for more effective treatment methods. Cognitive behavioral therapy (CBT) has shown some effect, but there is a lack of trained CBT practitioners. There is also a lack of knowledge about which form of CBT is most effective. The study compared two different forms of internet-delivered cognitive behavioral therapy in terms of how well they reduce the symptoms and functional impact of fibromyalgia.

In brief, exposure-based CBT involves the participant systematically and repeatedly approaching situations, activities, and stimuli that the patient has previously avoided because the experiences are associated with pain, psychological discomfort, or symptoms such as fatigue and cognitive problems.

In traditional CBT, the participant is presented with several different strategies to work on during treatment, such as relaxation, activity planning, physical exercise, or strategies for managing negative thoughts and improving sleep.

The study showed that traditional CBT was by and large equivalent to the newer treatment form of exposure-based CBT.

“This result was surprising because our hypothesis, based on previous research, was that the new exposure-based form would be more effective. Our study shows that the traditional form can provide an equally good result and thus contributes to the discussion in the field,” says Maria Hedman-Lagerlöf, licensed psychologist and researcher at the Center for Psychiatry Research at the Department of Clinical Neuroscience, Karolinska Institutet.

The randomized study involved 274 people with fibromyalgia, who were randomly assigned to be treated with traditional or exposure-based CBT. The treatments were delivered entirely online and all participants had regular contact with their therapist.

Participants answered questions about their mood and symptoms before, during, and after treatment. After the 10-week treatment, 60 percent of those who received exposure-based CBT and 59 percent of those who received traditional CBT reported that their treatment had helped them.

“The fact that both treatments were associated with a significant reduction in the participants’ symptoms and functional impairment and that the effects were sustained for 12 months after completion of the treatment, indicates that the internet as a treatment format can be of great clinical benefit for people with fibromyalgia,” says Maria Hedman-Lagerlöf. “This is good news because it enables more people to access treatment.”

The study is the second largest to compare different psychological treatment options for fibromyalgia, according to the researchers.

“Our study is also one of the first to compare with another active, established psychological treatment,” says Maria Hedman-Lagerlöf.

Male aggression in rodents is known to be blocked when they smell female tears. This is an example of social chemosignaling, a process that is common in animals but less common — or less understood — in humans. To determine whether tears have the same affect in people, the researchers exposed a group of men to either women’s emotional tears or saline while they played a two-person game. The game was designed to elicit aggressive behavior against the other player, whom the men were led to believe was cheating. When given the opportunity, the men could get revenge on the other player by causing them lose money. The men did not know what they were sniffing and could not distinguish between the tears or the saline, which were both odorless.

Revenge-seeking aggressive behavior during the game dropped more than 40% after the men sniffed women’s emotional tears. When repeated in an MRI scanner, functional imaging showed two aggression-related brain regions — the prefrontal cortex and anterior insula — that became more active when the men were provoked during the game, but did not become as active in the same situations when the men were sniffing the tears. Individually, the greater the difference in this brain activity, the less often the player took revenge during the game. Finding this link between tears, brain activity, and aggressive behavior implies that social chemosignaling is a factor in human aggression, not simply an animal curiosity.

The authors add, “We found that just like in mice, human tears contain a chemical signal that blocks conspecific male aggression. This goes against the notion that emotional tears are uniquely human.”

Two researchers at The Ohio State University were among a group of experts invited by the journal Science to discuss how the ESA has evolved and what its future might hold.

Tanya Berger-Wolf, faculty director of Ohio State’s Translational Data Analytics Institute, led a group that wrote on “Sustainable, trustworthy, human-technology partnership.” Amy Ando, professor and chair of the university’s Department of Agricultural, Environmental, and Development Economics, wrote on “Harnessing economics for effective implementation.”

Berger-Wolf and her colleagues wrote, “We are in the middle of a mass extinction without even knowing all that we are losing and how fast.” But technology can help address that.

For example, they note the value of tools like camera traps that survey animal species and smartphone apps that allow citizen scientists to count insects, identify bird songs and report plant observations.

New tech has allowed scientists to monitor animal and plant populations at scale for the first time, said Berger-Wolf, who is also a professor of computer science and engineering, evolution, ecology and organismal biology, and electrical and computer engineering. One challenge is to find new ways to extract all the information from these new sources of data.

“But even with all this data, we are still monitoring only a tiny fraction of the biodiversity out in the world,” she said. “Without that information, we don’t know what we have, how different species are doing and whether our policies to protect endangered species are working.”

Most important, Berger-Wolf said, is the need to make sure to keep humans in the process. Technology needs to connect data, connect different regions of the world, connect people to nature and connect people to people.

“We don’t want to sever the connection between people and nature, we want to strengthen it,” she said.

“We cannot rely on technology to save the world’s biodiversity. It has to be an intentional partnership between humans and technology and AI.”

Economics should be another partner in the fight to save endangered species, Ando said.

“There’s this tendency to think that protecting endangered species is all about biology and ecology,” Ando said. “But various tools in economics are very helpful in making sure the work we do to implement the Endangered Species Act is successful. That is not always obvious to people.”

For example, bioeconomic research is a multidisciplinary effort between economists and biologists to work together to see how human behavior interacts with ecological processes and systems.

“We have to take into account feedback effects. People take an action, and that changes the ecosystem and that changes what people do,” she said. “We need to capture those feedback effects.”

The result can be novel ways to protect endangered species, such as “pop-up” habitat modification. For example, ranchers can take down fences temporarily while elk are migrating to allow them to move freely. Rice fields can be temporarily flooded during shorebird migration to give them a place to rest and feed on their travels.

We can “draw upon economics to optimize the timing, location and extent of temporary actions to maximize their net benefits to society,” Ando wrote in Science.

Another way economics can help is to develop policies that protect species before they become so threatened that they need ESA protection.

A common issue is that multiple landowners will all need to work together to protect the habitat of threatened species. But often, if some landowners take actions to protect a species, other landowners will think they don’t have to.

“Economists have been working to understand how we can coordinate landowners where we don’t have to implement draconian land use regulations, but still protect habitat,” Ando said.

“That is a very promising tactic that can protect species and also reduce the cost to people of doing so.”

Using the latest tools in genetic sequencing, researchers at Mayo Clinic reconstructed how a collective of viral genomes colonized a human brain. The virus acquired distinct mutations that drove the spread of the virus from the frontal cortex outward.

“Our study provides compelling data that shows how viral RNA mutated and spread throughout a human organ — the brain, in this case,” says Roberto Cattaneo, Ph.D., a Mayo Clinic virologist who is a co-lead author on a new PLOS Pathogens study. “Our discoveries will help studying and understanding how other viruses persist and adapt to the human brain, causing disease. This knowledge may facilitate the generation of effective antiviral drugs.”

What is measles?

Measles is one of the most contagious diseases. The measles virus infects the upper respiratory tract where it uses the trachea, or windpipe, as a trampoline to launch and spread through droplets dispersed when an infected person coughs or sneezes.

Dr. Cattaneo pioneered studies on how the measles virus spreads throughout the body.

He first began to study the measles virus about 40 years ago and was fascinated by the rare, lethal brain disease called subacute sclerosing panencephalitis (SSPE), which occurs in about 1 in every 10,000 measles cases. It can take about five to 10 years after the initial infection for the measles virus to mutate and spread throughout the brain. Symptoms of this progressive neurological disease include memory loss, seizures and immobility. Dr. Cattaneo studied SSPE for several years until the lethal disease nearly disappeared as more people were vaccinated against measles.

However, measles is resurging due to vaccine hesitancy and missed vaccinations. During the COVID-19 pandemic, millions of children missed receiving their measles vaccinations, which has resulted in an estimated 18% increase in measles cases and 43% increase in death from measles in 2021 compared to 2022 worldwide, according to a recent Centers for Disease Control and Prevention (CDC) report.

“We suspect SSPE cases will rise again as well. This is sad because this horrible disease can be prevented by vaccination. But now we are in the position to study SSPE with modern, genetic sequencing technology and learn more about it,” says Iris Yousaf, co-lead author of the study and a fifth-year Ph.D. candidate at Mayo Clinic Graduate School of Biomedical Sciences.

Dr. Cattaneo and Yousaf had a unique research opportunity through a collaboration with the CDC. They studied the brain of a person who had contracted measles as a child and had succumbed to SSPE years later as an adult. They investigated 15 specimens from different regions of the brain and conducted genetic sequencing on each region to piece together the puzzle of how the measles virus mutated and spread.

The researchers discovered that, after the measles virus entered the brain, its genome — the complete set of genetic material for the virus — began to change in harmful ways. The genome replicated, creating other genomes that were slightly different. Then, these genomes replicated again — resulting in more genomes that were each a little different as well. The virus did this multiple times, creating a population of varied genomes.

“In this population, two specific genomes had a combination of characteristics that worked together to promote virus spread from the initial location of the infection — the frontal cortex of the brain — out to colonize the entire organ,” says Dr. Cattaneo.

The next steps in this research are to understand how specific mutations favor virus spread in the brain. These studies will be done in cultivated brain cells and in clusters of cells resembling the brain called organoids. This knowledge may help in creating effective antiviral drugs to combat virus spread in the brain. However, pharmacological intervention in advanced disease stages is challenging. Preventing SSPE through measles vaccination remains the best method.

The only Australian members of an international research team, scientists from Curtin’s WA-Organic and Isotope Geochemistry Centre (WA-OIGC) carried out controlled burnings of plants to produce PAHs.

ARC Laureate Fellow John Curtin Distinguished Professor Kliti Grice, director of WA-OIGC, said PAHs are organic compounds made up of carbon and hydrogen that are common on Earth but are also found in celestial bodies like asteroids and meteorites.

“We performed controlled burn experiments on Australian plants, which were isotopically compared to PAHs from fragments of the Ryugu asteroid that were returned to Earth by a Japanese spacecraft in 2020, and the Murchison meteorite that landed in Australia in 1969. The bonds between light and heavy carbon isotopes in the PAHs were analysed to reveal the temperature at which they were formed,” Professor Grice said.

“Select PAHs from Ryugu and Murchison were found to have different characteristics: the smaller ones likely in cold outer space, while bigger ones probably formed in warmer environments, like near a star or inside a celestial body.”

Study co-author Dr Alex Holman, also from WA-OIGC, said understanding the isotopic composition of PAHs helps unravel the conditions and environments in which these molecules were created, offering insights into the history and chemistry of celestial bodies like asteroids and meteorites.

“This research gives us valuable insights into how organic compounds form beyond Earth and where they come from in space,” Dr Holman said.

“The use of high-tech methods and creative experiments has shown that select PAHs on asteroids can be formed in cold space.”

The full research paper, ‘Polycyclic aromatic hydrocarbons in samples of Ryugu formed in the interstellar medium’ will be published in the journal Science.

To understand how a watch works, one might take it apart, piece by piece, and study the role played by each component in its timekeeping function. Similarly, in a protein such as a GPCR, each amino acid might play a different role in how the protein responds to an external signal. Researchers at St. Jude, in collaboration with scientists from Stanford University, the University of Montreal, the MRC Laboratory of Molecular Biology and Cambridge University, investigated the β2-adrenergic receptor (β2AR) by substituting one amino acid at a time to understand the contribution of each amino acid in this receptor to mediate a signaling response.

“Scientists learn how genes contribute to cell function by disrupting them one at a time. We asked, ‘Why don’t we take this one level deeper? Let’s understand how every amino acid contributes to the functioning of a receptor by mutating them, one amino acid at a time,'” said co-corresponding author M. Madan Babu, PhD, from St. Jude’s Department of Structural Biology, Center of Excellence for Data-Driven Discovery director and the George J. Pedersen Endowed Chair in Biological Data Science. “Through evolution, every amino acid in the receptor has been sculpted in some way or another to ensure that it binds the natural ligand, in this case adrenaline, and elicits the appropriate physiological response.”

Finding function in the form

GPCRs are proteins that span the cell’s membrane and connect the outside of the cell to its internal environment by transmitting external signals to the inside of the cell. In the case of the β2AR, adrenaline binds to the GPCR on the part outside of the cell, inducing a response inside the cell.

When a ligand binds, it causes changes in the shape of the receptor, especially in the intracellular region of the receptor where a G protein binds. The binding sites for the ligand and the G protein are on opposite sides of the protein but connect through a complex network of amino acid contacts that span the entire protein. Conformational (shape) changes within the GPCR activate the G protein to trigger a downstream signaling response within the cell. Through effects on multiple tissues and GPCRs, including the β2AR, adrenaline can trigger the fight-or-flight response, such as during an adrenaline surge.

To understand the role of each amino acid in a GPCR, Franziska Heydenreich, PhD, now of the Philipps University of Marburg, the lead and co-corresponding author of this project, mutated each of the 412 amino acids in the β2AR. She then evaluated each mutant’s response to the ligand adrenaline and determined the classical pharmacological properties of efficacy and potency. Efficacy measures the maximum response a ligand can elicit, and potency measures the amount of ligand required to elicit half of the maximum response. The aim was to reveal, on an atomic scale, how each amino acid contributes to these pharmacological properties.

“Surprisingly, only about 80 of the more than 400 amino acids contributed to these pharmacological properties. Of these pharmacologically relevant amino acids, only one-third were located within regions where the ligand or G protein bound to the receptor,” Heydenreich said.

“It was fascinating to observe that there are some amino acids that control efficacy, some that control potency and then there are others that affect both,” Babu said. “It means if you want to make a more potent or efficacious drug, you now know there are specific residues that the new ligand needs to influence.” The researchers also noted that the individual contribution of each residue to efficacy and potency was not equal, implying even more opportunities for fine-tuning drug responses while designing new therapeutic ligands.

“Efficacy and potency have been measured for numerous ligand-receptor signaling systems for several decades. Now we can understand how specific amino acids in a protein’s sequence can influence these pharmacological properties,” Babu explained.

“A fascinating aspect of the results is that potency and efficacy can be regulated independently of each other through distinct mechanisms. This provides a basis for understanding how genetic variation influences drug responses among individuals,” Michel Bouvier, PhD, co-corresponding author from the Department of Biochemistry and Molecular Medicine and General Director of the Institute for Research in Immunology and Cancer of the University of Montreal added.

A beautiful network

Prior research illustrated the structure of both the active and inactive states of the β2AR. Building on this knowledge, the researchers embarked on a new investigation. They explored whether the two-thirds of pharmacologically relevant amino acids previously demonstrated to be not involved in ligand or G-protein binding might play a role in the transition between the active and inactive states of the receptor.

“We systematically started looking at every residue contact unique to the active state,” Heydenreich said, “to understand whether all the amino acids that make an active-state contact are important.”

The researchers developed a data science framework to integrate pharmacological and structural data systematically and revealed the first comprehensive picture of GPCR signaling. “When we mapped the pharmacological data onto the structure, they formed a beautiful network,” said Babu.

“It provided new insights into the allosteric network linking the ligand binding pocket to the G protein binding site that governs efficacy and potency.” Added Brian Kobilka, co-corresponding author and the 2012 Nobel Prize winner in Chemistry from Stanford University School of Medicine.

By understanding GPCR signaling at the atomic level, the researchers are optimistic that they can begin probing even deeper — to see the transient sub-states between the active and inactive conformations and to explore the conformational landscape of proteins.

“We now know which mutants to go after, those that only affect efficacy, potency or both,” Heydenreich said.

“Now, we can perform molecular dynamics calculations and single-molecule experiments on those mutants to reveal the exact mechanisms by which the allosteric network influences efficacy and potency to mediate a signaling response. This is a direction we are pursuing through a St. Jude Research Collaborative on GPCRs that includes PIs from several institutions.” Babu explained.

Apart from these “driver” residues that are involved in mediating active state-specific contacts and affect pharmacology when mutated, Babu and his colleagues intend to probe other key findings revealed by this work. They aim to study “passenger” amino acids that, despite making contacts in the active state, do not affect efficacy or potency when mutated. They are also interested in “modulator” residues that don’t mediate active state-specific contacts but alter pharmacology when mutated. Their data science approach, integrating structural information and pharmacological measurements, isn’t limited to the β2AR. It can be extended to any GPCR to enhance our understanding of the mechanics governing this crucial class of drug targets.

At more than 12 billion years old, BRI 1335-0417 is the oldest and furthest known spiral galaxy in our universe.

Lead author Dr Takafumi Tsukui said a state-of-the-art telescope called ALMA allowed them to look at this ancient galaxy in much greater detail.

“Specifically, we were interested in how gas was moving into and throughout the galaxy,” Dr Tsukui said.

“Gas is a key ingredient for forming stars and can give us important clues about how a galaxy is actually fuelling its star formation.”

In this case, the researchers were able to not only capture the motion of the gas around BRI 1335-0417, but also reveal a seismic wave forming — a first in this type of early galaxy.

The galaxy’s disk, a flattened mass of rotating stars, gas and dust, moves in a way not dissimilar to ripples spreading on a pond after a stone is thrown in.

“The vertically oscillating motion of the disk is due to an external source, either from new gas streaming into the galaxy or by coming into contact with other smaller galaxies,” Dr Tsukui said.

“Both possibilities would bombard the galaxy with new fuel for star formation.

“Additionally, our study revealed a bar-like structure in the disk. Galactic bars can disrupt gas and transport it towards the galaxy’s centre. The bar discovered in BRI 1335-0417 is the most distant known structure of this kind.

“Together, these results show the dynamic growth of a young galaxy.”

Because BRI 1335-0417 is so far away, its light takes longer to reach Earth. The images seen through a telescope in the present day are a throwback to the galaxy’s early days — when the Universe was just 10 per cent of its current age.

“Early galaxies have been found to form stars at a much faster rate than modern galaxies. This is true for BRI 1335-0417, which, despite having a similar mass to our Milky Way, forms stars at rate a few hundred times faster,” co-author Associate Professor Emily Wisnioski said.

“We wanted to understand how gas is supplied to keep up with this rapid rate of star formation.

“Spiral structures are rare in the early Universe, and exactly how they form also remains unknown. This study also gives us crucial information on the most likely scenarios.

“While it is impossible to observe the galaxy’s evolution directly, as our observations only give us a snapshot, computer simulations can help piece the story together.”

This vast stellar nursery is located in the constellation Centaurus (the Centaur), at about 6500 light-years from Earth. Young stars within this nebula emit intense radiation that makes the surrounding hydrogen gas glow in shades of pink.

The Running Chicken Nebula actually comprises several regions, all of which we can see in this vast image that spans an area in the sky of about 25 full Moons [1]. The brightest region within the nebula is called IC 2948, where some people see the chicken’s head and others its rear end. The wispy pastel contours are ethereal plumes of gas and dust. Towards the centre of the image, marked by the bright, vertical, almost pillar-like, structure, is IC 2944. The brightest twinkle in this particular region is Lambda Centauri, a star visible to the naked eye that is much closer to us than the nebula itself.

There are, however, many young stars within IC 2948 and IC 2944 themselves — and while they might be bright, they’re most certainly not merry. As they spit out vast amounts of radiation, they carve up their environment much like, well, a chicken. Some regions of the nebula, known as Bok globules, can withstand the fierce bombardment from the ultraviolet radiation pervading this region. If you zoom in to the image, you might see them: small, dark, and dense pockets of dust and gas dotted across the nebula.

Other regions pictured here include, to the upper right, Gum 39 and 40, and to the lower right, Gum 41. Aside from nebulae, there are countless orange, white and blue stars, like fireworks in the sky. Overall in this image, there are more wonders than can be described — zoom in and pan across, and you’ll have a feast for the eyes.

This image is a large mosaic comprising hundreds of separate frames carefully stitched together. The individual images were taken through filters that let through light of different colours, which were then combined into the final result presented here. The observations were conducted with the wide-field camera OmegaCAM on the VST, a telescope owned by the National Institute for Astrophysics in Italy (INAF) and hosted by ESO at its Paranal site in Chile’s Atacama Desert that is ideally suited for mapping the southern sky in visible light. The data that went into making this mosaic were taken as part of the VST Photometric Hα Survey of the Southern Galactic Plane and Bulge (VPHAS+), a project aimed at better understanding the life cycle of stars.

Notes

[1] This image, edge to edge, is 270 light-years wide. It would take an average chicken almost 21 billion years to run across it. That’s much longer than our Universe has been around for.