Males of the study species, Alston’s singing mouse (Scotinomys teguina), produce songs with nearly a hundred audible notes. They challenge competitors by singing in turns, alternating like talking humans, say the study authors. In contrast, standard laboratory mice produce ultrasonic sounds without evident exchanges.

Thus, the new study, led by researchers at NYU School of Medicine, launches a new field by employing a novel mammalian model to examine brain mechanisms behind the sub-second precision of vocal turn-taking.

“Our work directly demonstrates that a brain region called the motor cortex is needed for both these mice and for humans to vocally interact,” says senior study author Michael Long, PhD, an associate professor of neuroscience at NYU School of Medicine.

“We need to understand how our brains generate verbal replies instantly using nearly a hundred muscles if we are to design new treatments for the many Americans for whom this process has failed, often because of diseases such as autism or traumatic events, like stroke,” says Long.

Published online as the cover story of Science on March 1, the study found that, along with brain areas that tell muscles to create notes, separate circuits in the motor cortex enable the fast starts and stops that form a conversation between vocal partners.

“By segregating sound production and control circuits, evolution has equipped the brains of singing mice with the tight vocal control also seen in cricket exchanges, bird duets, and possibly, human discussion,” adds study co-first author Arkarup Banerjee, PhD, a post-doctoral scholar in Long’s lab.

Despite the ubiquity of vocal exchanges in the natural world, he says, there are no suitable mammalian models in neuroscience for their study. Before the new report, the leading model for studying this back-and-forth was the marmoset, a primate whose conversational turns are considerably slower than human speech, and unlikely to result from the fast muscle response to sensory cues (e.g. motor cortical circuitry).

Social Songs Different

The research team found that S. teguina songs — series of notes that evolve predictably as the song goes on — changed in social situations as the mice had to “bend and break the songs” to converse. The tight connection between song patterns and readings taken by electromyography, which captures electrical signals as the brain generates muscle contractions, enabled the team to determine the relationships between brain centers and song musculature while two mice coordinated their responses.

In contrast to the findings of past studies, the researchers found that a functional “hotspot” located at the front of the motor cortex to one side — the orofacial motor cortex or OMC — regulated song timing.

To study the contributions of these specialized brain circuits to social singing, the team interfered with cortical regions in the mice using a number of techniques, including devices that cooled the OMC during songs. Long has helped to pioneer the cooling technique in the study of human brain circuits related to speech.

Called focal cooling, it is a safe way to slow the pace of vocalizations without changing the pitch, tone, or duration of individual notes, say the study authors. They argue that the observed, functional separation in the brain between sound generation and timing functions, this hierarchy, is what makes socially relevant exchanges possible.

Moving forward, the researchers are already using their mouse model to guide related exploration of speech circuits in human brains. By understanding the activity that helps to engage two brains in conversation, they can look for the processes that go awry when disease interferes with communication, potentially spurring the development of new treatments for many disorders.

Along with Long, study authors from the NYU Neuroscience Institute and Department of Otolaryngology at NYU School of Medicine were co-first authors Arkarup Banerjee and Daniel Okobi Jr, as well as Andrew Matheson. The work was done in collaboration with Steven Phelps, PhD, director of the Center for Brain, Behavior and Evolution at the University of Texas at Austin, whose lab pioneered the study of the singing mouse in the lab and field. Some of the authors are also members of the Center for Neural Science at New York University.

This research was supported by the New York Stem Cell Foundation, the Simons Foundation Society of Fellows, and the Simons Collaboration on the Global Brain.

The authors say this stem-cell model offers new insights into the effects of nicotine on individual organs and cells within the developing fetus and can be used to optimize drug and environmental toxicity screening.

“These results are especially important in that they provide a scientific basis for educating the public, especially young women, to keep away from smoking when they are pregnant or considering having a family,” says senior author Joseph C. Wu (@StanfordCVI) of the Stanford University School of Medicine. “Nicotine found in products such as tobacco, e-cigarettes, and nicotine gums may have wide-ranging, harmful effects on different organs of a developing embryo during pregnancy.”

Maternal smoking during pregnancy is an established risk factor for birth defects such as miscarriage, growth restriction, and premature birth. It is closely associated with long-term adverse neurobehavioral, cardiovascular, respiratory, endocrine, and metabolic outcomes in offspring. Nicotine, the main chemical constituent of tobacco smoking, is primarily responsible for the elevated risk. Unfortunately, the introduction and spread of new tobacco products containing nicotine, such as e-cigarettes, is reversing recent progress toward the reduction of tobacco use.

A large body of research has elucidated the negative effects of nicotine in animals, mainly in rodent models. Animal studies have demonstrated that nicotine exposure during pregnancy has detrimental effects on fetal development. But due to interspecies differences, it remains questionable whether this research can be translated to humans. While other studies have examined nicotine toxicity using human cells through bulk RNA-sequencing analysis, these conventional studies did not allow researchers to investigate effects at the single-cell level. As a result, the effects of nicotine on human embryonic development and the underlying molecular mechanisms remain poorly understood.

To address these limitations, Wu and his collaborators used single-cell RNA sequencing to analyze the effects of 21 days of nicotine exposure on the transcriptomes of a total of 12,500 cells generated from hESC-derived embryoid bodies, which are 3D aggregates of different types of pluripotent cells that give rise to the brain, heart, liver, blood vessels, muscles, and other organs. They found that cell survival decreased, suggesting that nicotine can affect embryo development as early as the preimplantation stage.

Nicotine exposure also decreased the size of the embryoid bodies, increased the level of damaging molecules called reactive oxygen species, and resulted in the aberrant formation and differentiation of the embryoid bodies. Moreover, nicotine exposure altered cell cycling in a broad range of progenitor cells differentiated from hESCs and caused dysregulated cell-to-cell communication, another adverse effect that has not been well studied.

“This is important because we know that smoking and nicotine have been shown to increase the pathological risk in endocrine, reproductive, respiratory, cardiovascular, and neurologic systems that rely on intricate and dynamic interactions amongst multiple cell types for homeostasis and function,” Wu says.

The researchers also found that nicotine exposure leads to altered expression of genes implicated in metal toxicity and mitochondrial function, brain malformations and intellectual disability, muscle development and disease, lung disease, and Ca2+-associated arrhythmias that affect the contractility of heart muscle cells.

“A major implication of our study is that we now have validated a new method for evaluating the effect of drugs and environmental toxicity on human embryonic development,” Wu says. “But one major limitation is that we are not able to recapitulate the whole-body physiology of a pregnant woman using differentiation of hESCs into embryoid bodies. For example, the influence of exercise, stress, food, or hormonal changes are not captured in this model.”

In the future, the researchers plan to further investigate the mechanisms of nicotine-induced fetal birth defects. “We hope this will lead to the discovery of novel biomarkers that can help doctors better prevent, diagnose, and treat these diseases,” Wu says. “In addition, we plan to utilize our hESC-derived embryoid body model and single-cell-sequencing technology to investigate the wider effects of other harmful conditions such as air pollution on human embryonic development.”

This study was funded by the National Institutes of Health.

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The University of Queensland-led study analysed crystals in Italy’s famous Mount Etna to reveal how quickly magma moves to the surface.

Dr Teresa Ubide, from UQ’s School of Earth and Environmental Sciences, said the research would provide a better understanding of volcanic systems and improve frameworks for monitoring volcanoes.

“By looking at the so-called magma plumbing systems — I think of them as the ‘inner personalities’ of volcanoes — we can better interpret the signs of magma movement under our feet,” Dr Ubide said.

“The new information on magma transport prior to past volcanic eruptions can provide context to help better respond to future monitoring signals, like seismic measurements from earthquakes.”

Dr Ubide and her team have analysed variations in the chemical composition of volcanic crystals, which form in a chemical pattern known as “sector zoning.”

“Volcanologists and mineralogists have observed sector zoning in crystals for decades, noticing that it might develop when crystals form rapidly,” she said.

“But because the exact origin and implications of sector-zoned crystals in magma were poorly understood, they were typically disregarded in the study of pre-eruptive processes inside volcanoes.

“Now we’ve discovered that they not only record detailed magmatic histories and eruption triggers, but might also provide information on the velocity of magma transport to the surface.”

The research, which builds on previous work analysing volcanic crystals, used a high-tech ultraviolet laser — similar to the technology used for eye surgery — at UQ’s Radiogenic Isotope Facility.

“We’ve been using a ‘cold’ beam laser to remove a thin layer from the surface of the crystals,” Dr Ubide said.

“Then this tiny amount of material is put into a mass spectrometer, an instrument that measures the composition of ‘trace’ elements, reading elements that might weigh lower than 0.1 per cent of the original object.

“We found that the changes in the trace elements in these crystals are extremely sensitive to the processes that take place inside volcanoes, like magma storage and cooling, magma mixing, magma transport and magma’s ascent to the surface.

“It’s an amazing snapshot of what is happening inside volcanoes, providing key insights into their internal plumbing system and helping us better understand these incredible natural wonders.”

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Researchers from the ARC Centre of Excellence for Coral Reef Studies at James Cook University (Coral CoE) and University of Technology Sydney (UTS) report that extreme and sudden changes in salinity, or the ocean salt concentration, cause a biochemical response in corals that is similar to marine heatwaves, but in some ways, more damaging to their cells ability to function.

“Corals are sensitive organisms, known to only tolerate slight changes in their environment. Thriving in clear, sunlit waters — the majority of reef-building corals are found in tropical and subtropical waters with a salinity between 32 to 42 parts per thousand,” said senior author Prof David Miller of Coral CoE.

“During the recent flooding, there are reports that nearshore reefs were exposed to roughly half the normal ocean salinity.”

“Our research shows that this kind of environmental change causes a shock response in corals that prevents normal cell function.”

The researchers used the sequenced genome — a biological blueprint — of the common reef-building coral, Acropora millepora to detect changes in the coral’s biology.

“Using the sophisticated labs at the National Sea Simulator, we put both young and adult corals under a salinity stress test to see how they respond to differing salinity concentrations,” said co-author Dr Jean-Baptiste Raina of UTS.

“We found that there was a common response between both coral life-stages — with the younger corals being more sensitive to low salinity conditions, but faring slightly better with exposure over time.”

“In general, we found that the coral’s cells launch a similar chemical response to reduced salinity as they do for heat stress,” Prof Miller explained.

“However, unlike the heat stress response, corals exposed to reduced salinity experience a complete collapse of their internal cellular protein balance, suggesting that their cells are in deep trouble.”

Although the central Great Barrier Reef may have been spared mass thermal bleaching due to higher-than-normal ocean temperatures this summer, there are many coastal reefs left battling dramatic changes in water conditions from the massive plumes of floodwater.

With the frequency and severity of heavy rainfall and runoff events predicted to increase by 2050, management interventions to increase the resilience of reefs are needed now more than ever.

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Black holes are objects with such strong gravity that everything, including light, is sucked in and cannot escape. Because black holes do not emit light, astronomers must infer their existence from the effects their gravity produces in other objects. Black holes range in mass from about 5 times the mass of the Sun to supermassive black holes millions of times the mass of the Sun. Astronomers think that small black holes merge and gradually grow into large ones, but no one had ever found an intermediate mass black hole, hundreds or thousands of times the mass of the Sun.

A research team led by Shunya Takekawa at the National Astronomical Observatory of Japan noticed HCN-0.009-0.044, a gas cloud moving strangely near the center of the Galaxy 25,000 light-years away from Earth in the constellation Sagittarius. They used ALMA (Atacama Large Millimeter/submillimeter Array) to perform high resolution observations of the cloud and found that it is swirling around an invisible massive object.

Takekawa explains, “Detailed kinematic analyses revealed that an enormous mass, 30,000 times that of the Sun, was concentrated in a region much smaller than our Solar System. This and the lack of any observed object at that location strongly suggests an intermediate-mass black hole. By analyzing other anomalous clouds, we hope to expose other quiet black holes.”

Tomoharu Oka, a professor at Keio University and coleader of the team, adds, “It is significant that this intermediate mass black hole was found only 20 light-years from the supermassive black hole at the Galactic center. In the future, it will fall into the supermassive black hole; much like gas is currently falling into it. This supports the merger model of black hole growth.”

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