“One quarter of the global population lives in or downstream from mountainous regions,” said Mohammed Ombadi, first author of the paper published today in Nature. “They are going to be directly affected by this risk.”

Scientists already expect climate change to increase the volume of water falling during extreme events (which typically take place over a few hours to a day), but this study is the first time researchers have looked at whether that extreme precipitation comes as rain or snow. They found that the fraction of water falling as snow decreased in mountainous regions, falling instead as rain — making mountains particularly susceptible to extreme rain hazards. They even put a number to it: For every 1 degree Celsius increase in the global temperature, researchers expect an average of 15% more rain at high elevations.

“This increase in rainfall extremes is not only something that is going to happen from now until the end of the 21^st century — we’re already seeing it,” Ombadi said. “That same rate was also evident in the data from 1950 to 2019. Rainfall extremes in mountains have already been increasing, and will continue to change with that 15% rate.”

While all the mountain ranges in the Northern Hemisphere are seeing the shift from snow to rain, those at greatest risk of extreme rainfall events are the North American Pacific mountain ranges (the Cascades, Sierra Nevada, and coastal ranges from Canada to Southern California), the Himalayas, and high-latitude regions. Researchers are still working to understand why those areas are at higher risk than other mountain ranges such as the Rockies or the Alps.

“We think that North American Pacific mountain ranges are more susceptible to the risk of rainfall extremes than other mountain ranges because a significant portion of snowfall in this region typically occurs at temperatures just below zero degrees Celsius,” Ombadi said. “The slightest change in air temperature will shift this snowfall to rainfall. This is unlike other mountain ranges where snowfall may occur at very low temperatures below zero degrees.”

Ombadi hopes that fellow climate scientists will incorporate the distinction between snowfall and rainfall to improve global climate models, and that civil engineers and planners will use the data to better prepare for intense rain events.

“We need to factor these results into how we design and build the infrastructure in these mountainous regions, so that they can withstand the negative consequences of increases in rainfall extremes,” Ombadi said.

Meanwhile, countries continue efforts to meet targets established by the Paris Agreement that would limit global warming to less than 2 degrees Celsius above pre-industrial levels.

“Our findings revealed a linear relationship between the level of warming and the increase in extreme rainfall: For instance, 1 degree of warming causes 15% more rain, while 3 degrees leads to a 45% increase in rainfall,” Ombadi said. “There are many technologies in progress that could help us reduce greenhouse gas emissions and how much the planet warms. To me, this study shows the need to invest in those clean solutions, and also start preparing for the consequences of warming now.”

This work was funded by the DOE Office of Science Biological and Environmental Research program.

To expand their X-ray spectroscopy observations to liquids, the researchers had to design an apparatus capable of producing a liquid jet with a diameter of less than one micrometre in a vacuum. This was essential because if the jet were any wider, it would absorb some of the X-rays used to measure it.

Molecular pioneer in biochemistry

Using the new method, the researchers were able to gain insights into the processes that led to the emergence of life on Earth. Many scientists assume that urea played a pivotal role here. It is one of the simplest molecules containing both carbon and nitrogen. What’s more, it’s highly likely that urea was present even when the Earth was very young, something that was also suggested by a famous experiment done in the 1950s: American scientist Stanley Miller concocted a mixture of those gases believed to have made up the planet’s primordial atmosphere and exposed it to the conditions of a thunderstorm. This produced a series of molecules, one of which was urea.

According to current theories, the urea could have become enriched in warm puddles — commonly called primordial soup — on the then lifeless Earth. As the water in this soup evaporated, the concentration of urea increased. Through exposure to ionising radiation such as cosmic rays, it’s possible that this concentrated urea produced malonic acid over multiple synthesis steps. In turn, this may have created the building blocks of RNA and DNA.

Why this exact reaction tool place

Using their new method, the researchers from ETH Zurich and the University of Geneva investigated the first step in this long series of chemical reactions to find out how a concentrated urea solution behaves when exposed to ionising radiation.

It’s important to know that the urea molecules in a concentrated urea solution group themselves into pairs, or what are known as dimers. As the researchers have now been able to show, ionising radiation causes a hydrogen atom within each of these dimers to move from one urea molecule to the other. This turns one urea molecule into a protonated urea molecule, and the other into a urea radical. The latter is highly chemically reactive — so reactive, in fact, that it’s very likely to react with other molecules, thereby also forming malonic acid.

The researchers also managed to show that this transfer of a hydrogen atom happens extremely quickly, taking only around 150 femtoseconds, or 150 quadrillionths of a second. “That’s so fast that this reaction preempts all other reactions that might theoretically also take place,” Wörner says. “This explains why concentrated urea solutions produce urea radicals rather than hosting other reactions that would produce other molecules.”

Reactions in liquids are highly relevant

In the future, Wörner and his colleagues want to examine the next steps that lead to the formation of malonic acid. They hope this will help them to understand the origins of life on Earth.

As for their new method, it can also generally be used to examine the precise sequence of chemical reactions in liquids. “A whole host of important chemical reactions take place in liquids — not just all biochemical processes in the human body, but also a great many chemical syntheses relevant to industry,” Wörner says. “This is why it’s so important that we have now expanded the scope of X-ray spectroscopy at high temporal resolution to include reactions in liquids.”

The researchers from ETH Zurich and the University of Geneva were assisted in this work by colleagues from Deutsches Elektronen-Synchrotron DESY in Hamburg, who performed calculations required to interpret measurement data.

The findings are published June 27 in PLOS Biology.

Mutations in Gjb2 cause more than a quarter of all hereditary forms of hearing loss at birth in people, according to some estimates. The connexin 26 protein coded by the gene is in a family of proteins known as GAP junctions, because these proteins span the tiny gap between cells and form a kind of tube that connects two cells to trade ions, metabolites and other molecules that communicate or maintain an equilibrium.

This unexpected finding, according to investigators, suggests a molecular mechanism for the observation that people with this hereditary mutation respond well to cochlear implants, the electronic devices that are designed to mimic sound conduction in the inner ear and can improve hearing in those with severe hearing loss. According to the National Institutes of Health, about 118,100 cochlear implants were implanted in adults and 65,000 in children between December 2019 and March 2021.

The connexin 26 protein in the cochlea, the spiral-like structure in the inner ear, is highly enriched in supportive cells, which, like their name implies, provide structural and nutritional help to surrounding hair cells and auditory neurons.

Previous studies have shown that, without connexin 26, the cochlea fails to develop its normal shape and is incapable of amplifying sound-induced vibrations necessary for efficient sound detection. Despite this disruption to the cochlear structure, this research shows the cochlea is still capable of producing the “spontaneous” activity needed to shape brain development.

“Supportive cells are extremely important for tissues and organs,” says neuroscientist Dwight Bergles, Ph.D., the Diana Sylvestre and Charles Homcy Professor at the Johns Hopkins University School of Medicine. “The new study shows how critical they are for training the auditory system and getting it ready to process sound.”

For the study, Bergles and Calvin Kersbergen, an M.D./Ph.D. candidate in Johns Hopkins’ Medical Scientist Training Program, created a mouse model that lacked connexin 26 specifically in supportive cells in the cochlea.

By using external electrodes to measure electrical responses in the auditory nerve in response to tones or clicks, they found that mice lacking connexin 26 only in supportive cells of the cochlea were, indeed, deaf, demonstrating the crucial role of these intercellular channels in hearing.

However, Bergles and Kersbergen wondered if this change in supportive cells and shape of the cochlea would also disrupt spontaneous activity in younger mice, less than 2 weeks old, before their ear canal opens.

The researchers found that mice without connexin 26 still exhibit bursts of electrical activity in auditory neurons at nearly the same levels as young mice with intact connexin 26. Further investigation revealed that spontaneous activity in supportive cells was able to activate sensory hair cells in the inner ear, leading to normal neuronal activity in sound-processing areas of the brain.

“Even in the absence of connexin 26, we still find robust spontaneous activity in the cochlea in these young mice,” says Bergles.

Bergles says there is now evidence that the role of supportive cells in this early period is to “train” the auditory system to respond to sound at certain frequencies. Since the ear canal isn’t open yet, supportive cells generate their own activity spontaneously to stimulate the mechanically sensitive hair cells in the fluid-filled cochlea.

“It’s as if the cochlea is producing its own ‘sounds’ at this stage of development,” Bergles says. “This practice may help the auditory neurons and circuits in the brain mature before the ear canal opens.”

“It’s like a baseball player in a batting cage, learning the basics of their swing and preparing to face the unpredictability of a real pitcher,” says Bergles.

Finally, the researchers found that spontaneous activity in supportive cells of deaf mice halts once the ear canal opens. At the same time, because the mice can’t process sound, their auditory neurons actually increase their sensitivity to sound.

This hypersensitivity to sound is similar to the phenomenon of hyperacusis, in which normal levels of sound can be painful. In humans, this hearing loss-induced hypersensitivity can also lead to constant ringing of the ears, called tinnitus.

Bergles says the research also suggests a molecular mechanism for why people with this hereditary mutation who receive cochlear implants early on tend to do better than those who receive them later.

“Spontaneous activity in supportive cells in the cochlea may provide the molecular evidence for empirical data showing better outcomes among people who have cochlear implants placed earlier in life,” says Bergles.

The research team plans to study whether they can tap into the spontaneous activity pathway in supportive cells to treat tinnitus and other auditory conditions.

Scientists Travis Babola and Patrick Kanold also contributed to this research.

Funding was provided by the National Institutes of Health (F30DC018711, F32DC019842, U19NS107464, R01DC009607, R01DC008860, P30NS050274).

The catastrophic destruction triggered by the asteroid hitting the Earth resulted in the death of all non-avian dinosaurs in an event termed the Cretaceous-Paleogene (K-Pg) mass extinction. Debate has long raged among researchers over whether placental mammals were present alongside the dinosaurs before the mass extinction, or whether they only evolved after the dinosaurs were done away with. Fossils of placental mammals are only found in rocks younger than 66 million years old, which is when the asteroid hit Earth, suggesting that the group evolved after the mass extinction. However, molecular data has long suggested an older age for placental mammals.

In a new paper published in the journal Current Biology, a team of palaeobiologists from the University of Bristol and the University of Fribourg used statistical analysis of the fossil record to determine that placental mammals originated before the mass extinction, meaning they co-existed with dinosaurs for a short time. However, it was only after the asteroid impact that modern lineages of placental mammals began to evolve, suggesting that they were better able to diversify once the dinosaurs were gone.

The researchers collected extensive fossil data from placental mammal groups extending all the way back to the mass extinction 66 million years ago.

Lead author Emily Carlisle of Bristol’s School of Earth Sciences said: “We pulled together thousands of fossils of placental mammals and were able to see the patterns of origination and extinction of the different groups. Based on this, we could estimate when placental mammals evolved.”

Co-author Daniele Silvestro (University of Fribourg) explained: “The model we used estimates origination ages based on when lineages first appear in the fossil record and the pattern of species diversity through time for the lineage. It can also estimate extinction ages based on last appearances when the group is extinct.”

Co-author Professor Phil Donoghue, also from Bristol, added: “By examining both origins and extinctions, we can more clearly see the impact of events such as the K-Pg mass extinction or the Paleocene-Eocene Thermal Maximum (PETM).”

Primates, the group that includes the human lineage, as well as Lagomorpha (rabbits and hares) and Carnivora (dogs and cats) were shown to have evolved just before the K-Pg mass extinction, which means their ancestors were mingling with dinosaurs. After they survived the asteroid impact, placental mammals rapidly diversified, perhaps spurred on by the loss of competition from the dinosaurs.

Published today in the journal Nature, this embryo model is an organised three-dimensional structure derived from pluripotent stem cells that replicate some developmental processes that occur in early human embryos.

Use of such models allows experimental modelling of embryonic development during the second week of pregnancy. They can help researchers gain basic knowledge of the developmental origins of organs and specialised cells such as sperm and eggs, and facilitate understanding of early pregnancy loss.

“Our human embryo-like model, created entirely from human stem cells, gives us access to the developing structure at a stage that is normally hidden from us due to the implantation of the tiny embryo into the mother’s womb,” said Professor Magdalena Zernicka-Goetz in the University of Cambridge’s Department of Physiology, Development and Neuroscience, who led the work.

She added: “This exciting development allows us to manipulate genes to understand their developmental roles in a model system. This will let us test the function of specific factors, which is difficult to do in the natural embryo.”

In natural human development, the second week of development is an important time when the embryo implants into the uterus. This is the time when many pregnancies are lost.

The new advance enables scientists to peer into the mysterious ‘black box’ period of human development — usually following implantation of the embryo in the uterus — to observe processes never directly observed before.

Understanding these early developmental processes holds the potential to reveal some of the causes of human birth defects and diseases, and to develop tests for these in pregnant women.

Until now, the processes could only be observed in animal models, using cells from zebrafish and mice, for example.

Legal restrictions in the UK currently prevent the culture of natural human embryos in the lab beyond day 14 of development: this time limit was set to correspond to the stage where the embryo can no longer form a twin.

Until now, scientists have only been able to study this period of human development using donated human embryos. This advance could reduce the need for donated human embryos in research.

Zernicka-Goetz says the while these models can mimic aspects of the development of human embryos, they cannot and will not develop to the equivalent of postnatal stage humans.

Over the past decade, Zernicka-Goetz’s group in Cambridge has been studying the earliest stages of pregnancy, in order to understand why some pregnancies fail and some succeed.

In 2021 and then in 2022 her team announced in Developmental Cell, Nature and Cell Stem Cell journals that they had finally created model embryos from mouse stem cells that can develop to form a brain-like structure, a beating heart, and the foundations of all other organs of the body.

The new models derived from human stem cells do not have a brain or beating heart, but they include cells that would typically go on to form the embryo, placenta and yolk sac, and develop to form the precursors of germ cells (that will form sperm and eggs).

Many pregnancies fail at the point when these three types of cells orchestrate implantation into the uterus begin to send mechanical and chemical signals to each other, which tell the embryo how to develop properly.

There are clear regulations governing stem cell-based models of human embryos and all researchers doing embryo modelling work must first be approved by ethics committees. Journals require proof of this ethics review before they accept scientific papers for publication. Zernicka-Goetz’s laboratory holds these approvals.

“It is against the law and FDA regulations to transfer any embryo-like models into a woman for reproductive aims. These are highly manipulated human cells and their attempted reproductive use would be extremely dangerous,” said Dr Insoo Hyun, Director of the Center for Life Sciences and Public Learning at Boston’s Museum of Science and a member of Harvard Medical School’s Center for Bioethics.

Zernicka-Goetz also holds position at the California Institute of Technology and is NOMIS Distinguished Scientist and Scholar Awardee.

The research was funded by the Wellcome Trust and Open Philanthropy.