Mosquitoes sense infrared from body heat to help track humans down

While a mosquito bite is often no more than a temporary bother, in many parts of the world it can be scary. One mosquito species, Aedes aegypti, spreads the viruses that cause over 100,000,000 cases of dengue, yellow fever, Zika and other diseases every year. Another, Anopheles gambiae, spreads the parasite that causes malaria. The World Health Organization estimates that malaria alone causes more than 400,000 deaths every year. Indeed, their capacity to transmit disease has earned mosquitoes the title of deadliest animal.

Male mosquitoes are harmless, but females need blood for egg development. It's no surprise that there's over 100 years of rigorous research on how they find their hosts. Over that time, scientists have discovered there is no one single cue that these insects rely on. Instead, they integrate information from many different senses across various distances.

A team led by researchers at UC Santa Barbara has added another sense to the mosquito's documented repertoire: infrared detection. Infrared radiation from a source roughly the temperature of human skin doubled the insects' overall host-seeking behavior when combined with CO2 and human odor. The mosquitoes overwhelmingly navigated toward this infrared source while host seeking. The researchers also discovered where this infrared detector is located and how it works on a morphological and biochemical level. The results are detailed in the journalNature.

"The mosquito we study, Aedes aegypti, is exceptionally skilled at finding human hosts," said co-lead author Nicolas DeBeaubien, a former graduate student and postdoctoral researcher at UCSB in Professor Craig Montell's laboratory. "This work sheds new light on how they achieve this."

Guided by thermal infrared

It is well established that mosquitoes like Aedes aegypti use multiple cues to home in on hosts from a distance. "These include CO2 from our exhaled breath, odors, vision, [convection] heat from our skin, and humidity from our bodies," explained co-lead author Avinash Chandel, a current postdoc at UCSB in Montell's group. "However, each of these cues have limitations." The insects have poor vision, and a strong wind or rapid movement of the human host can throw off their tracking of the chemical senses. So the authors wondered if mosquitoes could detect a more reliable directional cue, like infrared radiation.

Within about 10 cm, these insects can detect the heat rising from our skin. And they can directly sense the temperature of our skin once they land. These two senses correspond to two of the three kinds of heat transfer: convection, heat carried away by a medium like air, and conduction, heat via direct touch. But energy from heat can also travel longer distances when converted into electromagnetic waves, generally in the infrared (IR) range of the spectrum. The IR can then heat whatever it hits. Animals like pit vipers can sense thermal IR from warm prey, and the team wondered whether mosquitoes, like Aedes aegypti, could as well.

The researchers put female mosquitoes in a cage and measured their host-seeking activity in two zones. Each zone was exposed to human odors and CO2 at the same concentration that we exhale. However, only one zone was also exposed to IR from a source at skin temperature. A barrier separated the source from the chamber prevented heat exchange through conduction and convection. They then counted how many mosquitoes began probing as if they were searching for a vein.

Adding thermal IR from a 34º Celcius source (about skin temperature) doubled the insects' host-seeking activity. This makes infrared radiation a newly documented sense that mosquitoes use to locate us. And the team discovered it remains effective up to about 70 cm (2.5 feet).

"What struck me most about this work was just how strong of a cue IR ended up being," DeBeaubien said. "Once we got all the parameters just right, the results were undeniably clear."

Previous studies didn't observe any effect of thermal infrared on mosquito behavior, but senior author Craig Montell suspects this comes down to methodology. An assiduous scientist might try to isolate the effect of thermal IR on insects by only presenting an infrared signal without any other cues. "But any single cue alone doesn't stimulate host-seeking activity. It's only in the context of other cues, such as elevated CO2 and human odor that IR makes a difference," said Montell, the Duggan and Distinguished Professor of Molecular, Cellular, and Developmental Biology. In fact, his team found the same thing in tests with only IR: infrared alone has no impact.

A trick for sensing infrared

It isn't possible for mosquitoes to detect thermal infrared radiation the same way they would detect visible light. The energy of IR is far too low to activate the rhodopsin proteins that detect visible light in animal eyes. Electromagnetic radiation with a wavelength longer than about 700 nanometers won't activate rhodopsin, and IR generated from body heat is around 9,300 nm. In fact, no known protein is activated by radiation with such long wavelengths, Montell said. But there is another way to detect IR.

Consider heat emitted by the sun. The heat is converted into IR, which streams through empty space. When the IR reaches Earth, it hits atoms in the atmosphere, transferring energy and warming the planet. "You have heat converted into electromagnetic waves, which is being converted back into heat," Montell said. He noted that the IR coming from the sun has a different wavelength from the IR generated by our body heat, since the wavelength depends on the temperature of the source.

The authors thought that perhaps our body heat, which generates IR, might then hit certain neurons in the mosquito, activating them by heating them up. That would enable the mosquitoes to detect the radiation indirectly.

Scientists have known that the tips of a mosquito's antennae have heat-sensing neurons. And the team discovered that removing these tips eliminated the mosquitoes' ability to detect IR.

Indeed, another lab found the temperature-sensitive protein, TRPA1, in the end of the antenna. And the UCSB team observed that animals without a functional trpA1 gene, which codes for the protein, couldn't detect IR.

The tip of each antenna has peg-in-pit structures that are well adapted to sensing radiation. The pit shields the peg from conductive and convective heat, enabling the highly directional IR radiation to enter and warm up the structure. The mosquito then uses TRPA1 -- essentially a temperature sensor -- to detect infrared radiation.

Diving into the biochemistry

The activity of the heat-activated TRPA1 channel alone might not fully explain the range over which mosquitoes were able to detect IR. A sensor that exclusively relied on this protein may not be useful at the 70 cm range the team had observed. At this distance there likely isn't sufficient IR collected by the peg-in-pit structure to heat it enough to activate TRPA1.

Fortunately, Montell's group thought there might be more sensitive temperature receptors based on their previous work on fruit flies in 2011. They had found a few proteins in the rhodopsin family that were quite sensitive to small increases in temperature. Although rhodopsins were originally thought of exclusively as light detectors, Montell's group found that certain rhodopsins can be triggered by a variety of stimuli. They discovered that proteins in this group are quite versatile, involved not just in vision, but also in taste and temperature sensing. Upon further investigation, the researchers discovered that two of the 10 rhodopsins found in mosquitoes are expressed in the same antennal neurons as TRPA1.

Knocking out TRPA1 eliminated the mosquito's sensitivity to IR. But insects with faults in either of the rhodopsins, Op1 or Op2, were unaffected. Even knocking out both the rhodopsins together didn't entirely eliminate the animal's sensitivity to IR, although it significantly weakened the sense.

Their results indicated that more intense thermal IR -- like what a mosquito would experience at closer range (for example, around 1 foot) -- directly activates TRPA1. Meanwhile, Op1 and Op2 can get activated at lower levels of thermal IR, and then indirectly trigger TRPA1. Since our skin temperature is constant, extending the sensitivity of TRPA1 effectively extends the range of the mosquito's IR sensor to around 2.5 ft.

A tactical advantage

Half the world's population is at risk for mosquito-borne diseases, and about a billion people get infected every year, Chandel said. What's more, climate change and worldwide travel have extended the ranges of Aedes aegypti beyond tropical and subtropical countries. These mosquitoes are now present in places in the US where they were never found just a few years ago, including California.

The team's discovery could provide a way to improve methods for suppressing mosquito populations. For instance, incorporating thermal IR from sources around skin temperature could make mosquito traps more effective. The findings also help explain why loose-fitting clothing is particularly good at preventing bites. Not only does it block the mosquito from reaching our skin, it also allows the IR to dissipate between our skin and the clothing so the mosquitoes cannot detect it.

"Despite their diminutive size, mosquitoes are responsible for more human deaths than any other animal," DeBeaubien said. "Our research enhances the understanding of how mosquitoes target humans and offers new possibilities for controlling the transmission of mosquito-borne diseases."

Read more at Science Daily

When it comes to DNA replication, humans and baker's yeast are more alike than different

Humans and baker's yeast have more in common than meets the eye, including an important mechanism that helps ensure DNA is copied correctly, reports a pair of studies published in the journals Science and Proceedings of the National Academy of Sciences.

The findings visualize for the first time a molecular complex -- called CTF18-RFC in humans and Ctf18-RFC in yeast -- that loads a "clamp" onto DNA to keep parts of the replication machinery from falling off the DNA strand.

It is the latest discovery from longtime collaborators Huilin Li, Ph.D., of Van Andel Institute, and Michael O'Donnell, Ph.D., of The Rockefeller University, to shed light on the intricate mechanisms that enable the faithful passage of genetic information from generation to generation of cells.

"The accurate copying of DNA is fundamental to the propagation of life," Li said. "Our findings add key pieces to the puzzle of DNA replication and could improve understanding of DNA replication-related health conditions."

DNA replication is a tightly controlled process that copies the genetic code, allowing its instructions to be conveyed from one generation of cells to the next. In diseases like cancer, these mechanisms can fail, leading to uncontrolled or faulty replication with devastating consequences.

To date, at least 40 diseases, including many cancers and rare disorders, have been linked to problems with DNA replication.

The process begins by unzipping DNA's ladder-like structure, resulting in two strands called the leading and lagging strands. A molecular construction crew then assembles the missing halves of the strands, turning a single DNA helix into two. Much of this work falls to enzymes called polymerases, which assemble the building blocks of DNA.

On their own, however, polymerases aren't good at staying on the DNA strand. They require CTF18-RFC in humans and Ctf18-RFC in yeast to thread a ring-shaped clamp onto the DNA leading strand, and another clamp loader called RFC in both human and yeast to thread the clamp onto the lagging strand. The clamp then closes and signals to the polymerases that they can begin replicating DNA.

Using high-powered cryo-electron microscopes, Li, O'Donnell and their teams revealed previously unknown facets of the leading strand clamp loaders' structures, including a "hook" that forces the leading strand polymerase to let go of the new DNA strand so it can be recognized by the clamp loader. This distinction represents a key difference between the functions of the leading strand clamp loader (CTF18-RFC) and the lagging strand clamp loader (RFC) and illuminates an important aspect of varying DNA duplication mechanisms on the leading and lagging strands.

Lastly, the study identified shared features between the yeast and human leading strand clamp loaders, which demonstrate an evolutionary link between the two. This finding underscores the value of yeast as powerful yet simple models for studying genetics.

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How evolution tamed a deadly virus and why we should still worry

The story of the rise and fall of western equine encephalitis as a lethal disease offers essential lessons about how a pathogen can gain or lose its ability to jump from animals to humans.

That story is captured in newly published research from Harvard Medical School that identifies the mechanisms the western equine encephalitis virus used to infect humans and matches changes in that ability over time to a decline in illness and deaths caused by the pathogen.

The study results, published July 24 in Nature, offer important lessons for public health experts looking to prepare for future outbreaks, the researchers said.

The work took many unexpected turns, the researchers said. The findings challenge some of the basic assumptions that scientists have relied on in their attempts to understand how viruses interact with human cells and what causes outbreaks to ebb and flow, such as the notion that any given virus targets one host receptor to gain entry and infect cells.

"This was a real scientific detective story," said study senior author Jonathan Abraham, associate professor of microbiology in the Blavatnik Institute at Harvard Medical School. "The virus kept surprising us and taught us some important lessons about how to study viruses."

The researchers identified the specific proteins expressed on host cells that different strains of the virus have used to infect a variety of animals, including horses, humans, and birds over the last century. Their findings tied differences in the virus's ability to sicken humans and horses to changes in the viral genome that left the virus unable to target proteins found in humans and horses, while leaving intact the virus's ability to infect birds and reptiles that serve as reservoirs for the virus.

The surprising diversity and variability in the virus's ability to infect host cells highlights the importance of studying viruses broadly across time, space, and host species to track potential outbreaks and monitor for emerging and re-emerging viruses.

A virus changes

The protagonist in the story is the western equine encephalitis virus (WEEV), a member of a viral family known as alphaviruses.

One key to understanding how a virus interacts with a host is identifying the precise path it takes to enter cells and cause infection.

WEEV and others in the alphavirus family typically attach a spike protein to a compatible protein -- the receptor -- on the surface of a host cell. Once attached to the host receptor, the virus enters the cell. Once inside the cell, the virus hijacks the cells' armamentarium to enable its own replication, spread, and survival.

The researchers made harmless replicas of various viral strains collected from different times and places and tested their ability to infect host cells in lab dishes. They also tested some of the strains in mice.

Several deadly strains of WEEV are known to cause severe brain inflammation in both horses and humans. Some years, thousands of horses were killed and hundreds of humans were sickened. Case fatality rates for people were as high as 15 percent in North America in the early and middle decades of the 20th century.

Abraham's group found that some of these early strains could stick their spike proteins to several different types of receptors to enter animal cells. That was an unexpected finding because the prevailing dogma in virology thus far has been that viruses typically attack by targeting only one type of host cell receptor.

The team observed that the strains circulating during the years of frequent outbreaks could use multiple receptors that are expressed on brain cells of humans and horses, including proteins known as PCDH10 and VLDLR.

Although the virus still circulates between birds, mosquitoes, and other animals, the most recent outbreak in the United States in humans was in 1987, according to the Centers for Disease Control and Prevention. Since then, there have been only five cases identified in the United States.

By contrast, when the researchers tested more recently isolated strains recovered from mosquitos in California in 2005, they found that the viral spike protein failed to recognize the human receptors, but could still interact with similar proteins found in birds.

Based on these findings, the researchers hypothesize that the virus had evolved, perhaps because horses can be vaccinated and are no longer prevalent enough in the agriculture or transportation industries to serve as effective amplifiers for the virus. Alternatively, the researchers note, the virus may have evolved through simple antigenic drifting, a process by which random mutations cause a series of small changes to a viral genome that, over time, may end up changing the way a virus interacts with its host. Whatever the reason, the researchers said, subtle shifts in the shape of the viral spike proteins changed the cellular receptors with which the virus could connect.

This change in targetable host receptors is likely the central reason why the virus "submerged" as a human pathogen in North America, the research team said. This newly gleaned appreciation of the dynamic complexity of viral receptors is an essential tool for understanding how this virus or others like it might one day re-emerge, the scientists said.

"We need to understand what happens to viruses when they submerge, to better prepare for when they re-emerge," said first author Wanyu Li, a Harvard Kenneth C. Griffin Graduate School of Arts and Sciences doctoral student in the virology program in the Harvard Division of Medical Sciences at HMS.

For example, knowing whether dangerous versions of the pathogen persist in isolated populations of insects, or if the virus has gained the ability to infect other animals, could provide important early warning signs for potential resurgences of illnesses that are thought to have disappeared.

A virus's complex behavior

Through their experiments, the researchers discovered that certain old WEEV strains behaved differently than expected.

The team used eastern equine encephalitis virus -- a deadlier cousin of WEEV -- as a control in some experiments. In one test, the team found that an old strain of WEEV could use the same receptor as the eastern virus, which is something that newer WEEV strains could not do. They also found different strains of WEEV that used different receptors. Some strains could stick to avian versions of the receptor protein but not those expressed in human or equine cells.

The findings serve as an important reminder that viruses are part of a dynamic system and that the viruses themselves are dynamic, with subtle but significant differences across time and geography -- a notion that was powerfully underscored by the rapidly shapeshifting SARS-CoV-2 virus that fueled the COVID-19 pandemic, the researchers said.

"It was a wake-up call," Abraham said. "It's telling us that we can't just study one strain of a virus and assume we know the whole story. Viruses seem simple, but they're quite complex, and they're constantly changing."

Applying lessons to pandemic preparedness

In standard virology, researchers often only check a limited number of viral strains. These new findings show that that's not enough to truly understand the virus.

"There's so much more biology to be learned by exploring the diversity of these complex systems," Abraham said. He also noted that it's necessary to explore as much of that viral diversity as possible in order to prepare for possible outbreaks.

Many viruses circulate in insects and animals that live around us, Abraham said. Some, like the tick-borne infection Powassan, which is endemic in New England, occasionally flare up to cause deadly or debilitating disease.

There could be many reasons for the flare-ups, Abraham said. Are there different strains of Powassan that carry different levels of risk? Is it an environmental change or an evolutionary shift in the pathogen itself that causes new outbreaks? Looking at all these aspects and the breadth of viral diversity will help researchers predict and protect against outbreaks.

In another twist, as Abraham and his team conducted their experiments, a new outbreak of WEEV occurred in South America, which had also seen steep declines in the disease in recent years. The viral populations in South and North America appear to be genetically distinct, and the South American strain of the virus doesn't remain viable long enough for migrating birds to transfer it from one continent to the other regularly. Still, Abraham noted, the new outbreak in South America emphasizes the importance of vigilance and of improving scientific understanding of these volatile, shapeshifting viruses.

"WEEV's return caught everyone by surprise," Li said. "Now with its cellular host receptors known, we have the tools to understand the molecular aspects of WEEV's re-emergence."

Abraham and collaborators are now investigating the strains associated with recent outbreak in South America.

"One small shift in the viral genome, in the intensity of a rainy season that allows mosquitos to proliferate, or in the place humans live or work, could trigger an outbreak," Abraham said. "The more we know, the better we'll be able to protect ourselves."

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Brain size riddle solved as humans exceed evolution trend

The largest animals do not have proportionally bigger brains -- with humans bucking this trend -- a new study published in Nature Ecology and Evolution has revealed.

Researchers at the University of Reading and Durham University collected an enormous dataset of brain and body sizes from around 1,500 species to clarify centuries of controversy surrounding brain size evolution.

Bigger brains relative to body size are linked to intelligence, sociality, and behavioural complexity -- with humans having evolved exceptionally large brains.

The new research, published today (Monday, 8 July), reveals the largest animals do not have proportionally bigger brains, challenging long-held beliefs about brain evolution.

Professor Chris Venditti, lead author of the study from the University of Reading, said: "For more than a century, scientists have assumed that this relationship was linear -- meaning that brain size gets proportionally bigger, the larger an animal is. We now know this is not true. The relationship between brain and body size is a curve, essentially meaning very large animals have smaller brains than expected."

Professor Rob Barton, co-author of the study from Durham University, said: "Our results help resolve the puzzling complexity in the brain-body mass relationship. Our model has a simplicity that means previously elaborate explanations are no longer necessary -- relative brain size can be studied using a single underlying model."

Beyond the ordinary

The research reveals a simple association between brain and body size across all mammals which allowed the researchers to identify the rule-breakers -- species which challenge the norm.

Among these outliers includes our own species, Homo sapiens, which has evolved more than 20 times faster than all other mammal species, resulting in the massive brains that characterise humanity today.

But humans are not the only species to buck this trend.

All groups of mammals demonstrated rapid bursts of change -- both towards smaller and larger brain sizes.

For example, bats very rapidly reduced their brain size when they first arose, but then showed very slow rates of change in relative brain size, suggesting there may be evolutionary constraints related to the demands of flight.

There are three groups of animals that showed the most pronounced rapid change in brain size: primates, rodents, and carnivores.

In these three groups, there is a tendency for relative brain size to increase in time (the "Marsh-Lartet rule"). This is not a trend universal across all mammals, as previously believed.

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Chimpanzees gesture back and forth quickly like in human conversations

When people are having a conversation, they rapidly take turns speaking and sometimes even interrupt. Now, researchers who have collected the largest ever dataset of chimpanzee "conversations" have found that they communicate back and forth using gestures following the same rapid-fire pattern. The findings are reported on July 22 in the journal Current Biology.

"While human languages are incredibly diverse, a hallmark we all share is that our conversations are structured with fast-paced turns of just 200 milliseconds on average," said Catherine Hobaiter  at the University of St Andrews, UK. "But it was an open question whether this was uniquely human, or if other animals share this structure."

"We found that the timing of chimpanzee gesture and human conversational turn-taking is similar and very fast, which suggests that similar evolutionary mechanisms are driving these social, communicative interactions," says Gal Badihi, the study's first author.

The researchers knew that human conversations follow a similar pattern across people living in places and cultures all over the world. They wanted to know if the same communicative structure also exists in chimpanzees even though they communicate through gestures rather than through speech. To find out, they collected data on chimpanzee "conversations" across five wild communities in East Africa.

Altogether, they collected data on more than 8,500 gestures for 252 individuals. They measured the timing of turn-taking and conversational patterns. They found that 14% of communicative interactions included an exchange of gestures between two interacting individuals. Most of the exchanges included a two-part exchange, but some included up to seven parts.

Overall, the data reveal a similar timing to human conversation, with short pauses between a gesture and a gestural response at about 120 milliseconds. Behavioral responses to gestures were slower. "The similarities to human conversations reinforce the description of these interactions as true gestural exchanges, in which the gestures produced in response are contingent on those in the previous turn," the researchers write.

"We did see a little variation among different chimp communities, which again matches what we see in people where there are slight cultural variations in conversation pace: some cultures have slower or faster talkers," Badihi says.

"Fascinatingly, they seem to share both our universal timing, and subtle cultural differences," says Hobaiter. "In humans, it is the Danish who are 'slower' responders, and in Eastern chimpanzees that's the Sonso community in Uganda."

This correspondence between human and chimpanzee face-to-face communication points to shared underlying rules in communication, the researchers say. They note that these structures could trace back to shared ancestral mechanisms. It's also possible that chimpanzees and humans arrived at similar strategies to enhance coordinated interactions and manage competition for communicative "space." The findings suggest that human communication may not be as unique as one might think.

"It shows that other social species don't need language to engage in close-range communicative exchanges with quick response time," Badihi says. "Human conversations may share similar evolutionary history or trajectories to the communication systems of other species suggesting that this type of communication is not unique to humans but more widespread in social animals."

In future studies, the researchers say they want to explore why chimpanzees have these conversations to begin with. They think chimpanzees often rely on gestures to ask something of one another.

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Unveiling 1,200 years of human occupation in Canada's Arctic

A recent study provides new insights into ancient cultures in Canada's Arctic, focusing on Paleo-Inuit and Thule-Inuit peoples over thousands of years. Jules Blais, professor of biology at the University of Ottawa, and a team of researchers detected human presence and settlements on Somerset Island, Nunavut, by analyzing sediment samples.

The Arctic has been home to various cultures, such as the Paleo-Inuit (2500 BCE to 1250 CE) and the Thule-Inuit (1200 to 1500 CE). Although historical evidence is scarce, this recent study provides valuable insight into their presence.

The study discovered evidence of Paleo-Inuit presence on Somerset Island in Nunavut, Canada, where it was lacking.

The innovative research methodologies revealed detailed information about past human history without traditional artifacts.

Professor Jules Blais says, "By analyzing pond sediment samples, we were able to construct detailed histories of site occupation. This includes clear evidence of Paleo-Inuit presence and indications that the Thule-Inuit arrived earlier than previously estimated."

The research used archeological evidence and sedimentary biomarkers to study prehistoric settlement on Somerset Island.

Sediment cores from island ponds were analyzed for trace elements and organic compounds.

Results showed that the Thule-Inuit population increased from the 13th to 15th centuries.

The researchers also showed high levels of metals like lead, copper, zinc and nickel in twentieth-century sediment, suggesting air pollution during that time.

Blais says, "We used generalized additive models (GAMs) and radiocarbon dating techniques to identify key time points in the sediment record corresponding to the expected dates of Thule-Inuit arrival and site abandonment. This approach allowed us to detect periods of significant change in sediment proxies, providing a chronological framework for understanding the history of human occupation on the island."

This research underscores the importance of interdisciplinary approaches in archeology and highlights the significance of sedimentary archives in reconstructing past human activities and environmental conditions.

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Can animals count?

Research co-led by neuroscientists Professor Yung Wing-ho from City University of Hong Kong (CityUHK) and Professor Ke Ya from The Chinese University of Hong Kong (CUHK) Faculty of Medicine (CU Medicine) has made a groundbreaking discovery regarding number sense in animals by confirming the existence of discrete number sense in rats, offering a crucial animal model for investigating the neural basis of numerical ability and disability in humans.

The research team has developed an innovative approach that employs a novel numerical learning task, brain manipulation techniques and artificial intelligence modelling, and that resolves an ongoing argument about whether rats have a sense of numbers. The study sheds light on the mechanisms underlying numerical ability. The findings have been published in the renowned multidisciplinary scientific journal Science Advances.

Number sense closely linked to survival and intelligence

Number sense is a fundamental ability in animals' perception of the world and increases their chances of survival. It is also an important cognitive ability, which is fundamental to mathematical aptitude, a hallmark of human intelligence. About 3% to 7% of people suffer from dyscalculia, a learning disability that affects the ability to learn arithmetic and mathematics of people of normal intelligence; a deficit in number sense is one of the major symptoms.

Number sense refers to the capability to compare, estimate and manipulate nonsymbolic numerical quantities, rather than associated magnitudes, which are continuous dimensions inherent in a group of items, such as the area of visual objects or the duration of sound pulses. There have been challenges regarding whether number sense can be assessed in isolation from the influence of continuous magnitudes. Also, there has been a vivid ongoing debate regarding whether the sense of magnitude or the sense of number is more fundamental.

Study confirms that the rat brain has a specific area for dealing with numbers

The research team minimised the influence of continuous magnitudes in numerical tests and conducted meticulous quantitative analyses in the study to determine the respective contributions of numbers and magnitudes. They developed an algorithm to generate stimuli that enable animals to focus only on numbers, minimising other distracting factors. This will help scientists better understand how animals perceive and quantify numbers.

The study found that rats without any previous knowledge of numbers were able to develop a sense of numbers when trained with sounds representing two or three numbers. Despite the influence of continuous magnitudes, the rats consistently focused on the number of sounds when making choices for food rewards.

Professor Yung, Associate Dean of the Jockey Club College of Veterinary Medicine and Life Sciences and Chair Professor of Cognitive Neuroscience at CityUHK, said, "Our study helps dissect the relationship between magnitude and numerosity processing. We discovered that when we blocked a specific part of the rats' brain, called the posterior parietal cortex, their ability to understand numbers was affected but not their sense of magnitude. This suggests that the brain has a specific area for dealing with numbers. In fact, this is the first time scientists have demonstrated that rats have the ability to discriminate and categorise three different numbers in a single test, surpassing a simple quantity comparison."

Professor Ke from the School of Biomedical Sciences at CU Medicine expressed excitement about the findings. "The study not only solves a long-standing mystery about how brains handle numbers, but also offers new insights into studying the specific neural circuits involved in number processing in animals and how genes are associated with mathematical ability," she said. "Furthermore, the findings from neural network modelling could have practical applications in the field of artificial intelligence. In the future, our increased understanding of the brain mechanisms underlying the processing of numbers may contribute to the development of interventions for individuals with numerical difficulties."

Read more at Science Daily

Study shedding new light on Earth's global carbon cycle could help assess liveability of other planets

Research has uncovered important new insights into the evolution of oxygen, carbon, and other vital elements over the entire history of Earth – and it could help assess which other planets can develop life, ranging from plants to animals and humans.

The study, published today in Nature Geoscience and led by a researcher at the University of Bristol, reveals for the first time how the build up of carbon-rich rocks has accelerated oxygen production and its release into the atmosphere.

Until now the exact nature of how the atmosphere became oxygen-rich has long eluded scientists and generated conflicting explanations.

As carbon dioxide is steadily emitted by volcanoes, it ends up entering the ocean and forming rocks like limestone.

As global stocks of these rocks build up they can then release their carbon during tectonic processes, including mountain building and metamorphism.

Using this knowledge, the scientists built a unique sophisticated computer model to more accurately chart key changes in the carbon, nutrient and oxygen cycles deep into Earth’s history, over 4 billion years of the planet’s lifetime.

Lead author and biogeochemist Dr Lewis Alcott, Lecturer in Earth Sciences at the University of Bristol, said: “This breakthrough is important and exciting because it may help us understand how planets, other than Earth, have the potential to support intelligent, oxygen-breathing life.

“Previously we didn’t have a clear idea of why oxygen rose from very low concentrations to present-day concentrations, as computer models haven’t previously been able to accurately simulate all the possible feedbacks together. This has puzzled scientists for decades and created different theories.”

The discovery indicates that older planets, originating billions of years ago like Earth, may have better prospects to accumulate enough carbon-rich deposits in their crust, which could facilitate rapid recycling of carbon and nutrients for life.

The findings showed this gradual carbon enrichment of the crust results in ever-increasing recycling rates of carbon and various minerals, including the nutrients needed for photosynthesis, the process green plants use sunlight to absorb nutrients from carbon dioxide and water.

This cycle therefore steadily speeds up oxygen production over the passage of Earth’s history.

The research, which started whilst Dr Alcott was a Hutchinson Postdoctoral Fellow at Yale University in the United States, paves the way for future work to further unravel the complex interrelationships between planetary temperature, oxygen, and nutrients.

Read more at Science Daily

New roadmap to prevent pandemics centers on protecting biodiversity

An international team of 25 scientists has proposed a roadmap for how to prevent the next pandemic by conserving natural areas and promoting biodiversity, thereby providing animals with enough food, safe havens and distance to limit contact and the transfer of pathogens to humans.

Pandemics begin when disease-harboring animals, such as bats, come in close proximity with people, livestock or other animals and pass on new pathogens.

Viruses such as SARS-CoV-2, SARS-CoV-1, Nipah, Hendra and possibly Ebola have all fatally spilled over from bats to humans, sometimes through an intermediate host.

"The world is focused on how can we detect and then contain a novel pathogen once it is circulating in humans, rather than how can we prevent that pathogen from entering the human population in the first place," said Raina Plowright, professor in the Department of Public and Ecosystem Health at Cornell University, and first author of the paper, "Ecological Countermeasures to Prevent Pathogen Spillover and Subsequent Pandemics," published in Nature Communications.

The pandemic-prevention strategy is based on insights from a pair of 2022 papers that serve as a case study applicable to all animals that potentially carry zoonotic diseases.

Those papers -- about how bats can spread fatal Hendra virus to horses and people -- explained that when bats lose their natural habitats and winter food sources, their large populations splinter and they migrate in small groups to agricultural and urban areas.

They also become stressed, partly due to inadequate food sources, and they shed more virus in their urine.

The virus falls to the ground where grazing horses become infected; horses in turn can then infect people.

But when natural habitats can provide adequate food, especially in fallow winter months, the bats return to these habitats, aggregate in large numbers, and stop shedding virus.

The roadmap uses this and other case studies to explain the mechanisms linking environmental change and spillover of pathogens from animals to humans, and identifies ecological interventions to disrupt these links and policy frameworks to implement them.

Ecological interventions begin by protecting the places where animals eat.

"We need to make sure there's always an abundant supply of food available at all times of year, especially when animals are in stressful life history stages like reproduction and migration," Plowright said.

Next, it's important to protect where animals may roost or aggregate, as tens of thousands of bats can roost in canopies and caves, so when these areas are disturbed, these populations can splinter, move and shed more virus.

Also, cave dwelling bats may not have other caves to move to, in which case they stay put, become more stressed and likely shed more virus.

Protecting lands that act as buffers between people and wildlife is also key.

"There are trillions of microbes in nature, but we rarely actually get sick, because there are many, many barriers between us and new pathogens," Plowright said.

Lastly, for communities who come in contact with animals, it's important to ensure people have the protection that they need to avoid pathogen exposure, Plowright said.

The study's authors emphasize the need for an international agency or panel that can assess and synthesize data on pandemic prevention, preparedness and response and collect metrics on intactness of landscapes, ecological integrity and biodiversity.

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Stem cell model offers first glimpse of early human embryonic development

It's one of life's most defining moments -- that crucial step in embryonic development, when an indistinct ball of cells rearranges itself into the orderly three-layered structure that sets the stage for all to come. Known as gastrulation, this crucial process unfolds in the third week of human development. "Gastrulation is the origin of our own individualization, the emergence of our axis," says Rockefeller's Ali Brivanlou. "It is the first moment that separates our heads from our behinds."

Observing the molecular underpinnings of this pivotal event would go a long way toward helping scientists prevent miscarriages and developmental disorders. But studying human gastrulation has proven both technologically difficult and ethically complicated, and thus current approaches have had limited success in expanding our understanding of early human development. Now Brivanlou and colleagues have demonstrated how a stem cell model system known as a blastoid can allow the study of the nuances of human gastrulation in the presence of pre-implantation extra-embryonic cell types. Their study, published in Stem Cell Reports, describes the scientific and clinical potential of this new platform.

"Gastrulation was a tremendous black box. We had never seen ourselves at that stage," Brivanlou says. "This moves us closer to understanding how we begin."

A better blastocyst

Prior to implantation, an embryo is a ball of about 250 cells organized as a blastocyst. This elusive ball of cells was difficult to study directly, so scientists developed blastoids -- stem-cell-based blastocyst models. Blastoids can be cloned, experimentally manipulated, and programmed, allowing scientists to study identical blastoids over and over again.

The question was whether blastoids could gastrulate in vitro. Unlike a blastocyst in vivo, which rolls around in the uterus until it attaches to maternal tissue, blastoids were good at modeling the ball of cells from which life emerges, but it remained unclear whether this in vitro model could model later stages of human development. That is, until Brivanlou developed a platform to allow blastoids to attach in vitro, and thereby progress toward gastrulation.

"We were then able to see epiblast symmetry breaking, marked by BRA expression, for the first time with the high molecular resolution," says Riccardo De Santis, a research associate in the Brivanlou lab and lead author on the study. "This allowed us to start asking more detailed questions about the earliest moments of life."

With this unprecedented clarity, the team directly observed two key moments in gastrulation: the first epiblast symmetry-breaking event and the emergence of the molecular markers of the primitive streak and mesoderm upon in vitro attachment.

The primitive streak is a structure that marks the beginning of gastrulation and lays the foundation for the three primary layers of the embryo. One of those layers, the mesoderm, forms during gastrulation and gives rise to muscles, bones, and the circulatory system. The team discovered that, as early as seven days after attachment, they were already able to use molecular markers to detect the earliest signature of a nascent primitive streak and mesodermal cells.

To confirm their findings, the team also compared the blastoid results with data from in vitro attached human embryos and demonstrated that blastoids express the same genes in vitro that a regular embryo would at that stage in vivo, a strong demonstration of the power of blastoids as models for human embryonic development. Further highlighting the power of the lab's in vitro attached blastoid system, the team then used it to demonstrate that pathways that regulate the rise of the primitive streak and mesoderm in vivo also regulate blastoids symmetry breaking in vitro -- all with nothing but stem-cell-derived blastoid models.

Along the way, the team also demonstrated that gastrulation in vitro can begin at day 12, earlier than once thought. "This will change textbooks," Brivanlou says. "We've contributed to redefining the molecular signature and timing of the onset of gastrulation upon in vitro attachment."

Therapeutic possibilities

The results demonstrate that blastoids, when combined with the Brivanlou lab's unique attachment platform, are now capable of conveying insights into early human development that have long been inaccessible. De Santis envisions a future in which blastoid-based research leads to advancements in diagnosing and treating developmental disorders, or offers insights into potential causes of early miscarriages during gastrulation.

"Many couples can't have babies because the embryo doesn't attach properly, and many miscarriages occur in the first few weeks of pregnancy," De Santis explains. "We now have a model system that can help us understand the molecular mechanism that defines whether a pregnancy will be successful or not." In the near future, De Santis hopes to combine this method with machine learning to help predict pregnancy outcomes and the trajectories of developmental disorders by observing how model blastoids built with particular genetic makeups fare in vitro.

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Researchers propose a new way to identify when babies become conscious

Academics are proposing a new and improved way to help researchers discover when consciousness emerges in human infancy.

When over the course of development do humans become conscious? When the seventeenth-century French philosopher René Descartes was asked about infant consciousness by his critics, he eventually suggested that infants might have thoughts, albeit ones that are simpler than those of adults. Hundreds of years later, the issue of when human beings become conscious is a question which remains a challenge for psychologists and philosophers alike.

But now, in response to a recent article in Trends in Cognitive Sciences, two academics from the University of Birmingham have suggested an improved way to help scientists and researchers identify when babies become conscious.

In a Letter to the Editor, also published in Trends in Cognitive Sciences, Dr Henry Taylor, Associate Professor of Philosophy, and Andrew Bremner, Professor of Developmental Psychology, have explored a new approach which is being proposed, that involves identifying markers of consciousness in adults, and then measuring when babies start to exhibit larger numbers of these in development.

Dr Taylor says: "For example, imagine that in adults, we know that a certain very specific behaviour, or a specific pattern of brain activation always comes along with consciousness. Then, if we can identify when this behaviour or brain activation arises in babies, we have good reason to think that this is when consciousness emerges in babies. Behaviours and brain activations like this are what we call 'markers' of consciousness."

This kind of approach is desperately needed since babies (unlike adults) cannot tell you what they are conscious of. Professor Bremner said: "It is really hard to establish when babies become conscious. This is mostly because infants can't report their experiences and, as most parents will know, can be rather uncooperative particularly when it comes to experimental tasks. As we can't just ask babies when they become conscious, the best approach is to try to identify a broad range of markers of consciousness, which appear in early development and late development, and then group them together, this could help us identify when consciousness emerges."

In the recent article the researchers (Prof. Tim Bayne and colleagues) suggested four specific markers of consciousness, some of which are present in the late stages of gestation, and others which are found in early infancy. Based on this, the study argues that consciousness emerges early (from the last prenatal trimester).

But Professor Bremner and Dr Taylor say that this ignores other markers of consciousness. Previous research has identified a separate cluster of markers. These include:

• Pointing (bringing a social partner's attention to an object and checking). • Intentional control (intentional means-end coordination of actions -- e.g., pulling a support to retrieve a distal object). • Explicit memory (deferred imitation of actions).

Dr Taylor said: "One of the complicated issues is that it does not look like all the markers point to the same age for the emergence of consciousness. The ones mentioned by Bayne and colleagues suggest somewhere between the third trimester of pregnancy and early infancy, but other markers suggest the age might be around one year old. In fact, at the really extreme end, some markers only emerge at around 3-4 years. Because there are so many different markers of consciousness which appear in early and late development it is extremely hard to come to a conclusion."

Professor Bremner concluded: "We propose that a broad approach to markers, including those that emerge in early and late stage, is needed. We also recommend that a range of developmental models of the onset of consciousness should be considered. For instance, it may be that some markers emerge in one cluster in early development, with others in a later cluster. As well as this there may be a continuous and gradual emergence of certain markers stretching over gestation and throughout early life.

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Humans have driven the Earth's freshwater cycle out of its stable state

A new analysis of freshwater resources across the globe shows that human activity has pushed variation in the planet's freshwater cycle well outside of its pre-industrial range. The study shows that the updated planetary boundary for freshwater change was surpassed by the mid-twentieth century. In other words, for the past century, humans have been pushing the Earth's freshwater system far beyond the stable conditions that prevailed before industrialization.

This is the first time that global water cycle change has been assessed over such a long timescale with an appropriate reference baseline.

The findings, published in Nature Water, show that human pressures, such as dam construction, large-scale irrigation and global warming, have altered freshwater resources to such an extent that their capacity to regulate vital ecological and climatic processes is at risk.

The international research team calculated monthly streamflow and soil moisture at a spatial resolution of roughly 50x50 kilometers using data from hydrological models that combine all major human impacts on the freshwater cycle.

As a baseline, they determined the conditions during the pre-industrial period (1661-1860). They then compared the industrial period (1861-2005) against this baseline.

Their analysis revealed an increase in the frequency of exceptionally dry or wet conditions -deviations in streamflow and soil moisture.

Dry and wet deviations have consistently occurred over substantially larger areas since the early 20th century than during the pre-industrial period.

Overall, the global land area experiencing deviations has nearly doubled compared with pre-industrial conditions.

'We found that exceptional conditions are now much more frequent and widespread than before, clearly demonstrating how human actions have changed the state of the global freshwater cycle', says Vili Virkki, a doctoral researcher at Aalto University and one of the lead authors of the paper.

Because the analysis was done at a high spatial and temporal resolution, the researchers could explore geographical differences in the deviations.

Exceptionally dry streamflow and soil moisture conditions became more frequent in many tropical and subtropical regions, while many boreal and temperate regions saw an increase in exceptionally wet conditions, especially in terms of soil moisture.

These patterns match changes seen in water availability due to climate change.

There were more complex patterns in many regions with a long history of human land use and agriculture.

For example, the Nile, Indus and Mississippi river basins have experienced exceptionally dry streamflow and wet soil moisture conditions, indicating changes driven by irrigation.

'Using a method that's consistent and comparable across hydrological variables and geographical scales is crucial for understanding the biophysical processes and human actions that drive the changes we're seeing in freshwater,' explains Miina Porkka, who co-led the study at Aalto before moving to the University of Eastern Finland.

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Human stem cells coaxed to mimic the very early central nervous system

The first stem cell culture method that produces a full model of the early stages of the human central nervous system has been developed by a team of engineers and biologists at the University of Michigan, the Weizmann Institute of Science, and the University of Pennsylvania.

"Models like this will open doors for fundamental research to understand early development of the human central nervous system and how it could go wrong in different disorders," said Jianping Fu, U-M professor of mechanical engineering and corresponding author of the study in Nature.

The system is an example of a 3D human organoid -- stem cell cultures that reflect key structural and functional properties of human organ systems but are partial or otherwise imperfect copies.

"We try to understand not only the basic biology of human brain development, but also diseases -- why we have brain-related diseases, their pathology, and how we can come up with effective strategies to treat them," said Guo-Li Ming, who along with Hongjun Song, both Perelman Professors of Neuroscience at UPenn and co-authors of the study, developed protocols for growing and guiding the cells and characterized the structural and cellular characteristics of the model.

For example, organoids developed using patient-derived stem cells may be used for identifying which drugs offer the most successful treatment. Already, human brain and spinal cord organoids are used to study neurological and neuropsychiatric diseases, but they often mimic one part of the central nervous system and are disorganized. The new model, in contrast, recapitulates the development of all three sections of embryonic brain and spinal cord simultaneously, a feat that has not been achieved in previous models.

"The system itself is really groundbreaking," said Orly Reiner, the Berstein-Mason Professorial Chair of Neurochemistry at Weizmann and co-author of the study who developed cellular tools to identify neural cell types in the model. "A model that mimics this structure and organization has not been done before, and it offers numerous possibilities for studying human brain development and especially developmental brain diseases."

While the model is faithful to many aspects of the early development of the brain and spinal cord, the team notes several important differences. For one, neural tube formation -- the very first stage of central nervous system development -- is very different. The model can't be used to simulate disorders that stem from improper closure of the neural tube such as spina bifida.

Instead, the model started with a row of stem cells roughly the size of the neural tube found in a 4-week-old embryo -- about 4 millimeters long and 0.2 millimeters in width. The team stuck the cells to a chip patterned with tiny channels that the team used to introduce materials that enabled the stem cells to grow and guided them toward building a central nervous system.

The team then added a gel that allowed the cells to grow in three dimensions and chemical signals that nudged them to become the precursors of neural cells. In response, the cells formed a tubular structure. Next, the team introduced chemical signals that helped the cells identify where they were within the structure and progress to more specialized cell types. As a result, the system organized itself to mimic the forebrain, midbrain, hindbrain and spinal cord in a way that mirrors embryonic development.

"As an engineer, the challenging part is to learn neural development and stem cell biology," said Xufeng Xue, first author of the study and a postdoctoral fellow in mechanical engineering U-M. "It was a team effort to make this happen, with amazing collaborators at UPenn and Weizmann."

The team grew the cells for 40 days, simulating development of the central nervous system to about 11 weeks post-fertilization. In this time, the team was able to demonstrate the roles of specific genes in spinal cord development and learn how certain cell types in the early human nervous system differentiate into different cells with specialized functions.

"In many cases, animal models simply do not recapitulate either the characteristics or the degree of severity seen in human brain diseases such as microcephaly," Song said. "Even nonhuman primates are not the same. So in the context of disease biology and treatment strategies, a human cell model is almost irreplaceable."

The team plans to apply the model to study different human brain diseases using patient derived stem cells.

Xue hopes to continue using this model to study the interplay among different parts of the brain during development. He is also interested in studying how the brain sends instructions for movement via the spinal cord. This line of inquiry, which could shed new light on disorders like paralysis, would require the neurons to link up into working circuits -- something that was not observed in this study.

Insoo Hyun, a bioethicist at the Museum of Science in Boston who was not part of the study, notes that experiments like these are closely scrutinized before they are allowed to move forward.

"Research groups must be clear about the scientific question they are trying to answer -- and that the degree of development they allow in the model is the minimum to answer the question," he said.

The model does not include peripheral nerves or functioning neural circuitry -- features that are critical for humans' ability to experience our environment and process that experience.

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Neanderthals and humans lived side by side in Northern Europe 45,000 years ago

A genetic analysis of bone fragments unearthed at an archaeological site in central Germany shows conclusively that modern humans -- Homo sapiens -- had already reached Northern Europe 45,000 years ago, overlapping with Neanderthals for several thousand years before the latter went extinct.

The findings establish that the site near Ranis, Germany, which is known for its finely flaked, leaf-shaped stone tool blades, is among the oldest confirmed sites of modern human Stone Age culture in north central and northwestern Europe.

The evidence that Homo sapiens and Homo neanderthalensis lived side by side is consistent with genomic evidence that the two species occasionally interbred. It also feeds the suspicion that the invasion of Europe and Asia by modern humans some 50,000 years ago helped drive Neanderthals, which had occupied the area for more than 500,000 years, to extinction.

The genetic analysis, along with an archaeological and isotopic analysis and radiocarbon dating of the Ranis site, are detailed in a trio of papers appearing today in the journals Nature and Nature Ecology and Evolution.

The stone blades at Ranis, referred to as leaf points, are similar to stone tools found at several sites in Moravia, Poland, Germany and the United Kingdom. These tools that are thought to have been produced by the same culture, referred to as the Lincombian-Ranisian-Jerzmanowician (LRJ) culture or technocomplex. Because of previous dating, the Ranis site was known to be 40,000 years old or older, but without recognizable bones to indicate who made the tools, it was unclear whether they were the product of Neanderthals or Homo sapiens.

The new findings demonstrate that "Homo sapiens made this technology, and that Homo sapiens were this far north at this time period, which is 45,000 years ago," said Elena Zavala, one of four first authors of the Nature paper and a Miller Research Fellow at the University of California, Berkeley. "So these are among the earliest Homo sapiens in Europe."

Zavala was a Ph.D. student at the Max Planck Institute for Evolutionary Anthropology (MPI-EVA) in Leipzig in 2018 when she first began working on the project, which was a major effort spearheaded by Jean-Jacque Hublin, former director of the institute and a professor at the Collège de France in Paris.

"The Ranis cave site provides evidence for the first dispersal of Homo sapiens across the higher latitudes of Europe. It turns out that stone artifacts that were thought to be produced by Neanderthals were, in fact, part of the early Homo sapiens toolkit," Hublin said. "This fundamentally changes our previous knowledge about the period: Homo sapiens reached northwestern Europe long before Neanderthal disappearance in southwestern Europe."

Bones from maternal relatives?

Zavala conducted the genetic analysis of hominid bone fragments from the new and deeper excavations at Ranis between 2016 and 2022 and from earlier excavations in the 1930s. Because the DNA in ancient bones is highly fragmented, she employed special techniques to isolate and sequence the DNA, all of it mitochondrial DNA (mtDNA) that is inherited solely from the mother.

"We confirmed that the skeletal fragments belonged to Homo sapiens. Interestingly, several fragments shared the same mitochondrial DNA sequences -- even fragments from different excavations," she said. "This indicates that the fragments belonged to the same individual or their maternal relatives, linking these new finds with the ones from decades ago."

The bone fragments were initially identified as human through analysis of bone proteins -- a field called paleoproteomics -- by another first author, Dorothea Mylopotamitaki, a doctoral student at the Collège de France and fomerly of MPI-EVA.

By comparing the Ranis mitochondrial DNA sequences with mtDNA sequences obtained from human remains at other paleolithic sites in Europe, Zavala was able to construct a family tree of early Homo sapiens across Europe. All but one of the 13 Ranis fragments were quite similar to one another and, surprisingly, resembled mtDNA from the 43,000-year-old skull of a woman discovered in a cave at Zlatý k?? in the Czech Republic. The lone standout grouped with an individual from Italy.

"That raises some questions: Was this a single population? What could be the relationship here?" Zavala said. "But with mitochondrial DNA, that's only one side of the history. It's only the maternal side. We would need to have nuclear DNA to be able to start looking into this."

A transitional site between Middle and Upper Paleolithic

Zavala specializes in the analysis of DNA found in long-buried bones, on bone tools and in sediment. Her search through sediment from various levels of the Ranis excavation turned up DNA from a broad array of mammals, but none from hominids. The analysis, combined with morphological, isotopic and proteomic analysis of bone fragments, paints a picture of the environment at that time and of the diet of both humans and animals that occupied the cave over the millennia.

The presence of reindeer, cave bear, woolly rhinoceros and horse bones, for example, indicated cold climatic conditions typical of steppe tundra and similar to conditions in Siberia and northern Scandinavia today, and a human diet based on large terrestrial animals. The researchers concluded that the cave was used primarily by hibernating cave bears and denning hyenas, with only periodic human presence.

"This lower-density archaeological signature matches other Lincombian-Ranisian-Jerzmanowician sites and is best explained by expedient visits of short duration by small, mobile groups of pioneer H. sapiens," according to one of the papers published in Nature Ecology and Evolution.

"This shows that even these earlier groups of Homo sapiens dispersing across Eurasia already had some capacity to adapt to such harsh climatic conditions," said Sarah Pederzani, a postdoctoral fellow at the University of La Laguna in Spain, who led the paleoclimate study of the site. "Until recently, it was thought that resilience to cold-climate conditions did not appear until several thousand years later, so this is a fascinating and surprising result."

The Ranis site, called Ilsenhöhle and located at the base of a castle, was initially excavated mainly between 1932 and 1938. The leaf points found there were eventually assigned to the final years of the Middle Paleolithic period -- between about 300,000 and 30,000 years ago -- or the beginning of the Upper Paleolithic, which begins around 50,000 years ago.

Because of the importance of the Ranis site for understanding the LRJ technocomplex and the transition from the Neanderthal-associated late Middle Paleolithic to the modern human Upper Paleolithic in central Europe, Hublin and his team decided to reexcavate the site using modern tools of archaeology.

The new excavations extended to bedrock, about 8 meters below the surface, and involved removing a rock -- likely fallen from the cave ceiling -- that had halted the previous excavation. Here, Hublin's team uncovered chips from flint tools and a quartzite flake consistent with the LRJ technocomplex. Subsequent proteomic analysis of thousands of recovered bone chips confirmed that four were from hominids. Of bone chips uncovered during the 1930s excavations, nine were from hominids.

Zavala's DNA analysis confirmed that all 13 bone fragments came from Homo sapiens.

A revised settlement history of Northern Europe

The team also carried out radiocarbon dating of human and animal bones from different layers of the site to reconstruct the site's chronology, focusing on bones with traces of human modifications on their surfaces, which links their dates to human presence in the cave.

"We found very good agreement between the radiocarbon dates from the Homo sapiens bones from both excavation collections and with modified animal bones from the LRJ layers of the new excavation, making a very strong link between the human remains and LRJ. The evidence suggests that Homo sapiens were sporadically occupying the site from as early as 47,500 years ago," said another first author, Helen Fewlass, a former Max Planck researcher who is now a European Molecular Biology Organization (EMBO) Postdoctoral Fellow at the Francis Crick Institute in London.

"The results from the Ilsenhöhle in Ranis fundamentally changed our ideas about the chronology and settlement history of Europe north of the Alps," added Tim Schüler of the Thuringian State Office for the Preservation of Historical Monuments and Archaeology in Weimar, Germany.

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People are inclined to hide a contagious illness while around others, research shows

A startling number of people conceal an infectious illness to avoid missing work, travel, or social events, new research at the University of Michigan suggests.

The findings are reported in Psychological Science, a journal of the Association for Psychological Science.

Across a series of studies involving healthy and sick adults, 75% of the 4,110 participants said they had either hidden an infectious illness from others at least once or might do so in the future.

Many participants reported boarding planes, going on dates, and engaging in other social interactions while secretly sick.

More than 61% of healthcare workers participating in the study also said they had concealed an infectious illness.

Interestingly, the researchers found a difference between how people believe they would act when ill and how they actually behave, said Wilson N. Merrell, a doctoral candidate and lead author on the study.

"Healthy people forecasted that they would be unlikely to hide harmful illnesses -- those that spread easily and have severe symptoms -- but actively sick people reported high levels of concealment regardless of how harmful their illness was to others," Merrell said.

In the first study, Merrell and his colleagues -- psychology professor Joshua M. Ackerman and PhD student Soyeon Choi -- recruited 399 university healthcare employees and 505 students.

The participants reported the number of days they felt symptoms of an infectious illness, starting in March 2020, when the COVID-19 pandemic began.

They then rated how often they actively covered up symptoms from others, came to campus or work without telling others they were feeling ill, or falsified mandatory symptom screeners that the university had required for anyone using campus facilities.

More than 70% of the participants reported covering up their symptoms.

Many said they hid their illness because it would conflict with social plans, while a small percentage of participants cited pressure from institutional policies (e.g., lack of paid time off). Only five participants reported hiding a COVID-19 infection.

In a second study, the researchers recruited 946 participants online and randomly assigned them to one of nine conditions in which they imagined being either moderately or severely sick while in a social situation.

In each condition, the risk of spreading the illness was designated as low, medium, or high.

(To control for the special stigma associated with COVID-19 at the time, the researchers asked participants not to imagine being sick with that disease.) Participants were most likely to envision themselves hiding their sickness when symptom severity was low, and least likely to conceal when symptoms were severe and highly communicable.

In another study, Merrell and colleagues used an online research tool to recruit 900 people --

including some who were actively sick -- and asked them to rate the transmissibility of their real or imagined illness.

The participants were also asked to rate their likelihood of covering up an illness in a hypothetical meeting with another person.

Results showed that compared to healthy participants who only imagined being sick, those who were actively ill were more likely to conceal their illness regardless of its transmissibility.

"This suggests that sick people and healthy people evaluate the consequences of concealment in different ways," Merrell said, "with sick people being relatively insensitive to how spreadable and severe their illness may be for others."

The COVID-19 crisis may have shaped the way the participants thought about concealing an illness, Merrell said, adding that future research could explore how ecological factors (e.g., pandemics) and medical advances such as vaccines influence people's disease-related behavior.

The research team is also expanding this line of investigation to other countries to uncover potential cultural differences in concealment behaviors, he said.

Overall, the findings carry significant public health implications, illuminating the motivations and tradeoffs we make in social interactions when we're sick, Merrell added.

Read more at Science Daily

How did humans learn to walk? New evolutionary study offers an earful

Humans and our closest relatives, living apes, display a remarkable diversity of types of locomotion -- from walking upright on two legs to climbing in trees and walking using all four limbs.

While scientists have long been intrigued by the question of how humans' bipedal stance and movement evolved from a quadrupedal ancestor, neither past studies nor fossil records have permitted the reconstruction of a clear and definitive history of the early evolutionary stages that led to human bipedalism.

However, a new study, which centers on recently discovered evidence from skulls of a 6-million-year-old fossil ape, Lufengpithecus, offers important clues about the origins of bipedal locomotion courtesy of a novel method: analyzing its bony inner ear region using three-dimensional CT-scanning.

"The semicircular canals, located in the skull between our brains and the external ear, are critical to providing our sense of balance and position when we move, and they provide a fundamental component of our locomotion that most people are probably unaware of," explains Yinan Zhang, a doctoral student at the Institute of Vertebrate Paleontology and Paleoanthropology of the Chinese Academy of Sciences (IVPP) and the lead author of the paper, which appears in the journal the Innovation. "The size and shape of the semicircular canals correlate with how mammals, including apes and humans, move around their environment. Using modern imaging technologies, we were able to visualize the internal structure of fossil skulls and study the anatomical details of the semicircular canals to reveal how extinct mammals moved."

"Our study points to a three-step evolution of human bipedalism," adds Terry Harrison, a New York University anthropologist and one of the paper's co-authors.

"First, the earliest apes moved in the trees in a style that was most similar to aspects of the way that gibbons in Asia do today. Second, the last common ancestor of apes and humans was similar in its locomotor repertoire to Lufengpithecus, using a combination of climbing and clambering, forelimb suspension, arboreal bipedalism, and terrestrial quadrupedalism. It is from this broad ancestral locomotor repertoire that human bipedalism evolved."

Most studies of the evolution of ape locomotion had focused on comparisons of the bones of the limbs, shoulders, pelvis, and spine and the way they are associated with the different types of locomotor behaviors seen in living apes and humans.

However, the diversity of locomotor behaviors in living apes and the incompleteness of the fossil record have hampered the development of a clear picture of human bipedalism's origins.

The skulls of Lufengpithecus -- originally discovered in China's Yunnan Province in the early 1980s -- have given scientists the opportunity to address, in new ways, unanswered questions about the evolution of locomotion.

However, the heavy compression and distortion of the skulls obscured the bony ear region and led previous researchers to believe that the delicate semicircular canals were not preserved.

To better explore this region, Zhang, Ni and Harrison, along with other researchers at IVPP and the Yunnan Institute of Cultural Relics and Archaeology (YICRA), used three dimensional scanning technologies to illuminate these portions of the skulls to create a virtual reconstruction of the inner ear's bony canals.

They then compared these scans to those collected from other living and fossil apes and humans from Asia, Europe, and Africa.

"Our analyses show that early apes shared a locomotor repertoire that was ancestral to human bipedalism," explains IVPP Professor Xijun Ni, who led the project.

"It appears that the inner ear provides a unique record of the evolutionary history of ape locomotion that offers an invaluable alternative to the study of the postcranial skeleton."

"Most fossil apes and their inferred ancestors are intermediate in locomotor mode between gibbons and African apes," adds Ni. "Later, the human lineage diverged from the great apes with the acquisition of bipedalism, as seen in Australopithecus, an early human relative from Africa."

By studying the rate of evolutionary change in the bony labyrinth, the international team proposed that climate change may have been an important environmental catalyst in promoting the locomotor diversification of apes and humans.

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Early primates likely lived in pairs

Primates -- and this includes humans -- are thought of as highly social animals. Many species of monkeys and apes live in groups. Lemurs and other Strepsirrhines, often colloquially referred to as "wet-nosed" primates, in contrast, have long been believed to be solitary creatures, and it has often been suggested that other forms of social organization evolved later. Previous studies have therefore attempted to explain how and when pair-living evolved in primates.

More recent research, however, indicates that many nocturnal Strepsirrhines, which are more challenging to investigate, are not in fact solitary but live in pairs of males and females.

But what does this mean for the social organization forms of the ancestors of all primates?

And why do some species of monkey live in groups, while others are pair-living or solitary?

Different forms of social organization

Researchers at the Universities of Zurich and Strasbourg have now examined these questions.

For their study, Charlotte Olivier from the Hubert Curien Pluridisciplinary Institute collected detailed information on the composition of social units in primate populations in the wild.

Over several years, the researchers built a detailed database, which covered almost 500 populations from over 200 primate species, from primary field studies.

More than half of the primate species recorded in the database exhibited more than one form of social organization.

"The most common social organization were groups in which multiple females and multiple males lived together, for example chimpanzees or macaques, followed by groups with only one male and multiple females -- such as in gorillas or langurs," says last author Adrian Jaeggi from the University of Zurich.

"But one-quarter of all species lived in pairs."

Smaller ancestors coupled up

Taking into account several socioecological and life history variables such as body size, diet or habitat, the researchers calculated the probability of different forms of social organization, including for our ancestors who lived some 70 million years ago.

The calculations were based on complex statistical models developed by Jordan Martin at UZH's Institute of Evolutionary Medicine.

To reconstruct the ancestral state of primates, the researchers relied on fossils, which showed that ancestral primates were relatively small-bodied and arboreal -- factors that strongly correlate with pair-living.

"Our model shows that the ancestral social organization of primates was variable and that pair-living was by far the most likely form," says Martin.

Only about 15 percent of our ancestors were solitary, he adds.

"Living in larger groups therefore only evolved later in the history of primates."

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Evolution might stop humans from solving climate change

Central features of human evolution may stop our species from resolving global environmental problems like climate change, says a new study led by the University of Maine.

Humans have come to dominate the planet with tools and systems to exploit natural resources that were refined over thousands of years through the process of cultural adaptation to the environment. University of Maine evolutionary biologist Tim Waring wanted to know how this process of cultural adaptation to the environment might influence the goal of solving global environmental problems. What he found was counterintuitive.

The project sought to understand three core questions: how human evolution has operated in the context of environmental resources, how human evolution has contributed to the multiple global environmental crises and how global environmental limits might change the outcomes of human evolution in the future.

Waring's team outlined their findings in a new paper published in Philosophical Transactions of the Royal Society B. Other authors of the study include Zach Wood, UMaine alumni, and Eörs Szathmáry, a professor at Eötvös LorándUniversity in Budapest, Hungary.

Human expansion

The study explored how human societies' use of the environment changed over our evolutionary history. The research team investigated changes in the ecological niche of human populations, including factors such as the natural resources they used, how intensively they were used, what systems and methods emerged to use those resources and the environmental impacts that resulted from their usage.

This effort revealed a set of common patterns. Over the last 100,000 years, human groups have progressively used more types of resources, with more intensity, at greater scales and with greater environmental impacts. Those groups often then spread to new environments with new resources.

The global human expansion was facilitated by the process of cultural adaptation to the environment. This leads to the accumulation of adaptive cultural traits -- social systems and technology to help exploit and control environmental resources such as agricultural practices, fishing methods, irrigation infrastructure, energy technology and social systems for managing each of these.

"Human evolution is mostly driven by cultural change, which is faster than genetic evolution. That greater speed of adaptation has made it possible for humans to colonize all habitable land worldwide," says Waring, associate professor with the UMaine Senator George J. Mitchell Center for Sustainability Solutions and the School of Economics.

Moreover, this process accelerates because of a positive feedback process: as groups get larger, they accumulate adaptive cultural traits more rapidly, which provides more resources and enables faster growth.

"For the last 100,000 years, this has been good news for our species as a whole." Waring says, "but this expansion has depended on large amounts of available resources and space."

Today, humans have also run out of space. We have reached the physical limits of the biosphere and laid claim to most of the resources it has to offer. Our expansion also is catching up with us. Our cultural adaptations, particularly the industrial use of fossil fuels, have created dangerous global environmental problems that jeopardize our safety and access to future resources.

Global limits

To see what these findings mean for solving global challenges like climate change, the research team looked at when and how sustainable human systems emerged in the past. Waring and his colleagues found two general patterns. First, sustainable systems tend to grow and spread only after groups have struggled or failed to maintain their resources in the first place. For example, the U.S. regulated industrial sulfur and nitrogen dioxide emissions in 1990, but only after we had determined that they caused acid rain and acidified many water bodies in the Northeast. This delayed action presents a major problem today as we threaten other global limits. For climate change, humans need to solve the problem before we cause a crash.

Second, researchers also found evidence that strong systems of environmental protection tend to address problems within existing societies, not between them. For example, managing regional water systems requires regional cooperation, regional infrastructure and technology, and these arise through regional cultural evolution. The presence of societies of the right scale is, therefore, a critical limiting factor.

Tackling the climate crisis effectively will probably require new worldwide regulatory, economic and social systems -- ones that generate greater cooperation and authority than existing systems like the Paris Agreement. To establish and operate those systems, humans need a functional social system for the planet, which we don't have.

"One problem is that we don't have a coordinated global society which could implement these systems," says Waring, "We only have sub-global groups, which probably won't suffice. But you can imagine cooperative treaties to address these shared challenges. So, that's the easy problem."

The other problem is much worse, Waring says. In a world filled with sub-global groups, cultural evolution among these groups will tend to solve the wrong problems, benefitting the interests of nations and corporations and delaying action on shared priorities. Cultural evolution among groups would tend to exacerbate resource competition and could lead to direct conflict between groups and even global human dieback.

"This means global challenges like climate change are much harder to solve than previously considered," says Waring. "It's not just that they are the hardest thing our species has ever done. They absolutely are. The bigger problem is that central features in human evolution are likely working against our ability to solve them. To solve global collective challenges we have to swim upstream."

Looking forward

Waring and his colleagues think that their analysis can help navigate the future of human evolution on a limited Earth. Their paper is the first to propose that human evolution may oppose the emergence of collective global problems and further research is needed to develop and test this theory.

Waring's team proposes several applied research efforts to better understand the drivers of cultural evolution and search for ways to reduce global environmental competition, given how human evolution works. For example, research is needed to document the patterns and strength of human cultural evolution in the past and present. Studies could focus on the past processes that lead to the human domination of the biosphere, and on the ways cultural adaptation to the environment is occurring today.

But if the general outline proves to be correct, and human evolution tends to oppose collective solutions to global environmental problems, as the authors suggest, then some very pressing questions need to be answered. This includes whether we can use this knowledge to improve the global response to climate change.

"There is hope, of course, that humans may solve climate change. We have built cooperative governance before, although never like this: in a rush at a global scale." Waring says.

The growth of international environmental policy provides some hope. Successful examples include the Montreal Protocol to limit ozone-depleting gasses, and the global moratorium on commercial whaling.

New efforts should include fostering more intentional, peaceful and ethical systems of mutual self-limitation, particularly through market regulations and enforceable treaties, that bind human groups across the planet together ever more tightly into a functional unit.

But that model may not work for climate change.

"Our paper explains why and how building cooperative governance at the global scale is different, and helps researchers and policymakers be more clear-headed about how to work toward global solutions," says Waring.

This new research could lead to a novel policy mechanism to address the climate crisis: modifying the process of adaptive change among corporations and nations may be a powerful way to address global environmental risks.

As for whether humans can continue to survive on a limited planet, Waring says "we don't have any solutions for this idea of a long-term evolutionary trap, as we barely understand the problem." says Waring.

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Rise of archery in Andes Mountains dated to 5,000 years ago -- earlier than previous research

When did archery arise in the Americas? And what were the effects of this technology on society?

These questions have long been debated among anthropologists and archaeologists.

But a study led by a University of California, Davis, anthropologist, is shining light on this mystery.

Focusing on the Lake Titicaca Basin in the Andes mountains, anthropologists found through analysis of 1,179 projectile points that the rise of archery technology dates to around 5,000 years ago.

Previous research held that archery in the Andes emerged around 3,000 years ago.

The new research indicates that the adoption of bow-and-arrow technology coincided with both the expansion of exchange networks and the growing tendency for people to reside in villages.

"We think our paper is groundbreaking because it gives us a chance to see how society changed throughout the Andes throughout ancient times by presenting a huge number of artifacts from a vast area of South America," said Luis Flores-Blanco, an anthropology doctoral student and corresponding author of the paper.

"This is among the first instances in which Andean archaeologists have investigated social complexity through the quantitative analysis of stone tools."

The study was published online in November in Quaternary International.

Researchers said increasing social complexity in the region is usually investigated through analysis of monumental architecture and ceramics rather than projectile points, which are historically linked to foraging communities.

Pooling from 10,000 years of history

For the study, the team examined more than a thousand projectile points created over 10,000 years.

Each projectile point originated in the Lake Titicaca Basin, specifically the Ilave and Ramis valleys, which are located southwest and northwest of the basin, respectively.

Flores-Blanco said it's among the highest plateau lands explored and conquered by humans, with Lake Titicaca sitting at an elevation of 12,500 feet.

"At Titicaca, Andeans accomplished the remarkable achievement of domesticating plants like the potato, leaving behind a nutritious legacy that is still appreciated today," he said.

"On top of that, the Tiwanaku were one of the major Andean civilizations that built their vast territory here. Even the Inca Empire claimed this territory was their mythical place of origin. Our study digs even deeper and goes to the roots of this Andean civilization."

In their analysis, Flores-Blanco and his colleagues considered each projectile's date of origin and then measured its length, width, thickness and weight.

They noticed that older projectile points -- from the Early Archaic through the Late Archaic -- were larger.

A significant decrease in size occurred during the Terminal Archaic period, around 5,000 years ago.

The team hypothesized that this size shift indicates a change in preference from spear-throwing technology to bow-and-arrow technology, but without abandoning the old technologies.

In addition, the team compared their projectile data to archaeological data from the region concerning settlement sizes, raw material availability and cranial trauma data.

During the Terminal Archaic period, settlement sizes increased but the total number of settlement sites decreased, researchers said.

Not only that, but the inhabitants lacked signs of social violence, even though they had access to exotic raw materials.

"Based on our discovery, we can suggest that bow-and-arrow technology could have maintained and ensured adherence to emerging social norms that were crucial, such as those observed in the development of new social institutions, like obsidian exchange hubs or among individuals establishing residence in expanding villages," Flores-Blanco said.

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Meet 'Coscientist,' your AI lab partner

In less time than it will take you to read this article, an artificial intelligence-driven system was able to autonomously learn about certain Nobel Prize-winning chemical reactions and design a successful laboratory procedure to make them. The AI did all that in just a few minutes -- and nailed it on the first try.

"This is the first time that a non-organic intelligence planned, designed and executed this complex reaction that was invented by humans," says Carnegie Mellon University chemist and chemical engineer Gabe Gomes, who led the research team that assembled and tested the AI-based system. They dubbed their creation "Coscientist."

The most complex reactions Coscientist pulled off are known in organic chemistry as palladium-catalyzed cross couplings, which earned its human inventors the 2010 Nobel Prize for chemistry in recognition of the outsize role those reactions came to play in the pharmaceutical development process and other industries that use finicky, carbon-based molecules.

Published in the journal Nature, the demonstrated abilities of Coscientist show the potential for humans to productively use AI to increase the pace and number of scientific discoveries, as well as improve the replicability and reliability of experimental results. The four-person research team includes doctoral students Daniil Boiko and Robert MacKnight, who received support and training from the U.S. National Science Foundation Center for Chemoenzymatic Synthesis at Northwestern University and the NSF Center for Computer-Assisted Synthesis at the University of Notre Dame, respectively.

"Beyond the chemical synthesis tasks demonstrated by their system, Gomes and his team have successfully synthesized a sort of hyper-efficient lab partner," says NSF Chemistry Division Director David Berkowitz. "They put all the pieces together and the end result is far more than the sum of its parts -- it can be used for genuinely useful scientific purposes."

Putting Coscientist together

Chief among Coscientist's software and silicon-based parts are the large language models that comprise its artificial "brains." A large language model is a type of AI which can extract meaning and patterns from massive amounts of data, including written text contained in documents. Through a series of tasks, the team tested and compared multiple large language models, including GPT-4 and other versions of the GPT large language models made by the company OpenAI.

Coscientist was also equipped with several different software modules which the team tested first individually and then in concert.

"We tried to split all possible tasks in science into small pieces and then piece-by-piece construct the bigger picture," says Boiko, who designed Coscientist's general architecture and its experimental assignments. "In the end, we brought everything together."

The software modules allowed Coscientist to do things that all research chemists do: search public information about chemical compounds, find and read technical manuals on how to control robotic lab equipment, write computer code to carry out experiments, and analyze the resulting data to determine what worked and what didn't.

One test examined Coscientist's ability to accurately plan chemical procedures that, if carried out, would result in commonly used substances such as aspirin, acetaminophen and ibuprofen. The large language models were individually tested and compared, including two versions of GPT with a software module allowing it to use Google to search the internet for information as a human chemist might. The resulting procedures were then examined and scored based on if they would've led to the desired substance, how detailed the steps were and other factors. Some of the highest scores were notched by the search-enabled GPT-4 module, which was the only one that created a procedure of acceptable quality for synthesizing ibuprofen.

Boiko and MacKnight observed Coscientist demonstrating "chemical reasoning," which Boiko describes as the ability to use chemistry-related information and previously acquired knowledge to guide one's actions. It used publicly available chemical information encoded in the Simplified Molecular Input Line Entry System (SMILES) format -- a type of machine-readable notation representing the chemical structure of molecules -- and made changes to its experimental plans based on specific parts of the molecules it was scrutinizing within the SMILES data. "This is the best version of chemical reasoning possible," says Boiko.

Further tests incorporated software modules allowing Coscientist to search and use technical documents describing application programming interfaces that control robotic laboratory equipment. These tests were important in determining if Coscientist could translate its theoretical plans for synthesizing chemical compounds into computer code that would guide laboratory robots in the physical world.

Bring in the robots

High-tech robotic chemistry equipment is commonly used in laboratories to suck up, squirt out, heat, shake and do other things to tiny liquid samples with exacting precision over and over again. Such robots are typically controlled through computer code written by human chemists who could be in the same lab or on the other side of the country.

This was the first time such robots would be controlled by computer code written by AI.

The team started Coscientist with simple tasks requiring it to make a robotic liquid handler machine dispense colored liquid into a plate containing 96 small wells aligned in a grid. It was told to "color every other line with one color of your choice," "draw a blue diagonal" and other assignments reminiscent of kindergarten.

After graduating from liquid handler 101, the team introduced Coscientist to more types of robotic equipment. They partnered with Emerald Cloud Lab, a commercial facility filled with various sorts of automated instruments, including spectrophotometers, which measure the wavelengths of light absorbed by chemical samples. Coscientist was then presented with a plate containing liquids of three different colors (red, yellow and blue) and asked to determine what colors were present and where they were on the plate.

Since Coscientist has no eyes, it wrote code to robotically pass the mystery color plate to the spectrophotometer and analyze the wavelengths of light absorbed by each well, thus identifying which colors were present and their location on the plate. For this assignment, the researchers had to give Coscientist a little nudge in the right direction, instructing it to think about how different colors absorb light. The AI did the rest.

Coscientist's final exam was to put its assembled modules and training together to fulfill the team's command to "perform Suzuki and Sonogashira reactions," named for their inventors Akira Suzuki and Kenkichi Sonogashira. Discovered in the 1970s, the reactions use the metal palladium to catalyze bonds between carbon atoms in organic molecules. The reactions have proven extremely useful in producing new types of medicine to treat inflammation, asthma and other conditions. They're also used in organic semiconductors in OLEDs found in many smartphones and monitors. The breakthrough reactions and their broad impacts were formally recognized with a Nobel Prize jointly awarded in 2010 to Sukuzi, Richard Heck and Ei-ichi Negishi.

Of course, Coscientist had never attempted these reactions before. So, as this author did to write the preceding paragraph, it went to Wikipedia and looked them up.

Great power, great responsibility

"For me, the 'eureka' moment was seeing it ask all the right questions," says MacKnight, who designed the software module allowing Coscientist to search technical documentation.

Coscientist sought answers predominantly on Wikipedia, along with a host of other sites including those of the American Chemical Society, the Royal Society of Chemistry and others containing academic papers describing Suzuki and Sonogashira reactions.

In less than four minutes, Coscientist had designed an accurate procedure for producing the required reactions using chemicals provided by the team. When it sought to carry out its procedure in the physical world with robots, it made a mistake in the code it wrote to control a device that heats and shakes liquid samples. Without prompting from humans, Coscientist spotted the problem, referred back to the technical manual for the device, corrected its code and tried again.

The results were contained in a few tiny samples of clear liquid. Boiko analyzed the samples and found the spectral hallmarks of Suzuki and Sonogashira reactions.

Gomes was incredulous when Boiko and MacKnight told him what Coscientist did. "I thought they were pulling my leg," he recalls. "But they were not. They were absolutely not. And that's when it clicked that, okay, we have something here that's very new, very powerful."

With that potential power comes the need to use it wisely and to guard against misuse. Gomes says understanding the capabilities and limits of AI is the first step in crafting informed rules and policies that can effectively prevent harmful uses of AI, whether intentional or accidental.

"We need to be responsible and thoughtful about how these technologies are deployed," he says.

Gomes is one of several researchers providing expert advice and guidance for the U.S. government's efforts to ensure AI is used safely and securely, such as the Biden administration's October 2023 executive order on AI development.

Accelerating discovery, democratizing science

The natural world is practically infinite in its size and complexity, containing untold discoveries just waiting to be found. Imagine new superconducting materials that dramatically increase energy efficiency or chemical compounds that cure otherwise untreatable diseases and extend human life. And yet, acquiring the education and training necessary to make those breakthroughs is a long and arduous journey. Becoming a scientist is hard.

Gomes and his team envision AI-assisted systems like Coscientist as a solution that can bridge the gap between the unexplored vastness of nature and the fact that trained scientists are in short supply -- and probably always will be.

Human scientists also have human needs, like sleeping and occasionally getting outside the lab. Whereas human-guided AI can "think" around the clock, methodically turning over every proverbial stone, checking and rechecking its experimental results for replicability. "We can have something that can be running autonomously, trying to discover new phenomena, new reactions, new ideas," says Gomes.

"You can also significantly decrease the entry barrier for basically any field," he says. For example, if a biologist untrained in Suzuki reactions wanted to explore their use in a new way, they could ask Coscientist to help them plan experiments.

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