The study researchers and their enlisted volunteer “otter spotters” followed 196 radio-tagged southern sea otters off the coast of California to better understand how the threatened species uses tools in a rapidly changing environment. The research team from The University of Texas at Austin, University of California, Santa Cruz, Monterey Bay Aquarium and elsewhere monitored how the marine mammals used tools — such as rocks, shells and trash — to break open prey and identified links to the animals’ dietary patterns and dental health.

For the first time, researchers found that the use of tools among male and female otters led to a reduction in tooth injuries.

“Sea otters vary in how often they use tools,” said Chris Law, a postdoctoral researcher and an Early Career Provost Fellow at UT Austin who led the study while a graduate student at UC Santa Cruz. “The females are likely using tools to overcome their smaller body size and weaker biting ability in order to meet their calorie demands. Raising pups takes a lot of energy, and the females need to be efficient in their foraging. The study shows that tool use is an important behavior for survival.”

The study is published in Science.

In the southern sea otter’s range of coastal Central California, some of the preferred prey such as large abalone and sea urchins, are not difficult to break open. However, these food resources dwindle or disappeare in many areas. This leads otters to prey more often on crabs, clams, mussels and small marine snails whose hard shells can damage the otter’s teeth in the process of prying them open.

Tooth condition is important for survival because when an otter’s teeth become too worn or damaged, they could starve. Using tools helped individual otters to meet their calorie needs by branching out into different types of prey. The study found female otters had less tooth damage than male otters did.

Research shows that female otters are more likely to use tools, and in the study, those that did were able to access harder or larger prey than otters that did not use tools. In fact, females were able to consume prey that were up to 35% harder compared with that of males that used tools.

Female dolphins, chimps and bonobos are also known to use tools more than their male counterparts, probably for the same reasons. In these species, females tend to raise offspring, and they are often the ones that pass down tool-use behavior to offspring.

Listed as a threatened species under the U.S. Endangered Species Act, southern sea otters number only about 3,000 in California, where they play a critical role in marine ecosystems preying on sea urchins that feed on kelp forests.

Rita Mehta and Tim Tinker of the University of California, Santa Cruz; Jessica Fujii, Teri Nicholson and Michelle Staedler with the Monterey Bay Aquarium; Joseph Tomoleoni of the U.S. Geological Survey; and Colleen Young of the California Department of Fish and Wildlife were also authors on the paper. Chris Law was previously a postdoctoral scholar with University of Washington.

The research was funded by the U.S. National Science Foundation, Packard Foundation, Coastal Conservancy, U.S. Fish and Wildlife Service, Pacific Gas & Electric and Bureau of Ocean Energy Management.

AlphaFold2, an artificial intelligence system that predicts protein structures, has made it possible for scientists to identify and conjure an almost infinite number of drug candidates for the treatment of neuropsychiatric disorders. However recent studies have sown doubt about the accuracy of AlphaFold2 in modeling ligand binding sites, the areas on proteins where drugs attach and begin signaling inside cells to cause a therapeutic effect, as well as possible side effects.

In a new paper, Bryan Roth, MD, PhD, the Michael Hooker Distinguished Professor of Pharmacology and director of the NIMH Psychoactive Drug Screening Program at the University of North Carolina School of Medicine, and colleagues at UCSF, Stanford and Harvard determined that AlphaFold2 can yield accurate results for ligand binding structures, even when the technology has nothing to go off of. Their results were published in Science.

“Our results suggest that AF2 structures can be useful for drug discovery,” said Roth, senior author who holds a joint appointment at the UNC Eshelman School of Pharmacy. “With a nearly infinite number of possibilities to create drugs that hit their intended target to treat a disease, this sort of AI tool can be invaluable.”

AlphaFold2 and Prospective Modeling

Much like weather forecasting or stock market prediction, AlphaFold2 works by pulling from a massive database of known proteins to create models of protein structures. Then, it can simulate how different molecular compounds (like drug candidates) fit into the protein’s binding sites and produce wanted effects. Researchers can use the resulting combinations to better understand protein interactions and create new drug candidates.

To determine the accuracy of AlphaFold2, researchers had to compare the results of a retrospective study against that of a prospective study. A retrospective study involves researchers feeding the prediction software compounds they already know bind to the receptor. Whereas, a prospective study requires researchers to use the technology as a fresh slate, and then feed the AI platform information about compounds that may or may not interact with the receptor.

Researchers used two proteins, sigma-2 and 5-HT2A, for the study. These proteins, which belong to two different protein families, are important in cell communication and have been implicated in neuropsychiatric conditions such as Alzheimer’s disease and schizophrenia. The 5-HT2A serotonin receptor is also the main target for psychedelic drugs which show promise for treating a large number of neuropsychiatric disorders.

Roth and colleagues selected these proteins because AlphaFold2 had no prior information about sigma-2 and 5-HT2A or the compounds that might bind to them. Essentially, the technology was given two proteins for which it wasn’t trained on — essentially giving the researchers a “blank slate.”

First, researchers fed the AlphaFold system the protein structures for sigma-2 and 5-HT2A, creating a prediction model. Researchers then accessed physical models of the two proteins that were produced using complex microscopy and x-ray crystallography techniques. With a press of a button, as many as 1.6 billion potential drugs were targeted to the experimental models and AlphaFold2 models. Interestingly, every model had a different drug candidate outcome.

Successful Hit Rates

Despite the models having differing results, they show great promise for drug discovery. Researchers determined that the proportion of compounds that actually altered protein activity for each of the models were around 50% and 20% for the sigma-2 receptor and 5-HT2A receptors, respectively. A result greater than 5% is exceptional.

Out of the hundreds of millions of potential combinations, 54% of the drug-protein interactions using the sigma-2 AlphaFold2 protein models were successfully activated through a bound drug candidate. The experimental model for sigma-2 produced similar results with a success rate of 51%.

“This work would be impossible without collaborations among several leading experts at UCSF, Stanford, Harvard, and UNC-Chapel Hill,” Roth said. “Going forward we will test whether these results might be applicable to other therapeutic targets and target classes.”

Sabre teeth, those iconic elongated upper canine teeth, have long fascinated both scientists and the general public, notably because they have appeared several times in the fossil record, including two particularly well-known lineages of sabre-toothed tigers: the felids (the family of our domestic cats, lions, tigers, etc.) and the nimravids (a completely extinct family). However, the process by which these lineages acquired their elongated upper canines remains rather unclear.

Narimane Chatar, lead author of the study, who completed her doctorate at the EDDy Lab at the University of Liège and is now a post-doctoral fellow at UC Berkeley in the United States, has led an ambitious study to uncover the secrets of sabre tooth evolution. Using state-of-the-art 3D scanners and analytical methods, the team meticulously collected and analysed data from a diverse set of current and extinct species. “We quantified the shape of 99 mandibles and 91 skulls, from different eras and continents, giving us a better understanding of the evolution of these animals,” explains Dr Chatar. “Unlocking the secrets of sabre tooth evolution not only enriches our understanding of the Earth’s past, but also documents the mechanisms leading to evolutionary convergence,” says Professor Valentin Fischer, Director of the EDDyLab at ULiège.

The study revealed some surprising results. The first is that rather than contrasting two distinct cranial morphologies in species with elongated upper canines and those with short teeth, there is instead a continuum of form linking the smallest present-day cats and their extinct sabre-toothed counterparts. “From a morphological point of view, the skull of a present-day small cat is just as strange and modified as that of a large sabre-toothed felid,” says Dr Margot Michaud, a researcher at the University of French Guyana in Cayenne. These are therefore the two extremes of a continuum of forms that feline predators have seen evolve over geological time. “Our study suggests that what we often think of as examples of evolutionary patterns in textbooks are actually simplified for educational purposes. However, when we immerse ourselves in statistical analyses, we discover much more complex scenarios in these cases, as suggested by the results of our convergence tests,” explains Davide Tamagnini, post-doctoral researcher at the University of Rome La Sapienza.

The second surprise concerns the path taken by evolution to produce sabre-toothed species. In fact, the team’s work has revealed that sabre-toothed species show faster rates of morphological evolution at the start of their evolutionary history than species with shorter canines. “Among other fascinating discoveries, we have shown that craniomandibular integration in sabre-toothed species is reduced, facilitating greater adaptability and diversification in the jaw and cranial morphology,” points out Margot Michaud. Thus, rapid morphological diversification and a fairly plastic skull have been identified as two key components that facilitated the emergence of elongated upper canines in both felids and nimravids. “As a result, there appears to be a common recipe for evolving into sabre-toothed feline-like predators,” says Dr Chatar.

Finally, the team’s research highlighted the decline of sabre-toothed forms as well as the broader trends of feline-like predators over the course of their evolutionary history. Despite the relatively recent extinction of sabre-toothed forms ‘only’ a few thousand years ago, feline predators have in fact been in decline since the Miocene epoch (between -23 and -5 million years ago). “Some of these feline predators, particularly the sabre-toothed species, rapidly occupied fairly specialised niches, which made them more susceptible to extinction,” explains Dr Tamagnini. This phenomenon, known as ‘ratchet’ or macroevolutionary ratchet, has been proposed as a potential driver for the decline of certain groups, where evolution favours the loss of early generalised forms, leading to the emergence of more specialised, but also more vulnerable, forms later in the history of the lineage.

“Predators have their own evolutionary pathways and risks of extinction. Studying how ancient predators prospered and declined provides us with information about the possible futures of our ecosystems,” concludes Professor Fischer.

Patients who underwent infertility were particularly likely — 2.16 times as likely as those who conceived naturally — to undergo hospitalization for dangerously high blood pressure or hypertension.

“Postpartum checkups are necessary for all patients, but this study indicates they are particularly important for patients who undergo infertility treatment to achieve a conception,” said Rei Yamada, an obstetrics and gynecology resident at Rutgers Robert Wood Johnson Medical School and lead author of the study.

The study authors say their results support standards of care that now call for an initial postpartum checkup three weeks after delivery, standards that some health systems have yet to adopt. Much of the elevated risk came in the first month after delivery, particularly for patients who developed dangerously high blood pressure.

“And these results aren’t the only ones to indicate that follow-up should occur early,” said Cande Ananth, chief of the Division of Epidemiology and Biostatistics in the Department of Obstetrics, Gynecology, and Reproductive Sciences at Rutgers Robert Wood Johnson Medical School and senior author of the study. “We have been involved in a series of studies over the past few years that have found serious risks of heart disease and stroke to various high-risk patient populations within those initial 30 days after delivery — risks that could be mitigated with earlier follow-up care.”

The study analyzed the Nationwide Readmissions Database, which contains nationally representative data on about 31 million hospital discharges and readmissions per year. The database contains diagnosis codes, which let researchers find specific populations and identify reasons for readmission.

The researchers used data from more than 31 million patients who were discharged following delivery from 2010 to 2018, including 287,813 patients who had undergone any infertility treatment.

Although infertility treatment predicted a sharply elevated risk of heart disease, the study authors said the relative youth of infertility treatment patients kept their overall risk fairly low. Just 550 of every 100,000 women who received infertility treatment and 355 of every 100,000 who conceived naturally were hospitalized with cardiovascular disease in the year after delivery.

The cause of the elevated risk of heart disease associated with infertility treatment remains unclear. The increase in heart disease could stem from the infertility treatments themselves, the underlying medical issues that made patients infertile or some other cause.

“Looking forward, I’d like to see if different types of infertility treatment and, importantly, medications are associated with different risk levels,” said Yamada. “Our data gave no information about which patients had undergone which treatment. More detailed information might also provide insight into how infertility treatment impacts cardiovascular outcomes.”

Knowing more about nature’s effects on our bodies could not only help our well-being, but could also improve how we care for land, preserve ecosystems and design cities, homes and parks. Yet studies on the benefits of contact with nature have typically focused primarily on how seeing nature affects us. There has been less focus on what the nose knows. That is something a group of researchers wants to change.

“We are immersed in a world of odorants, and we have a sophisticated olfactory system that processes them, with resulting impacts on our emotions and behavior,” said Gregory Bratman, a University of Washington assistant professor of environmental and forest sciences. “But compared to research on the benefits of seeing nature, we don’t know nearly as much about how the impacts of nature’s scents and olfactory cues affect us.”

In a paper published May 15 in Science Advances, Bratman and colleagues from around the world outline ways to expand research into how odors and scents from natural settings impact our health and well-being. The interdisciplinary group of experts in olfaction, psychology, ecology, public health, atmospheric science and other fields are based at institutions in the U.S., the U.K., Taiwan, Germany, Poland and Cyprus.

At its core, the human sense of smell, or olfaction, is a complex chemical detection system in constant operation. The nose is packed with hundreds of olfactory receptors, which are sophisticated chemical sensors. Together, they can detect more than one trillion scents, and that information gets delivered directly to the nervous system for our minds to interpret — consciously or otherwise.

The natural world releases a steady stream of chemical compounds to keep our olfactory system busy. Plants in particular exude volatile organic compounds, or VOCs, that can persist in the air for hours or days. VOCs perform many functions for plants, such as repelling herbivores or attracting pollinators. Some researchers have studied the impact of exposures to plant VOCs on people.

“We know bits and pieces of the overall picture,” said Bratman. “But there is so much more to learn. We are proposing a framework, informed by important research from many others, on how to investigate the intimate links between olfaction, nature and human well-being.”

Nature’s smell-mediated impacts likely come through different routes, according to the authors. Some chemical compounds, including a subset of those from the invisible realm of plant VOCs, may be acting on us without our conscious knowledge. In these cases, olfactory receptors in the nose could be initiating a “subthreshold” response to molecules that people are largely unaware of. Bratman and his co-authors are calling for vastly expanded research on when, where and how these undetected biochemical processes related to natural VOCs may affect us.

Other olfactory cues are picked up consciously, but scientists still don’t fully understand all their impacts on our health and well-being. Some scents, for example, may have “universal” interpretations to humans — something that nearly always smells pleasant, like a sweet-smelling flower. Other scents are closely tied to specific memories, or have associations and interpretations that vary by culture and personal experience, as research by co-author Asifa Majid of the University of Oxford has shown.

“Understanding how olfaction mediates our relationships with the natural world and the benefits we receive from it are multi-disciplinary undertakings,” said Bratman. “It involves insights from olfactory function research, Indigenous knowledge, Western psychology, anthropology, atmospheric chemistry, forest ecology, Shinrin-yoku — or ‘forest bathing’ — neuroscience, and more.”

Investigation into the potential links between our sense of smell and positive experiences with nature includes research by co-author Cecilia Bembibre at University College London, which shows that the cultural significance of smells, including those from nature, can be passed down in communities to each new generation. Co-author Jieling Xiao at Birmingham City University has delved into the associations people have with scents in built environments and urban gardens.

Other co-authors have shown that nature leaves its signature in the very air we breathe. Forests, for example, release a complex chemical milieux into the air. Research by co-author Jonathan Williams at the Max Planck Institute for Chemistry and the Cyprus Institute shows how natural VOCs can react and mix in the atmosphere, with repercussions for olfactory environments.

The authors are also calling for more studies to investigate how human activity alters nature’s olfactory footprint — both by pollution, which can modify or destroy odorants in the air, and by reducing habitats that release beneficial scents.

“Human activity is modifying the environment so quickly in some cases that we’re learning about these benefits while we’re simultaneously making them more difficult for people to access,” said Bratman. “As research illuminates more of these links, our hope is that we can make more informed decisions about our impacts on the natural world and the volatile organic compounds that come from it. As we say in the paper, we live within the chemical contexts that nature creates. Understanding this more can contribute to human well-being and advance efforts to protect the natural world.”