The forerunners of mammals ruled the Earth for about 60 million years, long before the origin of the first dinosaurs. They diversified as the top predators on land between 315-251 million years ago.

Researchers studied the jaw anatomy and body size of carnivorous synapsids, using these traits to reconstruct the likely feeding habits of these ancient predators and chart their ecological evolution through time. They found a major shift in synapsid jaw function roughly 270 million years ago linked to a significant shift in predatory behaviour that has important implications for the evolution of our earliest ancestors.

As herbivores grew larger and faster, carnivores adapted to become bigger and better predators to survive.

“Earlier synapsid predators such as the famous sail backed Dimetrodon, had fairly long jaws with lots of teeth to ensure that once they ensnared their prey, it wouldn’t escape,” explained lead author Dr Suresh Singh based in Bristol’s School of Earth Sciences. “However, we saw a shift in jaw function toward shorter jaws with greater muscle efficiency and fewer teeth that were concentrated at the front of the jaw — these were jaws adapted to deliver deep, powerful bites.

“The change shows that later synapsid carnivores placed more emphasis on heavily injuring and so more quickly killing their prey. Among these later synapsids were the very first sabertoothed carnivores! This change highlights that predators were facing new selective pressures from their prey.”

This finding provides important context for a key step in synapsid evolution. “The reorganisation of synapsid jaws through this time has long been known as a big step towards the evolution of mammals,” added Dr Armin Elsler, a collaborator on the study. “These changes don’t just make the jaw more efficient; they also mark the very earliest redevelopment of the jaw that also created the complex ear found in mammals. What drove this first step? Our study suggests that it was partly driven by ecological pressures from their prey.”

Co-author Dr Tom Stubbs said: “The timing of the shift in jaw function corresponds with the evolution of new larger, faster herbivores that would have posed a greater challenge for predators to tackle.

“The risks to carnivores of getting injured or killed went up, so some synapsid carnivores became bigger, better killers to overcome these risks.”

This shift reflects a new dynamism in predator-prey interactions that shows that life on land was moving more quickly.

“The late Palaeozoic was the time when animals first began to live, eat and reproduce entirely on land,” said Professor Mike Benton, a co-supervisor on the study

“They became fully terrestrial, colonising new habitats and exploiting new resources further inland from the aquatic environments they’d previously relied on.

“Our findings show how the selective pressures on these early land animals changed as they became better adapted for life on land — catching another animal that can move fast and grow to larger sizes is much more difficult than catching a slippery little fish or amphibian.”

Professor Emily Rayfield also co-supervised the study. She added: “Predator-prey interactions are an important driver of animal behaviour today so it’s quite something to see that influence through anatomical evolution over millions of years, and find that they are potentially responsible for driving some big leaps in our own evolutionary history.

“It highlights how palaeontologists can use the relationship between form and function to explore how different prehistoric animals may have lived, which can tell us so much about the evolution of life on Earth.”

The researchers also found that synapsid carnivore morphological diversity increased following the shift, with the addition of new functional groups adapted for either faster biting speeds or even more powerful bites through the mid-late Permian — around 265-251 million years ago. By assessing how the sizes of these new carnivore species compared within different communities through time, they realised these communities may have begun to closely resemble those of modern carnivorous mammals.

According to a representative survey of 38,616 high school students from 22 public school districts in 14 U.S. states, the quarter of those adolescents who had experienced the highest number of days in a climate disaster within the past two years and the past five years — such as hurricanes, floods, tornadoes, droughts, and wildfire — had 20% higher odds of developing mental distress than their peers who experienced few or no disaster events.

The paper is the first large scale research looking at mental health of adolescents following multiple disaster events — including the timing, frequency, and duration of the events — spanning 83 federally declared climate disasters occurring within 10 years before the survey was completed. The findings, using May 2019 data on sadness/hopelessness and short sleep from the U.S. Youth Risk Behavior Survey and disaster data from the Federal Emergency Management Agency, were published this month in the journal Preventive Medicine Reports.

“We know that climate change has and will have catastrophic impacts across the globe,” said lead author Amy Auchincloss, PhD, an associate professor of epidemiology in the Dornsife School of Public Health. “But we were alarmed to find that climate related disasters already were affecting so many teens in the U.S. For example, within the past 2 years, many school districts in our study were subject to climate disasters for over 20 days.”

Respondents reported mental health distress by responding affirmatively to persistent feelings of sadness or hopelessness and short sleep duration, two factors that previous studies strongly link to mental health disorders among adolescents. The group controlled for other factors that may influence mental health, such as age, race, gender, experience of bullying, concerns about school safety and household income.

A positive, but not statistically significant, link between experiencing climate disasters and mental distress was also found when spanning ten years before the U.S. Youth Risk Survey.

“We found the strongest effects on mental distress in the 2 years immediately following a climate disaster — with the effect gradually weakening 5 to 10 years after the disaster,” said co-author Josiah Kephart, PhD, an assistant professor in the Dornsife School of Public Health.

As the results cannot prove causation, the authors say they would like to see more studies into the range of effects of climate change on youth and methods to improve preparing for potential worsening mental health among this population.

Already, roughly half of adolescents have experienced a mental health disorder in their childhood or teen years, according to the U.S. Department of Health and Human Services.

“Resources for the youth mental health crisis already have difficulty meeting demand and demand will increase as disasters increase,” said co-author Esther Chernak, MD, a clinical professor and director of the Center for Public Health Readiness and Communication at Dornsife School of Public Health. “The current study is evidence that clinicians, policymakers, parents, and many others with a stake in youth mental health can point to when advocating for increasing adolescent-specific mental health resources — particularly in lower-income communities who will be hit hardest by disasters.”

Drexel’s Dornsife School of Public Health is home to significant ongoing work addressing health and climate change. Among other projects, the school’s Urban Health Collaborative recently received National Institutes of Health funding to support establishment of the Drexel Climate Change and Urban Health Research Center (CCUH), which with foster research on the effects of climate change on health across the Americas. The Urban Health in Latin America Project (SALURBAL-Climate), of which Dornsife School of Public Health is an institutional partner, funds research on climate change’s links to health and health inequity impacts across Latin America using data on as any as 400 cities in 11 countries. Additional work at the school, in collaboration with the World Resources Institute (WRI), WRI Brasil, SALURBAL, and WRI Mexico, seeks to deepen our understanding of the relationship between neighborhood-scale heat mortality and neighborhood social characteristics in two Brazilian cities; the findings of which aim to inform public policy.

In addition to Auchincloss, additional authors on the study includes Dominic A. Ruggiero, and Meghan T. Donnelly, who were graduate students at Drexel at the time of this work.

For the study, recently published online in the journal Nature Chemical Biology, the team used X-ray crystallography to study NinaB, a protein found in insects that functions similarly to the RPE65 protein found in humans. Both are crucial for synthesis of 11-cis-retinal, and their absence results in severe visual impairment.

“Our study challenges traditional assumptions about the similarities and differences of human and insect vision,” said corresponding author Philip Kiser, UCI associate professor of physiology & biophysics as well as ophthalmology. “While these enzymes share a common evolutionary origin and three-dimensional architecture, we found that the process by which they produce 11-cis-retinal is distinct.”

Creation of 11-cis-retinal begins with the consumption of foods like carrots or pumpkins containing compounds used for vitamin A generation, such as beta-carotene. These nutrients are metabolized by carotenoid cleavage enzymes, including NinaB and RPE65. It was previously known that humans require two of these enzymes to produce 11-cis-retinal from beta-carotene, whereas insects can achieve the conversion with just NinaB. Gaining insight into how NinaB can couple the two steps into a single reaction along with the functional relationships between NinaB and RPE65 was a key motivation for the study.

“We found that structurally, these enzymes are very much alike, but the locations in which they perform their activity are different,” said lead author Yasmeen Solano, a graduate student in Kiser’s laboratory at the UCI Center for Translational Vision Research. “Understanding key features within the NinaB structure has led to an enhanced understanding of the catalytic machinery necessary to support the function of the retinal visual pigments. Through our study of NinaB, we were able to learn about the structure of a key portion of RPE65 that had not previously been resolved. This discovery is vital in understanding and addressing loss-of-function mutations in RPE65.”

Other team members included Michael Everett, a junior specialist in the Kiser lab, and Kelly Dang and Jude Abueg, biological sciences undergraduates at the time.

This work was supported by the National Science Foundation under grant CHE-2107713, the Department of Veterans Affairs under grant BX004939 and the National Institutes of Health under grant EY034519-01S1.

The compound, pantetheine, is the active fragment of Coenzyme A. It is important for metabolism — the chemical processes that maintain life. Earlier studies failed to synthesise pantetheine effectively, leading to suggestions that it was absent at life’s origin.

In the new study, published in the journal Science, the research team created the compound in water at room temperature using molecules formed from hydrogen cyanide, which was likely abundant on early Earth.

Once formed, the researchers said, it is simple to envisage how pantetheine might have aided chemical reactions that led from simple forerunners of protein and RNA molecules to the first living organisms — a moment that is thought to have occurred 4 billion years ago.

The study challenges the view among some researchers in the field that water is too destructive for life to originate in it and that life more likely originated in pools that periodically dried out.

Driving the reactions that produced pantetheine were energy-rich molecules called aminonitriles, which are closely chemically related to amino acids, the building blocks of proteins and of life.

Members of the same team, led by Professor Matthew Powner (UCL Chemistry), have already used similar chemistry powered by aminonitriles to demonstrate how other key biological ingredients could be created at the origin of life, including peptides (protein-creating chains of amino acids) and nucleotides (the building blocks of RNA and DNA).

Professor Powner, senior author of the paper, said: “This new study is further evidence that the basic structures of biology, the primary molecules that biology is built from, are predisposed to form through nitrile chemistry.

“The ease with which different classes of biological molecules can be made using nitriles has convinced me that, rather than life being preceded by one molecule such as RNA, and there being an ‘RNA world’ before life began, the basic molecules of biology emerged alongside each other — a network of RNAs, proteins, enzymes and cofactors leading to the first living organisms.

“Our future work will look at how these molecules came together, how pantetheine chemistry talks to RNA, peptide and lipid chemistry for instance, to deliver chemistry that the individual classes of molecule could not deliver in isolation.”

A notable earlier attempt to synthesise pantetheine was made in 1995 by the late American chemist Stanley Miller, who had started the field of origin of life experiments three decades earlier, creating amino acids from four simple chemicals in glass tubes.

However, in the later 1995 experiment, the yields of pantetheine were very low and required extremely high concentrations of chemicals that had been dried out and sealed in an airtight tube before they were heated to 100 degrees Centigrade.

Dr Jasper Fairchild (UCL Chemistry), a lead author of the study, who conducted the work as part of his PhD, said: “The major difference between Miller’s study and ours is whereas Miller tried to use acid chemistry, we used nitriles. It’s the nitriles that bring the energy and the selectivity. Our reactions just run in water and produce high yields of pantetheine with relatively low concentrations of chemicals needed.”

Professor Powner added: “It had been assumed you should make these molecules from acids, because using acids appears to be biological, and that is what we are taught at school and at university. We are taught peptides are made from amino acids.

“Our work suggests this conventional view has ignored an essential ingredient, the energy required to forge new bonds. The reactions look a little different with nitriles but the end products — the basic units of biology — are indistinguishable whether formed through acid or nitrile chemistry.”

While the paper focuses solely on the chemistry, the research team said that the reactions they demonstrated could plausibly have taken place in pools or lakes of water on the early Earth (but not likely in the oceans as the concentrations of the chemicals would likely be too diluted).

The new study was supported by the Engineering and Physical Sciences Research Council, the Simons Foundation and the Volkswagen Foundation. As a result of his work on the origins of life, Professor Powner was named a finalist in the 2021 Blavatnik Awards for Young Scientists. The awards are for scientists aged 42 or younger whose research “is already transforming technology and our understanding of the world.”

Now, a paradigm-shifting study led by researchers at the Icahn School of Medicine at Mount Sinai in New York in collaboration with the University of Helsinki and Massachusetts General Hospital sheds light on how variations in immune genetics influence lung cancer risk, potentially paving the way for enhanced prevention strategies and screening.

The findings were described in the February 22 online issue of Science.

The investigators utilized genetic epidemiology and multimodal genomic analyses of data from the UK Biobank, validating it in FinnGen. Their study focused on human leukocyte antigen (HLA) molecules — the most diverse genes in the human genome and at the core of immune recognition. These genes contain instructions to make proteins, which play a crucial role in presenting foreign antigens on cell surfaces. This process aids the immune system in identifying and eliminating threats such as cancer cells.

Surprisingly, the study found that individuals with heterozygosity (having different versions of a gene) at HLA-II, rather than HLA-I, experienced a decreased risk of lung cancer. This effect was particularly pronounced among smokers, a population already at higher risk for lung cancer due to exposure to carcinogens.

“Our findings challenge conventional thinking by demonstrating that immune genetics, specifically HLA-II heterozygosity, plays a significant role in lung cancer risk, especially among smokers,” says co-senior author Diego Chowell, PhD, Assistant Professor of Oncological Sciences, and Immunology and Immunotherapy at Icahn Mount Sinai. “Further, when we added polygenic risk scores — which is a measure of genetic predisposition based on multiple genes — to the analysis, it increased the lifetime risk of lung cancer, specifically in smokers who have identical versions of the HLA-II genes.

The implications of this research extend beyond lung cancer, offering a new perspective on cancer risk assessment, the researchers say. The conventional thinking on the causes of cancer is that the disease is caused by random mutations arising during DNA replication, inherited mutations, and environmental factors. The research showed that the immune system is also part of the etiology of cancer, Dr. Chowell says. By considering immune genetics alongside hereditary and environmental factors, the investigators’ aim to develop more effective prevention strategies, potentially harnessing the immune system to combat cancer.

“These results highlight a previously overlooked aspect of cancer risk assessment,” says co-senior author Robert Samstein, MD, PhD, Assistant Professor of Radiation Oncology, and Immunology and Immunotherapy at Icahn Mount Sinai. “Our study marks a big step toward understanding the intricate interplay between the immune system and cancer risk. We hope that by identifying individuals with increased susceptibility based on their immune genetics, we can implement more targeted screening, prevention, and treatment strategies.”

Next, the research team plans to delve deeper into the mechanisms underlying HLA heterozygosity’s protective effects, with a focus on preclinical models of disease. Additionally, they aim to explore the role of non-classical CD4 T cells and HLA class II in cancer biology, opening the door for potential progress in the mitigation and treatment of cancer.

The paper is titled “An immunogenetic basis for lung cancer risk.”

The remaining authors of the paper, all with Icahn Mount Sinai except where indicated, are: Chirag Krishna, PhD (Pfizer); Anniina Tervi, PhD (University of Helsinki); Miriam Saffern (PhD candidate); Eric A. Wilson, PhD; Seong-Keun Yoo, PhD; Nina Mars, MD, PhD (University of Helsinki and The Broad Institute of Harvard and MIT); Vladimir Roudko, PhD; Byuri Angela Cho, PhD; Samuel Edward Jones, PhD (University of Helsinki); Natalie Vaninov (PhD candidate); Myvizhi Esai Selvan, PhD; Zeynep H Gu?mu?s, PhD; FinnGen Consortium; Tobias L. Lenz, PhD (University of Hamburg); Miriam Merad, MD, PhD; Paolo Boffetta, MD (Stony Brook University in New York and University of Bologna); Francisco Marti?nez-Jime?nez, PhD (Stony Brook University in New York and Vall d’Hebron Institute of Oncology, Barcelona); and Hanna M. Ollila, PhD (Massachusetts General Hospital, Harvard Medical School, The Broad Institute, and University of Helsinki).

Then, in a burst of innovation in form and function, the ancestors of snakes evolved legless bodies that could slither across the ground, highly sophisticated chemical detection systems to find and track prey, and flexible skulls that enabled them to swallow large animals.

Those changes set the stage for the spectacular diversification of snakes over the past 66 million years, allowing them to quickly exploit new opportunities that emerged after an asteroid impact wiped out roughly three-quarters of the planet’s plant and animal species.

But what triggered the evolutionary explosion of snake diversity — a phenomenon known as adaptive radiation — that led to nearly 4,000 living species and made snakes one of evolution’s biggest success stories?

A large new genetic and dietary study of snakes, from an international team led by University of Michigan biologists, suggests that speed is the answer. Snakes evolved up to three times faster than lizards, with massive shifts in traits associated with feeding, locomotion and sensory processing, according to the study scheduled for online publication Feb. 22 in the journal Science.

“Fundamentally, this study is about what makes an evolutionary winner. We found that snakes have been evolving faster than lizards in some important ways, and this speed of evolution has let them take advantage of new opportunities that other lizards could not,” said University of Michigan evolutionary biologist Daniel Rabosky, senior author of the upcoming Science paper.

“Snakes evolved faster and — dare we say it — better than some other groups. They are versatile and flexible and able to specialize on prey that other groups cannot use,” said Rabosky, a curator at the U-M Museum of Zoology and a professor in the Department of Ecology and Evolutionary Biology.

For the study, researchers generated the largest, most comprehensive evolutionary tree of snakes and lizards by sequencing partial genomes for nearly 1,000 species. In addition, they compiled a huge dataset on lizard and snake diets, examining records of stomach contents from tens of thousands of preserved museum specimens.

They fed this mountain of data into sophisticated mathematical and statistical models, backed by massive amounts of computer power, to analyze the history of snake and lizard evolution through geological time and to study how various traits, such as limblessness, evolved.

This multipronged approach revealed that while other reptiles have evolved many snakelike traits — 25 different groups of lizards also lost their limbs, for instance — only snakes experienced this level of explosive diversification.

Take Australia’s legless gecko, for example.

Like snakes, this lizard lost its legs and evolved a flexible skull. Yet the creature has barely diversified over millions of years. No evolutionary explosion — just a couple of species scraping out a living in the Australian outback.

So, it seems there is something special about snakes that enabled them to hit the evolutionary jackpot. Maybe something in their genes that allowed them to be evolutionarily flexible while other groups of organisms are much more constrained.

“A standout aspect of snakes is how ecologically diverse they are: burrowing underground, living in freshwater, the ocean and almost every conceivable habitat on land,” said Alexander Pyron, study co-author and an associate professor of biology at George Washington University. “While some lizards do some of these things — and there are many more lizards than snakes — there are many more snakes in most of these habitats in most places.”

The ultimate causes, or triggers, of adaptive radiations is one of the big mysteries in biology. In the case of snakes, it’s likely there were multiple contributing factors, and it may never be possible to tease them apart.

The authors of the upcoming Science study refer to this once-in-evolutionary-history event as a macroevolutionary singularity with “unknown and perhaps unknowable” causes.

A macroevolutionary singularity can be viewed as a sudden shift into a higher evolutionary gear, and biologists suspect these outbursts have happened repeatedly throughout the history of life on Earth. The sudden emergence and subsequent dominance of flowering plants is another example.

In the case of snakes, the singularity started with the nearly simultaneous (from an evolutionary perspective) acquisition of elongated legless bodies, advanced chemical detection systems and flexible skulls.

Those crucial changes allowed snakes, as a group, to pursue a much broader array of prey types, while simultaneously enabling individual species to evolve extreme dietary specialization.

Today, there are cobras that strike with lethal venom, giant pythons that constrict their prey, shovel-snouted burrowers that hunt desert scorpions, slender tree snakes called “goo-eaters” that prey on snails and frog eggs high above the ground, paddle-tailed sea snakes that probe reef crevices for fish eggs and eels, and many more.

“One of our key results is that snakes underwent a profound shift in feeding ecology that completely separates them from other reptiles,” Rabosky said. “If there is an animal that can be eaten, it’s likely that some snake, somewhere, has evolved the ability to eat it.”

For the study, the researchers got an inside look at snake dietary preferences by reviewing field observations and stomach-content records for more than 60,000 snake and lizard specimens, mostly from natural history museums. The contributing museums included the University of Michigan Museum of Zoology, home to the world’s largest research collection of snake specimens.

“Museum specimens give us this incredible window into how organisms make a living in nature. For secretive animals like snakes, it’s almost impossible to get this kind of data any other way because it’s hard to observe a lot of their behavior directly,” said study co-lead author Pascal Title of Stony Brook University, who completed his doctorate at U-M in 2018.

The study’s 20 authors are from universities and museums in the United States, the United Kingdom, Australia, Brazil and Finland.

“What I love about this study is how it integrates hard-earned field and museum data with new genomic and analytical methods to show a basic biological truth: Snakes are exceptional and frankly quite cool,” said co-lead author Sonal Singhal of California State University, Dominguez Hills, who started work on the project as a U-M postdoctoral scholar.

The chemical structures of these molecules, which consist of a dense, highly complex knot of oxidized rings and nitrogen atoms, has attracted the interest of organic chemists worldwide, who aimed to recreate these structures from scratch in the laboratory. However, despite considerable effort, it has remained an elusive task. Until now, that is.

A team of Yale chemists, writing in the journal Science, has succeeded in synthesizing eight of the compounds for the first time using an approach that combines inventive chemical strategy with the latest technology in small molecule structure determination.

“These molecules have been an outstanding challenge in the field of synthetic chemistry,” said Seth Herzon, the Milton Harris ’29 Ph.D. Professor of Chemistry in Yale’s Faculty of Arts and Sciences and corresponding author of the new study. “A number of research groups have tried to recreate these molecules in the lab, but their structures are so dense, so intricately connected, that it hasn’t been possible. I’ve been reading about efforts to synthesize these compounds since I was a graduate student in the early 2000s.”

In nature, the molecules are found in some species of bryozoa — small, aquatic animals that feed by filtering prey from the water via tiny tentacles. Researchers worldwide consider bryozoans to be a potentially valuable source of new medications, and many molecules isolated from bryozoans have been studied as novel anticancer agents. However, the complexity of the molecules often limits their further development.

Herzon’s team looked at a particular species of bryozoa called Securiflustra securifrons.

“We worked on these molecules about a decade ago, and though we were not successful in recreating them at that time, we gleaned insight into their structure and chemical reactivity, which informed our thinking,” Herzon said.

The new approach involved three key strategic elements. First, Herzon and his team avoided constructing a reactive heterocyclic ring, known as an indole, until the end of the process. A heterocyclic ring contains two or more elements — and this specific ring is known to be reactive and create problems, Herzon said.

Second, the researchers used methods known as oxidative photocyclizations to construct some of the key bonds in the molecules. One of these photocyclizations involved the reaction of a heterocycle with molecular oxygen, which was first studied by Yale’s Harry Wasserman in the 1960s.

Lastly, Herzon and his team employed microcrystal electron diffraction (MicroED) analysis to help visualize the structure of the molecules. Herzon said conventional methods for structure determination were inadequate in this context.

The result of the new approach is eight new synthetic molecules with therapeutic potential — and the promise of more new chemistry to come.

“These molecules hit right at my love of complex synthetic challenges,” said Herzon, who is also a member of the Yale Cancer Center and holds joint appointments in pharmacology and therapeutic radiology at Yale School of Medicine. “On a molecular weight basis, they are modest relative to other molecules we’ve studied in my lab. But from the vantage point of chemical reactivity, they present some of the greatest challenges we’ve ever taken on.”

Co-first authors of the new study are Yale chemistry graduate students Brandon Alexander and Noah Bartfield. Co-authors are Vaani Gupta, a Yale chemistry graduate student; Brandon Mercado, a Yale X-ray crystallographer and lecturer in the Department of Chemistry; and Mark Del Campo of Rigaku Americas Corporation.

The National Science Foundation helped fund the research.