It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Monday, May 11, 2026
Bidirectional association between premenstrual disorders and psychiatric disorders
In this nationwide cohort study conducted in Sweden, bidirectional associations were found between premenstrual disorders and psychiatric disorders and conditions, highlighting the need for sex- and menstrual cycle–informed care in psychiatry. Further research is needed to understand the underlying mechanisms shared between premenstrual disorders and psychiatric disorders.
Corresponding Authors: To contact the corresponding authors, email Jing Zhou, MD, MSc (jing.zhou@ki.se) and Donghao Lu, MD, PhD (donghao.lu@ki.se).
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.
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About JAMA Network Open:JAMA Network Open is an online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.
Journal
JAMA Network Open
Causes of excess deaths in the US compared with other high-income countries
JAMA Network Open
About The Study:
In this repeated cross-sectional study of cross-national mortality, the U.S. had substantially higher death rates than other high-income countries between 1999 and 2022, despite having similar access to advanced medical technology. Many of these excess U.S. deaths could likely be avoided by adopting health and social policies that have benefited other high-income countries. These descriptive findings should be interpreted in light of uncertainty arising from differences in death coding, data completeness, and other aspects of data comparability across countries.
Corresponding Author: To contact the corresponding author, Jacob Bor, PhD, email jbor@bu.edu.
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.
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Embed this link to provide your readers free access to the full-text article
About JAMA Network Open: JAMA Network Open is an online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.
Journal
JAMA Network Open
Cardiovascular and metabolic diseases are primary drivers of excess US deaths compared to other high-income countries
Between 1999 and 2022, the US had substantially higher death rates than other wealthy nations, largely due to cardiovascular disease, metabolic diseases, Alzheimer’s disease and related dementias, and drug and alcohol complications
Boston University School of Public Health
Between 1999 and 2022, the US had substantially higher death rates than other wealthy nations, largely due to cardiovascular disease, metabolic diseases (including diabetes), Alzheimer’s disease and related dementias, and drug and alcohol complications. Policies are needed to address the underlying health, social, and economic conditions that increase Americans’ risk of developing these diseases.
Despite having similar access to advanced medical technology, the United States has substantially higher death rates than other high-income countries (HICs), and the gap has been growing for decades. Cardiovascular diseases were the leading cause of excess US deaths, according to a new study led by researchers at Boston University School of Public Health (BUSPH).
Published in JAMA Network Open, the study found that between 1999-2022, the annual number of excess US deaths—deaths that would not have occurred had the mortality rate in the US been the same as in other HICs—increased steadily through 2019 and then rose rapidly during the COVID-19 pandemic. By 2022, all-cause mortality rates in the US were 38 percent higher than in other HICs. An estimated 12.7 million US deaths could have been averted during this period if US mortality rates mirrored those of its peers. The authors refer to these excess US deaths as “missing Americans.”
The study investigated the causes of these excess US deaths, and found that cardiovascular diseases, including heart disease, hypertension, and stroke, were the leading cause of excess mortality nearly every year of this period. Together, cardiovascular and metabolic diseases accounted for over half of all excess US deaths in 2022. Drug poisonings, alcohol-related diseases, and suicides emerged as another major cause of excess mortality during this period, particularly among men and people under 45 years old. Homicide and HIV/AIDS also had mortality rates many times higher in the US than in other HICs; however, these causes were responsible for only a small share of excess US deaths.
The study builds upon previous findings by the researchers which showed that excess US deaths have increased since 1980 and continued to increase even after the COVID-19 pandemic. The new analysis is the first study to identify all leading causes responsible for these excess US deaths—what the authors refer to as a “population autopsy.” Quantifying causes of the US mortality disadvantage can reveal opportunities for intervention, including policies to prevent these fatal conditions from occurring in the first place.
“In public health, we know that death certificates only list the most proximate cause of death and not the full causal chain. Differences in social factors between the US and other HICs can lead to differences in behavioral risk factors, which in turn can lead to higher risks of specific causes of death,” says study lead and corresponding author Dr. Jacob Bor, associate professor of global health and epidemiology at BUSPH. “These findings pinpoint the issues that we should be focusing on if we want to address the US mortality disadvantage relative to peer countries.”
For the study, Dr. Bor and colleagues from BUSPH, Harvard Medical School, and Hunter College at the City University of New York analyzed US excess deaths by sex, age, and year. They utilized cause-of-death data from the World Health Organization Mortality Database for all deaths occurring from 1999-20222 in the US and 17 other HICs, including Australia, Canada, France, Japan, and the United Kingdom. The team compared excess mortality among the countries used three metrics: excess deaths, which is the difference between reported deaths and deaths that would have occurred if the US had the mortality rate of other HICs; years of life lost, which is the years of potential life lost due to premature deaths; and mortality rate ratios, which compare the risk of different causes of death between the US and other countries.
Among more than 63.5 million total deaths that occurred during this period, the US experienced an estimated 12,675,646 more excess deaths than would have occurred if their death rates were equal to other HICs. Despite declining between 1999-2009, cardiovascular diseases remained the leading cause of excess deaths during the entire study period, except for 2010, before rising sharply and continuously through 2022. Diabetes, kidney, and metabolic conditions also rose sharply from 2010-2022, following no significant increases from 1999-2009. In 2022, mental health and nervous system disorders such as Alzheimer’s disease and other dementias were the leading cause of excess death among people 85 and older. Respiratory illnesses, transportation accidents, and homicides were also major causes of US excess deaths. COVID-19 was a leading cause of US excess deaths from 2020-2022, representing 1 in 5 US excess deaths in 2020 and 2021, and also coinciding with sharp increases in other diseases.
Importantly, the study findings revealed stark differences in the burden of these causes of deaths, depending on whether they were viewed in absolute or relative terms. For example, in 2022, excess deaths from drug poisonings were 7.48 times higher in the US than in other countries, but only accounted for 10 percent of US excess deaths, while cardiovascular diseases were 1.63 times as high in the US than in other countries, but accounted for 40 percent of US excess deaths.
“In US population health research, examining the stagnation in US life expectancy that began in 2010 usually focuses on drug overdoses, alcohol-related deaths, and suicide, known as ‘deaths of despair,’” say study senior author Dr. Andrew Stokes, associate professor of global health at BUSPH. ”One dramatic finding from this study is that on an absolute scale, cardiometabolic diseases are key contributors to the increase in US death rates. If there was one thing we could address on a population scale, tackling cardiometabolic diseases would substantially reduce the US mortality gap with other wealthy nations.”
Drug poisonings are still a critical component of the US excess death conversation, the researchers note, particularly in terms of years of life lost, as this measure focuses on premature deaths and captures the societal burden of losing young people. These deaths represented the fastest increase in excess US deaths, rising from a near-equivalent level with peer countries in 1999 to more than 130,000 excess deaths in 2022, with a particular rise in 2013 after fentanyl entered the US drug supply. These causes also contributed to excess deaths among people ages 45-65.
The US did outperform peer countries in a couple of categories, comprising fewer excess deaths in 2022 for cancers (excluding lung cancer) and influenza, which Dr. Stokes attributes partly to advancements within the US healthcare system. “We’ve come a long way with medical innovations to screen and treat cancers,” he says.
The team says that more research is needed to understand the sharp rise in excess deaths after 2010, but that federal policy changes that address the root causes of these excess deaths with evidence-based interventions will help alleviate the current national mortality burden.
“While new therapeutics such as GLP-1s could make a major dent in cardiometabolic mortality, our findings suggest that other policies should be considered too,” says Dr. Bor. “Countries that have the same, or even worse, access to advanced medical technology perform far better on these metrics than the US. We need to identify the policies that other countries have implemented, and think about how we can emulate those policies in the US.”
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About Boston University School of Public Health
Founded in 1976, Boston University School of Public Health is one of the top ten ranked schools of public health in the world. It offers master's- and doctoral-level education in public health. The faculty in six departments conduct policy-changing public health research around the world, with the mission of improving the health of populations—especially the disadvantaged, underserved, and vulnerable—locally and globally.
The race to build “digital twins”—computational models of people’s biological and physiological systems—has accelerated. The promise is huge: predict disease, personalize care, and test treatments without risk. This essay points out that the ethics of the technology isn’t keeping pace.
Fleur O'Hare, Lauren N. Ayton, David Foran, Camille Paynter, Michelle Gallaher, Kelly Schulz, Myra B. McGuinness, Lauren Barina, Steven Y. C. Tong, Tessa Saunders
The four-foot-tall Emperor penguin of Antarctica may be the most iconic member of this unique family of birds, but 17 other species of penguins populate the Southern Hemisphere, many of them confined to isolated islands that make them hard to study.
That’s likely why an entirely new species of gentoo penguin has been overlooked on the Kerguelen Islands — or, as the French refer to them, the Desolation Islands — located nearly 2,000 miles from any permanently inhabited landmass. An international team of penguin experts led by Chilean and University of California, Berkeley biologists announced the discovery — the first new penguin species named in more than 100 years — in a paper published last month in the journal Communications Biology.
The scientists provided genetic evidence that what was once thought to be one widely dispersed species is actually four separate species of gentoo penguin. One of these was previously unrecognized because, except for slight differences in size and vocalization, it looks like every other gentoo: a white underside and black back, which are optimal for escaping predation while enabling prey capture in an ocean environment. Yet it is clearly genetically different — what scientists refer to as a cryptic species.
The researchers also concluded that three previously recognized subspecies of gentoo penguins are genetically distinct and should be elevated to full-fledged species status.
The fate of the newly recognized species — the southeastern gentoo penguin, Pygoscelis kerguelensis — and two others are uncertain as global warming affects the Antarctic and sub-Antarctic regions they occupy. Only the southern gentoo, now called Pygoscelis ellsworthi and the only species to reside in Antarctica, is predicted to be minimally affected or possibly even advantaged because of an expanded distributional range.
“It's very important that conservation institutions in all the different countries involved recognize and take appropriate action to save these three gentoo penguin species,” she added.
Biologists reach a consensus
Vianna and co-senior authors Rauri Bowie, a professor of integrative biology at UC Berkeley, and Elie Poulin, a professor at the University of Chile in Santiago, corralled penguin experts from around the world to collaborate on a new genomic analysis of gentoo penguin populations. Several of the authors had previously described subspecies of the gentoo — as many as six — though not all of them were in agreement. The paper represents a consensus, based on new whole genome sequences of 64 individuals from 10 breeding colonies, for the first time spanning nearly the entire geographical range of the gentoo penguin. The study also includes comparisons of physical characteristics, ranging from coloration and vocalizations to the timing of breeding, diet and feeding behaviors.
“There's probably no species of penguin where the taxonomy has been more debated than the gentoo penguin,” said Bowie, a curator in UC Berkeley’s Museum of Vertebrate Zoology. “For over 100 years it's been controversial as to how many species or how many subspecies there are. What this paper does is try to address that question using cutting-edge integrative approaches.”
Bowie and Vianna have worked together for nearly 10 years to understand the origins and diversity of penguins. In 2019, they published a landmark paper showing that penguins first arose around Australia and New Zealand about 22 million years ago, with Emperor and King penguins splitting off and occupying Antarctica and the sub-Antarctic, respectively. About 12 million years ago, with the rise of the circumpolar current, other penguins were carried throughout the sub-Antarctic, occupying many small islands and archipelagoes and spreading as far north as the African and South American continents.
The gentoos’ generalized diet indirectly led to the evolution of the new species, the researchers argue. Because the birds are content to eat what’s in front of them — including fish, krill, squid and cuttlefish — they don’t travel far from their breeding colony and nest in the same place year after year. As a result, the populations on isolated islands developed behavioral and ecological adaptations to their specific region that over time have been reinforced through selection across the genome. This led to speciation during the past 300,000 to 500,000 years, aided by the isolation of these remote islands and by the Antarctic Polar Front, a temperature and salinity barrier in the Southern Ocean that also is a barrier to animal movement.
North of the Polar Front, where the water is warmer and saltier, there’s now the eastern lineage — Pygoscelis taeniata — on the Crozet, Marion and Macquarie Islands, and the northern lineage — Pygoscelis papua — which is restricted to the Falkland/Malvinas and Martillo Islands in South America.
Right on the Polar Front lies the newly described, though low-population, southeastern lineage — Pygoscelis kerguelensis — which evolved on Kerguelen Island and likely nearby Heard Island. Below the Polar Front is found the southern and most populous lineage —Pygoscelis ellsworthi — which thrives on the Antarctic Peninsula, coastal Antarctica and South Georgia Island.
Genomes reveal genetic adaptations
The genomic analysis, which was led by the paper’s lead author, University of Chile graduate student Daly Noll, incorporated a more representative sample of genes across the entire genome than previous studies. It also involved thousands of genetic variations called single nucleotide polymorphisms (SNPs). The analysis showed how these species evolved to adapt to their environments. For example, the southern gentoo that is thriving in Antarctica shows genetic changes associated with adaptation to extreme polar environments, with a larger number of genes related to heat generation, fat and lipid storage and light perception. The latter likely reflects adaptations to seasonal daylight variation and ice reflectivity.
In contrast, the eastern gentoo has an increased number of genes linked to energy-efficient carbohydrate metabolism and enhanced diving capacity. These genes, which are associated with oxygen transport and use, blood vessel formation, mitochondrial activity and lung development, likely support prolonged underwater activity in low-productivity oceans.
The northern gentoo of South America, however, showed gene enrichment for digestion-related processes and pathways involved in cardiac contraction and muscle excitation. The researchers suggest that these patterns reflect metabolic and physiological adaptations that support sustained foraging activity in the water.
Vianna noted that many other non-Antarctic penguins are expected to suffer from habitat loss because of climate change and the increasing impacts of warming oceans, habitat destruction, predation by rats and dogs, competition from commercial fisheries and entrapment in nets.
“In terms of climate change, island species that have really low population sizes could be compared with the sub-Antarctic gentoo penguins,” she said. “Galapagos and other island penguin species, because they’re endemic to these islands, will find no place to go after a change in their environment. Those islands are very isolated, and these penguins cannot adapt easily to colonize any other region.”
The amount and variety of data acquired for the study is unprecedented and will have other uses, Bowie said. Vianna is already searching through penguin genomes to find the genetic changes associated with survival from avian influenza, which is now ravaging penguin, bird and mammal populations worldwide. Such studies could help identify populations most at risk from the disease.
“Whole genome sequencing has transformed our ability to not only look at adaptation from a perspective of how things diversify, but it has really important conservation value,” Bowie said.
Co-authors with Bowie and Vianna include biologists from Australia, Spain, Venezuela, South Africa, the United Kingdom, France, Argentina, Monaco and Brazil. Daly Noll of the University of Chile in Santiago is first author of the paper.
A gentoo penguin with chick.
Credit
Claudia Ulloa
Gentoo penguins engaged in a swimming technique known as porpoising.
When scientists think about how plants will respond to climate change, they often look north. As temperatures rise, many species are expected to shift their ranges toward cooler regions with a loss of populations in warmer habitats. But new research from the University of Virginia, published in the journal Evolution Letters, suggests the story may be more complicated and more hopeful.
The University of Virginia’s Commonwealth Professor of Biology Laura Galloway and postdoctoral research associate Antoine Perrier are studying what they call “rear-edge” populations, those found at the warmest edges of their geographic ranges. These populations, often descended from groups that survived the last ice age, have endured thousands of years of climate change.
“Because these populations have been there since the last glaciation, they’ve gone through warming in the past,” Galloway said. “We can use them as models for what we might expect in response to future warming.”
Their recent work on a native wildflower brings together multiple lines of evidence, including genomics, greenhouse experiments and field studies, to test how these populations evolved and what that might mean for the future.
Rethinking Vulnerability at the Warm Edge
Conventional ecological models predict that populations at the warm edge of a species’ range will be the first to disappear as temperatures rise. But Perrier and Galloway found something different.
“We often think that populations at the warmer edge are the ones that will go extinct,” Perrier said. “But it turns out there’s a lot that we don’t know about these populations.”
One possibility is that they harbor high genetic diversity, a legacy of their age and persistence since the last ice age, and therefore may be a resource for adapting to future change. Another is that as small, isolated populations, they might show signs of genetic drift, a process that reduces diversity and can make populations more fragile. A third possibility is that these populations have undergone local adaptation, evolving traits that allow them to thrive in conditions warmer than typical for the species.
The answer, in this case, was clear.
“We found patterns of local adaptation throughout the range,” Perrier said. “But what was very interesting is that in the deep south only the populations coming from very similar environments were able to actually grow and reproduce.”
In other words, southern populations have evolved specific traits that allow them to survive and reproduce in warmer climates. Northern populations transplanted into those same conditions failed to flower at all.
A Surprising Forecast for Climate Change
The findings challenge a central assumption about how species will respond to warming. Instead of southern populations disappearing first, the researchers’ data suggest that they are likely to persist, while populations in the middle of the range may struggle.
Many plant species use cold to cue reproduction, “As winters get warmer, populations are expected to experience a loss in reproduction,” Perrier said. “But this was not the case for the rear edge.”
Southern populations may be less affected by continued warming because they have already evolved to reproduce without relying on cold winter cues. By contrast, populations in regions like the mid-Atlantic could face new challenges.
“It’s almost the opposite of what we expect,” Galloway said, noting that both far-northern and far-southern populations may prove more resilient than those in between.
The work also points to practical applications. Traits that allow southern populations to thrive in warmer climates could potentially be introduced into more vulnerable populations through conservation strategies such as assisted gene flow.
Natural Laboratories for the Future
Beyond its immediate findings, the research highlights the value of studying long-term evolutionary history. Rear-edge populations, the researchers argue, act as “natural laboratories” for understanding how species respond to environmental change.
For Perrier, the work underscores both the urgency and the opportunity of climate research.
“We don’t often think of these populations as being the ones that might be the best adapted to future conditions,” he said. “But they could actually persist and change how we think about species responses to climate change.”
When an asteroid as big as Mount Everest struck Earth 66 million years ago, it wiped out all non-avian dinosaurs and roughly a third of life on the planet. But many plants survived the devastation.
In a new study publishing May 8 in the Cell Press journal Cell, researchers reveal that the accidental duplications of genomes—a natural phenomenon—might have helped many flowering plants survive some of the most extreme environmental upheavals in Earth’s history. This strategy could help plants adapt to the rapid climate changes unfolding today.
“Whole-genome duplication is often seen as an evolutionary dead end in stable environments,” says author Yves Van de Peer of Ghent University in Belgium. “But in harsh situations, it can provide unexpected advantages.”
Most organisms carry two sets of chromosomes, one from each parent. But in flowering plants, many species carry additional sets as a result of random whole-genome duplication. For example, most cultivated bananas have three sets of chromosomes while wheat plants can have as many as six, a condition known as polyploidy.
Whole-genome duplication occurs relatively frequently in plants, and it can be costly. Larger genomes require more nutrients to maintain, increase the risk of acquiring harmful mutations, and affect fertility. For these reasons, only a small fraction of duplicated genomes are retained and passed down through generations in the wild.
On the other hand, genome duplications can increase genetic variations, and genes can evolve new functions. These changes may help organisms better tolerate stress such as heat or drought.
To understand why some duplicated genomes persist, Van de Peer and his team analyzed the genomes of 470 species of flowering plants, constructing one of the largest datasets of its kind. They looked for blocks of genes that appear in almost identical pairs—a marker of past whole-genome duplication events. Then, they compared the data with information from 44 plant fossils to estimate when these duplications occurred.
Their analysis revealed a striking pattern. The researchers found that the genes that persist over time tend to originate from whole-genome duplications during major periods of environmental upheaval. These include the asteroid-triggered mass extinction 66 million years ago, several periods of global cooling when ecosystems collapsed, and the Paleocene-Eocene Thermal Maximum (PETM) about 56 million years ago—a period of rapid global warming.
The findings help explain a long-standing puzzle of why polyploidy is common, but only a few persevere in plant genomes over millions of years. Under these extreme conditions, polyploid plants might have gained an edge. Traits that are normally disadvantageous, such as maintaining a larger and more complex genome, can become beneficial, say the researchers.
The study also offers some clues about how plants may respond to climate change today. During the PETM, global temperatures rose by about 5 to 9°C (9 to 14°F) over roughly 100,000 years, a change comparable to the warming happening today.
“While the current climate is warming at a much faster rate, what we see from the past suggests that polyploidy may help plants cope with these stressful conditions,” Van de Peer says.
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This work was supported by Research Foundation–Flanders, the European Research Council, and Ghent University.
Cell (@CellCellPress), the flagship journal of Cell Press, is a bimonthly journal that publishes findings of unusual significance in any area of experimental biology, including but not limited to cell biology, molecular biology, neuroscience, immunology, virology and microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. Visit: http://www.cell.com/cell. To receive Cell Press media alerts, contact press@cell.com.
Photosynthesis is one of the most complex processes in nature. However, plants use only a fraction of the available light spectrum and are highly sensitive to environmental stressors such as changing light intensities, heat and drought. As climate change intensifies these stresses, safeguarding crop productivity is becoming an increasingly urgent challenge. To better understand the process of photosynthesis and at the same time identify starting points for improving it, researchers led by LMU biologist Dario Leister study model organisms such as the cyanobacterium Synechocystis.
In a study now published in Nature Communications, the scientists stressed Synechocystis by subjecting it to fluctuations in light intensity. “These kinds of conditions, in which high and low light intensities alternate at intervals ranging from one to several minutes, disrupt the process of photosynthesis and damage the photosystems,” explains Leister, who is Chair of Plant Molecular Biology at the Faculty of Biology in Martinsried. To find out how the blue-green algae can adapt to these unfavorable light conditions, the team recreated an accelerated evolutionary process in the laboratory.
Over time, this approach produced Synechocystis strains capable of tolerating light fluctuations that would normally be lethal. Genetic analysis of these adapted strains revealed mutations that influence the activity and relative quantity of biomolecules that are vital for photosynthesis. These include the protein-pigment complexes photosystem I and II and the light-harvesting antenna complexes. These evolutionary adaptations enhanced the resilience of Synechocystis to extreme variations in light intensity.
Plants growing in agricultural fields face similar challenges. Outdoor light conditions change constantly due to cloud cover, shading, and weather fluctuations, forcing crops to continuously adjust their photosynthetic machinery. “Photosynthesis works most efficiently at fairly low light intensity, whereas excessive light reduces efficiency. When the light levels change too quickly, the regulatory mechanisms cannot respond fast enough, which reduces efficiency and so also reduces the yield,” explains Dario Leister.
The findings from Synechocystis may provide new strategies for improving the ability of crops to cope with fluctuating light conditions. “The next step is to transfer the approach we used in our current study to eukaryotic algae because they are evolutionary closer to crop plants.” The biologist hopes that this will allow him to move step by step from relatively simple single-celled organisms toward applications in crops.
The study is part of the “PhotoRedesign: Redesigning the Photosynthetic Light Reactions” project, which has been funded by an ERC Synergy Grant from the European Union. In this research project, scientists from LMU are exploring new approaches for improving plant photosynthesis, using single-cell organisms like Synechocystis as model organisms because of their short generation times and the ease with which they can be genetically manipulated.
Ultimately, the goal is to produce crops that can utilize a broader range of light wavelengths. “To achieve this, it is important that optimized plants are also more robust and better able to cope with the additional absorbed light energy,” says Leister. The current study is providing new potential starting points for intervening in the complex photosynthetic apparatus of crops: “Our improved Synechocystis substrains contain point mutations that can also be transferred to related organisms using gene editing. With current legislative developments in the EU, such modifications may no longer be classified as transgenic in the future. Moreover, this strategy more closely resembles natural evolutionary processes than approaches based on overexpressing individual genes, which is a method often used by other researchers.”
Plants evolved distinct functions for two forms of a fundamental signaling molecule. These create redundancy and more robustness. Arabidopsis thaliana (mouse ear cress) plants at different developmental stages, photographed at the Plant Facility of the Institute of Science and Technology Austria (ISTA)
The molecule cAMP, which plays essential roles in mammalian cells, is less well understood in plants. In a new Science Advancespaper, researchers from the Institute of Science and Technology Austria (ISTA) and international collaborators demonstrate that plants use two forms of cAMP in parallel to regulate normal cellular processes and respond to stress, while maintaining crosstalk between them. That crosstalk provides redundancy, so that if one fails, the other can compensate, allowing plants to respond more robustly to a wider range of environmental factors. Ultimately, the findings could help improve crop resilience and productivity in a rapidly changing climate.
Plants can’t escape danger. To cope with stresses such as heat, freezing, flooding, drought, or infection, they rely on biological mechanisms evolved over millions of years.
Different life forms face unique environmental challenges, driving them to evolve distinct biological processes. Although animals, plants, and microbes share many molecular mechanisms, insights from animal models often don’t apply directly to other kingdoms.
Cyclic adenosine monophosphate, also known as cAMP, is a fundamental signaling molecule known to play essential roles in both animal and plant cells. However, although its production and role in mammalian cells are well understood, its functions in plants remain largely unknown.
Now, ISTA alum Mingyue Li and professor Jiřà Friml at the Institute of Science and Technology Austria (ISTA) have teamed up with scientists in Germany, Saudi Arabia, the Czech Republic, and the United States to shed light on cAMP in the plant model Arabidopsis thaliana, commonly known as mouse ear cress or thale cress.
Twin molecules with distinct but partially overlapping properties
In animal systems, the main form of cAMP, called 3’,5’-cAMP, is involved in the transfer of signals between nerve cells, hormone signaling, and the regulation of metabolic functions. This predominant form of cAMP is derived from the cell’s energy currency, ATP. However, cAMP has a ‘twin’ form: a molecule with the same chemical formula but different atomic bonds. Concretely, the phosphate group is attached to the adenosine molecule at a different location. This other form, called 2’,3’-cAMP, is associated with RNA degradation and stress response. Its levels are tightly controlled in mammalian cells because excessive amounts can be toxic.
Li, Friml, and their colleagues now show that, while both forms of cAMP exist in plants, the levels of 2’,3’-cAMP—the ‘other’ form of the molecule—are over 60 times higher than those of 3’,5’-cAMP, the main form found in animals.
Using a battery of molecular and cell biology techniques, the team demonstrates that the two forms of cAMP exhibit largely distinct functions in plant metabolism as well as in protein and gene regulation. While 3’,5’-cAMP appears to fine-tune responses related to growth, maintenance, nutrient status, and normal cell function, 2’,3’-cAMP triggers much broader effects in plants, including specialized metabolic pathways and broad stress responses. However, they also show that these functions partially overlap, suggesting that plants may have evolved distinct ways to adapt to environmental challenges.
Cross-talking signaling pathways
Maintaining two parallel but interconnected cAMP pathways could help plants fine-tune cellular regulation and distinguish among different external stimuli, including stress factors. Crosstalk between the pathways provides redundancy, so that if one fails, the other can compensate, allowing plants to respond more robustly to a wider range of environmental factors.
Ultimately, understanding how plants regulate stress and routine cellular functions could help boost crop productivity and enhance resilience to climate change.
Plants evolved distinct functions for two forms of a fundamental signaling molecule. These create redundancy and more robustness. Arabidopsis thaliana (mouse ear cress) plants at different developmental stages, photographed at the Plant Facility of the Institute of Science and Technology Austria (ISTA)
Arabidopsis thaliana plants at the Institute of Science and Technology Austria (ISTA).
Plants evolved distinct functions for two forms of a fundamental signaling molecule. Seedlings growing in the pink room at the Plant Facility of ISTA
Arabidopsis thaliana plants in pink room at the Institute of Science and Technology Austria (ISTA).
