Author: Futurity (National Geo)

New research sheds light on neural processing of diverse classes of rewards in mice, with potential implications for understanding substance use disorders in humans.

Drugs like morphine and cocaine fundamentally warp the brain’s reward system—creating the urge to use while, simultaneously, throwing natural urges to eat and drink off-kilter.

Now, researchers have identified, for the first time, a common reward pathway that may serve as a hub for rearranging such fundamental priorities.

The findings appear in Science.

“We’ve known for decades that natural rewards, like food, and drugs can activate the same brain region,” says  Jeffrey F. Friedman, a professor at Rockefeller University.

“But what we’ve just learned is that they impact neural activity in strikingly different ways. One of the big takeaways here is that addictive drugs have pathologic effects on these neural pathways, that’s distinct from, say, the physiologic response to eating a meal when you are hungry or drinking a glass of water when you are thirsty.”

Nestled in the forebrain, the nucleus accumbens (NAc) is involved in processing rewards from and desire for food, sex, social interaction—and addictive substances. The NAc, in close collaboration with the pleasure and mood modulating neurotransmitters dopamine and serotonin, influences decision-making by integrating motivation, reinforcement, and pleasure, essentially encouraging animals to repeatedly pursue activities that routinely feel good.

“The NAc is a key node where the underlying dopaminoceptive neurons direct and refine animals’ behaviors towards their goals,” says Bowen Tan, a graduate student in Friedman’s lab. “What we hadn’t been able to understand is how repeated exposure to drugs corrupts these neurons, resulting in escalated drug-seeking behaviors and a shift away from healthy goals.”

To answer that question, Friedman and Tan teamed up with Mount Sinai’s Eric J. Nestler, a psychiatrist and expert on the molecular neurobiology of drug addiction and depression. Together they turned to Rockefeller’s Alipasha Vaziri to overcome technical limitations that have hampered past work in the field. Brain imaging techniques developed in Vaziri’s lab are among the only tools capable of capturing the majority of the mouse cortex in real-time with high resolution. But in this case, the researchers also needed the capability to record neurons at large tissue depths, in order to image the neural activity at single-cell resolution in the NAc.

“Advancing our understanding of the intricately connected network within the brain demands the innovation of cutting-edge imaging technologies that can capture neuronal activity across distant brain regions, but also that of those at deeper regions,” Vaziri says.

The team ultimately discovered that cocaine and morphine each activate a specific subset of neurons that also respond to natural reward consumption in the mouse NAc. Both cocaine and morphine activated D1 medium spiny neurons in the NAc (involved in positive reinforcement and motivation), while morphine also activated D2 medium spiny neurons (involved in dampening or inhibiting responses to rewarding stimuli).

This cell type-specific response in the NAc was unexpected.

“Though both drugs and natural rewards activate an overlapping set of medium spiney neurons, cocaine and morphine each activate distinct cell types.” Tan says.

“Their distinct actions within the NAc underscore how the diverse neural dynamics elicited by drugs ultimately shape the different behavioral and physiological outcomes observed in regard to natural rewards.”

Then, using a combination of cutting-edge molecular and genomic techniques, including FOS-Seq, CRISPR-perturbation, and snRNAseq, the researchers went on to identify for the first time how drug addiction skews natural urge: by hijacking a molecular pathway that plays a crucial role neural plasticity, the process that neurons use reinforce learning and memory.

When drugs activate neurons expressing this gene, known as Rheb, it stimulates a pathway known as mTOR, likely altering how neurons communicate, learn, and remember stimuli from food and water. This may explain why mice and humans who are addicted to these substances seem to almost forget the need to eat and drink, stimuli that the brain should be reinforcing as rewards.

The team now plans to delve deeper into the cellular biology of addiction neuroscience, in part by identifying how other brain regions work in concert to influence addiction.

“A major part of our ongoing research will be directed to defining how the complex flow of information is incorporated into value computations in brain cells and how that crucial mechanism enables drugs to overtake the processing of natural rewards, leading to addiction,” Nestler says.

Source: Rockefeller University

Adding a pre-ketone supplement, a component of a high-fat, low-carb ketogenic diet, to a type of cancer therapy in a laboratory setting was highly effective for treating prostate cancer, researchers report.

As reported in the journal Cancer Research, the researchers tackled a problem oncologists have battled: Prostate cancer is resistant to a type of immunotherapy called immune checkpoint blockade (ICB) therapy. ICB therapy blocks certain proteins from binding with other proteins and paves the way for our body’s fighter cells, T cells, to kill the cancer.

“Prostate cancer is the most common cancer for American men, and immunotherapy has been really influential in some other cancers, like melanoma or lung cancer, but it hasn’t been working almost at all for prostate cancer,” says Xin Lu, associate professor in the biological sciences department at the University of Notre Dame, who is affiliated with the Boler-Parseghian Center for Rare and Neglected Diseases.

Adding a dietary supplement might overcome this resistance, suggests lead author Sean Murphy, a 2024 alumnus who was a doctoral student in Lu’s lab and had been following a keto diet himself.

Knowing that cancer cells feed off of sugar, he decided that depriving mouse models of carbohydrates—a key component of the keto diet—might prevent cancer growth.

He divided the models into different groups: immunotherapy alone, ketogenic diet alone, a pre-ketone supplement alone, the ketogenic diet with the immunotherapy, the supplement with the immunotherapy, and the control.

While the immunotherapy alone had almost no effect on the tumors (just like what happens to most patients with prostate cancer), both the ketogenic diet with the immunotherapy and the pre-ketone supplement with the immunotherapy reduced the cancer and extended the lives of the mouse models.

The supplement with the immunotherapy worked best.

“It turned out this combination worked really well,” Lu says. “It made the tumor become very sensitive to the immunotherapy, with 23% of the mice cured—they were tumor-free; in the rest, the tumors were shrinking really dramatically.”

The evidence points to the possibility that a supplement providing ketones, which are what is produced in the body when people eat a keto diet, might prevent the prostate cancer cells from being resistant to immunotherapy. This may lead to future clinical studies that examine how ketogenic diets or keto supplements could enhance cancer therapy.

While keto diets allow for minimal carbohydrates, the success of this study is not about the lack of carbohydrates, Murphy and Lu stress. It is about the presence of the ketone body, a substance produced by the liver and used as an energy source when glucose is not available. The ketones disrupt the cycle of the cancer cells, allowing the T cells to do their job to destroy them.

The discovery was also exciting on a molecular level, Lu says. Any type of dietary study can suffer from the potential issue of causation: Are the results from the diet or other changes made because of the diet? But Lu and his collaborators confirmed their results using single-cell RNA sequencing, which examines the gene expression of single cells within the tumor.

“We found that this combination of the supplement and the immunotherapy reprogrammed the whole immune profile of the tumors and recruited many T cells into the tumors to kill prostate cancer cells,” Lu says.

The successful therapy also reduced the number of a type of immune cell called neutrophils. Once in the tumor microenvironment, neutrophils’ natural properties become greatly distorted, and they become largely responsible for inhibiting T cell activities and allowing more tumor progression. Dysregulation of neutrophils is also associated with many other diseases.

“With the main ketone body depleting neutrophils, it opens the door for investigating the effects of the keto diet and the ketone supplement on diseases ranging from inflammatory bowel disease to arthritis,” Murphy says.

Lu agrees.

“What’s exciting is that we’re getting closer to the mechanism, backed up by genetic models and what we’re seeing in the tumors themselves, of why this works,” he says.

The American Institute for Cancer Research, the National Institutes of Health and a core facility grant from Indiana Clinical and Translational Sciences Institute funded the work. Other support included the Department of Defense and the Boler Family Foundation at the University of Notre Dame. A provisional patent application has been filed based on this study by the IDEA Center at Notre Dame.

Source: Deanna Csomo Ferrell for University of Notre Dame

Analysis suggests the baby teeth of saber tooth cats stayed in place for years to stabilize the growing permanent saber tooth, perhaps allowing adolescents to learn how to hunt without breaking them.

The fearsome, saber-like teeth of Smilodon fatalis—California’s state fossil—are familiar to anyone who has ever visited Los Angeles’ La Brea Tar Pits, a sticky trap from which more than 2,000 saber-toothed cat skulls have been excavated over more than a century.

Though few of the recovered skulls had sabers attached, a handful exhibited a peculiar feature: the tooth socket for the saber was occupied by two teeth, with the permanent tooth slotted into a groove in the baby tooth.

Paleontologist Jack Tseng, associate professor of integrative biology at the University of California, Berkeley, doesn’t think the double fangs are a fluke.

Nine years ago, he joined a few colleagues in speculating that the baby tooth helped to stabilize the permanent tooth against sideways breakage as it erupted. The researchers interpreted growth data for the saber-toothed cat to imply that the two teeth existed side by side for up to 30 months during the animal’s adolescence, after which the baby tooth fell out.

‘Double-fang’ stage

In a new paper published in the journal The Anatomical Record, Tseng provides the first evidence that the saber tooth alone would have been increasingly vulnerable to lateral breakage during eruption, but that a baby or milk tooth alongside it would have made it much more stable.

The evidence consists of computer modeling of saber-tooth strength and stiffness against sideways bending, and actual testing and breaking of plastic models of saber teeth.

“This new study is a confirmation—a physical and simulation test—of an idea some collaborators and I published a couple of years ago: that the timing of the eruption of the sabers has been tweaked to allow a double-fang stage,” says Tseng, who is a curator in the UC Museum of Paleontology.

“Imagine a timeline where you have the milk canine coming out, and when they finish erupting, the permanent canine comes out and overtakes the milk canine, eventually pushing it out. What if this milk tooth, for the 30 or so months that it was inside the mouth right next to this permanent tooth, was a mechanical buttress?”

He speculates that the unusual presence of the baby canine—one of the deciduous teeth all mammals grow and lose by adulthood—long after the permanent saber tooth erupted protected the saber while the maturing cats learned how to hunt without damaging them. Eventually, the baby tooth would fall out and the adult would lose the saber support, presumably having learned how to be careful with its saber.

Paleontologists still do not know how saber-toothed animals like Smilodon hunted prey without breaking their unwieldy sabers.

“The double-fang stage is probably worth a rethinking now that I’ve shown there’s this potential insurance policy, this larger range of protection,” he says. “It allows the equivalent of our teenagers to experiment, to take risks, essentially to learn how to be a full-grown, fully fledged predator. I think that this refines, though it doesn’t solve, thinking about the growth of saber tooth use and hunting through a mechanical lens.”

The study also has implications for how saber-toothed cats and other saber-toothed animals hunted as adults, presumably using their predatory skills and strong muscles to compensate for vulnerable canines.

Feline beam theory

Thanks to the wealth of saber-toothed cat fossils, which includes many thousands of skeletal parts in addition to skulls, unearthed from the La Brea Tar Pits, scientists know a lot more about Smilodon fatalis than about any other saber-toothed animal, even though at least five separate lineages of saber-toothed animals evolved around the world.

Smilodon roamed widely across North America and into Central America, going extinct about 10,000 years ago. Yet paleontologists are still confounded by that fact that adult animals with thin-bladed knives for canines apparently avoided breaking them frequently despite the sideways forces likely generated during biting.

One study of the La Brea predator fossils found that during periods of animal scarcity, saber-toothed cats did break their teeth more often than in times of plenty, perhaps because of altered feeding strategies.

The double-fanged specimens from La Brea, which have been considered rare cases of individuals with delayed loss of the baby tooth, gave Tseng a different idea—that they had an evolutionary purpose.

To test his hypothesis, he used beam theory—a type of engineering analysis employed widely to model structures ranging from bridges to building materials—to model real-life saber teeth. This is combined with finite element analysis, which uses computer models to simulate the sideways forces a saber tooth could withstand before breaking.

“According to beam theory, when you bend a blade-like structure laterally sideways in the direction of their narrower dimension, they are quite a lot weaker compared to the main direction of strength,” Tseng says. “Prior interpretations of how saber tooths may have hunted use this as a constraint. No matter how they use their teeth, they could not have bent them a lot in a lateral direction.”

He found that while the saber’s bending strength—how much force it can withstand before breaking—remained about the same throughout its elongation, the saber’s stiffness—its deflection under a given force—decreased with increasing length. In essence, as the tooth got longer, it was easier to bend, increasing the chance of breakage.

By adding a supportive baby tooth in the beam theory model, however, the stiffness of the permanent saber kept pace with the bending strength, reducing the chance of breaking.

“During the time period when the permanent tooth is erupting alongside the milk one, it is around the time when you switch from maximum width to the relatively narrower width, when that tooth will be getting weaker,” Tseng says. “When you add an additional width back into the beam theory equation to account for the baby saber, the overall stiffness more closely aligned with theoretical optimal.”

Though not reported in the paper, he also made 3D-printed resin replicas of saber teeth and tested their bending strength and stiffness on a machine designed to measure tensile strength. The results of these tests mirrored the conclusions from the computer simulations. He is hoping to 3D-print replicas from more life-like dental material to more accurately simulate the strength of real teeth.

Tseng notes that the same canine stabilization system may have evolved in other saber-toothed animals. While no examples of double fangs in other species have been found in the fossil record, some skulls have been found with adult teeth elsewhere in the jaws but milk teeth where the saber would erupt.

“What we do see is milk canines preserved on specimens with otherwise adult dentition, which suggests a prolonged retention of those milk canines while the adult tooth, the sabers, are either about to erupt or erupting,” he says.

The National Science Foundation’s Division of Biological infrastructure supports Tseng’s work.

Source: UC Berkeley

Dog aggression can be unsettling, stressful, and even dangerous, not only for the dog but also for other pets, family members, and strangers.

Because some forms of aggression are rare and unexpected, such as rage syndrome, Lori Teller, a clinical professor at the Texas A&M School of Veterinary Medicine and Biomedical Sciences, provides guidance on how owners can recognize and respond to the varying signs of aggression:

What is rage syndrome?

Rage syndrome, a serious and complex condition that causes dogs to become aggressive without any apparent trigger, can be challenging to diagnose and treat effectively.

“Dogs with rage syndrome have episodes of extreme aggression toward a person or other animals that occur seemingly out-of-the-blue and without provocation, yet they otherwise appear friendly and happy,” Teller says.

The exact cause of rage syndrome remains unclear, though Teller points out that there can be genetic and neurological factors involved. Nevertheless, owners should remain vigilant for varying signs of the disorder.

“No identifiable trigger leading up to the attack is one clear sign of rage syndrome,” Teller says. “Additional signs include confusion or seeming dazedness during or immediately after an episode, glazed eyes, dramatic escalation of aggression without any warning, and unpredictability of episodes.”

Other forms of dog aggression

On the other hand, it’s important not to confuse conflict- or fear-based aggression with rage syndrome. Aggressions stemming from conflict or fear are more common than rage syndrome because they are natural responses to perceived threats or conflicts in the environment.

“There is usually an identifiable trigger for other forms of aggression, unlike with rage syndrome, but some owners have a hard time reading a dog’s body language or recognizing the trigger, making it challenging at first to determine what type of aggression a dog may have,” Teller explains.

“With fear-based or conflict aggression, a dog will often exhibit warning signs before attacking, such as a hunched body posture, lip-licking, trembling, baring teeth, growling, or snapping.”

Aggression of this type is often defensive in nature, yet Teller says dogs also exhibit predatory behaviors that, while appearing aggressive, are actually offensive in nature and are driven by a dog’s natural instincts to pursue prey.

How should owners respond?

When a dog is in the midst of an aggressive episode, owners should avoid intervening physically, as this could lead to injuries. Once the dog has calmed down, owners should take them to their veterinarian for a thorough examination.

“The veterinarian will obtain a complete behavioral history and probably perform some diagnostic tests to rule out a medical problem that has led to the aggressive behaviors,” Teller explains. “An example of a medical problem that may trigger an aggressive response is when someone touches a painful area, such as with osteoarthritis or an ear infection.”

Teller also notes that rage syndrome can be caused by seizure-like activity in the brain, so veterinarians may recommend an electroencephalogram, a test that measures electrical activity in the brain, or an advanced imaging modality such as an MRI or CT scan, which takes detailed images of the brain to identify any abnormalities in its structure.

Managing aggression in dogs, however, will require a comprehensive approach that addresses both the underlying causes and immediate behavioral issues.

“Depending on the underlying cause of aggression, the dog may be put on an anxiolytic medication to relieve anxiety, an anticonvulsant to control the risk of seizures, or a combination of medications,” Teller says. “A behavioral modification plan will also be instituted, and in some cases, a referral may be made to a veterinary behaviorist.”

By understanding the differences between forms of aggression and seeking professional help when needed, owners can provide the necessary care and support for their dogs.

The impact of aggression on a dog’s life can be minimized as a result, leading to a safer and happier environment for both the dog and its owners.

Source: Texas A&M University

Researchers have discovered a link between birth mothers who experienced stressful childhood events and their own children’s behavior problems.

The finding held true even though the children were adopted as newborns, raised by their adoptive parents, and were never directly exposed to the stresses their birth mothers had experienced.

If a child’s adoptive mother also experienced stressful events as a youth, such as abuse, neglect, violence, or poverty, then the child’s behavior issues were even more pronounced, the researchers found.

This study underscores the importance of efforts to prevent child neglect, poverty, and sexual and physical abuse, and to intervene with help and support when children experience them.

“We can’t always prevent bad things from happening to young children,” says Leslie Leve, a professor in the University of Oregon College of Education, a scientist with the Prevention Science Institute, and lead author of the study in the journal Development and Psychopathology.

“But we can provide behavioral health supports to individuals who have been exposed to childhood trauma or neglect to help them develop coping skills and support networks, so that difficult childhood experiences are less likely to negatively impact them—or the next generation.”

In the only study of its kind, Leve and other researchers followed 561 adopted children, their birth parents, and adoptive parents for more than a decade. They recruited participants through 45 adoption agencies in 15 states nationwide. The researchers collected data from the birth parents when children in the study were infants and from the adoptive parents when the children were age 6-7 and again at age 11.

The researchers found when birth mothers reported more adverse childhood experiences and other life stress when they were young, their children showed less “effortful control” at age 7. Examples of “effortful control” include the child being able to wait before initiating new activities when asked and being able to easily stop an activity when told “No.”

At age 11, the children of these same mothers showed more “externalizing behavior,” such as rule-breaking and aggressive behavior.

The study also points the way for additional inquiry. For example, exactly how does stress in one generation become associated with behavior in the next generation?

“We know from nonhuman animal studies that stress can change the expression of genes by essentially changing which genes are turned ‘on’ or ‘off’ when passed on to the next generation,” Leve says. “That could be a plausible pathway.”

Further, what is the effect of the environment in which the child was raised?

“Can we find something positive in the rearing environment, perhaps parents’ warmth or sensitivity, that can help offset the child’s genetic or biologic risk for impulsive or externalizing behavior?” Leve asks. That is the next question the research team is exploring.

Additional coauthors are from the University of Oregon; the University of California, Riverside; the University of Cambridge; Penn State; George Washington University; and the University of Pittsburgh.

The research was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health & Human Development; the National Institute on Drug Abuse; National Institutes of Health Office of Behavioral and Social Sciences Research; National Institute of Mental Health; National Institute of Diabetes and Digestive and Kidney Disease; National Institute of Health’s Office of the Director; and the Andrew and Virginia Rudd Family Foundation.

Source: University of Oregon

An experimental monoclonal antibody drug appears to prevent and reverse the onset of clinical type 1 diabetes in mice, and in some cases, to lengthen the animals’ lifespan.

Researchers say the drug, called mAb43, is unique because it targets insulin-making beta cells in the pancreas directly and is designed to shield those cells from attacks by the body’s own immune system cells.

The drug’s specificity for such cells may enable long-term use in humans with few side effects, the researchers say. Monoclonal antibodies are made by cloning, or making identical replicas of, an animal (including human) cell line.

The findings, reported in the journal Diabetes, raise the possibility of a new drug for type 1 diabetes, an autoimmune condition that affects about 2 million American children and adults and has no cure or means of prevention.

Unlike type 2 diabetes, in which the pancreas makes too little insulin, in type 1 diabetes, the pancreas makes no insulin because the immune system attacks the pancreatic cells that make it. The lack of insulin interferes with the body’s ability to regulate blood sugar levels.

“People with type 1 diabetes face lifelong injections of insulin and many complications, including stroke and eyesight problems if the condition is not managed properly,” says Dax Fu,  associate professor of physiology at the Johns Hopkins University School of Medicine and leader of the study’s research team.

Fu says mAb43 binds to a small protein on the surface of beta cells, which dwell in clusters called islets. The drug was designed to provide a kind of shield or cloak to hide beta cells from immune system cells that attack them as “invaders.” The researchers used a mouse version of the monoclonal antibody, and will need to develop a humanized version for studies in people.

For the current study, the researchers gave 64 non-obese mice bred to develop type 1 diabetes a weekly dose of mAb43 via intravenous injection when they were 10 weeks old. After 35 weeks, all mice were non-diabetic. One of the mice developed diabetes for a period of time, but it recovered at 35 weeks, and that mouse had early signs of diabetes before the antibody was administered.

In five of the same type of diabetes-prone mice, the researchers held off giving weekly mAb43 doses until they were 14 weeks old, and then continued dosages and monitoring for up to 75 weeks. One of the five in the group developed diabetes, but no adverse events were found, the researchers say.

In the experiments in which mAb43 was given early on, the mice lived for the duration of the monitoring period of 75 weeks, compared with the control group of mice that did not receive the drug and lived about 18–40 weeks.

Next, the researchers, including postdoctoral fellows Devi Kasinathan and Zheng Guo, looked more closely at the mice that received mAb43 and used a biological marker called Ki67 to see if beta cells were multiplying in the pancreas. They say, after treatment with the antibody, immune cells retreated from beta cells, reducing the amount of inflammation in the area. In addition, beta cells slowly began reproducing.

“mAb43 in combination with insulin therapy may have the potential to gradually reduce insulin use while beta cells regenerate, ultimately eliminating the need to use insulin supplementation for glycemic control,” Kasinathan says.

The research team found that mAb43 specifically bound to beta cells, which make up about 1% or 2% of pancreas cells.

Another monoclonal antibody drug, teplizumab, was approved by the US Food and Drug Administration in 2022. Teplizumab binds to T cells, making them less harmful to insulin-producing beta cells. The drug has been shown to delay the onset of clinical (stage 3) type 1 diabetes by about two years, giving young children who get the disease time to mature and learn to manage lifelong insulin injections and dietary restrictions.

“It’s possible that mAb43 could be used for longer than teplizumab and delay diabetes onset for a much longer time, potentially for as long as it’s administered,” says Fu.

“In an ongoing effort, we aim to develop a humanized version of the antibody and conduct clinical trials to test its ability to prevent type 1 diabetes, and to learn whether it has any off-target side effects,” says Guo.

Additional coauthors are from Johns Hopkins, the University of Maryland, and the University of Colorado.

The National Institutes of Health funded the work.

Source: Johns Hopkins University

A new experimental drug targets insulin-making beta cells in the pancreas directly and is designed to shield those cells from attacks by the body’s own immune system cells.

Plants are not simply victims of circumstances, but have helped to shape climate conditions on Earth, researchers report.

Over the course of hundreds of millions of years, Earth has lived through a series of climatic shifts, shaping the planet as we know it today. Past changes in CO2 levels and temperature can help us understand the planet’s response to global warming today.

As part of a growing field called biogeodynamics, researchers are racing to understand how such changes have affected life on the planet in the past.

“We’re trying to understand processes relevant to the present using the geological past,” says Julian Rogger, who focuses on biogeodynamics at the Institute of Geophysics at ETH Zurich.

Rogger is fascinated by the interplay of plant life and climate. So far our planet is the only one we know of in the universe suited to support living organisms. Its climatic conditions allow for the presence of enough liquid water to enable plants and other complex organisms to thrive, or at least survive. When the planet’s climate shifts, it impacts plant life, forcing ecosystems to evolve and adapt to changing conditions.

“I’m interested in the role of life itself in the whole system,” Rogger says. “I find it really fascinating to reconstruct the world as it was millions of years ago.”

Plants aren’t passive

In a new paper, Rogger and colleagues from ETH and the University of Leeds argue that those plants aren’t just passive participants in Earth’s climate cycle—they can play an important role in shaping it.

“We could assume life is just reacting to changes, but it’s also possible it’s interacting with the system and regulates it,” Rogger says.

To show how, Rogger used computer models that simulate the interplay between climate change, movement of the continents, and plant life in the deep past. The models indicate plants probably help regulate the makeup of the planet’s atmosphere by trapping carbon and emitting oxygen, helping control CO2 levels. They also accelerate the process of mineral weathering in soils, a process that consumes CO2. Rogger’s models suggest the planet’s climate and atmosphere are part of a feedback loop: Life itself plays a role in regulating or accelerating climatic changes.

390 million years into the past

When change is slow—slow enough for plants to evolve or spread to new niches over millions of years—plant activity can act as a buffer, preventing temperatures from shifting too rapidly. But geology and the fossil record show there were also changes that took place too fast, and resulted in major disruptions of vegetation and even mass extinctions.

“What we want to know is how fast vegetation is able to change its characteristics when the world suddenly gets 5 or 6 degrees warmer,” Rogger says. “The overall goal is to understand the coevolution of climate, vegetation, and tectonics.”

Rogger and his coauthors created a computer model of the last 390 million years that took into account the shifting of the continents and climate and the vegetation’s response to these changes. Running simulations on powerful supercomputers can still take up to a month, given the complexity of the problem and the length of time they are supposed to represent.

Whenever possible, the team uses geological data to make the models as realistic as possible: Chemical analysis of sediments, for example, can be an indicator for carbon dioxide levels in the past. Fossils can show when dramatic shifts in climate led to mass extinctions, or the evolution of new ecosystems in response to changing conditions.

The models show that long periods of stability make it possible for vegetation to flourish, absorbing CO2 and stabilizing the Earth’s climate over time. In their models, the team saw that plants were able to evolve fast enough to adjust to gradual shifts in climate and landscapes due to continental drift, for example.

But when the climate system is disrupted and changes too rapidly for vegetation to adapt, the opposite happens: Plants are wiped out and can’t act as a buffer to slow down shifts in climate. Without plants to act as a brake, environmental changes happen even faster and push further towards the extreme.

“It’s like a feedback effect,” Rogger explains. “Because regulation falls away, you could have a stronger increase in CO2 and more climate change than was previously expected.”

How resilient is the Earth?

In the geological record, abrupt climate changes are often accompanied by mass extinction events.

“There are strong vegetation changes where it took thousands to millions of years for vegetation to adapt and recover,” Rogger says, “and what recovers can be very different than what was there before.”

That’s not good news.

“The rate of change we have at the moment is thought to be unprecedented over the past 400 million years,” Rogger says. “There could be a reduction in the capacity of vegetation to regulate climate if there is a strong change, like we’re experiencing now.”

At a time when the Earth’s climate is changing faster than ever before, Rogger’s research has practical implications: Information from the past can help people today understand how resilient the Earth’s interlocking systems are.

“How fast are ecosystems able to respond to changes in the climate and landscape? That’s one of the major unknowns,” he says. “It’s an acute question—how resilient is the Earth?”

The research appears in Science Advances.

Source: ETH Zurich

An expert has tips for you to help your cat breathe easy with feline asthma.

Spring is often described as a time of renewal and beauty, with flowers blooming and trees budding. However, spring flowers and budding trees also cause higher pollen counts, and for those with asthma, higher pollen counts can bring a greater risk of an asthma attack.

Fortunately for our feline friends, asthma attacks in cats are not as common as they are in humans, although cats who have the condition will still require a proper diagnosis and treatment plan to manage their condition.

Audrey Cook, a professor at the Texas A&M University School of Veterinary Medicine & Biomedical Sciences, explores how owners can monitor their cats for signs of asthma so that they may seek veterinary care early, helping to improve their cat’s quality of life and reduce the frequency of asthma attacks.

Diagnosing feline asthma

Feline asthma is a chronic respiratory condition characterized by inflammation and narrowing of the airways, leading to difficulty in breathing that makes daily activities difficult to accomplish.

“Most cats are young adults—between 3 and 4 years old—when diagnosed with asthma, but it can affect cats of any age,” Cook says. “Cats with asthma tend to be limited in their ability to play and climb, as they can become short of breath and exertion makes them feel worse. Affected cats may even hide or isolate themselves.”

Cook points out that wheezing is often a strong indication of asthma, but there are also other signs that can be used to help make a diagnosis.

Owners can help further reduce the risk of asthma attacks and improve their cat’s overall respiratory health by keeping them away from allergens and irritants.

“Signs include increased breathing effort and rate, breathing with an open mouth, and coughing,” Cook says. “Because most of the signs are less specific, testing is needed to confirm a diagnosis.”

Other conditions can mimic asthma symptoms, which is why a formal diagnosis by a veterinarian is necessary to determine the true underlying cause. This ensures that the cat receives the most appropriate treatment.

“Those signs are not specific to asthma and can also be seen in cats with respiratory infections, heartworm disease, heart failure, or cancer,” Cook says. “All of these conditions are serious, so it is very important to seek veterinary care quickly for any cat that experiences changes in breathing patterns.”

How to manage asthma in your cat

If a cat has been diagnosed with asthma, its veterinarian will prescribe medication to manage the condition. Without proper management, asthma symptoms can worsen over time and lead to serious complications, such as respiratory failure.

“The mainstay of therapy is glucocorticoids, a type of steroid that reduces the underlying airway inflammation,” Cook says. “These may be given by injection or by mouth during acute episodes, but we prefer to use inhaled steroids for long-term control as these have less side effects.

“Although it does not address inflammation and should not be used as a sole therapy, bronchodilators—a type of medication that relaxes the muscles in the airways—can provide short-term improvements in breathing and reduce coughing,” Cook continues. “These also can be given by injection, mouth, or inhaler.”

After determining the best medication for managing your cat’s asthma, a veterinarian can show you how to administer their treatment.

Regular veterinary check-ups also are helpful to ensure a cat’s asthma condition is properly managed, allowing veterinarians to monitor their respiratory health, assess the effectiveness of current treatments, and make any necessary adjustments to the treatment plan.

Additionally, owners can help further reduce the risk of asthma attacks and improve their cat’s overall respiratory health by keeping them away from allergens and irritants.

“We don’t fully understand what drives asthma in cats, but it is clear that environmental allergens (pollens or other pets) and irritants (cigarette smoke, air fresheners, or litter dust) can make things worse,” Cook explains. “Trying to limit a cat’s exposure to things that can exacerbate airway inflammation is very important.”

Despite the challenges it presents, many cats with asthma can lead happy and comfortable lives with the help of proper management and a little extra care from their owners.

Source: Texas A&M University

A new analysis of the economic toll of mental illness considers a host of adverse economic outcomes not considered in earlier estimates.

Mental illness costs the US economy $282 billion annually, which is equivalent to the average economic recession, according to the new study coauthored by Yale University economist Aleh Tsyvinski.

The first-of-its-kind study integrates psychiatric scholarship with economic modeling to better understand the macroeconomic effects of mental illness in the United States.

The study was prepared as a working paper of the National Bureau of Research, a private nonprofit US organization that includes researchers from leading US universities, economics professional organizations, and the business and labor communities.

The $282 billion estimate—which amounts to about 1.7% of the country’s aggregate consumption—is about 30% larger than previous approximations of mental illness’s overall cost in epidemiological studies.

While those earlier studies focused on income loss relating to mental illness and the costs of mental health treatment, the new study also accounted for a host of additional adverse economic outcomes associated with mental illness, including the fact that people with mental illness consume less, invest less in a house, stocks, and other risky assets, and may choose less-demanding jobs, Tsyvinski says.

“In this paper, we develop the first integrated model of macroeconomics and mental health building on classic and modern psychiatric theories,” says Tsyvinski, a professor of economics in Yale’s Faculty of Arts and Sciences and professor of global affairs in the Yale Jackson School of Global Affairs. “We show that mental illness alters people’s consumption, savings, portfolio choices, as well as the country’s labor supply, generating enormous annual costs to our economy.”

Nationwide, more than 20% of adults live with mental illness and about 5.5% experience serious mental illness, according to the US Substance Abuse and Mental Health Services Administration.

For the study, Tsyvinski and coauthors Boaz Abramson of Columbia Business School, and Job Boerma of the University of Wisconsin-Madison, analyzed the potential effects of policies aimed at improving treatment of mental illness. They found that expanding the availability of mental health services—by eliminating the shortage of mental health professionals, among other means—would reduce mental illness by 3.1% and bring societal benefits equivalent to 1.1% of aggregate consumption.

Providing mental health services to everyone between the ages of 16 and 25 experiencing mental illness would reap societal benefits equal to 1.7% of aggregate consumption, according to the study.

At the same time, their analysis found that lowering the out-of-pocket cost of mental health services does not substantially reduce the share of people with mental illness and provides only minor economic gains. The researchers suggest that the monetary costs of mental health services are relatively low, meaning that reducing costs does not lead to greater uptake in treatment nor does it significantly reduce instances of mental illness.

The researchers model mental illness as a state of negative thinking and a state of rumination—the uncontrollable and repetitive preoccupation with negative thoughts—that is reinforced through behavior. In that model, they say, individuals experiencing mental illness are pessimistic about their future productivity, risky investments, and the evolution of their mental health. They also lose time while ruminating. As a result, they work, consume, and invest less while also foregoing treatment, which reinforces their mental illness.

“Economics and psychiatry have developed over 50 years, but they don’t speak to each other very much,” Yale economist William Nordhaus says. “Here, we’ve put them in conversation in a way that enlightens both and provides us a stronger sense of the societal costs of mental illness as well as what can be gained through policies that seek to expand and improve mental health care.”

Source: Yale University

Researchers have engineered bacteria in the laboratory to efficiently use methanol.

The metabolism of these bacteria can now be tapped into to produce valuable products currently made by the chemical industry from fossil fuels.

To produce various chemicals such as plastics, dyes, or artificial flavors, the chemical industry currently relies heavily on fossil resources such as crude oil.

“Globally, it consumes 500 million tons per year, or more than one million tons per day,” says Julia Vorholt, professor at the Institute of Microbiology at ETH Zurich. “Since these chemical conversions are energy-intensive, the true CO2 footprint of the chemical industry is even six to 10 times larger, amounting to about 5% of total emissions globally.”

She and her team are looking for ways to reduce the chemical industry’s dependence on fossil fuels.

Bacteria that feed on methanol, known as methylotrophs, are at the center of these efforts. Containing just a single carbon atom, methanol is one of the simplest organic molecules and can be synthesized from the greenhouse gas carbon dioxide and water. If the energy for this synthesis reaction comes from renewable sources, the methanol is termed “green”.

“There are natural methylotrophs, but using them industrially remains difficult despite considerable research effort,” says Michael Reiter, a postdoctoral researcher in Vorholt’s research group, which instead works with the biotechnologically well-understood model bacterium Escherichia coli. Vorholt’s team has been pursuing the idea of equipping the model bacterium, which grows on sugar, with the ability to metabolize methanol for several years.

“This is a major challenge because it requires a complete restructuring of the cell’s metabolism,” says Vorholt. Initially, the researchers simulated this change using computer models. Based on these simulations, they chose two genes to remove and three new genes to introduce.

“As a result, the bacteria could take up methanol, albeit only in small quantities,” says Reiter.

They continued to grow the bacteria under special conditions in the laboratory for more than a year until the microbes could produce all cell components from methanol. Over the course of around 1,000 more generations, these synthetic methylotrophs became increasingly efficient, eventually doubling every four hours when fed only with methanol.

“The improved growth rate makes the bacteria economically interesting,” says Vorholt.

As Vorholt’s team describes in their recently published paper, several randomly occurring mutations are responsible for the increased efficiency of methanol utilization. Most of these mutations resulted in the loss of function of various genes. This is surprising at first glance, but upon closer inspection, it becomes apparent that the cells can save energy thanks to the loss of function of the genes. For example, some mutations cause the reverse reactions of important biochemical reactions to fail.

“This abolishes superfluous chemical conversions and optimizes the metabolic flux in the cells,” the researchers write.

To explore the potential of synthetic methylotrophs for the biotechnological production of industrially relevant bulk chemicals, Vorholt and her team have equipped the bacteria with additional genes for four different biosynthetic pathways. In their study, they now show that the bacteria indeed produced the desired compounds in all cases.

For the researchers, this is clear evidence that their engineered bacteria can deliver on what was originally promised: the microbes are a kind of highly versatile production platform into which biosynthesis modules can be inserted according to the “plug-and-play” principle, prompting the bacteria to convert methanol into desired biochemical substances.

However, the researchers still need to significantly increase the yield and productivity to enable economically viable use of the bacteria. Vorholt and her team recently received an innovation fund “to further expand plans towards applications and to select products to focus on first,” says Vorholt.

When Reiter talks about how the cultivation of bacteria in bioreactors can be optimized, he is filled with enthusiasm.

“Given the challenges of climate change, it is clear that alternatives to fossil resources are needed,” he says.

“We are developing a technology that does not emit additional CO2 into the atmosphere,” says Reiter. And since the synthetic methylotrophs, besides green methanol, do not require any additional carbon sources for their growth and products, they allow “renewable chemicals to be produced that do not burden the environment.”

The research appears in Nature Catalysis.

Source: Ori Shipper for ETH Zurich