Earth

The plasticisers contained in many everyday objects can impair important brain functions in humans. Biologists from the University of Bayreuth warn of this danger in an article in Communications Biology. Their study shows that even small amounts of the plasticisers bisphenol A and bisphenol S disrupt the transmission of signals between nerve cells in the brains of fish. The researchers consider it very likely that similar interference can also occur in the brains of adult humans. They therefore call for the rapid development of alternative plasticisers that do not pose a risk to the central nervous system.

Bisphenols are plasticisers that are found in a large number of plastic products worldwide - for example, in food packaging, plastic tableware, drinking bottles, toys, tooth fillings, and babies' dummies. In recent years, numerous health risks have already been associated with them, especially with bisphenol A (BPA). The Bayreuth research team led by Dr. Peter Machnik at the Animal Physiology research group (led by Prof. Dr. Stefan Schuster) has now for the first time investigated the effects of plasticisers on signal transmission between nerve cells in the adult brain. The study covers not only BPA, but also bisphenol S (BPS), which is often considered less harmful to health. Their findings: Both plasticisers impair communication between the nerve cells of the brain.

Permanent damage to the nervous system

The harmful effects on the brain mainly affect the delicate balance between different neuronal functions. While some brain cells transmit signals that trigger a state of excitation in downstream cells, other brain cells have the function of inhibiting downstream cells. However, the coordination of both excitation and inhibition is essential for an intact central nervous system. "It is well known that numerous disorders in the nervous system of vertebrates are triggered by the fact that excitatory signals and inhibitory signals are not or only inadequately coordinated. So, it is all the more alarming that the plasticisers BPA and BPS significantly impair precisely this coordination," explains Dr. Peter Machnik, lead author of the study.

"We were surprised how many vital brain functions in fish are affected by the plasticisers used in numerous industries. This damage, as we were able to show, does not occur immediately. However, when the brain cells are exposed to small amounts of BPA or BPS for a month, the damage is unmistakable," says Elisabeth Schirmer, a doctoral student from Bayreuth and first author of the study. It turns out that the plasticisers influence the action potential of brain cells. They alter the chemical and electrical transmission of signals through the synapses. In addition, they disrupt the circuits that are important for the perception and processing of acoustic and visual stimuli.

Studies on Mauthner cells in goldfish

The discovery of the damage caused by plasticisers came from detailed studies on live goldfish. The focus was on the two largest nerve cells in fish brain, the Mauthner cells. They integrate all sensory stimuli, all of which must be processed quickly and in a precisely coordinated manner when predators approach. In this case, the Mauthner cells trigger life-saving escape reactions. Due to this function, which is essential for survival, they have become particularly robust in the course of evolution. Mauthner cells are able to ward off damaging influences to a certain extent, or to compensate for damage afterwards. This makes it all the more significant that plasticisers are able to cause considerable damage to these cells.

Transferability of the results to humans - Demand for alternative plasticisers

"The findings obtained through studies on fish brains justify the assessment that BPA and BPS can also seriously damage the brains of adult humans. Against this background, it is essential that science and industry develop new plasticisers to replace these bisphenols, while being safe for human health," says Dr. Peter Machnik. Prof. Dr. Stefan Schuster adds: "The efficiency of the research techniques we used in our study could, in addition, prove a valuable aid in the development of alternative plasticisers. They make it possible to quickly and inexpensively test how a substance under consideration affects brain cells."

New research from McMaster University suggests the pandemic has created a paradox where mental health has become both a motivator for and a barrier to physical activity.

People want to be active to improve their mental health but find it difficult to exercise due to stress and anxiety, say the researchers who surveyed more than 1,600 subjects in an effort to understand how and why mental health, physical activity and sedentary behavior have changed throughout the course of the pandemic.

The results are outlined in the journal PLOS ONE.

"Maintaining a regular exercise program is difficult at the best of times and the conditions surrounding the COVID-19 pandemic may be making it even more difficult," says Jennifer Heisz, lead author of the study and an associate professor in the Department of Kinesiology at McMaster.

"Even though exercise comes with the promise of reducing anxiety, many respondents felt too anxious to exercise. Likewise, although exercise reduces depression, respondents who were more depressed were less motivated to get active, and lack of motivation is a symptom of depression," she says.

Respondents reported higher psychological stress and moderate levels of anxiety and depression triggered by the pandemic. At the same time, aerobic activity was down about 20 minutes per week, strength training down roughly 30 minutes per week, and sedentary time was up about 30 minutes per day compared to six months prior to the pandemic.

Those who reported the greatest declines in physical activity also experienced the worst mental health outcomes, the researchers reported, while respondents who maintained their physical activity levels fared much better mentally.

Researchers also found economic disparities played a role, particularly among younger adults.

"Just like other aspects of the pandemic, some demographics are hit harder than others and here it is people with lower income who are struggling to meet their physical activity goals," says Maryam Marashi, a graduate student in the Department of Kinesiology and co-lead author of the study. "It is plausible that younger adults who typically work longer hours and earn less are lacking both time and space which is taking a toll."

After analysing the data, the researchers designed an evidence-based toolkit which includes the following advice to get active:

Adopt a mindset: Some exercise is better than none.

Lower exercise intensity if feeling anxious.

Move a little every day.

Break up sedentary time with standing or movement breaks.

Plan your workouts like appointments by blocking off the time in your calendar.

"Our results point to the need for additional psychological supports to help people maintain their physical activity levels during stressful times in order to minimize the burden of the pandemic and prevent the development of a mental health crisis," says Heisz.

In the earliest stage of life, animals undergo some of their most spectacular physical transformations. Once merely blobs of dividing cells, they begin to rearrange themselves into their more characteristic forms, be they fish, birds or humans. Understanding how cells act together to build tissues has been a fundamental problem in physics and biology.

Now, UC Santa Barbara professor Otger Campàs, who also holds the Mellichamp Chair in Systems Biology and Bioengineering, and Sangwoo Kim, a postdoctoral fellow in professor Campàs lab, have approached this question, with surprising findings.

"When you have many cells physically interacting with each other, how does the system behave collectively? What is the physical state of the ensemble?" said Campàs.

Indeed, he explained, embryonic cellular tissue is a "weird material," with each cell consuming chemical energy and using it to apply forces to its neighbors and coordinate their actions. In-vitro studies with cells in synthetic dishes provide only part of the picture, he added; by studying cells in their native environment, the living embryo, they could find out how cells control their collective state and the phase transitions that emerge from their symphony of pushes and pulls.

In a paper published in Nature Physics, Campàs, Kim and colleagues report the development of a computational framework that captures the various interactions between cells and connects them to embryonic tissue dynamics. Unlike previous simulations, this framework takes into account several key features relevant to cell interactions, such as spaces between cells, cell shapes and tension fluctuations where the cells meet.

"To fully understand the physical behavior of embryonic tissues, all key aspects of embryonic tissues at cellular scales should be taken into account in the model as emergent tissue properties derives from interactions at the cellular scale," said Kim, the lead author of the study. "There are numerous models to study embryonic tissues, but there is no general framework that includes those key features, hindering the holistic understanding of the physical behaviors of embryonic tissues."

Jiggling Cells

Embryonic tissue, according to the researchers, behaves physically somewhat like an aqueous foam, a system composed of individual pockets of air clumped together in a liquid. Think soap suds or beer froth.

"In the case of foam, its structure and dynamics are governed by surface tension," Kim said. Analogous forces are found where cells come into contact with each other in embryonic tissue, on both the inner faces of the cell membranes and between cells.

"Effective forces acting on cell-to-cell junctions are governed by cortical tension and cell-to-cell adhesion," Kim said, "so the net force at the cell-to-cell contacts can be modeled as an effective surface tension."

However, unlike the more static forces between cells in typical foams, the forces between cells in embryonic tissue are dynamic.

"Cells in tissues do not generate static forces, but rather display dynamic pushing and pulling over time," Campàs explained. "And we find that it is actually these tension fluctuations that effectively 'melt' the tissue into a fluid state." It is this fluidity of the tissue that allows cells to reorganize and shape the tissues, he explained.

The researchers put their model to the test by measuring how forces change over time in embryonic zebrafish, a popular model organism for those studying vertebrate development. Relying on a technique developed in the Campàs Lab using tiny magnetic droplets inserted between cells in embryonic zebrafish, they were able to confirm, by the way the droplet deformed, the dynamic forces behind the fluid state of the tissue.

Their finding that tension fluctuations are responsible for the fluidity of tissue during development stands in contrast to the generally accepted notion that changes in adhesion between cells is the critical factor that controlled the fluidity of the tissue -- if the adhesion between cells reached a certain high threshold, the tissue would become fluid.

"But since cell forces and tensions fluctuate in embryos, it could be that these played an important role in tissue fluidization," Campàs said. "So when we ran the simulations and did the experiments, we realized that actually the jiggling was way more important for the fluidization than the adhesion." The fluid state of the tissue is the result of the dynamics of forces, rather than changes in static cell tension or adhesion.

The findings of this study could have implications in the field of physics, particularly in the realm of active matter -- systems of many individual units that each consume energy and apply mechanical forces that collectively exhibit emergent collective behaviors. The study could also inform studies in biology, in investigations of how changes in individual cell parameters could control the global state of the tissue such as with embryonic development or with tumors.

UNIVERSITY PARK, Pa. -- When the COVID-19 pandemic hit in early 2020, many families found themselves suddenly isolated together at home. A year later, new research has linked this period with a variety of large, detrimental effects on individuals' and families' well-being and functioning.

The study -- led by Penn State researchers -- found that in the first months of the pandemic, parents reported that their children were experiencing much higher levels of "internalizing" problems like depression and anxiety, and "externalizing" problems such as disruptive and aggressive behavior, than before the pandemic. Parents also reported that they themselves were experiencing much higher levels of depression and lower levels of coparenting quality with their partners.

Mark Feinberg, research professor of health and human development at Penn State, said the results -- recently published in the journal Family Process -- give insight into just how devastating periods of family and social stress can be for parents and children, and how important a good coparenting relationship can be for family well-being.

"Stress in general -- whether daily hassles or acute, crisis-driven stress -- typically leads to greater conflict and hostility in family relationships," Feinberg said. "If parents can support each other in these situations, the evidence from past research indicates that they will be able to be more patient and more supportive with their children, rather than becoming more harsh and angry."

Feinberg added that understanding what can help parents maintain positive parenting practices, such as a positive coparenting relationship, is key for helping protect children during future crises -- whether those crises are pandemics, economic shocks or natural disasters.

While cross-sectional studies have suggested there has been a negative impact of the pandemic on families, the researchers said this study is one of the first to measure just how much these factors have changed within families before and after the pandemic hit.

According to the researchers, previous research has found that periods of financial stress, such as the Great Depression and the 2008 recession, have led to higher levels of parent stress, mental health problems and interparental conflict, which can all lead to more harsh, and even abusive, parenting.

When the COVID-19 pandemic hit, Feinberg said it led to not only financial stress within families, but also problems related to being isolated together, issues managing work and childcare, and general fear related to the sudden health threat that was poorly understood.

"When the pandemic hit, like many people, I was very anxious and worried," Feinberg said. "I saw the tensions and difficulties my daughter and I were having being home together 24/7. So, when I realized that our existing studies and samples of families gave us an opportunity to learn something about how families would cope during the crisis, my team and I moved into action."

For the study, the researchers used data from 129 families, which included 122 mothers and 84 fathers, with an average of 2.3 children per family. The parents answered an online questionnaire that asked them about their depressive symptoms, anxiety, the quality of their relationship with their coparent, and externalizing and internalizing behavior they observed in their children, among other measures.

Because the participants were part of a longer study measuring these factors over prior years, the researchers already had data on these parents and children from before the pandemic.

The researchers found that parents were 2.4 times more likely to report "clinically significant" high levels of depression after the pandemic hit than before. They were also 2.5 times and 4 times more likely to report externalizing and internalizing problems, respectively, in their children at levels high enough that professional help might be needed.

Feinberg said that while it makes sense that families would experience these difficulties, he was shocked at the magnitude of the declines in well-being.

"The size of these changes are considered very large in our field and are rarely seen," Feinberg said. "We saw not just overall shifts, but greater numbers of parents and children who were in the clinical range for depression and behavior problems, which means they were likely struggling with a diagnosable disorder and would benefit from treatment."

Feinberg put the size of the declines in parent and child well-being in perspective by pointing out that the increase in parents' levels of depressive symptoms in the first months of the pandemic was about twice as large as the average benefit of antidepressants.

The researchers said that as the risk of future pandemics and natural disasters increases with the effects of climate change, so will the likelihood of families facing stressful conditions again in the future

"Getting ready for these types of crises could include helping families prepare -- not just by stocking up on supplies, but also by improving family resiliency and psychological coping resources," Feinberg said. "In my view, that means providing the kinds of family prevention programs we've been developing and testing at the Prevention Research Center for the past 20 years."

For example, Feinberg explained that their research shows that the Family Foundations program helps new parents develop stronger capacities for cooperation and support in their relationship with each other as coparents, which is a key dimension of family resiliency.

Feinberg said future research will examine whether families who went through Family Foundations or other programs were more resilient, maintained better family relationships, and experienced smaller declines in mental health during the pandemic.

WOODS HOLE, Mass. -- Nitrogen is an element basic for life -- plants need it, animals need it, it's in our DNA -- but when there's too much nitrogen in the environment, things can go haywire. On Cape Cod, excess nitrogen in estuaries and salt marshes can lead to algal blooms, fish kills, and degradation of the environment.

In a study published in Environmental Research Letters, scientists at the Marine Biological Laboratory (MBL) Ecosystems Center examine ways to reduce the nitrogen footprint of smaller institutions, like the MBL, by focusing on a bottom-up approach.

"This bottom-up approach is all about balancing the needs of various stakeholders to come up with the best, most feasible solution for the institution," says Sarah Messenger, lead author and research assistant in the MBL Ecosystems Center.

At the MBL, and many institutions like it, the biggest sources of nitrogen are food production and consumption. That's because nitrogen is used as fertilizer to grow our food and produce the feed that supports livestock animals.

Researchers found that switching to an all-vegan diet (no animal products) in dining halls would make a huge dent in the institution's nitrogen footprint, but MBL's dining team called it a non-starter. The kitchen staff isn't trained for that, nor would the customers be open to it, they said. It would also mean big changes for the department's budget.

"The problem here is not just at an institutional level, but at a family level, at the community level, at regional, state, and national levels. The problem is that these things cost a lot of money and they are difficult to implement," says Javier Lloret, MBL research scientist.

The scientists also found that upgrading the institution's HVAC systems, fitting new, more efficient windows, or going 100% solar could cut the institution's nitrogen footprint. But all of those solutions come with a large price tag.

"The MBL is really small, so we don't have the personnel resources of larger Institutions," says Messenger. "We don't have a sustainability department. We have limited manpower, limited resources, and limited money that we can put towards making these big changes."

But what the MBL and many smaller institutions have are people who are experts at what they do. So instead of searching for a solution to the institution's nitrogen footprint that could require a large budget commitment from the director or the board of trustees, the scientists identified on-the-ground stakeholders in the departments that were responsible for the biggest portion of MBL's nitrogen footprint--food and facilities--and modeled "low-effort" solutions for those departments. They focused on ideas that didn't require new personnel, a large investment or a change in normal operations, and could be accomplished over the short term (three to five years).

"The goal was to only model changes that these department leaders could implement in their departments without needing sweeping changes and institution approval," says Messenger, adding that the team "completely disregarded any reduction strategies that weren't acceptable to the people that know their department best."

For dining services, an all-vegan or all-vegetarian menu was a no-go, but replacing 20% of MBL's beef use with chicken or fish resulted in a 2.6% reduction in the institution's nitrogen footprint, according to the researchers' model. Swapping out 10% of meat meals with vegetarian options would reduce the MBL's nitrogen footprint by 5.7%. They found that serving less meat could also result in a reduction of costs to the catering department.

The MBL's facilities team was already implementing an upgrade of the institution's lighting, so the research team adding those upgrades to their model -- calculating a 7.3% drop in the nitrogen footprint of the utilities sector and a 2% drop in the MBL's overall nitrogen footprint. Purchasing extra renewable energy credits to power the MBL with solar energy was also modeled.

Combining all the approaches, the scientists calculated a 7.7% drop in the MBL's nitrogen footprint with no major disruption to operations and no additional monetary support from the institution.

"It might not seem like a lot, but 8% is a lot of nitrogen," said Lloret. "These small changes do make a difference."

While no measures have been implemented yet, the team said they were optimistic by the response from the department stakeholders and hoped that the MBL, and other small institutions like it, could use this paper to examine ways to minimize their nitrogen and carbon footprints.

"We all want the same thing," says Messenger. "We would all love the MBL to reduce the impact on our environment as much as possible, but exactly how to get there is challenging. We're hoping that this paper can be a map forward."

Researchers have genetically engineered a probiotic yeast to produce beta-carotene in the guts of laboratory mice. The advance demonstrates the utility of work the researchers have done to detail how a suite of genetic engineering tools can be used to modify the yeast.

"There are clear advantages to being able to engineer probiotics so that they produce the desired molecules right where they are needed," says Nathan Crook, corresponding author of the study and an assistant professor of chemical and biomolecular engineering at North Carolina State University. "You're not just delivering drugs or nutrients; you are effectively manufacturing the drugs or nutrients on site."

The study focused on a probiotic yeast called Saccharomyces boulardii. It is considered probiotic because it can survive and thrive in the gut, whereas most other yeast species either can't tolerate the heat or are broken down by stomach acid. It also can inhibit certain gut infections.

Previous research had shown that it was possible to modify S. boulardii to produce a specific protein in the mouse gut. And there are many well-established tools for genetically engineering baker's yeast, S. cerevisiae - which is used in a wide variety of biomanufacturing applications. Crook and his collaborators wanted to get a better understanding of which genetic engineering tools would work in S. boulardii.

Specifically, the researchers looked at two tools that are widely used for gene editing with the CRISPR system and dozens of tools that were developed specifically for modifying S. cerevisiae.

"We were a little surprised to learn that most of the S. cerevisiae tools worked really well in S. boulardii," Crook says. "Honestly, we were relieved because, while they are genetically similar, the differences between the two species are what make S. boulardii so interesting, from a therapeutic perspective."

Once they had established the viability of the toolkit, researchers chose to demonstrate its functionality modifying S. boulardii to produce beta-carotene. Their rationale was both prosaic and ambitious.

"On the one hand, beta-carotene is orange - so we could tell how well we were doing just by looking at the colonies of yeast on a petri dish: they literally changed color," Crook says. "On a more ambitious level, we knew that beta-carotene is a major provitamin A carotenoid, which means that it can be converted into vitamin A by the body - and we knew that vitamin A deficiency is a major public health problem in many parts of the world. So why not try to develop something that has the potential to be useful?"

Researchers tested the modified S. boulardii in a mouse model and found that the yeast cells successfully created beta-carotene in the guts of mice.

"This is a proof of concept, so there are a lot of outstanding questions," Crook says. "How much of this beta-carotene is getting absorbed by the mice? Are these biologically relevant amounts of beta-carotene? Would it work in humans? All of those are questions we'll have to address in future work. But we're excited to see what happens. And we're excited that these tools are now publicly available for use by others in the research community."

Spanking may affect a child's brain development in similar ways to more severe forms of violence, according to a new study led by Harvard researchers.

The research, published recently in the journal Child Development, builds on existing studies that show heightened activity in certain regions of the brains of children who experience abuse in response to threat cues.

The group found that children who had been spanked had a greater neural response in multiple regions of the prefrontal cortex (PFC), including in regions that are part of the salience network. These areas of the brain respond to cues in the environment that tend to be consequential, such as a threat, and may affect decision-making and processing of situations.

"We know that children whose families use corporal punishment are more likely to develop anxiety, depression, behavior problems, and other mental health problems, but many people don't think about spanking as a form of violence," said Katie A. McLaughlin, John L. Loeb Associate Professor of the Social Sciences, director of the Stress & Development Lab in the Department of Psychology, and the senior researcher on the study. "In this study, we wanted to examine whether there was an impact of spanking at a neurobiological level, in terms of how the brain is developing."

According to the study's authors, corporal punishment has been linked to the development of mental health issues, anxiety, depression, behavioral problems, and substance use disorders. And recent studies show that approximately half of parents in U.S. studies reported spanking their children in the past year and one-third in the past week. However, the relationship between spanking and brain activity has not previously been studied.

McLaughlin and her colleagues--including Jorge Cuartas, first author of the study and a doctoral candidate in the Harvard Graduate School of Education, and David Weissman, a post-doctoral fellow in the Department of Psychology's Stress & Development Lab--analyzed data from a large study of children between the ages of three and 11. They focused on 147 children around ages 10 and 11 who had been spanked, excluding children who had also experienced more severe forms of violence.

Each child lay in an MRI machine and watched a computer screen on which were displayed different images of actors making "fearful" and "neutral" faces. A scanner captured the child's brain activity in response to each kind of face, and those images were analyzed to determine whether the faces sparked different patterns of brain activity in children who were spanked compared to those who were not.

"On average, across the entire sample, fearful faces elicited greater activation than neutral faces in many regions throughout the brain... and children who were spanked demonstrated greater activation in multiple regions of PFC to fearful relative to neutral faces than children who were never spanked," researchers wrote.

By contrast, "(t)here were no regions of the brain where activation to fearful relative to neutral faces differed between children who were abused and children who were spanked."

The findings are in line with similar research conducted on children who had experienced severe violence, suggesting that "while we might not conceptualize corporal punishment to be a form of violence, in terms of how a child's brain responds, it's not all that different than abuse," said McLaughlin. "It's more a difference of degree than of type."

Researchers said the study is a first step towards further interdisciplinary analysis of spanking's potential effects on children's brain development and lived experiences.

"These findings aligned with the predictions from other perspectives on the potential consequences of corporal punishment," studied in fields such as developmental psychology and social work, said Cuartas. "By identifying certain neural pathways that explain the consequences of corporal punishment in the brain, we can further suggest that this kind of punishment might be detrimental to children and we have more avenues to explore it."

However, they noted that their findings are not applicable to the individual life of each child.

"It's important to consider that corporal punishment does not impact every child the same way, and children can be resilient if exposed to potential adversities," said Cuartas. "But the important message is that corporal punishment is a risk that can increase potential problems for children's development, and following a precautionary principle, parents and policymakers should work toward trying to reduce its prevalence."

Ultimately, added McLaughlin, "we're hopeful that this finding may encourage families not to use this strategy, and that it may open people's eyes to the potential negative consequences of corporal punishment in ways they haven't thought of before."

Scientists from Queen Mary University of London, funded by the charity Brain Tumour Research, have found a new way to starve cancerous brain tumour cells of energy in order to prevent further growth.

The pre-clinical research in human tissue samples, human cell lines and mice could lead to changes in the way that some children with medulloblastoma are treated in the future, if the findings are confirmed in human clinical trials.

Medulloblastoma is the most common high-grade brain tumour in children. Some 70 are diagnosed in the UK each year. Survival rate is 70 per cent for those whose tumour has not spread but it is almost always fatal in cases of recurrent tumour.

The research, published in the high impact journal Nature Communications, looks at inositol hexaphosphate (IP6), a naturally occurring compound present in almost all plants and animals, and showed how it inhibits medulloblastoma and can be combined with chemotherapy to kill tumour cells.

Lead researcher Professor Silvia Marino from the Brain Tumour Research Centre of Excellence at Queen Mary University of London said: "Medulloblastoma occurs in four distinct subgroups (WNT, SHH, G3 and G4). Despite our growing knowledge of the molecular differences between these subgroups, current options are surgery together with radiotherapy and/or chemotherapy for all patients. We desperately need to understand the key molecular events driving tumour growth in each subgroup to design new, less toxic, targeted treatments."

"G4 medulloblastoma is the least understood of all subgroups, despite being the most common and associated with poor prognosis. We have identified a novel way that this type of medulloblastoma is able to adapt its metabolism and grow uncontrollably. Significantly, we have also shown how this energy supply can be blocked. These exciting results bring hope of developing new targeted treatments for patients with this aggressive paediatric brain tumour."

Normal cells are able to switch specific genes on and off as required to control their growth. Known as epigenetics, this process can be disrupted in cancer, leading to over production of specific proteins that contribute to the development and growth of a tumour.

It is already known that epigenetic changes can contribute to the development of medulloblastoma. Furthermore, a protein involved in this process - known as BMI1 - is found in high levels in a broad range of cancers including brain tumours. In medulloblastoma, high levels of it are found in the G4 subgroup, where it sustains tumour growth.

Professor Marino's team has previously demonstrated that, alongside high levels of BMI1, G4 medulloblastoma cells also lack a protein called CHD7. This combination of changes, or signature, is thought to contribute to the development of G4 medulloblastoma.

Now the team has shown that high levels of BMI1 enable the cancer cells to adapt their metabolism and grow aggressively. This change can be reversed by treating the cells with inositol hexaphosphate (IP6). The team also showed that when IP6 was combined with chemotherapy - in this case cisplatin - they observed an increased ability to kill the tumour cells in mice.

Hugh Adams, Head of Stakeholder Relations at Brain Tumour Research said: "These very exciting results reveal a new way for epigenetics to control metabolism within tumour cells. Clinical trials are now required to test the ability of combining IP6 with chemotherapy to treat G4 medulloblastoma, offering promise to a particularly vulnerable group of patients.

"It is great news and brings some much-needed hope for the future. There is still some way to go but we hope that a clinical trial could be up and running in the near future.

"Brain tumours kill more children and adults under the age of 40 yet, historically, just 1% of the national cancer spend has been allocated to this devastating disease. Brain Tumour Research is determined to change this."

Peter Gardiner, from Aston Clinton, near Aylesbury, lost his 13-year-old son to medulloblastoma in November 2017. Next month, May marks six years since his diagnosis.

"I can only describe our experience as a long hell. Firstly, Ollie was diagnosed, then he went through surgery and extensive treatment. When we were told there were no further options for him in the UK, we crowdfunded £500,000 so he could have immunotherapy in Germany. It was our only hope and, sadly, it didn't work," he said.

Ollie's family generously donated £187,000 of the residue of their fundraising to Brain Tumour Research which is funding post-doctoral researcher Sara Badodi who works alongside Prof Marino.

Pete said: "We were overwhelmed by the support of friends, family and strangers who stood by us in our hour of need and came together to help us do the very best we could for our son. It means the world to think that, because of him and the love people showed to us, others might not have to go through what we did."

A new study shows that thick sea-ice can increase the sensitivity of Greenlandic fjords to climate warming. Understanding the factors that control how fast glaciers move, break up and deposit chunks of ice (icebergs) into the fjords - and eventually the sea - is vital for predicting how the Greenland ice sheet will change under a warming climate and for predicting global rates of sea-level rise.

A new study led by Stockholm University Assistant Professor Christian Stranne, shows that thick sea-ice outside the fjords can actually increase the sensitivity of Greenlandic fjords to warming. Stranne and a team of researchers from Sweden, Greenland, the Netherlands, the USA, and Canada report on expeditions to two distinct fjords in northern Greenland during the 2015 and 2019 summers. "These fjords were practically inaccessible to researchers until quite recently because the sea-ice was too thick - they are some of the least-studied areas on the planet, and require a large icebreaker to reach them, even in the summer," says Stranne. The inaccessibility and sea-ice build-up is due to the direction of Arctic Ocean currents; the Beaufort Gyre and Transpolar Drift push ice from across the Arctic up against the northern Greenland coast.

Writing in Communications Earth & Environment, the research team report on measurements made during the Petermann 2015 and Ryder 2019 expeditions, when the Swedish icebreaker Oden made detailed studies of Petermann Fjord and Sherard Osborn Fjord in northern Greenland. Even in summer, the entrance to Sherard Osborn Fjord on the northern coast of Greenland is blocked by thick sea-ice, but the more southerly located Petermann Fjord has for several years opened to the Nares Strait, connecting the Arctic Ocean with Baffin Bay. Both fjords host large glaciers with floating ice tongues extending from Greenland glaciers many kilometers into the fjords. Unsurprisingly, warmer water temperatures will tend to melt these floating portions of the glaciers and icebergs in the fjord faster than cooler water. But how does the presence or absence of the thick sea-ice barrier outside a fjord affect water temperatures inside?

In 2019, air temperatures in northern Greenland reached record highs. Despite similar high air temperatures and conditions, Petermann Fjord's near surface sea temperatures never exceeded 0ºC. "But in the Sherard Osborn Fjord, cut off from the open ocean by thick sea-ice, near surface sea temperatures reached 4ºC - which was 3ºC higher than any previous seawater measurement north of Greenland," explains Stranne.

Summertime melt produces a warm freshwater layer floating atop saltier water in the fjord; here the sea-ice barrier trapped this meltwater inside the fjord. Because of the difference in salt content, the surface water became isolated also from the water below, allowing time for intense solar heating of the fresher surface water. Such warmer water temperatures can contribute to faster melting of the Ryder Glacier in Sherard Osborn Fjord, as well as changing the biogeochemistry in the fjord waters. Conversely, the researchers suggest, that neighboring Petermann Fjord, which was open to the sea during 2015 and 2019, experienced colder surface water temperatures because its surface water was not isolated within the fjord by a sea-ice barrier.

These observations are counterintuitive: thick sea-ice is associated with colder climates, yet it can lead to warmer surface water temperatures inside the fjords. For this reason, fjords along the northern Greenland coast are more sensitive to climate warming than fjords without a sea-ice barrier.

But each fjord is a little different. Last year, another study from the 2015 and 2019 expeditions pointed out that Ryder Glacier in Sherard Osborn Fjord is less affected by melting of the ice tongue from underneath, compared to Petermann Glacier in Petermann Fjord. In this case the explanation is not sea-ice but the shape of the seafloor that produces a shallower opening to the sea. The physical block of rock and sediment dampens intrusions of deeper warm water from outside the fjord (of Atlantic origin) which tends to make Ryder Glacier less sensitive to climate warming--while at the same time, surface sea-ice in the adjacent Lincoln Sea can make it more sensitive. "It's a complex interaction. Overall, we know that warming climate will lead to faster moving glaciers and less ice on Greenland. But how fast this happens, and to what extent, remains a key research topic," says Stranne.

Patients with non-small cell lung cancer (NSCLC) whose cancer cells have low levels of aneuploidy - an abnormal number of chromosomes - tend to respond better to immune checkpoint inhibitor drugs than patients with higher levels, Dana-Farber Cancer Institute researchers will report at the virtual AACR Annual Meeting 2021.

In analyzing data from hundreds of patients with NSCLC who were treated with these drugs, the researchers found that those whose cancer receded tended to have less aneuploidy in their tumor cells than those whose disease remained stable or worsened. These findings suggest that aneuploidy testing can have an important role in determining which treatment is most likely to benefit patients, according to the researchers.

"Aneuploidy is a widespread feature of non-small cell lung cancer and is associated with altered immune signaling; however, the functional significance of cancer aneuploidy remains unclear," said João Alessi, MD, of Dana-Farber who will be presenting the study findings. "Despite the availability of biomarkers for predicting which patients are most likely to respond to checkpoint-inhibiting drugs, less than 50 percent do respond, highlighting the need for new and better markers."

The checkpoint inhibitors used to treat NSCLC target the proteins PD-1 or PD-L1, which deter immune system T cells from attacking tumor cells. By blocking these proteins, the drugs allow the attack to proceed. The discovery by Dana-Farber scientists that PD-1 and PD-L1 can stymie an immune attack on cancer cells laid the foundation for the development of a new generation of checkpoint inhibitors.

For this study, Alessi and his colleagues analyzed data from 279 patients with NSCLC who had been treated with PD-1 or PD-L1 inhibitors. Each tumor was assigned an aneuploidy score from 0-39 based on the number of altered chromosome arms within its cells. The researchers used this information to explore whether aneuploidy score was linked to the effectiveness of treatment.

They found that patients with complete or partial responses (complete or partial shrinkage of their tumors) to checkpoint inhibitors had significantly lower aneuploidy scores than those with stable or progressive disease. Patients with cancer aneuploidy scores less than or equal to 2 had significantly higher overall response rates (43% vs. 19.8%), significantly longer progression-free survival (6.2 vs. 2.9 months), and significantly longer overall survival (19.8 vs. 13.8 months) than patients with aneuploidy scores greater than 2.

Aneuploidy score was significantly associated with progression-free and overall survival even after adjusting for other factors, such as performance status, oncogenic driver mutation, PD-L1 expression, tumor mutational burden, and line of treatment. After adjustment, patients with aneuploidy scores less than or equal to 2 were 28% and 36% more likely to have improved progression-free and overall survival, respectively, compared with patients with aneuploidy scores greater than 2.

Alessi and his colleagues also found that tumors with low aneuploidy scores had significantly higher numbers of immune cells positive for the CD8, Foxp3, and PD-1 proteins. The presence of these inflammatory markers indicates that tumors with low aneuploidy may be more likely to come under immune system attack than those with higher aneuploidy levels, which could contribute to increased responses to immune checkpoint inhibition. Aneuploidy score was not associated with PD-L1 expression or tumor mutational burden, suggesting that aneuploidy score could serve as an independent predictive biomarker.

"Our report provides a sizeable advance to understanding how aneuploidy correlates with response to treatment, making it a potential biomarker for the effectiveness of immunotherapy in patients with NSCLC," said Alessi. "Incorporating aneuploidy score in molecular testing may aid treatment decisions and clinical trial design."

A dementia diagnosis turns the world upside down, not only for the person affected but also for their relatives, as brain function gradually declines. Those affected lose their ability to plan, remember things or behave appropriately. At the same time, their motor skills also deteriorate. Ultimately, dementia patients are no longer able to handle daily life alone and need comprehensive care. In Switzerland alone, more than 150,000 people share this fate, and each year a further 30,000 new cases are diagnosed.

To date, all attempts to find a drug to cure this disease have failed. Dementia, including Alzheimer's - the most common of several forms of dementia - remains incurable. However, a clinical study carried out in Belgium with the involvement of ETH researcher Eling de Bruin has now shown for the first time that cognitive motor training improves both the cognitive and physical skills of significantly impaired dementia patients. A fitness game, known as "Exergame", developed by the ETH spin-off Dividat was used in the study.

Better cognitive ability thanks to training

In 2015, a team of scientists led by ETH researcher Patrick Eggenberger showed that older people who train both body and mind simultaneously demonstrate better cognitive performance and can thereby also prevent cognitive impairment (as reported by ETH News). However, this study was carried out on healthy subjects only.

"It has been suspected for some time that physical and cognitive training also have a positive effect on dementia," explains de Bruin, who worked with Eggenberger at the Institute of Human Movement Sciences and Sport at ETH Zurich. "However, in the past it has been difficult to motivate dementia patients to undertake physical activity over extended periods."

ETH spin-off combines exercise and fun

With a view to changing this, Eva van het Reve, a former ETH doctoral student, founded the ETH spin-off Dividat in 2013 together with her PhD supervisor Eling de Bruin and another doctoral student. "We wanted to devise a customised training programme that would improve the lives of older people," says van het Reve. Fun exercises were developed in order to encourage people who were already experiencing physical and cognitive impairments to participate in training, and the Senso training platform was born.

The platform consists of a screen with the game software and a floor panel with four fields that measure steps, weight displacement and balance. The users attempt to complete a sequence of movements with their feet as indicated on the screen, enabling them to train both physical movement and cognitive function simultaneously. The fact that the fitness game is also fun makes it easier to motivate the subjects to practice regularly.

Eight weeks' training for dementia patients

An international team led by Nathalie Swinnen, a doctoral student at KU Leuven, and co-supervised by ETH researcher de Bruin, recruited 45 subjects for the study. The subjects were residents of two Belgian care homes, aged 85 years on average at the time of the study and all with severe dementia symptoms.

"The participants were divided into two groups on a random basis," explains de Bruin. "The first group trained for 15 minutes with the Dividat Senso three times a week for eight weeks, while the second group listened to and watched music videos of their choice." Following the eight-week training programme, the physical, cognitive and mental capacity of all subjects was measured in comparison with the start of the study.

Regular play has an effect

The results offer hope to dementia patients and their relatives: training with this machine indeed enhanced cognitive skills, such as attention, concentration, memory and orientation. "For the first time, there's hope that through targeted play we will be able not only to delay but also weaken the symptoms of dementia," emphasises de Bruin.

It is particularly striking that the control group deteriorated further over the eight-week period, while significant improvements were recorded in the training group. "These highly encouraging results are in line with the expectation that dementia patients are more likely to deteriorate without training," adds de Bruin.

But playful training not only has a positive impact on cognitive ability - researchers were also able to measure positive effects on physical capability, such as reaction time. After just eight weeks, the subjects in the training group reacted significantly more quickly, while the control group deteriorated. This is encouraging in that the speed with which older people respond to impulses is critical in determining whether they can to avoid a fall.

A better understanding of brain processes

The research group led by de Bruin is currently working on replicating the results of this pilot study with people with mild cognitive impairment - a precursor of dementia. The aim is to use MRI scans to investigate more closely the neural processes in the brain responsible for the cognitive and physical improvement.

COLUMBUS, Ohio - In some men, having traditional masculine characteristics such as competitiveness and adventurousness was linked to being better fathers to infants, a new study found.

But the men in this study - highly educated and from dual-earner couples - combined those stereotypically masculine traits with the belief that they should be nurturing, highly involved fathers.

The researchers were surprised that traits often seen as old-fashioned male stereotypes were linked to more positive parenting behaviors, said study lead author Sarah Schoppe-Sullivan, professor of psychology at The Ohio State University.

It suggests that some men are looking for new ways to be fathers, Schoppe-Sullivan said.

"These men are combining traditional aspects of masculinity with new nurturing ideals to create new fathering identities. They may be in the midst of transforming fatherhood."

The study was published this week in the journal Psychology of Men and Masculinities.

The seven stereotypical masculine characteristics linked to positive parenting in this study - competitive, daring, adventurous, dominant, aggressive, courageous and stands up to pressure - are generally seen as positive traits, Schoppe-Sullivan noted.

But a negative masculine attitude that the researchers also measured in this study - hostile sexism - was not linked to positive parenting. In addition, the quality of fathers' parenting of their infants was unrelated to the belief that men should be primary economic providers in the family.

The men in the study were participating in the New Parents Project, a long-term study led by Schoppe-Sullivan that is investigating how dual-earner couples adjust to becoming parents for the first time.

In the third trimester of their partners' pregnancy, the expectant fathers completed a variety of questionnaires. They were asked to rate themselves on a four-point scale (not at all like me to very much like me) on the seven stereotypically masculine characteristics.

Hostile sexism was rated by asking male participants how much they agreed with 11 statements like "Feminists are making unreasonable demands of men." Participants were also asked whether men or women should provide the majority of income for the family.

Their nurturing father role beliefs were measured by asking men to rate how much they agreed with nine statements like "Men should share with child care such as bathing, feeding and dressing the child."

Nine months after the child was born, the researchers watched the fathers interact with their infants by themselves and with the mother. The researchers rated the fathers on their positive parenting behavior and on how well they co-parented together with mothers.

Results showed, as the researchers had predicted, that men who believed they should have a nurturing father role had higher-quality interactions with their child and were better at co-parenting with their partner.

But the researchers were surprised to find that the more men said they fit the stereotypical definition of "real men," the more they were also rated as showing good parenting behavior.

"The fathers who see themselves as competitive and adventurous and the other masculine traits tended to be really engaged with their kids. They were not checked out," Schoppe-Sullivan said.

It may be that men who used these traditionally masculine characteristics to succeed in their careers are trying to find ways to apply them to their jobs as parents.

"These dads may be saying that being a father is an important job, too, and I'm going to use the same traits that help me succeed at work to make me a successful father," she said.

Schoppe-Sullivan emphasized that the fathers in this sample were highly educated and had partners who also worked. The findings here may not apply to all fathers.

But the results are encouraging, she said.

"If fathers can preserve the best of these stereotypically masculine characteristics, without the negatives like hostile sexism, that would be good for families."

Over the past decade, the CRISPR-Cas9 gene editing system has revolutionized genetic engineering, allowing scientists to make targeted changes to organisms' DNA. While the system could potentially be useful in treating a variety of diseases, CRISPR-Cas9 editing involves cutting DNA strands, leading to permanent changes to the cell's genetic material.

Now, in a paper published online in Cell on April 9, researchers describe a new gene editing technology called CRISPRoff that allows researchers to control gene expression with high specificity while leaving the sequence of the DNA unchanged. Designed by Whitehead Institute Member Jonathan Weissman, University of California San Francisco assistant professor Luke Gilbert, Weissman lab postdoc James Nuñez and collaborators, the method is stable enough to be inherited through hundreds of cell divisions, and is also fully reversible.

"The big story here is we now have a simple tool that can silence the vast majority of genes," says Weissman, who is also a professor of biology at MIT and an investigator with the Howard Hughes Medical Institute. "We can do this for multiple genes at the same time without any DNA damage, with great deal of homogeneity, and in a way that can be reversed. It's a great tool for controlling gene expression."

The project was partially funded by a 2017 grant from the Defense Advanced Research Projects Agency to create a reversible gene editor. "Fast forward four years [from the initial grant], and CRISPRoff finally works as envisioned in a science fiction way," says co-senior author Gilbert. "It's exciting to see it work so well in practice."

Genetic engineering 2.0

The classic CRISPR-Cas9 system uses a DNA-cutting protein called Cas9 found in bacterial immune systems. The system can be targeted to specific genes in human cells using a single guide RNA, where the Cas9 proteins create tiny breaks in the DNA strand. Then the cell's existing repair machinery patches up the holes.

Because these methods alter the underlying DNA sequence, they are permanent. Plus, their reliance on "in-house" cellular repair mechanisms means it is hard to limit the outcome to a single desired change. "As beautiful as CRISPR-Cas9 is, it hands off the repair to natural cellular processes, which are complex and multifaceted," Weissman says. "It's very hard to control the outcomes."

That's where the researchers saw an opportunity for a different kind of gene editor -- one that didn't alter the DNA sequences themselves, but changed the way they were read in the cell.

This sort of modification is what scientists call "epigenetic" -- genes may be silenced or activated based on chemical changes to the DNA strand. Problems with a cell's epigenetics are responsible for many human diseases such as Fragile X syndrome and various cancers, and can be passed down through generations.

Epigenetic gene silencing often works through methylation -- the addition of chemical tags to to certain places in the DNA strand -- which causes the DNA to become inaccessible to RNA polymerase, the enzyme which reads the genetic information in the DNA sequence into messenger RNA transcripts, which can ultimately be the blueprints for proteins.

Weissman and collaborators had previously created two other epigenetic editors called CRISPRi and CRISPRa -- but both of these came with a caveat. In order for them to work in cells, the cells had to be continually expressing artificial proteins to maintain the changes.

"With this new CRISPRoff technology, you can [express a protein briefly] to write a program that's remembered and carried out indefinitely by the cell," says Gilbert. "It changes the game so now you're basically writing a change that is passed down through cell divisions -- in some ways we can learn to create a version 2.0 of CRISPR-Cas9 that is safer and just as effective, and can do all these other things as well."

Building the switch

To build an epigenetic editor that could mimic natural DNA methylation, the researchers created a tiny protein machine that, guided by small RNAs, can tack methyl groups onto specific spots on the strand. These methylated genes are then "silenced," or turned off, hence the name CRISPRoff.

Because the method does not alter the sequence of the DNA strand, the researchers can reverse the silencing effect using enzymes that remove methyl groups, a method they called CRISPRon.

As they tested CRISPRoff in different conditions, the researchers discovered a few interesting features of the new system. For one thing, they could target the method to the vast majority of genes in the human genome -- and it worked not just for the genes themselves, but also for other regions of DNA that control gene expression but do not code for proteins. "That was a huge shock even for us, because we thought it was only going to be applicable for a subset of genes," says first author Nuñez.

Also, surprisingly to the researchers, CRISPRoff was even able to silence genes that did not have large methylated regions called CpG islands, which had previously been thought necessary to any DNA methylation mechanism.

"What was thought before this work was that the 30 percent of genes that do not have a CpG island were not controlled by DNA methylation," Gilbert says. "But our work clearly shows that you don't require a CpG island to turn genes off by methylation. That, to me, was a major surprise."

CRISPRoff in research and therapy

To investigate the potential of CRISPRoff for practical applications, the scientists tested the method in induced pluripotent stem cells. These are cells that can turn into countless cell types in the body depending on the cocktail of molecules they are exposed to, and thus are powerful models for studying the development and function of particular cell types.

The researchers chose a gene to silence in the stem cells, and then induced them to turn into nerve cells called neurons. When they looked for the same gene in the neurons, they discovered that it had remained silenced in 90 percent of the cells, revealing that cells retain a memory of epigenetic modifications made by the CRISPRoff system even as they change cell type.

They also selected one gene to use as an example of how CRISPRoff might be applied to therapeutics: the gene that codes for Tau protein, which is implicated in Alzheimer's disease. After testing the method in neurons, they were able to show that using CRISPRoff could be used to turn Tau expression down, although not entirely off. "What we showed is that this is a viable strategy for silencing Tau and preventing that protein from being expressed," Weissman says. "The question is, then, how do you deliver this to an adult? And would it really be enough to impact Alzheimer's? Those are big open questions, especially the latter."

Even if CRISPRoff does not lead to Alzheimer's therapies, there are many other conditions it could potentially be applied to. And while delivery to specific tissues remains a challenge for gene editing technologies such as CRISPRoff, "we showed that you can deliver it transiently as a DNA or as an RNA, the same technology that's the basis of the Moderna and BioNTech coronavirus vaccine," Weissman says.

Weissman, Gilbert, and collaborators are enthusiastic about the potential of CRISPRoff for research as well. "Since we now can sort of silence any part of the genome that we want, it's a great tool for exploring the function of the genome," Weissman says.

Plus, having a reliable system to alter a cell's epigenetics could help researchers learn the mechanisms by which epigenetic modifications are passed down through cell divisions. "I think our tool really allows us to begin to study the mechanism of heritability, especially epigenetic heritability, which is a huge question in the biomedical sciences," Nuñez says.

Researchers at IMBA - Institute of Molecular Biotechnology of the Austrian Academy of Sciences - demonstrate that different viruses can lead to brain malformations through diverse mechanisms by using human brain organoid models. The results are published in the journal Cell Stem Cell.

Microcephaly, a term referring to developmental malformations of the fetal brain, can be caused by diverse infections during pregnancy. The infectious agents in question are grouped under the general term of TORCH pathogens, in reference to Toxoplasma gondii, Other, Rubella, Human Cytomegalovirus (HCMV), Herpes Simplex Viruses 1 and 2 (HSV-1 and HSV-2), as well as the more recently emerged Zika virus (ZIKV), which was also added to the group. The question whether all TORCH pathogens lead to microcephaly through the same mechanism has remained obscured due to the absence of suitable experimental models. Now, a team of researchers around IMBA Scientific Director Jürgen Knoblich provides the first comparative analysis of mechanisms linked to virus-induced microcephaly using a human brain organoid (HBO) model derived from human pluripotent stem cells (hPSCs).

"The two major difficulties in researching these conditions are, first, the delicate topic of testing noxious effects on fetal brain development during pregnancy which, understandably, prevents direct research on human fetuses, and second, the unsuitability of laboratory animal models, as they are neither the natural hosts of the viruses nor do they represent an accurate model of human brain development. To this end, our group was able to compare 3D human brain organoid models infected with different viruses. These infection models give us the closest possible insight into the human brain developmental outcomes of the viruses we study, and help us dissect the underlying structural, cellular, transcriptional and immunological parameters," explains first author Veronica Krenn, a postdoctoral researcher in the Knoblich group at IMBA. In the present study, the researchers are able to bypass these difficulties and gain precious insights on phenotypes reminiscent of microcephaly in organoids. Krenn and her colleagues do so by infecting 3D HBO cultures with TORCH viruses such as ZIKV and HSV-1 and demonstrate that both ZIKV and HSV-1 spread in organoids and halt their growth by promoting cell death. Through transcriptional profiling, the team shows a unique feature of HSV-1 infection in organoids, namely a propensity to impair their neuroepithelial identity. Another major finding is that, although both ZIKV and HSV-1 attenuate the Type I interferon (IFN) immune response system in organoids, they appear to do so through different mechanisms, as is made evident by rescue experiments using distinct Type I IFNs.

The findings highlight the distinct paths used by various TORCH viruses to cause microcephaly and reveal complex cellular immune defenses, such as a neuroprotective role of various Type I IFN responses. The importance of these findings also resides in their unique observation in 3D brain organoid cultures, and not in 2D culture systems, thus stressing the superiority of HBO models in reproducing virus-induced neuropathological conditions and their relevance in studying the mechanisms of viral infections.

Taken together, this new research from the Knoblich lab presents organoid infection models that could help test therapeutic agents against ZIKV and HSV-1 infections and better dissect the human interferon responses. "By specifically infecting organoids with viruses, we can not only learn a great deal about the critical brain development interactions that are typically complex in humans. We will also be able to better target weak points of these viruses to find possibilities for new therapies," summarizes IMBA Scientific Director Jürgen Knoblich, the corresponding author of the study.

Throughout the last ice age, the climate changed repeatedly and rapidly during so-called Dansgaard-Oeschger events, where Greenland temperatures rose between 5 and 16 degrees Celsius in decades. When certain parts of the climate system changed, other parts of the climate system followed like a series of dominos toppling in succession. This is the conclusion from an analysis of ice-core data by a group of researchers that included postdoc Emilie Capron and associate professor Sune Olander Rasmussen from the Section for the Physics of Ice, Climate and Earth at the Niels Bohr Institute, University of Copenhagen, in Denmark. This discovery, just published in the journal Nature Communications, is concerning because the extent of sea ice in the Arctic played an important part in these dramatic climate shifts of the past. Today, sea-ice extent is being rapidly reduced, and it is uncertain whether this part of the climate system can trigger sudden future climate change.

Understanding abrupt climate changes in the past is critical to our ability to confidently predict whether something similar will occur today or in the near future.

Over the last several decades, this has led climate scientists to search for causal relationships of abrupt climate change during the ice age when Greenland temperatures repeatedly rose by as much as 16 degrees Celsius in just decades before slowly falling back to normal ice-age levels.

The question

"Many studies have tried to answer this long-standing question: Which part of the climate system changed first when these approximately 30 abrupt climate changes, called Dansgaard-Oeschger events, began? Was it, for example, the ocean currents in the North Atlantic, the wind and rainfall patterns in the Northern Hemisphere, or the spread of sea ice in the Arctic that triggered climate change?" says ice-core scientist Emilie Capron from the Niels Bohr Institute (University of Copenhagen) and the Institute of Environmental Geosciences (CNRS/Université Grenoble Alpes/IRD/Grenoble INP), who led the study now published in Nature Communications.

This new analysis reveals a surprisingly diverse set of dynamics within the Dansgaard-Oeschger events. The same physical processes changed together like a row of cascading dominoes, but surprisingly, neither the rate of change nor the order of the processes were the same from one event to the other.

In search of an explanation

The team of researchers used data from two parallel Greenland ice cores that spanned the last ice age to create an image of a typical Dansgaard-Oeschger event and to determine in what order the parts of the climate system changed at the onset of the abrupt climate transitions.

The goal is to be able to transfer this knowledge of the past to today's climate and use the fingerprint of past climate change as a kind of warning signal for possible abrupt climate changes in the future.

The analysis, funded by the EU as a Marie Sk?odowska-Curie Action and from a research grant from the Carlsberg Foundation, showed that changes in different parts of the climate system - ocean currents, sea-ice and wind patterns - were so closely intertwined that they likely triggered and reinforced each other, and led to these reoccurring abrupt climate changes.

Confirmed by a model

The results led the international team of scientists to compare the ice-core data with new results from climate model simulations of the last ice age developed by co-author Guido Vettoretti, postdoc at the Niels Bohr Institute. This IPCC-class of climate model is the same type as those used to make projections of future climate change. The comparison revealed that the model showed the same type of entangled behaviour of sea ice, strength of ocean currents, and wind and precipitation patterns.

This is positive news in that it increases our confidence that these complex models demonstrably capture the physical processes needed to simulate these past abrupt climate changes. However, the result is also worrisome: One of the climate dominoes that could disrupt the entire system during the ice age was the extent of sea-ice cover in the North Atlantic, and the modern extent of sea ice has been declining at a significant rate since the 1980s, highlighting the risk of a similar domino effect due to man-made climate change.

Implications for future climate

Unfortunately, our understanding of the interplay between the many parts of the Earth's climate system is insufficient to allow us to assess the risk of similar occurrences of abrupt climate change in the future.

Likewise, following the domino analogy: We do not know to what extent the initial conditions of the dominoes are different in today's climate system compared to the situation during the last ice age.

"In any case, the results emphasize the importance of trying to limit climate change by, for example, cutting anthropogenic emissions of CO2 and other greenhouse gases, both to reduce the predictable, gradual climate change and to reduce the risk of future abrupt climate change," says co-author Sune Olander Rasmussen, associate professor at the Niels Bohr Institute, and adds: "If you do not want the dominoes to topple over, you are better off not to push the table they stand on too much."