“If you’re in a resource-rich environment — meaning for a child that you’re safe, your meals are coming, someone is at home for you, you’re surrounded by adults that are protecting you — you’ll try new things,” says Seth Pollak, a University of Wisconsin-Madison professor of psychology who studies childhood adversity. “And that’s how you discover and learn about the world.”

But not every exploration will be rewarding and, according to a new study of childhood exploration and parental predictability that Pollak and collaborators today published in the Proceedings of the National Academy of Sciences, kids who don’t believe they have the support of reliable parents are less willing to risk the unknown.

“What’s unseen around that corner could be golden, but you could also end up in some bad situations,” Pollak says. “You could end up ordering a bad meal or touching something that hurts you. You could end up in a bad relationship or with an empty wallet. And so, we thought, in order to have the confidence to try something new, you have to feel like you’re supported and relatively safe — like you can afford to make a bad call.”

The researchers studied decisions that more than 150 children ages 10 to 13 made while playing games designed by C. Shawn Green, a UW-Madison psychology professor. The games offered the children opportunities to risk a little and explore for potential gains.

One game, fashioned after a pair of casino slot machines, gave players a history of payouts on just one of the machines — information that helped them understand their expected winnings if they kept pulling that machine’s handle. The other machine’s history was a mystery, and investing a pull there was more of a risk, but also potentially a bigger return.

The other game, in which the kids collected apples in virtual orchards, featured diminishing returns as players continued to pick from an individual tree. With limited time, would the players move to new trees, with unknown bounties? Or would they plug away at the tree they knew best?

The kids and their parents also participated in a battery of surveys and assessments. The researchers gauged the stress the children experience and the predictability of their lives — based on factors like parental job loss, divorce, death or illness in the family, and changing schools and homes — as well as children’s own views about whether or not their parents were reliable and predictable.

Yuyan Xu, a UW-Madison graduate student and first author of the study, asked children to respond to questions about how they’ve experienced their relationships, such as: When my parents say they’re going to pick me up, can I count on them to be there? When my parent makes a promise, do they follow through on it? Do I typically know how my parents are going to react to different kinds of situations?

The less reliable and predictable the kids felt their parents were, the less likely they were to take exploratory risks in the games they played. They were less likely to give the mysterious slot machine a chance or choose to move to a different apple tree.

“The children from more stable backgrounds, they play around and experiment in our games. They use that to get a sense of how things work, maybe earning them more money or more points,” Pollak says. “Kids from unstable backgrounds just don’t play that way. They stay within a narrower range of possibilities. They prefer to stick with what they already know, even if it’s limited, rather than taking a chance at a higher possible reward.”

The researchers found those self-imposed limits on risk were not related to the more objective measures of stress and unpredictability on the kids’ lives or even on parental reports that didn’t necessarily agree with their child’s perceptions of their relationships. There wasn’t a correlation between lack of risk-taking and levels of anxiety or neuroses, or of the kids’ feelings about the rest of the world outside their family. If they felt their parents were unreliable and unpredictable, they were less willing to explore.

“I think it makes sense,” Pollak says. “Their brains are doing exactly what we want our brains to do, right? If you really feel things are not predictable and you don’t know how things are going to land, you’d stick to what works and what’s familiar. You wouldn’t waste your resources on something that could all fall apart.”

The researchers ran their experiments first with a group of nearly 80 kids, then repeated it with a second group of just over 80 more to confirm their results.

“The interesting thing here is that there seems to be a way in which our early childhood experiences are calibrating how we decide to make these decisions years and years down the line and in these really different kinds of situations,” says Xu.

Openness to exploration wouldn’t be the only important aspect of childhood enhanced by stability. Language development, sleep quality, stress regulation and other subjects of childhood development research have been tied to predictability in children’s lives. Pollak plans to delve further into the relationship between predictability and exploration to see how rifts might be healed.

“What can we do for kids who view their history of interpersonal relationships as unstable?” he says. “We might not be able to change the relationships by the time we understand them to be unpredictable. But could we change the way kids think about them, how they act on them? If that is flexible, maybe we can tune those kids into the benefits and rewards of exploration to help foster kids’ learning.”

This research was supported by grants from the National Institutes of Health (R01MH61285 and P50HD105353).

The study was published in the journal Neuropsychopharmacology.

Previous research has shown that not only are high levels of stress and depression harmful to the person experiencing them, but they can also have long-lasting effects on their children if experienced during pregnancy. In recent years, studies have also revealed that discrimination and acculturation — or the changes that occur due to migration and the subsequent balancing of multiple, different cultures — can affect the adult brain. What’s less clear is how children might be affected by their parents’ experiences of discrimination and acculturation.

For the new study, the researchers assessed the degree of discrimination, acculturation, and distress experienced by 165 people while pregnant using established questionnaires. The participants were 14 to 19 years old, mostly Hispanic (88%), and lived in or near the Washington Heights neighborhood of New York City. The researchers then performed magnetic resonance imaging (MRI) to evaluate brain connectivity in 38 of the participants’ infants after birth.

The first step, researchers said, was to determine whether discrimination and acculturation are distinct from other types of stress or depression.

“We thought that some of these experiences might go hand-in-hand or overlap, in which case it would be difficult to measure the effects of discrimination or acculturation on their own,” said Dustin Scheinost, associate professor of radiology and biomedical imaging at Yale School of Medicine and senior author of the study.

Scheinost and his colleagues from Columbia and Children’s Hospital of Los Angeles used a data analysis program that assessed all of their separate questionnaire measures of acculturation, discrimination, stress, depression, childhood trauma, and socioeconomic status, and organized them into groups by how similar the data anlaysis program determined them to be. Doing this, researchers say, helped them understand the degree to which different measures might be used to evaluate similar experiences.

“That analysis clustered measures of stress and depression and separately pulled out discrimination and acculturation measures as their own distinct variables,” said Scheinost. “That told us that while these experiences of discrimination are related to stress and depression, they are separate enough that we can look at their unique effects.”

When the research team analyzed the MRI images of the infants’ brains, they found differences in the children whose parents reported experiencing discrimination while pregnant.

The amygdala is an area of the brain associated with emotional processing and it’s very vulnerable to prenatal stress, said the researchers. Prior research has found that early experiences of adversity can have measurable impacts on amygdala connectivity in infants, children, adolescents, and adults. A growing body of evidence also suggests the amygdala is involved in ethnic and racial processing, such as differentiating faces of people from different races or ethnicities, for example.

When the researchers assessed connectivity between the amygdala and another region of the brain called the prefrontal cortex, which is associated with higher-order functioning, they found that children of people who experienced more discrimination while pregnant had weaker connectivity between the two brain regions.

“Our finding was consistent with what you expect to see in the brain of those affected by early life adversity either pre- or postnatally,” said Scheinost.

The takeaway, said Scheinost, is that while discrimination and acculturation affect the brain in ways other types of stress do, there is something unique and important about these particular experiences that should be better understood. Future research, he said, should focus on whether other populations are affected in similar ways and what underlies the effects.

“We don’t fully know why this happens,” said Scheinost. “So we need to investigate the biological mechanisms that carry these experiences of adversity from parent to offspring.”

Scientists from the University of Cambridge studied hundreds of tree trunks, dug up by Fenland farmers while ploughing their fields. The team found that most of the ancient wood came from yew trees that populated the area between four and five thousand years ago.

These trees, which are a nuisance when they jam farming equipment during ploughing, contain a treasure trove of perfectly preserved information about what the Fens looked like thousands of years ago.

The Fen yew woodlands suddenly died about 4,200 years ago, when the trees fell into peat and were preserved until today. The researchers hypothesise that a rapid sea level rise in the North Sea flooded the area with salt water, causing the vast woodlands to disappear.

The climate and environmental information these trees contain could be a valuable clue in determining whether this climate event could be related to other events that happened elsewhere in the world at the same time, including a megadrought in the Middle East that may have been a factor in the collapse of ancient Egypt’s Old Kingdom. Their results are reported in the journal Quaternary Science Reviews.

Yew (Taxus baccata) trees are one of the longest-lived species in Europe, and can reach up to 20 metres in height. While these trees are fairly common in Cambridge College gardens and churchyards across southern England, they are absent in the Fens, the low-lying marshy region of eastern England. Much of the Fens was a wetland until it was drained between the 17^th and 19^th centuries using artificial drainage and flood protection. Today, the area is some of the most productive farmland in the UK, thanks to its rich peat soil.

While the area is great for farming and does have its own charms, few people would describe the Fens as spectacular: for the most part, the area is extremely flat and dominated by fields of potatoes, sugar beet, wheat and other crops. But five thousand years ago, the area was a huge forest.

“A common annoyance for Fenland farmers is getting their equipment caught on big pieces of wood buried in the soil, which can often happen when planting potatoes, since they are planted a little deeper than other crops,” said lead author Tatiana Bebchuk, a PhD student from Cambridge’s Department of Geography. “This wood is often pulled up and piled at the edge of fields: it’s a pretty common sight to see these huge piles of logs when driving through the area.”

For farmers, these logs are a nuisance. But for Bebchuk and her colleagues, they are buried treasure. The Cambridge team approached several Fenland farmers and took samples of hundreds of logs that had been dug up and discarded, to find out what secrets they might hold.

“I remember when I first saw this enormous pile of abandoned trees, it was incredible just how many there were,” said Bebchuk. “But when we got them back to lab, we were even more surprised: these trees were so well-preserved, it looked as if they were cut down just yesterday.”

To put current anthropogenic climate change in a long-term context of natural variability, scientists need accurate evidence from the past, and trees are some of the best recorders of past conditions: their annual growth rings contain information about temperature and hydroclimate for every growing season they witnessed. “But the further back in time we go, the less reliable evidence we have, since very old trees and well-preserved wood materials are extremely rare,” said Professor Ulf Büntgen, the senior author of the study.

However, analysis by the Cambridge Tree-Ring Unit (TRU) showed that the yew trees dug up from Fenland fields were very old indeed: some of these ancient trees were 400 years old when they died. The new find provides unique climate information for over a millennium from around 5,200 years ago until about 4,200 years ago, when much of the Fens was a woodland of yew and oak: completely different than it looks today.

“Finding these very old trees in the Fens is completely unexpected — it would be like turning a corner in rural Cambridgeshire and seeing an Egyptian pyramid — you just wouldn’t expect it,” said Bebchuk. “It’s the same with nature — wood rots and decomposes easily, so you just don’t expect a tree that died five or four thousand years ago to last so long.”

Given that most of the Fens are barely above sea level, about 4,200 years ago, a sudden rise in sea level most likely killed the Fen woodlands. The period that the Fen woodlands died coincided with major climatic changes elsewhere in the world: at roughly the same time, a megadrought in China and the Middle East was a possible trigger of the collapse of several civilisations, including Egypt’s Old Kingdom and the Akkadian Empire in Mesopotamia.

“We want to know if there is any link between these climatic events,” said Bebchuk. “Are the megadroughts in Asia and the Middle East possibly related to the rapid sea level rise in northern Europe? Was this a global climate event, or was it a series of unrelated regional changes? We don’t yet know what could have caused these climate events, but these trees could be an important part of solving this detective story.”

“This is such a unique climate and environmental archive that will provide lots of opportunities for future studies, and it’s right from Cambridge’s own backyard,” said Büntgen. “We often travel all over the world to collect ice cores or ancient trees, but it’s really special to find such a unique archive so close to the office.”

Our bodies are, in some ways, like cars — to keep functioning, they need to be checked and repaired regularly. In the case of our bodies, any cells that are damaged or dead need to be replaced to keep organs functioning. This replacement occurs thanks to tissue-resident adult stem cells. In contrast with embryonic stem cells, which can form any cell type in the body, adult stem cells will only form the cell types that are found in the tissue they belong to. But how do tissue-specific stem cells know which cell type to give rise to? Gabriele Colozza, a postdoctoral researcher in the lab of Bon-Kyoung Koo at IMBA — now director at the Center for Genome Engineering, Institute for Basic Science in South Korea — decided to investigate this question using intestinal stem cells.

Intestines — a constant construction site

“In our intestines, cells are exposed to extreme conditions,” Colozza explains. Mechanical wear and tear, but also digestive enzymes and varying pH values all affect intestinal cells. In turn, stem cells in the intestine’s mucosa differentiate to form new intestinal cells. “Damaged cells have to be replaced, but it is a delicate balance between stem cell renewal and differentiation into other cell types: uncontrolled stem cell proliferation may lead to tumor formation; on the other hand, if too many stem cells differentiate, the tissue will be depleted of stem cells and ultimately unable to self-renew.”

This balance is delicately tuned by signaling pathways and feedback loops, which allow cells to communicate with each other. One important pathway is called Wnt. The Wnt pathway is known for its role in embryonic development, and if left unchecked, an overactive Wnt pathway can lead to excessive cell division and the formation of tumors.

Molecular partner identified

A well-known antagonist of Wnt signalling — keeping Wnt in check — is Rnf43, which was originally identified by Bon-Kyoung Koo. Prior to this study, Rnf43 was known to target the Wnt receptor Frizzled and mark it for degradation. “We wanted to know how Rnf43 works, and also what — in turn — controls Rnf43 and helps it to regulate Wnt signalling.” From earlier research, the scientists knew that Rnf43 on its own was not sufficient to break down the Wnt receptor Frizzled, which sits in the plasma membrane. “In our project, we used biochemical assays to identify which proteins interact with Rnf43.” A key partner of Rnf43 turned out to be the protein Daam1.

To understand how Daam1 regulates Rnf43 and affects the tissues it acts in, Colozza turned to intestinal organoids. “We found that Daam1 is required for Rnf43 to be active, so for Rnf43 to regulate Wnt signaling at all. Further work in cells showed Rnf43 needs Daam1 to move the Wnt receptor Frizzled into vesicles called endosomes. From the endosomes, Frizzled is shuttled to the lysosomes where it is degraded, dampening Wnt signaling,” Colozza adds.

Intestinal organoids are three-dimensional cell cultures grown from adult intestinal stem cells, allowing the researchers to mimic the intestinal mucosa. For Colozza, organoids were an opportunity to understand how Rnf43 and Daam1 affect the delicate balance of stem cell renewal and differentiation in the intestine. “We found that when we knock-out Rnf43 or Daam1, the organoids grow into tumor-like structures. These tumor-like organoids keep on growing, even if we withdraw the growth factors they usually depend on, such as R-spondin.”

Switching on Paneth cell formation

When Colozza followed up this result in mouse tissue, the researchers were in for a surprise. “When Rnf43 was missing, the intestines grew tumors — as expected. But when Daam1 was missing, no tumors grew. We were puzzled by this striking difference: how can the loss of factors in the same pathway, that behave similarly in organoids, lead to such different outcomes?”

Looking closely at the intestines, Colozza saw that intestines lacking Rnf43 were full of a specific type of secretory cells, the Paneth cells. Intestines lacking Daam1, on the other hand, contained no extra Paneth cells. Paneth cells secrete growth factors, such as Wnt, that stimulate cell division. “Daam1 is required for the efficient formation of Paneth cells. When Daam1 is active, stem cells differentiate to form Paneth cells. When Daam1 is not active, the stem cells differentiate into another cell type.”

Tumors modify their niche to grow

This link between the molecular results and Paneth cells explains the puzzling difference between intestines and organoids. “In organoid culture, we scientists provide growth factors, so the knockout of both Rnf43 and Daam1 lead to tumor-like organoids. But in the intestine, there is no little scientist providing growth factors. Instead, Paneth cells provide growth factors, like Wnt, and create the right conditions for stem cells to survive and divide. When Paneth cells are lacking — such as when Daam1 is not active to drive cells into becoming Paneth cells — stem cells will not divide much. But when there are too many Paneth cells — such as in intestines lacking Rnf43 — the excessive growth factors can contribute to the formation of tumors.”

Colozza’s and colleagues’ study is the first genetic proof that Daam1, a member of the non-canonical Wnt pathway, is important for specifying Paneth cells, and directly involved in the development of this crucial secretory cell. The results also shed light on the importance of the stem cell niche. “We show that tumor cells modify their microenvironment, and influence their supporting environment so that they can grow better.”