AML, which affects four out of 100,000 patients in the U.S. every year, according to the National Cancer Institute, is a type of cancer that first attacks the bone marrow before moving to infect the blood. The current treatment plan includes targeted chemotherapy followed by a stem cell transplant. Unfortunately, up to 40% of these patients relapse after transplant and have a median survival of six months. At that stage, the only hope for remission is through immunotherapy.

Led by Elham Azizi, associate professor of biomedical engineering at Columbia Engineering, the research explores how coordinated immune networks in leukemia bone marrow microenvironments influence responses to cellular therapy, raising the question: why do some patients benefit from immunotherapy while others do not? The current treatment for relapsed AML, donor lymphocyte infusion (DLI) — a therapy involving donor immune cells — has a 5-year survival rate of only 24%, according to research conducted by Pfizer.

This new study finds that a unique population of T cells found in patients who are responding to DLI might be the key. These cells fight leukemia by boosting the immune response. Additionally, the study shows that patients with a healthier, more active and diverse immune environment in the bone marrow are better able to support these cells and their cancer-fighting abilities.

Utilizing the team’s proprietary computational DIISCO approach, the researchers discovered key interactions between the unique T cell population and other immune cells may lead to patient remission. They also traced these T cells back to the donor product. However, it was discovered that the donor’s immune cell composition has little to no effect on the patient’s success. In fact, the success of this treatment is determined by the patient’s immune environment. DIISCO is a machine learning method used to analyze how cell interactions change over time with a focus on cancer and immune cells profiled in clinical specimens.

The study’s findings can lead to new intervention options such as improving the immune environment before starting the standard DLI treatment and exploring combinations of immunotherapies. This will help patients who don’t typically respond well to find a personalized option that works for them.

“This research exemplifies the power of combining computational and experimental methods through close collaboration to answer complex biological questions and uncover unexpected insights,” said Azizi, who is a member of the Irving Institute for Cancer Dynamics, the Herbert Irving Comprehensive Cancer Center, and Columbia’s Data Science Institute. “Our findings not only shed light on mechanisms underlying successful immunotherapy response in leukemia, but also provide a roadmap for developing effective treatments guided by innovative machine learning tools.”

“Seeing our findings validated through functional experiments is incredibly exciting and offers real hope for improving cancer immunotherapy,” said Cameron Park, a PhD student in the Azizi lab, who co-led this study with Katie Maurer at the Catherine Wu Lab at Dana Farber-Cancer Institute. Park was also a co-developer of the DIISCO algorithm.

In this particular research’s future, the team plans to explore interventions that enhance the effectiveness of DLI while focusing on modulating the tumor microenvironment. Although exciting, much more work has to be done before the team can head to clinical trials with the hope to improve outcomes for patients with relapsed AML.

Sepsis is one of the most frequent causes of death worldwide, according to the World Health Organization (WHO), killing 11 million people each year. It’s characterized by runaway inflammation, usually sparked by an infection. It can lead to shock, multiple organ failure, and death if treatment is not rapid enough or effective.

But recent research has shown that it isn’t actually the infection that causes the spiraling inflammation: it’s the cells caught up in it. Even if those cells aren’t infected, they act as if they are, and die. As they die, they send out messages to other cells. Those messages somehow cause the recipient cells to die. If scientists understood what caused this deadly message chain, they might be able to stop it. And that could help heal sepsis.

The deadly message mystery may now be solved. It appears that the “messages” are a byproduct of the cells trying to stay alive, UConn School of Medicine researchers report in Cell.

The process starts with cells that really are infected. To prevent the infection from spreading, those cells destroy themselves by sending a protein called gasdermin-D to their surface. Several gasdermin-D proteins will link together to create a round pore on the cell, like a hole punched in a balloon. The cell’s contents leak out, the cell collapses, and dies.

But the collapse isn’t inevitable. Sometimes cells can act quickly and eject the section of their surface membrane with the gasdermin-D pore. The cell then zips the membrane closed and survives. The ejected membrane forms a little bubble, called a vesicle, that just happens to carry the deadly gasdermin-D pore. The vesicle floats around, and when it encounters a cell nearby, that deadly gasdermin-D pore punches into the healthy nearby cell’s membrane and causes that cell to spill and die.

“When a dying cell releases these vesicles, they can transplant these pores to a neighboring cell’s surface, which leads to the neighboring cell’s death,” says Vijay Rathinam, an immunologist in the UConn School of Medicine. In other words, the deadly messages are a side effect of cells just trying to save themselves. A group of dying cells can release enough gasdermin-D vesicles to kill a considerable number of nearby cells. That spreading message of death fuels the spiraling inflammation of sepsis.

Rathinam and his colleagues are now looking for a way to damp down the deadly gasdermin-D vesicles. If successful, it could lead to a treatment for inflammatory diseases like sepsis.

This study led by Skylar Wright, an MD/PhD student in the Rathinam lab, was done in collaboration with the laboratories of Drs. Jianbin Ruan, Beiyan Zhou, Sivapriya Kailasan Vanaja of UConn Health and Dr. Katia Cosentino of University of Osnabrück, Germany. This project was funded by grants from the National Institutes of Health to Dr. Rathinam.

To address this challenge, a team led by researchers at the National Synchrotron Light Source II (NSLS-II) — a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Brookhaven National Laboratory — used complementary X-ray techniques at two different beamlines to gain new insights into these materials. Their results were published in Physical Review Letters.

New discoveries in a long history

Superconductivity was first discovered in mercury more than 100 years ago. Superconducting materials allow current to flow through them with no resistance and therefore have no power loss. As these materials enter a superconducting state, the persistent electric current allows them to expel a magnetic field and levitate over magnetic materials as well.

Initially, superconducting properties seemed to only appear at extremely low temperatures — -415 degrees Fahrenheit. In the mid-1980s, however, researchers found that copper-based oxide materials, or “cuprates,” can display these properties at -297.7 degrees Fahrenheit. This spearheaded research in “high-temperature” superconductivity and the search for other cuprate-like high-temperature superconductors. If researchers can find a way to engineer materials to superconduct at higher, more practical temperatures, they might one day contribute to eliminating energy losses in the power grid and paving the way for other novel technologies like maglev trains, more efficient MRI machines, and high-capacity energy storage for electric vehicles.

More recently, nickel-based materials have attracted attention as a new family of high temperature superconductors analogous to cuprates. Neodymium nickelate becomes particularly interesting when strontium is added to its structure. This compound is known as an “infinite layer nickelate,” since nickel atoms are arranged in a two-dimensional square lattice that repeats indefinitely in two dimensions, earning the moniker “infinite.”

Superconductivity in nickelates has, so far, only been observed in very thin films. This raises questions about whether the superconducting properties depend on interactions at the interfaces between the nickelate material and its substrate or capping layer. Early studies provided conflicting results on the properties of these materials.

“This system is sensitive to water and oxygen,” explained Jonathan (Johnny) Pelliciari, a beamline scientist at NSLS-II’s Soft Inelastic X-ray Scattering (SIX) beamline, “so past studies used a very thin protective capping layer and attributed electronic orders to the lack of a thick surface layer. Given how sensitive these systems are, small changes or defects can also affect the material’s properties. We wanted to see how much of a role this capping layer was playing and what signals may be spurious.”

To answer this question, the team employed two beamlines at NSLS-II to investigate high quality nickelate thin film samples with and without a capping layer of strontium titanate to see if the layer has an effect on magnetic and electronic properties. Magnetic properties are critical because they relate to the material’s intrinsic electronic structure, which is directly linked to its superconductivity.

Complementary techniques complete the picture

Resonant Elastic X-Ray Scattering (REXS), performed at the Coherent Soft X-ray Scattering (CSX) beamline at NSLS-II, offers researchers a detailed view of a material’s structural properties. This part of the experiment revealed the atomic and electronic structure of the infinite-layer nickelate thin films. Resonant Inelastic X-ray Scattering (RIXS), performed at the SIX beamline, then measured how X-rays lose energy as they scatter off the films. By analyzing the density, motion, and interactions of electrons and spins, researchers gained valuable insight into processes related to electronic and magnetic properties in the material.

Combining these perspectives gave a complete picture of how the material behaved, especially any changes introduced by capping. The group found that the material’s magnetic fluctuations, or “spin excitations,” are present whether or not the capping layer is applied, showing that magnetism is an inherent quality of these nickelates. In capped samples, these magnetic properties are only slightly stronger because of interfacial effects, which might be due to slight structural adjustments at the interface where the capped layer meets the nickelate, crystal defects, or lattice disorder. The data also confirmed that spin excitations in these materials are stable in the superconducting phase, similar to what is seen in cuprates.

“RIXS is very sensitive to magnetism,” said Shiyu Fan, a postdoctoral researcher at SIX and lead author of this study. “Perhaps the most important finding of this research is the evolution of the spin wave in the presence or absence of the capping layer, which points to the magnetic and superconducting properties being intrinsic to the infinite layer nickelate material.”

“The similarity between copper oxide planes in superconducting cuprates and nickel oxide planes in nickelates have had scientists searching for superconductivity in nickelates for 25 years,” said Claudio Mazzoli, lead beamline scientist at CSX. “Now that it has finally been found, we need to understand the differences and commonalities in these two cases and the physics behind them to gain control of this fascinating phenomenon for technological applications.”

The research and the facilities used were funded by the DOE Office of Science.

In order to find out which of a million different molecules would conduct positive charges and make perovskite solar cells particularly efficient, one would need to synthesize and test all of them — or do as the researchers headed by Tenure-track Professor Pascal Friederich, who specializes in the applications of AI in materials science at KIT’s Institute of Nanotechnology, and Professor Christoph Brabec from the Helmholtz Institute Erlangen-Nürnberg (HI ERN). “With only 150 targeted experiments, we were able to achieve a breakthrough that would otherwise have required hundreds of thousands of tests. The workflow we have developed will open up new ways to quickly and economically discover high-performance materials for a wide range of applications,” Brabec said. With one of the discovered materials, they increased the efficiency of a reference solar cell by approximately two percentage points to 26.2 percent. “Our success shows that enormous amounts of time and resources can be saved by applying skillful strategies for the discovery of new energy materials,” Friedrich said.

The starting point at HI ERN was a database with structural formulae for approximately one million virtual molecules that could be synthesized from commercially available substances. From these virtual molecules, 13,000 were selected at random. The KIT researchers used established quantum mechanical methods to determine their energy levels, polarity, geometry and other properties.

Training AI with Data from Just 101 Molecules

From the 13,000 molecules, the scientists chose 101 with the greatest differences in their properties, synthesized them with robotic systems at HI ERN, used them to produce otherwise identical solar cells, and then measured the efficiency of the solar cells. “Being able to produce truly comparable samples thanks to our highly automated synthesis platform, and thus being able to determine reliable efficiency values, was crucial to our strategy’s success,” said Brabec, who headed the work at HI ERN.

The researchers at KIT used the achieved efficiencies and the properties of the associated molecules to train an AI model, which suggested 48 other molecules to synthesize. Its suggestions were based on two criteria: high expected efficiency and unforeseeable properties. “When the machine learning model is uncertain about the predicted efficiency, it’s worthwhile to synthesize the molecule and take a closer look at it,” Friederich said, explaining the second criterion. “It might surprise us with a high efficiency level.”

Using the molecules suggested by the AI, it was indeed possible to build solar cells with above-average efficiency, including some exceeding the capabilities of the most advanced materials currently used. “We can’t be sure we’ve really found the best one of a million molecules, but we’re certainly close to the optimum,” Friederich said.

AI Versus Chemical Intuition

Since the researchers used an AI that indicates which of the virtual molecules’ properties its suggestions were based on, they were able to gain some insight into the molecules it suggested. For example, they determined that the AI-suggestions are based in part on the presence of certain chemical groups, such as amines, that chemists had previously neglected.

Brabec and Friederich believe that their strategy holds promise for other applications in materials science or can be extended to the optimization of entire components.

The findings, which are the result of research conducted in collaboration with scientists from FAU Erlangen-Nürnberg, South Korea’s Ulsan National Institute of Science, and China’s Xiamen University and University of Electronic Science and Technology, were published recently in the journal Science.

In recent years, immunotherapies have had significant success in the treatment and cure of a wide range of cancers. However, for some patients, these agents are still not sufficiently effective. As part of a preclinical study, Maria Sibilia, Head of the Center for Cancer Research at the Medical University of Vienna, therefore investigated the effects of a combination immunotherapy consisting of systemic administration of the tissue hormone interferon (IFN)-I and local imiquimod therapy. Imiquimod is an active substance that activates the innate receptors TLR7/8 and used to treat basal cell carcinomas. The researchers employed various preclinical mouse tumor models of melanoma and breast cancer. What both tumors have in common is that they are accessible to local therapy and often form distant metastases.

Effective for local tumors and distant metastases

Immunotherapies use the body’s own immune system to fight cancer cells. Plasmacytoid dendritic cells (pDCs), which are activated by Imiquimod via TLR7/8, play an important role in this process. The study showed that oral imiquimod stimulates pDCs to produce the tissue hormone IFN-I. This sensitized other dendritic cells and macrophages in the tumor environment to topical imiquimod therapy, which inhibited the formation of new blood vessels via the cytokine IL12 leading to the death of tumor cells. The combination immunotherapy not only had an effect on the treated tumors, but also on distant metastases. It reduced the formation of new metastases thus preventing tumor relapses and increasing the sensitivity of melanomas to checkpoint inhibitors.

“These findings illustrate that the combination of systemic treatment with imiquimod or IFN-I and topical therapy with imiquimod has the potential to expand treatment options for patients and improve therapy outcomes in locally accessible tumors such as melanoma or breast cancer,” emphasizes Maria Sibilia. “Topical treatment of the primary tumor with imiquimod is essential for this combination therapy with systemic IFN-I to be effective at the treated site and also to clear distant metastases,” adds Philipp Novoszel, MedUni Vienna, one of the first authors of the study.

The results suggest that this therapeutic strategy has the potential to improve treatment outcomes in superficial and thus locally accessible tumors such as melanoma and breast cancer — on the one hand through therapy-associated cancer cell death at the locally treated tumors, but also through the induction of a T cell-induced anti-tumor immune response at distant metastases, which is further enhanced by checkpoint inhibitors.

“Our aim is to continue developing immunotherapeutic strategies in order to improve the long-term prospects for patients who are not yet responding well to these agents,” says Maria Sibilia, who is also Deputy Head of the Comprehensive Cancer Center of MedUni Vienna and University Hospital Vienna.

“As systemic interferon is a well-known cancer therapy and dendritic cells are activated in a similar way to our preclinical models, we believe that the new combination therapy can show an effect in patients,” adds Martina Sanlorenzo, dermato-oncologist at MedUni Vienna and co-first author of the study.

A new study from the Salk Institute has revealed that a protein called BCL6 is key to maintaining healthy muscle mass. The experiments showed that mice with lower levels of BCL6 had significantly reduced muscle mass and strength, but increasing BCL6 successfully reversed those losses. The results suggest that pairing GLP-1 medications with a BCL6-boosting drug may help counteract unwanted muscle loss. Similar therapies could also be used to treat other populations prone to muscle loss, such as older adults and patients with systemic diseases like sepsis or cancer.

The findings were published in Proceedings of the National Academy of Sciences on January 22, 2025.

“Muscle is the most abundant tissue in the human body, so its maintenance is critical to our health and quality of life,” says Ronald Evans, professor and director of the Gene Expression Laboratory at Salk. “Our study reveals how our bodies coordinate the upkeep of all this muscle with our nutrition and energy levels, and with this new insight, we can develop therapeutic interventions for patients losing muscle as a side effect of weight loss, age, or illness.”

Going too long without eating puts your body in a fasted state. When this happens, your empty stomach sends a hormone called ghrelin to your brain to say, “I’m hungry!”The brain responds by releasing growth hormone into the rest of your body, where it regulates growth and metabolism in your many cells, tissues, and organs. As it travels through your body, growth hormone latches on to cells and directs them to make another protein called insulin-like growth factor 1 (IGF1), which then does the important work of controlling muscle growth.

In the time between growth hormone’s arrival and IGF1 synthesis, there is a complex web of proteins that determine how much IGF1 is made. One such protein is SOCS2, which slows down IGF1 production. Without SOCS2, IFG1 production runs out of control and causes gigantism. On the other hand, too much SOCS2 means not enough IFG1, leading to losses in body size and strength.

Still, SOCS2 is only one player in the path between growth hormone and IGF1. To protect people from rapid muscle loss, Salk scientists needed to get a clearer picture of the mechanisms underlying muscle maintenance. In search of other potential players, the researchers scoured a national database of human tissue samples and noticed an abundance of BCL6 in muscle cells — a clue that it may play an important role in this process.

To determine whether BCL6 was involved in muscle maintenance, the team compared mice with and without functional BCL6 proteins. Mice lacking BCL6 had 40% less muscle mass than their healthy counterparts, and the muscle they did have was compromised both in structure and function. However, when the researchers increased the expression of BCL6 in the animals’ muscles, this successfully reversed the losses in muscle mass and strength. And when they compared normal mice and those that had fasted overnight, they found fasting mice had less BCL6 in their muscles.

Clearly, BCL6 was controlling muscle maintenance — but how?

Through a series of subsequent experiments, the steps along the path became clear. Fasting promotes the secretion of growth hormone, which reduces BCL6 levels in muscle cells. BCL6 is a regulator of SOCS2, so less BCL6 leads to less SOCS2. At normal levels, this allows BCL6 to control how much SOCS2 is expressed and therefore how much IGF1 is made. In animals without BCL6, the lack of control over SOCS2 slowed IGF1 production so much that muscles became weaker and smaller.

“We are excited to reveal BCL6’s important role in maintaining muscle mass,” says first author of the study Hunter Wang, a postdoctoral researcher in Evans’ lab. “These were very surprising and special findings that open the door for a lot of new discoveries and potential therapeutic innovations.”

For GLP-1 patients hoping to lose weight while retaining muscle mass, it’s possible that a BCL6-boosting injectable could hit the market one day. In the meantime, the researchers plan to investigate what effects longer-term fasting has on BCL6 and muscle maintenance. Wang also notes that hormones tend to operate in cycles and that BCL6 naturally rises and falls with a strong circadian rhythm. A better understanding of this pattern may help further elucidate BCL6’s relationship with growth hormone and muscle growth.

Other authors include Hui Wang, Weiwei Fan, Sihao Liu, Kyeongkyu Kim, Satoshi Ogawa, Hyun Gyu Kang, Jonathan Zhu, Gabreila Estepa, Mingxiao He, Lillian Crossley, Morgan Truitt, Ruth Yu, Annette Atkins, and Michael Downes of Salk; Ayami Matsushima of Kyushu University; Christopher Liddle of University of Sydney; and Minseok Kim of Daegu Gyeongbuk Institute of Science and Technology.

The work was supported by the National Institutes of Health (P01 HL147835, DK057978, DK120515, CCSG P30 CA23100, CCSG P30 CA014195, CCSG P30 CA014195, P30 AG068635), Department of the Navy Office of Naval Research (N00014-16-1-3159), Larry Hillblom Foundation (2021-D-001-NET), Wu Tsai Human Performance Alliance, American Heart Association (916787), Salk GT3 (RRID:SCR_014847) and Waitt Advanced Biophotonics (RRID:SCR_014838) Core Facilities, San Diego Nathan Shock Center, Henry L. Guenther Foundation, and Waitt Foundation.

“This is a surface where pathogens can sneak in,” says La Jolla Institute for Immunology (LJI) Assistant Professor Miguel Reina-Campos, Ph.D. “That’s a massive challenge for the immune system.”

So how do immune cells keep the gut safe? New research led by scientists at LJI, UC San Diego, and the Allen Institute for Immunology shows that pathogen-fighting immune cells called tissue-resident memory CD8 T cells (T_RM cells) go through a surprising transformation — and relocation — as they fight infections in the small intestine.

In fact, these cells literally rise up higher in the tissue to fight infections before pathogens can spread to deeper, more vulnerable areas.

“The tissue in the gut has evolved to provide signals to immune cell infiltrates — to put immune cells in specific places so they have a better ability to stop pathogens,” says Reina-Campos, who served as first author of the new Nature study alongside co-first author Alexander Monell of UC San Diego and co-senior authors Maximilian Heeg, M.D., and Ananda W. Goldrath, Ph.D., of the Allen Institute for Immunology and UC San Diego.

The new findings add to the growing body of evidence that immune cells adapt to protect specific tissues. Reina-Campos thinks these “tissue-resident” immune cells may be key players in future cancer immunotherapies that target tumors in specific organs.

T cells on the move

Reina-Campos and his colleagues investigated the formation of T_RM cells in the small intestine. The team harnessed a cutting-edge technology called spatial transcriptomics to track these cells in both human and mouse tissue samples.

Their work showed that the small intestine holds two types of T_RM cells. These cells are split between the tiny, finger-like “villi” structures that line the small intestine or the “crypts” between the protruding villi.

The researchers found that progenitor-like T_RM cells live closer to the crypts between the villi. On the other hand, differentiated T_RM occupy more exposed regions at the top of the villi. “Differentiated immune cells are more exposed at the top of the villi, and that’s where they have a better ability to protect you from infections,” says Reina-Campos.

Meanwhile, a reserve population of progenitor-like T_RM cells continues to lie low in the crypts. “These cells can replenish the pool of effector T cells, so the immune system keeps them as back-ups in the deeper parts of the tissue,” adds Reina-Campos.

What keeps these populations organized and in check?

To spy on these important immune cells within their natural habitat, Reina-Campos and colleagues used a new technology — called spatial transcriptomics — to observe millions of messenger RNA molecules simultaneously at subcellular resolution.

“For the first time, we were able to capture the formation of immunological memory in space and time,” says Reina-Campos.

Looking at small intestines after a viral infection, the scientists found that the gut releases chemical signals to instruct immune cells where to go and what to do. “This study offers a new resource for finding signals that position immune residents to strengthen our gut immunity,” says Reina-Campos.

Checkmate for disease?

Reina-Campos credits his mentor, Goldrath, as well as Heeg’s and Monell’s expertise for making this study possible. As Reina-Campos explains, Heeg and Monell developed new computational approaches to make sense of the massive amounts of data captured through spatial transcriptomics.

“It’s led to a breakthrough in our ability to look at hundreds to thousands of genes simultaneously in intact tissues,” says Reina-Campos. “With this study, we’ve opened up a new path for discovery.”

Reina-Campos compares the battle between immune cells and pathogens to a chess match.

“To be a chess grandmaster, you need to know not only about the pieces: the bishops, pawns, rooks, etc, but also how they move in concert on the chessboard,” he says.

For a long time, scientists have studied the chess pieces — by analyzing cells extracted from tissue — but they haven’t gotten a good look at the chess match itself. “We don’t know as much about how the chessboard works — and we know even less about the rules that apply to our chess pieces as they move across the board,” says Reina-Campos.

The new study gives researchers a detailed look at how immune cells interact with each other and their cellular gameboard.

Reina-Campos says the new finding should guide future research into how immune cells develop and move through other organs with different tissue structures, such as the kidneys and lungs — and how immune cells might fight tumors in these organs.

Influence of very early life stages

The research team investigated how maternal stress affects the stress hormone system of the offspring. They found that the activation of the hypothalamic-pituitary-adrenal (HPA) axis, which plays a central role in coping with stress, can be significantly influenced by exposure to maternal glucocorticoids during development. The early phase of organ differentiation in the first half of pregnancy proved to be a particularly critical period. “Our results show that the HPA-axis activity of offspring was enhanced, the more adversity the other had experienced during early pregnancy — which could be food shortages or social conflicts for example,” says Simone Anzá, former doctoral student at the University of Göttingen and the German Primate Center and first author of the study.

Investigation in the wild

In contrast to studies in the laboratory, the monkeys were observed in their natural habitat. Over a period of nine years, the researchers repeatedly collected fecal samples from pregnant females and measured the concentration of glucocorticoid metabolites in them in order to determine the animals’ exposure to environmental factors such as food scarcity, temperature fluctuations and social interactions. These values were compared with the stress hormone levels of the offspring at different ages. The effects on the stress axis of the offspring were evident from infancy through the juvenile period and into adulthood at nine to ten years of age. Previous analyses from the same study had already shown that early prenatal stress was also associated with altered growth, negative changes in the gut microbiome and impaired immune function, underlining the comprehensive influence of the environment in the early prenatal period on various physiological systems. In contrast, maternal glucocorticoid levels in late pregnancy or during lactation had no or different influences.

Relevance for health research

“Our research results indicate that the timing of maternal stress hormone exposure during and after pregnancy crucially affects the consequences for the development and health of the offspring. It is also important to note that these effects do not require catastrophic events, but that even moderate changes in environmental conditions are sufficient,” says Oliver Schülke, scientist at the University of Göttingen and the German Primate Center and head of the study. Stress in early pregnancy can also have a long-term effect on health in humans and increase the risk of stress disorders and immune problems. “Our findings may help to identify the timing and mechanisms that preventive measures should address in order to reduce long-term health risks,” says Oliver Schülke.