Obesity and postnatal depression are significant global health problems. Postnatal depression affects more than one in 10 women within a year of giving birth and is linked to an increased risk of suicide, which accounts for as many as one in five maternal deaths in high income countries. Meanwhile, obesity has more than doubled in adults since 1990 and quadrupled in adolescents, according to the World Health Organization.

While investigating two boys from different families with severe obesity, anxiety, autism, and behavioural problems triggered by sounds or smells, a team led by scientists at the University of Cambridge, UK, and Baylor College of Medicine, Houston, USA, discovered that the boys were missing a single gene, known as TRPC5, which sits on the X chromosome.

Further investigation revealed that both boys inherited the gene deletion from their mothers, who were missing the gene on one of their X chromosomes. The mothers also had obesity, but in addition had experienced postnatal depression.

To test if it was the TRPC5 gene that was causing the problems in the boys and their mothers, the researchers turned to animal models, genetically-engineering mice with a defective version of the gene (Trpc5 in mice).

Male mice with this defective gene displayed the same problems as the boys, including weight gain, anxiety, a dislike of social interactions, and aggressive behaviour. Female mice displayed the same behaviours, but when they became mothers, they also displayed depressive behaviour and impaired maternal care. Interestingly, male mice and female mice who were not mothers but carried the mutation did not show depression-like behaviour.

Dr Yong Xu, Associate Director for Basic Sciences at the USDA/ARS Children’s Nutrition Research Center at Baylor College of Medicine, said: “What we saw in those mice was quite remarkable. They displayed very similar behaviours to those seen in people missing the TRPC5 gene, which in mothers included signs of depression and a difficulty caring for their babies. This shows us that this gene is causing these behaviours.”

TRPC5 is one of a family of genes that are involved in detecting sensory signals, such as heat, taste and touch. This particular gene acts on a pathway in the hypothalamus region of the brain, where it is known to control appetite.

When the researchers looked in more detail at this brain region, they discovered that TRPC5 acts on oxytocin neurons — nerve cells that produce the hormone oxytocin, often nicknamed the ‘love hormone’ because of its release in response to displays of affection, emotion and bonding.

Deleting the gene from these oxytocin neurons led to otherwise healthy mice showing similar signs of anxiety, overeating and impaired sociability, and, in the case of mothers, postnatal depression. Restoring the gene in these neurons reduced body weight and symptoms of anxiety and postnatal depression.

In addition to acting on oxytocin neurons, the team showed that TRPC5 also acts on so-called POMC neurons, which have been known for some time to play an important role in regulating weight. Children in whom the POMC gene is not working properly often have an insatiable appetite and gain weight from an early age.

Professor Sadaf Farooqi from the Institute of Metabolic Science at the University of Cambridge said: “There’s a reason why people lacking TRPC5 develop all of these conditions. We’ve known for a long time that the hypothalamus plays a key role in regulating ‘instinctive behaviours’ — which enable humans and animals to survive — such as looking for food, social interaction, the flight or fight response, and caring for their infants. Our work shows that TRPC5 acts on oxytocin neurons in the hypothalamus to play a critical role in regulating our instincts.”

While deletions of the TRPC5 gene are rare, an analysis of DNA samples from around 500,000 individuals in UK Biobank revealed 369 people — around three-quarters of whom were women — that carried variants of the gene and had a higher-than-average body mass index.

The researchers say their findings suggests that restoring oxytocin could help treat people with missing or defective TRPC5 genes, and potentially mothers experiencing postnatal depression.

Professor Farooqi said: “While some genetic conditions such as TRPC5 deficiency are very rare, they teach us important lessons about how the body works. In this instance, we have made a breakthrough in understanding postnatal depression, a serious health problem about which very little is known despite many decades of research. And importantly, it may point to oxytocin as a possible treatment for some mothers with this condition.”

There is already evidence in animals that the oxytocin system is involved in both depression and in maternal care and there have been small trials into the use of oxytocin as a treatment. The team say their work provides direct proof of oxytocin’s role, which will be crucial in supporting bigger, multi-centre trials.

Professor Farooqi added: “This research reminds us that many behaviours which we assume are entirely under our control have a strong basis in biology, whether that’s our eating behaviour, anxiety or postnatal depression. We need to be more understanding and sympathetic towards people who suffer with these conditions.”

This work was supported by Wellcome, the National Institute for Health and Care Research (NIHR), NIHR Cambridge Biomedical Research Centre, Botnar Fondation and Bernard Wolfe Health Neuroscience Endowment.

The study, published in the Journal of Ethnicity in Substance Abuse, reviewed 18 RCTs conducted over the last 15 years that tested treatments for post-traumatic stress and alcohol use disorder. The researchers found that despite women having double the rates of post-traumatic stress and alcohol use disorder than men, and people of color having worse chronicity than white people, most participants were white (59.5%) and male (about 78%).

“Because RCTs are the gold standard for treatment studies and drug trials, we rarely ask the important questions about their limitations and failings,” said Nicole Buchanan, co-author of the study and professor in MSU’s Department of Psychology. “For RCTs to meet their full potential, investigators need to fix barriers to inclusion. Increasing representation in RCTs is not simply an issue for equity, but it is also essential to enhancing the quality of our science and meeting the needs of the public that funds these studies through their hard-earned tax dollars.”

The researchers found that the design and implementation of the randomized controlled trials contributed to the lack of representation of people of color and women. This happened because trials were conducted in areas where white men were the majority demographic group and study samples almost always reflected the demographic makeup where studies occurred. Additionally, those designing the studies seldom acknowledged race or gender differences, meaning they did not intentionally recruit diverse samples.

Furthermore, the journals publishing these studies did not have regulations requiring sample diversity, equity or inclusion as appropriate to the conditions under investigation.

“Marginalized groups have unique experiences from privileged groups, and when marginalized groups are poorly included in research, we remain in the dark about their experiences, insights, needs and strengths,” said Mallet Reid, co-author of the study and doctoral candidate in MSU’s Department of Psychology. “This means that clinicians and researchers may unknowinglyremain ignorant to how to attend to the trauma and addiction challenges facing marginalized groups and may unwittingly perpetuate microaggressions against marginalized groups in clinical settings or fail to meet their needs.”

They published their results in Advanced Materials.

“People have been developing soft and stretchable conductors for almost a decade, but the conductivity is not usually very high,” said corresponding author Tao Zhou, Penn State assistant professor of engineering science and mechanics and of biomedical engineering in the College of Engineering and of materials science and engineering in the College of Earth and Mineral Sciences. “Researchers realized they could reach high conductivity with liquid metal-based conductors, but the significant limitation of that is that it requires a secondary method to activate the material before it can reach a high conductivity.”

Liquid metal-based stretchable conductors suffer from inherent complexity and challenges posed by the post-fabrication activation process, the researchers said. The secondary activation methods include stretching, compressing, shear friction, mechanical sintering and laser activation, all of which can lead to challenges in fabrication and can cause the liquid metal to leak, resulting in device failure.

“Our method does not require any secondary activation to make the material conductive,” said Zhou, who also has affiliations with the Huck Institutes of the Life Sciences and the Materials Research Institute. “The material can self-assemble to make its bottom surface be very conductive and its top surface self-insulated.”

In the new method, the researchers combine liquid metal, a conductive polymer mixture called PEDOT:PSS and hydrophilic polyurethane that enables the liquid metal to transform into particles. When the composite soft material is printed and heated, the liquid metal particles on its bottom surface self-assemble into a conductive pathway. The particles in the top layer are exposed to an oxygen-rich environment and oxidize, forming an insulated top layer. The conductive layer is critical for conveying information to the sensor — such as muscle activity recordings and strain sensing on the body — while the insulated layer helps prevent signal leakage that could lead to less accurate data collection.

“Our innovation here is a materials one,” Zhou said. “Normally, when liquid metal mixes with polymers, they are not conductive and require secondary activation to achieve conductivity. But these three components allow for the self-assembly that produces the high conductivity of soft and stretchable material without a secondary activation method.”

The material can also be 3D-printed, Zhou said, making it easier to fabricate wearable devices. The researchers are continuing to explore potential applications, with a focus on assistive technology for people with disabilities.

The papers other authors are Salahuddin Ahmed, Marzia Momin and Jiashu Ren, all doctoral students in the Penn State engineering science and mechanics department, and Hyunjin Lee, a doctoral student in the biomedical engineering department at Penn State. This work was supported by the National Taipei University of Technology-Penn State Collaborative Seed Grant Program and by the Department of Engineering Science and Mechanics, the Materials Research Institute and the Huck Institutes of the Life Sciences at Penn State.

The research team, led by scientists from the U.S. National Science Foundation National Center for Atmospheric Research (NSF NCAR), used an innovative model that allows for higher-resolution simulations of hurricane formation than ever before. This allowed researchers to study the effects of increased regional moisture over Africa, which is the birthplace of weather systems that later produce hurricanes over the Atlantic.

Past research has suggested that warmer ocean water and a moister atmosphere could cause hurricanes to become more intense with greater amounts of rainfall. But how atmospheric moisture, which is predicted to increase in a warming climate, may be impacting hurricane formation itself has not been studied in detail until now.

The researchers found that a moister environment produced weaker and slower-moving African easterly waves, or disturbances which are the primary precursor or “seed” for hurricanes in the Atlantic. The addition of moisture moved the location of thunderstorms within the wave, making it harder for the wave to grow. Increased moisture also slowed the movement of the wave resulting in weaker and delayed hurricane seed formation by the time it reached eastern Atlantic waters.

“Considerable work during the last two decades has emphasized the role of deep moist convection to explain the development of African easterly waves,” said NSF NCAR scientist and lead author Kelly Núñez Ocasio. “But, the precise role of moisture has proven somewhat elusive. With the development of new modeling capabilities, I was able to focus on the role of moisture in cyclogenesis stemming from the hurricane seed.”

The study is funded by NSF NCAR and published in the Journal of Advances in Modeling Earth Systems. Núñez Ocasio pursued the research through the NSF NCAR Advanced Study Program which allows graduate and postdoctoral students to focus on emerging areas of science.

Next-gen modeling

The birth of hurricanes and other tropical cyclones, known as cyclogenesis, is a complex process where small-scale weather events and large-scale atmospherics happen simultaneously. This complexity has made it difficult to study and model the formation of tropical cyclones. Most climate models provide only a grainy picture of what is happening with localized weather, which makes it difficult to learn anything about the role of individual ingredients, like moisture, that mix together to create cyclogenesis.

To address this, the research team turned to the Model for Prediction Across Scales (MPAS). MPAS has the ability to model weather both locally and globally. This capability allowed Núñez Ocasio and her colleagues to zoom out and simulate global moisture and then zoom in to see how that would interact with localized weather events that lead to the formation of tropical cyclones.

The researchers started the experiment by using MPAS to reproduce a moisture-driven African easterly wave that became hurricane Helene in 2006. The team used that base to add or take away moisture and study what happened with those changes.

“When I increased the moisture we saw more convection and thunderstorms, which is to be expected; however, we discovered that the waves struggled to pair with the more intense and deep convection,” said Núñez Ocasio. “With increased moisture, the energy source of tropical cyclone seeds moved north and further away, reducing the kinetic energy available to the African easterly wave, which led to weak, energy-starved tropical cyclone seeds.”

Studying the evolution of tropical cyclones after this initial phase was outside the scope of this study. More research is needed to discover whether these weaker seeds lead to weaker tropical cyclones and hurricanes or if it will just take them longer to form.

The conditions leading to tropical cyclone formation are complex, but researchers hope these newer modeling techniques will lead to better predictions. For instance, Núñez Ocasio is beginning to run simulations where she alters other atmospheric variables key to generating tropical cyclones.

“In addition to moisture, I’m altering other variables in the model to more realistically reproduce a future climate scenario in collaboration with Erin Dougherty, NSF NCAR project scientist,” she said. “So far, I’m seeing similarities to the results of this study even as I alter those other significant pieces.”