Publisher Health

The World Health Organization lists bacteria that are resistant to antibiotics as one of the top 10 global health threats. Therefore, researchers are looking for new antibiotics to counter this resistance. Adéla Melcrová, biophysicist at the University of Groningen (the Netherlands), and her colleagues discovered that the relatively new antibiotic AMC-109 affects the cell membrane of bacteria by disordering its organization. This differs from most other antibiotics and could open up new directions for future treatment and drug development. The results were published in Nature Communications on 7 July.
AMC-109, developed at the UiT Arctic University of Norway, has shown promising results in the lab as well as in clinical trials against the notoriously difficult-to-treat methicillin-resistant Staphylococcus aureus (MRSA). It will be tested on humans soon (phase 3 of clinical trials). However, it was not known exactly how AMC-109 works on bacteria. ‘I found it surprising that no one knew exactly how it worked,’ says Melcrová. ‘So, I decided to have a look at it.’
Many antibiotics operate by punching holes in the membrane of the bacterium, which forms a boundary between the inside and the outside of the bacterium. This membrane is vital to regulating what comes in and what stays out, as well as to building the protective cell wall around the bacterium. ‘The developers of the drug, who collaborated in this study, thought that AMC-109 makes holes in the membrane of the bacterium, just like other antibiotics,’ says Melcrová. But this is not what she found.
Disorganization leads to death
Melcrová took the membrane of Staphylococcus aureus, extracted for her by the University of Groningen Molecular Microbiology group. Melcrová herself is based in the Biophysics group of Professor Wouter Roos, where, as she explains, ‘we study biology with methods from physics.’ Together with her colleague Sourav Maity, Melcrová studied the bacterial membrane with a High-Speed Atomic Force Microscope (HS-AFM), which speedily taps the material with a tiny tip, measuring thickness and stiffness of the material.
What Melcrová and Maity saw with the HS-AFM were small areas of a higher membrane thickness, indicating some sort of structural organization. Upon adding AMC-109 to the membrane, these thicker areas clustered together and then dissolved. ‘A bit like an iceberg that melts: the material is still there, but the structure is gone,’ Melcrová says. ‘And apparently, the disruption of these areas is sufficient to lead to the death of the bacterium.’

Clumps: for once a good thing
In collaboration with the Molecular Dynamics group, Josef Melcr has built a simulation model of the interaction between the membrane and the antibiotic, using the Martini forcefield. Melcrová: ‘While the experiments show us what happens, a simulation allows us to interpret what we see.’ And what the simulation showed was that the AMC-109 forms small clumps. Subsequently, these clumps infiltrate the bacterial membrane.
‘Any doctor would tell you that aggregation is a bad thing,’ says Melcrová. ‘Several diseases are caused by aggregating proteins: Alzheimer’s disease, for instance. But in this case, it is a very good thing.’ On its own, AMC-109 would also attack human cells. But by clumping together, some properties are ‘hidden’ on the inside of the bunched-up AMC-109, making it safe for the human body.
Boosting other antibiotics
Now that the effect of AMC-109 on the membrane of bacteria is clearer, new possibilities for future drug development open up. ‘For instance,’ says Melcrová, ‘drugs could be developed that explicitly aim to disorganize the membrane structure.’ There is also evidence suggesting that the disorganization breaks down the resistance of the bacteria to old-fashioned antibiotics. ‘This is still a hypothesis,’ Melcrová explains, ‘but it could mean that a treatment with AMC-109 could potentially also boost the effect of a “classic” antibiotic.’
Four long years
‘I am happy that this work is finally out,’ says Melcrová. ‘It took four long years of work. We went through a lot of stress, frustration, and arguments but we also enjoyed the great discoveries and putting the puzzle of this unique antibiotic action together. The fact that one of the collaborators, Josef Melcr, is also my husband meant that this project was always with me, even at home,’ says Melcrová with a smile.

Brand new research from University of Limerick in Ireland has revealed that even moderate daily physical activity can reduce the risk of depression.
The new study, conducted by physical activity and mental health experts at University of Limerick and Trinity College Dublin, has shown that a physical activity dose equivalent to just 20 minutes a day (for five days a week) of moderate-intensity physical activity, like brisk walking, was linked with less risk of depressive symptoms and odds of major depression.
The study, funded by Ireland’s Health Research Board, has just been published in the JAMA Network Open journal.
Depression is unfortunately increasingly common among older adults, and has significant risk factors for major chronic conditions, including cognitive decline, cardiovascular disease and chronic pain, and increased risk of death and suicide.
Depression causes over 5-10% of the burden of all diseases in Europe and the economic cost in the United States alone is estimated to be over $210.5 billion. Identifying potentially easy and low-cost health and lifestyle solutions that could reduce the risk of depression remains a top priority.
Recent research has shown moderate-to-vigorous physical activity (MVPA) was linked with benefits for depression.

“However,” explained Dr Eamon Laird, lead author on the paper and a post-doctoral researcher in the Department of Physical Education and Sport Sciences at UL, “there is no agreement on how much physical activity is protective for depression overall, or how this may vary among adults with disease.
“For this work, we used 10 years of data from the Irish Longitudinal Study On Ageing which included information on depression, MVPA, and other key health-related variables such as disease, lifestyle factors and socio-economic status.
“We sought to identify the lowest dose of MVPA associated with protection against Major Depression and depressive symptoms and the extent to which this varied based on the presence of chronic disease,” added Dr Laird.
Key findings from the study include: A physical activity dose equivalent to 20 minutes a day of MVPA (brisk walking) for five days per week was associated with a 16% lower rate of depressive symptoms and 43% lower odds of Major Depression A dose-response effect was found, such that more MVPA was associated with greater protection for Depression;- Specifically, doses equivalent to ~30 minutes a day of MVPA were associated with 7% lower risk of depressive symptoms and 44% lower odds of Major Depression;
– Doses equivalent to ~60 minutes a day of MVPA were associated with: 16% lower risk of depressive symptoms and 41% lower odds of Major Depression;

– Doses equivalent to ~120 minutes a day of MVPA were associated with: 23% lower risk depressive symptoms and 49% lower odds of Major Depression These findings remained significant even after controlling for relevant health-related factors like biological sex, education, age, smoking and alcohol, obesity, antidepressant use and time. These findings were also materially the same for older adults with and without a chronic illness.According to Dr Laird: “This study is very relevant given the high prevalence of depression in our increasing older adult population. Physical activity at lower doses than World Health Organization recommendations for overall health may offer protection against depressive symptoms and Major Depression — at minimum, try to engage in 20 minutes a day of moderate-intensity activity at least five days per week, with more benefits seen at higher doses.
“Try and build it into a routine with hobbies or activities you enjoy and trying to do it with others as social interactions particularly with activity can also have mental health benefits. Remember that it is one component, and that nutrition and healthy lifestyle will also give additive benefits in addition to the physical activity.”
Dr Matthew Herring, a Senior Lecturer and Investigator in the Physical Activity for Health Research Centre at UL and Principal Investigator of this HRB-funded research, added: “The current findings have significant implications in highlighting that significant antidepressant benefits appear to be associated with doses of physical activity that are lower than current World Health Organization recommendations for overall health, though greater doses were associated with stronger protection.
“We are clearly not advocating for lower physical activity among the older adult population, but findings suggest that the largest improvements in protection against depression among older adults may be made by engaging inactive older adults in physical activity even at doses below those recommended for overall health.”

Scientists have found a new use for copper in magnetic resonance imaging (MRI) contrast agent design, that could help to create better images which help doctors diagnose patients’ conditions more easily and safely.
Researchers discovered a novel copper protein binding site, which does not occur in nature, that has real potential for use in MRI contrast agents used to improve the visibility of internal body structures in scans.
The discovery overturns conventional medical wisdom that copper is unsuitable for use in MRI contrast agents and could help to develop new imaging agents with potentially fewer risks and side effects than exist with current commonly used contrast agents.
Researchers from the Universities of Birmingham and St Andrews, as well as Diamond Light Source, published their findings in PNAS after creating a highly elusive abiological copper site bound to oxygen donor atoms within a protein scaffold.
The experts found that the new structure displayed highly effective levels of relaxivity -the ability of a contrast agent to influence the relaxation times of protons, which helps create clearer and more informative images during an MRI scan.
Co-author Dr Anna Peacock, Reader in Bioinorganic Chemistry at the University of Birmingham, commented: “We prepared a new-to-biology copper-binding site which shows real potential for use in contrast agents and challenges existing dogma that copper is unsuitable for use in MRI.”
“Despite copper largely being disregarded for use in MRI contrast agents, our binding site was shown to display extremely promising contrast agent capabilities, with relaxivities equal and superior to the Gd(III) agents used routinely in clinical MRI. Our discovery showcases a powerful approach for accessing new tools or agents for imaging applications.”

The researchers note that imaging agents based on copper could also be used in Positron emission tomography (PET) scans, which produce detailed 3-dimensional images of the inside of the body.
Their study shows use of an artificial coiled coil to create the copper site within a protein scaffold has achieved function and performance not normally associated with copper.
“Metal sites that are not part of the repertoire of biology are vital in providing protein designers with an expanded toolbox of chemistries they can use to design new functional systems such as the promising imaging capabilities reported here,” added Dr Peacock.
“This opens up applications beyond what biology is currently capable of and showcases some of the advantages of using simple miniature protein scaffolds as a means with which we can engineer new, and maybe currently unknown, metal-binding sites.”
In MRI scanners, sections of the body are exposed to a strong magnetic field causing hydrogen nuclei of water in tissues to be polarised in the direction of the magnetic field. The magnitude of the spin polarisation detected is used to form the MR image but decays with a characteristic time constant known as the T1 relaxation time.
Water protons in different tissues have different T1 values, which is one of the main sources of contrast in MR images. A contrast agent usually shortens, but in some instances increases, the value of T1 of nearby water protons — altering contrast in the image and improving the visibility of internal body structures, with the most used compounds being gadolinium-based contrast agents (GBCAs).
Gadolinium (in the form of Gd3+) is often used as a contrast agent, but there are environmental and patient safety concerns making exploration of new contrast agents an important and active research area. Although more work needs to be done to secure the stability of this new copper protein site, the study authors believe their work is a promising first step towards designing new copper-based contrast agents for clinical MRI scanning.

A study in mice suggests that inflammation in the brain’s barrier, the meninges, may spill over into grey matter and cause changes that can contribute to progressive multiple sclerosis (MS).
The research, published today as a Reviewed Preprint in eLife, is described by the editors as an important study that advances our understanding of the mechanisms of brain damage in this autoimmune disease. It involves the use of novel methods to provide what they say is convincing evidence for a gradient of immune genes and inflammatory markers from the meninges to the adjacent brain tissue in mice.
Inflammation within the meninges is found in all types of MS. There is mounting evidence to suggest this inflammation plays a pivotal role in the progression of the disease, including loss of the protective coating on nerves (demyelination), loss of new nerve sprouts (neurites) and decreased volume of grey matter.
“Grey matter injury is linked to disabling MS symptoms like cognitive dysfunction and depression,” explains Sachin Gadani, a neuroimmunology fellow at Johns Hopkins University School of Medicine, Baltimore, US, and a co-first author of the study alongside Saumitra Singh, Postdoctoral Research Fellow at Johns Hopkins University School of Medicine. “Meningeal inflammation appears to be a critical driver of cortical grey matter pathology, but attempts to characterise the mechanism in an unbiased manner have been limited by the absence of spatially resolved data — that is, critical information about the anatomical relationship between meningeal inflammation and the underlying brain tissue. We set out to determine the patterns of gene activity in the meninges and the surrounding grey matter, while preserving the context about the position of those cells in the brain.”
Gadani, Singh and colleagues used an approach called spatial transcriptomics, whereby the pattern of gene activity in a tissue is measured and the information is then pieced back together to show the pattern of gene activity in the original location. They started by measuring gene activity in the inflamed meninges in a mouse model of MS against the meninges in healthy mice, and then compared this to the expression of genes in the surrounding grey matter in both groups of mice.
As the team expected, they found an increased expression (upregulation) of genes related to immune cells and pathways, immune cell infiltration, and the activation of brain-specific immune cells called microglia. To understand more about the proximity of this gene activity to the meningeal region, they analysed patterns of gene activity along a path from the meninges to the thalamus. All the groups of genes declined in activity with increasing distance from the inflamed meningeal region. However, some genes showed a more gradual decline — particularly those involved in immune processes such as antigen processing and presentation. This suggests that some upregulation of pro-inflammatory genes had spilled over from the brain’s meningeal region into the grey matter.
“This is the first time a study has characterised a mouse model of meningeal inflammation and grey matter injury using spatial transcriptomics,” says co-first author Saumitra Singh. “We’ve provided a publicly available dataset from our work that we hope others can use in future research.”
A limitation of this study is that the spatial resolution may not be sufficient to distinguish between the meninges and surrounding grey matter with certainty. Additionally, while the authors used a mouse model that represents many pathological features of MS, it does not fully represent human disease, and the analysis does not consider different timepoints in the development of MS. Despite this, the authors say their findings could pave the way for future studies using human samples.
“Our findings have revealed several candidate pathways in the development of grey matter injury. Future work should focus on spatial transcriptomics in human samples which, thanks to advances in technology, is now becoming more feasible,” concludes senior author Pavan Bhargava, Associate Professor of Neurology at Johns Hopkins University School of Medicine.

Bacteria found in 74 kitchens spread among 5 European countries were mostly harmless according to new research published in Applied and Environmental Microbiology, a journal of the American Society for Microbiology.
“We have previously found considerable variations in kitchen standards, food preparation practices, and cleaning regimes between France, Norway, Portugal, Romania, and Hungary,” said Birgitte Moen, Ph.D., Scientist — Department of Food Safety and Quality, Nofima — Norwegian Institute of Food, Fisheries, and Aquaculture Research, Ås, Norway.
In the study, the researchers sampled bacteria populations from sinks, cutting boards, counter tops, handles and cleaning utensils — sponges and cloths — used in kitchens.
Despite large numbers of species and considerable differences in bacterial diversity between samples, the researchers identified 8 bacterial genera commonly associated with environmental sources in most of the kitchens they sampled, which they characterized as “core microbiota.” These included Acinetobacter, Pseudomonas, Enhydrobacter, Enterobacteriaceae, Psychrobacter, Chryseobacterium, Bacillus and Staphylococcus.
In the report, the authors stressed that the core microbiota persisted despite considerable differences between kitchens in the study. Some kitchens lacked running water, some lacked an indoor sink and some lacked dishwashers. They also persisted despite differing food preparation methods, dietary habits and differences in hand and kitchen hygiene, both of which affect the probability of infection.
The study was motivated by the authors’ curiosity, said Moen. Bacteria in food, in the gut, in hospitals and in professional food production had been well researched, but little was known about the microbes that inhabit the domestic kitchen. With an already existing collaboration across countries, “we had a unique opportunity to dig into this,” Moen added.
The team knew that harmful bacteria enter kitchens via contaminated food, and that the type of these bacteria varied across countries. For example, Salmonella is not a problem in Norway, but it is the most commonly reported cause of foodborne illness in mainland Europe. Knowledge of the bacteria inhabiting the domestic kitchen could be used to help prevent human illness, and perhaps could even lead to more hygienic kitchen designs and better cleaning utensils, said Moen.

Mania, in which mood and energy level are extremely elevated for at least a week, and hypomania, which is less severe and lasts at least four days, are the defining features of bipolar spectrum disorders (BSD) and can be the most disruptive symptoms. A new study in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier, now identifies a signature of risk for developing future mania or hypomania.
BSD are psychiatric conditions that typically emerge in young adulthood, often severely disrupting lives and requiring intensive treatments. Mania risk has remained challenging for clinicians to predict; the ability to do so would aid in directing treatments to at-risk patients sooner.
The researchers, led by Adriane M. Soehner, PhD, at the University of Pittsburgh, built on previous research showing that heightened reward motivation and sleep-circadian rhythm disruption are associated with mania/hypomania onset. Brain imaging studies have also shown that BSD is associated with elevated reward expectancy activation in the left ventrolateral prefrontal cortex, a key reward- and salience-processing hub.
For the current study, Dr. Soehner and colleagues clustered these markers together; they hypothesized that a signature of increased mania risk would be marked by elevated reward sensitivity, impulsivity, and sleep-circadian characteristics. Young adult participants, who did not have a diagnosis of BSD, completed assessments and underwent functional magnetic resonance imaging. About half the participants also underwent follow-up assessments at six and 12 months.
Three “profiles” emerged from the sample: one healthy, one at moderate risk, and one at high risk. Individuals at high risk had elevated mania symptoms at baseline compared to the other two groups. Over the 12-month follow-up interval, mania symptoms in both the high-risk and moderate-risk groups exceeded the healthy group.
Dr. Soehner said of the findings, “Here, we identified neurobehavioral profiles based on reward sensitivity, impulsivity, and sleep-circadian characteristics that help distinguish those with elevated mania vulnerability. These characteristics, in combination, may help detect mania risk and provide targets to guide and monitor early interventions.”
Cameron Carter, MD, Editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, said of the work, “New findings such as these highlight our emerging ability to combine neurobiological and clinical measures to identify groups of patients at highest risk for serious mental health problems such as mania, allowing for early identification and intervention for those at highest risk. Future research is needed to show that this can lead to reduced suffering and better outcomes in individuals identified in this way.”

A strange mystic swings a pocket watch back and forth, repeating the phrase “You’re getting sleepy, very sleepy,” giving them absolute command over their subject. That’s not how hypnotism really works, but it’s the way it’s often depicted in pop culture. Even some clinicians and hypnosis educators propagate harmful myths about hypnosis.
Steven Jay Lynn, a professor of psychology at Binghamton University, State University of New York, is an expert on hypnosis who has made major contributions to the judicial system for his insight on the practice. Lynn believes that hypnosis has many useful clinical applications, but that myths keep it from being utilized to its full potential.
In a recent paper published in BJPsych Advances, “Reconciling myths and misconceptions about hypnosis with scientific evidence,” he and his colleagues, Madeline Stein and Devin Terhune from the Institute of Psychiatry, Psychology & Neuroscience at King’s College, addressed a number of errors and misconceptions regarding the characteristics and practice of hypnosis. These are a few of the common myths that are widely believed and commonly circulated in popular culture.
Hypnotized people can’t resist suggestions
A deeply hypnotized person is believed to display “blind obedience,” going along automatically with whatever the hypnotist suggests. Yet individuals do not lose control over their actions during hypnosis — contrary to the notion the media reinforces that hypnosis is something done to you and that hypnosis can be used to control someone. In fact, people can resist and even oppose hypnotic suggestions. Their experience of control during hypnosis depends on their intentions and expectations regarding whether or not they retain voluntary control.
Hypnosis is a “special state”
Hypnosis is often mischaracterized as a “special state” where defense mechanisms are reduced and a “unique state of physical relaxation and conscious unconsciousness’ allows us to ‘enter our subconscious depths through hypnosis. However, people can respond to hypnotic suggestions even while they are alert and on an exercise bicycle. Aside from being a contradiction in terms, ‘conscious unconsciousness’ is an inaccurate depiction, because during hypnosis even the most highly suggestible individuals remain fully conscious and cognizant of their surroundings. It is more accurate to consider hypnosis as a set of procedures in which verbal suggestions are used to modulate awareness, perception and cognition, rather than to unnecessarily invoke ‘special states.’

People are either hypnotizable or they are not
People’s responsiveness to hypnosis can be relatively stable over time. Yet it is inaccurate to assume that people are either hypnotizable or not. People vary greatly in their responsiveness and often respond to some suggestions but not others. Still, most people are sufficiently hypnotizable to reap substantial benefits from therapeutic suggestions.
Responsiveness to suggestions reflects nothing more than compliance or faking
Suggested behaviors during hypnosis can seem so much a departure from the mundane that questions inevitably arise regarding whether hypnotic responses are genuine. However, neuroimaging studies reveal that the effects of hypnotic suggestions activate brain regions (e.g, visual processing) consistent with suggested events (e.g., hallucinating an object).These findings provide convincing evidence that hypnotic effects are represented at the neurophysiological level consistent with what people report.
Hypnotic methods require great skill to administer
One popular misconception is that of the mesmerist, or magician-like hypnotist with special powers of influence who can “hypnotize” anyone. This widespread idea is pure myth; in actuality, administering a hypnotic induction and specific suggestions do not require any special skills or abilities beyond those required for basic social interactions and administration of experimental or clinical procedures, such as the ability to establish rapport. However, hypnosis should be practiced only by professionals trained in the use of hypnosis.
Hypnotic age regression can retrieve accurate memories from the distant past
TV shows and movies often feature people being able to recall extremely accurate memories from a distant past life under hypnosis. But research suggests a contrary view. When researchers check the accuracy of memories of people who are “age regressed” to an earlier time (e.g., 10th century) against factual information from the suggested period, they find that the information is almost invariably incorrect. What people report is mostly consistent with information experimenters provide regarding their supposed past life experiences and identities (e.g., different race, culture, sex). These findings imply that “recall” reflects participants’ expectancies, fantasies, and beliefs regarding personal characteristics and events during a given historical period.

Compared to artificial tears, or eye drops, human tears are significantly more complex liquids, with a wide range of components including lipids, carbohydrates, proteins, water, and salt. It is this complex mixture that gives tears the perfect thickness and ability to moisturize the eye, a design that is hard to replicate with fewer ingredients.
In Physics of Fluids, from AIP Publishing, Vega et al. researched human tears at the micron level to reveal new ways of customizing artificial tears to address individual symptoms of dry eye disease. The detailed insights they gained about the composition and behavior of tears could also apply to the study of ocular pathogens, as well as other biological fluids.
“Tailoring formulations and characteristics to meet individual requirements are key considerations in achieving efficacy,” author Juan F. Vega said. “The ultimate goal is to provide an effective and personalized solutionthat alleviates dry eye syndrome.”
The authors collected healthy human tears and tested 10 different formulations of artificial tears, probing these liquids to understand properties such as viscosity (flow), elasticity and stability and the effects of different concentrations of components in the liquids. They also tested the behavior of the liquids under stress, such as when the eye blinks.
To study the tiny volumes of liquid in tears, the authors applied microrheology methods, which monitor the movement of micron-sized particles in liquids, using a technique that measures how light reflects off particles suspended in liquid to reveal how the liquid behaves in different scenarios, known as dynamic light scattering, or DLS.
The authors’ unique application of these methods to the study of tears has implications both for the fundamental knowledge of microbiological fluids and for the design of functional materials with specific desired properties, Vega said.
“The goal of investigating these characteristics is to understand the behavior of the fluid and gain insights into its performance and potential applications — for example, cosmetics, pharmaceuticals, or food — where understanding the viscoelastic properties helps in formulating products with desirable textures, stability, and flow behavior,” Vega said.
The authors plan to continue to explore more complex formulations of artificial tears and extend their work to the study of human tears with different pathologies.
“Through careful tuning, artificial tears can be tailored to meet specific needs, such as stability, lubrication, and moisturization, and mimicking natural tears,” Vega said. “Ultimately, this work aims to enhance the comfort and well-being of individuals experiencing dry eye symptoms.”

Fetuses use a copy of a gene inherited from their dad to force their mum to release as much nutrients as possible during pregnancy, Cambridge scientists have discovered.
The unborn baby ‘remote controls’ its mother’s metabolism so the two are in a nutritional tug of war. The mother’s body wants the baby to survive but needs to keep enough glucose and fats circulating in her system for her own health, to be able to deliver the baby, breastfeed and to reproduce again.
A new study from the University of Cambridge published today (11 July 2023) examines how the placenta communicates with the mother through the release of hormones so she will accommodate her baby’s growth. The placenta is a vital organ that develops with the fetus in pregnant women and other female mammals to support the developing fetus. In pregnant mice, scientists selectively altered the signalling cells in the placenta that tell mothers to allocate nutrients to her developing fetuses.
Professor Amanda Sferruzzi-Perri, Professor in Fetal and Placental Physiology, a Fellow of St John’s College and co-senior author of the paper, said: “It’s the first direct evidence that a gene inherited from the father is signalling to the mother to divert nutrients to the fetus.”
Dr Miguel Constancia, MRC Investigator based at the Wellcome-MRC Institute of Metabolic Science and co-senior author of the paper, said: “The baby’s remote control system is operated by genes that can be switched on or off depending on whether they are a ‘dad’s’ or ‘mum’s’ gene’, the so-called imprinted genes.
“Genes controlled by the father are ‘greedy’ and ‘selfish’ and will tend to manipulate maternal resources for the benefit of the fetuses, so to grow them big and fittest. Although pregnancy is largely cooperative, there is a big arena for potential conflict between the mother and the baby, with imprinted genes and the placenta thought to play key roles.”
The findings by researchers from the Centre for Trophoblast Research at Cambridge’s Department of Physiology, Development and Neuroscience and the Medical Research Council Metabolic Diseases Unit, part of the Wellcome-MRC Institute of Metabolic Science, have been published in Cell Metabolism.

The baby’s genes controlled by the father tend to promote fetal growth and those controlled by the mother tend to limit fetal growth.
Professor Sferruzzi-Perri explained: “Those genes from the mother that limit fetal growth are thought to be a mother’s way of ensuring her survival, so she doesn’t have a baby that takes all the nutrients and is too big and challenging to birth. The mother also has a chance of having subsequent pregnancies potentially with different males in the future to pass on her genes more widely.”
Researchers deleted the expression of an important imprinted gene called Igf2, which provides instructions for making a protein called ‘Insulin Like Growth Factor 2’. Similar to the hormone insulin, which is responsible for making and controlling glucose levels in our circulation, the gene promotes fetal growth and plays a key part in the development of fetal tissues including the placenta, liver and brain.
Dr Jorge Lopez-Tello, a lead author of the study based at the University’s Department of Physiology, Development and Neuroscience, said: “If the function of Igf2 from the father is switched off in signalling cells, the mother doesn’t make enough amounts of glucose and lipids — fats — available in her circulation. These nutrients therefore reach the fetus in insufficient amounts and the fetus doesn’t grow properly.”
The scientists found that deleting Igf2 from the placenta’s signalling cells affects the production of other hormones that modulate the way the mother’s pancreas produces insulin, and how her liver and other metabolic organs respond.

“We found Igf2 controls the hormones responsible for reducing insulin sensitivity in the mother during pregnancy. It means the mother’s tissues don’t absorb glucose so nutrients are more available in the circulation to be transferred to the fetus,” said Professor Sferruzzi-Perri.
Babies with Igf2 gene defects can be overgrown or growth-stunted. “Until now, we didn’t know that part of the Igf2 gene’s role is to regulate signalling to the mother to allocate nutrients to the fetus,” added Professor Sferruzzi-Perri.
The mice studied were smaller at birth and their offspring showed early signs of diabetes and obesity in later life.
Professor Sferruzzi-Perri said: “Our research highlights how important the controlled allocation of nutrients to the fetus is for the lifelong health of the offspring, and the direct role the placenta plays.
“The placenta is an amazing organ. At the end of pregnancy, the placenta is delivered by the mother, but the memories of how the placenta was functioning leaves a lasting legacy on the way those fetal organs have developed and then how they’re going to function through life.”
The next step is to understand how placental hormones are controlled by Igf2 and what those hormones are doing. Future research could help scientists discover new strategies to target the placenta to improve health outcomes for mums and babies.

Double Olympic 800m champion Caster Semenya was discriminated against by rules forcing her to lower her testosterone levels in order to compete, the European Court of Human Rights has found.The 32-year-old South African was born with differences of sexual development (DSD) and is not allowed to compete in any track events without taking testosterone-reducing drugs.On Tuesday the ECHR ruled in favour of Semenya in a case involving testosterone levels in female athletes.A three-time 800m world champion and 800m and 1500m Commonwealth champion, Semenya has been in a long-running dispute with World Athletics since regulations requiring her to have hormone treatment were introduced by the governing body in 2018.She has twice failed in legal battles to overturn the decision.The case at the ECHR was against the government of Switzerland for not protecting Semenya’s rights and dates back to a Swiss Supreme Court ruling three years ago.In a lengthy judgement published on Tuesday, the ECHR found the Swiss government did not protect Semenya from being discriminated against when its Supreme Court refused to overturn a decision by the Court of Arbitration for Sport (Cas), which upheld the World Athletics rules.An ECHR statement read: “The court found in particular that the applicant had not been afforded sufficient institutional and procedural safeguards in Switzerland to allow her to have her complaints examined effectively, especially since her complaints concerned substantiated and credible claims of discrimination as a result of her increased testosterone level caused by differences of sex development.”The decision, made by a panel of seven people at the ECHR, was split 4-3 in favour of Semenya and may allow her to challenge the Supreme Court or Cas rulings.World Athletics described the ECHR chamber as “deeply divided” and said it will ask the Swiss government to refer the case to the ECHR Grand Chamber for a “final and definitive decision”.A World Athletics statement read: “We remain of the view that the DSD regulations are a necessary, reasonable and proportionate means of protecting fair competition in the female category as the Court of Arbitration for Sport and Swiss Federal Tribunal both found, after a detailed and expert assessment of the evidence.”We will liaise with the Swiss government on the next steps. In the meantime, the current DSD regulations, approved by the World Athletics Council in March 2023, will remain in place.”Under the regulations introduced in 2018, athletes with DSD were only allowed to compete without restrictions in track events between 400m and the mile.However, in March World Athletics ruled that DSD athletes must have hormone-suppressing treatment for six months before being eligible to compete in all events.Semenya ran in the 5,000m at last year’s World Championships in Oregon but failed to qualify for the final.She has argued that taking testosterone-reducing medication could endanger her health and that the ruling denied her and other athletes with DSD the right to rely on their natural abilities.Because of the ruling, she could not defend her 800m title at the Tokyo Olympics, which took place a year later than planned in 2021.Semenya, who has always been legally identified as female, has said she should be able to compete in women’s events even if her testosterone levels are higher than her competitors.In 2019 she told BBC Sport she had been “crucified” but will “never stop fighting” against the regulations brought in by World Athletics, then known as the IAAF.