ANIMAL EXPERIMENTATION; STARVATION

Hunger influences the behaviour of female mice towards pups

The Francis Crick Institute

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

Researchers at the Francis Crick Institute have found that hunger can make virgin female mice aggressive towards pups, but only in certain hormonal states. These mice would usually ignore other females’ pups or show parent-like caring behaviour.

In a study published today in Nature, the team found that the switch towards aggression only occurs at certain stages of the reproductive cycle and that hunger and hormone signals are integrated in a particular brain region to elicit this response.

In order to understand how specific bodily states shape information processing in the brain, the team investigated how virgin female mice interact with pups when sated or hungry. After just a few hours after food is removed, a substantial number of these females became aggressive towards pups, an effect that was diminished when the mice were fed.  

These mice were only aggressive towards pups, and continued to act normally in other contexts, such as towards other adult mice or prey. This suggested to the research team that hunger and parenting circuits in the brain somehow interact.  

Finding the control centre in the brain

The researchers focused on neurons in the hypothalamus that are responsible for regulating appetite, the so-called AgRP neurons. They found that these neurons also mediated the effect of food deprivation on behaviour towards pups. Artificially switching on AgRP neurons increased pup-directed aggression in satiated mice, and silencing them diminished pup-directed aggression in hungry mice.

By tracing and manipulating projections from AgRP neurons, the researchers found that a region called the medial preoptic area (MPOA), important for parental behaviour, was a key downstream region for the influence of hunger on parental behaviour.

Coordinating hunger and reproductive state

Interestingly, only about 60% of females showed aggression towards pups even when hunger levels were the same in all the mice. So the team set out to investigate whether reproductive state might influence aggression.

They found that mice at certain stages of the reproductive ‘estrous’ cycle were more likely to become aggressive towards pups. Specifically, the ratio of the ovarian hormones oestradiol and progesterone, which fluctuates across the cycle, sets the responsiveness of MPOA neurons.

The team then showed that hunger information carried by AgRP neurons dampens neuronal activity in the MPOA, stimulating the switch from caring behaviour to pup-directed aggression.

The team believe that these behavioural changes during the estrous cycle reflect a change in priorities as the mouse’s internal states fluctuate.

Jonny Kohl, Group Leader of the State-Dependent Neural Processing Laboratory at the Crick, said: “Our work focuses on mouse behaviour, and we know that humans don’t experience the same simple behavioural switches, but these findings stress the importance of understanding hormones when looking at how different physical states interact in the brain.

“Humans experience many internal states at once, and how the brain integrates these signals and how they shape behaviour remains largely unknown. Work like this can begin to unravel the mechanisms underlying the integration of states, as brain architecture and hormones are very similar between species.”

Mingran Cao, former PhD student in the State-Dependent Neural Processing Laboratory at the Crick and first author of the study, said: “Female mice have to decide how to behave towards pups based on their current internal state, as parental interactions are usually very energetically costly. We’ve shown that their brains integrate hunger and reproductive state in the same region to elicit a state-dependent behavioural response. It would be interesting to next look at how this integrated signal brings about behavioural changes downstream of the MPOA.”

-ENDS-

For further information, contact: press@crick.ac.uk or +44 (0)20 3796 5252

Notes to Editors

Reference: Cao, M. et al. (2025). Integration of hunger and hormonal state gates infant-directed aggression. Nature. DOI.

The Francis Crick Institute is a biomedical discovery institute with the mission of understanding the fundamental biology underlying health and disease. Its work helps improve our understanding of why disease develops which promotes discoveries into new ways to prevent, diagnose and treat disease.

An independent organisation, its founding partners are the Medical Research Council (MRC), Cancer Research UK, Wellcome, UCL (University College London), Imperial College London and King’s College London.

The Crick was formed in 2015, and in 2016 it moved into a brand new state-of-the-art building in central London which brings together 1500 scientists and support staff working collaboratively across disciplines, making it the biggest biomedical research facility under a single roof in Europe.

http://crick.ac.uk/

---

Journal

Nature Neuroscience

DOI

10.1038/s41586-025-09651-2 

Article Title

). Integration of hunger and hormonal state gates infant-directed aggression

Article Publication Date

22-Oct-2025

MISOGYNISTIC MEDICINE

Fewer women receive lung transplants despite policy changes

UCLA Health study finds gender disparities persist under new national organ allocation system

University of California - Los Angeles Health Sciences

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

New research from UCLA Health reveals that women continue to face barriers in accessing lung transplants compared to men, despite recent national policy changes aimed at making organ distribution more equitable.  

“Female lung transplant candidates have historically faced unique challenges in organ allocation due to a combination of biological and social factors,” said Dr. Abbas Ardehali,  director of the UCLA Heart, Lung, and Heart-Lung Transplant Programs at UCLA Health and senior author of the study, published in The Annals of Thoracic Surgery.   

Women often have a smaller body size, which limits the number of donor lungs that are physically compatible. They are also more likely to develop antibodies from prior pregnancies, blood transfusions, or autoimmune conditions, making it harder for their bodies to accept many potential donor organs. Together, these factors significantly narrow the pool of compatible donors, Ardehali said.  

Efforts to reduce these disparities have been ongoing. The Lung Allocation Score (LAS) system, introduced in 2005, prioritized transplants based on medical urgency but did not fully account for biological differences that affect women. To improve fairness, the Organ Procurement and Transplantation Network (OPTN) implemented the Composite Allocation Score (CAS) system in March 2023. The new system added variables such as height, blood type, and immune sensitivity to better match donors and recipients. 

However, researchers found that even with this improved system, inequities remain. Before CAS was implemented, women were 32% less likely than men to receive a lung transplant. After CAS went into effect, women were 16% less likely to undergo transplantation.  

“There was a modest improvement in narrowing the gap, but we still have a lot of work to do,” Ardehali said. “Further refinements to the scoring system are needed to ensure a fair and effective organ allocation system for all patients, regardless of gender.” 

---

Journal

The Annals of Thoracic Surgery

DOI

10.1016/j.athoracsur.2025.09.013 

Method of Research

Data/statistical analysis

Subject of Research

People

Article Publication Date

18-Oct-2025

 

‘Chronic lung-transplant rejection has been a black box.’ New study gives answers, drug targets.

More than 50% of lung-transplant recipients experience a rejection of their new lung within five years

Northwestern University

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

 

image: 

Photo from inside Dr. Ankit Bharat's laboratory at Northwestern University Feinberg School of Medicine in Chicago, IL.

view more 

Credit: Northwestern Medicine

• 
  
• 
  
• 
  
• Study found which abnormal cells talk to each other in harmful ways and perpetuate lung damage
• Scientists are already exploring therapeutic strategies based on this study’s discoveries
• Treatments also could help patients with other lung-scarring diseases (COPD, COVID-19, etc.)

CHICAGO --- More than 50% of lung-transplant recipients experience a rejection of their new lung within five years of receiving it, yet the reason why this is such a prevalent complication has remained a medical mystery. 

Now, a new Northwestern Medicine study has found that, following transplant and in chronic disease states, abnormal cells emerge and “conversations” between them drives the development of lung damage and transplant rejection.  

These findings not only help answer why rejection occurs, but they also have spurred immediate exploration of new drugs to treat transplant rejection and other lung-scarring diseases.

“Chronic lung-transplant rejection has been a ‘black box.’ We knew it happened but did not exactly know why,” said corresponding author Dr. Ankit Bharat, professor of thoracic surgery at Northwestern University Feinberg School of Medicine and executive director of the Northwestern Medicine Canning Thoracic Institute. “Our study provides the first comprehensive cellular and molecular roadmap of the disease.”

The study will be published Oct. 22 in JCI Insight. 

Leading cause of death after the first year of transplantation

Surgeons perform approximately 3,000 to 3,500 lung transplants each year in the U.S., and more than 69,000 have been performed worldwide to date. Chronic lung allograft dysfunction (CLAD), which encompasses several manifestations of chronic lung rejection, remains the leading cause of death after the first year of transplantation. There currently are no effective treatments for CLAD once it develops, leaving patients with only one option: re-transplantation. 

In the new study, after evaluating almost 1.6 million cells, scientists distinguished between abnormal cells from the donor lung versus cells from the recipient’s own immune system. They discovered the donor-derived structural cells and recipient’s immune cells talk to each other in harmful ways that perpetuate lung damage. The findings could lead to new drug targets and provide insights that could help patients with various lung-scarring diseases, not just transplant recipients.

More findings

The scientists discovered a rogue cell type (KRT17 and KRT5 cells) that drives lung scarring across multiple diseases, including idiopathic pulmonary fibrosis, interstitial lung disease, COPD, COVID-19 lung damage and transplant rejection. By integrating data from this array of scarring lung diseases, the scientists created the first comprehensive reference map showing which molecular features are shared across conditions and which are unique to each disease.

“By comparing chronic rejection to other scarring lung diseases, we identified both shared and unique features,” said Bharat, who also is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “This means treatments developed for one condition might help others. The benefits extend far beyond transplant patients.”

The scientists also identified previously unrecognized cell populations in rejected lungs. These include “exhausted” T cells (which participate in immune response) that remain activated but dysfunctional, and “super-activated” macrophages (immune cells that act like the body’s “clean-up crew”) that promote inflammation and scarring.

Lastly, the scientists developed new computational methods to analyze data from multiple studies together, overcoming technical barriers that previously prevented this kind of comprehensive analysis, Bharat said.

New drug targets identified

The scientists pinpointed specific genes and signaling pathways (like PDGF, GDF15 and TWEAK) that drive scarring, which allows them to identify potential targets for new drugs, Bharat said. Some existing medications, such as nintedanib (sold under the brand names Ofev and Vargatef), and pirfenidone (commonly sold under the brand name Esbriet), which are approved for other lung diseases, might be repurposed for transplant rejection, he said. 

“The findings have immediate translational potential,” Bharat said. “We’re already exploring therapeutic strategies based on these discoveries.”

Broad impact on pulmonary fibrosis

While addressing CLAD was the main focus of the paper, this research has major implications for understanding and treating all forms of pulmonary fibrosis, Bharat said. 

“The molecular pathways and cell types we identified are relevant to conditions affecting hundreds of thousands of patients with various lung-scarring diseases, not just transplant recipients,” Bharat said. “This work essentially provides a ‘Rosetta Stone’ for understanding lung scarring regardless of the initial trigger.”

Other Northwestern study authors include Dr. Yuanqing Yan, Taisuke Kaihou, Emilia Lecuona, Xin Wu, Masahiko Shigemura,Haiying Sun, Chitaru Kurihara, Ruli Gao, Felix L Nunez and G. R. Scott Budinger.

---

Journal

JCI Insight

 

Underwater thermal vents may have given rise to the first molecular precursors of life

To test the hypothesis, researchers from Brazil, the United States, and Japan built bench-scale reactors that simulate the interaction between hydrothermal fluids and primitive ocean water

Fundação de Amparo à Pesquisa do Estado de São Paulo

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

A study published in the Journal of the American Chemical Society recreated in the laboratory chemical reactions that may have occurred on Earth about 4 billion years ago, producing the first molecular precursors for the emergence of life. The experiment showed that, without the presence of enzymes, natural gradients of pH, redox potential, and temperature present in underwater hydrothermal vents could have promoted the reduction of carbon dioxide (CO₂) to formic acid (CH₂O₂) and the subsequent formation of acetic acid (C₂H₄O₂). Redox potential is a measure of the tendency of a substance to gain or lose electrons in an oxidation-reduction reaction. The results confirmed the hypothesis that underwater hydrothermal vents played a key role in the process.

“The hypothesis is that these physical-chemical contrasts present in the vicinity of the thermal vents generate a natural voltage, as occurs between the inside and outside of the mitochondria. It’s this voltage that sustains the chemical reactions,” said the first author of the study, Thiago Altair Ferreira. Ferreira holds a PhD in science from the Department of Physical Chemistry at the São Carlos Institute of Chemistry at the University of São Paulo (IQSC-USP) in Brazil and is currently a researcher at the Institute of Physical and Chemical Research (RIKEN) in Wako, Japan.

Alkaline hydrothermal vents release hot fluids (typically around 70 °C) that are basic (with a pH between 9 and 12) and rich in molecular hydrogen (H₂). These fluids mix with the colder water (around 5 °C) from the primitive ocean, which is slightly acidic (pH around 5.5). In these environments, mineral walls rich in micropores and capable of conducting electrons form from iron and nickel sulfides. The contrast generates natural gradients analogous to those that sustain cellular metabolism today.

“In the Hadean, there would have been a colder, more acidic ocean and, emanating from hydrothermal vents, a hot, alkaline fluid. That alone would have produced a certain voltage, comparable to what we know exists in cellular processes today. Our experiment sought to determine whether this voltage alone could trigger a carbon fixation reaction. And we found that it could,” Ferreira summarizes.

The Hadean is the oldest eon in Earth’s history. A geological eon is the largest unit of time on the geological scale. It can last from hundreds of millions to billions of years and is subdivided into geological eras. The Hadean corresponds to the period from approximately 4.6 billion years ago, when the planet formed, to about 4 billion years ago, when the next eon, the Archean, began.

To test the hypothesis, the researchers built bench-scale reactors that simulate the interaction between hydrothermal fluids and primitive ocean water. These reactors have independent controls for temperature, mineral composition, and the passage of electrical currents, whether spontaneous or induced. Iron-sulfur (Fe-S) minerals and their nickel-containing variants (Fe-Ni-S) were used as mineralogical mediators of the process. “Iron-sulfur and iron-nickel-sulfur minerals are very similar to the metal centers we see today in various enzymes. This allows us to consider protometabolism – a metabolism without enzymes – as the trigger for the process,” Ferreira says.

In the experiments, micromolar concentrations of formic acid and acetic acid were detected on the “oceanic” side of the reactor under pH gradients and in the presence of Fe-S or Fe-Ni-S. This indicates coupling between H₂ oxidation on the “hydrothermal” side and CO₂ reduction on the “oceanic” side through the conductive mineral barrier. These are the first two steps of the Wood-Ljungdahl pathway.

Named after American biochemist Harland Wood (1907-1991) and Swedish biochemist Lars Ljungdahl (1926-2023), this pathway is a metabolic route for carbon fixation that uses hydrogen as an electron donor. In this pathway, methanogenic and acetogenic bacteria convert CO₂ into acetyl coenzyme A (acetyl-CoA), which has phosphate bonds that can store considerable amounts of energy, similar to those in adenosine triphosphate (ATP). ATP is the main molecule responsible for energy storage and transport in all living cells. The Wood-Ljungdahl pathway is considered one of the oldest biochemical pathways on Earth and was possibly active as early as the Hadean eon.

“We focused on two products: formic acid and acetic acid. The first step – converting CO₂ into formic acid and then into acetic acid – is the limiting factor in the process, the most difficult part in terms of energy. We solved it using only minerals,” Ferreira explains.

The study also examined the role of electric currents and found that tiny currents, on the order of nanoamperes (10⁻⁹ A), were enough to efficiently reduce CO₂. “This suggests that very small but constant electric currents at the bottom of the primitive sea would be enough to sustain a protometabolism,” Ferreira comments.

The results of the study reinforce the role of alkaline hydrothermal vents on primitive Earth, showing that two protometabolic stages can emerge from natural gradients and mineral surfaces without the need for complex biological machinery. “The initial condition for life is not a ‘soup’ of organic molecules, but order in the right place and at the right time, maintained by exchanges of energy and entropy. We worked on the logic of physical-chemical gradients triggering reactions in the presence of mineral surfaces that resemble the active sites of enzymes,” Ferreira summarizes.

Although the study focused on basic science with possible astrobiological applications (proposing scenarios for oceanic environments on Jupiter’s moon Europa and Saturn’s moon Enceladus), the approach also inspires technological applications. “Given the importance of metal sites analogous to those of enzymes, we can conceive of more stable and effective materials and conditions for electrocatalysis and hydrogen production, which is currently a major focus as a sustainable energy alternative, as well as for reducing atmospheric CO2, which is a fundamental problem in the context of climate change,” Ferreira suggests.

The study brought together researchers from Brazil, Japan, the United Kingdom, and the United States. Among them was Professor Hamilton Varela, Ferreira’s doctoral advisor.

“The work, developed by Ferreira during his doctoral studies and then refined during his postdoctoral studies, provided experimental evidence of the role of temperature, pH, and potential gradients in CO₂ reduction and opened up important perspectives in the field. This study was developed as part of a Thematic Project of the Electrochemistry Group at IQSC-USP and corroborates the transdisciplinary aspect of electrocatalysis and the importance of basic research,” Varela says.

The study also received support from FAPESP through a research internship abroad.

About São Paulo Research Foundation (FAPESP)
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

---

Journal

Journal of the American Chemical Society

DOI

10.1021/jacs.5c01948 

Article Title

Carbon Reduction Powered by Natural Electrochemical Gradients under Submarine Hydrothermal Vent Conditions