Q: How would you summarize your study for a lay audience?

In short: We found that the defense protein “Resistin like molecule gamma” (Relmy), produced by neutrophils, punches holes into heart cells after a heart attack. This promotes dangerous, fast, and irregular heart rhythm and cell death in the heart.

The longer version: The most lethal complications of coronary artery disease are myocardial infarction (MI) and sudden cardiac death.

In MI, the blockage of a heart artery leads to insufficient oxygen supply to heart muscle cells (cardiomyocytes). This compromises their ability to maintain a stable rhythm and can give rise to a dangerous, unstable heart rhythms (arrhythmia) called ventricular tachycardia (VT) and ventricular fibrillation (VF).

VT and VF are both serious arrhythmias that can lead to sudden cardiac arrest and death within minutes. In VT, the heart beats very rapidly, but in a coordinated rhythm. In VF, the rhythm is chaotic and uncoordinated.

Most arrhythmias occur within 48 hours after MI and coincide with massive immune cell infiltration into the heart tissue. We were interested in how these immune cells may promote arrhythmia.

We found neutrophils that get recruited into the infarct (the area of dead tissue resulting from the cutoff of oxygen supply) in large numbers upregulate the gene “Retnlg,” coding the protein resistin like molecule gamma (RELMy). We also found a comparable gene, “RETN,” in human infarcted heart tissue. When we removed this protein from neutrophils in mice, the arrhythmia burden after MI was reduced 12-fold.

Q: What question were you investigating?

We were investigating the question of how neutrophils, a specific kind of immune cell, promote ventricular arrhythmia (a dangerous fast irregular heartbeat) after heart attacks. Cardiomyocytes as the main actors in arrhythmia are very well studied, but if and how immune cells can promote arrythmia is less clear. This work is important because ventricular arrhythmia is the most lethal complication after myocardial infarction. We need to understand better what promotes arrythmia to help us develop new antiarrhythmic drugs.

Q: What methods or approach did you use?

We used a plethora of methods to figure this out. For an initial understanding about which proteins in neutrophils might be important, we used deposited data on gene expression generated by single cell and spatial RNA-sequencing from mice that underwent myocardial infarction. But we also used data from human studies to find similarities in human tissue.

We also relied on confocal and super-high resolution microscopy in isolated mouse heart muscle cells that were treated with the labeled protein. Further, we deployed in vitro assays such as a liposome model and cell culture techniques to investigate the mouse and the human version of the protein to find out if they work similar.

Q: What did you find?

We found that after MI in mouse models, neutrophils upregulatethe expression of “Retnlg,” the gene coding for RELMy. We also found that the human biological homolog “RETN,” the genecoding for Resistin, was higher expressed in human infarcted myocardial tissue compared to non-infarcted tissue, similar to mice.

We saw that deleting the gene from bone marrow derived cells (such as neutrophils) and deleting the gene from neutrophils specifically significantly reduced incidents of ventricular arrhythmia in the mouse models.

Q: What are the implications?

The implications are that immune cells play a crucial role in sudden death and arrhythmia.

We should think about treating both the myocardial infarction both by quick recanalization of the vessel to restore oxygenated blood supply and also by targeting immune cells to mitigate the arrhythmic effects of the injury.

When we understand the underlying mechanisms better, we can pursue therapeutic targets that go beyond the broad immune suppression that is used today.

If we can treat targets more specifically, we can reduce unwanted side effects and unravel the full potential of immune modulation in cardiovascular disease.

Q: What are the next steps?

The next steps are to find a way to neutralize the harmful protein and test if this can reduce VT burden and infarct size. First in the mouse models, but, we hope, eventually also in humans.

We should gather more evidence about the significance of this protein in human disease. It is also interesting to see these findings have implications for other diseases with neutrophil recruitment and activation.

Authorship: In addition to Nina Kumowski and Matthias Nahrendorf, Mass General Brigham authors include Steffen Pabel, Jana Grune, Noor Momin, Kyle I. Mentkowski, Yoshiko Iwamoto, Yi Zheng, I-Hsiu Lee, Fadi E. Pulous, Hana Seung, Alexandre Paccalet, Charlotte G. Muse, Kenneth K. Y. Ting, Paul Delgado, Andrew J. M. Lewis, Vaishali Kaushal, Antonia Kreso, Dennis Brown, Kamila Naxerova, Michael A. Moskowitz, and Maarten Hulsmans.

Funding: This work was supported by grants from the Leducq Foundation, the National Institutes of Health (NIH grants HL155097, HL149647, HL142494, HL176359, NS136068, DP2AR075321); the Deutsche Forschungsgemeinschaft (DFG) Walter Benjamin Programm (491497342 and 530157297); the British Heart Foundation (FS/ICRF/24/26111 and RE/18/3/342140), and the NIHR Oxford Biomedical Research Centre.

Disclosures: Nahrendorf has received funds or material research support from Alnylam, Biotronik, CSL Behring, GlycoMimetics, GSK, Medtronic, Novartis, and Pfizer, and has received consulting fees from Biogen, Gimv, IFM Therapeutics, Molecular Imaging, Sigilon, Verseau Therapeutics and Bitterroot. Matthias and Wirth are employees of the company Abberior Instruments America, which commercializes the MINFLUX technology. Lewis is on the advisory board of Abbott, AstraZeneca, and Novartis. Pabel is employed by the Novartis Institute of Biomedical Research. Hayat is a cofounder and shareholder of Sequantrix GmbH and has received research funding from Novo Nordisk and AskBio. The remaining authors declare no competing interests.

For more than two decades, finasteride has been prescribed to millions of men seeking to slow or reverse hair loss. Behind its cosmetic appeal, however, evidence has continued to emerge suggesting serious mental health consequences, including depression, anxiety, and in some cases, suicide.

Prof. Mayer Brezis of the Hebrew University of Jerusalem argues that both the medical community and regulators have repeatedly failed to protect the public by overlooking signs of psychiatric harm associated with the drug.

His review analyzed data from eight large studies published between 2017 and 2023. The findings show a clear trend: people who used finasteride were far more likely to experience mood disorders and suicidal thoughts than those who did not. This pattern appeared consistently across various national databases, including the FDA’s adverse event system and healthcare records from Sweden, Canada, and Israel.

“The evidence is no longer anecdotal,” said Prof. Brezis, a professor emeritus of medicine and public health. “We now see consistent patterns across diverse populations. And the consequences may have been tragic.”

The report estimates that hundreds of thousands of users may have suffered from finasteride-related depression, and that hundreds — possibly more — may have died by suicide. Originally approved by the FDA in 1997 for male pattern baldness, the drug has remained popular for its perceived safety and effectiveness, particularly among younger men. Critics say, however, that its risks were downplayed or ignored.

A Delayed Response, With a High Cost

Although the FDA recognized depression as a possible side effect in 2011 and added suicidal thoughts to the label in 2022, researchers had been warning of potential dangers as early as 2002. Internal FDA files from 2010, cited in Brezis’ review, contained entire sections redacted as “confidential,” including estimates of how many people might have been affected.

By 2011, only 18 suicides linked to finasteride had been reported to the FDA. Based on worldwide usage, Brezis concluded the actual number should have been in the thousands. “It wasn’t just underreporting,” Dr. Brezis wrote. “It was a systemic failure of pharmacovigilance.”

Unlike drugs used to treat obesity or psychiatric disorders, which are often closely monitored after approval, finasteride’s classification as a cosmetic treatment may have shielded it from deeper scrutiny. None of the data-mining studies referenced in the review were initiated by Merck, the company that developed the drug, nor were they commissioned by regulatory authorities.

A Cosmetic Drug With Life-Altering Risks

Brezis argues the drug’s classification as a non-essential, appearance-enhancing medication changes the risk calculus. “This wasn’t about life or death medical necessity,” he said. “This was about hair.”

The biological rationale is clear. Finasteride works by blocking the conversion of testosterone into dihydrotestosterone (DHT), but in doing so, it may also disrupt neurosteroids like allopregnanolone — linked to mood regulation in the brain. Animal studies have shown long-term effects on neuroinflammation and even changes in hippocampal structure.

For some patients, the consequences don’t end when the pills do. Reports of lingering symptoms — dubbed “post-finasteride syndrome” — include insomnia, panic attacks, cognitive dysfunction, and suicidal thoughts that persist months or even years after stopping treatment.

Regulatory Gaps, Corporate Silence

The report is especially scathing toward the FDA and Merck. Despite having access to millions of patient records and robust pharmacovigilance tools, neither party acted in time, Brezis argues. The industry’s silence was strategic, he suggests, driven by market pressures and legal liability — echoing past controversies like Merck’s handling of Vioxx.

“Nothing is more important to Organon than the safety of our medicines,” the company recently claimed in a public statement. Yet none of the safety studies cited were initiated by the manufacturer.

The FDA, meanwhile, took five years to respond to a citizen petition calling for a black-box warning. Its final decision? To add suicidal ideation to the label — but not as a formal warning.

What Now?

Brezis is calling for immediate changes in how drugs like finasteride are approved, monitored, and prescribed. His recommendations include suspending marketing of the drug for cosmetic purposes until safety is re-established, mandatory post-approval studies with strict enforcement, and systematic recording of drug histories in suicide investigations.

“For many, those changes come too late. The paper is dedicated to one such individual — a previously healthy man who took finasteride “just” to improve his hair. Within days, he spiraled into severe psychiatric distress. He never recovered. Months later, he took his own life.”

Their research reveals why the first movements of electrons, which are crucial for transferring energy, occur through only one side of a key protein-pigment structure. The findings were published in the Proceedings of the National Academy of Sciences.

Photosynthesis is a sequence of reactions in which electrons pass between multiple pigment molecules. Although it has been examined for decades, the process remains difficult to fully explain because it involves numerous intricate components, operates at extremely fast timescales, and varies slightly across different species. Gaining a deeper understanding of these steps could help scientists develop efficient artificial systems, such as synthetic leaves and solar-based fuel technologies, that replicate nature’s design.

In most life forms that use photosynthesis, the process begins with a protein-pigment complex known as Photosystem II (PSII). This complex captures sunlight and splits water molecules, releasing oxygen and sending electrons onward to other molecules in the chain of energy transfer.

PSII contains two nearly identical branches, known as D1 and D2, surrounded by four chlorophyll molecules and two related pigments called pheophytins. These are symmetrically arranged and connected to electron carriers known as plastoquinones. In theory, electrons should move from chlorophyll to pheophytin and then to plastoquinone along both branches.

However, experiments have consistently shown that electrons move only through the D1 branch — a finding that has baffled scientists for years. “Despite the structural symmetry between the D1 and D2 protein branches in PSII, only the D1 branch is functionally active,” explains Aditya Kumar Mandal, the study’s first author and a PhD student in the Department of Physics at IISc.

To investigate this imbalance, the team combined molecular dynamics simulations, quantum mechanical analyses, and Marcus theory (a Nobel Prize-winning model that describes how electrons are transferred) to chart the energy patterns in both pathways. “We assessed the electron transfer efficiency step-by-step through both D1 and D2 branches,” says Shubham Basera, PhD student in the Department of Physics and one of the authors.

The team found that the D2 branch has a much higher energy barrier, which makes electron transport energetically unfavourable. Specifically, the transfer of electrons from pheophytin to plastoquinone in D2 requires twice as much activation energy as D1 — a barrier that electrons seem unable to overcome, preventing energy from flowing forward.

The researchers also simulated the current-voltage characteristics of both branches and found that the resistance against electron movement in D2 was two orders of magnitude higher than that in D1.

The asymmetry in electron flow may also be influenced by subtle differences in the protein environment around the PSII and how the pigments are embedded in it, the researchers suggest. For example, the chlorophyll pigment in D1 has an excitation state at a lower energy than its D2 counterpart, suggesting that the D1 pigment has a better chance of attracting and transferring electrons.

The researchers also suggest that tweaking some of these components can boost or rewire electron flow across PSII. For example, swapping chlorophyll and pheophytin in D2 could overcome the electron block, because chlorophyll needs lower activation energy than pheophytin.

“Our research presents a significant step forward in understanding natural photosynthesis,” says Prabal K Maiti, Professor at the Department of Physics and one of the corresponding authors of the study. “These findings may help design efficient artificial photosynthetic systems capable of converting solar energy into chemical fuels, contributing to innovative and sustainable renewable energy solutions.”

This is a beautiful combination of theory at various levels to address a long-standing problem culminating in a new level of understanding, but still leaving mysteries to be challenged, says Bill Goddard, Professor at Caltech and one of the corresponding authors.

Launched in 2013 after the University of Navarra received an Advanced Grant of over €2 million from the European Research Council (ERC), PREDIMED-Plus is the largest nutrition trial ever conducted in Europe. Between 2014 and 2016, additional institutions joined the effort, bringing total funding above 15 million euros. Most of the support came from the Carlos III Health Institute (ISCIII) and the Center for Biomedical Research Network (CIBER), through its divisions on Physiopathology of Obesity and Nutrition (CIBEROBN), Epidemiology and Public Health (CIBERESP), and Diabetes and Associated Metabolic Diseases (CIBERDEM).

The study, published in Annals of Internal Medicine, followed 4,746 adults between the ages of 55 and 75 who were overweight or obese and had metabolic syndrome but no prior history of cardiovascular disease or diabetes. Over six years, researchers compared two groups. One group adopted a calorie-reduced Mediterranean diet (about 600 fewer kilocalories per day), engaged in moderate exercise such as brisk walking and strength and balance training, and received professional counseling. The other group continued a traditional Mediterranean diet without calorie limits or exercise advice.

The results revealed that the participants who followed the calorie-reduced diet and exercise plan not only reduced their diabetes risk but also lost more weight and trimmed more from their waistlines. On average, they lost 3.3 kg and 3.6 cm from their waist, compared to 0.6 kg and 0.3 cm in the control group. This translated to preventing about three new cases of type 2 diabetes for every 100 participants — a meaningful benefit for public health.

“Diabetes is the first solid clinical outcome for which we have shown — using the strongest available evidence — that the Mediterranean diet with calorie reduction, physical activity and weight loss is a highly effective preventive tool,” said Miguel Ángel Martínez-González, Professor of Preventive Medicine and Public Health at the University of Navarra, Adjunct Professor of Nutrition at Harvard University, and one of the principal investigators of the project. “Applied at scale in at-risk populations, these modest and sustained lifestyle changes could prevent thousands of new diagnoses every year. We hope soon to show similar evidence for other major public health challenges.”

Type 2 Diabetes: A Preventable Global Epidemic

According to the International Diabetes Federation, type 2 diabetes now affects over 530 million people around the world. Its rise is fueled by urbanization (unhealthy diets, sedentary lifestyles, reduced physical activity), an aging population, and increasing rates of overweight and obesity. In Spain, an estimated 4.7 million adults live with diabetes — mostly type 2 — giving the country one of the highest rates in Europe, where total cases exceed 65 million. In the United States, roughly 38.5 million people have diabetes, and the disease carries some of the highest per-patient healthcare costs worldwide. Experts emphasize that prevention is crucial to slow this escalating crisis, which greatly increases the risk of heart, kidney, and metabolic complications.

“The Mediterranean diet acts synergistically to improve insulin sensitivity and reduce inflammation. With PREDIMED-Plus, we demonstrate that combining calorie control and physical activity enhances these benefits,” explained Miguel Ruiz-Canela, Professor and Chair of Preventive Medicine and Public Health Department at the University of Navarra’s School of Medicine and first author of the study. “It is a tasty, sustainable and culturally accepted approach that offers a practical and effective way to prevent type 2 diabetes — a global disease that is, to a large extent, avoidable.”

International Relevance and Support for a Realistic and Scalable Strategy

Annals of Internal Medicine accompanied the publication with an editorial by Sharon J. Herring and Gina L. Tripicchio, nutrition and public health experts at Temple University (Philadelphia, USA). They praised the intervention’s clinical relevance and its potential as a preventive model for type 2 diabetes. Furthermore, they warn that replicating similar strategies outside the Mediterranean context — such as in the U.S. — requires overcoming structural barriers, including unequal access to healthy foods, the limitations of the urban environment, and the lack of professional guidance. In this scenario, they advocate strengthening public policies that promote more nutritious and more equitable environments. At a time when new drugs against obesity and diabetes are grabbing headlines, PREDIMED-Plus demonstrates that modest, sustained lifestyle changes can still deliver powerful health benefits.

The PREDIMED-Plus project (2013-2024), which involves different patients, is a continuation of the PREDIMED study (2003-2010). This study demonstrated that following a Mediterranean diet enriched with extra-virgin olive oil or nuts reduces the risk of cardiovascular disease by 30%. Researchers emphasize that primary care providers can integrate the new intervention as a sustainable, cost-efficient strategy to prevent type 2 diabetes on a large scale.

Participating Institutions

The PREDIMED-Plus trial has assembled a broad network of investigators from across Spain. In order of the number of participants, the study included researchers from the following institutions: the University of Navarra and the Navarra Health Service (2 centers), Hospital Clínic de Barcelona (2 centers), University of Valencia, Rovira i Virgili University (Reus), IMIM-Hospital del Mar, Miguel Hernández University (Alicante), Son Espases Hospital (Palma de Mallorca), University of Malaga, Reina Sofía Hospital (Córdoba) and University of Granada. In addition, Bioaraba and the UPV/EHU (Vitoria), the University of the Balearic Islands, the Hospital Virgen de la Victoria (Malaga), the University of Las Palmas de Gran Canaria, the University of Leon, the Primary Health Care District of Seville, the Fundación Jiménez Díaz (Madrid), the Hospital de Bellvitge, the Hospital Clínico San Carlos (Madrid), the University of Jaen, and the IMDEA Food Institute (Madrid) have also participated.

The project also benefited from international collaboration with the Harvard T.H. Chan School of Public Health (USA). Most of the participating researchers are affiliated with the CIBEROBN, CIBERESP, or CIBERDEM research networks.

Most residents of the state are accustomed to the idea of earthquakes, but scientists say a particularly dangerous type has been largely ignored: “supershear” earthquakes that move so quickly they overtake their own seismic waves.

In an opinion article in Seismological Research Letters, experts from the USC Dornsife College of Letters, Arts and Sciences explained that these rare events cause far stronger shaking across a wider region than typical quakes. They argue that California needs to strengthen its hazard planning and update building codes to address the greater potential for destruction.

“While California is no more likely to have supershear earthquakes than other, similar regions with large fault systems like the San Andreas, the threat has gone unnoticed for too long,” said Yehuda Ben-Zion, professor of Earth sciences and director of the Statewide California Earthquake Center (SCEC), based at USC Dornsife. “The frequency of these supershear ruptures has been greatly underappreciated.”

Scientists describe supershear earthquakes as being similar to sonic booms. When a jet surpasses the speed of sound, it produces a shock wave in the air. Likewise, when a supershear rupture travels faster than seismic shear waves, it creates powerful ground shock fronts, said Ahmed Elbanna, professor of Earth sciences and director-designate of SCEC. “It breaks the shear wave speed barrier in the rocks and produces destructive waves that are stronger than what’s generated by a normal earthquake,” he said.

This added energy can cause severe damage. Supershear quakes send intense shaking farther from the epicenter and strike twice, according to Elbanna — a sharp initial blow from the shock front followed by the trailing waves.

Globally, about one in three major strike-slip earthquakes are supershear. This is especially significant for California, where many faults near large cities are strike-slip and capable of producing magnitude 7 or higher events.

“We cannot say exactly when and where the next earthquake will be and which one will be supershear,” Ben-Zion said, “but we can say with certainty that over the next few decades, we will have multiple magnitude 7 earthquakes in California.

“They are coming, whether we are prepared or not,” he added.

The authors warn that current design standards don’t fully account for a supershear quake’s extra punch. Buildings and infrastructure are generally engineered for the strongest shaking perpendicular to faults, but supershear quakes direct their energy along the fault line itself.

“Critical structures should be built to this higher standard, and so far, they are not,” Ben-Zion said.

To prepare, the team calls for denser monitoring near major faults, advanced computer simulations of supershear scenarios, and stronger building codes.

“This is a collaborative effort where everybody has to chip in,” Elbanna said. “And I think here at USC and SCEC, with their reputation in the community, this is the right time and right place to get this effort started.”

Elbanna and Ben-Zion co-authored the opinion piece with researchers from Caltech and the University of Illinois Urbana-Champaign.

These findings highlight the overwhelming odds against discovering Earth-like planets that possess both plate tectonics and a nitrogen-oxygen atmosphere containing the right balance of oxygen and carbon dioxide.

Taking these planetary requirements into account, the chances of success for SETI (Search for Extraterrestrial Intelligence) appear slim, say Dr. Manuel Scherf and Professor Helmut Lammer of the Space Research Institute at the Austrian Academy of Sciences in Graz.

“Extraterrestrial intelligences, ETIs, in our galaxy are probably pretty rare,” says Scherf.

A planet’s carbon dioxide level plays a key role in sustaining life. Higher levels of CO₂ help maintain photosynthesis and keep the atmosphere from leaking into space, but too much can trigger a runaway greenhouse effect or make the air toxic. Plate tectonics are essential because they regulate carbon dioxide through the carbon-silicate cycle, recycling the gas between the atmosphere and the planet’s crust. Over time, however, carbon dioxide becomes trapped in rocks and is no longer returned to the atmosphere.

“At some point enough carbon dioxide will be drawn from the atmosphere so that photosynthesis will stop working,” says Scherf. “For the Earth, that’s expected to happen in about 200 million to roughly one billion years.”

Today, Earth’s atmosphere consists mostly of nitrogen (78 percent) and oxygen (21 percent), with only a trace of carbon dioxide (0.042 percent). Scherf and Lammer modeled what would happen on other worlds. A planet with ten percent carbon dioxide — if located farther from its sun or orbiting a dimmer, younger star — could support a biosphere for up to 4.2 billion years. By comparison, a planet with one percent carbon dioxide would remain habitable for about 3.1 billion years.

For advanced life to emerge, such planets would also need at least 18 percent oxygen. Complex animals require higher oxygen levels, and earlier studies have shown that if oxygen drops below this threshold, there would not be enough free oxygen for open-air combustion. Without fire, metalworking would be impossible, preventing the rise of any technological civilization.

Scherf and Lammer compared these potential biosphere lifetimes with how long it took life on Earth to evolve technology — about 4.5 billion years — and with the expected longevity of intelligent species. The longer a civilization endures, the higher the likelihood that it overlaps in time with another.

From these calculations, the researchers concluded that a technological species on a planet with ten percent carbon dioxide would need to persist for at least 280,000 years for even one other civilization to exist in the Milky Way at the same time as ours.

“For ten civilizations to exist at the same time as ours, the average lifetime must be above 10 million years,” says Scherf. “The numbers of ETIs are pretty low and depend strongly upon the lifetime of a civilization.”

This means that if we do detect an ETI, it is almost certainly going to be much older than humanity.

It’s these numbers that also lead to the estimate that the next closest technological civilization is about 33,000 light years away. Our Sun is about 27,000 light years from the galactic center, which means that the next closest technological civilization to our own could be on the other side of the Milky Way.

These numbers are not absolutes – Scherf points out that there are other factors that should be included, such as the origin of life, the origin of photosynthesis, the origin of multi-cellular life and the frequency with which intelligent life develops technology, but they cannot be quantified at present. If each of these factors has a high probability, then ETIs might not be as rare. If each of these factors has a low probability, then a more pessimistic outlook is required.

Nevertheless, Scherf strongly believes that SETI should continue the search.

“Although ETIs might be rare there is only one way to really find out and that is by searching for it,” says Scherf. “If these searches find nothing, it makes our theory more likely, and if SETI does find something, then it will be one of the biggest scientific breakthroughs ever achieved as we would know that we are not alone in the Universe.”