Plants cannot use nitrogen on their own. The nutrient must first be converted into a usable form through a process called nitrogen fixation, which relies on microorganisms in the soil. This process takes place in natural ecosystems as well as on farmland. “While this process has been significantly overestimated in nature, it has increased by 75 percent over the past 20 years due to agriculture,” says Bettina Weber, a biologist at the University of Graz, summarizing findings from a study published earlier this year.

Building on those results, a new analysis shows that the way nitrogen fixation is calculated in some Earth System models has now been reassessed. These models are widely used to project climate trends and inform major assessments, including the World Climate Report. The updated findings were published in the scientific journal PNAS.

New Findings Prompt Climate Model Revisions

The study was led by Sian Kou-Giesbrecht of Simon Fraser University in Burnaby, Canada. The work was carried out by an international research group focused on biological nitrogen fixation, which includes Bettina Weber. This working group receives support from the U.S. Geological Survey (USGS) John Wesley Powell Centre for Analysis and Synthesis.

“We compared different Earth System models with current nitrogen fixation values and found that they overestimate the nitrogen fixation rate on natural surfaces by about 50 percent,” Weber explains. Because plants depend on this process to access nitrogen, the overestimate has meaningful consequences. According to the study, it results in an overall reduction of about 11 percent in the projected CO₂ fertilization effect.

Why Updating Models Is Critical

Weber emphasizes the importance of adjusting climate models to reflect these updated measurements. “This is because gases such as nitrogen oxides and nitrous oxide are produced as part of the nitrogen cycle. These can be released into the atmosphere through conversion processes and alter or disrupt climate processes.” Accurately accounting for nitrogen dynamics, she says, is essential for making reliable predictions about how ecosystems and the climate will respond in the future.

The study, published in EMBO Molecular Medicine, was led by Dr. Benjamin Hunter and Associate Professor Sean Lal from the School of Medical Sciences. The team examined donated human heart tissue from patients receiving heart transplants in Sydney, comparing it with tissue from healthy donors. Their analysis revealed that diabetes drives specific molecular changes inside heart cells and alters the physical makeup of heart muscle. These effects were most pronounced in patients with ischemia cardiomyopathy, which is the leading cause of heart failure.

“We’ve long seen a correlation between heart disease and type 2 diabetes,” said Dr. Hunter, “but this is the first research to jointly look at diabetes and ischemia heart disease and uncover a unique molecular profile in people with both conditions.

“Our findings show that diabetes alters how the heart produces energy, maintains its structure under stress, and contracts to pump blood. Using advanced microscopy techniques, we were able to see direct changes to the heart muscle as a result of this, in the form of a build-up of fibrous tissue.”

Heart disease remains the leading cause of death in Australia, and more than 1.2 million Australians are living with type 2 diabetes.

Associate Professor Lal said: “Our research links heart disease and diabetes in ways that have never been demonstrated in humans, offering new insights into potential treatment strategies that could one day benefit millions of people in Australia and globally.”

Looking Inside Diseased Human Hearts

To better understand how diabetes affects the heart, the researchers studied heart tissue from both transplant recipients and healthy individuals. This direct examination allowed them to see how diabetes influences heart biology in real human patients rather than relying solely on animal models.

The results showed that diabetes is more than a co-morbidity for heart disease. It actively accelerates heart failure by interfering with essential biological processes and reshaping heart muscle at the microscopic level.

“The metabolic effect of diabetes in the heart is not fully understood in humans,” said Dr. Hunter.

How Diabetes Disrupts the Heart’s Energy Supply

In healthy hearts, energy is mainly generated from fats, with glucose and ketones also contributing. Previous research has shown that glucose use increases during heart failure. However, diabetes interferes with this process by reducing how sensitive heart cells are to insulin.

“Under healthy conditions, the heart primarily uses fats but also glucose and ketones as fuel for energy. It has previously been described that glucose uptake is increased in heart failure, however, diabetes reduces the insulin sensitivity of glucose transporters — proteins that move glucose in and out of cells — in heart muscle cells.

“We observed that diabetes worsens the molecular characteristics of heart failure in patients with advanced heart disease and increases the stress on mitochondria — the powerhouse of the cell which produces energy.”

Structural Damage and Fibrosis in the Heart Muscle

Beyond energy production, the researchers found that diabetes affects the proteins responsible for heart muscle contraction and calcium regulation. In patients with both diabetes and ischemic heart disease, these proteins were produced at lower levels. At the same time, excess fibrous tissue accumulated within the heart, making the muscle stiffer and less able to pump blood efficiently.

“RNA sequencing confirmed that many of these protein changes were also reflected at the gene transcription level, particularly in pathways related to energy metabolism and tissue structure, which reinforces our other observations,” said Dr. Hunter.

“And once we had these clues at the molecular level, we were able to confirm these structural changes using confocal microscopy.”

Implications for Future Treatment and Care

Associate Professor Lal said identifying mitochondrial dysfunction and fibrosis-related pathways opens the door to new treatment approaches.

“Now that we’ve linked diabetes and heart disease at the molecular level and observed how it changes energy production in the heart while also changing its structure, we can begin to explore new treatment avenues,” he said.

“Our findings could also be used to inform diagnosis criteria and disease management strategies across cardiology and endocrinology, improving care for millions of patients.”

Scientists at Cold Spring Harbor Laboratory (CSHL) have now identified a promising way to jump-start intestinal repair. Their strategy relies on CAR T-cell therapy, a powerful form of immunotherapy best known for treating certain cancers. By applying this approach to the gut, the researchers hope to open the door to future clinical trials aimed at improving intestinal health, particularly in people affected by age-related decline.

Targeting Aging Cells That Refuse to Die

This work builds on earlier research led by CSHL Assistant Professor Corina Amor Vegas, whose laboratory studies cellular senescence. As the body ages, it accumulates senescent cells, which no longer divide but also do not die off. These lingering cells have been linked to many age-related conditions, including diabetes and dementia. In earlier studies, Amor Vegas and her team engineered immune cells known as anti-uPAR CAR T cells that selectively remove senescent cells in mice, leading to major improvements in the animals’ metabolism.

The researchers next asked whether removing senescent cells could help restore the intestine’s ability to heal. Amor Vegas partnered with CSHL Assistant Professor Semir Beyaz and graduate student Onur Eskiocak to investigate. They delivered CAR T cells directly to the intestines of both younger and older mice. According to Amor Vegas, the results were striking. “In both cases, we see really significant improvements,” she says. “They’re able to absorb nutrients better. They have much less inflammation. When irritated or injured, their epithelial lining is able to regenerate and heal much faster.”

Protection Against Radiation-Induced Gut Damage

Leaky gut syndrome is particularly common among cancer patients who receive pelvic or abdominal radiation therapy. To model this, the team exposed mice to radiation that damaged their intestinal epithelial cells. Mice treated with CAR T cells recovered far more effectively than those that did not receive the therapy. Notably, a single dose of CAR T-cell treatment continued to support healthier gut function for at least one year.

The researchers also found compelling evidence that anti-uPAR CAR T cells encourage regeneration in human intestinal and colorectal cells, Eskiocak notes. While the precise biological mechanisms behind this effect are still being explored, the findings point to strong therapeutic potential. Beyaz emphasizes the broader significance of the work. “This is one good step toward a long journey in understanding how we can better heal the elderly,” he said.