“Liver fibrosis is the critical feature that creates chronic liver disease and liver cancer. If we can keep fibrosis in check then we can meaningfully impact liver disease,” said Tamer Sallam, MD, corresponding author of the study and vice chair and associate professor in the department of medicine at the David Geffen School of Medicine at UCLA.

“For decades we have believed that targeting inflammation is one of the most important ways to reduce MAFLD. But this new research indicates that inflammation, while still important, may not be the main driver of fibrosis.”

The study, published in the Journal of Clinical Investigation, looked specifically at a protein called lipopolysaccharide binding protein (LBP), which is involved in the body’s immune response, and how LBP functions in mice. Findings showed that mice without LBP in their liver cells had lower levels of liver inflammation and better liver function but no change in fibrosis.

In addition to mouse models, the researchers also studied genetic analyses from large human datasets and human tissue samples from MAFLD patients at different stages in the disease, to examine the consequence of loss of LBP function. The evidence combined showed that the LBP does not alter scar tissue markers.

Sallam indicated a need to further explore how LBP influences inflammation and whether other factors can offer a more potent reduction in inflammation and have an impact on reducing fibrosis.

“Reducing scar burden is one of the holy grails in the treatment of advanced liver diseases,” Sallam said. “These results suggest that certain ways of targeting inflammation may not be a viable option and that more directed therapies against other pathways could help us better target fibrosis and improve outcomes for patients.”

The remarkable two-day event, which occurred in mid-January 2022, injected vast amounts of volcanic aerosols and water vapor into the atmosphere. Historically, large volcanic eruptions like Tambora in 1815 and Mt. Pinatubo in 1991 have led to significant cooling effects on the global climate by blocking sunlight with their aerosols. However, Hunga Tonga’s eruption presented a unique scenario: As a submarine volcano, it introduced an unprecedented amount of water vapor into the stratosphere, increasing total stratospheric water content by about 10%.

Because water vapor is a powerful greenhouse gas, Dessler says there was initial speculation that it might account for the extreme global warmth in 2023 and 2024. Instead, the results of the team’s research, published Wednesday (July 24) in the Journal of Geophysical Research: Atmospheres, reveal the opposite: The eruption actually contributed to cooling the Earth, similar to other major volcanic events.

A Volcanic Eruption’s Cooling Effect

The team’s paper, titled “Evolution of the Climate Forcing During the Two Years after the Hunga Tonga-Hunga Ha’apai Eruption,” includes insight and analysis from Dessler, a professor in the Texas A&M Department of Atmospheric Sciences and the director of the Texas Center for Climate Studies; first author Dr. Mark Schoeberl, chief scientist at the Virginia-based Science and Technology Corporation in Hamburg, Virginia; and multiple scientists from the National Aeronautics and Space Administration (NASA).

Their methodology involved analyzing NASA and National Oceanic and Atmospheric Administration (NOAA) satellite data observations of aerosols and water vapor, among other variables, to estimate the energy balance of the Earth’s climate system. Their analysis revealed that the eruption resulted in more energy leaving the climate system than entering it, thereby inducing the slight cooling effect.

“Our paper pours cold water on the explanation that the eruption caused the extreme warmth of 2023 and 2024,” Dessler explained. “Instead, we need to focus primarily on greenhouse gases from human activities as the main cause of the warming, with a big assist from the ongoing El Nino.”

Implications And Future Research

According to Dessler, this research has important implications for both scientists and the general public. By dismissing the volcanic eruption as a major factor in the recent warming, the team’s study reinforces his point that human-induced greenhouse gas emissions are the primary driver of climate change. This focus is particularly relevant, given the ongoing debate and misinformation about the causes of global warming.

Moreover, Schoeberl says the study underscores the importance of continued investment in satellite-based stratospheric measurements.

“Our understanding of the Hunga Tonga eruption is largely thanks to the investment in stratospheric satellite measurements by NOAA and NASA over the past two decades,” Schoeberl added. “However, we need to be cautious about a potential ‘stratospheric data desert,’ as some of the most critical instruments are not being replaced.”

The Challenging Path Ahead

While this paper answers several important questions, Dessler acknowledges that it simultaneously introduces new ones. For instance, the researchers highlighted some unresolved issues related to the Hunga Tonga eruption, such as the unexpectedly low levels of sulfur dioxide produced by such a violent eruption and the minimal impact the eruption had on the 2023 ozone hole. The 2023 ozone hole refers to a significant thinning of the ozone layer over Antarctica, which allows more harmful UV radiation to reach the Earth’s surface. Additionally, the persistence of water vapor in the stratosphere beyond what was predicted by models suggests that there is still much to learn about stratospheric circulation processes.

As scientists work to resolve ongoing questions and deepen our understanding of the stratosphere, Schoeberl says the team’s work highlights the critical need for continued research and precise data to tackle the challenges of climate change.

Roland Kays, lead author of a paper on the work, said the study’s goal was to compare the importance of climate versus human factors in where mammals chose to live. To do so, researchers collected data on 25 mammal species from 6,645 locations across the United States. The study is one of the largest camera trap data analyses ever done. The data came largely from Snapshot USA, which is a national mammal camera trap survey conducted with collaborators across the country.

“One of our ideas was that humans may have changed our landscape so much that we have become the primary determinants of which animals live where,” said Kays, who is a research professor at NC State and scientist at the N.C. Museum of Natural Sciences. “What we found was that in fact humans were not the most important. Climate, including temperature and the amount of rainfall, was the most important factor across most of the species we observed.”

However, human activity in the form of large population centers and agriculture was still a significant factor in where mammals chose to live. Some species struggled in the presence of cities and farms, Kays said, but many thrived.

“There are a lot of species that do well when humans are around. The Eastern gray squirrel for instance is the most common squirrel in Raleigh, and it does great around people. But there’s another species called the Eastern fox squirrel, and that one does well around agriculture but not as well around people,” he said. “We can see those differences in many other species. The snowshoe hare does poorly around both people and around agriculture. This study allows us to see the species that are sensitive to our impacts, and which ones benefit.”

This information helped researchers create maps which predict how common various mammals are across the contiguous U.S., which allowed them to separate the country into regions based on what kinds of mammals were common in each. These regions, known as ecoregions, are commonly used when studying plants but have never before been applied to mammal populations.

“When you look at something like the Eastern deciduous forest, that is an ecoregion classified by how common a type of tree is,” Kays said. “We’re now able to do that with mammal species and then compare that to the plant ecoregions. What we found was a striking similarity between the two. For instance, in the east where there is more rainfall, you have more plants growing. That lined up with a greater abundance of mammals that we saw in that region as well, because more plants mean more food for those animals to eat.”

The open access paper, “Climate, food and humans predict communities of mammals in the United States” is available to read in Diversity and Distributions. In identifying climate as the number one influence on mammal habitat choice, the study presents a new tool for predicting the impacts of climate change on mammal populations. Rising global temperatures will cause shifts in where animals are able to live, as well as influence precipitation levels and plant growth. Understanding these factors will be important to making sustainable decisions about mammal population management in the future.

Electron transport, the energy-generating process inside living cells that enables photosynthesis and respiration, is enhanced in peptides with a collapsed, folded structure. Interdisciplinary researchers at the Beckman Institute for Advanced Science and Technology combined single-molecule experiments, molecular dynamics simulations and quantum mechanics to validate their findings.

“This discovery provides a new understanding of how electrons flow through peptides with more complex structures while offering new avenues to design and develop more efficient molecular electronic devices,” said lead investigator Charles Schroeder, the James Economy Professor in Materials Science and Engineering at the University of Illinois Urbana-Champaign.

Proteins reside in all living cells and are integral to cellular activities like photosynthesis, respiration (taking in oxygen and expelling carbon dioxide) and muscle contraction.

Chemically, proteins are long sequences of amino acids strung like holiday lights, the different colors representing different amino acids like tryptophan and glutamine.

In a protein’s simplest form (its primary structure) the amino acid string lies flat. But amino acids are prone to mingling; when they interact with one another, the string tangles, causing the structural collapse referred to as protein folding (or secondary structure).

The researchers asked if and how a protein’s structure impacts its ability to conduct electricity — a question not clearly answered by existing literature.

Rajarshi “Reeju” Samajdar, a graduate student in the Schroeder Group, was patiently probing this protein problem by experimenting on one molecule at a time. But Samajdar was not looking at proteins at all. Instead, he focused on peptides, fragments of proteins with a fraction of the amino acids. For this study, Samajdar used peptides with about four or five amino acids, which permitted more granular observation, he said.

Samajdar saw something surprising: stretched-out peptides with a primary structure seemed to be less effective energy conductors than their folded counterparts with a secondary structure. The stark difference between the peptides’ behavior in each state piqued his curiosity.

“Peptides are very flexible. We were interested in understanding how the conductance properties changed as you stretch them out and the peptides transition from a folded secondary structure to an extended conformation. Interestingly, I saw a distinct jump between those two structures, with different electronic properties in each,” Samajdar said.

To verify his observations, Samajdar called on Moeen Meigooni, a graduate research assistant working with Emad Tajkhorshid, a Beckman researcher, professor and the J. Woodland Hastings Endowed Chair in Biochemistry.

The team simulated the peptides’ conformational behavior with computer modelling, confirming the jerky structural shifts Samajdar observed. Leaving no scientific stones unturned, the researchers worked with Martin Mosquera, an assistant professor of chemistry at Montana State University, and Nicholas Jackson, a Beckman researcher and an assistant professor of chemistry at Illinois, to use quantum mechanical calculations to confirm that these two discrete structures were indeed linked to the changes in conductivity.

“We believe that our approach combining single-molecule experiments, structural modelling with molecular dynamics and quantum mechanics is a very powerful approach for understanding molecular electronics,” Samajdar said. “We could have gone straight to quantum, but we didn’t. The computer simulation piece allowed us to study the entire conformational space of the peptides.”

The researchers’ triple-checked results indicate that peptides with a folded secondary structure do conduct electricity better than peptides with an unfolded primary structure. The specific secondary structure they observed formed a shape called the 3₁₀ helix.

Because this work was conducted on peptides, the results lend themselves to a greater understanding of electron transport in larger, more complex proteins and other biomolecules, pointing toward applications in molecular electronic devices like semiconductors that work by switching between two distinct structures.

For the first time, researchers at Tulane National Primate Research Center found that a cancer drug significantly reduced levels of SIV, the nonhuman primate equivalent of HIV, in the brain by targeting and depleting certain immune cells that harbor the virus.

Published in the journal Brain, this discovery marks a significant step toward eliminating HIV from hard-to-reach reservoirs where the virus evades otherwise effective treatment.

“This research is an important step in tackling brain-related issues caused by HIV, which still affect people even when they are on effective HIV medication,” said lead study author Woong-Ki Kim, PhD, associate director for research at Tulane National Primate Research Center. “By specifically targeting the infected cells in the brain, we may be able to clear the virus from these hidden areas, which has been a major challenge in HIV treatment.”

Antiretroviral therapy (ART) is an essential component of successful HIV treatment, maintaining the virus at undetectable levels in the blood and transforming HIV from a terminal illness into a manageable condition. However, ART does not completely eradicate HIV, necessitating lifelong treatment. The virus persists in “viral reservoirs” in the brain, liver, and lymph nodes, where it remains out of reach of ART.

The brain has been a particularly challenging area for treatment due to the blood-brain barrier — a protective membrane that shields it from harmful substances but also blocks treatments, allowing the virus to persist. In addition, cells in the brain known as macrophages are extremely long-lived, making them difficult to eradicate once they become infected.

Infection of macrophages is thought to contribute to neurocognitive dysfunction, experienced by nearly half of those living with HIV. Eradicating the virus from the brain is critical for comprehensive HIV treatment and could significantly improve the quality of life for those with HIV-related neurocognitive problems.

Researchers focused on macrophages, a type of white blood cell that harbors HIV in the brain. By using a small molecule inhibitor to block a receptor that increases in HIV-infected macrophages, the team successfully reduced the viral load in the brain. This approach essentially cleared the virus from brain tissue, providing a potential new treatment avenue for HIV.

The small molecule inhibitor used, BLZ945, has previously been studied for therapeutic use in amyotrophic lateral sclerosis (ALS) and brain cancer, but never before in the context of clearing HIV from the brain.

The study, which took place at the Tulane National Primate Research Center, utilized three groups to model human HIV infection and treatment: an untreated control group, and two groups treated with either a low or high dose of the small molecule inhibitor for 30 days. The high-dose treatment lead to a notable reduction in cells expressing HIV receptor sites, as well as a 95-99% decrease in viral DNA loads in the brain .

In addition to reducing viral loads, the treatment did not significantly impact microglia, the brain’s resident immune cells, which are essential for maintaining a healthy neuroimmune environment. It also did not show signs of liver toxicity at the doses tested.

The next step for the research team is to test this therapy in conjunction with ART to assess its efficacy in a combined treatment approach. This could pave the way for more comprehensive strategies to eradicate HIV from the body entirely.

This research was funded by the National Institutes of Health, including grants from the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke, and was supported with resources from the Tulane National Primate Research Center base grant of the National Institutes of Health, P51 OD011104.