The study, “Hepatocyte Adenosine Kinase Promotes Excessive Fat Deposition and Liver Inflammation,” appeared in September in the scientific journal Gastroenterology.

Hepatocytes are cells that play pivotal roles in liver function, including in metabolism, detoxification, protein synthesis and innate immunity.

An important player in the proper function of hepatocytes is an enzyme called adenosine kinase, ADK. However, the current study shows that ADK can also drive liver disease progression.

“We aimed to study whether hepatocyte ADK functions to promote excessive fat deposition and liver inflammation,” said Chaodong Wu, M.D., Ph.D., an AgriLife Research Faculty Fellow in the Texas A&M Department of Nutrition. Wu is also a Presidential Impact Fellow of Texas A&M University and the corresponding author for the study.

Wu said NAFLD is highly associated with obesity and progresses to an advanced stage when the liver develops overt inflammatory damage.

This study pointed to the idea that hepatocyte ADK may be an important therapeutic target for managing obesity and NAFLD.

“The research demonstrated that hepatocyte adenosine kinase promotes excessive fat deposition and liver inflammation and is a key factor in the pathogenesis of nonalcoholic fatty liver disease,” he said. “There is already some evidence as to how making dietary changes can be effective in helping prevent or reduce the severity of NAFLD. If further research validates the effects of dietary components on inhibiting adenosine kinase in hepatocytes, scientists could develop new approaches for managing this disease.

About the study

The researchers examined how changes in ADK activity relate to levels of liver inflammation and amount of fat in the liver. The team studied mice that were genetically engineered to have either more or less ADK activity than normal.

The team fed the mice a high-fat diet for 12 weeks or a methionine-choline deficient diet, which is known to contribute to liver injury, for five weeks.

Under these diets, mice with lowered ADK activity in their hepatocytes had lower levels of fat and inflammation in the liver than controls. In contrast, mice with elevated ADK activity had greater body weight and increased body fat, liver fat and liver inflammation levels than normal mice.

Going further, the team conducted experiments to clarify exactly how ADK activity causes these effects.

Wu said the study included the analysis of cell-to-cell crosstalk using single-cell RNA sequencing, which was done with assistance from James Cai, Ph.D., a researcher in Texas A&M’s Department of Veterinary Integrative Biosciences.

“The study’s analysis of lipid profiles in mouse liver samples indicated increased presence of lipids that promote mitochondrial dysfunction, leading in turn to liver inflammation,” Wu said.

The team went on to analyze ADK activity and liver health in human liver samples. Like in mice, the data showed that decreased levels of ADK correlated with lower levels of NAFLD, while increased levels of the enzyme were linked to exacerbated liver steatosis and inflammation. The results also showed that ADK promotes excessive fat deposition and liver inflammation through suppressing fatty acid oxidation in liver cells.

“The amount of hepatocyte ADK protein was positively correlated with the degrees of hepatic steatosis in livers from human subjects,” Wu said. “This novel finding highlights the enzyme’s pathological importance in human NAFLD.”

Diet and NAFLD

A 2020 study by Chaidong Wu, Ph.D., and his team showed that indole, a natural compound found in cruciferous vegetables, may be effective against nonalcoholic fatty liver disease. (Photo courtesy of Texas A&M Department of Horticultural Sciences)

Wu said the new study strongly indicates that an unhealthy diet, such as a diet with enriched saturated fatty acids, has a stimulatory effect on increasing the adenosine kinase protein amount in the liver.

“This, in turn, positively correlates with the degrees of obesity, NAFLD and systemic insulin resistance,” he said.

Wu previously investigated the role of diet in NAFLD in a 2020 study led by AgriLife Research scientists. The study, published in Hepatology, showed that indole — a natural compound found in gut bacteria and cruciferous vegetables such as cabbage, kale, cauliflower and Brussels sprouts — may be effective in fighting the disease.

“This natural compound may lead to new treatments or preventive measures for NAFLD,” Wu said. “Healthy foods with high capacity for indole production are important in preventing NAFLD and are beneficial for improving the health of those with it.”

He said preventing NAFLD’s development and progression may depend on nutritional approaches to ensure that gut microbes allow indole and other metabolites to function effectively.

Because interacting with animals, particularly dogs, is known to help people cope with stress and depression, researchers think that a better understanding of the associated brain activity could help clinicians design improved systems for animal-assisted therapy. The prefrontal cortex might be particularly relevant because it helps regulate and process social and emotional interactions.

In the study, activity in the prefrontal cortex of the brain was non-invasively measured with infrared neuroimaging technology as 19 men and women each viewed a dog, reclined with the same dog against their legs, or petted the dog. Each of these conditions was also performed with Leo, a stuffed lion with fur that was filled with a water bottle to match the temperature and weight of the dogs.

Results showed that prefrontal brain activity was greater when participants interacted with the real dogs, and that this difference was largest for petting, which was the most interactive condition. Another key difference was that prefrontal brain activity increased each time people interacted with the real dog. This was not observed with successive interactions with the stuffed lion, indicating that the response might be related to familiarity or social bonding.

Future studies will be needed to examine the issue of familiarity in detail and whether petting animals can trigger a similar boost of prefrontal brain activity in patients with socioemotional deficits.

The authors add: “The present study demonstrates that prefrontal brain activity in healthy subjects increased with a rise in interactional closeness with a dog or a plush animal, but especially in contact with the dog the activation is stronger. This indicates that interactions with a dog might activate more attentional processes and elicit stronger emotional arousal than comparable nonliving stimuli.”

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For many students, college is a major transition that can facilitate either psychological growth or maladaptive behaviors and psychological problems. Previous studies have found an association between FoMO and disruptive/harmful social media use. A greater understanding of how FoMO influences individual behavior is important to reducing FoMO’s negative influence.

For the new study, 472 college students completed a hard copy questionnaire packet assessing FoMO levels, unethical and illegal behavior while in college, and demographic variables. The researchers analyzed this data both by using standard statistical approaches and by applying a supervised machine learning approach.

With the first analysis approach, the team discovered associations between FoMO and nearly all the behaviors they examined. Higher levels of FoMO were found to be correlated with higher rates of classroom incivility (p<0.001), plagiarism (p=0.003), greater weekly alcohol consumption (p<0.001), lower age when beginning drinking alcohol, increased use of cannabis (p=0.007), stimulants (p<0.001), depressants (p<0.001) and hallucinogens, as well as illegal activities including giving away drugs (p<0.001) and stealing (p<0.001). The machine learning algorithm found similar associations and highlighted the modifying effect of living situation, socioeconomic status and gender on several of the relationships.

The authors suggest that brief FoMO assessments, including just 10 questions, may be valuable risk prediction tools for counselors focused on assisting students in the transition to college or university.

The authors add: “Using Fear of Missing Out (FoMO) and demographic information, we were able to predict class membership (offender/user vs non-offender/non-user) of college students across multiple domains (alcohol and drug use, academic misconduct, illegal behavior) well above baseline (e.g., 50% at baseline vs 87% for academic misconduct). These results suggest that FoMO exists not just as an aversive phenomenon, but it also leads to concrete consequences for individuals and society.”

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Chemical compounds in a planet’s atmosphere that could indicate life, called biosignatures, typically include gases found in abundance in Earth’s atmosphere today.

“There’s been a lot of thought put into oxygen and methane as biosignatures. Fewer researchers have seriously considered nitrous oxide, but we think that may be a mistake,” said Eddie Schwieterman, an astrobiologist in UCR’s Department of Earth and Planetary Sciences.

This conclusion, and the modeling work that led to it, are detailed in an article published today in the Astrophysical Journal.

To reach it, Schwieterman led a team of researchers that determined how much nitrous oxide living things on a planet similar to Earth could possibly produce. They then made models simulating that planet around different kinds of stars and determined amounts of N₂O that could be detected by an observatory like the James Webb Space Telescope.

“In a star system like TRAPPIST-1, the nearest and best system to observe the atmospheres of rocky planets, you could potentially detect nitrous oxide at levels comparable to CO₂ or methane,” Schwieterman said.

There are multiple ways that living things can create nitrous oxide, or N₂O. Microorganisms are constantly transforming other nitrogen compounds into N₂O, a metabolic process that can yield useful cellular energy.

“Life generates nitrogen waste products that are converted by some microorganisms into nitrates. In a fish tank, these nitrates build up, which is why you have to change the water,” Schwieterman said

“However, under the right conditions in the ocean, certain bacteria can convert those nitrates into N₂O,” Schwieterman said. “The gas then leaks into the atmosphere.”

Under certain circumstances, N₂O could be detected in an atmosphere and still not indicate life. Schwieterman’s team accounted for this in their modeling. A small amount of nitrous oxide is created by lightning, for example. But alongside N₂O, lightning also creates nitrogen dioxide, which would offer astrobiologists a clue that non-living weather or geological processes created the gas.

Others who have considered N₂O as a biosignature gas often conclude it would be difficult to detect from so far away. Schwieterman explained that this conclusion is based on N₂O concentrations in Earth’s atmosphere today. Because there isn’t a lot of it on this planet, which is teeming with life, some believe it would also be hard to detect elsewhere.

“This conclusion doesn’t account for periods in Earth’s history where ocean conditions would have allowed for much greater biological release of N₂O. Conditions in those periods might mirror where an exoplanet is today,” Schwieterman said.

Schwieterman added that common stars like K and M dwarfs produce a light spectrum that is less effective at breaking up the N₂O molecule than our sun is. These two effects combined could greatly increase the predicted amount of this biosignature gas on an inhabited world.

The research team included UCR astrobiologists Daria Pidhorodetska, Andy Ridgwell, and Timothy Lyons, as well as scientists from Purdue University, the Georgia Institute of Technology, American University, and the NASA Goddard Space Flight Center.

The research team believes now is the time for astrobiologists to consider alternative biosignature gases like N₂O because the James Webb telescope may soon be sending information about the atmospheres of rocky, Earth-like planets in the TRAPPIST-1 system.

“We wanted to put this idea forward to show it’s not out of the question we’d find this biosignature gas, if we look for it,” Schwieterman said.

UC researchers led by Alberto Espay, MD, and Andrea Sturchio, MD, in collaboration with the Karolinska Institute in Sweden, published the research on Oct. 4 in the Journal of Alzheimer’s Disease.

Questioning the dominant hypothesis

The research is focused on a protein called amyloid-beta. The protein normally carries out its functions in the brain in a form that is soluble, meaning dissolvable in water, but it sometimes hardens into clumps, known as amyloid plaques.

The conventional wisdom in the field of Alzheimer’s research for more than 100 years stated that Alzheimer’s was caused by the buildup of amyloid plaques in the brain. But Espay and his colleagues hypothesized that plaques are simply a consequence of the levels of soluble amyloid-beta in the brain decreasing. These levels decrease because the normal protein, under situations of biological, metabolic or infectious stress, transform into the abnormal amyloid plaques.

“The paradox is that so many of us accrue plaques in our brains as we age, and yet so few of us with plaques go on to develop dementia,” said Espay, professor of neurology in the UC College of Medicine, director and endowed chair of the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders at the UC Gardner Neuroscience Institute and a UC Health physician. “Yet the plaques remain the center of our attention as it relates to biomarker development and therapeutic strategies.”

Sturchio noted that many research studies and clinical trials over the years have aimed at reducing amyloid plaques in the brain, and some have lessened plaques, but until the September 27 announcement of a positive trial by Biogen and Eisai (lecanemab), none slowed the progression of Alzheimer’s disease. More importantly, in support of their hypothesis, in some clinical trials that reduced the levels of soluble amyloid-beta, patients showed worsening in clinical outcomes.

“I think this is probably the best proof that reducing the level of the soluble form of the protein can be toxic,” said Sturchio, first author of the report and adjunct research instructor at UC’s College of Medicine. “When done, patients have gotten worse.”

Research results

Previous research from the team found that regardless of the buildup of plaques in the brain, people with high levels of soluble amyloid-beta were cognitively normal, while those with low levels of the protein were more likely to have cognitive impairment.

In the current study, the team analyzed the levels of amyloid-beta in a subset of patients with mutations that predict an overexpression of amyloid plaques in the brain, which is thought to make them more likely to develop Alzheimer’s disease.

“One of the strongest supports to the hypothesis of amyloid toxicity was based on these mutations,” Sturchio said. “We studied that population because it offers the most important data.”

Even in this group of patients thought to have the highest risk of Alzheimer’s disease, the researchers found similar results as the study of the general population.

“What we found was that individuals already accumulating plaques in their brains who are able to generate high levels of soluble amyloid-beta have a lower risk of evolving into dementia over a three-year span,” Espay said.

The research found that with a baseline level of soluble amyloid-beta in the brain above 270 picograms per milliliter, people can remain cognitively normal regardless of the amount of amyloid plaques in their brains.

“It’s only too logical, if you are detached from the biases that we’ve created for too long, that a neurodegenerative process is caused by something we lose, amyloid-beta, rather than something we gain, amyloid plaques,” Espay said. “Degeneration is a process of loss, and what we lose turns out to be much more important.”

Next steps

Sturchio said the research is moving forward to study if increasing the levels of soluble amyloid-beta in the brain is a beneficial therapy for patients with Alzheimer’s.

Espay said it will be important to ensure that the elevated levels of the protein introduced into the brain do not then turn into amyloid plaques, since the soluble version of the protein is needed for normal function to make an impact in the brain.

On a larger scale, the researchers said they believe a similar hypothesis of what causes neurodegeneration can be applied to other diseases including Parkinson’s and Creutzfeldt-Jakob disease, with research ongoing in these areas as well.

For example, in Parkinson’s disease, a normal soluble protein in the brain called alpha-synuclein can harden into a deposit called a Lewy body. The researchers hypothesize that Parkinson’s is not caused by Lewy bodies aggregating in the brain, but rather by a decrease in levels of normal, soluble alpha-synuclein.

“We’re advocating that what may be more meaningful across all degenerative diseases is the loss of normal proteins rather than the measurable fraction of abnormal proteins,” Espay said. “The net effect is a loss not a gain of proteins as the brain continues to shrink as these diseases progress.”

Espay said he envisions a future with two approaches to treating neurodegenerative diseases: rescue medicine and precision medicine.

Rescue medicine looks like the current work, studying if boosting levels of key proteins like amyloid-beta leads to better outcomes.

“Interestingly, lecanemab, the anti-amyloid drug recently reported as beneficial, does something that most other anti-amyloid treatments don’t do in addition to reducing amyloid: it increases the levels of the soluble amyloid-beta,” Espay said.

Alternatively, precision medicine entails going deeper to understand what is causing levels of soluble amyloid-beta to decrease in the first place, whether it is a virus, a toxin, a nanoparticle or a biological or genetic process. If the root cause is addressed, the levels of the protein wouldn’t need to be boosted because there would be no transformation from soluble, normal proteins to amyloid plaques.

Espay said precision medicine would take into account the fact that no two patients are alike, providing more personalized treatments. The researchers are making progress in precision medicine through the Cincinnati Cohort Biomarker Program, a project aiming to divide neurodegenerative diseases by biological subtypes in order to match therapies based on biomarkers to those most likely to benefit from them.

“The Cincinnati Cohort Biomarker Program is dedicated to working toward deploying the first success in precision medicine in this decade,” Espay said. “By recognizing biological, infectious and toxic subtypes of Parkinson’s and Alzheimer’s, we will have specific treatments that can slow the progression of those affected.”

One solution to water scarcity is harvesting water from air. Dr. Xianming “Simon” Dai, assistant professor of mechanical engineering in the Erik Jonsson School of Engineering and Computer Science at The University of Texas at Dallas, is working on technology to make it possible for anyone to have an affordable, portable device that could access water anywhere, anytime conceivably using no external energy.

Dai and his team of researchers recently advanced that technology by developing a novel platform to accelerate the harvesting process. The team demonstrated the platform in a study published online Aug. 29 in Proceedings of the National Academy of Sciences.

The platform solves a key problem in water harvesting: Collected water droplets form a thermal barrier that prevents further condensation, so they need to be removed from the surface as rapidly as possible to make room for more harvesting.

The UTD team addressed this problem by developing a platform with a unique shape. They cut a series of mushroom-like channels — smaller in diameter than a human hair — into the collection surface so that part of the surface material overhangs each channel. As droplets collect on the surface, they are absorbed into the channels, but the mushroom design prevents the water from flowing back onto the initial collection surface. Harvested water is collected through those channels.

Key to the platform’s success is a novel flow-separation slippery surface built on the foundation of Dai’s prior work in 2018 to capture water from fog and air. Inspired by rice leaves and pitcher plants that can trap and direct water droplets, the hydrophilic slippery liquid-infused porous surface (SLIPS) has a unique water-absorbing property that helps direct water droplets into the channels. The channels also are lined with SLIPS, which helps keep liquid from backwashing onto the initial collection surface.

“Surface tension force moves the liquid from the collection surface into the channel, which is good for continuous water harvesting,” Dai said. “The mushroom-like channels are unique because they lock the liquid inside.”

The publication marked a major achievement for Zongqi Guo PhD’21, first author of the study, who earned his degree in December.

“This work is a summary of my PhD research. We combined microfluidics, microfabrication and surface chemistry to unveil the new fundamentals for water sustainability, which is flow separation,” said Guo, now a postdoctoral fellow at the University of Minnesota.

The technology has a variety of applications, including military uses. Dai received an Army Research Office Young Investigator Program award in 2019 to advance the research, which is also funded by the National Science Foundation.

“Soldiers need to be able to drink water wherever they are,” Dai said. “This requires a decentralized water harvesting technology.”

Because the technology removes moisture from air, it also could be useful in food processing and other environments that require humidity control, he said. Dai’s team continues to improve the technology and work toward making broader impacts.

Dr. Joshua Summers, professor and department head of mechanical engineering, said Dai’s research addresses the importance of improving the welfare of all people.

“Hopefully, this publication can help stimulate the scientific discovery and engineering of solutions that can be widely deployed where moisture should be harvested,” Summers said. “As a huge ‘Star Wars’ fan, I am excited to see that we are moving closer to the ‘moisture farms’ of Luke’s youth.”

Co-authors of the study include Dylan Boylan, mechanical engineering graduate student, and Dr. Li Shan, mechanical engineering research associate.

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