Their findings are published March 10 in the journal Cell Metabolism.

The discovery can advance CAR-T cell therapy, which harnesses the immune response of T cells to cancers by introducing tumor-detecting molecules into the cells. In the last decade, the U.S. Food and Drug Administration has approved six CAR-T cell therapies to treat B cell lymphomas and multiple myeloma. But despite early successes, the effectiveness of the treatment tends to diminish over time, which has launched a search for ways to boost function of T cells.

Also, there are currently no approved CAR-T cell therapies to treat solid tumors.

For the new study, researchers in the lab of Sidi Chen, associate professor of genetics at Yale and senior author of the paper, devised an ingenious way to efficiently scan the genome of CD8 T cells for specific genes that might enhance the cells’ ability to attack cancer cells.

“We developed a new kind of genome-wide gain of function screen to find a molecular enzyme that acts like a foot on a gas pedal to increase metabolic activity in T cells,” Chen said.

They found high levels of activity in several genes, including PRODH2, a gene involved in cell metabolism, stimulate increased CAR-T cell activity in mouse models used to study three different types of cancers, including solid-tumor breast cancer. The findings show it is possible to produce hyper-metabolic CAR-T cells that outperform existing cell therapies, researchers say.

Using these systems and findings, future studies can test the newly identified types of metabolically enhanced CAR-Ts in clinical settings, to identify other T cell super-chargers, and to extend cell-based immunotherapy to different cancer types, especially solid tumors, Chen said.

Chen is affiliated with the Yale Cancer Center, the Yale Stem Cell Center, the Yale Center for Biomedical Data Science, and the Systems Biology Institute and Center for Cancer Systems Biology at Yale’s West Campus.

Yale’s Lupeng Ye, Jonathan Park, Lei Peng, and Quanjun Yang are co-first authors of the paper.

The research was primarily funded by the National Institutes of Health and the U.S. Department of Defense.

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Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.

In fact, ponds lose more carbon via gas than they store in the muck, a new University of Florida study found.

“That finding means some ponds are doing us an ecosystem ‘disservice,'” said Mary Lusk, a UF/IFAS assistant professor of soil and water sciences. “Globally, we expect that as urbanization continues, there will be more and more of these small human-made ponds in urban landscapes.”

This research will inform scientists’ attempts to estimate how much carbon is entering the atmosphere from these ponds on a regional basis, said Lusk, a faculty member at the UF/IFAS Gulf Coast Research and Education Center.

“Then, once people start to understand that better, we hope they will take stormwater ponds into account for policies related to carbon control,” she said. “Stormwater ponds are everywhere in Florida. But they are understudied in terms of how they are impacting local ecosystems. Because they are human-made parts of the landscape, they sort of get overlooked, and people might assume they’re not very important ecologically.”

The sheer number of ponds compelled Lusk to study if they could have larger environmental effects than people think. She originally wanted to focus on nitrogen and phosphorus in ponds, but one of her graduate students, Audrey Goeckner, wanted to study carbon.

“When I learned that I had the chance to work in stormwater ponds, similar to what I had grown up in around in my neighborhood, I immediately asked myself, well what about these little urban ponds? How do they compare to other aquatic ecosystems?” asked Goeckner, now a Ph.D. student in soil and water sciences on the main UF/IFAS campus in Gainesville. “Turns out that despite their small size,

they can rapidly store and process carbon, which adds up when you consider how many of them exist in developed landscapes and how many continue to be built.”

For the study, done as part of her master’s thesis at GCREC, Goeckner designed a way to measure the amount of carbon leaving ponds. Although Goeckner studied ponds in Manatee County, her findings hold implications for pond carbon emissions globally.

Goeckner took two canoes (attached to each other) into the ponds. She and a lab technician each sat in one canoe to balance the weight. Goeckner then collected muck from the bottom of the ponds and measured the depth of muck above a sandy layer of sediment, indicating when the pond was constructed and the amount of organic carbon stored in it.

That’s how Goeckner found the amount of carbon buried in the ponds.

Secondly, she modified a chamber that is normally used to measure greenhouse gases — carbon dioxide and methane — from soil. Instead, Goeckner used the chamber to measure these gases from the surface of the ponds.

She found the quantity of these gases that escapes from the ponds each year, and then compared carbon stored in the pond muck vs. carbon lost via gaseous loss. As a result, scientists now know that ponds give off more carbon than they store and that the amount lost changes over the lifetime of a pond.

As Florida continues to grow, it’s going to become more urbanized. With new development often comes new stormwater ponds, which are not as good at storing carbon as older ones, Lusk said.

As ponds age, their sediment and biogeochemical properties may promote the amount of carbon stored, rather than emitted as a gas, Goeckner said. That translates to better storage efficiency of organic carbon that enters the water.

“Our results suggest that when they’re new, they emit large proportions of carbon from the landscape and potentially increase storage over time,” Lusk said. “This means the older ponds are doing less of an ecosystem disservice to us than the younger ponds. But if you think about the rate of new housing development in Florida, and how fast new stormwater ponds are being built in all that new development, it means we will always have a fresh new batch of young ponds that are just pumping carbon out to the atmosphere.”

That’s why a team of researchers, including one at the University of Missouri, utilized a motion-sensor video game, Recovery Rapids, to allow patients recovering from a stroke to improve their motor skills and affected arm movements at home while checking in periodically with a therapist via telehealth.

The researchers found the game-based therapy led to improved outcomes similar to a highly regarded form of in-person therapy, known as constraint-induced therapy, while only requiring one-fifth of the therapist hours. This approach saves time and money while increasing convenience and safety as telehealth has boomed in popularity during the COVID-19 pandemic.

“As an occupational therapist, I have seen patients from rural areas drive more than an hour to come to an in-person clinic three to four days a week, where the rehab is very intensive, taking three to four hours per session, and the therapist must be there the whole time,” said Rachel Proffitt, assistant professor in the MU School of Health Professions. “With this new at-home gaming approach, we are cutting costs for the patient and reducing time for the therapist while still improving convenience and overall health outcomes, so it’s a win-win. By saving time for the therapists, we can also now serve more patients and make a broader impact on our communities.”

Traditional rehab home exercises tend to be very repetitive and monotonous, and patients rarely adhere to them. The Recovery Rapids game helps patients look forward to rehabilitation by completing various challenges in a fun, interactive environment, and the researchers found that the patients adhered well to their prescribed exercises.

“The patient is virtually placed in a kayak, and as they go down the river, they perform arm motions simulating paddling, rowing, scooping up trash, swaying from side to side to steer, and reaching overhead to clear out spider webs and bats, so it’s making the exercises fun,” said Rachel Proffitt, assistant professor in the MU School of Health Professions. “As they progress, the challenges get harder, and we conduct check-ins with the participants via telehealth to adjust goals, provide feedback and discuss the daily activities they want to resume as they improve.”

Nearly 800,000 Americans have a stroke each year according to the CDC, and two-thirds of stroke survivors report they cannot use their affected limbs to do normal daily activities, including making a cup of coffee, cooking a meal or playing with one’s grandchildren.

“I am passionate about helping patients get back to all the activities they love to do in their daily life,” Proffitt said. “Anything we can do as therapists to help in a creative way while saving time and money is the ultimate goal.”

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Materials provided by University of Missouri-Columbia. Note: Content may be edited for style and length.

A team led by Roya Zandi, a professor of physics and astronomy at the University of California, Riverside, has developed a theory and performed a series of simulations that may help explain how a virus finds its native genome and how capsids form around it and not around other RNAs in the cell.

“A better understanding of how capsids form is of vital importance to material scientists and a crucial step in the design of engineered nano-shells that could serve as vehicles for delivering drugs to specific targets in the body,” Zandi said.

The researchers’ work, published in ACS Nano, shows that the interplay of the mechanical properties of proteins, the size of the genome, and the strength of the interaction between the genome and capsid proteins can significantly modify the symmetry, structure, and stability of the capsid.

When a virus enters a cell, the capsid breaks open to release the genome, which then uses the cell’s reproductive machinery to replicate. The newly formed genomes begin to acquire their capsids, a process mainly driven by the attractive electrostatic interaction between the positive charges on capsid proteins and the negative charges on the genomes. But how the virus selects and packages its native RNA inside the crowded environment of a host cell cytoplasm in the presence of many nonviral RNA and other polymers has remained a mystery.

The simulations run by Zandi’s team show that capsid proteins could, in theory, pick any nonviral genome to encapsulate. But the viral genome, she said, is best suited for capsid proteins to form a shell around due to an interplay of energies at the molecular level.

“The stress distribution of the capsid proteins is lower when the capsids encapsulate their own genome, the one for which they were coded,” Zandi said. “The energy of the whole system is lower. While smaller nonviral RNAs are available in the cell in plenty, the capsid proteins are inclined toward forming a shell around a viral RNA because the resulting soccer ball-like shell has a lower stress distribution.”

Zandi said the work lays out a systematic comparison of theory and experiments, which will allow a better understanding of the role of RNA in the capsid assembly pathway, stability, and structure.

“A deeper understanding of the role of the genome in virus assembly mechanisms could lead to design principles for alternative antivirals,” she said.

The new work is an early step in understanding viral assembly. The process is not well understood because viruses measure in nanometers and the assembly occurs in milliseconds.

“Theoretical work and simulations are necessary to understand how a virus grows,” Zandi said.

Zandi was joined in the research by graduate student Sanaz Panahandeh at UCR; Siyu Li at Songshan Lake Materials Laboratory in China; and Bogdan Dragnea at Indiana University, Bloomington. Li is a former graduate student at UCR.

The research was funded by the National Science Foundation.

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Materials provided by University of California – Riverside. Original written by Iqbal Pittalwala. Note: Content may be edited for style and length.