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Researchers Gain Insights Into How Ultrasmall Bacteria From the Environment Have Adapted to Live Inside Humans

Carly Russell

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The microbes that live inside our mouths, collectively known as the oral microbiome, impact our overall health in many ways that are not yet fully understood. Some bacteria cause inflammation, leading to periodontitis and other systemic diseases, such as cardiovascular disease and diabetes. Other oral organisms have been associated with certain types of cancer. Scientists are working to understand how these microbes interact with one another and our bodies to tease out their individual roles in health and disease.

Credit: Dr. Jing “Janet” Tian, Pediatric Dentist, Peking University Hospital of Stomatology, visiting scholar, The Forsyth Institute.

The microbes that live inside our mouths, collectively known as the oral microbiome, impact our overall health in many ways that are not yet fully understood. Some bacteria cause inflammation, leading to periodontitis and other systemic diseases, such as cardiovascular disease and diabetes. Other oral organisms have been associated with certain types of cancer. Scientists are working to understand how these microbes interact with one another and our bodies to tease out their individual roles in health and disease.

Among the diverse bacterial species living within our mouths is a group belonging to the Candidate Phyla Radiation (CPR). These bugs are especially mysterious because they are ultra-small, adopt a unique symbiotic lifestyle with their host bacteria, and most have yet to be cultured by scientists and studied in the lab. The only bacteria within the CPR to be examined in-depth are a group called TM7, which were cultivated for the first time by Forsyth Institute researcher Dr. Xuesong He in 2014.

In an important step toward better understanding these elusive bacteria, Dr. He and his collaborator, Dr. Jeffrey S. McLean at the University of Washington, have developed a new model system using the first isolated human oral TM7 strain, TM7x, and its host bacterium, Actinomyces odontolyticus. Researchers used the model system to experimentally study these tiny bacteria, testing a hypothesis for how TM7 adapted to live inside humans, and providing empirical data to confirm previous genomic studies. Their findings were published today in the journal Proceedings of the National Academy of Sciences (PNAS).

Scientists have found TM7 in many different environments, including soil, groundwater, and the bodies of other mammals. Studies have shown that while maintaining a remarkably similar genome overall, the TM7 found in human mouths are unique from those in other environments because they have acquired a gene cluster encoding the arginine deiminase system, or ADS.

“This was intriguing to us since there seem to be very few genomic changes that occurred in this group of tiny bacteria with already small genomes as they transitioned from the environment to mammals,” said Dr. McLean.

Researchers hypothesized that TM7 acquired ADS as an evolutionary advantage to help them adapt and survive in the human oral cavity. To test this hypothesis, Dr. Jing “Janet” Tian, first author of the study, used the model system to experimentally investigate the function and impact of ADS on TM7x and its host bacterium. She found that ADS helped TM7x break down arginine, a process that produces the compounds Adenosine triphosphate (ATP) and ammonia. The increased abundance of ATP and ammonia benefitted TM7x by increasing its infectivity, or ability to multiply. It also protected TM7x and its host bacterium from acid stress, a condition that microbes frequently encounter in the human oral cavity due to the acid created when bacteria feed on and metabolize dietary carbohydrates.

Ultimately, the experiment showed TM7x were able to survive in the experimental environment for longer than they could without the addition of arginine, thanks to ADS.

“Most of the current studies on CPR bacteria are based on a culture-independent genomic approach. Using this TM7 bacterial model system, we are able to directly test a hypothesis generated from genome analysis, which helps move the CPR research field from genome-focused studies toward hypothesis-driven studies to better understand their biology,” said Dr. He.

“The production of ammonia through TM7-encoded ADS raises the pH level in the human oral microenvironment, which poses an intriguing question about the role of TM7 in the development of dental caries,” said Dr. Tian, a Pediatric Dentist at Peking University Hospital of Stomatology and visiting scholar at Forsyth. In a previous study of dental caries in children, Dr. Tian found that the abundance of TM7 increased significantly after treatment of the caries. “We think this indicates that TM7 may be more associated with a caries-free state, and we are planning to do more research in this area,” Dr. Tian said.

This study also adds to a growing body of evidence that TM7 bacteria may play a more protective role in oral health than researchers initially thought. For example, abundance of TM7 is found to increase drastically in the mouths of patients with periodontal disease, which led scientists to assume the bacteria contributed to the disease. But a recent study by led by Dr. Batbileg Bor at Forsyth showed the opposite effect—TM7 decreased periodontal inflammation and bone loss in a mouse model.

“We are still in the early stages of understanding how each of the many different types of these ultrasmall parasitic bacteria, which we basically just uncovered within humans, are impacting health and disease,” said Dr. McLean.

“That’s why it’s so important to have a bacterial model system to not only achieve better understanding of the unique lifestyle of TM7, but experimentally test whether the hypotheses based on genomic studies or clinical observation actually stands,” Dr. He said. “Now, we have a manipulatable model system for TM7, which is truly a major advantage.”

Co-authors of the study include: Dr. Jing Tian, Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Key Laboratory of Digital Stomatology; Dr. Daniel R. Utter, Division of Geological and Planetary Sciences, California Institute of Technology; Dr. Lujia Cen, Department of Microbiology, The Forsyth Institute; Dr. Pu-Ting Dong, Department of Microbiology, The Forsyth Institute, and Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine; Dr. Wenyuan Shi, CEO and Chief Scientific Officer, The Forsyth Institute; Dr. Batbileg Bor, Department of Microbiology, The Forsyth Institute; Dr. Man Qin, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Diseases; Jeffrey S. McLean, Department of Periodontics, University of Washington; and Dr. Xuesong He, Department of Microbiology, The Forsyth Institute, and Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine.

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Article: bioengineer.org

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UNLV Research: No, the Human Brain Did Not Shrink 3,000 Years Ago

Carly Russell

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Did the 12th century B.C.E. — a time when humans were forging great empires and developing new forms of written text — coincide with an evolutionary reduction in brain size? Think again, says a UNLV-led team of researchers who refute a hypothesis that’s growing increasingly popular among the science community.

Did the 12th century B.C.E. — a time when humans were forging great empires and developing new forms of written text — coincide with an evolutionary reduction in brain size? Think again, says a UNLV-led team of researchers who refute a hypothesis that’s growing increasingly popular among the science community.

Last year, a group of scientists made headlines when they concluded that the human brain shrank during the transition to modern urban societies about 3,000 years ago because, they said, our ancestors’ ability to store information externally in social groups decreased our need to maintain large brains. Their hypothesis, which explored decades-old ideas on the evolutionary reduction of modern human brain size, was based on a comparison to evolutionary patterns seen in ant colonies.

Not so fast, said UNLV anthropologist Brian Villmoare and Liverpool John Moores University scientist Mark Grabowski.

In a new paper published last week in Frontiers in Ecology and Evolution, the UNLV-led team  analyzed the dataset that the research group from last year’s study used and dismissed their findings.

“We were struck by the implications of a substantial reduction in modern human brain size at roughly 3,000 years ago, during an era of many important innovations and historical events — the appearance of Egypt’s New Kingdom, the development of Chinese script, the Trojan War, and the emergence of the Olmec civilization, among many others,” Villmoare said. 

“We re-examined the dataset from DeSilva et al. and found that human brain size has not changed in 30,000 years, and probably not in 300,000 years,” Villmoare said. “In fact, based on this dataset, we can identify no reduction in brain size in modern humans over any time-period since the origins of our species.” 

Key Takeaways

The UNLV research team questioned several of the hypotheses that DeSilva et. al gleaned from a dataset of nearly 1,000 early human fossil and museum specimens, including:

The UNLV team says the rise of agriculture and complex societies occurred at different times around the globe — meaning there should be variation in timing of skull changes seen in different populations. However, DeSilva’s dataset sampled only 23 crania from the timeframe critical to the brain shrinkage hypothesis and lumped together specimens from locations including England, China, Mali, and Algeria. 
The dataset is heavily skewed because more than half of the 987 skulls examined represent only the last 100 years of a 9.8-million-year span of time — and therefore don’t give scientists a good idea of how much cranial size has changed over time. 
Multiple hypotheses on causes of reduction in modern human brain size need to be reassessed if human brains haven’t actually changed in size since the arrival of our species.

Publication Details

“Did the transition to complex societies in the Holocene drive a reduction in brain size? A reassessment of the DeSilva et al. (2021) hypothesis” was published July 29 in Frontiers in Ecology and Evolution.

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Growing Cereal Crops With Less Fertilizer

Carly Russell

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Researchers at the University of California, Davis, have found a way to reduce the amount of nitrogen fertilizers needed to grow cereal crops. The discovery could save farmers in the United States billions of dollars annually in fertilizer costs while also benefiting the environment.

Researchers at the University of California, Davis, have found a way to reduce the amount of nitrogen fertilizers needed to grow cereal crops. The discovery could save farmers in the United States billions of dollars annually in fertilizer costs while also benefiting the environment.

The research comes out of the lab of Eduardo Blumwald, a distinguished professor of plant sciences, who has found a new pathway for cereals to capture the nitrogen they need to grow.

The discovery could also help the environment by reducing nitrogen pollution, which can lead to contaminated water resources, increased greenhouse gas emissions and human health issues. The study was published in the journal Plant Biotechnology.

Nitrogen is key to plant growth, and agricultural operations depend on chemical fertilizers to increase productivity. But much of what is applied is lost, leaching into soils and groundwater. Blumwald’s research could create a sustainable alternative.

“Nitrogen fertilizers are very, very expensive,” Blumwald said. “Anything you can do to eliminate that cost is important. The problem is money on one side, but there are also the harmful effects of nitrogen on the environment.”

Blumwald’s research centers on increasing the conversion of nitrogen gas in the air into ammonium by soil bacteria — a process known as nitrogen fixation.

Legumes such as peanuts and soybeans have root nodules that can use nitrogen-fixing bacteria to provide ammonium to the plants. Cereal plants like rice and wheat don’t have that capability and must rely on taking in inorganic nitrogen, such as ammonia and nitrate, from fertilizers in the soil.

“If a plant can produce chemicals that make soil bacteria fix atmospheric nitrogen gas, we could modify the plants to produce more of these chemicals,” Blumwald said. “These chemicals will induce soil bacterial nitrogen fixation and the plants will use the ammonium formed, reducing the amount of fertilizer used.”

Blumwald’s team used chemical screening and genomics to identify compounds in rice plants that enhanced the nitrogen-fixing activity of the bacteria.

Then they identified the pathways generating the chemicals and used gene editing technology to increase the production of compounds that stimulated the formation of biofilms. Those biofilms contain bacteria that enhanced nitrogen conversion. As a result, nitrogen-fixing activity of the bacteria increased, as did the amount of ammonium in the soil for the plants.

“Plants are incredible chemical factories,” he said. “What this could do is provide a sustainable alternative agricultural practice that reduces the use of excessive nitrogen fertilizers.”

The pathway could also be used by other plants. A patent application on the technique has been filed by the University of California and is pending.  

Dawei Yan, Hiromi Tajima, Howard-Yana Shapiro, Reedmond Fong and Javier Ottaviani from UC Davis contributed to the research paper, as did Lauren Cline from Bayer Crop Science. Ottaviani is also a research associate at Mars Edge.

The research was funded by the Will W. Lester Endowment. Bayer Crop Science is supporting further research on the topic.

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Illinois Tech ‘spinout’ Startup Influit Energy Has Created the World’s First Rechargeable, Safe, Electric Fuel

Carly Russell

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CHICAGO, Aug. 5, 20222—It was only a matter of time—before Influit Energy would need to hire more scientists, before the 2,100-square-foot lab space that the company occupies in Chicago’s West Loop neighborhood would grow too small, and before the three co-founders of the startup whose history is inextricably linked to Illinois Institute of Technology would be ready to publicly disclose what they have created: the world’s first rechargeable, safe, electric fuel.

CHICAGO, Aug. 5, 20222—It was only a matter of time—before Influit Energy would need to hire more scientists, before the 2,100-square-foot lab space that the company occupies in Chicago’s West Loop neighborhood would grow too small, and before the three co-founders of the startup whose history is inextricably linked to Illinois Institute of Technology would be ready to publicly disclose what they have created: the world’s first rechargeable, safe, electric fuel.

“We have created a new type of flow battery that is predicated upon a composite material that we invented, which is a nanofluid where the nanoparticles are battery-active materials, which we called nanoelectrofuel, or NEF,” says John Katsoudas (M.S. PHYS ’03), co-founder and CEO of Influit Energy. “All of the technology has come together—we have a crystal-clear path before us.”

Katsoudas calls Influit Energy a “spinout” of Illinois Tech. Leading the company alongside him are two co-founders: Elena Timofeeva, chief operating officer, director of research and development, and a research associate professor of chemistry at Illinois Tech, and Carlo Segre, chief technology officer, chief financial officer, and a professor of physics at Illinois Tech. Segre is also director of the Center for Synchrotron Radiation Research and Instrumentation at Illinois Tech, which operates two sectors of the Advanced Photon Source at Argonne National Laboratory, a resource that Influit Energy occasionally utilizes.

“[Influit Energy’s research] started back in 2009 as a basic science investigation when we were at Illinois Tech and Argonne National Laboratory, and we have taken our technology from basic science development, to applied science, to building prototypes, and now our first product development,” Katsoudas says.

The United States government has also played a critical role in Influit Energy’s growth, awarding the company more than $10 million in contracts to fund the design and fabrication of NEF flow battery prototypes that will allow several agencies to utilize Influit Energy’s batteries in electric vehicles and aircraft.

“The unique high-energy density liquid format of the NEF flow batteries allows use of the same fluids in different devices, meaning fluid, charged at the recharging station from renewable energy sources or a grid, can be used to rapidly refuel vehicles, or for stationary storage and other large portable applications,” Timofeeva says. “Discharged fluid can be returned to a recharge/refuel station for recharging or be charged inside the device by plugging into the power source.”

The company’s current client roster includes NASA, the U.S. Department of Defense’s Defense Advanced Research Project Agency (DARPA), and two grant-awarding programs operated by the U.S. Air Force: AFWERX, a team of innovators fostering collaborations across the military, academia, and industry, and the Small Business Innovation Research program (AFRL SBIR).

“We are using multiple small business innovation grants to demonstrate different elements of this closed loop energy ecosystem,” Segre says. “It takes time when you’re trying to do something transformational and new like this, and you have to not overreach, but ultimately, we’re moving toward the same goal—to actually get technology commercialization.”

Five separate projects funded by the government have been strategically designed by Influit Energy to work together as components of a closed loop energy ecosystem that will one day be able to be commercialized more broadly.

“Everything we’re doing right now is geared toward the specific goal of developing what we call the closed-loop energy cycle, whereby your batteries are not solid materials, they are liquids. You can treat the battery as a fuel that gets pumped in to mobility devices—cars, trucks, airplanes, anything that needs to be electrified,” Katsoudas says. “Every one of our contracts is funding a different aspect of the totality development of that ecosystem.”

The fuel utilized by this new system can be charged using either renewable energy or an electrical grid.

“Components of such ecosystems are batteries for devices like cars and electric utility vehicles funded by DARPA as of now; a refueling nozzle and control system, funded by AFWERX; and a charger for fast charging of the fluids, funded by NASA,” Timofeeva says.

Influit Energy has two separate projects underway with DARPA. One is focused on demonstrating the effectiveness of the batteries in a utility electric vehicle, and the other is a study looking at how to optimize and scale up the manufacturing of the NEF batteries. The goal is to reduce the mass and volume of the batteries.

“The fifth project is related to the development of [second-generation nanoelectrofuel] and funded by AFRL SBIR funding,” Timofeeva says. “This new second generation of NEF chemistry in our unique and proprietary nanofluid format will ultimately provide a four-to-five-times increase in energy density compared to state-of-the art [lithium-ion] batteries and could meet Air Force needs and demand with significantly improved energy density, increased operating temperature range, no fire/explosion hazard, and are made of inexpensive, domestically sourced, Earth-abundant materials.”

Because the fluid in the batteries can be recharged in any location using whatever charging mechanisms are available in that market, Katsoudas envisions tremendous growth and opportunity for the use of Influit Energy’s batteries in the future.

“That in a nutshell is what Influit Energy is going after, and every one of the contracts that we have is geared toward,” he says. “[Each of our sponsors are] funding a different section of the vision. The neat thing is that, from Influit Energy’s perspective, they’re funding this complete vision, pieces of it. For [each of the funding agencies], they’re getting a specific pain point addressed that is specific to each of our sponsors, so it’s sort of a win-win-win. And effectively that’s why we’re going to win this—the complete and total electrification of transportation, the electrification of transportation that doesn’t crash the grid, and the distribution of energy that doesn’t cost us to have to rebuild trillions of dollars of infrastructure.”

In June of 2022, the Influit team successfully completed their first NEF flow battery testing for the electric utility vehicle, which was demonstrated at a commercialization partner site. Katsoudas also spoke at the South by Southwest festival and a few academic conferences earlier this year about Influit Energy’s work, and is now in conversation with venture capitalists regarding the future of Influit Energy. As contracts continue to accumulate, the company is hiring new scientists and is actively seeking to expand its square footage—from 2,100 square feet to 20,000—through the acquisition of a new lab space. Where the lab will be located remains to be seen. The co-founders hope to stay in Chicago, but say they are also considering opportunities in Austin, Texas.

ILLINOIS INSTITUTE OF TECHNOLOGY

Illinois Institute of Technology, also known as Illinois Tech, is a private, technology-focused research university. Illinois Tech is the only university of its kind in Chicago, and its Chicago location offers students access to the world-class resources of a great global metropolis. It offers undergraduate and graduate degrees in engineering, science, architecture, business, design, human sciences, applied technology, and law. One of 22 institutions that comprise the Association of Independent Technological Universities, Illinois Tech provides an exceptional education centered on active learning, and its graduates lead the state and much of the nation in economic prosperity. Illinois Tech uniquely prepares students to succeed in professions that require technological sophistication, an innovative mindset, and an entrepreneurial spirit. 

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