Aiming to shorten recovery times, an Osaka Metropolitan University-led research group is focusing on plasma irradiation as a treatment method to speed up bone healing.

The Department of Orthopedic Surgery’s Kosuke Saito, a graduate student in the Graduate School of Medicine, Associate Professor Hiromitsu Toyoda, and Professor Hiroaki Nakamura, and Graduate School of Engineering Professor Jun-Seok Oh were among the researchers who used laboratory rats for their experiment.

The researchers broke the legs of the rats in two ways. One group of 24 rats had normal fractures that are generally easy to heal. The other group of 20 rats had fractures known as non-union ones where healing is usually prolonged or does not happen. Some were then irradiated with non-thermal atmospheric-pressure plasma, which didn’t offer the normal fracture group any significant advantages but boosted the healing and recovery time of the rats with non-union fractures. The strength of the healed areas of the irradiated non-union rats was also about 3.5 times stronger than that of the nonirradiated ones.

Furthermore, in vitro study of pre-osteoblastic cells irradiated with the plasma for 5 to 15 seconds showed that the activity of a protein that is an indicator of osteoblast differentiation increased, indicating that maturation of these bone-forming cells was progressing.

“Collaboration between the medical and engineering fields creates new medical technologies that have never before existed,” Professor Toyoda declared. “In the future, combining this treatment method with current fracture treatments is expected to contribute to more reliable bone fusion and shorter recovery times.”

Their findings are set for publication inPLOS ONEon April 16, 2024.

The research team, led by scientists at the U.S. National Science Foundation National Center for Atmospheric Research (NSF NCAR), used satellite observations and machine learning techniques to produce a unique database of WUI areas and fires worldwide, dating back about two decades.

The overall number of all fires worldwide has declined, as has the total area burned.

However, the scientists found that the fraction of global fires that occur in WUI areas increased by about 23% from 2005 to 2020. Even more significantly, the global area burned by WUI fires during the same time increased by about 35% as a fraction of all burned areas.

The research found that WUI areas are expanding worldwide, especially in rapidly urbanizing regions in Africa. As newly constructed developments move into areas of wild vegetation, the risk of fires increases. The paper did not focus on the role of climate change, although the authors said the database can help scientists better fingerprint the role of climate change in fires.

WUI areas are generally defined as the location where urban land use and wildland vegetation come into contact or intermingle. Fires in such areas are especially dangerous, both because they imperil large numbers of people and structures and because, by burning manufactured materials instead of vegetation, they emit far more toxins than forest and grassland fires.

“Wildland-urban interface fires are a major concern for many people in the United States and globally, and through this study we now know they have increased in recent years and will likely continue doing so in the future,” said NSF NCAR scientist Wenfu Tang, the lead author of the new paper. “This is important as a first step to looking at emissions from these fires and their impacts on human health.”

Funding for the research came from NOAA. The study was published in Environmental Research Letters.

Constructing a global database

WUI fires have caused catastrophic destruction in recent years, sometimes burning down thousands of buildings and killing 100 or more people. Especially destructive fires include the 2009 Black Saturday bushfires in Australia, which left 173 dead, and the 2017 Pedrosa Grande Fire in Portugal, which killed 66 people. Last year’s Lahaina Fire in Hawaii was the deadliest in the United States in more than a century, killing 100 people and destroying more than 2,200 structures.

To understand more about trends in WUI fires, Tang and her colleagues turned to a global high-resolution map of WUI fires in 2020, which had been created by Franz Schug of the University of Wisconsin-Madison. They also analyzed data about Earth’s surface from NASA’s Moderate Resolution Imaging Spectroradiometer (MODIS) satellite instrument.

By applying machine learning techniques to the map and satellite data, they quantified the relationship of fires with such variables as land cover and population density. They then used those quantitative relationships to generate a global database of WUI areas and WUI fires, going back 20 years at a resolution of 9 kilometers (5.6 miles).

The researchers successfully confirmed the accuracy of the database by comparing it with independent WUI datasets previously developed for a few years within the same time period, including for the continental United States and globally.

In analyzing the new database, the researchers found that WUI areas have grown in all populated continents by 24% from 2001 to 2020, with the largest increase occurring in Africa.

Largely as a result, fires in WUI areas have also become more common. Since 2005, they have increased from 3.5% to 4.3% of all fires. In North America, the WUI fraction of all fire counts is even higher (up to 9%), with WUI fires in 2015-2020 becoming particularly large and more destructive.

“This is the first map of its kind that enables us to look at how WUI fires have been evolving globally over the past two decades,” said NSF NCAR scientist Cenlin He, a co-author of the study. “It shows that WUI fires have increased on every populated continent.”

Even as WUI blazes loom as a greater threat, the scientists noted that fires overall have been on the decline. Since 2005, the total number of fires worldwide decreased by 10%, and the amount of burned areas decreased by 22%, according to satellite observations analyzed in their research.

Tang and her colleagues then turned to the future. They integrated the WUI database with the NSF NCAR-based Community Earth System Model, which simulates global climate and fires, to determine the likely trends in WUI fires through 2030 and 2040.

If WUI areas continue to expand and greenhouse gases continue to be emitted at a high rate, they found that the WUI fraction of burned areas worldwide will likely increase by about 2.6-3.2% by 2040. However, the picture can change somewhat depending on changes in WUI areas and greenhouse gas emissions under different future scenarios, according to their analysis.

“This study is an important step in quantifying WUI fires and how they are changing worldwide,” Tang said. “As WUI areas rapidly expand and WUI fires become more frequent, it is critical to understand the interactions between WUI fires and human activities as well as the impacts of the fires on air quality, human health, and the environment.”

Over the past few years, people have generally become more conscious about the food they consume. Thanks to easier access to information as well as public health campaigns and media coverage, people are more aware of how nutrition ties in with both health benefits and chronic diseases. As a result, there is an ongoing cultural shift in most countries, with people prioritizing eating healthily. In turn, the demand for healthier food options and nutritional supplements is steadily growing.

In line with these changes, Assistant Professor Kyohei Yamashita from Tokyo University of Science (TUS), Japan, has been studying a promising “superfood” called Euglena gracilis for over half a decade. A species of edible microalgae, E. gracilis has a rich nutritional profile, with a unique combination of vitamins, fibers, lipids, and proteins. Like most other photosynthetic plants, E. gracilis also contains carotenoids — natural substances with a wide variety of health benefits.

In a study published in 2023, a research team from TUS found a simple method to efficiently grow E. gracilis in an inexpensive medium (solid or liquid that contains nutrients and is used to grow bacteria) based on tomato juice. Now, in a new study, the researchers have explored a promising technique to make cultured E. gracilis produce carotenoids at a higher rate, rendering it even more nutritious. This study, which was co-authored by Dr. Kengo Suzuki from Euglena Co., Ltd., as well as Professor Tatsuya Tomo and Professor Eiji Tokunaga from TUS, was published in Volume 13, Issue 4 of the journal Plants in February 12, 2024.

The proposed approach is quite straightforward, and so is its rationale. When a plant is exposed to high-intensity light for extended periods of time, it undergoes a light-stress response. This, in turn, can cause the organism to produce molecules that protect it from further light exposure, including carotenoids. Based on these facts, the researchers investigated whether they could induce such a reaction in E. gracilis to enhance its carotenoid content ratio.

To this end, the team ran a series of experiments on multiple batches of cultured E. gracilis. They exposed cultures to light of different wavelengths (or colors) and at different intensities looking for a “reddening reaction,” which is a tell-tale sign of higher carotenoid production in many plant species. Moreover, they also tested a new culture medium based on bonito stock, a soup stock extracted from Katsuobushi, a traditional Japanese dish made from smoked bonito fish.

Interestingly, the researchers found that strong red-light irradiation at 605-660 nm triggered a reddening reaction in E. gracilis when cultured in bonito stock. They also looked at the chemical profiles of the cultures using high-performance liquid chromatography, both at the culture and single-cell level. These analyses revealed that reddened cells not only had a high concentration of diadinoxanthin, the most abundant carotenoid in E. gracilis, but also produced an unidentified xanthophyll-type carotenoid. On top of these, the team also noted that bonito stock cultures grew quicker and reached higher densities than cultures grown on conventional media, and likely produced more types or amounts of carotenoids.

Together, the results of this study could pave the way for an innovative and easily scalable technique for growing nutritious E. gracilis. The method’s simplicity is certainly one of its strengths, as Dr. Yamashita remarks, “Our approach does not involve genetic modifications and could thus be readily adopted by the food industry to expand the use of E. gracilis, both in food and as a nutritional supplement.” Notably, bonito stock is a nutritious food and using it in the culture medium would, therefore, provide additional health benefits.

Aside from its benefits to us humans, growing E. gracilis can also help the environment. “E. gracilis cultivation, which requires relatively few resources, can be a sustainable food resource,” explains Dr. Yamashita. “Our research marks an important step toward the development of new food technologies that contribute to people’s lives from both health and environmental perspectives.“

With the carotenoid market poised to become a multi-billion-dollar industry by 2030, this study will help deepen our understanding of carotenoid biosynthetic pathways, hopefully leading to the development of sustainable practices in the production of nutritional supplements and emerging foods.

Bacterial infections pose significant challenges to agriculture and medicine, especially as cases of antibiotic-resistant bacteria continue to rise. In response, scientists at Texas A&M AgriLife Research are elucidating the ways that bacteria-infecting viruses disarm these pathogens and ushering in the possibility of novel treatment methods.

In their recent study published in Science, Lanying Zeng, Ph.D., a professor, and Junjie Zhang, Ph.D., an associate professor, both in the Texas A&M College of Agriculture and Life Sciences Department of Biochemistry and Biophysics, detailed a precise mechanism by which phages disable bacteria.

The collaborative effort also involved:

• Yiruo Lin, Ph.D., research assistant professor in the Texas A&M College of Engineering Department of Computer Science and Engineering.
• Matthias Koch, Ph.D., assistant professor in the Texas A&M College of Arts and Sciences Department of Biology.
• Zemer Gitai, Ph.D., and Joshua Shaevitz, Ph.D., professors in the Princeton University Department of Molecular Biology and Department of Physics, respectively.
• Yinghao Wu, Ph.D., associate professor in the Albert Einstein College of Medicine Department of Systems and Computational Biology.

Together, the team worked to explain a series of interactions scientists have sought to understand since the early 1970s.

The need for new treatments

Pseudomonas aeruginosa is a type of bacteria that can cause infections in the blood, lungs and occasionally other parts of the body. These infections are especially common in healthcare settings, which often encounter drug-resistant bacteria. According to the Centers for Disease Control and Prevention, there were over 30,000 cases of multi-drug resistant P. aeruginosa infections among hospitalized patients in 2017.

The prevalence of antibiotic-resistant Pseudomonas infections makes them a practical point of focus for phage therapy, a type of treatment method using bacteriophages, or phages, that researchers at the Texas A&M Center for Phage Technology are exploring as an alternative to typical drugs.

Zeng and Zhang, co-directors at the center along with Jason Gill, Ph.D., associate professor in the Department of Animal Science, are exploring the usefulness of phages, even beyond phage therapy, by diving into the structures and mechanisms at play.

Targeting the pilus

One of the factors that allows P. aeruginosa to transmit antimicrobial-resistant genes among each other, as well as move around and create difficult-to-treat structures called biofilms, is an appendage called a pilus, named after the Latin word for spear. These cylindrical structures extend from the surface of bacteria.

Some phages make use of bacterial pili by attaching to them and allowing bacteria to reel the phage to the surface, where the phage can start infecting the bacteria.

In their study in Science, co-first authored by Texas A&M graduate students Jirapat Thongchol and Zihao Yu, the researchers studied this process step by step using fluorescence microscopy, cryogenic-electron microscopy and computational modeling. They observed how a phage called PP7 infects P. aeruginosa by attaching to the pilus, which then retracts and pulls the phage to the cell surface.

At the point of entry for the virus, the pilus bends and snaps off, and the loss of the pilus makes P. aeruginosa much less capable of infecting its own host.

Ongoing research

This work is a continuation of previous research published in 2020, when Zeng’s team found a phage that can similarly break off the pili of E. coli cells, preventing the bacteria from sharing genes among each other — a common way that antibiotic resistance spreads.

From left to right: Lanying Zeng, Ph.D., Junjie Zhang, Ph.D., Zihao Yu and Jirapat Thongchol. Along with others, these researchers at the Texas A&M Center for Phage Technology are searching for solutions to antibiotic-resistant bacterial infections and characterizing phage-bacterium interactions. (Zihao Yu/Texas A&M AgriLife)

The Science study on Pseudomonas is part of the team’s recent suite of research studies. Last month, they published findings in Nature Communications on the interaction between another genus of bacteria, Acinetobacter, and a phage that infects it. Another study, expected to be published next month, will cover a third genus of bacteria and additional phage.

The team’s progress in determining precise protein structures and molecular interactions has been made possible with AgriLife Research’s new cryo-electron microscope, which opened at Texas A&M at the end of 2022 and can resolve structures at the atomic level.

“In our earlier study on E. coli, we did not really explore much about the mechanism,” Zeng said. “In our study of Pseudomonas, we were able to explain much more about what exactly is going on, including the force and speed of pilus detachment, and understand why and how this happens.”

Uses in medicine

The implications of this ongoing research could prove to be important in treating antimicrobial infections. Zhang said doctors wouldn’t need to use phages to kill the bacteria — as is done in phage therapy — but could simply allow the viruses to disarm the bacteria, which may give the immune system the chance to fight the infection on its own or allow doctors to treat patients with lower doses of antibiotics.

“If you simply kill the bacteria, you break the cells, and they’re going to release toxic material from inside the cell into the host,” Zhang said. “Our approach is to use a particular type of phage that disarms the bacteria. We remove their ability to exchange drug-resistance genes or to move around by breaking off this appendage.”

The team of phage scientists said they will continue looking for similar instances of phages dampening the virulence of pathogenic bacteria.

“We’re taking a synergistic approach,” Zhang said. “We’re trying to understand a universal mechanism for this type of phage and how they’re capable of affecting other types of bacteria. That’s the overall aim of our collaborative effort: to try to tackle the problem of multi-drug resistant bacteria.”

At first glance, the star of the new study may not seem particularly impressive: only a few centimetres long, Platynereis dumerilii is a species of polychaete worm that can be found in temperate to tropical coastal waters around the globe; if your goal is to find outstanding animal personalities, surely there are better suited candidates. But that wasn’t the primary goal of the study, which experts from the AWI, the Max Perutz Labs in Vienna, the Universities of Vienna and Oldenburg, and the Katholieke Universiteit Leuven in Belgium contributed to. First and foremost, the researchers were interested in the internal clocks that dictate countless organisms’ daily rhythms.

“Biological timing is important at a number of levels,” explains Kristin Tessmar-Raible, a biologist at the AWI. “The ecological ties between species depend just as much on it as they do on biochemical processes at the cellular level.” But how do organisms’ internal clocks react when human beings warm the climate or use artificial light to turn night into day? “When it comes to marine organisms, we still know very little,” says Sören Häfker, the study’s main author. In this regard, rhythms are especially important in their lives: temperature, available light and food, and various other factors change throughout the day, and the organisms have to respond accordingly. They adapt their behaviour, metabolism, and genetic activity to these external rhythms.

However, it remains unclear whether they’ll be equally successful at doing so in the future. And when their internal clocks no longer match their environment, it can become a matter of survival. “As such, we need a much better understanding of how the rhythms of the oceans are changing and what it will mean for individual species and populations,” the biologist stresses — which means there’s a wealth of reasons to take a closer look at the daily behaviour of Platynereis dumerilii. In fact, for chronobiology, which focuses on organisms’ internal clocks, this distant relative of the dew worm has become one of the most important model species.

In past experiments, the team had noticed how the worms had quite disparate daily rhythms. Among human beings, it’s a familiar phenomenon: early birds rarely turn into night owls, and vice versa. But what about in marine polychaete worms? Are their behavioural differences just random variations or do they also have a personal tact? To find out, the group systematically observed the worms’ daily activities when there was a new moon. What they saw: some individuals became active at exactly the same time every night. In turn, others appeared to be arrhythmic “couch potatoes” that were only occasionally active — plus, there were various “shades of grey” between these two extremes. When the same worms were observed again several weeks later, their behaviour remained largely unchanged: once a couch potato, always a couch potato. “We were very surprised to see how reproducible the individual behavioural rhythms were,” says Tessmar-Raible. “This shows us that even worms have tiny, rhythmic personalities, so to speak.”

More individuality = more resiliency

To gain further insights into these behavioural differences, the group systematically compared the genetic activity in the heads of worms prone to particularly rhythmic and arrhythmic behaviour. Surprisingly, they found that the daily internal clock worked perfectly fine in all specimens, even the arrhythmic “couch potatoes,” and that the number of genes with rhythmic activity was nearly as high as in the “punctual” worms. The wide range of strategies they employ could offer the worms an evolutionary edge, as the experts surmise. After all, they live in a coastal environment with highly variable conditions; as such, lifestyle A might be the best choice for a given spot, while not far away, lifestyle B might be a better fit. In addition, this form of individuality could make them more resilient to major anthropogenic changes — in a transforming world, this diversity increases the chances of at least some worms being able to cope with their new circumstances.

But the study doesn’t just offer new insights into marine rhythms; it also underscores the fact that the processes at work within a given organism aren’t necessarily reflected in its behaviour: even among the couch potato worms, the genetic activity follows a daily rhythm, even if it’s not externally recognisable. And that’s likely true not just for worms, but for human beings as well. “That’s why such findings are also exciting for fields like chronomedicine,” says Tessmar-Raible.

In recent years, there have been intensified and successful efforts to bear patients’ individual daily rhythms in mind in the context of treating them. But, just as with the worms observed, they consist of various components, ranging from behaviour to genetic activity, which can react differently to medications and the timing of when they are administered. Accordingly, especially when it comes to human beings, it is important for chronomedical analyses to consider several different levels — if even worms can be so individualistic, our species is likely no exception.