A new study suggests that stem cells are able to integrate cues from their surroundings and coordinate their behavior across the tissue through networks of vasculature in their close vicinity.

Rockefeller scientists found that lymphatic capillaries — fine vessels that transport immune cells and drain fluids from tissues — represent a signaling hub that communicates with stem cells to regulate their activity. With molecular guidance from the lymphatics, the stem cells produce daughter cells to repopulate the intestinal lining or self-renew to restock the stem cell reserve.

The findings, published in the journal Cell Stem Cell, provide new insights about primary intestinal components whose disrupted communication may contribute to intestinal disorders, such as inflammatory bowel disease. “The key to treating these diseases will be to figure out who talks to whom in this ecosystem and how we can reset the communication networks,” says Rachel Niec, a clinical scholar in the laboratory of Elaine Fuchs.

Communications in the crypt

The intestinal stem cells reside in so-called crypts, found at the base of densely packed indentations in the intestinal lining. The stem cells may renew and stay in the crypt, or differentiate into specialized cells, which then migrate out of the crypt to replenish the gut lining. “To understand how stem cells balance self-renewal with differentiation, we needed a more complete picture of crypt niches,” says Marina Schernthanner, a graduate student in the Fuchs lab.

To zoom in on the crypt, the team used a suite of techniques, including single-cell and spatial transcriptomics, which allowed them to identify cell types at specific locations and study their signaling molecules. The results showed that lymphatic capillaries, which form an intimate connection with the stem cells in the crypt, produce a number of proteins known to be important for stem cell functioning.

One previously underappreciated protein, REELIN, emerged as a top candidate for mediating communications between lymphatics and stem cells. By manipulating the amount of REELIN in lab-grown intestinal organoid cultures in some experiments and genetically suppressing it in mice in others, the researchers found that REELIN directly governs the regenerative behavior of intestinal stem cells.

The involvement of the lymphatic system in stem cell functioning is a relatively new concept. A previous study by the Fuchs team revealed that lymphatics are also closely involved with stem cells of the skin and play a key role in hair regeneration. There, however, it is the hair follicle stem cells that signal to lymphatic capillaries. By controlling their interactions with lymphatics, the stem cells synchronize hair regeneration across the tissue. “This suggests that lymphatics may be a conserved feature of stem cell niches, but their relationship to stem cells are likely tailored around the needs of each tissue,” Niec says.

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A new study suggests that indeed, ants as a group behave similar to networks of neurons in a brain.

Rockefeller’s Daniel Kronauer and postdoctoral associate Asaf Gal developed a new experimental setup to meticulously analyze decision-making in ant colonies. As reported in the Proceedings of the National Academy of Sciences, they found that when a colony evacuates due to rising temperatures, its decision is a function of both the magnitude of the heat increase and the size of the ant group.

The findings suggest that ants combine sensory information with the parameters of their group to arrive at a group response — a process similar to neural computations giving rise to decisions.

“We pioneered an approach to understand the ant colony as a cognitive-like system that perceives inputs and then translates them into behavioral outputs,” says Kronauer, head of the Laboratory of Social Evolution and Behavior. “This is one of the first steps toward really understanding how insect societies engage in collective computation.”

A new paradigm

At its most basic level, decision-making boils down to a series of computations meant to maximize benefits and minimize costs. For instance, in a common type of decision-making called sensory response thresholding, an animal has to detect sensory input like heat past a certain level to produce a certain costly behavior, like moving away. If the rise in temperature isn’t big enough, it won’t be worth it.

Kronauer and Gal wanted to investigate how this type of information processing occurs at the collective level, where group dynamics come into play. They developed a system in which they could precisely perturb an ant colony with controlled temperature increases. To track the behavioral responses of individual ants and the entire colony, they marked each insect with different colored dots and followed their movements with a tracking camera.

As the researchers expected, colonies of a set size of 36 workers and 18 larvae dependably evacuated their nest when the temperature hit around 34 degrees Celsius. This finding makes intuitive sense, Kronauer says, because “if you become too uncomfortable, you leave.”

However, the researchers were surprised to find that the ants were not merely responding to temperature itself. When they increased the size of the colony from 10 to 200 individuals, the temperature necessary to trigger the decision to vacate increased. Colonies of 200 individuals, for example, held out until temperatures soared past 36 degrees. “It seems that the threshold isn’t fixed. Rather, it’s an emergent property that changes depending on the group size,” Kronauer says.

Individual ants are unaware of the size of their colony, so how can their decision depend on it? He and Gal suspect that the explanation has to do with the way pheromones, the invisible messengers that pass information between ants, scale their effect when more ants are present. They use a mathematical model to show that such a mechanism is indeed plausible. But they do not know why larger colonies would require higher temperatures to pack up shop. Kronauer ventures that it could simply be that the larger the colony’s size, the more onerous it is to relocate, pushing up the critical temperature for which relocations happen.

In future studies, Kronauer and Gal hope to refine their theoretical model of the decision-making process in the ant colony by interfering with more parameters and seeing how the insects respond. For example, they can tamper with the level of pheromones in the ants’ enclosure or create genetically altered ants with different abilities to detect temperature changes. “What we’ve been able to do so far is to perturb the system and measure the output precisely,” Kronauer says. “In the long term, the idea is to reverse engineer the system to deduce its inner workings in more and more detail.”

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The work, led by UAF Geophysical Institute postdoctoral researcher Alex Witsil, was published recently in the journal Geophysical Research Letters.

Witsil, at the Geophysical Institute’s Wilson Alaska Technical Center, and colleagues created a library of synthetic infrasound explosion signals to train computers in recognizing the source of an infrasound signal. Infrasound is at a frequency too low to be heard by humans and travels farther than high-frequency audible waves.

“We used modeling software to generate 28,000 synthetic infrasound signals, which, though generated in a computer, could hypothetically be recorded by infrasound microphones deployed hundreds of kilometers from a large explosion,” Witsil said.

The artificial signals reflect variations in atmospheric conditions, which can alter an explosion’s signal regionally or globally as the sound waves propagate. Those changes can make it difficult to detect an explosion’s origin and type from a great distance.

Why create artificial sounds of explosions rather than use real-world examples? Because explosions haven’t occurred at every location on the planet and the atmosphere constantly changes, there aren’t enough real-world examples to train generalized machine-learning detection algorithms.

“We decided to use synthetics because we can model a number of different types of atmospheres through which signals can propagate,” Witsil said. “So even though we don’t have access to any explosions that happened in North Carolina, for example, I can use my computer to model North Carolina explosions and build a machine-learning algorithm to detect explosion signals there.”

Today, detection algorithms generally rely on infrasound arrays consisting of multiple microphones close to each other. For example, the international Comprehensive Test Ban Treaty Organization, which monitors nuclear explosions, has infrasound arrays deployed worldwide.

“That’s expensive, it’s hard to maintain, and a lot more things can break,” Witsil said.

Witsil’s method improves detection by making use of hundreds of single-element infrasound microphones already in place around the world. That makes detection more cost-effective.

The machine-learning method broadens the usefulness of single-element infrasound microphones by making them capable of detecting more subtle explosion signals in near real-time. Single-element microphones currently are useful only for retroactively analyzing known and typically high-amplitude signals, as they did with January’s massive eruption of the Tonga volcano.

Witsil’s method could be deployed in an operational setting for national defense or natural hazards mitigation.

This work was funded by the Defense Threat Reduction Agency.

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Materials provided by University of Alaska Fairbanks. Original written by Rod Boyce. Note: Content may be edited for style and length.

“We found that in some children, illness with COVID-19 is associated with reporting persistent symptoms after 3 months,” said Principal Investigator Stephen Freedman, MDCM, MSc, with the Cumming School of Medicine at University of Calgary, and Alberta Health Services. “Our results suggest that appropriate guidance and follow-up are needed, especially for children at high risk for long COVID.”

The study included 1,884 children with COVID-19 who had 90-day follow-up. Long COVID was found in nearly 10 percent of hospitalized children and 5 percent in children discharged from the ED.

“Reported rates of long COVID in adults are substantially higher than what we found in children,” said Co-Principal Investigator Nathan Kuppermann, MD, MPH, from University of California, Davis School of Medicine, Sacramento. “Our findings can inform public health policy decisions regarding COVID-19 mitigation strategies for children and screening approaches for long COVID among those with severe infections.”

The most reported persistent symptoms in children were fatigue or weakness, cough, difficulty breathing or shortness of breath.

“Our finding that children who had multiple COVID-19 symptoms initially were at higher risk for long COVID is consistent with studies in adults,” said Co-Principal Investigator Todd Florin, MD, MSCE, from Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University Feinberg School of Medicine. “Unfortunately, there are no known therapies for long COVID in children and more research is needed in this area. However, if symptoms are significant, treatment targeting the symptoms is most important. Multidisciplinary care is warranted if symptoms are impacting quality of life.”

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Climate change accelerated by excess CO₂ emissions has been a major concern over the past few years. To deal with this problem, technologies that can not only reduce and remove excess CO₂ emissions but also transform them into value-added chemicals are being developed. One such method is the hydrogenation of CO₂ using renewable hydrogen to produce alternative fuels.

Over the years different strategies have been developed to improve CO₂ hydrogenation in the presence of metallic catalysts. The most promising among them is nonthermal plasma (NTP). It promotes hydrogenation of CO₂ beyond the thermodynamic limit even at low temperatures without deactivating metallic catalysts, which are vulnerable to higher temperatures. Despite the rising popularity of this technique, the interactions between the NTP-activated species and metallic catalysts are still not well understood.

Fortunately, a team of researchers from Tokyo Institute of Technology (Tokyo Tech), Japan, led by Prof. Tomohiro Nozaki, devised a study to overcome this gap in understanding. In their recent breakthrough, published in the Journal of the American Chemical Society, the researchers revealed the reaction dynamics for NTP-assisted CO₂ hydrogenation on the surface of Pd₂Ga/SiO₂ alloy catalysts that lead to the formation of formate. Prof Nozaki explains “Reaction mechanisms like Eley-Rideal or E-R pathway have been proposed to explain efficient CO₂ conversion at lower temperatures and the activation energy for this reaction decreases dramatically. Moreover, NTP produces a copious amount of vibrationally activated CO₂ which is the key to enhancing CO₂ conversion beyond the thermal equilibrium.”

The team investigated the reactions between NTP activated CO₂ and Pd₂Ga/SiO₂ alloy catalysts in a fluidized-bed dielectric barrier discharge reactor  and compared them to conventional thermal catalysis. The results revealed that the CO₂ conversion into formate was more than two-fold in the case of NTP-assisted hydrogenation when compared to thermal conversion. To further establish the mechanics of the mentioned conversion, the scientists adopted in situ spectroscopic analysis and density functional theory (DFT) calculations.

The results revealed that the NTP activation gave rise to vibrationally excited CO₂ molecules which directly react with hydrogen atoms adsorbed by the Pd sites on the catalyst via the E-R pathway. One of the O atoms from the reacted species then got adsorbed at the neighboring Ga site resulting in the formation of monodentate-formate or m-HCOO. The DFT calculations also deduced a decomposition pathway for the same m-HCOO species.

This experimental-theoretical study showed that NTP can promote CO₂ hydrogenation to limits those conventional thermal methods can hardly reach. It also provided mechanistic insights into NTP activated CO₂ and catalyst interaction, which can be utilized to develop better catalysts and improve the hydrogenation process. “With our research, we wanted to accelerate the waste to wealth initiative. Capturing CO₂ and using it as feedstock for synthesis of fuels and valuable chemicals will not only help us deal with climate problem but also slow down fossil fuel depletion to some extent,” concludes Prof. Nozaki.

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Materials provided by Tokyo Institute of Technology. Note: Content may be edited for style and length.