Scientists have long observed that not-yet-specialized cells move in a way that ensures that cell groups destined for a specific tissue stay together. In 1964, American biologist Malcolm Steinberg proposed that cells with similar adhesiveness move to come in contact with each other to minimize energy use, producing a thermodynamically stable structure. This is known as the differential adhesion hypothesis.

“Many other theoretical works have emphasized the importance of differences in cell-to-cell adhesion for separating cell populations and maintaining the boundaries between them, but this had not yet been demonstrated in living animal epithelial tissues,” says Erina Kuranaga of Tohoku University’s Laboratory for Histogenetic Dynamics, who led the investigations. “Our study showed, for the first time, that cell sorting is regulated by changes in adhesion.”

Kuranaga and her team conducted experiments in fruit fly pupae, finding that a gene, called Toll-1, played a major role in this adhesion process.

As fruit flies develop from the immature larval stage into the mature adult, epithelial tissue-forming cells, called histoblasts, cluster together into several ‘nests’ in the abdomen. Each nest contains an anterior and a posterior compartment. Histoblasts are destined to replace larval cells to form the adult epidermis, the outermost layer that covers the flies. The cells in each compartment form discrete cell populations, so they need to stick together, with a distinct boundary forming between them.

Using fluorescent tags, Kuranaga and her team observed the Toll-1 protein is expressed mainly in the posterior compartment. Its fluorescence also showed a sharp boundary between the two compartments.

Further investigations showed Toll-1 performs the function of an adhesion molecule, encouraging similar cells to stick together. This process keeps the boundary between the two compartments straight, correcting distortions that arise as the cells divide to increase the number.

Interestingly, Toll proteins are best known for recognizing invading pathogens, and little is known about their work beyond the immune system. “Our work improves understanding of the non-immune roles of Toll proteins,” says Kuranaga. She and her team next plan to study the function of other Toll genes in fruit fly epithelial cells.

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As a result, many areas, including the St. Louis region, saw increases in cases in July.

Using mathematical modeling, new interdisciplinary research from the lab of Arye Nehorai, the Eugene & Martha Lohman Professor of Electrical Engineering in the Preston M. Green Department of Electrical & Systems Engineering at Washington University in St. Louis, determines the best course of action when it comes to walking the line between economic stability and the best possible health outcomes.

The group — which also includes David Schwartzman, a business economics PhD candidate at Olin Business School, and Uri Goldsztejn, a PhD candidate in biomedical engineering at the McKelvey School of Engineering — published their findings Dec. 22 in PLOS ONE.

The model indicates that of the scenarios they consider, communities could maximize economic productivity and minimize disease transmission if, until a vaccine were readily available, seniors mostly remained at home while younger people gradually returned to the workforce.

“We have developed a predictive model for COVID-19 that considers, for the first time, its intercoupled effect on both economic and health outcomes for different quarantine policies,” Nehorai said. “You can have an optimal quarantine policy that minimizes the effect both on health and on the economy.”

The work was an expanded version of a Susceptible, Exposed, Infectious, Recovered (SEIR) model, a commonly used mathematical tool for predicting the spread of infections. This dynamic model allows for people to be moved between groups known as compartments, and for each compartment to influence the other in turn.

At their most basic, these models divide the population into four compartments: Those who are susceptible, exposed, infectious and recovered. In an innovation to this traditional model, Nehorai’s team included infected but asymptomatic people as well, taking into account the most up-to-date understanding of how transmission may work differently between them as well as how their behaviors might differ from people with symptoms. This turned out to be highly influential in the model’s outcomes.

People were then divided into different “sub-compartments,” for example age (seniors are those older than 60), or by productivity. This was a measure of a person’s ability to work from home in the case of quarantine measures. To do this, they looked at college degrees as a proxy for who could continue to work during a period of quarantine.

Then they got to work, developing equations which modeled the ways in which people moved from one compartment to another. Movement was affected by policy as well as the decisions an individual made.

Interestingly, the model included a dynamic mortality rate — one that shrunk over time. “We had a mortality rate that accounted for improvements in medical knowledge over time,” said Uri Goldsztejn, a PhD candidate in biomedical engineering. “And we see that now; mortality rates have gone down.”

“For example,” Goldsztejn said, “if the economy is decreasing, there is more incentive to leave quarantine,” which might show up in the model as people moving from the isolated compartment to the susceptible compartment. On the other hand, moving from infectious to recovered was based less on a person’s actions and can be better determined by recovery or mortality rates. Additionally, the researchers modeled the mortality rate as decreasing over time, due to medical knowledge about how to treat COVID-19 becoming better over time.

The team looked at three scenarios, according to Schwartzman. In all three scenarios, the given timeline was 76 weeks — at which time it assumed a vaccine would be available — and seniors remained mostly quarantined until then.

• If strict isolation measures were maintained throughout.
• If, after the curve was flattened, there was a rapid relaxation of isolation measures by younger people to normal movement.
• If, after the curve was flattened, isolation measures were slowly lifted for younger people.

“The third scenario is the case which was the best in terms of economic damage and health outcomes,” he said. “Because in the rapid relaxation scenario, there was another disease spread and restrictions would be reinstated.”

Specifically, they found in the first scenario, there are 235,724 deaths and the economy shrinks by 34%.

In the second scenario, where there was a rapid relaxation of isolation measures, a second outbreak occurs for a total of 525,558 deaths, and the economy shrinks by 32.2%.

With a gradual relaxation, as in the third scenario, there are 262,917 deaths, and the economy shrinks by 29.8%.

“We wanted to show there is a tradeoff,” Nehorai said. “And we wanted to find, mathematically, where is the sweet spot?” As with so many things, the “sweet spot” was not at either extreme — total lockdown or carrying on as if there was no virus.

Another key finding was one no one should be surprised to hear: “People’s’ sensitivity to contagiousness is related to the precautions they take,” Nehorai said. “It’s still critical to use precautions — masks, social distancing, avoiding crowds and washing hands.”

Now, a team of researchers based in Korea has found the mechanism underlying plasticity and, potentially, neurological disorders in adult brains. They published their findings on December 23 in Nature.

“Our findings have profound implications for our understanding of how neural circuits change during learning and memory, as well as in diseases,” said paper author Won-Suk Chung, an assistant professor in the Department of Biological Sciences at KAIST. “Changes in synapse number have strong association with the prevalence of various neurological disorders, such as autism spectrum disorder, schizophrenia, frontotemporal dementia, and several forms of seizures.”

Gray matter in the brain contains microglia and astrocytes, two complementary cells that, among other things, support neurons and synapses. Microglial are a frontline immunity defense, responsible for eating pathogens and dead cells, and astrocytes are star-shaped cells that help structure the brain and maintain homeostasis by helping to control signaling between neurons. According to Professor Chung, it is generally thought that microglial eat synapses as part of its clean-up effort in a process known as phagocytosis.

“Using novel tools, we show that, for the first time, it is astrocytes and not microglia that constantly eliminate excessive and unnecessary adult excitatory synaptic connections in response to neuronal activity,” Professor Chung said. “Our paper challenges the general consensus in this field that microglia are the primary synapse phagocytes that control synapse numbers in the brain.”

Professor Chung and his team developed a molecular sensor to detect synapse elimination by glial cells and quantified how often and by which type of cell synapses were eliminated. They also deployed it in a mouse model without MEGF10, the gene that allows astrocytes to eliminate synapses. Adult animals with this defective astrocytic phagocytosis had unusually increased excitatory synapse numbers in the hippocampus. Through a collaboration with Dr. Hyungju Park at KBRI, they showed that these increased excitatory synapses are functionally impaired, which cause defective learning and memory formation in MEGF10 deleted animals.

“Through this process, we show that, at least in the adult hippocampal CA1 region, astrocytes are the major player in eliminating synapses, and this astrocytic function is essential for controlling synapse number and plasticity,” Chung said.

Professor Chung noted that researchers are only beginning to understand how synapse elimination affects maturation and homeostasis in the brain. In his group’s preliminary data in other brain regions, it appears that each region has different rates of synaptic elimination by astrocytes. They suspect a variety of internal and external factors are influencing how astrocytes modulate each regional circuit, and plan to elucidate these variables.

“Our long-term goal is understanding how astrocyte-mediated synapse turnover affects the initiation and progression of various neurological disorders,” Professor Chung said. “It is intriguing to postulate that modulating astrocytic phagocytosis to restore synaptic connectivity may be a novel strategy in treating various brain disorders.”

At just twenty centimeters long, the least weasel is considered the world’s smallest carnivore alive today. The mammal that researchers at the University of Bonn have now studied is unlikely to have been any bigger. However, the species to which it belongs has long been extinct: Priacodon fruitaensis (the scientific name) lived almost 150 million years ago, at a time when dinosaurs dominated the animal world and the triumph of mammals was still to come.

In their study, the paleontologists from the Institute for Geosciences at the University of Bonn analyzed parts of the upper and lower jaw bones of a fossil specimen. More precisely: its cheek teeth (molars). Because experts can tell a lot from these, not only about the animal’s diet, but also about its position in the family tree. In P. fruitaensis, each molar is barely larger than one millimeter. This means that most of their secrets remain hidden from the unarmed eye.

The researchers from Bonn therefore used a special tomography method to produce high-resolution three-dimensional images of the teeth. They then analyzed these micro-CT images using various tools, including special software that was co-developed at the Bonn-based institute. “Until now, it was unclear exactly how the teeth in the upper and lower jaws fit together,” explains Prof. Thomas Martin, who holds the chair of paleontology at the University of Bonn. “We have now been able to answer that question.”

How did creatures chew 150 million years ago?

The upper and lower jaws each contain several molars. In the predecessors of mammals, molar 1 of the upper jaw would bite down precisely on molar 1 of the lower jaw when chewing. In more developed mammals, however, the rows of teeth are shifted against each other. Molar 1 at the top therefore hits exactly between molar 1 and molar 2 when biting down, so that it comes into contact with two molars instead of one. But how were things in the early mammal P. fruitaensis?

“We compared both options on the computer,” explains Kai Jäger, who wrote his doctoral thesis in Thomas Martin’s research group. “This showed that the animal bit down like a modern mammal.” The researchers simulated the entire chewing motion for both alternatives. In the more original version, the contact between the upper and lower jaws would have been too small for the animals to crush the food efficiently. This is different with the “more modern” alternative: In this case, the cutting edges of the molars slid past each other when chewing, like the blades of pinking shears that children use today for arts and crafts.

Its dentition therefore must have made it easy for P. fruitaensis to cut the flesh of its prey. However, the animal was probably not a pure carnivore: Its molars have cone-shaped elevations, similar to the peaks of a mountain. “Such cusps are particularly useful for perforating and crushing insect carapaces,” says Jäger. “They are therefore also found in today’s insectivores.” However, the combination of carnivore and insectivore teeth is probably unique in this form.

The cusps are also noticeable in other ways: They are practically the same size in all molars. This made the dentition extremely precise and efficient. However, these advantages came at a price: Small changes in the structure of the cusps would probably have dramatically worsened the chewing performance. “This potentially made it more difficult for the dental apparatus to evolve,” Jäger says.

This type of dentition has in fact survived almost unchanged in certain lineages of evolutionary history over a period of 80 million years. At some point, however, its owners became extinct — perhaps because their teeth could not adapt to changing food conditions.

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It’s easiest to understand the emotions of the people around you by taking in all the hints they’re dropping, on purpose or otherwise. Yet when people cover some of their facial expressions, they take some of those cues away.

“We now have this situation where adults and kids have to interact all the time with people whose faces are partly covered, and a lot of adults are wondering if that’s going to be a problem for children’s emotional development,” says Ashley Ruba, a postdoctoral researcher in UW-Madison’s Child Emotion Lab.

The researchers showed more than 80 children, ages 7 to 13, photos of faces displaying sadness, anger or fear that were unobstructed, covered by a surgical mask, or wearing sunglasses. The kids were asked to assign an emotion to each face from a list of six labels. The faces were revealed slowly, with scrambled pixels of the original image falling into their proper place over 14 stages to better simulate the way real-world interactions may require piecing things together from odd angles or fleeting glimpses.

The kids were correct about the uncovered faces as often as 66 percent of the time, well above the odds (about 17 percent) of guessing one correct emotion from the six options. With a mask in the way, they correctly identified sadness about 28 percent of the time, anger 27 percent of the time, and fear 18 percent of the time.

“Not surprisingly, it was tougher with parts of the faces covered. But even with a mask covering the nose and mouth, the kids were able to identify these emotions at a rate better than chance,” says Ruba, who published results today in the journal PLOS ONE with co-author Seth Pollak, a UW-Madison psychology professor.

Variations in the results reflect differences in the way emotional information is conveyed by the face. Sunglasses made anger and fear difficult to identify, suggesting the eyes and eyebrows are important to those facial expressions. Fear, often confused with surprise, was also the trickiest for children to spot behind a mask — which may have complicated matters by covering clues like surprise’s signature mouth shape. :O

If children can do better than guessing at emotions even with a mask in place, they’re likely to do even better in real-life situations.

“Emotions aren’t conveyed solely through your face,” Ruba says. “Vocal inflections, the way that someone positions their body, and what’s going on around them, all that other information helps us make better predictions about what someone is feeling.”

It all adds up to kids growing in their emotional capabilities, even if some of their interactions with others are happening through face coverings.

“I hope this settles some nerves,” Ruba says. “Kids are really resilient. They’re able to adjust to the information they’re given, and it doesn’t look like wearing masks will slow down their development in this case.”

This research was supported by grants from the National Institutes of Health (R01-MH61285, U54-HD090256, T32-MH018931).

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Materials provided by University of Wisconsin-Madison. Original written by Chris Barncard. Note: Content may be edited for style and length.

The study, published in PLOS ONE, also reveals that Victorian weedy seadragons may form a subspecies which has implications for conservation management. The researchers recommend that, as a precautionary approach, these distinct populations be managed separately by each state.

Lead investigator Dr Selma Klanten, from the University of Technology Sydney (UTS) Fish Ecology Laboratory, said that despite the public popularity of these fish few scientific studies exist.

“The research aimed to understand the genetic structure and diversity of weedy seadragon populations along Australia’s east coast,” Dr Klanten said.

“This is important because like all sygnathids, seadragons are endemic to temperate Australia. As adults they might only move 50-500 metres away from where they were born. This can make them susceptible to loss of habitat and changing environmental conditions.

“Although ‘weedies’ aren’t listed as endangered, there is concern that populations are in decline and recent surveys confirm this. If numbers continue to fall this might lead to further loss of genetic diversity which could have an impact on future generations of weedy seadragons,” she said.

Using the latest genomics (NGS, or next generation sequencing), the researchers identified four distinct genetic clusters — central NSW, southern NSW, Victoria and Tasmania. High-resolution images were also used to measure seadragon length and shape, revealing NSW individuals differed in a few measurements to those from Mornington Peninsula in Victoria.

The combined results suggest that not only are weedy seadragon populations significantly different along the east coast of Australia but that the Victorian weedy seadragons may form a subspecies.

“They are highly distinct to NSW and Tasmania and do not interbreed with any of the other populations. Biologists refer to this as being reproductively isolated.

“Because Victorian ‘weedies’ are the only animals used in the aquarium trade, worldwide, a bias towards this population exists in captivity. This has implications for conservation management,” Dr Klanten said.

Co-author Professor David Booth, also of UTS Fish Ecology Lab, noted “as an ecologist it was clear to me that weedies from the populations were shaped differently and occupied different habitat types, but we were surprised how different they were genetically.

“Most global aquariums that exhibit weedies have sourced them from the Melbourne area, and this was quite distinct in our study, so we recommend extra care in managing the wild populations there,” Professor Booth said.

The study sites were located in Sydney, Jervis Bay and Eden in NSW; Mornington Peninsula in Victoria; and Tasmania, and were surveyed over three years between 2016 and 2019. Sampling these masters of camouflage involved removing a small piece of tissue from their leaf-like appendages. Tissue samples were also taken from dead individuals washed up onshore and collected by citizen scientists.

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Traditionally, ammonia production has been performed through the “Haber-Bosch” process, which, despite being effective, requires high temperature conditions (400-500°C), making the process expensive. Consequently, scientists have been trying to find a way to reduce the reaction temperatures of ammonia synthesis.

Recently, scientists have reported ruthenium — a transition metal — as an efficient “catalyst” for ammonia synthesis, as it operates under milder conditions than traditional iron-based catalysts. However, there is a caveat: nitrogen molecules need to stick to the catalyst surface to undergo dissociation into atoms before reacting with hydrogen to form ammonia. For ruthenium, however, the low temperature often causes hydrogen molecules to stick to its surface instead — a process called hydrogen poisoning — which impedes the production of ammonia. To work with ruthenium, therefore, it is necessary to suppress its hydrogen poisoning.

Fortunately, certain materials can boost the catalytic activity of ruthenium when used as a “catalyst support.” A team of scientists from Tokyo Tech, Japan, recently revealed that lanthanide hydride materials of the form LnH2+x is one such group of support materials. “The enhanced catalytic performance is realized by two unique properties of the support material. First, they donate electrons, which guide the dissociation of nitrogen on the ruthenium surface. Second, these electrons combine with hydrogen on the surface to form hydride ions, which readily react with nitrogen to form ammonia and release the electrons, suppressing hydrogen poisoning of ruthenium,” explains Associate Prof. Maasaki Kitano, who led the study.

Suspecting that hydride ion mobility might have a role to play in ammonia synthesis, the team, in a new study published in Advanced Energy Materials, investigated the performance of lanthanide oxyhydrides (LaH3-2xOx) — reportedly fast hydride ion conductors at 100-400°C — as a support material for ruthenium, with the aim of uncovering the relationship between ammonia synthesis and hydride ion mobility.

They found that while the “bulk” hydride ion conductivity had little bearing on the activation of ammonia synthesis, the surface or “local” mobility of hydride ions did play a crucial role in catalysis by helping to build up a strong resistance against hydrogen poisoning of ruthenium. They also found that, compared with other support materials, lanthanum oxyhydrides required a lower onset temperature for ammonia formation (160°C) and showed a higher catalytic activity.

Furthermore, the team observed that the presence of oxygen stabilized the oxyhydride framework and the hydride ions against nitridation — the transformation of lanthanum oxyhydride to lanthanum nitride and its subsequent deactivation — which tends to impede catalysis and is a major drawback in using hydride support materials. “The resistance to nitridation is a tremendous advantage as it helps to preserve the electron donating ability of the hydride ions for longer duration of the reaction,” comments Prof. Kitano.

The superior catalytic performance and lower synthesis onset temperature achieved using lanthanide oxyhydrides could thus be the much sought-after solution to turn the heat down on ammonia production!

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Mitochondria provide our cells with energy and cellular building blocks necessary for normal tissue and organ function. For a long time, the growth of cancer cells was assumed to be independent of mitochondrial function. However, this long-standing dogma has been challenged in recent years. Especially cancer stem cells are highly dependent on mitochondrial metabolism. Due to the central role of mitochondria for normal tissue function, and because drugs that target mitochondrial functions are usually very toxic, it has so far proven difficult to target mitochondria for cancer treatment.

Now an international team of researchers has found a way to overcome these difficulties. “We managed to establish a potential cancer drug that targets mitochondrial function without severe side effects and without harming healthy cells,” explains Nina Bonekamp, one of the lead authors of the study. Mitochondria contain their own genetic material, the mitochondrial DNA molecules (mtDNA), whose gene expression is mediated by a dedicated set of proteins. One such protein is the enzyme “mitochondrial RNA polymerase,” abbreviated to POLRMT. “Previous findings of our group have shown that rapidly proliferating cells, such as embryonic cells, are very sensitive to inhibition of mtDNA expression, whereas differentiated tissues such as skeletal muscle can tolerate this condition for a surprisingly long time. We reasoned that POLRMT as a key regulator of mtDNA expression might provide a promising target,” says Nils-Göran Larsson, head of the research team.

Compound inhibits mitochondrial RNA polymerase

In collaboration with the Lead Discovery Center, a translational drug discovery organization established by Max Planck Innovation, the research team designed a high-throughput test method for identifying a chemical compound that inhibits POLRMT. The POLRMT inhibitor strongly decreased cancer cell viability and tumour growth in tumour-bearing mice, but was generally well tolerated by the animals. “Our data suggest that we basically starve cancer cells into dying without large toxic side effects, at least for a certain amount of time. This provides us with a potential window of opportunity for treatment of cancer,” says Nina Bonekamp. “Another advantage of our inhibitor is that we exactly know where it binds to POLRMT and what it does to the protein. This is in contrast to some other drugs that are even in clinical use.” With the help of ACUS Laboratories in Cologne and the Max Planck Institute for Biophysical Chemistry in Göttingen, the team identified the chemical binding site of the inhibitor and obtained structural information of the POLRMT-Inhibitor complex.

Bonekamp and Larsson agree that it has been an exciting journey to translate basic findings into a potential drug. They are all the more excited about the possibilities that their findings will open up. “Given the central role of mitochondrial metabolism within the cell, I am sure that our inhibitor of mitochondrial gene expression can be used as a tool in a variety of different areas,” explains Bonekamp. “Of course, it is intriguing to further pursue its potential as an anti-cancer drug, but also as a model compound to further understand the cellular effects of mitochondrial dysfunction and mitochondrial diseases.”

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