Brain

The famous patient Henry Molaison (long known as H.M.) suffered damage to his hippocampus after a surgical attempt to cure his epilepsy. As a result, he had anterograde amnesia, which meant that things he learned never made it past his short-term memory. Though his memories of childhood remained intact, H.M. might meet with his doctor and five minutes later say, 'Oh, I don't think I've ever met you. What's your name?'.

H.M. helped scientists understand the role of the hippocampus in learning, but a mystery remains around how signals from it somehow get shared with the billions of neurons throughout the cortex that change in a coordinated fashion when we learn. In a paper published today in the prestigious journal Science, a collaboration between University of Ottawa and Humbolt University of Berlin reveals a critical role for a brain area called the perirhinal cortex in managing this learning process.

The study involved mice and rats learning a rather strange brain-based skill. A single neuron in the sensory cortex was stimulated, and the rodent had to show it had felt the buzz by licking a dispenser to receive some sweetened water. No one can say for sure what that brain stimulation feels like for the animal, but the team's best guess is that it mimics the feeling of something touching its whiskers.

As they watched the brain responding to this learning experience, the team observed that the perirhinal cortex was serving as a waystation between the nearby hippocampus, which processes place and context, and the outer layer of the cortex.

"The perirhinal cortex happens to be at the very top of the hierarchy of processing of information in the cortex. It accumulates information from multiple senses and then sends it back to the rest of the cortex," says Dr. Richard Naud, an assistant professor in the Faculty of Medicine's Department of Cellular and Molecular Medicine, and in the Brain and Mind Research Institute. "What we are showing is that it has a very important role in coordinating learning. Without these projections coming back from the conceptual area, the animals are not able to learn anymore."

Previous studies have focused on communication from the hippocampus upward into the decision-making regions of the brain like the perirhinal cortex, but there has not been as much attention paid to what the perirhinal cortex does with that information, and what it sends back down to Layer 1 of the cortex. It turns out this step is a key part of the process, without which learning is impossible.

"When the connection from the perirhinal cortex back to those layer 1 neurons was cut, the animals acted a lot like H.M. They were improving a little bit, but it wouldn't stick. They would just learn and forget, learn and forget, learn and forget," says Dr. Naud.

A computational neuroscientist with a background in physics, Dr. Naud was responsible for statistical analyses, as well as the creation of computational models that map out the brain's information processing. Of particular interest to him was confirmation of what he had long suspected: that rapid bursts of firing from a neuron have a distinctive meaning, apart from what is meant by a slower pace of electrical activity. When the animals were in the midst of learning, these rapid-fire action potentials lit up the monitored cells.

The team was able to recreate the burst effect artificially as well.

"If you force the same number of action potentials but at a high frequency, then the animal is better at detecting it," says Dr. Naud. "This would imply that bursts are correlated with learning and causally related to perception. Meaning that you are more likely to perceive something if it creates a burst in your neurons."

The next challenge is to figure out exactly what that learning signal from the perirhinal cortex to the lower order brain areas looks like. Dr. Naud is busy working on a computational model relating our existing knowledge of physiology to what this experiment is seeing.

Skoltech's evolutionary biologists discovered recombination in bdelloid rotifers, microscopic freshwater invertebrates, which have long been regarded as 'an evolutionary scandal' due to their presumed ancient asexuality. The existence of such anciently asexual groups calls into question the hypothesis that sexual reproduction is indispensable for long-term evolutionary success of species. However, the recent study published in Nature Communications provides evidence of recombination and genetic exchange in bdelloids.

Sexual reproduction which involves recombination and exchange of genetic material between individuals of the same species is thought to be essential for the long-term survival of species. Although transitions to asexual reproduction are quite frequent in eukaryotes, they typically result in rapid extinction. On these grounds, transition to asexual reproduction is usually regarded as an evolutionary dead end. However, there are a few notable exceptions to this rule, such as bdelloid rotifers which were long assumed to have switched to asexual reproduction several tens of millions of years ago.

An international team of scientists led by Georgii Bazykin, a professor at the Skoltech Center for Life Sciences (CLS), and Alexey Kondrashov, a professor at Moscow State University (MSU), obtained whole-genome sequencing data for several individuals of Adineta vaga and found evidence suggesting recombination in this bdelloid species.

The scientists analyzed whole genomes of 11 A. vaga individuals revealing signatures of recombination and interindividual genetic exchange.

"We have shown that variation within the population of A. vaga is inconsistent with strict clonality and lack of recombination. Bdelloid rotifers are frequently referred to as 'an evolutionary scandal'. However, our results suggest that the status of bdelloid rotifers as an ancient asexual group should probably be reconsidered. Our findings underscore the importance of recombination for the long-term evolutionary success of species. Although some data hint at the existence of meiosis in bdelloid rotifers, mechanisms of genetic exchange in this group of species remain obscure and are subject to further research," comments Olga Vakhrusheva, the lead author and a junior research scientist at Skoltech.

Organoids are organ-like tissues derived from stem cells that are grown in labs, often referred to as miniature organs. Because they can imitate the structure and function of human organs, it is considered as the next-generation technology for creating artificial organs or developing new drugs. Recently, a research team in Korea introduced a new concept of mini-organs called assembloid that surpasses these organoids to structurally and functionally recapitulate human tissues. These findings were announced on December 17 (KST) in Nature, one of the most prestigious journals in science and technology.

A team led by Professor Kunyoo Shin of POSTECH's Department of Life Sciences has developed multi-layered miniature organs called assembloids that precisely mimic human tissues by three-dimensionally reconstituting stem cells together with various cell types in tissue stroma. The assembloid is a novel, innovative technology that can present a new paradigm for the next-generation drug discovery of intractable diseases as patient-customized human organs that transcend the conventional organoids.

Organoids are miniature organs that are similar to human organs. However, the current organoid technology has a fundamental limitation in that they cannot mimic the mature structure of organs and lack the microenvironment within the tissues. Furthermore, critical interactions between various cells within the human tissues is lacking. This limitation has been considered a major issue in precisely modeling various intractable diseases including cancer.

To overcome these limitations, Shin's team developed reconstituted in-vitro human organs called assembloids, which have organized structures of epithelial cells, stromal layers, and outer muscle cells. The researchers found that these assembloids were identical to mature adult organs in terms of cell composition and gene expression at the single cell level, and that they mimic the in-vivo regenerative response of normal tissues to the injury.

In addition, the team developed patient-specific tumor assembloids that perfectly mimic the pathological characteristics of in vivo tumors. Using this tumor assembloid platform with genetic engineering technologies, the team revealed the novel mechanisms in which the signals from the tumor microenvironment determines the plasticity of the tumor cells. These findings show that the signaling feedback between the tumor and stromal cells play a critical role in controlling the tumor plasticity. This discovery will lead to a novel paradigm in the development of cell differentiation therapy for the treatment of various aggressive types of solid cancers.

"These assembloids are the world's first in-vitro reconstituted organoids," explained Eunjee Kim, the first author of the paper. She added, "We can precisely model a variety of complex intractable diseases such as cancer, degenerative diseases, and various neurological diseases including schizophrenia and autism, and understand the pathogenesis of such diseases to ultimately develop better therapeutic options."

"To our knowledge, our efforts to generate assembloids that structurally and functionally recapitulate the pathophysiology of original tissues have not been previously described," commented Professor Shin who led the study. He added, "Generating such artificial tissues is particularly relevant to modern research because the importance of tissue microenvironments in epithelial tissue homeostasis and the growth of various tumors is increasingly being recognized. We anticipate our study to open a new era of a drug discovery that will revolutionize the advancement of patient-customized treatment for various intractable diseases."

Professor Tae-Young Roh, who contributed to the study, remarked, "This study is a great model for interdisciplinary science, and presents a new direction for precise and personalized therapy for various human diseases."

Less traffic on the roads during the first lockdown led to a reduction in air pollution but may have caused potentially damaging surface ozone levels to rise, a new study has revealed.

The study - led by the University of York - shows levels of nitrogen dioxide (NO2) down on average across the UK by 42 per cent, but surface ozone (O3) increased by 11 per cent on average.

Surface, or ground-level ozone, can trigger a variety of health problems, particularly for children, the elderly, and people of all ages who have lung diseases such as asthma.

Scientists believe our warm and sunny spring weather may have been a contributing factor.

The report concludes that if the Covid-19 lockdown is taken as an example of how air quality will respond to future reductions in vehicle emissions - with more electric vehicles being introduced - it serves as a warning that the problem of O3 must also be considered.

Professor James Lee from the Department of Chemistry and the National Centre for Atmospheric Science said during the first lockdown levels of O3 were the worst in the South of England.

Professor Lee added: "The problem is being created by the change in chemistry between NOx (nitrogen oxide) and O3. The main reason is the change in the nitrogen dioxide levels but the warm sunny weather in April and May also increased the ozone level. As a result we found UV radiation across the UK was higher in 2020 compared to previous years, with the largest increases in southern England.

"London, Chilton in Oxfordshire and Camborne in Cambridgeshire saw increases of around 50% compared to previous years, with Glasgow and Inverness showing smaller increases of around 30%.

"These results are a cautionary tale. As well as looking at how we reduce levels of nitrogen dioxide by cutting diesel and petrol emissions, we also need to keep an eye on what is happening with ozone so we don't create other forms of pollution dangerous to human health."

The report says in China nitrogen oxide reductions have also led to increases in O3 and air quality abatement strategies are being developed in order to offset the problem. This can be achieved by controlling volatile organic compounds (VOCs) - which are gases emitted into the air from products or processes of industry and other man-made activity.

Professor Lee added: "Our research shows it will be vital to control man-made VOCs to avoid any health gains made by the reduction of NO2 being offset by O3 increases."

University of Minnesota Twin Cities researchers in the Department of Chemistry have created a new polymer to deliver DNA and RNA-based therapies for diseases. For the first time in the industry, the researchers were able to see exactly how polymers interact with human cells when delivering medicines into the body. This discovery opens the door for more widespread use of polymers in applications like gene therapy and vaccine development.

The research is published in the Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed multidisciplinary scientific journal.

Gene therapy involves altering the genes inside the body's cells to treat or cure diseases. It requires a carrier that "packages" the DNA to deliver it into the cell--oftentimes, a virus is used as a carrier. Packaging of nucleic acids is also used in vaccines, such as the recently developed messenger RNA (mRNA) COVID-19 vaccine, which is enclosed in a lipid.

The research team is led by chemistry professor Theresa Reineke and associate professor Renee Frontiera. Reineke's lab synthesizes polymers, which are long-chain molecules that make up plastics, to use for packaging the nucleic acids instead.

"It's kind of like ordering something from Amazon, and it's shipped in a box," Reineke explained. "Things get broken if they're not delivered in a package. That's basically what we're doing here but on a nano-level. We're taking these really sensitive RNA and DNA cargo that are susceptible to enzymatic degradation, that won't get to their target unless you have something to protect them."

The researchers designed the copolymer using quinine, a naturally occurring substance used in tonic water, and 2-hydroxyethyl acrylate (HEA), which makes the material soluble and is used in a variety of personal care and medical materials. Because quinine is fluorescent, the research team was able to track the DNA package throughout the body and into the cells using Raman spectroscopy, a chemical imaging technique.

"We've discovered a new packaging tool with this natural product that's important for all of these high-flying, important fields like gene therapy and vaccines," said Reineke, who is also a Distinguished McKnight University Professor. "And, it works in a variety of cell-types. On top of that, it's got all of these cool features--it's fluorescent, we can track it, it's Raman active, and that allowed us to understand a lot of fundamentals about these packaging systems that were impossible to probe before we incorporated this natural product."

Polymer-based drug delivery is significantly cheaper than using viruses, especially for gene therapy, which can cost up to $2 million for a single injection. However, the main barrier preventing widespread polymer use was that scientists didn't know a lot about how the polymer package actually interacts with cells in the body.

This research helps clear up that uncertainty. Frontiera's lab specializes in chemical imaging. Using Raman spectroscopy, they discovered that a cell's own proteins play a key role in unpacking the nucleic acid cargo once the polymer carrier enters the cell.

"It's very satisfying to know how this is actually happening, what the process of delivery is, and to actually see that in real-time," Frontiera said. "A key point is that these polymers also work very well. For all the beneficial attributes, they're also incredibly effective at getting the payload into cells, and we were able to tell why, which doesn't always happen in this field."

As glaciers flow outward from the Greenland Ice Sheet, what lies beneath them offers clues to their role in future ice thinning and sea-level rise contribution.

Outlet glaciers are rivers of ice flowing within the cracks of the bedrock and draining into the surrounding sea. They retreat and start to thin as climate warms, and this thinning works its way toward the center of the ice sheet. Now, by looking at the bed topography beneath the ice, scientists have a better understanding of which glaciers could have a significant impact on the Greenland Ice Sheet's contribution to sea-level rise in coming years. They found that some glaciers flowing over gentler slopes could have a greater impact than previously thought. The gentle slopes allow thinning to spread from the edge of the ice sheet far into the interior, whereas glaciers with steep drops in their bed topographies limit how far into the interior thinning can spread.

The research, which was published December 11th in Geophysical Research Letters, analyzed 141 outlet glaciers on the Greenland Ice Sheet to predict how far into the interior thinning may spread along their flow lines, starting from the ocean edge.

"What we discovered is some glaciers flow over these steep drops in the bed, and some don't," said lead author Denis Felikson with NASA's Goddard Space Flight Center in Greenbelt, Maryland, and the Universities Space Research Association (USRA). "For the glaciers that do have that steep drop in the bed, thinning can't make its way past those drops." Borrowing a term from geomorphology - the study of Earth's physical features - they coined these steep drop features "knickpoints."

When a river flows over a knickpoint, it often results in a waterfall or a lake. But for glaciers, steep is a relative term which in reality translates to just about three degrees of incline. "It's not like the ice is going over a cliff," said Felikson. "But in terms of glacier dynamics, they are very steep - an order of magnitude more steep than a typical bed that the ice flows over."

The researchers were able to identify these "steep" changes in topography using digital elevation models of the ice sheet bed and surface topography. Surface topography came from the Greenland Ice Mapping Project, created using NASA's Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) instrument that flies aboard NASA's Terra satellite, in conjunction with data from NASA's Ice, Cloud, and land Elevation Satellite (ICESat) mission. The bed topography digital elevation model, known as the BedMachine data set, is a high-resolution model of the bed beneath the Greenland Ice Sheet, created using data from NASA's Operation IceBridge airborne surveys of polar ice.

"This bed topography data set was critical to us doing our work," Felikson said. "And it is thanks to NASA remote sensing, namely the Operation IceBridge surveys, that we were able to do this." Using the remote sensing data, scientists were able to compare topography measures to produce a single metric along a glacier's flow line. This helped them identify a break point between the upstream and downstream parts of the glacial ice.

Ice below the knickpoint is susceptible to thinning from the glacier's edge. But the thinning does not extend beyond this point upstream, so the interior of the ice sheet is not impacted.

Of all the glaciers observed, a majority (65 percent) had discernable knickpoints. Especially steep knickpoints are prevalent in the more mountainous regions of Greenland, where several of the biggest and fastest moving glaciers also show knickpoints that are relatively close to the coast. By sheer size alone these glaciers could contribute significantly to ice sheet thinning and melt, but because their knickpoints are near the coast, thinning is not expected to spread far inland.

However, glaciers that flow through gentle topography are found to either have gradual knickpoints, or no knickpoint at all. Such glaciers are of interest, and concern, because even those that are smaller in size have the potential to let thinning expand hundreds of kilometers inland, eroding the heart of the ice sheet.

"They could be impactful in terms of sea level rise, not because they are big and deep, but because they have access to more ice that they can eat away," said Felikson. "It will take them a lot longer to respond, but over the long term they could end up contributing just as much to sea level rise, maybe, as the big glaciers."

Over the gentle topography of the northwest coast of Greenland, nine of twelve neighboring glaciers are predicted to thin more than 250 km (155.3 miles) into the interior of the ice sheet, over a ?140-km (86.9 mile) wide region. The northwest sector of the ice sheet is also the only region experiencing an ongoing increase in ice discharge over the last couple decades, and Felikson predicts that it will continue to do so given the characteristics of these glaciers.

Wildfire smoke contains microbes, a fact that's often ignored, but one that may have important health repercussions.

In an article published Dec. 18 in Science, Leda Kobziar and George Thompson called the attention of the scientific community to the health impacts of wildfire smoke's microbial content.

Smoky skies caused by wildland fires are becoming seasonal norms, especially in some parts of the United States and Australia. In 2020, raging wildfires in the Western U.S. have set new records and led to extremely unhealthy or hazardous air quality levels for many weeks in a row.

It's well-documented that exposure to wildfire smoke can damage the heart and lungs. Respiratory allergic and inflammatory diseases, including asthma and bronchitis, are also worsened by smoke exposure.

"The health impact of inhaling wildfire smoke increases dramatically during high-emissions wildfires and with long exposure," said Kobziar, associate professor of Wildland Fire Science at the University of Idaho. "Yet, the risk of infection to the respiratory tract after this exposure is frequently overlooked."

What role do microbes in wildfire smoke play in the spread of disease?

Wildland fire is a source for bioaerosol, airborne particles made of fungal and bacterial cells and their metabolic byproducts. Once suspended in the air, particles smaller than 5 μm can travel hundreds or even thousands of miles. Their movement depends on the fire behavior and the atmospheric conditions. Eventually, they are deposited or inhaled.

Bacteria and fungi can be transported in these wildland fire smoke emissions. While microbial concentration in smoke is higher near the fire source, these microbes may be active agents spreading infection. For example, coccidioidomycoses - a fungus that becomes airborne when soils are disturbed- is the cause of Valley fever, a potentially serious infection.

"We don't know how far and which microbes are carried in smoke," said Thompson, associate professor of Clinical Medicine at UC Davis. "Some microbes in the soil appear to be tolerant of, and even thrive under, high temperatures following wildfires."

As Kobziar explained, "At the scale of a microbe, fire behavior research has shown that heat flux is highly variable, so it may be that many microbes aren't even subjected to the high temperatures for very long. They may also be protected in small clusters of particulate matter."

Kobziar and Thompson proposed a multidisciplinary approach to understanding the nature of the relationship between microbes, wildfire smoke and health. The complexity of the phenomenon calls for the expertise of scientists from different fields such as fire ecology, environmental microbiology, epidemiology, atmospheric sciences and public health and infectious disease.

"With longer wildfire seasons and higher severity trends, there is an urgency to work together in studying the behavior of the microbes carried by the smoke and their impact on human health," Thompson said.

The jagged terrain of Greenland's mountains is protecting some of the island's outlet glaciers from warm coastal waters, according to a team of researchers that included scientists from The University of Texas at Austin and NASA.

Outlet glaciers protrude from the ice sheet into the sea, where surging ocean heat can speed up the loss of ice, making the glaciers thinner and raising sea levels. The scientists found that steep slopes in the bedrock under the ice form stabilizing areas the researchers termed "knickpoints" that prevent coastal thinning from reaching further inland.

The findings were published Dec. 11 in the journal Geophysical Research Letters.

"Thinning in glaciers originates at the edge of the ice, and makes its way inland," said lead author Denis Felikson, a NASA research scientist. "When the thinning reaches a knickpoint that is steep enough, it's halted."

However, in regions where the flat bedrock offers no such protection and knickpoints are absent, runaway thinning can reach far into the ice sheet and eat away at previously unaffected ice and contribute to sea level rise.

Coauthor Ginny Catania, a professor of glaciology at the UT Jackson School of Geosciences, said that most glaciers are thinning as scientists expect in a warming climate, but not at the same rates or amounts. The variability makes it more difficult to predict how quickly sea levels will rise as the planet gets hotter.

"Some glaciers are thinning right next to others that are thickening," she said. "Until now we didn't know how to explain such variability. Denis' research has provided a framework for that understanding, and it's very likely that all of the variability we observe in outlet glaciers is linked to variability in the bed topography between glaciers."

The researchers use the term knickpoints to describe steep slopes in the bedrock because of their similarities to river knickpoints--places that often form waterfalls or rapids. Like a waterfall, glaciers pour over the knickpoints, creating a physical barrier that prevents changes happening downstream near the coast from reaching further upstream.

Greenland's ice sheet covers an area twice the size of Texas. The barrier effect of knickpoints is important because warmer ocean currents are one of the principal reasons Greenland's glaciers are losing mass more quickly than they were 20 years ago.

The study gives scientists a better understanding of how the loss of ice will play out as the world gets hotter and can also focus scientific resources on learning more about the glaciers most likely to contribute to sea level rise.

Felikson began the research while earning a Ph.D. at the Jackson School working with Catania and coauthor Tim Bartholomaus (now at the University of Idaho) at the University of Texas Institute for Geophysics (UTIG). By comparing the start-stop motion of glacial creep to congested traffic, the UTIG group had shown that a glacier's shape controls the spread of thinning in a 2017 Nature Geoscience paper.

The current paper builds on that research but extends the analysis from 16 to 141 (the majority) of Greenland's outlet glaciers, and in doing so, revealed the armoring effect of glacial knickpoints.

The research shows that glacial knickpoints are surprisingly prevalent. Although that might be good news, the research also revealed vulnerability in northwest Greenland, an overlooked region of the ice sheet.

"The glaciers in this region could be important over the next 100 years because the relatively flat bedrock beneath them means they can transfer thinning much further into the interior of the ice sheet than some of the larger glaciers in mountainous topography," Felikson said.

Catania said this means that sea levels will rise regardless.

"You're still going to drain the ice sheet you're just going to do so through a different area than we thought," she said.

The research team agreed that investigations of the bedrock near the coast is urgently required to learn how effective knickpoints are at holding back coastal warming, as is investigation of unprotected glaciers. Catania and Felikson have already proposed an early warning system that will use machine learning to watch for instability in glaciers identified by the knickpoint analysis.

For understanding the structure and function of catalysts in action, researchers of Karlsruhe Institute of Technology (KIT), in cooperation with colleagues from the Swiss Light Source SLS of Paul Scherrer Institute (PSI) in Switzerland and the European Synchrotron Radiation Facility (ESRF) in France, have developed a new diagnostic tool. Operando X-ray spec-troscopy visualizes the structure and gradients of complex technical catalysts in three dimensions, thus allowing us to look into functioning chemical reactors. The results are re-ported in Nature Catalysis. (DOI: 10.1038/s41929-020-00552-3)

Catalysis is indispensable for many branches. 95% of all chemicals are produced using catalysts. Catalysts also play a key role in energy technologies and environmental protection. Catalysts are materials used to accelerate chemical reactions in order to reduce energy consumption and undesired by-products. This chemico-physical principle is the basis of entire systems, examples being catalytic converters in cars or catalysts in power plants to remove pollutants from their exhausts. Technical and industrial catalysts are also applied in fertilizer and polymer production. Often, they must exhibit high pressure resistance and mechanical strength, while additionally operating under dynamic environmental condi-tions. Even smallest efficiency increases in the removal of pollu-tants, such as carbon monoxide, nitrogen oxides, and fine dust, from exhaust gases or in the production of green hydrogen will result in major advantages for humans and the environment. To improve existing catalytic materials and processes, however, exact understanding of their function is required. "Whether in a large chemical reactor, in a battery, or underneath your car - technical and industrial catalysts often have a highly complex structure," says Dr. Thomas Sheppard from the Institute for Chemical Tech-nology and Polymer Chemistry (ITCP) of KIT. "To really under-stand how these materials function, we need to take a look inside the reactor when the catalyst is working, ideally with an analytical tool to detect the complex 3D structure of the active catalyst."

Operando X-ray Spectroscopy Provides 3D Images and Major Chemical Information

Thomas Sheppard directed a study on automotive catalytic con-verters, the results of which are now reported in Nature Catalysis by the researchers involved from KIT, PSI, and ESRF. For their studies, the team used a newly developed setup and carried out tomography experiments at synchrotron radiation facilities in Swit-zerland and France. Computer tomography produces 3D images of a sample, including the exterior and interior, without needing to cut it open. By using a special reactor, the researchers performed to-mography and X-ray spectroscopy to track an active catalytic pro-cess. In this way, they succeeded in observing the 3D structure of an emission control catalyst under conditions just like those in a real automotive exhaust. This so-called operando X-ray spectros-copy provides not only the 3D structure of the sample, but also important chemical information.

Method Suited for Various Catalysts

"Since catalysts often have a rather complex and non-uniform structure, it is important to know whether the entire catalyst volume or only parts of it are performing their chemical function as intend-ed," explains Johannes Becher from ITCP, one of the main authors of the study. "Operando X-ray spectroscopy lets us see the specif-ic structure and function of every single piece. This tells us wheth-er the catalyst is performing at maximum efficiency or not and, more importantly, it helps us understand the underlying process-es." During reaction, the team observed a structural gradient of the active copper species within the catalyst, which could not be de-tected previously using conventional analytical tools. This is im-portant diagnostic information in the performance of emission con-trol catalysts. The method itself can be applied to many different catalysts and chemical processes.

New Opportunities for Materials and Reaction Diagnostics

The team's studies show how visualizing the chemical state of an active catalyst in 3D can bring new opportunities for materials and reaction diagnostics. "Until now, it was not possible to freely select any piece of a working catalyst and understand which reactions take place in there without disturbing it. Now, we can follow exactly which reactions are occurring, where, and why," says Professor Jan-Dierk Grunwaldt from ITCP. "This is the key to improving our understanding of chemical processes and designing better and more efficient catalysts in future." Studies using operando X-ray spectroscopy can be carried out at different synchrotron radiation sources, provided that an appropriate sample environment exists. The groups of Jan-Dierk Grunwaldt and Thomas Sheppard will continue their investigations as part of the new Collaborative Re-search Center "TrackAct" at KIT. "TrackAct" is aimed at under-standing and improving the design and efficiency of emission con-trol catalysts.

CHAMPAIGN, Ill. -- A drug widely used to treat fungal infections improved key biomarkers in lung tissue cultures as well as in the noses of patients with cystic fibrosis, a clinical study by researchers at the University of Illinois Urbana-Champaign and the University of Iowa found.

Cystic fibrosis is caused by a missing or defective ion channel in the lining of the lungs, called CFTR. This leaves patients vulnerable to lung infections. Treatments called modulators can help some but not all patients, based on which type of genetic mutation causes the symptoms.

The patients who participated in the clinical study were among the 10% of patients who cannot respond to modulator treatments, suggesting the antifungal drug, amphotericin B, could benefit all patients regardless of their mutation, said study leader Dr. Martin D. Burke. Burke is a professor of chemistry at Illinois and the associate dean for research for the Carle Illinois College of Medicine, as well as a medical doctor. The study was published in the Journal of Cystic Fibrosis.

In previous work, Burke's group demonstrated that amphotericin forms ion channels in cell membranes that perform similarly to the missing protein, acting as a prosthetic on the molecular scale to restore function on a cellular level.

"This is the first clinical study," Burke said. "We have a long way to go, but this has increased our optimism that a molecular prosthetics approach could provide a new way to treat all people with cystic fibrosis, including those who cannot benefit from modulators. The mechanism should work the same for everyone, regardless of mutation."

In the new study, Burke's group, in collaboration with Dr. Michael J. Welsh at Iowa, tested the drug in cultures of lung tissue from patients with cystic fibrosis. They confirmed that the drug increased ion secretion in the cultures. Then, in experiments designed to replicate the first clinical studies of the modulator drugs, they tested it in patients' noses.

Patients with cystic fibrosis lack the CFTR channel in the airway cells in their nose as well as in their lungs, so testing the drug in the nose is the first step to demonstrating that it could be effective in the rest of the airway as well, Burke said.

The researchers assessed whether the drug increased ion flow in the nose cells by measuring a biomarker known as nasal potential difference. In the study, the nasal form of amphotericin B changed the nasal potential difference in a way that suggested that amphotericin was performing the job of the missing CFTR channels.

"Though amphotericin B is an imperfect surrogate for the CFTR protein, these results provide the first evidence that small-molecule ion channels can impact physiology in people with cystic fibrosis," said Rajeev Chorghade, the first author of the study, who was a graduate student in Burke's group at the time of the study and is now a postdoctoral fellow at the Massachusetts Institute of Technology. "These results encourage further clinical trials to determine whether inhaled amphotericin B can improve lung function and health-related quality of life in people with CF, especially those not on modulators."

Next, the researchers plan to perform a clinical study to determine whether amphotericin inhaled directly to the lungs would improve lung function and immune response in patients with cystic fibrosis. To accomplish this, they have started a new company, cystetic Medicines, with the goal of developing a powder-based inhaler. The company has already raised $25 million in initial investments.

"One of the big advantages of amphotericin B is that it's already clinically approved. That's why we've been able to move so fast," Burke said. "We used a form of amphotericin that has been used widely to treat fungal infections in the nose, so it was a nice opportunity for us to better understand the potential for cystic fibrosis applications quickly and safely. Now we need to develop a safe and effective mechanism to deliver it to the lungs."

Animals that have never been domesticated, such as kangaroos, can intentionally communicate with humans, challenging the notion that this behaviour is usually restricted to domesticated animals like dogs, horses or goats, a first of its kind study from the University of Roehampton and the University of Sydney has found.

The research which involved kangaroos, marsupials that were never domesticated, at three locations across Australia*, revealed that kangaroos gazed at a human when trying to access food which had been put in a closed box. The kangaroos used gazes to communicate with the human instead of attempting to open the box themselves, a behaviour that is usually expected for domesticated animals.

Ten out of 11 kangaroos tested actively looked at the person who had put the food in a box to get it (this type of experiment is known as "the unsolvable problem task"). Nine of the 11 kangaroos additionally showed gaze alternations between the box and the person present, a heightened form of communication where they look between the box and human.

The research builds on previous work in the field which has looked at the communication of domesticated animals, such as dogs and goats, and whether intentional communication in animals is a result of domestication. Lead author Dr Alan McElligott, University of Roehampton (now based at City University of Hong Kong), previously led a study which found goats can understand human cues, including pointing, to gather information about their environment. Like dogs and goats, kangaroos are social animals and Dr McElligott's new research suggests they may be able to adapt their usual social behaviours for interacting with humans.

Dr Alan McElligott said: "Through this study, we were able to see that communication between animals can be learnt and that the behaviour of gazing at humans to access food is not related to domestication. Indeed, kangaroos - showed a very similar pattern of behaviour we have seen in dogs, horses and even goats when put to the same test.

"Our research shows that the potential for referential intentional communication towards humans by animals has been underestimated, which signals an exciting development in this area. Kangaroos are the first marsupials to be studied in this manner and the positive results should lead to more cognitive research beyond the usual domestic species."

Dr Alexandra Green, School of Life and Environmental Sciences at the University of Sydney, said: "Kangaroos are iconic Australian endemic fauna, adored by many worldwide but also considered as a pest. We hope that this research draws attention to the cognitive abilities of kangaroos and helps foster more positive attitudes towards them."

Two groundbreaking studies at the UC Davis MIND Institute provide clues about possible types of autism linked to brain structure, including size and white matter growth.

The research is based on brain scans taken over many years as part of the Autism Phenome Project (APP) and Girls with Autism, Imaging of Neurodevelopment (GAIN) studies. It shows the value of longitudinal studies that follow the same children from diagnosis into adolescence.

"There is no other single site data set like ours anywhere," said Christine Wu Nordahl, associate professor in the Department of Psychiatry and Behavioral Sciences, MIND Institute faculty member and co-senior author on both papers. "In one of the studies we have over 1,000 MRI scans from 400 kids, which is unheard of. It's been 15 years of work to get here."

Big brains: An autism subtype?

In the first study, published in Biological Psychiatry, the researchers used magnetic resonance imaging (MRI) to track brain size (volume) in 294 children with autism and 135 children without autism between the ages of 3 and 12. In children with autism, they found evidence of larger brain size relative to height - or disproportionate megalencephaly - a subtype that has been linked to higher rates of intellectual disability and poorer overall prognosis.

Previous cross-sectional research had found that children with autism have larger brains at early ages, but no evidence of larger brains in later childhood. The widely accepted theory is that these brains "normalized" or shrank as the children grew up.

The MIND Institute study found that wasn't the case. The children who had bigger brains at age 3 still had bigger brains at age 12. Why? Unlike most research, which studies different individuals at different time points, this research studied the same children longitudinally, or over time.

Also, unlike most other studies, this one includes children with significant intellectual disabilities. These were the children who tended to have the "big brain" form of autism.

David Amaral, co-senior author on both studies, suggested that the difference between this and previous research was that children with intellectual disability were left out of previous cross-sectional studies focused on older children.

"Bigger brain size in autism has been linked to lower IQ, and children with intellectual disabilities are harder to scan as they get older," said Amaral, a distinguished professor of psychiatry and behavioral sciences and MIND Institute faculty member. "It's a matter of sampling bias and the previous "dogma" appears to be an artefact of who got scanned when," he explained.

Children under age 5 can be scanned while they're asleep, but Nordahl and her team have created unique, innovative protocols that allow researchers to more easily scan older children with intellectual disabilities while they're awake.

"It's so critical that we include those aspects of the autism spectrum that most impact quality of life, such as intellectual disability, anxiety and verbal functioning." said Joshua Lee, postdoctoral scholar at the MIND Institute and the lead author on the study. "It's important to capture everyone who has autism, not just the ones who are easiest to get images from."

White matter: Connecting the clinical dots

The second study, also published in Biological Psychiatry, linked changes in the brain's white matter growth with autism traits in some children.

The researchers used a type of MRI scan called diffusion-weighted imaging, which allowed them to look at white matter regions, or tracts, in the brain. White matter provides the structural connections in the brain, allowing different regions to communicate with each other.
The study included 125 children with autism and 69 typically developing children who served as controls, between the ages of 2.5 and 7.

The researchers found that the development of the white matter tracts in the brain was linked to changes in autism symptom severity. They observed slower development in children whose symptom severity increased over time, and faster development in those with decreased severity over time.

"From a biological standpoint, this emphasizes the role of white matter development in autism and autism symptoms," said Derek Sayre Andrews, postdoctoral scholar at the MIND Institute and lead author on the paper. "We hope that in the future, measurements like this can identify children who would benefit from more intensive intervention - and serve as a marker to determine the effectiveness of an intervention for a particular child," he said.

Changes in autism severity over time

The white matter research builds on a previous MIND Institute study, which found that while many children experience fairly stable levels of autism symptoms throughout childhood, a significant portion can be expected to increase or decrease in their symptom severity over time.

"This new analysis provides an important clue about the brain mechanism that may be involved in some of these changes," said Amaral.

Studying sex differences

The studies are unusual not only because they include children with severe intellectual disability, but also because they include a larger number of girls, who tend to be under-represented in autism research.

"For the first time, we are able to have a large enough sample of girls, where we are able to evaluate their brain trajectories separate from boys to see how they're different," said Nordahl. "For example, we don't see the big brain subtype as frequently in girls, but we do see subtle differences in how autistic girls' brains are growing."

Nordahl, who has also studied the role amygdala size may play in psychiatric challenges for young girls, noted that the MIND Institute's longitudinal data set is likely to play a key role in many future studies about sex differences in autism.

"Collectively, I believe these studies are so important because they get us closer to a point where we can use our understanding of the underlying biology of autism to directly improve the quality of life for individuals in the autistic community," Andrews said. "And that really is the ultimate goal of our research."

Many efforts are being made worldwide to replace fossil fuels with greener alternatives. Hydrogen (H2) is a promising option that is currently in the spotlight; it can be used to generate electricity in fuel cells with water generated as the only byproduct. However, the technology is not quite ready for commercialization because proton-exchange membrane fuel cells, the most widely studied type, suffer from high cost and stability issues.

In contrast, anion-exchange membrane (AEM) fuel cells use cheaper catalysts and can offer superior performance. In these cells, hydroxide ions (OH-) are circulated instead of protons through the use of a polymer electrolyte composed of a polymer backbone and ion-conducting groups. One way to improve the properties of such electrolytes is by crosslinking--physically or chemically linking polymer units to each other through molecular side chains.

Although oxygen-containing crosslinkers improve the stability and ion conductivity of AEMs by virtue of their hydrophilicity, or affinity for water, the effects of crosslinker length, which defines the number of oxygen atoms, are not understood in detail.

To gain deeper insight into this issue, scientists at Incheon National University recently carried out a study where they prepared long AEM polymers with ammonium ion-conducting groups and bound these molecules together using ethylene oxide (EO)-containing crosslinkers of various lengths. Through a wide variety of experiments, they compared AEMs with different crosslinker lengths in terms of their mechanical and thermal properties, water retention capacity, OH- ion conductivity, morphology, and stability. Their findings are published in the Journal of Membrane Science, a top journal in the field of polymer science.

The experiments helped the scientists elucidate the mechanisms by which excessive crosslinker length can ultimately degrade the performance of AEMs. Professor Tae-Hyun Kim, who led the study, explains: "Though it was easy to predict that oxygen-containing crosslinkers would increase hydrophilicity and possibly lead to better ionic conductivity, our results reveal that an excessively large number of repeating oxygen units increases the crystallinity--or degree of order--of the resulting material. In turn, this actually reduces hydrophilicity and ultimately compromises many physicochemical properties of the AEM."

After establishing the optimal length for their crosslinker, the researchers prepared an AEM fuel cell and found that the resulting performance was markedly better than when using AEMs without oxygen-containing crosslinkers. Excited about the results, Professor Kim comments: "The main takeaway from our study is that adding molecules with high water affinity, such as ethylene oxide, to crosslinkers of optimal length is a valid strategy to improve the fundamental properties of AEMs and their performance in actual fuel cells."

Although there is still room for improvement before AEM fuel cells can be effectively used in practice and commercialized, this study takes our society a step further towards the popularization of next-generation ecofriendly energy sources.

(COLUMBUS, Ohio) - Sledding is a popular winter activity in communities across the country, but it may not be as risk-free as many people think. A new study conducted by researchers at the Center for Injury Research and Policy at Nationwide Children's Hospital found that 220,488 patients were treated in U.S. emergency departments for injuries related to sledding from 2008 through 2017. Nearly 70% of these patients were children age 19 years and younger. Compared to adults, children were almost seven times as likely to be treated in an emergency department for a sledding-related injury.

The study, published in Clinical Journal of Sports Medicine, found that the majority of patients were injured as the result of a collision (63%). Collision injuries occurred when the patient made contact with an object in the environment (47%), when they hit the ground (16%), or when they ran into another person (10%) or sled (7%).

"Collision is particularly concerning because of the outcomes," said Rebecca McAdams, MA, MPH, co-author of this study and senior research associate in the Center for Injury Research and Policy at Nationwide Children's. "We found that patients who were injured from a collision were more likely to injure their head, be diagnosed with a concussion or closed-head injury (CHI), and were more than twice as likely to be hospitalized than patients injured by all other mechanisms."

Head injuries are a serious concern during sledding. The head was the most frequently injured body part for both children and adults. In fact, nearly 82% of children treated for a sledding-related injury sustained an injury to the head. The type of sled can also impact the risk of head injury. Children injured while riding snow tubes and disks had a greater risk of sustaining a concussion or CHI than children who were riding sleds or toboggans. Researchers recommend wearing a helmet while sledding to reduce the risk and severity of head injuries.

While less frequent (3% of all cases), injuries occurring as a result of the sled being pulled by a motorized vehicle such as a car, ATV or snowmobile resulted in more serious injuries that required hospitalization (14%) and have even resulted in death. This practice should be avoided.

The good news is that the rate of sledding-related injuries treated in U.S. hospital emergency rooms among both children and adults decreased during the ten-year study period. However, despite this decrease, 13,228 patients were still treated for sledding-related injuries in the most recent year of the study.

"While we were happy to see that the number of sledding-related injuries have gone down in recent years, the fact that these injuries are still happening at this rate means we need to do a better job getting the information out about the potential dangers associated with sledding and what families can do to prevent the injuries from occurring so this can remain a fun family activity," said Lara McKenzie, PhD, MA, senior author of the study and principal investigator in the Center for Injury Research and Policy at Nationwide Children's.

Researchers recommend that parents and caregivers help children stay safer while sledding by following these tips:

Wear a helmet: Make it a rule that everyone has to wear a helmet if they are going to sled. Properly fitted snow sport helmets or bicycle helmets are best.

Pick your sled: Sleds that can be steered and have braking features may allow for more control than flat sheets, snow discs, tubes and toboggans. Also make sure to follow manufacturer guidelines for the number of passengers a sled can safely hold.

Check the environment: A safe sledding environment should:

be free of obstacles (e.g., trees, rocks, light posts, walls, etc.).

have plenty of space at the end of the hill to allow the sled to safely slow down (avoid driveways or hills that end in a street, drop off, parking lot, or a body of water like a river or pond).

be free of motorized vehicles like ATVs, snowmobiles, cars, etc. Use of these types of vehicles to pull a sled can lead to serious injury and even death.

Follow the rules: Always ride the sled while seated with your feet facing the bottom of the hill. Only ride during daylight hours. Teach children to roll off the sled if it is going too fast or is going to crash so they can avoid collisions.

Stay for the fun: Having an adult present to check the environment for hazards and make sure kids are following safety guidelines while sledding can prevent injuries.
Data for this study were obtained from the National Electronic Injury Surveillance System (NEISS), which is operated by the U.S. Consumer Product Safety Commission. The NEISS database provides information on consumer product-related and sports- and recreation-related injuries treated in hospital emergency departments across the country.

LAWRENCE -- When you imagine a visit to a natural history museum, the first thing that springs to mind could be dinosaur bones or taxidermized animals.

Behind the visitor displays, however, advanced research on specimens collected from around the world is taking place. What's more, this work forms an essential front line of defense in pandemic preparedness.

According to Jocelyn Colella, research affiliate with the University of Kansas Biodiversity Institute and incoming assistant curator of mammals with the KU Natural History Museum, museums act as a kind of decentralized pathogen surveillance network. In a recent piece published in Science, Colella and colleagues argue that expanded biodiversity infrastructure will be an essential front line of defense in pandemic preparedness in the wake of COVID-19.

"Museum visitors see specimens on display, but hundreds and thousands of others are safely preserved behind the scenes -- museum curators are responsible for making sure that those specimens are preserved and available for research going into the future," she said. "Fifty years ago, we weren't sequencing DNA. But now we are -- and specimens preserved over decades, or even centuries, can now be used for molecular research. We have a couple of liquid nitrogen dewars here at the Biodiversity Institute that hold frozen tissues from all sorts of animals, from all over the world. Those tissues can be used to sequence whole genomes to identify how animals are adapting or responding to changing conditions."

Colella said such collections preserve specimens and also capture the community of microorganisms that use the organism as a host.

"You can also sequence viruses, bacteria and fungi from all of those frozen tissues -- so you not only get information on the host organism or mammal, but you also get information about their entire community," she said.

Because more than half of all emerging diseases in humans come from wildlife, such as COVID-19 (which scientists think jumped to humans from horseshoe bats), museum specimens hold the genetic clues needed to determine where they came from and better understand and fight these pathogens -- especially in countries at high risk for emerging zoonotic disease, such as those with high species diversity and a high frequency of human-wildlife contact.

"As the human population grows, we continue to come into contact with new, different and more animals. That increases the risk of these disease spillover events," Colella said. "The cool thing with natural history museum collections is that we have sampling through time. You can survey the same areas over and over, sampling all sorts of different animals, which gives us a sense of how long a virus has been there and where it came from."

The KU researcher pointed to hantavirus as an example where biodiversity collections collaborated with the Centers for Disease Control to help fight off a disease that had entered the human population from animals.

"Parallel to the current COVID-19 pandemic, there was a spillover event in 1993 of hantavirus in the American Southwest that led to the deaths of many people, and we had no idea where it came from," Colella said. "The CDC asked the Museum of Southwestern Biology to help find the reservoir host of the virus, and they identified deer mice as the source. Researchers were then able to go back into these historic mammal collections and found that this disease had been in rodent populations for over 10 years before it spilled over into humans. That type of information allows us to have an evolutionary perspective on what happened between when this virus emerged in rodents and when it became harmful to humans -- what changed? That allows us to respond and prevent outbreaks in the future."

While the importance of natural history museums to human health has never been higher, in recent years the number of specimens being deposited in biodiversity collections actually has been declining.

A second paper written by Colella and colleagues, just published in BioScience, outlines ways to reverse this downward trend.

"Another reason scientists are having trouble identifying reservoir hosts and finding novel viruses is because the sampling base in museums just isn't there, and it's not because scientists aren't taking samples," she said. "It's because there are no requirements for samples to land at museums or public institutions. There's an ethical issue with collecting animals and then keeping all those samples in your personal freezer forever until you retire or lose all the IDs and can't associate the material with XYZ, and it was all for naught. We can do better."

According to Colella, several studies have tracked the number of deposited specimens across the past few decades and show "dramatic declines" starting in the late 1990s. "There are plenty of permits out there and specimens being sampled. The samples are just not ending up in museums," she said.

The KU researcher and her co-authors propose treating specimens collected in the field exactly like other types of scientific data and using the open-data model to ensure scientists have access to museum specimens for research today and into the future.

"We propose increased open-data requirements by journals, integration of specimens into existing requirements for data management plans and a cultural shift in biological sciences. That must be collectively propelled by researchers, editors and reviewers as part of the solution," Colella said.

She differentiates between the ideas of specimen "ownership" and "stewardship."

"Specimen stewardship promotes the democratization of specimens to maximize access and research potential through the use and re-use of specimens' resources to answer multiple scientific questions, instead of private ownership for use in a single project," Colella said. "If samples never get archived with a museum, it's a loss to the entire scientific community. We're saying if you have private specimen collections, there needs to be a plan to get those samples archived eventually, so that if you're not around anymore or you need someone else to archive them, they know what to do. There needs to be a plan from the very beginning when the specimens are collected. Stewardship is making sure that the resources you're collecting are taken care of into the future and museum exist to do just that."