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URBANA, Ill. - Chances are you've heard of or even taken probiotics: supplements delivering "good microbes" to the gut, providing a wide range of health benefits. If you're really up on your gut health, you may also be aware of prebiotics: supplements designed to fuel the good microbes already living in our guts.

The next wave of gut-health supplements, known as synbiotics, essentially combine pre- and probiotics. To keep research and development efforts on the right track, an international panel of experts - including two from the University of Illinois - recently redefined the term and developed guidelines on the scientific investigation of the supplements.

The consensus report, published in Nature Reviews: Gastroenterology & Hepatology, is expected to serve as the definitive reference in the development of new synbiotic products.

"Synbiotics are starting to gain traction in the marketplace, but there's a lot of confusion around the term, even among scientists," says Kelly Swanson, consensus panel chair and professor in the Department of Animal Sciences at Illinois. "The panel's main goal was to clarify what synbiotics are and provide guidance for future research and innovation."

The general idea of synbiotics was first proposed in 1995 when prebiotics were defined. But the concept was left open to interpretation, and since the U.S. Food and Drug Administration regulates supplements loosely, companies can sell products that may or may not provide health benefits.

"This consensus statement provides guidance for different stakeholders, including scientists in academia and industry, consumers, and even journalists. We want to remind each group that these terms should be used consistently, avoiding sensationalizing or overstating health claims," says Hannah Holscher, panel member and assistant professor in the Department of Food Science and Human Nutrition at Illinois.

The updated definition for synbiotics is "a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host."

The terms prebiotic and probiotic have their own definitions and standards. By omitting those specific terms from the definition of synbiotic, the expert panel allows for the use of microorganisms and selectively utilized substrates that may work together to elicit a health benefit but may not fit the definitions of pre- and probiotics when administered independently.

"The old definition of synbiotic included pre- and probiotics, which may have restricted innovation," Holscher explains.

Pre- and probiotics can still be combined under the new definition, as long as they're tested together and shown to still provide positive, if not necessarily related, health outcomes. For example, a prebiotic might aid in digestive health while a probiotic may boost immunity after a flu vaccine. As long as they still provide those benefits in the host, they can be considered complementary synbiotics.

"The key there is testing. Even if the pre- and probiotics work separately, there could be some antagonism when put together. So really, they need be tested together in the target animal or human. We don't want companies just randomly throwing things together," Swanson says.

In contrast, the ingredients in synergistic synbiotics are additive, working together to produce a single, targeted health benefit. These are most likely to be made with novel ingredients not already categorized under the current definitions of pre- and probiotics.

"In synergistic synbiotics, the substrate would support probiotic survival," Holscher says. "For example, providing an energy source for the probiotic or changing the microbiome to support the survival of the probiotic."

In either case, testing the ingredients together is critical. The consensus panel lays out testing protocols for multiple hosts, including humans, pets, and livestock animals, and encourages researchers to consider the effects of age, health status, sex, and other important factors.

With better guiding documentation, the market for synbiotics is likely to grow. But before plunging into the new supplements, the researchers advise consumers to consult with medical professionals to choose the right product for their specific needs.

"Just because there's a pre-, pro-, or synbiotic on the market, that doesn't mean they'll work across the board from infants to adults to geriatrics, from heart disease to gastrointestinal health. They're all really there for a specific purpose," Swanson says.

Holscher adds, "The question is not whether you should take a pre-, pro-, or synbiotic. The question is, 'what do you need those products to do?' We know a lot about the specific health outcomes of these products, so it's a matter of finding what you need rather than thinking of them as a blanket cure-all."

A team of researchers from University of Toronto Engineering and the University of Michigan has redesigned and enhanced a natural enzyme that shows promise in promoting the regrowth of nerve tissue following injury.

Their new version is more stable than the protein that occurs in nature, and could lead to new treatments for reversing nerve damage caused by traumatic injury or stroke.

"Stroke is the leading cause of disability in Canada and the third leading cause of death," says University of Toronto Engineering professor Molly Shoichet, senior author on a new study published in the journal Science Advances.

"One of the major challenges to healing after this kind of nerve injury is the formation of a glial scar."

A glial scar is formed by cells and biochemicals that knit together tightly around the damaged nerve. In the short term, this protective environment shields the nerve cells from further injury, but in the long term it can inhibit nerve repair.

About two decades ago, scientists discovered that a natural enzyme known as chondroitinase ABC -- produced by a bacterium called Proteus vulgaris -- can selectively degrade some of the biomolecules that make up the glial scar.

By changing the environment around the damaged nerve, chondroitinase ABC has been shown to promote regrowth of nerve cells. In animal models, it can even lead to regaining some lost function.

But progress has been limited by the fact that chondroitinase ABC is not very stable in the places where researchers want to use it.

"It's stable enough for the environment that the bacteria live in, but inside the body it is very fragile," says Shoichet. "It aggregates, or clumps together, which causes it to lose activity. This happens faster at body temperature than at room temperature. It is also difficult to deliver chondroitinase ABC because it is susceptible to chemical degradation and shear forces typically used in formulations."

Various teams, including Shoichet's, have experimented with techniques to overcome this instability. Some have tried wrapping the enzyme in biocompatible polymers or attaching it to nanoparticles to prevent it from aggregating. Others have tried infusing it into damaged tissue slowly and gradually, in order to ensure a consistent concentration at the injury site.

But all of these approaches are mere Band Aids -- they don't address the fundamental problem of instability.

In their latest paper, Shoichet and her collaborators tried a new approach: they altered the biochemical structure of the enzyme in order to create a more stable version.

"Like any protein, chondroitinase ABC is made up of building blocks called amino acids," says Shoichet. "We used computational chemistry to predict the effect of swapping out some building blocks for others, with a goal of increasing the overall stability while maintaining or improving the enzyme's activity."

"The idea was probably a little crazy, because just like in nature, a single bad mutation can wreck the structure," says Mathew O'Meara, a professor of computational medicine and bioinformatics at the University of Michigan, and co-lead author of the new paper.

"There are more than 1,000 links in the chain that forms this enzyme, and for each link you have 20 amino acids to choose from," he says. "There are too many choices to simulate them all."

To narrow down the search space, the team applied computer algorithms that mimicked the types of amino acid substitutions found in real organisms. This approach -- known as consensus design -- produces mutant forms of the enzyme that don't exist in nature, but are plausibly like those that do.

In the end, the team ended up with three new candidate forms of the enzyme that were then produced and tested in the lab. All three were more stable than the wild type, but only one, which had 37 amino acid substitutions out of more than 1,000 links in the chain, was both more stable and more active.

"The wild type chondroitinase ABC loses most of its activity within 24 hours, whereas our re-engineered enzyme is active for seven days," says Marian Hettiaratchi, the other co-lead author of the paper. A former postdoctoral fellow in Shoichet's lab, Hettiaratchi is now a professor of bioengineering at the University of Oregon's Phil and Penny Knight Campus for Accelerating Scientific Impact.

"This is a huge difference. Our improved enzyme is expected to even more effectively degrade the glial scar than the version commonly used by other research groups," says Hettiaratchi.

The next step will be to deploy the enzyme in the same kinds of experiments where the wild type was previously used.

"When we started this project, we were advised not to try as it would be like looking for a needle in a haystack," says Shoichet. "Having found that needle, we are investigating this form of the enzyme in our models of stroke and spinal cord injury to better understand its potential as a therapeutic, either alone or in combination with other strategies."

Shoichet points to the multidisciplinary nature of the project as a key to its success.

"We were able to take advantage of the complementary expertise of the authors to bring this project to fruition, and we were shocked and overjoyed to be so successful," she says. "It went well beyond our expectations."

COLUMBUS, Ohio - Splitting one type of cancer drug in half and delivering the pieces separately to cancer cells could reduce life-threatening side effects and protect healthy, non-cancerous cells, a new study suggests.

The study, published today in the Proceedings of the National Academy of Sciences, suggests that splitting immunotoxins into two inactive and benign parts may set the stage for future, targeted treatments of cancers.

Immunotoxins combine an immune substance with a toxin. The immune substance attaches to cancer cells, allowing the toxin to enter the cancer cell and kill it without harming nearby healthy cells.

The research was designed as a proof-of-concept study, but the researchers found that the functional toxin can be reconstructed in cancer cells in both laboratory cell cultures and in mice.

The search for a cancer cure has led to a number of treatments that destroy cancer cells, but also destroy healthy, non-cancerous cells. That destruction often causes life-threatening side effects.

"The problem is not to kill the healthy cells," said Dmitri Kudryashov, an associate chemistry professor at The Ohio State University and senior author of the study. "What is difficult is to kill only the cancer cells and nothing else."

And while some cancer treatments have been successful at targeting cancer cells, few have been able to do so without also affecting healthy cells.

The key to split immunotoxins is that only cancer cells will receive both parts of the split toxin, said Elena Kudryashova, a co-senior author on the study and a research scientist at Ohio State.

"We have confirmed that when separated, the parts of the split toxin do not harm cells. But when they recombine into the original toxin, the treatment destroys the cancer.

"But to achieve that, both parts must enter cancer cells," Kudryashova said. "What we have achieved so far is the reconstruction of the fully functional toxin upon specific delivery of one part of the split immunotoxin to the cells expressing the other part. The specific delivery of this other part in sufficient quantity is yet to be achieved and is being pursued in the laboratory."

Essentially, when the toxin protein is split and goes into the human body as a cancer treatment, it can't cause harm to healthy cells. But if biochemists can find a way to get both pieces of the protein to enter a cancer cell, the two pieces of toxin can then destroy the cancer.

Macrophages are white blood cells that, depending on the signals they get from the immune system, become specialized in either increasing or decreasing inflammation. When macrophages are programmed to be pro-inflammatory, they help to increase inflammation, which is beneficial for fighting infections; when they are programmed to be anti-inflammatory, they help to decrease inflammation.

This regulated programming allows the body to fight off infections but also ensures that inflammation naturally subsides after the initial immune response and promotes tissue repair. The emergence of anti-inflammatory macrophages helps prevent an immune response from becoming excessive and dangerous, like what is observed in autoimmune diseases or in Acute Respiratory Distress Syndrome, or ARDS, which has been affecting some COVID-19 patients.

A new study from researchers at the University of Illinois Chicago published in the journal Nature Immunology suggests that macrophage programming is more complex than previously thought.

"We found that macrophage programming is driven by more than the immune system -- it is also driven by the environment in which the macrophages reside," said lead study author Asrar Malik, the UIC Schweppe Family Distinguished Professor and head of pharmacology and regenerative medicine at the College of Medicine.

The study specifically looked at macrophage programming in animal models of lung injury.

"We demonstrated that lung endothelial cells -- which are the cells that line blood vessels -- are essential in programming macrophages with potent tissue-reparative and anti-inflammatory functions," said Dr. Jalees Rehman, UIC professor of medicine and pharmacology and regenerative medicine and co-lead author of the paper.

The research team first analyzed the proteins, which function as chemical signals, released by blood vessel cells and then they conducted experiments to see whether those signals affected how macrophages functioned.

They found that one protein, called Rspondin3, was released at high levels during inflammatory injury and played a key role in macrophage programming.

"When we removed the gene responsible for Rspondin3 from the blood vessel endothelial cells, we observed that macrophages did not decelerate inflammation. Instead, the lungs became more injured," said Bisheng Zhou, UIC research assistant professor of pharmacology and regenerative medicine and first author of the study. "We tried this in multiple models of inflammatory lung injury and found consistent results, suggesting that blood vessels play an important instructive role in guiding the programming of macrophages."

In addition to providing a new avenue for drug developers to explore, Rehman said this finding provides a clue as to why some people may have better outcomes.

"The majority of people recover from a lung infection but, unfortunately, a subset of patients develop severe lung injury in the form of ARDS, which is what we have seen in the recent COVID-19 pandemic," Rehman said.

"It could be that these patients have underlying and perhaps undiagnosed poor vascular health and as a result, the blood vessels fail to send the appropriate cues to macrophages and turn off the inflammation," he said. "The lack of an adequate automatic braking system to slow inflammation once the bacteria or viruses have been eliminated leads to a situation in which our body's own unchecked immune system becomes the cause of even greater damage to vulnerable tissues and organs such as the lung."

Rehman said that even though the study focused on lungs, its findings could be also relevant to diseases in other organs such as the heart, intestines, brain and liver, where immune cells can cause damage if the necessary balance between pro-inflammatory and anti-inflammatory cells is disrupted.

Degradation of platinum, used as a key electrode material in the hydrogen economy, severely shortens the lifetime of electrochemical energy conversion devices, such as fuel cells. For the first time, scientists elucidated the movements of the platinum atoms that lead to catalyst surface degradation. Their results are published today in Nature Catalysis.

For more than half a century, platinum has been known as one of the best catalysts for oxygen reduction, one of the key reactions in fuel cells. However, it is difficult to meet the catalysts' long-term high activity and stability needed for the massive deployment of the hydrogen technology in the transportation sector.

Scientists led by Kiel University (Germany), in collaboration with the ESRF, University of Victoria (Canada), University of Barcelona (Spain) and Forschungszentrum Jülich (Germany), have now found out why and how platinum degrades. "We have come up with an atomistic picture to explain it", says Olaf Magnussen, professor at Kiel University and corresponding author of the article.

In order to achieve this, the team went to ESRF's beamline ID31 to study the different facets of platinum electrodes in electrolyte solution. They discovered how atoms arrange themselves and move on the surface during the processes of oxidation, the main reaction responsible for platinum dissolution.

The findings open doors to atomistic engineering: "With this new knowledge, we can imagine targeting certain shapes and surface arrangements of nanoparticles to enhance the stability of the catalyst. We can also find how the atoms move, so we could potentially add surface additives to suppress atoms moving the wrong way", explains Jakub Drnec, scientist at beamline ID31 and co-author of the study.

The fact that the experiments took place under electrochemical conditions similar to what happens in the actual device was key to translate the findings into fuel cell technology. "Because platinum surface rapidly changes during oxidation, these measurements became possible only thanks to a new, very fast technique for surface structure characterization. This method, high-energy surface X-ray diffraction, has been co-developed at the ESRF" explains Timo Fuchs, from Kiel University and co-author of the study. "And it is, in fact, the only technique that can provide this kind of information in the real environment", he adds. This is the first publication where atomic movements were determined by the technique under such conditions.

This research owes its success to the combination of the X-ray measurements at the ESRF with highly sensitive dissolution measurements performed at Forschungszentrum Jülich and advanced computer simulations. "Only such a combination of different characterization techniques and theoretical calculations provides a full picture of what goes on with the atoms at the nanoscale level in a platinum catalyst", notes Federico Calle-Vallejo from University of Barcelona, in charge of the simulations.

The next step for the team is to continue experiments that provide insight into the degradation mechanisms of further model facets mimicking edges and corners on catalyst particles. These results will provide a map of platinum stability under reaction conditions and allow researchers to develop rational strategies for the design of more stable catalysts in the future.

Palaeontologists from the Natural History Museums in Luxembourg and Maastricht have discovered a previously unknown species of brittle star that lived in the shallow, warm sea which covered parts of the present-day Netherlands at the end of the Dinosaur Era. The starfish-like creature was unearthed more than 20 years ago but has only now been identified as new to science. The name of the new fossil pays tribute to Dutch metal vocalist Floor Jansen, in recognition of the mutual inspiration between science and music.

Like so many exciting discoveries, the new fossil species had long passed unnoticed. It was a stroke of luck when a fossil collector noted the fossil of a tiny, starfish-like creature during one of his excursions to the world-famous ENCI HeidelbergCement company quarry near the Dutch city of Maastricht. The specimen was much smaller than other brittle-star fossils occasionally found at the same locality and thus much less likely to be collected. Dr John Jagt, palaeontologist at the Natural History Museum in Maastricht, soon identified the specimen as a long-spined brittle-star. "I reckoned the specimen belonged to a group of brittle-stars that is particularly rare in the fossil record but its true identity remained puzzling with the information at hand", Jagt explains. "When examining microfossils extracted from the same rocks that yielded the brittle-star fossil, I noticed microscopic skeletal fragments that seemed to belong to the same species", he continues. 20 years later, Jagt was proved right when Dr Ben Thuy and Dr Lea Numberger, palaeontologists at the Natural History Museum in Luxembourg, examined the brittle-star fossils from Maastricht from a different angle, taking into account the latest progress of knowledge in the field. "We were incredibly lucky to have both microscopic skeletal remains and a complete fossil skeleton of the same brittle-star species," Thuy highlights. "This provided an exceptionally complete picture of the species" Numberger continues. That the species turned out to be new to science was exciting in itself but there was more: "The new brittle star must have lived in a shallow, warm sea while its living relatives are found in the deep sea. This shows that there was a major shift in distribution over the past million years," Thuy explains. The experts were even able to gain insights into the mode of life of the new species. "Because the fossil individual was found wrapped around the stalk of a sea lily, we assume that the species lived with and probably even clung to these flower-like echinoderms," Jagt remarks. Interactions or associations between species are only rarely preserved in the fossil record. When scientists discover a new species, they have the privilege to name it. Often, species names refer to a locality or a specific character. Some also honour other experts in the field. In the case of the Maastricht brittle star, Jagt, Thuy and Numberger decided to combine their passions for fossils and heavy metal music and paid tribute to Dutch metal vocalist Floor Jansen and her band Nightwish. "Rock music and fossils are a perfect match. They have been inspiring each other for a long time" Numberger explains. The new fossil, Ophiomitrella floorae, is in excellent company, as can be experienced in the travelling exhibition "Rock Fossils on Tour", celebrating fossils named after rock bands and musicians like Kalloprion kilmisteri, an ancient worm honouring Motörhead's Ian "Lemmy" Kilmister, and currently on display (until January 3, 2021) at the Natural History Museum in Maastricht.

Ice is melting at a surprisingly fast rate underneath Shirase Glacier Tongue in East Antarctica due to the continuing influx of warm seawater into the Lützow-Holm Bay.

Hokkaido University scientists have identified an atypical hotspot of sub-glacier melting in East Antarctica. Their findings, published in the journal Nature Communications, could further understandings and predictions of sea level rise caused by mass loss of ice sheets from the southernmost continent.

The 58th Japanese Antarctic Research Expedition had a very rare opportunity to conduct ship-based observations near the tip of East Antarctic Shirase Glacier when large areas of heavy sea ice broke up, giving them access to the frozen Lützow-Holm Bay into which the glacier protrudes.

"Our data suggests that the ice directly beneath the Shirase Glacier Tongue is melting at a rate of 7-16 meters per year," says Assistant Professor Daisuke Hirano of Hokkaido University's Institute of Low Temperature Science. "This is equal to or perhaps even surpasses the melting rate underneath the Totten Ice Shelf, which was thought to be experiencing the highest melting rate in East Antarctica, at a rate of 10-11 meters per year."

The Antarctic ice sheet, most of which is in East Antarctica, is Earth's largest freshwater reservoir. If it all melts, it could lead to a 60-meter rise in global sea levels. Current predictions estimate global sea levels will rise one meter by 2100 and more than 15 meters by 2500. Thus, it is very important for scientists to have a clear understanding of how Antarctic continental ice is melting, and to more accurately predict sea level fluctuations.

Most studies of ocean-ice interaction have been conducted on the ice shelves in West Antarctica. Ice shelves in East Antarctica have received much less attention, because it has been thought that the water cavities underneath most of them are cold, protecting them from melting.

During the research expedition, Daisuke Hirano and collaborators collected data on water temperature, salinity and oxygen levels from 31 points in the area between January and February 2017. They combined this information with data on the area's currents and wind, ice radar measurements, and computer modelling to understand ocean circulation underneath the Shirase Glacier Tongue at the glacier's inland base.

The scientists' data suggests the melting is occurring as a result of deep, warm water flowing inwards towards the base of the Shirase Glacier Tongue. The warm water moves along a deep underwater ocean trough and then flows upwards along the tongue's base, warming and melting the ice. The warm waters carrying the melted ice then flow outwards, mixing with the glacial meltwater.

The team found this melting occurs year-round, but is affected by easterly, alongshore winds that vary seasonally. When the winds diminish in the summer, the influx of the deep warm water increases, speeding up the melting rate.

"We plan to incorporate this and future data into our computer models, which will help us develop more accurate predictions of sea level fluctuations and climate change," says Daisuke Hirano.

It is not every day that scientists are able to produce an entirely new kind of light, but when they do the implications can be dramatic. When twisted light beams carrying orbital angular momentum were uncovered in 1992, researchers realized the potential to increase data transmission speeds over current approaches. Separately, in 2005, the Nobel prize in physics was awarded for the invention of the optical frequency comb - a device that creates a spectrum of equally spaced frequencies of non-twisted light. Such combs have become fundamental tools for metrology and atomic clocks.

Now, thanks to research from Alan Willner, professor of electrical and computer engineering at USC Viterbi and his recently graduated PhD student Zhe Zhao, we can add a new structure to this list. In a paper published in Nature Communications, the pair showed how combining twisted light and frequency combs together can produce an even more novel structure of light.

For some time, Willner's lab, the Optical Communications Lab in the Ming Hsieh Department of Electrical Engineering, had separately researched twisted light beams and frequency combs. These two research paths were relatively separate in his lab until Zhao had a realization: What if we combined different optical frequencies and different twisted light? Combining these together resulted in something completely new.

At a given distance, the light can dynamically rotate around its center and revolve around another central axis. "It's analogous to the Earth rotating on its axis and at the same time revolving around the Sun, simultaneously experiencing two forms of dynamic motion. This new structure of light carries two forms of orbital angular momentum," Willner said. "Using different light frequencies and different twisted-light modes, combined together, can produce new dynamic structures of light."

The team's research sheds insight on our basic understanding of light generation and propagation. This innovation may have future applications in fields such as sensing, imaging, manufacturing, and metrology - anywhere that you may want light to have novel dynamic motion.

"Simply put, through this technique light can be tailored in more detailed and exquisite ways than ever before," said Zhao. Advances in how light can be dynamically structured may lead to major breakthroughs across a variety of areas. Its creation opens the door to a new set of tools.

For now, Willner, Zhao, and the rest of the research group are focused on what other unique designed light they can build from this new tool.

Osaka, Japan - Researchers at Osaka University have identified a fault in the RNA quality control system of cells that leads to the haywire production of toxic proteins in frontotemporal lobar degeneration and amyotrophic lateral sclerosis (FTLD/ALS). Their new study, published in The EMBO Journal, shows that an abnormality of the C9orf72 gene produces toxic proteins that hinder the cells' ability to destroy defective C9orf72 RNA, which leads to the buildup of more toxic proteins. Ultimately, this creates a vicious cycle that accelerates the disease process.

The incurable neurodegenerative disorders FTLD and ALS share genetic features, including their most common genetic cause: an expansion of the repeating portion of the C9orf72 gene. Cells use DNA codes to write instructions for manufacturing new proteins in the form of RNA. In C9orf72-associated FTLD/ALS, the repeat DNA is transcribed into defective repeat RNA, which clusters in the cell and manufactures toxic proteins.

"Repeat RNA can be toxic itself and is the source of highly toxic protein. So reducing repeat RNA could be a therapeutic option in FTLD/ALS caused by this genetic abnormality," says Kohji Mori, corresponding author of the study.

The researchers used cellular models to investigate the RNA exosome, the system responsible for destroying defective RNA. Damaging EXOSC10, a key player in the RNA exosome, increased the accumulation of repeat RNA and its toxic protein products. Cells with an accumulation of the toxic proteins showed EXOSC10 function going awry. The researchers confirmed the findings in cells derived from patients with the disorders, solidifying the RNA exosome as the site for degradation of pathogenic C9orf72-derived repeat RNA.

"The RNA exosome works to degrade the defective RNA until it becomes swamped by inhibitory effects of the toxic proteins, initiating a downward spiral that may exacerbate neurodegeneration in C9orf72-associated FTLD/ALS," says lead author Yuya Kawabe.

Typically, a DNA code is read in one direction, but the repeat expansion in C9orf72 is bidirectionally transcribed. The researchers tested RNA transcribed from both directions, referred to as sense and antisense RNAs. Both RNAs accumulated, produced toxic protein, and were degraded by EXOSC10.

The findings provide a look into the machinery that drives disease progression at the cellular level. People with FTLD/ALS have few options—no treatments can prevent FTLD/ALS, cure it, or even slow its progression. But this new understanding of the pathological process opens up avenues to explore for therapy options.

DALLAS - Aug. 24, 2020 - The immune protein STING has long been noted for helping protect against viruses and tumors by signaling a well-known immune molecule. Now, UT Southwestern scientists have revealed that STING also activates a separate pathway, one that directly kills tumor-fighting immune cells. Among other implications, the finding could lead to development of longer-lasting immunotherapies to fight cancer.

"This is a major surprise for the field and really broadens what is known about STING," says study leader Nan Yan, Ph.D., associate professor of immunology and microbiology at UTSW. "We're already pursuing ways to harness this mechanism to treat tumors."

STING was first identified about a decade ago as a protein that can activate the type I interferon (IFN) response in immune cells. The IFN response is a powerful and well-studied immune reaction that the body uses to fight everything from viruses and bacteria to rogue tumor cells. Since STING was found to have antiviral and antitumor properties, and to activate IFN, most researchers assumed the IFN pathway was the primary way STING carried out its immune activities. However, some have hypothesized that STING also has other functions; after all, it is found not only in humans and other mammals, but in ancient single-celled organisms that lived hundreds of million years ago, way before the emergence of IFN.

In this study published last month in the journal Immunity, Yan and his colleagues developed a version of STING that can't turn on the IFN response but is otherwise functional. Then, they began testing what STING could do independent of its ability to activate IFN. The first surprise, says Yan, was that mice carrying this engineered version of STING could still protect against herpes simplex virus type 1 (HSV-1) infection. This finding reveals that STING can fight against infection without engaging the IFN response.

"It looks like it was this historical misunderstanding that since STING can activate interferon, that's the only way it's controlling viruses," says Yan, a member of the Harold C. Simmons Comprehensive Cancer Center and a Rita C. and William P. Clements, Jr. Scholar in Medical Research. "We showed otherwise."

STING likely does fight viruses, in part, through its interactions with the IFN pathway, Yan adds. But the important lesson learned here is that IFN is not the only weapon STING has to fight viruses.

When the research team analyzed the immune cells in which STING couldn't signal the IFN pathway, they discovered something else - T cells quickly died when STING was activated. T cells, types of white blood cells, are main components of the adaptive immune system.

When they looked at T cells that were actively responding to a melanoma tumor in mice, Yan's group found that the tumor was producing molecules that signaled STING and, in turn, caused the death of the T cells trying to fight the tumor.

"We know that tumors have a number of ways to fight back against the immune system," says Yan. "The most well-known of these is that they turn off T cells, and that process is what many immunotherapies, such as checkpoint inhibitors, try to target. What we discovered is that tumors are also actively trying to kill T cells using the STING pathway. This reveals another opportunity for checkpoint inhibition immunotherapy."

When the researchers deleted STING from the mice, the animals' immune systems more effectively controlled melanoma tumors and fewer T cells died. Based on the results, Yan hypothesizes that drugs targeting STING could help T cells better fight tumors. In addition, methods of reducing levels of STING either through drugs or genetically engineered T cells could be combined with existing immunotherapies to make them more effective, by allowing T cells to survive for longer in the vicinity of a tumor.

Yan and his colleagues are already studying how drugs that target STING may work against cancer and are trying to better understand the molecules that link STING to T cell death.

In a paper published in NANO, a team of researchers from Xinjiang University, China have prepared Au@CDs photocatalyst with core-shell structure by combining coal-based carbon dots (CDs) with gold sol. With its high photocatalytic activity in the synthesis and visible-light photocatalytic N2/H2O to ammonia, this has far-reaching significance for the further development of coal resources to prepare high-performance materials.

Synthesis and visible-light photocatalytic N2/H2O to ammonia at atmospheric pressure and room temperature is considered to be the most ideal ammonia synthesis technology. However, fixing N2 to NH3 under mild conditions remains a major challenge.

In this study, coal-based carbon dots (CDs) were prepared by H2O2 oxidation method using cheap and ubiquitous coal as the carbon source. Then the gold sol was connected to CDs to obtain a core-shell structure photocatalyst Au@CDs by sodium borohydride (NaBH4) reduction method. While characterizing the material structure, the photocatalytic N2/H2O to ammonia performance of Au@CDs was investigated.

The results show that the prepared Au@CDs has higher photocatalytic activity for photocatalytic N2/H2O to ammonia, the yield of Au@CDs photocatalytic N2/H2O to ammonia about 3.5-fold higher than that of bare CDs. Using N2-TPD, UV-Visible, EPR, and electrochemical tests to study the photoelectric properties of the prepared photocatalysts. The photocatalyst Au@CDs prepared by CDs coated with precious metal Au not only improves the carrier performance of the catalyst under visible light but also inhibits the recombination of photocatalyst hole pair, promote the charge transfer ability, and make the photocatalyst and hold move smoothly to the photocatalyst surface. At the same time, it also improves the adsorption and dissociation ability of N2 on the catalyst surface, thus promoting the photocatalytic N2/H2P ammonia synthesis reaction.

This work will contribute to the better design of carbon nanoparticle-coated metal-type photocatalytic materials, which will be of far-reaching significance for the further development of coal resources to prepare high-performance materials. The Xinjiang University team is currently exploring the preparation of more suitable photocatalysts to improve photocatalytic nitrogen fixation for ammonia synthesis.

This work was grateful for the financial support of the National Natural Science Foundation of China (21862020)

Researchers at Tokyo Institute of Technology (Tokyo Tech) have used artificial intelligence (AI) to predict the degree of water repulsion and protein adsorption by ultra-thin organic materials. By enabling accurate predictions of water repulsion and protein adsorption even by hypothetical materials, the team's approach opens up new possibilities for the screening and design of organic materials with desired functions.

Using informatics[1] in the field of inorganic material design has led to the rise of new types of catalysts, batteries and semiconductors. In contrast, informatics-based design of biomaterials (i.e. organic as opposed to inorganic solid-state materials) is only just beginning to be explored.

Now, a team of researchers at Tokyo Tech led by Associate Professor Tomohiro Hayashi has successfully made inroads into this emerging field. They used machine learning[2] with an artificial neural network (ANN) [3] model to predict two key properties -- the degree of water repulsion and affinity to protein molecules -- of ultra-thin organic materials known as self-assembled monolayers (SAMs) [4] . SAMs have been widely used to create model organic surfaces to explore the interaction between proteins and materials due to their ease of preparation and versatility.

By training the ANN using a literature-based database of 145 SAMs, the ANN became capable of predicting water repulsion (measured in terms of the degree of water contact angle[5]) and protein adsorption accurately. The team went on to demonstrate the prediction of water repulsion and protein adsorption even for hypothetical SAMs.

SAMs are attractive for the development of many applications in organic electronics and the biomedical field. The two properties investigated in the study are of enormous interest to biomedical engineers. "For example, implant materials that exhibit low water contact angle enable fast integration with the surrounding hard tissues," Hayashi says. "In the case of artificial blood vessels, the resistance to the adsorption of blood proteins, in particular fibrinogen, is a critical factor to prevent platelet adhesion and blood clotting."

Overall, the study opens the door to advanced material screening and design of SAMs with potentially greatly reduced costs and time scales.

The researchers plan to continue scaling up their database and, within a few years, to expand their approach to include polymers, ceramics and metals.

Forest restoration is a crucial element in strategies to mitigate climate change and conserve global biodiversity in the coming decades, and much of the focus is on formerly tree-covered lands in the tropics.

But recent forest restoration research rarely acknowledges the social dimensions or environmental justice implications of such projects. A new study finds that nearly 300 million people in the tropics live on lands suitable for forest restoration, and about a billion people live within 5 miles of such lands. Many of these people live in poverty.

Just and equitable implementation of restoration projects will require that communities be empowered to manage and use local forests, according to the authors of the study published in the journal Nature Ecology & Evolution. Community management of forest areas includes the rights to access the forests, withdraw forest resources, and manage lands for community benefit.

"We argue that the success of global forest restoration critically depends on prioritizing local communities," said study lead author James Erbaugh of Dartmouth College, who earned a doctorate from the University of Michigan School for Environment and Sustainability.

"Empowering local communities to restore forests can provide human well-being benefits to millions of the most deprived and marginalized people, as well as environmental benefits for all."

Study co-authors include SEAS professor Arun Agrawal, as well as other current and former graduate students and postdoctoral researchers at the U-M school.

Their analysis examines the overlap between opportunities for tropical forest restoration, human populations, development and national policies for community forest ownership. The researchers focused on the opportunities in tropical countries because of the potential there for removing atmospheric carbon, promoting biodiversity conservation and contributing to the well-being of local residents.

For the study, the researchers combined two datasets: one that classifies forest restoration opportunities using demographic, geographic and land-cover data, and another that uses estimates from a land-change model to predict carbon removal from forest restoration.

They found that 294.5 million people live in recently tree-covered areas in the tropics that hold promise for forest restoration--places the researchers call forest restoration opportunity areas. About 1 billion people live within 5 miles of land predicted to be suitable for forest restoration over the next 30 years if a moderate carbon-tax incentive of around $20 per ton of carbon dioxide is implemented.

Brazil, the Democratic Republic of the Congo, India and Indonesia have the greatest number of people living in or near forest restoration opportunity areas with the greatest potential to remove heat-trapping carbon dioxide from the atmosphere and sequester it in forests, according to the study.

Within low-income countries in the tropics, 12% of the population lives in forest restoration opportunity areas, a finding that highlights the potential for improving the livelihood and well-being of millions of people who are often underserved by standard investments in infrastructure and development, according to the authors.

Nighttime satellite images showing the brightness and extent of artificial lighting on the Earth's surface can be used as a proxy for multiple development indicators. In the current study, areas in low-income nations with the least nighttime light radiance and the greatest carbon-removal potential indicated the places where forest restoration projects might best complement sustainable development agendas.

"There are many opportunities in central, eastern and southern Africa to restore forests and provide socioeconomic and infrastructure benefits to local people facing many multidimensional deprivations," said U-M's Agrawal, who is also editor-in-chief of the journal World Development.

"Forest landscape restoration that prioritizes local communities by affording them rights to manage and restore forests provides a promising option to align global agendas for climate mitigation, conservation, environmental justice and sustainable development."

On the other hand, denying decision-making powers to affected locals could pose serious ethical problems, especially if some of those individuals are displaced by forest-restoration projects designed to help mitigate human-caused climate change and preserve biodiversity.

Such exclusion would force some of the most multidimensionally poor people--those who live in rural areas within low-income countries--to move or give up their current livelihood for a global carbon and biodiversity debt to which they contributed little, according to the researchers.

And while local communities should be empowered to manage forests for restoration, opportunities to expand community forest ownership must also be explored, they say..

Most of the forest restoration opportunity areas analyzed in the study are in countries with preexisting legal frameworks for community forest ownership, which represents a stronger set of resource rights than community forest management.

Continued efforts to expand community forest ownership are especially important in countries with a substantial proportion of people living in forest restoration opportunity areas, such as the Central African Republic, the Democratic Republic of the Congo, Thailand and the Lao People's Democratic Republic.

Forest restoration projects in the tropics involve planting trees on land previously cleared for agriculture, timber harvesting or other purposes. Increasing support for such efforts is becoming available from both government agencies and nongovernmental organizations, Agrawal says.

The authors of the Nature Ecology & Evolution paper support the use of a landscape planning and management tool called forest landscape restoration, or FLR, as a way to include local communities in forest-restoration projects in the tropics. FLR "aims to restore ecological integrity and enhance human well-being on deforested and degraded lands through the inclusion and engagement of local stakeholders," according to the researchers.

Proponents of FLR say it contributes to human well-being through the use and sale of forest products, that it promotes increases in local food and water security, and that it respects diverse cultural values that local peoples hold for trees and forests.

"Our study highlights the critical need for close ties between researchers, decision makers and local communities to secure greater wellbeing for people and ecosystems," Agrawal said. "Those working on forests--whether government agencies or researchers--forget far too often the necessity of working with people, not against them."

A congenital disorder of the fat metabolism can apparently cause chronic hyperreaction of the immune system. This is the conclusion reached by researchers from the University of Bonn in a recent study. The results are published in the journal Autophagy.

Some individuals suffer from a genetic defect that causes their cells to form an unusual kind of fat. The consequences of this very rare disorder are grave. In some patients, the nerve cells responsible for transmitting pain die over time; others lose their hearing or suffer early-onset dementia. A frequent symptom are also skin defects that only heal with great difficulty or even become chronic.

It has been known for several years that the underlying mutations alter an important enzyme in the fat metabolism. The enzyme normally produces a certain type of fat. Due to the mutations, however, it now uses the wrong building block. This causes large quantities of so-called deoxysphingolipids to be produced in the body's cells - around ten times more than normal. "These exotic molecules have the disadvantage that they can only be degraded very slowly," explains Dr. Lars Kürschner from the LIMES Institute at the University of Bonn (the acronym stands for "Life and Medical Sciences"). "In high concentrations they also form crystal-like lumps in the affected cells."

The consequences for the cells are anything but pleasant, as the adjunct professor together with colleagues already noted in 2017: The fat crystals massively disrupt the function of the mitochondria, i.e. the cell's internal powerhouses. Particularly cell types with a high energy requirement can suffer so much that they perish. "This mainly affects the nerve cells," says Kürschner. "This is also the reason for the impaired pain transmission and other neurological symptoms." In their current work, the researchers were also able to detect such mitochondrial defects in connective tissue cells of mice.

The fact that they were also able to track down another effect is due in part to preliminary work by colleagues in Bonn: Some time ago, the immunologist Prof. Dr. Eicke Latz from the University Hospital in Bonn showed that cholesterol crystals can cause inflammatory reactions. Cholesterol is also a fat. "We therefore wanted to find out whether the deoxysphingolipid crystals also have an effect on the immune system," explains Kürschner.

Double dose of fat crystals

To this end, the researchers examined certain immune cells of the mouse, the macrophages. In a sense, they are the body's own garbage collection system: After a cell has died, its remains are taken up by macrophages, digested and thereby disposed of. In the course of the disease, macrophages, like nerve or connective tissue cells, also produce large amounts of deoxysphingolipids. At the same time, they also absorb the abnormal fats of dead cells in their capacity as garbage trucks. In other words, they get twice the dose of fat crystals.

This process massively disrupts the function of various cell components, such as the mitochondria, in these macrophages (as in neurons and other cells). They respond by dismantling the damaged powerhouses in order to produce new mitochondria from their components - a mechanism known as autophagy. "Nerve cells and connective tissue cells also do this," says Mario Lauterbach, lead author of the study. "However, macrophages are immune cells; this means that they have additional options for perceiving damage and reacting to it. One of them is that in autophagy they activate a molecular complex that promotes inflammation, known as the inflammasome."

The activated inflammasome in turn causes the macrophage to release inflammatory messengers. In this way it calls on other immune cells for help, including other macrophages, which further intensify this effect. "One consequence of the accumulation of these abnormal fats is therefore a manifesting inflammation," explains Lauterbach. This may be responsible for the poorly healing wounds observed in many patients. The researchers now hope that these symptoms can be treated with drugs that inhibit autophagy. "There are already some candidates that are currently being tested," emphasizes Lars Kürschner.

The results could also shed new light on a much more common condition: diabetes. In diabetes patients, deoxysphingolipid production is also increased in some cells; the cause is still largely unknown. And in diabetes, too, physicians regularly observe severe chronic inflammation, which contributes to the serious effects of the disease.

The success of the study is also the result of the excellent cooperation between the LIMES Institute and the Institute of Innate Immunity on the Venusberg, headed by Prof. Latz, emphasizes Kürschner. Both groups have been working together intensively for years, including in the Transregional Collaborative Research Center 83 and the Cluster of Excellence ImmunoSensation at the University of Bonn. He adds that a further factor is the outstanding equipment with state-of-the-art microscopes and analysis devices, which has been further improved by the success in the Excellence Initiative and is unparalleled in the university landscape.

How can you turn something flat into something three-dimensional? In architecture and design this question often plays an important role. A team of mathematicians from TU Wien (Vienna) has now presented a technique that solves this problem in an amazingly simple way: You choose any curved surface and from its shape you can calculate a flat grid of straight bars that can be folded out to the desired curved structure with a single movement. The result is a stable form that can even carry loads due to its mechanical tension.

The step into the third dimension

Suppose you screw ordinary straight bars together at right angles to form a grid, so that a completely regular pattern of small squares is created. Such a grid can be distorted: all angles of the grid change simultaneously, parallel bars remain parallel, and the squares become parallelograms. But this does not change the fact that all bars are in the same plane. The structure is still flat.

The crucial question now is: What happens if the bars are not parallel at the beginning, but are joined together at different angles? "Such a grid can no longer be distorted within the plane," explains Przemyslaw Musialski. "When you open it up, the bars have to bend. They move out of the plane into the third dimension and form a curved shape."

At the Center for Geometry and Computational Design (GCD) (Institute for Discrete Mathematics and Geometry) at TU Wien, Musialski and his team developed a method that can be used to calculate what the flat, two-dimensional grid must look like in order to produce exactly the desired three-dimensional shape when it is unfolded. "Our method is based on findings in differential geometry, it is relatively simple and does not require computationally intensive simulations," says Stefan Pillwein, first author of the current publication, which was presented at the renowned SIGGRAPH conference and published in the journal ACM Transactions on Graphics.

Experiments with the laser scanner

The team then tried out the mathematical methods in practice: The calculated grids were made of wood, screwed together and unfolded. The resulting 3D shapes were then measured with a laser scanner. This proved that the resulting 3D structures did indeed correspond excellently to the calculated shapes.

Now even a mini pavilion roof was produced; measuring 3.1 x 2.1 x 0.9 metres. "We wanted to know whether this technology would also work on a large scale - and it worked out perfectly," says Stefan Pillwein.

"Transforming a simple 2D grid into a 3D form with a single opening movement not only looks amazing, it has many technical advantages," says Przemyslaw Musialski. "Such grids are simple and inexpensive to manufacture, they are easy to transport and set up. Our method makes it possible to create even sophisticated shapes, not just simple domes".

The structures also have very good static properties: "The curved elements are under tension and have a natural structural stability - in architecture this is called active bending," explains Musialski. Very large distances can be spanned with very thin rods. This is ideal for architectural applications.