Culture

The work of Leonardo Da Vinci is an invaluable heritage of the 15th century. From engineering to anatomy, the master paved the way for many scientific disciplines. But what else could the drawings of Da Vinci teach us? Could molecular studies reveal interesting data from the past? These questions led an interdisciplinary team of researchers, curators and bioinformaticians, from both the University of Natural Resources and Life Science and the University of Applied Science of Wien in Austria, as well as the Central Institute for the Pathology of Archives and Books (ICPAL) in Italy, to collaborate and study the microbiome of seven different drawings of Leonardo Da Vinci. 

The molecular study of art pieces has already proved to be a valuable approach, and Dr Piñar, first author of the study, is not at her first try. In 2019, her team was able to investigate the storage conditions and even the possible geographical origin of three statues requisitioned from smugglers through the study of their microbiome and, earlier this year, the microbiome of ancient parchments allowed to elucidate the animal origin of the skins used for their manufacture 1,000 years ago. In the study presented here, the Austrian team is using an innovative genomic approach called Nanopore, considered as third-generation sequencing, to reveal for the first time the complete microbiome composition of several of Da Vinci's drawings. The study is published today in Frontiers in Microbiology.

Overall, the results show a surprising dominance of bacteria over fungi. Until now, fungi were thought to be a dominant community in paper-supported art and tended to be the main focus of microbial analysis due to their biodeterioration potential. Here, a high proportion of these bacteria are either typical of the human microbiome, certainly introduced by intensive handling of the drawings during restoration works, or correspond to insects microbiomes, which could have been introduced, a long time ago, through flies and their excrements. 

A second interesting observation is the presence of a lot of human DNA. Unfortunately, we cannot assume that this DNA comes from the master himself but it might rather have been introduced by the restoration workers over the years. Finally, for both bacterial and fungal communities, correlation with the geographical location of the drawings can be observed. 

Altogether, the insects, the restoration workers, and the geographic localization seem to all have left a trace invisible to the eye on the drawings. While it is difficult to say if any of these contaminants originate from the time when Leonardo Da Vinci was sketching its drawings, Dr Piñar highlights the importance that tracking these data could have: "The sensitivity of the Nanopore sequencing method offers a great tool for the monitoring of objects of art. It allows the assessment of the microbiomes and the visualization of its variations due to detrimental situations. This can be used as a bio-archive of the objects' history, providing a kind of fingerprint for current and future comparisons." Thus, scientists could develop new methods to not only conserve the visual appearance of art but also to document the invisible journey of our artistic and cultural heritage.

Philadelphia, November 20, 2020--Researchers at Children's Hospital of Philadelphia (CHOP) have resolved a severe lymphatic disorder in a girl with Noonan Syndrome that had led to upper gastrointestinal bleeding, fluid collection around the lungs, and numerous surgeries that had been unable to resolve her symptoms. By identifying a genetic mutation along a pathway related to lymphatic vessel development and function, the research team was able to target the pathway using an existing drug they had used in a previous case to remodel a patient's lymphatic system.

The case study, which was published today in Pediatrics, describes a resolution of the patient's symptoms within three months while on the medication.

"This study is quite significant," said first author Yoav Dori, MD, PhD, Director of the Jill and Mark Fishman Center for Lymphatic Disorders at CHOP. "Inhibiting this pathway seems to have sweeping, widespread effects on the lymphatic system. How this process occurs is not fully understood, but is remarkable in its speed and breadth. This gives us a lot of hope for treating other patients with genetic mutations along this same pathway in the future."

The patient described in the paper, Maria, first came to CHOP when she was 14, after experiencing severe anemia due to upper gastrointestinal bleeding, as well as other symptoms including fluid build-up in the cavity around her lungs, chronic fatigue, delayed puberty, and difficulty gaining weight. Maria had been born with Noonan Syndrome, a genetic disorder that prevents normal development in various parts of the body and often results in short stature, heart defects and other physical problems, including an abnormal lymphatic system. Despite aggressive medical therapy elsewhere, Maria continued to bleed internally, and she underwent multiple blood transfusions to try to stabilize her health.

Within two days of transferring to CHOP, the lymphatics team, led by Dori, determined Maria had many lymphatic irregularities, which were leading to internal bleeding and lung problems, so they scheduled Maria's first intervention, a lymphatic embolization procedure that would seal the leaky vessels in her gut.

However, within two months of the procedure, Maria's gastrointestinal bleeding recurred. Over the following 8 months, she underwent two additional procedures, as well as a cauterization procedure to close off some of the blood vessels in her gut, but the benefits of each procedure lasted only about three months before the bleeding and her symptoms returned.

Based on whole exome sequencing done at CHOP's Center for Applied Genomics, the research team learned that Maria had a genetic mutation in the SOS1 gene, which operates along the RAS-MAPK pathway. This pathway involves mitogen-activated protein kinase (MEK), and Maria's mutation caused an overproduction of MEK, which resulted in the uncontrolled proliferation of her lymphatic vessels.

The research team had previously used a MEK inhibitor in another patient with a severe lymphatic disorder with great success. That patient had a mutation in the ARAF gene, which is also on the RAS-MAPK pathway. Within months of beginning treatment with trametinib, a MEK inhibitor, the patient saw a resolution of his symptoms and a complete remodeling of his lymphatic system.

Given that SOS1 operates on the same pathway as ARAF, Jean Belasco, MD, an oncologist in CHOP's Cancer Center who co-led the study, applied for compassionate use of the drug in Maria's case, given the lack of other treatment options.

"The success of trametinib in another patient with a mutation on the RAS-MAPK pathway encouraged us to try this approach, since other procedures and therapies continued to be unsuccessful," Belasco said. "Although we are in the early days of this type of personalized medicine, the hope is that by looking at patients' mutations, we can find more drugs and better care for patients with genetic diseases."

Within three months of starting the drug, Maria's vital signs stabilized. The bleeding stopped, her electrolyte, hemoglobin, and albumin levels returned to normal, and she began to gain weight. Maria's mother noticed that Maria wasn't going through periods of exhaustion anymore, and her pallor improved.

"She looks better than she's ever looked," her mother said. "She looks like a normal teenager. It's like night and day. She's also a lot happier. I think she knew deep down she was dying. The medicine gave her hope."

Hakon Hakonarson, Director of the Center for Applied Genomics and co-author of the paper, said that although Maria's SOS1 mutation is distinctly different than the ARAF mutation seen in the other patient, the drug was equally effective because it targets and blocks the function of MEK. He likened the scenario to a pathway where 15 events need to occur for a cell to function. Maria's SOS1 mutation might occur at step nine, whereas the ARAF mutation might occur at step three, but both genes are on a chain that ultimately passes through a tunnel that leads to phosphorylation and overactivity of MEK. Since both mutations were so-called gain of function mutations, MEK - and thus lymphatic activity - was overexpressed in both patients. The MEK inhibitor put the brakes on a system in overdrive.

"Remarkable advances in genetics have allowed us to uncover these mutations and cluster them into selective pathways and determine effective therapies based on genetic mutations with very high precision," said Hakonarson. "No one could have guessed that this drug would have worked for Maria without knowing the underlying genetics. This discovery is extremely important because Noonan Syndrome has the biggest patient population with alterations in MEK signaling. Not all Noonan patients will have mutations that respond to this therapy, but a very good number of them will."

He added that the treatment could also benefit patients with other genetic defects, though he noted the ongoing use of the drug treats the symptoms caused by these mutations, but does not fix the gene or cure the underlying condition.

"MEK inhibition has the potential to have significant effects on other organ systems affected by RAS-MAPK gene defects, such as the heart, eyes, skin and the coagulation system," Hakonarson said.

Hakonarson is also part of CHOP's Comprehensive Vascular Anomalies Program (CVAP), a CHOP Frontier Program that uses state-of-the-art genomics and personalized research strategies to determine the causes of complex vascular conditions and identify targeted therapies. The program works closely with the Lymphatic Imaging and Interventions Frontier Program, which is led by Dori. CHOP's Frontier Programs conduct cutting-edge research that translates into advanced clinical care. The CVAP, in particular, draws on the extensive clinical and genomic research capacity within the Cancer Center and Center for Applied Genomics.

Even with the success of the breakthrough treatment pioneered by these programs, it is not entirely clear why MEK inhibitors not only resolve patients' symptoms but also completely remodel their lymphatic systems. Hakonarson said one possibility is that when mutated genes cause uncontrolled growth of the lymphatic system, the body's vessels leak fluid everywhere in the body. When you shut down the unregulated growth, other homeostatic mechanisms that are balancing the system come into effect, so the overreactive cells that were growing out of control die and are replaced by normal cells that gradually build up the lymphatic system.

Whatever the mechanism, Maria's mother said her daughter had no hesitation at being the first patient with Noonan Syndrome to try this treatment to resolve a lymphatic issue.

"Maria saw the value from the beginning," she said. "She saw the value for herself, but she was also thinking of other Noonan kids, some of whom have passed away from lymphatic issues. She was willing and eager."

A new synthetic probe offers a safe and straightforward approach for visualizing chromosome tips in living cells. The probe was designed by scientists at the Institute for Integrated Cell-Material Science (iCeMS) and colleagues at Kyoto University, and could advance research into aging and a wide range of diseases, including cancers. The details were published in the Journal of the American Chemical Society.

"Chromosome ends are constantly at risk of degradation and fusion, so they are protected by structures called telomeres, which are made of long repeating DNA sequences and bound proteins," says iCeMS chemical biologist Hiroshi Sugiyama, who led the study. "If telomeres malfunction, they are unable to maintain chromosome stability, which can lead to diseases such as cancer. Also, telomeres normally shorten with each cell division until they reach their limit, causing cell death."

Visualizing telomeres, especially their physical arrangements in real-time, is important for understanding their relevance to disease and aging. Several visualization approaches already exist, but they have disadvantages. For example, some can only observe telomeres in preserved, or 'fixed', cells. Others are time-consuming or involve harsh treatments that denature DNA.

Sugiyama and his colleagues overcame these issues by using a synthetic pyrrole-imidazole polyamide (PIP) probe that can precisely deliver a fluorescent compound to telomeres on the tips of chromosomes.

"PIPs are a class of small molecules made from pyrrole and imidazole molecules that can be pre-programmed to bind to a selected DNA sequence," explains Yutaro Tsubono, the first author of this study.

The team designed a PIP that targets the DNA repeating sequence found in telomeres. A fluorescent compound, called silicon-rhodamine, was attached to the PIP. The probe, called SiR-TTet59B, binds to telomeres in living cells. When the low-intensity near-infrared light is shone on the cells, the silicon-rhodamine fluoresces, showing the telomeres in action.

"Our study on this programmable, near-infrared probe creates opportunities to use these molecules in biological and medical applications," says iCeMS bioengineer Ganesh Pandian Namasivayam.

The team used their probe to observe telomere dynamics during different phases of cell division and to gauge telomere length by measuring the fluorescence intensity. Being able to visualize telomere length was both surprising and exciting, says Namasivayam, as it can be developed to create an efficient and robust approach for detecting severe telomere shortening in diseases, such as age-related retinal degeneration, with low energy light.

Since PIPs can be designed to target any DNA sequence in the genome by changing their arrangement, the scientists anticipate the approach can be adapted to make near-infrared fluorescent probes for visualizing other important DNA sequences related to disease.

Researchers analyzing snow and stream samples from the National Geographic and Rolex Perpetual Planet Everest Expedition have found evidence of microplastic pollution on Mount Everest. While the highest concentrations of microplastics were around Base Camp where hikers and trekkers spend the most time, the team also found microplastics as high up as 8,440 meters above sea level, just below the summit. The findings appear November 20 in the journal One Earth.

"Mount Everest has been described as 'the world's highest junkyard,'" says first author Imogen Napper (@Imogennapper), a National Geographic Explorer and scientist based at the University of Plymouth who is described by her colleagues as a "plastic detective." "Microplastics haven't been studied on the mountain before, but they're generally just as persistent and typically more difficult to remove than larger items of debris."

Microplastics--tiny particles of plastic that come from the slow breakdown of larger litter--pose a huge ecological threat because they are easily consumed by animals and are so small that they are difficult to clean up. Microplastics are common in the ocean, but are not as carefully studied on land, especially remote mountaintops.

"I didn't know what to expect in terms of results, but it really surprised me to find microplastics in every single snow sample I analyzed. Mount Everest is somewhere I have always considered remote and pristine. To know we are polluting near the top of the tallest mountain is a real eye-opener."

While some members of the research team climbed the mountain collecting samples during the Everest expedition in the spring of 2019, much of the work was done in a lab many miles away, where Napper and her team analyzed the samples. "The closest I got to Mount Everest was in my lab at University of Plymouth in the UK," Napper jokes. She wanted to determine not only whether there was plastic on the mountain, but what type of plastic was there. This is an important step in figuring out where the pollution originated.

"The samples showed significant quantities of polyester, acrylic, nylon, and polypropylene fibers," says Napper. "Those materials are increasingly being used to make the high-performance outdoor clothing climbers use as well as tents and climbing ropes, so we highly suspect that these types of items are the major source of pollution rather than things like food and drink containers."

While this study clearly demonstrated the presence of microplastics on Mount Everest, the best way to clean this pollution remains to be seen.

"Currently, environmental efforts tend to focus on reducing, reusing, and recycling larger items of waste. This is important, but we also need to start focusing on deeper technological solutions that focus on microplastics, like changing fabric design and incorporating natural fibers instead of plastic when possible," she says.

The researchers also hope that their work will help clarify the extent to which plastic pollution jeopardizes all environments, not just the ocean.

"These are the highest microplastics discovered so far," says Napper. "While it sounds exciting, it means that microplastics have been discovered from the depths of the ocean all the way to the highest mountain on Earth. With microplastics so ubiquitous in our environment, it's time to focus on informing appropriate environmental solutions. We need to protect and care for our planet."

More evidence has emerged that food labelling can encourage manufacturers to improve product nutrition, but University of Melbourne experts say the star labelling system must be compulsory to make a big difference.

A team from the University of Melbourne, the University of Auckland, and the George Institute for Global Health analysed product nutrition labels in Sydney and Auckland supermarkets to see if the Health Star Rating system (HSR) made a difference to how the food industry formulates food.

Nutritional information is mandatory on the back of packaged Australian and New Zealand foods but HSR labels, which have appeared on the front since 2014 and rate a food from 0.5 (least healthy) to five (most healthy) stars, are voluntary.

The most comprehensive study of food industry response to the HSR system, published in PLOS Medicine, has confirmed that HSR labelling causes some products to become healthier.

The Australia and New Zealand Ministerial Forum on Food Regulation introduced the voluntary front-of-pack HSR and a published HSR calculator decides how many stars a food gets. HSR labels aim to improve diets by encouraging consumers to choose healthier products and prompting manufacturers to reformulate their products to be healthier.

This study looked at the reformulation effects of HSR labels. Researchers analysed nutrition and labelling information on packaged products in four major New Zealand supermarkets annually from 2013, and Sydney supermarkets Aldi, Coles, IGA, and Woolworths from 2014.

They tracked the nutrition information of 58,905 unique packaged food products to see if HSR labelling led to nutrient composition changes. Using the HSR calculator, they also scored unlabelled products to allow control comparisons.

Products that elected to display the HSR on-pack were 6.5 and 10.7 per cent more likely to increase their HSR score by 0.5 stars than those that didn't display the stars in Australia and New Zealand respectively.

New Zealand products with HSR showed a four per cent decline in salt content, while Australian products fell by 1.4 per cent. The HSR was associated with a 2.3 per cent decrease in sugar content in New Zealand and a statistically insignificant 1.1 per cent decline in Australia.

The healthiest products that would have scored four to five stars showed little healthier reformulation - most reformulation occurred in less healthy products with HSR labels.

In Australia, an average product with HSR that scored 0.5 to 1.5 stars lost 14kJ of energy per 100g (1.3 per cent), compared to a product that scored four to five stars which saw almost no changes in energy. Similar patterns were observed for almost all nutrients studied in both countries.

Lead author and University of Melbourne Research Fellow Dr Laxman Bablani said while the improvements sounded small, even modest changes could lead to big health impacts at a population level.

"If the labels were compulsory the impact could be much greater, as HSR adoption by the unhealthiest products was less than half that of the healthiest products," Dr Bablani said.

In 2019, around 15 per cent of products that scored two stars had HSR labels in both countries, compared to more than 35 per cent of those that scored four stars and above. Examples of positive reformulation included:

A popular flavoured cracker now has six per cent less fat and roughly 10 per cent less sodium per 100g than before it adopted HSR labels in 2016. This took it from 1.5 to two stars.

Several instant soup varieties cut sodium and energy to increase their rating from three to 3.5 stars in the year they were labelled.

A major supermarket branded barbeque sauce cut sugar by 4.5g per 100g (9.6 per cent) in 2017 when it adopted HSR labels.

University of Auckland Professor Cliona Ni Mhurchu said the HSR could have a much bigger impact if more unhealthy products adopted it.

"Our study suggests that the total effect of HSR on supporting healthier population diets could be markedly increased if it was adopted by many more products," Professor Ni Mhurchu said.

"In short, it suggests that making the HSR mandatory would generate substantially greater public health benefits than the current voluntary system."

Senior author and University of Melbourne Professor Tony Blakely agreed compulsory HSR labels could improve unhealthy foods.

"There is little incentive for manufacturers to label unhealthy foods voluntarily," Professor Blakely said.

"If it was compulsory, the quality of packaged food would improve, and consumers may possibly make better choices about healthy and unhealthy foods."

A plant used in traditional Chinese medicine has evolved to become less visible to humans, new research shows.

Scientists found that Fritillaria delavayi plants, which live on rocky slopes of China's Hengduan mountains, match their backgrounds most closely in areas where they are heavily harvested.

This suggests humans are "driving" evolution of this species into new colour forms because better-camouflaged plants have a higher chance of survival.

The study was carried out by the Kunming Institute of Botany (Chinese Academy of Sciences) and the University of Exeter.

"It's remarkable to see how humans can have such a direct and dramatic impact on the colouration of wild organisms, not just on their survival but on their evolution itself," said Professor Martin Stevens, of the Centre for Ecology and Conservation on Exeter's Penryn Campus in Cornwall.

"Many plants seem to use camouflage to hide from herbivores that may eat them - but here we see camouflage evolving in response to human collectors.

"It's possible that humans have driven evolution of defensive strategies in other plant species, but surprisingly little research has examined this."

In the new study, the researchers measured how closely plants from different populations matched their mountain environment and how easy they were to collect, and spoke to local people to estimate how much harvesting took place in each location.

They found that the level of camouflage in the plants was correlated with harvesting levels.

In a computer experiment, more-camouflaged plants also took longer to be detected by people.

Fritillaria delavayi is a perennial herb that has leaves - varying in colour from grey to brown to green - at a young age, and produces a single flower per year after the fifth year.

The bulb of the fritillary species has been used in Chinese medicine for more than 2,000 years, and high prices in recent years have led to increased harvesting.

"Like other camouflaged plants we have studied, we thought the evolution of camouflage of this fritillary had been driven by herbivores, but we didn't find such animals," said Dr Yang Niu, of the Kunming Institute of Botany. "Then we realised humans could be the reason."

Professor Hang Sun, of the Kunming Institute of Botany, added: "Commercial harvesting is a much stronger selection pressure than many pressures in nature.
"The current biodiversity status on the earth is shaped by both nature and by ourselves."

An international research team led by UCSF scientists has shown, for the first time, that gut immune cells travel to the brain during multiple sclerosis (MS) flare-ups in patients. These gut cells seem to be playing a protective role, helping drive MS symptoms back into remission.

Scientists know that in MS, other types of immune cells go haywire and attack myelin, crucial insulation material that helps nerve cells communicate with one another quickly and reliably. The resulting damage leads to periodic MS attacks that can leave patients struggling with vision loss, memory problems, pain and other symptoms. These "relapse" symptoms often subside on their own after days or weeks, but medical experts still don't have a good understanding of what flips the switch from flare-up to remission and back again.

The new findings, published November 20, 2020 in Science Immunology, suggest that an unexpected new player might help bring flare-ups under control: immune cells from the gut that express a type of antibody called IgA. In the gut, these cells serve as a critical first line of defense against foreign invaders and, scientists think, help keep the teeming bacteria of our gut microbiome from growing out of control. Recently, a UCSF-led international research team made the surprising discovery that, in animal models of MS, these gut immune cells leave the digestive system and travel to the brain where they appear to help cut inflammation.

"It was a very new idea," said Sergio Baranzini, PhD, a professor of neurology and member of the UCSF Weill Institute for Neurosciences, lead author on the new study. "Nobody thought to look for this type of immune cell."

Now the team, including scientists in Canada, Germany, Sweden and Switzerland, has gone a step further, finding traces of the IgA antibody in the cerebrospinal fluid of MS patients during flare-ups, but not when episodes are in remission. They also found signs of IgA-producing immune cells in donated postmortem brain tissue that had been damaged during MS attacks. The findings confirm for the first time that gut immune cells are involved in MS relapses in humans.

"Only at the time of an attack was there an increase in these cells and the antibodies they produce," Baranzini said. "That really caught our attention."

In the hopes of determining what these gut immune cells were doing in the brain, the team then looked to see what kinds of molecules the IgA antibody reacted to. Recent research has provided evidence that an unhealthy gut microbiome plays a role in MS, when certain potentially damaging species of bacteria proliferate. While the team found that IgA did not bind to myelin protein, it did bind to some of these harmful bacteria species, suggesting that, unlike other immune cells, which are known to cause damage in MS, IgA-expressing immune cells play a protective role, possibly chasing these harmful bacteria to the brain and mounting a defense against them there.

"This opens up a whole new line of research," said Anne-Katrin Pröbstel, MD, a former UCSF postdoctoral researcher, now at the University of Basel in Switzerland and first author on the paper. "I think it has huge potential for therapeutics."

Collaborations within the UCSF Benioff Center for Microbiome Medicine allowed researchers to work with the various bacteria thought to be hallmarks of the MS microbiome, and the work relied heavily on data and biological samples collected through the multidisciplinary UCSF EPIC Study, which has followed hundreds of MS patients over 16 years.

"I think UCSF is one of the only places where we could have done this, because of the access to patient samples that allow us to look at bacteria in the gut, immune cells from the blood, immune cells from the spinal fluid and brain tissue," said Pröbstel. "It's really a unique resource."

Aconvolutional neural network is a type of artificial neural network in which the neurons are organized into receptive fields in a very similar way to neurons in the visual cortex of a biological brain. Today, convolutional neural networks (CNNs) are found in a variety of autonomous systems (for example, face detection and recognition, autonomous vehicles, etc.). This type of network is highly effective in many artificial vision tasks, such as in image segmentation and classification, along with many other applications.

Convolutional networks were inspired by the behaviour of the human visual system, particularly its basic structure formed by the concatenation of compound modules comprising a linear operation followed by a non-linear operation. A study published in the advanced online edition of the journal Vision Research examines the phenomenon of visual illusions in convolutional networks compared to their effect on human vision. A study by Alexander Gómez Vila, Adrian Martín, Javier Vázquez-Corral and Marcelo Bertalmío, members of the Department of Information and Communication Technologies (DTIC) with the participation of the researcher Jesús Malo of the University of Valencia.

"Because of this connection of CNNs with our visual system, in this paper we wanted to see if convolutional networks suffer from similar problems to our visual system. Hence, we focused on visual illusions. Visual illusions are images that our brain perceives differently from how they actually are", explains Gómez Vila, first author of the study.

In their study, the authors trained CNNs for simple tasks also performed by human vision, such as denoising and deblurring. What they observed is that these CNNs trained under these experimental conditions are also "deceived" by brightness and colour visual illusions in the same way that visual illusions deceive humans.

Furthermore, as Gómez Villa explains, "for our work we also analyse when such illusions cause responses in the network that are not as physically expected, but neither do they match with human perception", that is to say, cases in which CNNs obtain a different optical illusion than the illusion that humans would perceive.

The results of this study are consistent with the long-standing hypothesis that considers low-level visual illusions as a by-product of the optimization to natural environments (that a human sees in their everyday). Meanwhile, these results highlight the limitations and differences between the human visual system and CNNs artificial neural networks.

People who are dogmatic about their views seek less information and make less accurate judgements as a result, even on simple matters unrelated to politics, according to a study led by UCL and Max Planck Institute for Biological Cybernetics researchers.

The researchers say their findings, published in PNAS, point to differences in thinking patterns that lead people to hold rigid opinions.

First author Lion Schulz, a PhD candidate at the Max Planck Institute in Germany who began the research while at UCL, said: "Anecdotally, it seems that dogmatic people are less interested in information that might change their mind. However, it was unclear if this is because a specific opinion is of high importance to them or if more fundamental processes are at play that transcend specific opinions."

Dogmatic people are characterised by a belief that their worldview reflects an absolute truth and are often resistant to change their mind, for example when it comes to partisan issues. This tendency can have societal impacts by polarising political, scientific and religious debates. However, the cognitive drivers of dogmatism are still poorly understood.

To investigate this, the researchers asked over 700 people to perform a simple decision-making task. Participants saw two boxes with flickering dots and had to decide which box contained more of the dots. Critically, after the participants had made an initial choice, the researchers gave them the chance to view another, clearer version of the boxes. They then made a final decision.

Schulz explained: "This mirrors many real-life situations - for example, when we hear a rumour but aren't sure if it's true. Do we share it, or do we check a credible source beforehand?"

Joint first author, Dr Max Rollwage (Wellcome Centre for Human Neuroimaging at UCL and Max Planck UCL Centre for Computational Psychiatry & Ageing Research) said: "By using simple tasks, we were able to minimise motivational or social influences and pin down drivers of altered evidence processing that contribute to dogmatic beliefs."

The task was followed by a comprehensive set of questionnaires that allowed the researchers to measure participants' political orientation and levels of dogmatism.

Dogmatic individuals and moderates did not differ in their accuracy or confidence of their decisions. However, the researchers found that more dogmatic participants were more likely to decline the helpful additional information.

The differences between more and less dogmatic participants were especially large when participants had little confidence in a decision. Senior author Dr Steve Fleming (Wellcome Centre for Human Neuroimaging at UCL, Max Planck UCL Centre for Computational Psychiatry & Ageing Research and UCL Experimental Psychology) said: "Previous work has found that there is a close link between how confident we feel and whether or not we seek out new information. In the current study we found that this link was weaker in more dogmatic individuals."

In general, the reduced search was detrimental, with more dogmatic people being less accurate in their final judgements.

Dr Fleming added: "It is striking that we could detect links between dogmatism about issues such as politics, and information-seeking in a simple online game. This tells us that real-world dogmatism isn't just a feature of specific groups or opinions but may be associated with more fundamental cognitive processes."

The study highlights that simply having corrective information available does not necessarily mean people will consume it.

Schulz said: "This is particularly relevant today. We have never been so free to decide if we have enough evidence about something or whether we should seek out further information from a reliable source before believing it.

"It is also important to stress that the differences between more and less dogmatic people were subtle, and we don't know yet how they would manifest when considering real-world information such as news about political parties. In the end, it's a cautionary tale, whether we think of ourselves as dogmatic or not: when uncertain, it might be wise to check the information again."

The researchers are now trying to further unravel the underlying cognitive algorithms which trigger people to search for further information in situations of uncertainty.

An international team comprising researchers from the University of Bristol, and Hunan and Central South Universities in China, have prepared biocompatible protocells that generate nitric oxide gas - a known reagent for blood vessel dilation - that when placed inside blood vessels expand the biological tissue.

In a new study published today in Nature Chemistry, Professor Stephen Mann and Dr Mei Li from Bristol's School of Chemistry, together with Associate Professor Jianbo Liu and colleagues at Hunan University and Central South University in China, prepared synthetic protocells coated in red blood cell fragments for use as nitric oxide generating bio-bots within blood vessels.

Coating the protocells led to increased levels of biocompatibility and longer blood circulation times. Critically, the team trapped an enzyme inside the protocells which, in the presence of glucose, produced hydrogen peroxide. This was then used by haemoglobin in the protocell membrane to degrade the drug molecule hydroxyurea into nitric oxide gas.

When placed inside small pieces of blood vessels, or injected into a carotid artery, the protocells produced sufficient amounts of nitric oxide to initiate the biochemical pathways responsible for blood vessel vasodilation.

Although at a very early stage of development, the new approach could have significant benefits in biomedicine, cellular diagnostics and bioengineering.

Professor Stephen Mann, Co-Director of the Max Planck Bristol Centre for Minimal Biology at Bristol, said: "This work could open up a new horizon in protocell research because it highlights the opportunities for creating therapeutic, cell-like objects that can directly interface with living biological tissues."

Associate Professor Jianbo Liu at Hunan University added: "We are all really excited about our proof-of-concept studies but there is a lot of work still to be done before protocells can be used effectively as bio-bots in therapeutic applications. But the potential looks enormous."

HERSHEY, Pa. -- A genetic modification in the 'coat' of a brain infection-causing virus may allow it to escape antibodies, according to Penn State College of Medicine researchers. They say testing people for this and other viral mutations may help identify patients at risk for developing a fatal brain disease.

Dr. Aron Lukacher, professor and chair of the Department of Microbiology and Immunology at the College of Medicine, and Susan Hafenstein, professor of medicine and microbiology and immunology at the College of Medicine and professor of biochemistry and molecular biology at Penn State Eberly College of Science, co-led a research team that used high-resolution microscopy to study the capsid, or outer shell of mouse polyomavirus (MuPyV). This virus is a genetic model of JC polyomavirus (JCPyV), which is present and harmless in most people and can cause progressive multifocal leukoencephalopathy (PML), a brain disease, in people taking immunosuppressive therapies.

Genetic mutations in the capsid of JCPyV are common in PML patients and scientists have struggled to understand whether they allow the virus to infect brain cells or whether the resulting changes allow the virus to evade elimination by antiviral antibodies and then cause brain infection. Lukacher and Hafenstein studied the mouse equivalent of a common genetic mutation in JC polyomavirus to try and better understand how it may cause PML.

"Not much is known about how this particular genetic mutation in the JC polyomavirus capsid leads to PML," Lukacher said. "It has been detected in the blood, cerebrospinal fluid and brain tissues of PML patients but not in their urine. This unmutated virus typically sits dormant in the kidneys of healthy people, which got us wondering how this particular mutation contributes to disease progression."

The researchers introduced a genetic mutation in the MuPyV capsid similar to one found in JCPyV and conducted a series of experiments to compare outcomes between MuPyV and the altered virus. The virus mutates by swapping out one amino acid, the chemical ingredients used to build the capsid, for another. They found the virus was still able to cause central nervous system infection and hydrocephalus, or brain swelling.

To study how the mutation allows the virus to evade antibodies, the research team, including doctoral student Matthew Lauver and medical scientist training program student Daniel Goetschius, used cryogenic electron microscopy to determine the 3D, atomic resolution structure of the virus particles bound to monoclonal antibodies. The results of their analyses were published in the journal eLife.

The team examined the structural features to see how the monoclonal antibodies recognize the virus capsid and neutralize it. They found that the capsid mutation prevents the monoclonal antibody from being able to interact with the virus, increasing the chances that the virus can infect the brain when patients become immune-suppressed.

"We studied how other mutations affected MuPyV and found many of them result in impaired kidney and retained brain viral infection," said Lukacher, a Penn State Cancer Institute researcher. "However, only a few of these result in the ability of the virus to evade the immune response."

According to Lukacher, more research is needed to determine which JCPyV mutations cause the virus to evade antibodies. He said the goal would be to develop screenings for patients with multiple sclerosis receiving immune-modulating therapies, as well as those immune-compromised by cancers and AIDS, to see who might be at increased risk for developing PML.

Study of patients attending a hospital-based obesity service shows no difference in weight loss between those under 60 years old and those from 60 to 78 years old

The University of Warwick-led study conducted at University Hospitals Coventry and Warwickshire (UHCW) concludes that lifestyle changes to manage weight loss are effective in reducing obesity regardless of age

Aims to dispel myths about effectiveness of weight loss in older people

Obese patients over the age of 60 can lose an equivalent amount of weight as younger people using only lifestyle changes, according to a new study from the University of Warwick and University Hospitals Coventry and Warwickshire (UHCW) NHS Trust that demonstrates that age is no barrier to losing weight.

The researchers hope that their findings will help to correct prevailing societal misconceptions about the effectiveness of weight loss programmes in older people, as well dispel myths about the potential benefits of older people trying to reduce their weight.

The findings are based on analysis of patient records from a hospital-based obesity service and are reported in the journal Clinical Endocrinology.

This retrospective study was conducted at the Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM) at UHCW. The researchers randomly selected 242 patients who attended the WISDEM-based obesity service between 2005 and 2016, and compared two groups (those aged under 60 years and those aged between 60 and 78 years) for the weight loss that they achieved during their time within the service.

All patients had their body weight measured both before and after lifestyle interventions administered and coordinated within the WISDEM-based obesity service, and the percentage reduction in body weight calculated across both groups. When compared, the two groups were equivalent statistically, with those aged 60 years and over on average reducing their body weight by 7.3% compared with a body weight reduction of 6.9% in those aged under 60 years. Both groups spent a similar amount of time within the obesity service, on average 33.6 months for those 60 years and over, and 41.5 months for those younger than 60 years.

The hospital-based programme used only lifestyle-based changes tailored to each individual patient, focusing on dietary changes, psychological support and encouragement of physical activity. Most of the patients referred to the obesity service were morbidly obese with BMIs typically over 40Kgm-2.

There are more than fifty co-morbidities of obesity that can be lessened as we lose weight, including diabetes, psychiatric conditions such as depression and anxiety, osteoarthritis and other mechanical problems. Obesity is also linked to increased mortality and poor wellbeing.

Lead author Dr Thomas Barber of Warwick Medical School at the University of Warwick said: "Weight loss is important at any age, but as we get older we're more likely to develop the weight-related co-morbidities of obesity. Many of these are similar to the effects of aging, so you could argue that the relevance of weight loss becomes heightened as we get older, and this is something that we should embrace.

"There are a number of reasons why people may discount weight loss in older people. These include an 'ageist' perspective that weight-loss is not relevant to older people and misconceptions of reduced ability of older people to lose weight through dietary modification and increased exercise. Older people may feel that hospital-based obesity services are not for them. Service providers and policymakers should appreciate the importance of weight loss in older people with obesity, for the maintenance of health and wellbeing, and the facilitation of healthy ageing. Furthermore, age per se should not contribute towards clinical decisions regarding the implementation of lifestyle management of older people.

"Age should be no barrier to lifestyle management of obesity. Rather than putting up barriers to older people accessing weight loss programmes, we should be proactively facilitating that process. To do otherwise would risk further and unnecessary neglect of older people through societal ageist misconceptions."

Conclusion:

The cytokine family including interleukin-2 and -15 (IL-2 and IL-15) started out in a primitive vertebrate species with three related cytokines IL-2, IL-15, and IL-15-like (IL-15L), all sharing binding capacity for receptor chain IL-15Rα. IL-15L was conserved in fishes, reptiles, and some mammals but lost in human and mouse. Researchers in Japan, Germany, and the UK, have now determined the function of IL-15L using rainbow trout. Data suggest that in the jawed vertebrate ancestor IL-15 and IL-15L, forming "heterodimer cytokine" complexes with IL-15Rα, selectively induced type 1 (aka Th1) and type 2 (aka Th2) immunity, respectively, whereas free IL-2 efficiently stimulated activated and regulatory T cells by binding their surface IL-15Rα. Insights into their evolution should inspire further studies of human IL-2 and IL-15, both of which are used or tested in cancer immunotherapy.

Background:

In human and mouse, the closely related cytokines IL-2 and IL-15 both signal through IL-2Rβ heterodimer receptors, and also bind to a third receptor chain of a different molecular family, cytokine-specific IL-2Rα or IL-15Rα, which has no homologues in receptors for other human or murine cytokines. IL-2 is secreted by activated T cells, and predominantly functions as a free cytokine that binds IL-2Rαβ heterotrimer complexes on target cells. IL-2Rαβ complexes are abundant on activated T cells and, constitutively, on regulatory T cells (Tregs). Therefore, IL-2 both participates in an immuno-stimulatory positive feedback loop through activated T cells and an immuno-inhibitory negative feedback loop through Tregs. IL-15, on the other hand, predominantly uses IL-15Rα as a "heterodimer cytokine" partner at the membrane of the expressing cells or as released free IL-15+IL-15Rα complexes. IL-15 predominantly stimulates "type 1 immunity" by specifically stimulating natural killer (NK) cells and CD8+ cytotoxic T cells, and is important for the maintenance of several lymphocyte populations in intestine, lung, and skin. Recombinant IL-2 is an established anti-cancer drug (e.g. "proleukin"), but in several clinical trials IL-15 (complexed or not with IL-15Rα) is preferred as IL-15 does not have the complicating factor of specifically stimulating Tregs.

The findings:

Associate Professor Johannes M. Dijkstra and co-workers at Fujita Health University, Japan, together with the groups of Professor Uwe Fischer at the Friedrich-Loeffler-Institute, Germany, and Professor Christopher J. Secombes, University of Aberdeen, UK, have been instrumental in elucidating the evolution of IL-2 and IL-15. In their recent study [1], for which most experiments were done by the first author Dr. Takuya Yamaguchi at the Friedrich-Loeffler-Institute, they determined that in rainbow trout all the three cytokines IL-2, IL-15, and IL-15L can bind to IL-15Rα. The tandem gene duplication that resulted in IL-15Rα plus IL-2Rα probably occurred in a primitive tetrapod species, and in fish only a single molecule of this receptor chain family is found that is very similar to mammalian IL-15Rα while quite different from mammalian IL-2Rα that acquired substantial modifications during its evolution [2]. Dijkstra and co-workers previously determined that cytokine IL-15L already existed at the evolutionary level of sharks [3] and is conserved in some mammals like cattle but inactivated in human and mouse [2]. In cattle, they found that IL-15 and IL-15L selectively bind to IL-15Rα, whereas IL-2 selectively binds to IL-2Rα [1,3], which for IL-2 and IL-15 agrees with human and mouse. However, for mammalian IL-15L a function could not be determined so far. The Yamaguchi et al. study [1], using rainbow trout, now is the first to identify the function of IL-15L. This function is the stimulation of the expression of cytokines IL-4 and IL-13 homologs, as shown both in vitro and in vivo, and thereby of type 2 immunity. Under similar conditions, trout IL-15 was found to selectively stimulate cytokine interferon-g expression, a marker for type 1 immunity, concluding that IL-15 and IL-15L have opposing immune functions; meanwhile, trout IL-2 was found to induce a broader cytokine palette than either IL-15 or IL-15L [1]. All three trout cytokines IL-2, IL-15, and IL-15L, were found to induce activation of transcription factor STAT5 [1]. IL-15 and IL-15L transcripts are abundant and also found in epithelial cells and fibroblasts, and Yamaguchi et al. speculate that the multiple AUG codons in their 5' untranslated regions prohibit translation unless the cell experiences proper signals for inducing type 1 or type 2 immunity [1]. In mammals, such "alarmin" function of IL-15L for inducing type 2 immunity may have been taken over by newer cytokines that seem to be absent in fish, such as IL-25, IL-33, and TSLP. The trout cells most sensitive to IL-15L appear to be innate lymphocytes and they may be equivalent to mammalian ILC2 cells [1].

Reminiscent of IL-15 and IL-2 in mammals, trout IL-15 is more dependent on co-presentation with IL-15Rα than IL-2 [1], and also in fish IL-2 appears to participate in an immune-stimulatory positive feedback loop involving activated T cells [4] and an immuno-inhibitory negative feedback loop through the stimulation of IL-15Rα-expressing Tregs [5]. The dependency of IL-15L on co-presentation with IL-15Rα was found to be even larger than that of IL-15, since for unbound IL-15 but not for unbound IL-15L functional activity could be observed [1]. Retainment of IL-15+IL-15Rα complexes at the surface of expressing cells can contain cytokine activity within confined niches, which may explain why in both mammals and fish IL-15 was selected over IL-2 for stimulation of lymphocytes in mucosal tissues [1]. However, to some extent, as known in mammals for IL-2+IL-2Rα, trout IL-2 can be presented at the cell surface together with IL-15Rα [1], and this type of IL-2 presentation probably deserves more attention including in mammals. Similarly, the ease with which a function of free IL-15 can be found in both mammals and trout, whereas not found for free IL-15L [1], underlines that the possibility of free IL-15 representing a distinct function from IL-15+IL-15Rα should be given more consideration. For trout IL-2 and IL-15L probable homodimer complexes were found [1], suggesting that previous observations of IL-2 and IL-15 homodimers in mammals should be studied more seriously as a potentially important trait of the IL-2/15/15L family.

Professor Dijkstra, who wrote and largely conceptualized the Yamaguchi et al. study [1] and is one of the two corresponding authors together with Professor Fischer, explains why understanding the evolution of this cytokine family is important: "Although IL-2 and IL-15 are very powerful and important cytokines, we only partially understand them. IL-2 and IL-2Rα are relatively simple to understand at the molecular level but complicated at the functional level because IL-2 simultaneously induces opposing functions. On the other hand, IL-15 and IL-15Rα seem relatively simple to understand at the functional level but are far from understood at the molecular level. Peculiarities such as the extremely long "leader" sequence of IL-15, multiple AUG codons in the IL-15 transcript 5'UTR, and multiple splicing forms of IL-15Rα, are poorly understood, yet seem to be important since conserved in both mammals and fish. Basically, finding similar features despite evolutionary separation for hundreds of millions of years indicates the importance of those features, and urges us to study them better not only in the non-model species but also in human and mouse."

In short, the recent Yamaguchi et al. study, Ancient cytokine interleukin 15-like (IL-15L) induces a type 2 immune response, published in Frontiers in Immunology https://doi.org/10.3389/fimmu.2020.549319 [1], concludes that the IL-2/15/15L cytokine family already played a major role in immune polarizations in an ancestor of jawed vertebrates, with opposing functions for IL-15 and IL-15-like.

Can schools safely remain open or reopen during periods of significant community spread of COVID-19? According to predictions from a model of SARS-CoV-2 transmission in the school setting, yes - if appropriate precautions are followed both in school and in the community.

The study results are published in BMC Public Health.

School closures during the COVID-19 pandemic have been based predominantly on models of pandemic influenza transmission. However, say the study's authors, recent evidence suggests that "children under the age of 10, are less susceptible to SARS-CoV-2 infection and rarely transmit the infection to adults or schoolmates."

For their study, University of Vermont researchers adapted a previously-published model using contact data from Shanghai, China to investigate the impact of open schools on community spread of SARS-CoV-2 infection.

A critical feature of the model is the measurement of contact structure across all age groups, with a focus on the rate of daily contacts in the community and social contacts in school - and how a reduction in contact frequency affects transmission risk.

The team combined contact patterns observed between different age groups during pre- and post-pandemic "lockdown" periods to simulate various levels of school reopening and also tested these effects across a range of estimates of lower susceptibility rates to infection in younger children.

According to first author Benjamin Lee, M.D., associate professor of pediatrics and a pediatric infectious diseases specialist, the model helped identify conditions that would support keeping schools open. Ideally, he said, the average number of daily social contacts in the community needs to be reduced to about 40 percent of pre-pandemic baseline, and total contacts for children aged 10 to 19 needs to be reduced to 33 percent of pre-pandemic baseline. If this can be achieved, having open schools would be feasible even starting from a point of significant community transmission.

"In other words, necessary restrictions in the community with careful mitigation for older kids is the trade-off that will enable schools to remain open," said Lee. "Schools should be the last to close and first to re-open."

The study demonstrates how considering a combination of different measures is beneficial in creating a path to having schools be open to the extent possible, within a broader set of restrictions.

"It's not just about the scale of restrictions, but also about how targeted these restrictions are, because the structure of contacts matters," said senior author Laurent Hébert-Dufresne, Ph.D., assistant professor of computer science.

"This study provides a basic proof-of-principle that we believe can be applicable to many settings that have similar contact structures," said Lee.

WASHINGTON -- U.S. Naval Research Laboratory researchers led a team of scientists who discovered some of the youngest known radio jets launched by growing supermassive black holes in the centers of distant galaxies.

Watching and recording the jets, which are believed to be only decades old, in their infancy allows researchers to observe their formation and growth and study how they influence their environments.

"Timing and navigation are a fundamental portion of the Navy mission and constitute part of the key infrastructure the DOD relies on," said Henrique Schmitt, Ph.D., an astronomer at NRL. "Understanding the evolution of jets in active galaxies is important for day-to-day tools like GPS. Such active galaxies define the celestial reference frame from which precision timing and positioning are derived."

The team discovered the jets after reviewing images from the Very Large Array Sky Survey (VLASS) that contained unusually bright radio sources in comparison to previous studies with the Karl G. Jansky Very Large Array (VLA) in Socorro, New Mexico. The paper was accepted into publication by the Astrophysical Journal.

"This is a new topic that has yet to be fully explored," said Kristina Nyland, Ph.D., a National Research Council postdoctoral fellow in residence at NRL. "Studying the launching of powerful jets is important for us to understand how galaxies and supermassive black holes grow in tandem over billions of years."

According to Nyland, older jets shine for millions of years and may extend far beyond the confines of their host galaxies, while newborn jets stay within the boundaries of their hosts. Known as the interstellar medium, this area contains the raw materials that give rise to new stars and planetary systems. It is hypothesized newborn jets may interact with these dense clouds of gas and play an important role in galaxy formation and evolution.

"When you have compact, powerful jets of radio plasma colliding with a reservoir of star-forming gas, the jets may alter the efficiency of new stellar births and the future appearance and properties of the galaxy," Nyland said. "Studying young jets in particular is essential for understanding our cosmic origins. It is important for us to measure the rate at which new jets are launched by supermassive black holes to ultimately understand how they influence the lives of the galaxies in which they reside."

The U.S. Naval Observatory (USNO) maintains a celestial reference frame used to provide a reference of the skies and space. That celestial reference frame appears in grid form and encompasses more than 4,000 known radio sources. New radio sources, like newborn jets, can add reference points to the grid.

Living on the grid

Reference points on the grids can change in appearance over time. Researchers are trying to fill in sparse areas of the grid by coupling an optical reference frame to the celestial reference frame. However, the physics of the optical and radio energy emissions from the supermassive black holes are not fully understood. These emissions look different over time and researchers find that when optical and celestial grids are overlaid they do not always match up perfectly.

"Without understanding the physics of those radio sources, what you see is those two reference frames don't always line up," said Tracy Clarke, Ph.D., a radio astronomer in NRL's Remote Sensing Division. "That's because we are looking at a different part of the radio source compared to the optical host galaxy--they are shifted a bit."

"Understanding the source of radio emission from AGN is a key area of interest to the USNO and the Navy, and helps us better understand the nature of the quasar sources that comprise the International Celestial Reference Frame," said Megan Johnson, Ph.D. at USNO.

Numerous studies are underway to gain a better understanding of the physics. That information could be used to build a more comprehensive and predictive reference frame. Navy assets can utilize the reference frame in a GPS constrained environment. To do that, researchers want to give operators the sources of bias in a fixed grid (such as a shift in brightness in one of the jet sources) to offset the reference frame.

"The physics of what Kristina Nyland is doing helps us understand how to tie those two reference frames tightly together, and that's going to give the Navy a fantastic multiwavelength reference frame," Clarke said.

Clarke currently serves as co-chair of the Survey Science Group for the VLA Sky Survey (VLASS). This group played a key role in developing the VLASS survey and it currently serves as the interface to the scientific community.

Astronomical collaboration

VLASS is building a richer understanding of space by combining imagery and data of the entire sky visible from a telescope taken multiple times over several years. NRL is supporting the VLASS through commensal observations with the VLA Low Band Ionosphere and Transient Experiment (VLITE), operated out of NRL. VLITE is a powerful addition to the survey, providing complementary information on radio source properties over a different range of frequencies and spatial scales.

"While VLASS data have allowed the discovery of these newly formed jets, understanding the history of galaxy evolution may require additional radio data," Clarke said. "This is where VLITE comes in. VLITE operates at longer observing wavelengths and observes in parallel to VLASS."

Clarke believes VLITE is a powerful addition to the survey since it provides complementary information on radio source properties that allows NRL researchers to better understand the evolution of the supermassive black hole that is powering each newborn radio jet.

Nyland is leading the research project in the remote sensing division of NRL through the NRC postdoctoral fellowship program. She continues to study the newborn jets and observe how they change over time.

"This research contributes overall to human exploration," said Nyland. "It contributes to a richer understanding of fundamental physics and the fascinating link between supermassive black holes and galaxy evolution."