Culture

Fukuoka, Japan--According to the Global Burden of Disease Study 2017, close to nine percent of the global population lives with some form of chronic kidney disease, or CKD. Not only does the condition affect renal function, CKD has long been associated with increased risk of cardiovascular disease.

Now, in a new study that could aid the development of therapeutic drugs to reduce these cardiac complications, researchers led by Kyushu University have found an underlying molecular pathway that can explain how chronic kidney disease induces heart failure.

Studying mice, the researchers found that a key driver is the dysfunction of a type of white blood cell called a monocyte. The dysfunction is caused by increased levels of vitamin A and its binding protein--a common symptom of chronic kidney disease--breaking a well-known genetic pathway: the circadian clock.

The circadian clock is one of the most indispensable biological functions in living organisms. Common understanding of the pathway is that it controls our sleep patterns. However, the circadian clock plays a much larger role, affecting blood pressure, metabolic rate, and even hormone levels. In fact, nearly 10% of our genes are directly influenced by the circadian clock.

These properties made it a natural target for Shigehiro Ohdo, professor of Kyushu University's Faculty of Pharmaceutical Sciences, and his team for investigating the causes of chronic kidney disease-induced heart inflammation and fibrosis.

"We found that mice with a mutated Clock gene--one of the main regulators of the circadian clock--have decreased symptoms of heart problems related to chronic kidney disease, despite having high blood pressure," explains Yuya Yoshida, one of the first authors of the study published in the journal Nature Communications.

To search for the underlying cause of this protective effect, the team looked for abnormalities in genes that connect Clock and kidney dysfunction.

"Our investigation led us to find that a protein called 'G protein-coupled receptor 68,' or GPR68, produced in monocytes was playing a key role. GPR68 is known to increase the production of proteins that cause inflammation, and more importantly, it is regulated by the Clock gene," states Naoya Matsunaga, another author of the study.

One sign of kidney dysfunction is elevated levels of vitamin A and its binding protein, two molecules that are usually carefully controlled. The researchers found that this elevation disrupts the normal activity of the circadian clock in monocytes, which in turn over-express GPR68.

These high-GPR68-expressing monocytes then infiltrate the heart and cause inflammation and fibrosis. This explains why mice with defective Clock genes have less severe CKD-induced heart problems: there is no Clock gene to produce GPR68.

"Our study reveals a previously unknown role of monocytic clock genes in CKD-induced heart failure," concludes Ohdo. "The findings will help us develop therapeutic drugs such as ones targeting GPR68. We also can investigate better treatments for abnormal vitamin A accumulation in the blood."

Coral insights into 1,000 years of seasonal changes in the Arabian Sea warn of significant impacts caused by global warming.

Every year, the southwesterly winds of the summer monsoon sweep down the Arabian Peninsula, pushing the surface waters of the Arabian Sea away from the coast and driving an upwelling of deep waters to the surface. This rising seawater is colder and less saline than the surface water and is rich in nutrients, providing energy for the various organisms living in the Arabian Sea and Indian Ocean.

Scientists from Japan, Taiwan and Germany, including coral reef scientist Dr. Tsuyoshi Watanabe of Hokkaido University, have uncovered evidence from corals off the coast of Oman suggesting that global warming is causing changes to the Arabian Sea that could impact the climate, ecosystems and socioeconomics of the densely populated areas surrounding the Indian Ocean. The findings were published in the journal Geophysical Research Letters.

Stronger summer monsoon winds lead to a stronger upwelling in the Arabian Sea. Stronger winds form when the air over the Indian subcontinent warms more rapidly than the air over the Indian Ocean. Recently, however, the opposite has been happening. Scientists wanted to know how this change affects the Arabian Sea upwelling, but the phenomenon has not been monitored continuously, so available measurements aren't enough to tell the whole story.

Watanabe and his colleagues analysed fossil and modern corals off an Omani island in the Arabian Sea. They identified the ages of the corals they collected and established a correlation between coral data and seawater temperature changes over a very fine timescale, and used that information to extrapolate salinity changes. The four fossil corals they used dated to approximately 1167 CE, 1624 CE, 1703 CE and 1968 CE, respectively. They took samples from the corals at different depths towards their cores, and then analysed the ratio of strontium to calcium in the samples, as well as the amounts of oxygen and carbon isotopes. The growth rate of the corals is steady over centuries, and the skeletons contain a record of the changes in elements. Generally, as water temperatures rise, the strontium-to-calcium ratio and isotope oxygen-18 in coral decrease.

The results showed that the summer Arabian Sea upwelling was relatively stable through the warmer period of the medieval climate anomaly in the 12th century; the cooler little ice age, which extended between the 14th and 19th centuries AD; and up until the mid-20th century. After this period, however, the scientists observed a clear weakening of the Arabian Sea upwelling. They reason this can most likely be explained by faster warming of the northern Indian Ocean, caused by greenhouse gases, and slowed warming of the Indian subcontinent, caused by the absorption of sunrays by aerosol emissions over South Asia. This then weakens the summer monsoon winds, impacting the strength of the Arabian Sea upwelling.

"The seasonal upwelling is vital for commercial fishing and has significant impacts on the regional climate, ecosystems and socioeconomics," says Tsuyoshi Watanabe. "Our findings imply that weakening of the Arabian Sea upwelling is likely to continue along with global warming, impacting monsoon rainfalls, sea levels, fisheries and even agricultural production."

Delicious to some, but a bitter bane to others' taste buds, vegetables like broccoli rabe, bok choy and turnips are a dinner staple ---and picky eater conflict --- around the world.

It all likely started in the mountains near present-day Afghanistan, where humans first domesticated turnips 3,500 to 6,000 years ago, according to a new study recently published in the journal Molecular Biology and Evolution. University of Wisconsin-Madison Professor of Botany Eve Emshwiller and her former graduate student Alex McAlvay (now an assistant curator assistant curator of economic botany at The New York Botanical Garden) led the research.

To identify the genetic root of it all, the research team reconstructed an evolutionary tree from a comparative DNA sequences analysis of more than 400 different varieties of the species Brassica rapa from around the world.

Just as varieties of ancient corn look very different than the hybrid crops of today's farms, Brassica revealed a similar past.

From this tree, they discovered that Central Asian turnips were the most genetically diverse crops. That in turn suggested that humans in the region may have valued most the fatter, starch-rich taproots that became turnips several thousand years ago, as agriculture took root around the world.

The research team identified both the Hindu Kush mountains as the epicenter of domestication, and weeds from the Caucasus region as among the most likely wild relatives of the species' vegetable crops. Turnips then spread west to Europe and east to East Asia, where farmers later selected for larger leaves. These leafy versions became bok choy, napa cabbage and broccoli rabe, among other vegetables found in today's grocery stores.

Interestingly, ancient cultures also pointed to evidence that matched the genetic analysis. Ancient literary references to turnips in the region, and the apparent existence of the word for "turnip" in the ancestor of languages from the region, also supported the turnip as the original domesticated form.

"It's important to know where your crops are from," said McAlvay. "In this work, we had a broader data set than had been used previously. And we also had more wild collections than had been used previously. Having enough of those non-cultivated forms allowed us to distinguish between those feral or escaped weeds and the ones that are likely truly wild."

Before the study, it remained unclear if turnips or oilseeds were the first tamed varieties.

This confusion has stemmed from the ubiquity of Brassica rapa and its many weedy forms, which could be truly wild or merely escaped crops turned feral. While wild and feral forms look similar, their genetic histories are vastly different.

"That parallel selection for leafy forms is interesting and gives us an evolutionary system to compare how this leafiness trait can arise," said McAlvay. Other farmers selected other lineages for their oil-rich seeds.

The true identities of these wild relatives -- which have been hidden for years because of the tangled web of family relationships in the species -- also provides valuable information to evolutionary biologists and crop breeders alike.

"We might want this information in order to conserve those wild relatives, so they don't disappear in the course of habitats being lost," said Emshwiller. Wild plants can confer valuable traits when crossed with crops, which typically lose their hardiness during domestication.

"And domestication is a good way to study evolution in general," Emshwiller adds. "If we understand how crops evolved under human influence, that can help us extrapolate to how wild plants might evolve under different kinds of selection."

For their next steps, the researchers want to include more weedy samples mainly from the original site of domestication, the Hindu Kush region. The region should be host to many different wild versions of Brassica rapa.

The study may also provide important information for this worldwide important crop and preserve important genetic resources to make brassica varieties more resilient as climate change and new pests may threaten some crops in the future.

Proteins are the key players in our cellular processes. Their generation follows principles called transcription and translation. First, DNA copies its genetic information to messenger RNA (mRNA), which then determines the sequence in a chain of amino acids, which finally fold into a protein. The reality, however, is more complex: More than 90 per cent of our genes do not result in only one mRNA and then one protein, but a process called alternative splicing produces several mRNA variants, only some of which are then translated into a specific protein isoform in a specific cell at a given time. Conventional techniques to detect alternative splicing are mostly single time-point measurements that are work-intense and cannot reliably monitor over time which protein isoforms are actually translated in the cell.

Researchers at Helmholtz Zentrum München and the Technical University of Munich (TUM) thus developed a new bioengineered reporter system called EXSISERS. The idea behind it is to generate a signal such as light as soon as a specific protein isoform is being translated. "This is possible via designer reporter proteins that can cut themselves out of the nascent amino acid chain- they are self-excising," says Dong-Jiunn Jeffery Truong. "In analogy to the famous cut and restore rope trick in magic performances, the excision of the reporter leaves no scar in the natural protein isoforms." The researchers have already applied this method to human cells in culture. One of their aims was to analyze the expression of isoforms of a protein called Tau, which is associated with neurodegenerative diseases such as Parkinson's. This makes Tau isoforms a potential target for future molecular therapies.

"Bioengineering inspired by natural biomolecular processes will make it possible to observe many other fundamental cellular processes non-invasively," says Gil Gregor Westmeyer. "The more cellular parameters we can monitor, the better we can develop targeted molecular interventions for future cellular therapies, for example, to treat neurodegenerative diseases." Westmeyer and his team are already collaborating with several academic laboratories that use the new reporter system to obtain a more comprehensive understanding of isoform expression in cells and its implication in diseases.

The first evidence of a genetic link explaining why some people who catch Covid-19 don't become sick has been discovered

A scientific and medical team led by Newcastle University, UK, has demonstrated that the gene, HLA-DRB1*04:01, is found three times as often in people who are asymptomatic. This suggests that people with this gene have some level of protection from severe Covid.

The study, funded by Innovate UK, the UK's innovation agency, compared asymptomatic people to patients from the same community who developed severe Covid but had no underlying illnesses, and is published in the HLA journal.

The study team believe this is the first clear evidence of genetic resistance because this study compared severely affected people with an asymptomatic COVID group and used next generation sequencing to focus in detail and at scale on the HLA genes which are packed together on chromosome 6. Other studies have scanned the whole genome but that approach is less effective in the tissue typing complex.

Genome wide studies can be likened to a satellite image. The high density and complexity of the histocompatibility complex and variation in different populations means significant variation can be overlooked. For example, different alleles or versions of the same gene could have opposite effects on the immune response. This study was much more focused and compared symptomatic to asymptomatic in the same population revealing the "protective" qualities of the allele.

It is known that the human leukocyte antigen gene identified, HLA-DRB1*04:01, is directly correlated to latitude and longitude. This means more people in the North and West of Europe are likely to have this gene.

This suggests that populations of European descent will be more likely to remain asymptomatic but still transmit the disease to susceptible populations.

Dr Carlos Echevarria from the Translational and Clinical Research Institute, Newcastle University who also works as a Respiratory Consultant in the Newcastle Hospitals NHS Foundation Trust and is a co-author of the paper says: "This is an important finding as it may explain why some people catch Covid but don't get sick.

"It could lead us to a genetic test which may indicate who we need to prioritise for future vaccinations."

"At a population level, this is important for us to know because when we have lots of people who are resistant, so they catch Covid but don't show symptoms, then they risk spreading the virus while asymptomatic."

The effect of genes being linked to geolocation is an accepted scientific concept and it is well known that HLA genes develop over generations in reaction to disease-causing pathogens.

Study author, David Langton, whose company ExplantLab helped fund the study through an Innovate UK research award, added: "Some of the most interesting findings were the relationships between longitude and latitude and HLA gene frequency. It has long been known that the incidence of multiple sclerosis increases with increasing latitude. This has been put down in part to reduced UV exposure and therefore lower vitamin D levels. We weren't aware, however, that one of the main risk genes for MS, that is DRB1*15:01, directly correlates to latitude.

"This highlights the complex interaction between environment, genetics and disease. We know some HLA genes are vitamin D responsive, and that low vitamin D levels are a risk factor for severe COVID and we are doing further work in this area."

The study used samples from 49 patients with severe Covid who had been hospitalised with respiratory failure, samples from an asymptomatic group of 69 hospital workers who had tested positive through routine blood antibody testing and a control group from a study into the relationship between HLA genotypes and the outcomes of joint replacement surgery.

The research used next generation sequencing machines to study the different versions, or alleles, of the HLA genes in depth which was combined with a variety of expertise and modelling. The work was limited to samples from North East England during the first lockdown, this reduced variation in the study groups but more studies will be needed in the UK and other populations as there may be different copies of the HLA genes providing resistance in other populations.

They recently published their findings in the renowned journal "Advanced Materials". Cells are not only our biological building blocks, but also highly dynamic, active systems. The research group led by Professor Käs has succeeded in significantly reducing these dynamics with heavy water, without damaging the cells.

"Generally, a lot of people know heavy water for its important technical use in nuclear power plants. We took a different approach here and were able to show that for cells, time - or, more specifically, their dynamics - can be significantly slowed down in the presence of heavy water," said Käs, who has devoted himself to researching the physical properties of cells and tissue. The research showed on various biological levels that the movement of cells and their dynamics was only taking place in slow motion. "It is very intriguing that cellular dynamics can be slowed down at the same temperature. So far, only the theory of relativity has offered such possibilities in the physical context," explained Käs. He added that the results form the basis of a method to offer cells and organs longer-lasting protection against degeneration.

The researchers confirmed this effect with a variety of complementary methods and attributed the observations to an increased interaction between the structural proteins. "Heavy water also forms hydrogen bonds, but these are stronger than in normal aqueous environments. As a result, structural proteins such as actin seem to interact more strongly with one another and briefly stick together. What is spectacular here is that the effects are reversible, with cells showing their native properties again as soon as they are transferred into a normal aqueous medium," said Dr Jörg Schnauß. "What is even more astonishing is that these changes show the fingerprint of a passive material. However, cells are highly active and far from thermodynamic equilibrium. If they behave like a passive material, they are usually dead," added Käs.

However, as the researchers were able to show, this was not the case in their experiments. They now hope to be able to use the knowledge gained to keep cells or even tissue vital for longer. If this approach is confirmed, heavy water could be used for longer storage times, for example during organ transplants.

Graphene may be among the most exciting scientific discoveries of the last century. While it is strikingly familiar to us--graphene is considered an allotrope of carbon, meaning that it essentially the same substance as graphite but in a different atomic structure--graphene also opened up a new world of possibilities for designing and building new technologies.

The material is two-dimensional, meaning that each "sheet" of graphene is only 1 atom thick, but its bonds make it as strong as some of the world's hardest metal alloys while remaining lightweight and flexible. This valuable, unique mix of properties have piqued the interest of scientists from a wide range of fields, leading to research in using graphene for next-generation electronics, new coatings on industrial instruments and tools, and new biomedical technologies.

It is perhaps graphene's immense potential that has consequently caused one of its biggest challenges--graphene is difficult to produce in large volumes, and demand for the material is continually growing. Recent research indicates that using a liquid copper catalyst may be a fast, efficient way for producing graphene, but researchers only have a limited understanding of molecular interactions happening during these brief, chaotic moments that lead to graphene formation, meaning they cannot yet use the method to reliably produce flawless graphene sheets.

In order to address these challenges and help develop methods for quicker graphene production, a team of researchers at the Technical University of Munich (TUM) has been using the JUWELS and SuperMUC-NG high-performance computing (HPC) systems at the Jülich Supercomputing Centre (JSC) and Leibniz Supercomputing Centre (LRZ) to run high-resolution simulations of graphene formation on liquid copper.

A window into experiment

Graphene's appeal primarily stems from the material's perfectly uniform crystal structure, meaning that producing graphene with impurities is wasted effort. For laboratory settings or circumstances where only a small amount of graphene is needed, researchers can place a piece of scotch tape onto a graphite crystal and "peel" away atomic layers of the graphite using a technique that resembles how one would use tape or another adhesive to help remove pet hair from clothing. While this reliably produces flawless graphene layers, the process is slow and impractical for creating graphene for large-scale applications.

Industry requires methods that could reliably produce high-quality graphene cheaper and faster. One of the more promising methods being investigated involves using a liquid metal catalyst to facilitate the self-assembly of carbon atoms from molecular precursors into a single graphene sheet growing on top of the liquid metal. While the liquid offers the ability to scale up graphene production efficiently, it also introduces a host of complications, such as the high temperatures required to melt the typical metals used, such as copper. When designing new materials, researchers use experiments to see how atoms interact under a variety of conditions. While technological advances have opened up new ways for gaining insight into atomic-scale behavior even under extreme conditions such as very high temperatures, experimental techniques do not always allow researchers to observe the ultra-fast reactions that facilitate the correct changes to a material's atomic structure (or what aspects of the reaction may have introduced impurities). This is where computer simulations can be of help, however, simulating the behavior of a dynamic system such as a liquid is not without its own set of complications.

"The problem describing anything like this is you need to apply molecular dynamics (MD) simulations to get the right sampling," Andersen said. "Then, of course, there is the system size--you need to have a large enough system to accurately simulate the behavior of the liquid." Unlike experiments, molecular dynamics simulations offer researchers the ability to look at events happening on the atomic scale from a variety of different angles or pause the simulation to focus on different aspects.

While MD simulations offer researchers insights into the movement of individual atoms and chemical reactions that could not be observed during experiments, they do have their own challenges. Chief among them is the compromise between accuracy and cost--when relying on accurate ab initio methods to drive the MD simulations, it is extremely computationally expensive to get simulations that are large enough and last long enough to accurately model these reactions in a meaningful way.

Andersen and her colleagues used about 2,500 cores on JUWELS in periods stretching over more than one month for the recent simulations. Despite the massive computational effort, the team could still only simulate around 1,500 atoms over picoseconds of time. While these may sound like modest numbers, these simulations were among the largest done of ab initio MD simulations of graphene on liquid copper. The team uses these highly accurate simulations to help develop cheaper methods to drive the MD simulations so that it becomes possible to simulate larger systems and longer timescales without compromising the accuracy.

Strengthening links in the chain

The team published its record-breaking simulation work in the Journal of Chemical Physics, then used those simulations to compare with experimental data obtained in their most recent paper, which appeared in ACS Nano.

Andersen indicated that current-generation supercomputers, such as JUWELS and SuperMUC-NG, enabled the team to run its simulation. Next generation machines, however, would open up even more possibilities, as researchers could more rapidly simulate larger numbers or systems over longer periods of time.

Andersen received her PhD in 2014, and indicated that graphene research has exploded during the same period. "It is fascinating that the material is such a recent research focus--it is almost encapsulated in my own scientific career that people have looked closely at it," she said. Despite the need for more research into using liquid catalysts to produce graphene, Andersen indicated that the two-pronged approach of using both HPC and experiment would be essential to further graphene's development and, in turn, use in commercial and industrial applications. "In this research, there is a great interplay between theory and experiment, and I have been on both sides of this research," she said.

Engaged listening techniques such as eye contact, nodding and using key words to praise openness helps teenagers when they admit bad behaviour and share hurt feelings with their parents, a new study has shown.

University of Reading and Haifa researchers asked 1001 13 to 16-year-olds to watch a staged conversation between a parent and teenager about a difficult situation, with the parent adopting different body language and listening behaviour in different versions.

The participants who watched the versions where the parent was visibly attentive stated that they would have felt better about themselves as the teenager and would be more likely to open up about their feelings again in the future.

The study, the first to look at quality of listening in isolation from other parenting techniques, revealed that being more engaged while listening made the teenagers feel more authentic and connected with the parent.

Dr Netta Weinstein, associate professor in clinical and social psychology at the University of Reading, who co-led the study, said:

"We all know that listening to someone talk about their problems is an effective way of reassuring them and establishing a connection. However, until now there has been little thought given to the quality of that listening, and the difference that makes."

"This study shows that in parent-teenager relationships, quietly listening to a teenager while showing them they are valued and appreciated for their honesty has a powerful effect on their willingness to open up."

For the study published in the Journal of Experimental Child Psychology, a roughly even split of male and female adolescents were recruited, with three identifying as another gender. The team found that active listening was equally important across all participants.

The first video conversation scenario portrayed a teenage boy admitting to his mother that he had tried vaping and felt ashamed, and in the second he tells his mother he was rejected by his peers after refusing to vape and felt hurt.

Each video scenario had a version where the parent listened attentively, and another where they appeared more distracted, and used less eye contact.

Dr Weinstein said:

"With such a large group of participants, it is reassuring to see that active listening was universally beneficial across these years of adolescence."

"The study has some important implications for teenage wellbeing as well. The participants said that the good listening model observed in the videos would lead to better wellbeing. Although we don't know how often the expectations meets reality, but it's clear that active listening is more likely to lead to a good outcome for teenagers than the more passive style we tested it against."

Highlights

Among adults with kidney failure undergoing hemodialysis in New York City, Black and Hispanic patients were more likely to develop symptomatic COVID-19 than White patients.

Neighborhood-level social vulnerability factors were associated with COVID-19 incidence among White patients, but these factors did not explain racial/ethnic disparities.

Washington, DC (June 1, 2021) -- In an analysis of patients on hemodialysis in New York City, there were substantial racial/ethnic disparities in COVID-19 rates that were not explained by neighborhood social vulnerability. The findings appear in an upcoming issue of JASN.

The COVID-19 pandemic has disproportionately affected socially disadvantaged groups, including Black and Hispanic individuals, those with limited English proficiency, and persons of low socioeconomic status. To examine potential racial/ethnic and socioeconomic disparities in COVID-19 in individuals with kidney failure who are undergoing hemodialysis (which puts them at risk of acquiring COVID-19 because they travel several times each week to receive treatment in a congregate setting), Sri Lekha Tummalapalli, MD, MBA, MAS (Weill Cornell Medicine and The Rogosin Institute) and her colleagues analyzed information on 1,378 patients receiving in-center hemodialysis in New York City between March 1, 2020 and August 3, 2020.

A total of 247 patients (17.9%) developed symptomatic COVID-19. Compared with non- Hispanic White patients, non-Hispanic Black patients and Hispanic patients were 1.76-times and 2.66-times more likely to develop symptomatic COVID-19, respectively, after adjustments. "Racial/ethnic disparities in COVID-19 incidence among patients on hemodialysis largely mirrored community transmission patterns, and likely reflect neighborhood spread to this vulnerable population," said Dr. Tummalapali.

The investigators found that neighborhood-level social vulnerability factors--such as income, education level, languages spoken, and housing crowding--were associated with COVID-19 incidence among non-Hispanic White patients, but these factors did not explain racial/ethnic disparities. Black and Hispanic patients on hemodialysis faced an excess risk of acquiring COVID-19, regardless of the neighborhood they lived in.

"These results suggest that other unmeasured household and community exposures contribute to racial/ethnic disparities in acquiring COVID-19," said Dr. Tummalapalli. "Understanding factors that drive disparities could inform policies and interventions designed to mitigate disparities."

A first encounter with the dengue virus typically causes very mild symptoms; however, a subsequent infection is a different story. For a small proportion of people who are reinfected, the virus can cause severe symptomatic disease, which is often life-threatening.

"The main hypothesis for some time has been that antibodies generated the first time around, instead of providing protection against disease, can actually exacerbate it," says Stylianos Bournazos, research assistant professor at Rockefeller. "But even in secondary infection, we see a wide range of symptoms--so the presence of antibodies alone cannot explain why only some cases turn deadly."

Now new findings published in Science by the lab of Jeffrey V. Ravetch in collaboration with the Pasteur Institute in Cambodia suggest that the susceptibility and severity of dengue disease comes down to a particular type of antibody that is missing a specific sugar, fucose, on its stem. This impacts the antibody's so-called Fc region, which is responsible for binding and passing instructions along to other immune cells.

Previously, researchers in the Ravetch lab found that patients with severe dengue disease have unusually high levels of these fucose-less antibodies. However, it was not clear whether the absence of fucose was the result of severe disease or its cause.

By analyzing samples from a variety of dengue patients early in the onset of their disease, the team found that those who eventually developed the most severe disease also had significantly higher levels of fucose-deficient antibodies at the time of hospital admission. As a result of this change to their structure, the antibodies bind too strongly to white blood cells, increasing inflammation and leading to the destruction of platelets crucial for blood clotting. The result is hemorrhagic fever and shock syndrome often seen in severe dengue disease.

The findings suggest that the fucose status of antibodies represents a robust prognostic tool, says Ravetch, Theresa and Eugene M. Lang Professor and head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology. "It can help us identify patients at risk of severe illness so they can receive appropriate medical care early on."

As India continues to be ravaged by the pandemic, a Swansea University academic is investigating how green tea could give rise to a drug capable of tackling Covid-19.

Dr Suresh Mohankumar carried out the research with colleagues in India during his time at JSS College of Pharmacy, JSS Academy of Higher Education and Research in Ooty prior to taking up his current role at Swansea University Medical School.

He said: "Nature's oldest pharmacy has always been a treasure of potential novel drugs and we questioned if any of these compounds could assist us in battling the Covid-19 pandemic?

"We screened and sorted a library of natural compounds already know to be active against other coronaviruses using an artificial intelligence-aided computer programme.

"Our findings suggested that one of the compounds in green tea could combat the coronavirus behind Covid-19."

The researchers' work has now been highlighted by online journal RSC Advances and has been included in its prestigious hot articles collection chosen by editors and reviewers.

Associate Professor Dr Mohankumar emphasised that the research was still in its early days and a long way from any kind of clinical application.

"The compound that our model predicts to be most active is gallocatechin, which is present in green tea and could be readily available, accessible, and affordable. There now needs to be further investigation to show if it can be proven clinically effective and safe for preventing or treating Covid-19.

"This is still a preliminary step, but it could be a potential lead to tackling the devastating Covid-19 pandemic.

Dr Mohankumar has worked in pharmacy education, research and administration around the world for more than 18 years and recently moved to Swansea to join its new MPharm programme.

Head of Pharmacy Professor Andrew Morris said: "This is fascinating research and demonstrates that natural products remain an important source of lead compounds in the fight against infectious diseases. I'm also really pleased to see this international research collaboration continuing now that Dr Mohankumar has joined the Pharmacy team."

Dr Mohankumar added he is now looking forward to seeing how the work can be developed: "There now needs to be appropriate pre-clinical and clinical studies and we would welcome potential collaborators and partners to help carry this work forward."

EAST LANSING, Mich. - New research from MSU shows that an infant's gut microbiome could contain clues to help monitor and support healthy neurological development

Why do some babies react to perceived danger more than others? According to new research from Michigan State University and the University of North Carolina, Chapel Hill, part of the answer may be found in a surprising place: an infant's digestive system.

The human digestive system is home to a vast community of microorganisms known as the gut microbiome. The MSU-UNC research team discovered that the gut microbiome was different in infants with strong fear responses and infants with milder reactions.

These fear responses -- how someone reacts to a scary situation -- in early life can be indicators of future mental health. And there is growing evidence tying neurological well-being to the microbiome in the gut.

The new findings suggest that the gut microbiome could one day provide researchers and physicians with a new tool to monitor and support healthy neurological development.

"This early developmental period is a time of tremendous opportunity for promoting healthy brain development," said MSU's Rebecca Knickmeyer, leader of the new study published June 2 in the journal Nature Communications. "The microbiome is an exciting new target that can be potentially used for that."

Studies of this connection and its role in fear response in animals led Knickmeyer, an associate professor in the College of Human Medicine's Department of Pediatrics and Human Development, and her team to look for something similar in humans. And studying how humans, especially young children, handle fear is important because it can help forecast mental health in some cases.

"Fear reactions are a normal part of child development. Children should be aware of threats in their environment and be ready to respond to them" said Knickmeyer, who also works in MSU's Institute for Quantitative Health Science and Engineering, or IQ. "But if they can't dampen that response when they're safe, they may be at heightened risk to develop anxiety and depression later on in life."

On the other end of the response spectrum, children with exceptionally muted fear responses may go on to develop callous, unemotional traits associated with antisocial behavior, Knickmeyer said.

To determine whether the gut microbiome was connected to fear response in humans, Knickmeyer and her co-workers designed a pilot study with about 30 infants. The researchers selected the cohort carefully to keep as many factors impacting the gut microbiome as consistent as possible. For example, all of the children were breastfed and none was on antibiotics.

The researchers then characterized the children's microbiome by analyzing stool samples and assessed a child's fear response using a simple test: observing how a child reacted to someone entering the room while wearing a Halloween mask.

"We really wanted the experience to be enjoyable for both the kids and their parents. The parents were there the whole time and they could jump in whenever they wanted," Knickmeyer said. "These are really the kinds of experiences infants would have in their everyday lives."

Compiling all the data, the researchers saw significant associations between specific features of the gut microbiome and the strength of infant fear responses.

For example, children with uneven microbiomes at 1 month of age were more fearful at 1 year of age. Uneven microbiomes are dominated by a small set of bacteria, whereas even microbiomes are more balanced.

The researchers also discovered that the content of the microbial community at 1 year of age related to fear responses. Compared with less fearful children, infants with heightened responses had more of some types of bacteria and less of others.

The team, however, did not observe a connection between the children's gut microbiome and how the children reacted to strangers who weren't wearing masks. Knickmeyer said this is likely due to the different parts of the brain involved with processing potentially frightening situations.

"With strangers, there is a social element. So children may have a social wariness, but they don't see strangers as immediate threats," Knickmeyer said. "When children see a mask, they don't see it as social. It goes into that quick-and-dirty assessment part of the brain."

As part of the study, the team also imaged the children's brains using MRI technology. They found that the content of the microbial community at 1 year was associated with the size of the amygdala, which is part of the brain involved in making quick decisions about potential threats.

Connecting the dots suggests that the microbiome may influence how the amygdala develops and operates. That's one of many interesting possibilities uncovered by this new study, which the team is currently working to replicate. Knickmeyer is also preparing to start up new lines of inquiry with new collaborations at IQ, asking new questions that she's excited to answer.

"We have a great opportunity to support neurological health early on," she said. "Our long-term goal is that we'll learn what we can do to foster healthy growth and development."

EAST LANSING, Mich. - It can be easy to forget that the human skin is an organ. It's also the largest one and it's exposed, charged with keeping our inner biology safe from the perils of the outside world.

But Michigan State University's Sangbum Park is someone who never takes skin or its biological functions for granted. He's studying skin at the cellular level to better understand it and help us support it when it's fighting injury, infection or disease.

In the latest installment of that effort, Park, who works in IQ -- MSU's Institute for Quantitative Health Science & Engineering -- has helped reveal how the skin's immune cells organize themselves to ward off would-be intruders. Park and his colleagues published their work in the journal Nature Cell Biology.

"Immune cells are the soldiers of our body. In our skin, that army is maintained according to two factors: density and distribution," said Park, an assistant professor in the College of Human Medicine's Department of Medicine and Department of Pharmacology and Toxicology.

"We need enough immune cells to cover the whole area of our skin uniformly for proper protection. Otherwise, our skin would be vulnerable to damage and infection," Park said. "As sensible as that might sound, it was unclear how, or even if, these immune cells were organized before this study. Many researchers thought the cells' distribution was random."

Skin's immune cells have a history of being misunderstood. Many people don't realize that our outermost layer of skin, the epidermis, is home to immune cells. And when the German scientist Paul Langerhans first discovered one type of these immune cells in the late 1800s -- cells that are now called Langerhans cells -- he mistook them for cells from our nervous system (to be fair, they do have a similar morphology).

To bring more clarity to how skin's immune cells do their jobs, Park and his co-workers used state-of-the-art microscopy tools. The researchers illuminated how live immune cells arranged themselves in the skin of mice, a popular animal model with a skin biology similar to that of humans.

"IQ has so many advantages for a young investigator like me," said Park, who joined MSU in January 2020. Just two months later, he had to start working from home due to the coronavirus pandemic. But thanks to IQ's strong microscopy core, Park's team was able to work almost immediately as restrictions lifted.

"I didn't have to wait to set up microscopes in my own lab or train my students how to use them," he said. "At IQ, we already have many different microscopes for a wide range of animal models."

As a result, Park's team is revealing the skin's structure and function like never before. Having validated these new techniques and observing how immune cells are organized in the healthy skin of mice, Park's team can start probing new questions about how skin heals.

"My lab is interested in how skin regenerates and recovers from injury," he said. That injury could be a cut, an infection, an allergic reaction or an even more persistent disorder, such as psoriasis. "We can answer so many questions with our intravital imaging technique that you just can't with conventional methods."

Toronto -- Math continues to be a powerful force against COVID-19.

Its latest contribution is a sophisticated algorithm, using municipal wastewater systems, for determining key locations in the detection and tracing of COVID-19 back to its human source, which may be a newly infected person or a hot spot of infected people. Timing is key, say the researchers who created the algorithm, especially when COVID-19 is getting better at transmitting itself, thanks to emerging variants.

"Being quick is what we want because in the meantime, a newly-infected person can infect others," said Oded Berman, a professor of operations management and statistics at the University of Toronto's Rotman School of Management.

This latest research builds on previous work Prof. Berman did with co-investigators Richard Larson of the Massachusetts Institute of Technology and Mehdi Nourinejad of York University. The trio initially developed two algorithms for identifying choice locations in a sewer system for manual COVID-19 testing and subsequent tracing back to the source. Sewers are a rich environment for detecting presence of the disease upstream because genetic remnants of its virus are shed in the stool of infected people up to a week before they may even know they are sick.

The investigators' new research refines and optimizes that initial work by more accurately modelling a typical municipal sewer system's treelike network of one-way pipes and manholes, and by speeding up the detection/tracing process through automatic sensors installed in specific manholes, chosen according to an easier-to-use algorithm.

Under this scenario, a sensor sends out an alert any time COVID-19 is detected. Manual testing is then done at a few manholes further upstream, also chosen according to the algorithm, until the final source is located, be that a small group of homes or a "hotspot" neighbourhood. Residents in that much smaller area can then be contacted for further testing and isolation as needed, limiting potential new outbreaks.

Applying this approach to a wastewater system with 2,000 manholes shows that only seven sensors would have to be installed along the network to detect and trace COVID-19 back to its origin within one day.

"The sensors allow us to manually sample a smaller number of manholes than in our earlier work and to detect the infection much sooner," said Prof. Berman.

Although such sensors are not yet available, such technology is under development. An accurate and rapid on-site test for COVID-19 and field testing for finetuning the system will also be needed.

The results hold promise not only for detecting COVID-19 but other viruses too, such as noroviruses which are highly infectious and cause vomiting and diarrhea. There is also potential for the work to be used in surveillance for crystal meth labs and illegal bomb production, because of the chemical by-products that end up in wastewater.

Prof. Berman typically works on problems of the future, such as the introduction of autonomous cars, making his wastewater research the first time that he has applied his expertise to an urgent global issue.

"It's exciting to work on something that is very much needed and might have the potential to help people soon," he said. "It's very different from what I've done before."

ROCHESTER, Minn. -- A study by researchers at Mayo Clinic Cancer Center has found that cancer patients diagnosed with COVID-19 who received care at home via remote patient monitoring were significantly less likely to require hospitalization for their illness, compared to cancer patients with COVID-19 who did not participate in the program. Results of the study were presented Friday, June 4, at the American Society of Clinical Oncology Annual Meeting and published in the Journal of Clinical Oncology.

"For our study, we evaluated 224 Mayo Clinic patients with cancer who were found to have COVID-19 through standardized screening prior to receiving cancer treatment, or due to symptoms or close exposure," says Tufia Haddad, M.D., a Mayo Clinic medical oncologist and the study's senior author. Researchers followed the patients March 18-July 31, 2020.

Dr. Haddad says that at the outset of the COVID-19 pandemic, Mayo Clinic rapidly developed and implemented a remote patient monitoring program to support Mayo Clinic patients who were diagnosed with COVID-19 and at risk for severe illness.

The program featured the use of in-home technology to monitor oxygen levels, vital signs and symptoms of COVID-19 infection, and a centralized virtual care team of nurses and physicians to manage patients. Dr. Haddad says the program had served more than 8,000 patients in rural and urban locations across 41 states by November 2020.

Researchers found that among patients who did not require urgent hospitalization at the time of their COVID-19 diagnosis, those whose care was managed by the remote patient monitoring program were significantly less likely to require hospitalization for their illness, compared with those who were not managed by the program.

"After balancing the two groups of patients who were or were not managed by the remote monitoring program for factors known to impact COVID-19 outcomes, such as old age, male gender and obesity, there was a 78% reduction in the risk of hospitalization (a 2.8% risk for patients on the remote monitoring program, compared to 13% for patients not on the program) attributed to the remote monitoring program," says Dr. Haddad.

In addition, Dr. Haddad says that when cancer patients who had been managed through the remote monitoring program were hospitalized, they experienced fewer hospitalizations of more than a week, ICU admissions and deaths.

"It is possible that our results were due to early detection of adverse symptoms and vital sign trends that enabled earlier care interventions to alter the trajectory of disease." Dr. Haddad is encouraged by the results, but she cautions that further research will be necessary to confirm them.