Culture

Diamonds have a firm foothold in our lexicon. Their many properties often serve as superlatives for quality, clarity and hardiness. Aside from the popularity of this rare material in ornamental and decorative use, these precious stones are also highly valued in industry where they are used to cut and polish other hard materials and build radiation detectors.

More than a decade ago, a new property was uncovered in diamonds when high concentrations of boron are introduced to it - superconductivity. Superconductivity occurs when two electrons with opposite spin form a pair (called a Cooper pair), resulting in the electrical resistance of the material being zero. This means a large supercurrent can flow in the material, bringing with it the potential for advanced technological applications. Yet, little work has been done since to investigate and characterise the nature of a diamond's superconductivity and therefore its potential applications.

New research led by Professor Somnath Bhattacharyya in the Nano-Scale Transport Physics Laboratory (NSTPL) in the School of Physics at the University of the Witwatersrand in Johannesburg, South Africa, details the phenomenon of what is called "triplet superconductivity" in diamond. Triplet superconductivity occurs when electrons move in a composite spin state rather than as a single pair. This is an extremely rare, yet efficient form of superconductivity that until now has only been known to occur in one or two other materials, and only theoretically in diamonds.

"In a conventional superconducting material such as aluminium, superconductivity is destroyed by magnetic fields and magnetic impurities, however triplet superconductivity in a diamond can exist even when combined with magnetic materials. This leads to more efficient and multifunctional operation of the material," explains Bhattacharyya.

The team's work has recently been published in an article in the New Journal of Physics, titled "Effects of Rashba-spin-orbit coupling on superconducting boron-doped nanocrystalline diamond films: evidence of interfacial triplet superconductivity". This research was done in collaboration with Oxford University (UK) and Diamond Light Source (UK). Through these collaborations, beautiful atomic arrangement of diamond crystals and interfaces that have never been seen before could be visualised, supporting the first claims of 'triplet' superconductivity.

Practical proof of triplet superconductivity in diamonds came with much excitement for Bhattacharyya and his team. "We were even working on Christmas day, we were so excited," says Davie Mtsuko. "This is something that has never been before been claimed in diamond," adds Christopher Coleman. Both Mtsuko and Coleman are co-authors of the paper.

Despite diamonds' reputation as a highly rare and expensive resource, they can be manufactured in a laboratory using a specialised piece of equipment called a vapour deposition chamber. The Wits NSTPL has developed their own plasma deposition chamber which allows them to grow diamonds of a higher than normal quality - making them ideal for this kind of advanced research.

This finding expands the potential uses of diamond, which is already well-regarded as a quantum material. "All conventional technology is based on semiconductors associated with electron charge. Thus far, we have a decent understanding of how they interact, and how to control them. But when we have control over quantum states such as superconductivity and entanglement, there is a lot more physics to the charge and spin of electrons, and this also comes with new properties," says Bhattacharyya. "With the new surge of superconducting materials such as diamond, traditional silicon technology can be replaced by cost effective and low power consumption solutions".

The induction of triplet superconductivity in diamond is important for more than just its potential applications. It speaks to our fundamental understanding of physics. "Thus far, triplet superconductivity exists mostly in theory, and our study gives us an opportunity to test these models in a practical way," says Bhattacharyya.

Ultraviolet light from giant stellar flares can destroy a planet's habitability. New research from the University of North Carolina at Chapel Hill will help astrobiologists understand how much radiation planets experience during super flares and whether life could exist on worlds beyond our solar system.

Super flares are bursts of energy that are 10 to 1,000 times larger than the biggest flares from the Earth's sun. These flares can bathe a planet in an amount of ultraviolet light huge enough to doom the chances of life surviving there.

Researchers from UNC-Chapel Hill have for the first time measured the temperature of a large sample of super flares from stars, and the flares' likely ultraviolet emissions. Their findings, published Oct. 5 ahead of print in Astrophysical Journal, will allow researchers to put limits on the habitability of planets that are targets of upcoming planet-finding missions.

"We found planets orbiting young stars may experience life-prohibiting levels of UV radiation, although some micro-organisms might survive," said lead study author Ward S. Howard, a doctoral student in the Department of Physics and Astronomy at UNC-Chapel Hill.

Howard and colleagues at UNC-Chapel Hill used the UNC-Chapel Hill Evryscope telescope array and NASA's Transiting Exoplanet Survey Satellite (TESS) to simultaneously observe the largest sample of super flares.

The team's research expands upon previous work that has largely focused on flare temperatures and radiation from only a handful of super flares from a few stars. In expanding the research, the team discovered a statistical relationship between the size of a super flare and its temperature. The temperature predicts the amount of radiation that potentially precludes on-surface life.

Super flares typically emit most of their UV radiation during a rapid peak lasting only five to 15 minutes. The simultaneous Evryscope and TESS observations were obtained at two-minute intervals, ensuring multiple measurements were taken during the peak of each super flare.

This is the first time the temperatures of such a large sample of super flares has ever been studied. The frequency of observations allowed the team to discover the amount of time super flares can cook orbiting planets with intense UV radiation.

The flares observed have already informed the TESS Extended Mission to discover thousands of exoplanets in orbit around the brightest dwarf stars in the sky. TESS is now targeting high priority flare stars from the UNC-Chapel Hill sample for more frequent observations.

"Longer term these results may inform the choice of planetary systems to be observed by NASA's James Webb Space Telescope based on the system's flaring activity," said study co-author Nicholas M. Law, associate professor of physics and astronomy at UNC-Chapel Hill and principal investigator of the Evryscope telescope.

"We found that - over the longer term - the links between plant traits and ecosystem functions were indeed very weak, as we could only explain about 12 per cent of the variance in ecosystem functioning," said the paper's lead author, Dr Fons van der Plas from the Institute of Biology at Leipzig University. Together with colleagues from the German Centre for Integrative Biodiversity Research (iDiv) and other research institutions in Germany and abroad, he found different patterns than in previous studies - which had focused on short-term links between plant traits and ecosystem functions. These had previously assumed much stronger links between plant traits and ecosystem functioning.

"The main difference between our studies and earlier ones was that we carried out our work over a period of ten years, while most other studies were based on data measured in just one year," said the biologist. The relationships between plant traits and ecosystem functions changed from year to year: some species become locally extinct, while others replace them.

Scientists often ask themselves how this change in biodiversity affects the way ecosystems function, for example in terms of biomass production, carbon sequestration and pollination. In predicting these consequences, they rely on the traits in which plants differ. For example, some plant species are pollinated by insects, and others by the wind. They hope that knowing which species will be more common in the future and what traits these species have will enable them to make more precise predictions.

The research team led by van der Plas has now discovered, for example, that plant biomass production was maximised in plant communities dominated by species with thick roots in some years and by completely different plant communities in others. In almost every year, a different plant trait was found to have been important for maximising biomass production. According to van der Plas, it is therefore extremely difficult to predict exactly how changes in plant communities affect the functioning of ecosystems over long periods of time.

Ganoderma lucidum, known as Yeongji mushroom in Korea, is called a modern-day elixir plant and has long been used medicinally in China, Japan and Korea. Ganoderic acid, an active ingredient found in the mushroom, is known for its excellence in enhancing the immune function of cells. Due to the hard texture of the mushroom, it has been ingested in powder or liquid form, but it has been noted that the active ingredient becomes destroyed when the mushroom is dried for an extended period of time or the extraction is performed at high heat (80 °C or higher).

The Korea Institute of Science and Technology (KIST) announced that a team led Dr. Ho-Youn Kim of the Smart Farm Research Center of the Gangneung Natural Products Informatics Center determined the conditions for enhancing the anti-inflammatory, anti-diabetic, and antioxidant effects of Ganoderma lucidum and confirmed its marketability as an anti-inflammatory agent for the skin.

In order to reduce the amount of the active ingredient destroyed and increase the efficacy, the KIST research team extracted the active ingredient after drying the mushroom at various temperatures and times, through which they pinpointed the optimal conditions to achieve the best possible anti-inflammatory, antioxidant and anti-diabetic effects. As a result, it was confirmed that drying with hot air at 60°C led to excellent anti-inflammatory properties, as it led to the extraction of a large amount of ganoderic acid, while outstanding antioxidant and antidiabetic activities resulted from freeze-drying the mushroom at -50°C.

Also, an experiment was carried out using the extract from hot air-dried Ganoderma lucidum on inflammation-induced keratinocytes, and the results showed that it effectively suppressed skin inflammation. The extraction conditions yielding such an effective active ingredient for skin inflammation have never been revealed before, and thus a patent application has been filed (Patent No.: 10-2020-0041577).

It is believed that the results of this study regarding the effect of varying the drying and extraction conditions on the antioxidant, antidiabetic, and anti-inflammatory activities of Ganoderma lucidum will be useful in developing processed products with the mushroom in the future.

Dr. Kim from KIST who spearheaded the research said, "Since the efficacy of Yeongji mushrooms (Ganoderma lucidum) varies depending on the drying and extraction methods, the drying method should be selected according to the purpose of use. It is expected that the findings of this study will not only raise the utility of the mushroom but also lead to the development of therapeutic agents for inflammatory skin conditions such as psoriasis and atopic dermatitis in the future."

Trust in public institutions is linked to fewer COVID-19 deaths, but trust and belonging to groups is associated with more deaths, according to a wide-ranging, McGill-led study of 30-day COVID-19 mortality rates in 84 countries. Greater economic inequality is also associated with COVID-19 mortality.

The study led by McGill researchers published in Social Science & Medicine, is the first to show how global differences in COVID-19 mortality relate to income inequality. It also includes surveys on social trust and confidence in public institutions representing 86% of the global population.

The trouble with trust

The analysis reveals that COVID-19 mortality is linked to differences in trust. A lack of confidence in state institutions was associated with more deaths - consistent with research during the SARS and H1N1 pandemics. Surprisingly, however, the researchers found that social trust and belonging is also associated with mortality. While connecting with friends and family is a natural response in times of crisis, in some countries, this trust and the desire to socialize may be interfering with efforts to contain transmission through physical distancing.

Moreover, strong group bonds can sometimes reinforce risky health behaviours, so that high-trusting societies may be more susceptible to misinformation about the severity of COVID-19, bogus treatments, or dismissive attitudes towards physical distancing. "People expect there are health benefits to trusting others and belonging to groups - and there usually are. But in the context of a pandemic, when you need people to self-isolate, blind trust in others can get in the way," says lead author Frank Elgar, a professor at McGill University and Canada Research Chair in Social Inequality in Child Health.

On the other hand, confidence in public institutions and civic participation were linked to fewer deaths, possibly because they mobilise people to wear masks, wash their hands, and practice physical distancing. The researchers note that being engaged in the community is particularly beneficial when groups are asked to compromise some personal freedom for the common good, like wearing a mask in public.

"Governments and other organisations can capitalise on this engagement during a pandemic by supporting safe ways for people to socialise and remain involved in their communities and cultural activities."

Inequality, not just poverty, a health problem during the pandemic

The researchers also found that income inequality is associated with more deaths, even after accounting for other social factors like national wealth and population age. "Countries with a larger gap between rich and poor, like the United States, Russia, and Brazil are experiencing a more deadly pandemic," says Elgar, who is also a member of the Department of Psychiatry in the Faculty of Medicine.

"In many countries, lower-wage workers are over-represented among the essential workers in retail, public transit, and health care settings who cannot easily practice physical distancing," says Elgar. Greater exposure to the virus and less access to health services among the poor could explain why more economically unequal countries - not necessarily the poorest countries - experienced significantly higher mortality rates. The researchers note, however, that wealthier countries may also have more accurate data or shorter lags in supplying death counts to health officials.

"There is a serious message here about the new challenges we will likely face in this second wave of the pandemic, and our capacity to mount a defense," says Elgar.

New Haven, Conn. -- A growing body of research suggests the planet Venus may have had an Earth-like environment billions of years ago, with water and a thin atmosphere.

Yet testing such theories is difficult without geological samples to examine. The solution, according to Yale astronomers Samuel Cabot and Gregory Laughlin, may be closer than anyone realized.

Cabot and Laughlin say pieces of Venus -- perhaps billions of them -- are likely to have crashed on the moon. A new study explaining the theory has been accepted by the Planetary Science Journal.

The researchers said asteroids and comets slamming into Venus may have dislodged as many as 10 billion rocks and sent them into an orbit that intersected with Earth and Earth's moon. "Some of these rocks will eventually land on the moon as Venusian meteorites," said Cabot, a Yale graduate student and lead author of the study.

Cabot said catastrophic impacts such as these only happen every hundred million years or so -- and occurred more frequently billions of years ago.

"The moon offers safe keeping for these ancient rocks," Cabot said. "Anything from Venus that landed on Earth is probably buried very deep, due to geological activity. These rocks would be much better preserved on the moon."

Many scientists believe that Venus might have had an Earth-like atmosphere as recently as 700 million years ago. After that, Venus experienced a runaway greenhouse effect and developed its current climate. The Venusian atmosphere is so thick today that no rocks could possibly escape after an impact with an asteroid or comet, Cabot said.

Laughlin and Cabot cited two factors supporting their theory. The first is that asteroids hitting Venus are usually going faster than those that hit Earth, launching even more material. The second is that a huge fraction of the ejected material from Venus would have come close to Earth and the moon.

"There is a commensurability between the orbits of Venus and Earth that provides a ready route for rocks blasted off Venus to travel to Earth's vicinity," said Laughlin, who is professor of astronomy and astrophysics at Yale. "The moon's gravity then aids in sweeping up some of these Venusian arrivals."

Upcoming missions to the moon could give Cabot and Laughlin their answer soon. The researchers said NASA's Artemis program is the perfect opportunity to collect and analyze unprecedented amounts of lunar soil.

Laughlin said there are several standard chemical analyses that can pinpoint the origin of moon rocks, including any that came from Venus. Different ratios of specific elements and isotopes offer a kind of fingerprint for each planet in the solar system.

"An ancient fragment of Venus would contain a wealth of information," Laughlin said. "Venus' history is closely tied to important topics in planetary science, including the past influx of asteroids and comets, atmospheric histories of the inner planets, and the abundance of liquid water."

A team of psychologists at the Universities of Sussex and Portsmouth have purr-fected the art of building a bond with cats.

The new study 'The role of cat eye narrowing movements in cat-human communication', published online in the Nature journal Scientific Reports, has shown for the first time that it is possible to build rapport with a cat by using an eye narrowing technique with them. This eye narrowing action by humans generates something popularly known as a cat smile - the so called "slow blink" - and seems to make the human more attractive to the cat. Eye narrowing movements in cats have some parallels with the genuine smile in humans (the Duchenne smile), as well as eye narrowing movements given in positive situations in some other species.

The team, led by Dr Tasmin Humphrey and Professor Karen McComb, animal behaviour scientists at the University of Sussex, undertook two experiments. The first revealed that cats are more likely to slow blink at their owners after their owners have slow blinked at them, compared to when they don't interact at all. The second experiment, this time with a researcher from the psychology team, rather than the owner, found that the cats were more likely to approach the experimenter's outstretched hand after they'd slow blinked at the cat, compared to when they had adopted a neutral expression. Taken together, the study shows that this slow blinking technique can provide a form of positive communication between cats and humans.

The study found:

· Cats were more likely to slow blink at their owners if their owners had slowed blinked at them, compared to when the owner was present in the room but not delivering a slow blink stimulus.

· Cats were more likely to slow blink when an unfamiliar experimenter slow blinked at them, compared to when they had maintained a neutral expression.

· Cats preferred to approach an experimenter after they had slow blinked at the cat than if they had maintained a neutral expression.

Professor Karen McComb, from the School of Psychology at the University of Sussex, who supervised the work, said: "As someone who has both studied animal behaviour and is a cat owner, it's great to be able to show that cats and humans can communicate in this way. It's something that many cat owners had already suspected, so it's exciting to have found evidence for it.

"This study is the first to experimentally investigate the role of slow blinking in cat-human communication. And it is something you can try yourself with your own cat at home, or with cats you meet in the street. It's a great way of enhancing the bond you have with cats. Try narrowing your eyes at them as you would in a relaxed smile, followed by closing your eyes for a couple of seconds. You'll find they respond in the same way themselves and you can start a sort of conversation."

Dr Tasmin Humphrey, a PhD student in the School of Psychology at the University of Sussex during the work, who was the first author of the study said: "Understanding positive ways in which cats and humans interact can enhance public understanding of cats, improve feline welfare, and tell us more about the socio-cognitive abilities of this under-studied species.

"Our findings could potentially be used to assess the welfare of cats in a variety of settings, including veterinary practices and shelters.

"In terms of why cats behave in this way, it could be argued that cats developed the slow blink behaviours because humans perceived slow blinking as positive. Cats may have learned that humans reward them for responding to slow blinking. It is also possible that slow blinking in cats began as a way to interrupt an unbroken stare, which is potentially threatening in social interaction.

Dr Leanne Proops at University of Portsmouth who co-supervised the work said: "It's definitely not easy to study natural cat behaviour so these results provide a rare insight in to the world of cat-human communication."

How the experiments worked

Two experiments were conducted to explore the significance of the slow blink in cat-human communication. The first experiment included a total of 21 cats from 14 different households. Fourteen different owners participated in experiment 1. Ten of the cats were male and 11 of the cats were female, with cat age ranging from an estimated 0.45-16 years. The experiments took place in each cat's home. The psychologist advised the cat's owner on how to slow blink. Once the cat had settled down in one place, the psychologist asked the owner to either sit approximately 1 m away from the cat.

Experiment 2 included a total of 24 additional cats. Twelve cats were male and 12 cats were female, with cat age ranging from an estimated 1-17 years old. The cats included in the final analyses were from 8 different households. In this experiment, the researcher, who was unfamiliar to the cat, either slow blinked at the cat or adopted a neutral face without direct eye contact. This experiment also tested which context the cats preferred to approach the unfamiliar experimenter, by them offering the cat a flat hand with palm faced upwards whilst sat or crouched directly opposite the cat. Both experiments were video recorded.

Cat psychology - the existing context

In the new paper, the authors provide some context for their findings. The psychology of cats hasn't been studied as extensively as dogs, but what is already known includes:

· That cats have been shown to attract and manipulate human attention effectively through 'solicitation purring'.

· That cats can discriminate their name from other words, even when unfamiliar humans are calling.

· That cats may be sensitive to human emotional cues, and will rub or butt their head against a an owner who feels sad.

'The role of cat eye narrowing movements in cat-human communication' by Tasmin Humphrey, Leanne Proops, Jemma Forman, Rebecca Spooner and Karen McComb published in Scientific Reports is open access, Link to the paper here: https://www.nature.com/articles/s41598-020-73426-0

DALLAS - Oct. 7, 2020 - Endocannabinoids, signaling molecules produced in the body that share features with chemicals found in marijuana, can shut down genes needed for some pathogenic intestinal bacteria to colonize, multiply, and cause disease, new research led by UT Southwestern scientists shows.

The findings, published online today in Cell, could help explain why the cannabis plant - the most potent part of which is marijuana - can lessen the symptoms of various bowel conditions and may eventually lead to new ways to fight gastrointestinal infections.

Discovered in 1992, endocannabinoids are lipid-based neurotransmitters that play a variety of roles in the body, including regulating immunity, appetite, and mood. Cannabis and its derivatives have long been used to relieve chronic gastrointestinal conditions, including irritable bowel syndrome and inflammatory bowel disease. Studies have shown that dysregulation of the body's endocannabinoid system can lead to intestinal inflammation and affect the makeup of gut microbiota, the population of different bacterial species that inhabit the digestive tract.

However, study leader Vanessa Sperandio, Ph.D., professor of microbiology and biochemistry at UTSW, says it's been unknown whether endocannabinoids affect susceptibility to pathogenic gastrointestinal infections.

To help answer this question, Sperandio and her colleagues worked with mice genetically altered to overproduce the potent mammalian endocannabinoid 2-arachidonoyl glycerol (2-AG) in various organs, including the intestines. When the researchers infected these animals and their unmodified littermates with Citrobacter rodentium, a bacterial pathogen that attacks the colon and causes marked inflammation and diarrhea, the mutant mice developed only mild symptoms compared with the more extreme gastrointestinal distress exhibited by their littermates. Examination of the mutant animals' colons showed far lower inflammation and signs of infection. These mice also had significantly lower fecal loads of C. rodentium bacteria and cleared their infection days faster than their unmodified littermates. Treating genetically unmodified animals with a drug that raised levels of 2-AG in the intestines produced similar positive effects.

Sperandio's team found that increased levels of 2-AG could also attenuate Salmonella typhimurium infections in mice and impede enterohemorrhagic Escherichia coli - a particularly dangerous gastrointestinal bacteria that infects humans - in order to express the virulence traits needed for a successful infection.

Conversely, when the researchers treated mammalian cells in petri dishes with tetrahydrolipstatin, a Food and Drug Administration-approved compound sold commercially as Alli that inhibits 2-AG production, they became more susceptible to the bacterial pathogens.

Further experiments showed that 2-AG exerted these effects on C. rodentium, S. typhimurium, and E. coli by blocking a bacterial receptor known as QseC. When this receptor senses the host signaling molecules epinephrine and norepinephrine, it triggers a molecular cascade necessary to establish infection. Plugging this receptor with 2-AG prevents this virulence program from activating, Sperandio explains, helping to protect against infection.

Sperandio notes that these findings could help explain some of the effects of cannabis use on inflammatory bowel conditions. Although studies have shown that cannabis can lower inflammation, recent research has shown that these conditions also tend to have a bacterial component that might be positively affected by plant cannabinoids.

In addition, cannabis compounds or synthetic derivatives could eventually help patients kick intestinal bacterial infections without antibiotics. This could be particularly useful for infections caused by enterohemorrhagic Escherichia coli, Sperandio says, which produces a deadly toxin when it's treated with antibiotics, rendering these drugs not only counterproductive but extremely dangerous. Because many virulent bacteria that colonize areas elsewhere in the body also have the QseC receptor, she adds, this strategy could be used more broadly to fight a variety of infections.

"By harnessing the power of natural compounds produced in the body and in plants," she says, "we may eventually treat infections in a whole new way."

Irvine, Calif., Oct. 7, 2020 - Electrical engineers, computer scientists and biomedical engineers at the University of California, Irvine have created a new lab-on-a-chip that can help study tumor heterogeneity to reduce resistance to cancer therapies.

In a paper published today in Advanced Biosystems, the researchers describe how they combined artificial intelligence, microfluidics and nanoparticle inkjet printing in a device that enables the examination and differentiation of cancers and healthy tissues at the single-cell level.

"Cancer cell and tumor heterogeneity can lead to increased therapeutic resistance and inconsistent outcomes for different patients," said lead author Kushal Joshi, a former UCI graduate student in biomedical engineering. The team's novel biochip addresses this problem by allowing precise characterization of a variety of cancer cells from a sample.

"Single-cell analysis is essential to identify and classify cancer types and study cellular heterogeneity. It's necessary to understand tumor initiation, progression and metastasis in order to design better cancer treatment drugs," said co-author Rahim Esfandyarpour, UCI assistant professor of electrical engineering & computer science as well as biomedical engineering. "Most of the techniques and technologies traditionally used to study cancer are sophisticated, bulky, expensive, and require highly trained operators and long preparation times."

He said his group overcame these challenges by combining machine learning techniques with accessible inkjet printing and microfluidics technology to develop low-cost, miniaturized biochips that are simple to prototype and capable of classifying various cell types.

In the apparatus, samples travel through microfluidic channels with carefully placed electrodes that monitor differences in the electrical properties of diseased versus healthy cells in a single pass. The UCI researchers' innovation was to devise a way to prototype key parts of the biochip in about 20 minutes with an inkjet printer, allowing for easy manufacturing in diverse settings. Most of the materials involved are reusable or, if disposable, inexpensive.

Another aspect of the invention is the incorporation of machine learning to manage the large amount of data the tiny system produces. This branch of AI accelerates the processing and analysis of large datasets, finding patterns and associations, predicting precise outcomes, and aiding in rapid and efficient decision-making.

By including machine learning in the biochip's workflow, the team has improved the accuracy of analysis and reduced the dependency on skilled analysts, which can also make the technology appealing to medical professionals in the developing world, Esfandyarpour said.

"The World Health Organization says that nearly 60 percent of deaths from breast cancer happen because of a lack of early detection programs in countries with meager resources," he said. "Our work has potential applications in single-cell studies, in tumor heterogeneity studies and, perhaps, in point-of-care cancer diagnostics - especially in developing nations where cost, constrained infrastructure and limited access to medical technologies are of the utmost importance."

A recent report published in Science Translational Medicine by MUSC Hollings Cancer Center investigator Sophie Paczesny, M.D., Ph.D., sheds light on immune cell biomarkers that may reveal which patients are most at risk for graft-versus-host disease (GVHD), a life-threatening condition that can arise after hematopoietic stem cell transplantation (HSCT) for treatment of liquid cancers such as leukemia.

"Allogeneic HSCT remains the only validated treatment to cure leukemia," explained Paczesny, chairwoman of the MUSC Department of Microbiology and Immunology. "In HSCT, donor-matched cells are infused into the bloodstream of sick patients and ultimately travel to the bone marrow. Some of these cells are immune cells, which help eliminate residual leukemic cells not killed by chemotherapy. Yet despite careful donor-recipient matching and use of immunosuppressive therapies following transplantation, some of the donor's immune cells may begin to attack the patient's tissues, which is called graft-versus-host disease."

GVHD impacts up to 50% of patients receiving HSCT and can manifest in multiple organs. About a third of those with GVHD experience localized effects within the gastrointestinal tract (GI-GVHD), which carries the highest risk for fatality.

Paczesny described the phenomenon further. "For patients with leukemia, you are providing donor cells that have a different biological, or antigen, signature as compared to the recipient. That is how these immune cells recognize the leukemia and destroy it. However, these antigens are also present in normal tissue, particularly in areas of the body with the most microbiota, like the gut. So that is where the donor immune cells attack and where symptoms are the hardest to treat."

A biomarker story

Bone marrow-derived stem cells are referred to as multipotent, meaning they can mature into many different types of cells. This includes red and white blood cells as well as other immune cell types such as dendritic cells and T-cells that are responsible for balancing immunity and tolerance.

Dendritic cells exchange messages with T-cells by displaying short protein chains on the cell surface, called antigens. T-cells, which become activated when they recognize "non-self" antigens, then play a key role in triggering the body's other defense systems against foreign invaders that can include transplanted cells from a different host.

Previous work from the Paczesny laboratory has shown that immune cell signaling pathways in GI-GVHD increased numbers of "super activated" pathogenic T-cells (Th17 cells) in the blood of these patients. The presence of these aggressive T-cells correlated with lower survival as compared to patients either lacking GVHD or those with less severe forms of GVHD in the skin. These cells were also unique in their ability to be induced by a T-cell signaling receptor called ICOS, short for "inducible T-cell co-stimulator."

"This started as a biomarker story," Paczesny said. "We were trying to understand where the activation of these T-cells was coming from. What was the antigen presenting cell? If you have markers of ICOS signaling on the T-cell side, there should be an ICOS ligand somewhere on the antigen presenting cell in that same cohort of patients."

Because ICOS ligand is located on the surface of antigen-presenting cells, such as dendritic cells, it can easily be detected using existing technologies like flow cytometry that can scan for these external markers on cells in the blood. In this way, individuals who are actively developing symptoms of GI-GVHD following HSCT could potentially be flagged.

Paczesny's group showed that levels of dendritic cells (specifically a population known as plasmacytoid dendritic cells) expressing the ICOS ligand were increased in patients with GI-GVHD as compared to controls. Critically, patients with high levels of these cells had significantly lower three-year survival outcomes compared to those with low levels.

Djamilatou Adom, Ph.D., a postdoctoral fellow working with Paczesny, further explored the role of ICOS signaling in GI-GVHD using mice. First, they showed that genetic elimination of ICOS ligand production in donor-mouse bone marrow cells prior to transplanting them into recipient mice protected the recipient mice from GVHD-related death. Also, using "humanized" mice with nonfunctional immune systems, the researchers discovered that transplanting human ICOS ligand-expressing plasmacytoid dendritic cells into these mice (whose own bone marrow had been destroyed through radiation) led to GVHD with increased levels of Th17 cells within the intestines.

The involvement of plasmacytoid dendritic cells in GVHD was an interesting finding, said Paczesny. "If these cells are not stimulated, they are usually considered more tolerogenic. In other words, they are the good guys. They lessen the severity of GVHD. However, if they become T-cell activating - for instance the ICOS ligand is one of the factors that will activate them by binding ICOS - then they become more toxic and might drive the development of GVHD. This point has previously been controversial in the field; however, past studies have only looked at overall numbers of plasmacytoid dendritic cells in these patients, not the activation status of these cells."

A new drug target in GVHD

Next, Paczesny explored whether targeting cell-to-cell ICOSL-ICOS signaling might prevent GI-GVHD. Classical T-cell activation is induced by the CD28/B7 co-stimulation pathway, in concert with the recognition of foreign antigens by the T-cell receptor. The CD28/B7pathway can be disrupted by the currently approved drugs abatacept and belatacept (Figure 1). However, through mechanisms that are still not well understood, immune cells can escape the CD28/B7 pathway blockade by rerouting or reinforcing their activation through alternative costimulatory pathways like ICOS/ICOSL.

In collaboration with researchers at Alpine Immune Sciences in Seattle, Washington, Paczesny's team found that dosing mice with the drug candidate ALPN-101, a recombinant human Fc fusion molecule that binds and blocks both ICOS and CD28 on T-cells, conferred complete protection from GVHD while also preserving anti-tumor effects of the transplant. It also performed better than drugs targeting CD28 (belatacept) or ICOS pathways individually.

"This is the first time I've seen a drug work as a treatment for GVHD that also preserves anti-leukemic activity of HSCT. This is new," explained Paczesny. "What's also interesting is that the drug was effective when we provided it early, directly after transplantation, and also when we provided it as a later treatment, after disease had already built up. This is important because most of the time GVHD symptoms appear much later, and that's when we need to intervene."

Clinical trials with ALPN-101 have begun, and Paczesny hopes that her biomarker research, which was supported by more than $1.5 million in funding from the National Cancer Institute, will open doors for the treatment of GVHD and other immune-related diseases such as lupus.

"There has been a big jump in the number of transplantations recently because clinicians have improved their HSCT technique and expanded its applications. There is now also more demand for mitigation of allogeneic responses and more need because cellular therapies with third-party donors are also expanding. Therefore, GVHD will continue to be an issue. But now, we have a biomarker that, when it is elevated, will help us know when to begin a specifically targeted treatment."

The team's findings have been published in Nature: Scientific Reports: "Transition delay using biomimetic fish scale arrays", and in the Journal of Experimental Biology: "Streak formation in flow over biomimetic fish scale arrays".

Reducing drag means faster aircraft speeds and less fuel consumption - an important area of study for aerodynamicists such as Professor Bruecker, City's Royal Academy of Engineering Research Chair in Nature-Inspired Sensing and Flow Control for Sustainable Transport, and City's Sir Richard Oliver BAE Systems Chair for Aeronautical Engineering.

Through their biomimetic study, Professor Bruecker's team has discovered that the fish-scale array produces a zig-zag motion of fluid in overlapping regions of the surface of the fish, which in turn causes periodic velocity modulation and a streaky flow that can eliminate Tollmien-Schlichting wave induced transition to reduce skin friction drag by more than 25 percent.

An examination of oil flow visualisation using computational fluid dynamics (CFD) on sea bass and common carp enabled the authors to come up with a working hypothesis:

"Computation Fluid Dynamics (CFD) was used to study the flow pattern over the surface and revealed a hitherto unknown effect of the scales as a mechanism to generate a regular pattern of parallel streamwise velocity streaks in the boundary layer. To prove their existence also on the real fish skin, oil flow visualisation was done on sea bass and common carp, which indeed confirmed their presence in a regular manner along their real body, with the same arrangement relative to the scale array as observed along the biomimetic surface. These results let the authors hypothesize about a possible mechanism for transition delay, inspired by various previous fundamental transition studies, where streaky structures generated by cylindrical roughness elements or vortex generator arrays have shown a delay of transition".

Using the specially equipped laminar water tunnel at the University of Stuttgart in Germany, Professor Bruecker and Professor Rist (University of Stuttgart) have tested the hypothesis of a transition (drag) delay by experimenting with a smooth flat plate and a flat plate covered with biomimetic fish scale arrays.

Their surprising research outcome runs counter to the common belief that roughness promotes by-pass transition. Instead, the scales largely increase the stability of the base flow similar to an array of vortex generators.

A technical realisation of such patterns on aerodynamic surfaces will pave the way towards the drastic reduction in fuel consumption and future zero-emission flight.

CATONSVILLE, MD, October 7, 2020 - New research has shed light on how various political campaign activities influence voters. It found that a candidate's mass media advertising is more likely to influence independent voters, while the campaign's "ground game," targeting voters through grassroots outreach, is more effective at reaching a candidate's base.

The research study, to be published in the October issue of the INFORMS journal Marketing Science, "The Air War versus the Ground Game: An Analysis of Multi-Channel Marketing in U.S. Presidential Elections," is authored by Lingling Zhang of the University of Maryland and Doug J. Chung of Harvard University.

"We decided to study the effects of multichannel marketing in the context of the U.S. presidential elections to determine which approaches are not only more powerful in political applications, but also to see what we can learn and apply across other applications of multichannel marketing," said Chung.

Through their work, the researchers analyzed the multichannel marketing strategies of U.S. presidential campaigns from 2004 through 2012 to identify harbingers for how successful elections are won and will be won in battleground states (states that are considered largely undecided) going forward.

"With more technologies to better target individual voters, the question of how different campaign activities work in different voter segments presented itself to us as increasingly important," said Zhang. "As a result, we saw an opportunity to compare the 'air war' and the 'ground game' of campaigns to gauge effectiveness."

The air war constitutes mass media advertising, consisting mostly of television advertising, whereas the ground game represents door-to-door canvassing, phone calls to households, direct mail to homes, and neighborhood signage.

The study's authors found that since the ground game emerged as more influential among partisan voters, or those who already know who they plan to vote for, the primary objective of the ground game is to encourage voter turnout. And while the air war was determined to have less impact on turnout, it does have greater influence in persuading voters to see a candidate more or less favorably.

"While field campaigning tends to specifically focus on turnout of those whose minds are made up, television advertising, which is less targeted but more informational in nature, tends to be better received by those who are undecided and could still change their minds," said Chung. However, advertising by outside political groups, which has become more prevalent in recent elections, tends to be more negative in nature and is better received by a candidate's base.

A new species of an ancient marine reptile evolved to strike terror into the hearts of the normally safe, fast-swimming fish has been identified by a team of University of Alberta researchers, shedding light on what it took to survive in highly competitive ecosystems.

Gavialimimus almaghribensis, a new type of mosasaur, was catalogued and named by an international research team led by master's student Catie Strong, who performed the research a year ago as part of an undergrad honours thesis guided by vertebrate paleontologist Michael Caldwell, professor in the Faculty of Science, along with collaborators from the University of Cincinnati and Flinders University.

More than a dozen types of mosasaur--which can reach 17 metres in length and resemble an overgrown komodo dragon--ruled over the marine environment in what is now Morocco at the tail end of the Late Cretaceous period between 72 and 66 million years ago.

What differentiates Strong's version, however, is that it features a long, narrow snout and interlocking teeth--similar to the crocodilian gharials, a relative of crocodiles and alligators.

Strong said this discovery adds a layer of clarity to a diverse picture seemingly overcrowded with mega-predators all competing for food, space and resources.

"Its long snout reflects that this mosasaur was likely adapted to a specific form of predation, or niche partitioning, within this larger ecosystem."

Strong explained there is evidence that each species of the giant marine lizard shows adaptations for different prey items or styles of predation.

"For some species, these adaptations can be very prominent, such as the extremely long snout and the interlocking teeth in Gavialimimus, which we hypothesized as helping it to catch rapidly moving prey," she said.

She added another distinctive species would be Globidens simplex--described last year by the Caldwell lab--which has stout, globular teeth adapted for crushing hard prey like shelled animals.

"Not all of the adaptations in these dozen or so species are this dramatic, and in some cases there may have been some overlap in prey items, but overall there is evidence that there's been diversification of these species into different niches," Strong noted.

Alternatively, the main contrasting hypothesis would be a scenario of more direct competition among species. Strong said given the anatomical differences among these mosasaurs, though, the idea of niche partitioning seems more consistent with the anatomy of these various species.

"This does help give another dimension to that diversity and shows how all of these animals living at the same time in the same place were able to branch off and take their own paths through evolution to be able to coexist like that," she said.

The remains of the G. almaghribensis included a metre-long skull and some isolated bones. There was nothing to explain the cause of death of the specimen, which was uncovered in a phosphate mine in Morocco that is rich in fossils.

"Morocco is an incredibly good place to find fossils, especially in these phosphate mines," Strong said. "Those phosphates themselves reflect sediments that would have been deposited in marine environments, so there are a lot of mosasaurs there."

Irvine, CA - Oct. 7, 2020 - N-acetylglucosamine, a simple sugar found in human breast milk and sold as an over-the-counter dietary supplement in the United States, promotes myelin repair in mouse models and correlates with myelination levels in multiple sclerosis patients according to a new University of California, Irvine-led study.

Published in the Journal of Biological Chemistry, the study also demonstrates that in mice, delivering N-acetylglucosamine orally to lactating mothers drove primary myelination in their nursing offspring. N-acetylglucosamine is a simple sugar that is metabolically attached to proteins at the cell surface to control cellular function.

"We found that N-acetylglucosamine activates myelin stem cells to promote primary myelination and myelin repair," said Michael Demetriou, MD, PhD, FRCP(C), professor of neurology, microbiology and molecular genetics at UCI School of Medicine and leader of the study. "Our data raises the intriguing possibility that N-acetylglucosamine may be a simple therapy to promote myelin repair in multiple sclerosis patients". Formal human studies will be required to test this theory.

The failure of robust re-myelination following inflammatory demyelination in multiple sclerosis leads to chronic disability and neurodegeneration. Myelin insulates the long, cable-like nerve cell branches called axons, and serves to increase the speed of electrical signal conduction between neurons. Myelination in the central nervous system also plays an important role in cognitive development during childhood.

"Interestingly, since N-acetylglucosamine is a major component of human breast milk but not baby formula, it may explain some of the cognitive function and myelination benefits realized by children fed breast milk as opposed to formula." said Michael Sy, MD, PhD, assistant professor of neurology at UCI School of Medicine, co-director of the regional MS program at the VA Long Beach Healthcare System, and first author of the study.

Dr. med. Alexander Brandt, MD, who led the clinical parts of the study together with Dr. med. Friedemann Paul, MD, added, "The association of reduced N-acetylglucosamine serum levels with white matter changes in the brain of patients with multiple sclerosis suggests that N-acetyglucosamine deficiency may contribute to disease severity."

The Gerontological Society of America's highly cited, peer-reviewed journals are continuing to publish scientific articles on COVID-19. The following were published between September 24 and October 7; all are free to access:

Intersectionality and inequalities in medical risk for severe COVID-19 in the Canadian Longitudinal Study on Aging: Research article in The Gerontologist by Shen (Lamson) Lin, MA

Older people's non-physical contacts and depression during the COVID-19 lockdown: Research article in The Gerontologist by Bruno Arpino, PhD, Marta Pasqualini, PhD, Valeria Bordone, PhD, and Aïda Solé-Auró, PhD

Problems of Data Availability and Quality for COVID-19 and Older People in Low- and Middle-Income Countries: Forum article in The Gerontologist by Peter Lloyd-Sherlock, PhD, Lucas Sempe, MSc, Martin McKee, DSc, and Aravinda Guntupalli, PhD