Culture

Long live the efficient, pure-blue OLED

image: Highly efficient, pure-blue organic light-emitting diodes (OLEDs) developed by researchers at Kyushu University in Japan are being tested to measure their lifetime. Based on hyperfluorescence, which uses a two-molecule process to emit light, the OLEDs emit pure-blue emission and exhibit significantly improved lifetimes compared to other highly efficient devices, all without using expensive metal atoms.

Image: 
Masaki Tanaka, Kyushu University

Using a new combination of emitter molecules, researchers in Japan have demonstrated the promise of a novel approach to finally overcome a major challenge facing displays using organic light-emitting diodes: a blue light source matching the excellent performance of the red and green ones.

By splitting energy conversion and emission processes between two molecules, the researchers achieved devices that produce pure-blue emission with high efficiency, maintain brightness for relatively long times, and lack any expensive metal atoms--a set of properties that has so far been difficult to obtain simultaneously.

Acclaimed for their vibrant colors and ability to form thin and even flexible devices, organic light-emitting diodes, or OLEDs for short, use carbon-containing molecules to convert electricity into light.

Unlike LCD technologies employing liquid crystals to selectively block emission from a filtered backlight covering many pixels, the separate red, green, and blue emitting pixels of an OLED display can be completely turned on and off individually, producing deeper blacks and reducing power consumption.

However, blue OLEDs in particular have been a bottleneck in terms of efficiency and stability.

"A growing number of options exist for red and green OLEDs with excellent performance, but devices emitting high-energy blue light are more of a challenge, with tradeoffs almost always occurring among efficiency, color purity, cost, and lifetime," says Chin-Yiu Chan, a researcher at Kyushu University's Center for Organic Photonics and Electronics Research (OPERA) and author on the study reporting the results in Nature Photonics.

While stable blue emitters based on a process known as fluorescence are often used in commercial displays, they suffer from a low maximum efficiency. So-called phosphorescent emitters can achieve an ideal quantum efficiency of 100%, but they generally exhibit shorter operational lifetimes and require an expensive metal such as iridium or platinum.

As an alternative, OPERA researchers have been developing molecules that emit light based on the process of thermally activated delayed fluorescence, commonly abbreviated as TADF, which can achieve excellent efficiency without the metal atom but often exhibits emission containing a wider range of colors.

"The range of colors a display can produce is directly related to the purity of the red, green, and blue pixels," explains Chihaya Adachi, director of OPERA. "If blue emission is not pure with a narrow spectrum, filters are needed to improve the color purity, but this wastes emitted energy."

Takuji Hatakeyama's group at Kwansei Gakuin University recently reported a promising path to overcome the purity issue based on a unique molecular design for a highly efficient, pure-blue TADF emitter, but the molecule, named ν-DABNA, quickly degrades under operation.

Collaborating with Hatakeyama, the OPERA researchers have now found that lifetime can be greatly improved while still obtaining narrow emission by combining ν-DABNA with an additional TADF molecule developed at OPERA as an intermediate, high-speed energy converter.

"Three-fourths of electrical charges combine to form energy states called triplets in OLEDs, and TADF molecules can convert these non-emitting triplets into light-emitting singlets," explains Masaki Tanaka, an OPERA researcher who worked closely with Chan on the study.

"However, ν-DABNA is somewhat slow at converting the high-energy triplets, which often play a role in degradation. To get rid of the dangerous triplets more quickly, we included an intermediary TADF molecule that can more rapidly convert triplets into singlets."

Though the intermediary molecule is fast at converting triplets to singlets, it has a wide emission spectrum producing a sky-blue emission. Nonetheless, the intermediary can transfer many of its singlets in a high-energy state to ν-DABNA for fast and pure blue emission.

"Compared to most emitters, the wavelengths that ν-DABNA can absorb are very close to the color it emits. This unique property makes it able to receive much of the energy from the wide-emission intermediary and still emit a pure blue," says Chan.

Using this two-molecule approach, which has been termed hyperfluorescence, the researchers achieved longer operational lifetimes at high brightness than previously reported for highly efficient OLEDs having a similar color purity.

"That this kind of approach can extend the lifetime of pure-blue emission from a molecule we previously developed is really exciting," says Hatakeyama.

Adopting a tandem structure that basically stacks two devices on top of each other to effectively double the emission for the same electrical current, lifetime was nearly doubled at high brightness, and the researchers estimated that devices could maintain 50% of their brightness for over 10,000 hours at more moderate intensities.

"Though this is still too short for practical applications, stricter control of fabrication conditions often leads to even longer lifetimes, so these initial results point to a very promising future for this approach to finally obtain an efficient and stable pure-blue OLED," says Adachi.

"In the near future, I hope that blue hyperfluorescence OLEDs can replace current blue OLEDs for ultra-high-definition displays," adds Chan.

Credit: 
Kyushu University

For moms, oxygen during childbirth often unnecessary

Babies who suffer oxygen deficiencies during birth are at risk of brain damage that can lead to developmental delays, cerebral palsy and even death. To prevent this, most women in labor undergo continuous monitoring of the baby's heart rate and receive supplemental oxygen if the heart rate is abnormal, with the thought that this common practice increases oxygen delivery to the baby. However, there is conflicting evidence about whether the long-recommended practice improves infant health.

Now, a comprehensive analysis - led by Washington University School of Medicine in St. Louis - looking at 16 previous trials of the practice has found no benefit in providing supplemental oxygen to mothers during labor and delivery. Infants born to women who received supplemental oxygen fared no better or no worse than those born to women who had similar labor experiences but breathed room air.

The findings are published Jan. 4 in JAMA Pediatrics.

Each year, 1.5 million women in the U.S. -- two out of three pregnant women -- receive supplemental oxygen at some point during childbirth, according to the researchers.

The decades-long practice is recommended by the American College of Obstetricians and Gynecologists to treat abnormal fetal heart rates, which may indicate the baby's oxygen levels are low and pose health risks.

"It is such a common practice because the thought is that by giving mom oxygen, we are increasing oxygen transfer to the baby," said the study's first author, Nandini Raghuraman, MD, an assistant professor of obstetrics and gynecology in the Division of Maternal-Fetal Medicine. "However, the results of this study suggest that oxygen is not helpful in these cases and that the practice could be safely discontinued for many women."

Raghuraman added that supplemental oxygen is given mostly as a preventive measure, a practice that began during the 1960s. "Fetal monitoring can indicate a possible abnormal issue such as oxygen deprivation," she said. "But about 80% of the time, women giving birth fall into an intermediate category, in which cases are not completely benign but also not high-risk. And in cases such as these, supplementing oxygen offers no additional benefits."

For the analysis, the researchers examined 16 studies published from 1982 through 2020 of randomized controlled trials in humans -- including one from School of Medicine researchers -- involving more than 2,052 women in childbirth. "Overall, the studies produced mixed results, with some indicating a benefit and others indicating no benefit," Raghuraman said. "That was the reason for doing a meta-analysis. By pooling the numbers of patients across the studies we could get a more definitive answer than looking at individual studies."

The researchers evaluated the pH levels of the babies' blood from samples taken shortly after birth. The pH measures the body's acidity and alkalinity in blood and other fluids, with neutral equaling pH value of 7. For infants, Raghuraman said anything less than 7.1 is considered abnormal and indicates oxygen deprivation.

The researchers also compared neonatal intensive care admission rates and Apgar scores - a well-established test to evaluate newborn health at one and five minutes after birth. Apgar scores check a baby's heart rate, breathing and other signs to determine if the baby needs additional medical care.

"Comparing the health of the babies whose mothers received oxygen and those whose mothers didn't, we found that the differences were essentially zero," Raghuraman said.

Forgoing oxygen supplementation would help reduce an unnecessary intervention and likely reduce health-care costs. "It's been shown that moms, despite having health insurance, often incur steep out-of-pocket costs related to childbirth," Raghuraman said. "Although oxygen is generally an inexpensive intervention compared with other labor and delivery services, minimizing any unnecessary procedure is important."

At Barnes-Jewish Hospital, where Raghuraman delivers babies, the findings have begun to influence clinical care. "We're being more judicious about giving supplemental oxygen to women during labor."

Past studies have indicated that supplementing oxygen may be beneficial to women delivering via cesarean section; however, Raghuraman said more research is needed. "We also want to look at whether exposing mom and baby to prolonged oxygen during labor may be harmful," she said. "Outside of labor and delivery, a lot of research shows that over-oxygenation is associated with oxidative stress that can cause the kind of cellular damage that has been implicated in conditions such as cerebral palsy and Alzheimer's disease. Our findings contradict a general myth that oxygen bars and other ways of increasing oxygen intake is healthy and helpful to a person's overall well-being."

Credit: 
Washington University School of Medicine

Subscriptions to satellite alerts linked to decreased deforestation in Africa

image: The research covered 22 tropical countries, outlined in orange, across South America, Africa and Asia. Forest cover in 2010 is indicated in green.

Image: 
Fanny Moffette / University of Wisconsin–Madison

MADISON, Wis. -- Deforestation dropped by 18 percent in two years in African countries where organizations subscribed to receive warnings from a new service using satellites to detect decreases in forest cover in the tropics.

The carbon emissions avoided by reducing deforestation were worth between $149 million and $696 million, based on the ability of lower emissions to reduce the detrimental economic consequences of climate change.

Those findings come from new research into the effect of GLAD, the Global Land Analysis and Discovery system, available on the free and interactive interface Global Forest Watch. Launched in 2016, GLAD provides frequent, high-resolution alerts when it detects a drop in forest cover. Governments and others interested in halting deforestation can subscribe to the alerts on Global Forest Watch and then intervene to limit forest loss.

The research was led by Fanny Moffette, a postdoctoral researcher in applied economics in the Nelson Institute for Environmental Studies and the Department of Agricultural and Applied Economics at the University of Wisconsin-Madison. Moffette collaborated with Jennifer Alix-Garcia at Oregon State University, Katherine Shea at the World Resources Institute and Amy Pickens at the University of Maryland.

The researchers published their findings Jan. 4 in Nature Climate Change. They studied deforestation in 22 tropical countries across South America, Africa and Asia from 2011 to 2018.

Moffette and her co-authors set out to understand whether these kinds of automated alerts could achieve their goal of reducing forest loss, which has global climate implications. Land-use changes like deforestation account for 6 percent to 17 percent of global carbon emissions. And avoiding deforestation is several times more effective at reducing carbon emissions than regrowing forests.

"The first question was to look at whether there was any impact from having access to this free alert system. Then we were looking at the effect of users subscribing to this data to receive alerts for a specific area," says Moffette.

Simply being covered by GLAD did not help a country combat deforestation. Only those African countries in which organizations had actually subscribed to receive alerts saw a decrease in deforestation. Intuitively, this finding makes sense, says Moffette. Having access to information is good. But what you need to change the course of deforestation are people committed to using that information and acting.

However, deforestation did not decrease in South American or Asian countries, even where organizations subscribed to receive warnings. There are multiple potential causes for this continental discrepancy.

"We think that we see an effect mainly in Africa due to two main reasons," says Moffette. "One is because GLAD added more to efforts in Africa than on other continents, in the sense that there was already some evidence of countries using monitoring systems in countries like Indonesia and Peru. And Colombia and Venezuela, which are a large part of our sample, had significant political unrest during this period."

The GLAD program is still young, and as more governments and organizations sign on to receive warnings, and decide how to intervene at sites of deforestation, the system's influence may grow.

Developed by a team at the University of Maryland that includes one of Moffette's collaborators, GLAD made several improvements over its predecessors. It has very high spatial resolution, roughly 900 square meters, which is orders of magnitude more precise than older tools. And it can provide alerts up to every eight days if the skies are cloud-free when satellites re-image a section of Earth. Users can define custom areas to monitor. They then receive weekly emails, available in six languages, that contain geographic coordinates of the alerts within the monitored areas.

Going forward, the team is looking to evaluate the effect of new features of the monitoring platform, such as data that can inform forest restoration, while supporting efforts of organizations that try to intervene to halt deforestation.

"Now that we know subscribers of alerts can have an effect on deforestation, there's potential ways in which our work can improve the training they receive and support their efforts," says Moffette.

Credit: 
University of Wisconsin-Madison

How to identify heat-stressed corals

image: The rice coral Montipora capitata in waters near the Hawai'i Institute of Marine Biology on Moku o Lo?e in Kāne'ohe Bay, Hawaii.

Image: 
D. Bhattacharya

Researchers have found a novel way to identify heat-stressed corals, which could help scientists pinpoint the coral species that need protection from warming ocean waters linked to climate change, according to a Rutgers-led study.

"This is similar to a blood test to assess human health," said senior author Debashish Bhattacharya, a Distinguished Professor in the Department of Biochemistry and Microbiology in the School of Environmental and Biological Sciences at Rutgers University-New Brunswick. "We can assess coral health by measuring the metabolites (chemicals created for metabolism) they produce and, ultimately, identify the best interventions to ensure reef health. Coral bleaching from warming waters is an ongoing worldwide ecological disaster. Therefore, we need to develop sensitive diagnostic indicators that can be used to monitor reef health before the visible onset of bleaching to allow time for preemptive conservation efforts."

Coral reefs provide habitat, nursery and spawning grounds for fish, food for about 500 million people along with their livelihoods, and coastline protection from storms and erosion. But global climate change threatens corals by warming ocean waters, resulting in coral bleaching and disease. Other threats to corals include sea-level rise, a more acidic ocean, unsustainable fishing, damage from vessels, invasive species, marine debris and tropical cyclones, according to the National Oceanic and Atmospheric Administration.

The study, published in the journal Science Advances, examined how Hawaiian stony corals respond to heat stress, with a goal of identifying chemical (metabolite) indicators of stress. Heat stress can lead to the loss of algae that live in symbiosis with corals, resulting in a white appearance (bleaching) and, potentially, the loss of reefs.

YouTube video: How to build a Coral Hospital

Scientists subjected the heat-resistant Montipora capitata and heat-sensitive Pocillopora acuta coral species to several weeks of warm seawater in tanks at the Hawai'i Institute of Marine Biology. Then they analyzed the metabolites produced and compared them with other corals not subjected to heat stress.

"Our work, for the first time, identified a variety of novel and known metabolites that may be used as diagnostic indicators for heat stress in wild coral before or in the early stages of bleaching," Bhattacharya said.

The scientists are validating their coral diagnosis results in a much larger study and the results look promising. The scientists are also developing a "coral hospital" featuring a new lab-on-a-chip device, which could check coral health in the field via metabolite and protein indicators.

Credit: 
Rutgers University

Frequent travel could make you 7% happier

VANCOUVER, Wash. --People dreaming of travel post-COVID-19 now have some scientific data to support their wanderlust.

A new study in the journal of Tourism Analysis shows frequent travelers are happier with their lives than people who don't travel at all.

Chun-Chu (Bamboo) Chen, an assistant professor in the School of Hospitality Business Management at Washington State University, conducted a survey to find out why some individuals travel more frequently than others and whether or not travel and tourism experiences have a prolonged effect on happiness and wellness.

The results of his analysis show individuals who pay more attention to tourism-related information and frequently discuss their travel plans with friends are more likely to go on regular vacations than those who aren't constantly thinking about their next trip.

Additionally, participants in the survey who reported regularly traveling at least 75 miles away from home also reported being about 7% happier when asked about their overall well-being than those who reported traveling very rarely or not at all.

"While things like work, family life and friends play a bigger role in overall reports of well-being, the accumulation of travel experiences does appear to have a small yet noticeable effect on self-reported life satisfaction," Chen said. "It really illustrates the importance of being able to get out of your routine and experience new things."

Previous studies have examined the stress relief, health and wellness benefits of tourism experiences, but they have tended to examine the effect of a single trip or vacation. Chen's research takes these previous studies one step further by looking at the sustained benefits of travel over the course of a year.

Participants in the study were asked about the importance of travel in their lives, how much time they spent looking into and planning future vacations, and how many trips they went on over a year. They were also asked about their perceived life satisfaction. Out of the 500 survey participants, a little over half reported going on more than four pleasure trips a year. Only 7% of respondents did not take any vacations.

As travel restrictions due to COVID-19 begin to relax in the future, the research could have important implication for both tourists and the tourism industry. Based on the results of the study, Chen said travel companies, resorts and even airlines could launch social media campaigns, such as creating hashtags about the scientific benefits of vacation, to spark people's interest in discussing their opinions about travel.

"This research shows the more people talk about and plan vacations the more likely they are to take them," he said. "If you are like me and chomping at the bit to get out of dodge and see someplace new, this research will hopefully be some additional good motivation to start planning your next vacation."

Credit: 
Washington State University

Results of comprehensive SARS-CoV-2 animal model study published in Nature Microbiology

San Antonio, Texas (January 4, 2020) - Scientists at Texas Biomedical Research Institute (Texas Biomed) and Southwest National Primate Research Center (SNPRC) published their findings regarding a comprehensive animal model study of SARS-CoV-2 in the peer-reviewed journal Nature Microbiology. These findings were originally posted online in BioRxiv in June of 2020. The study evaluated three nonhuman primate (NHP) species (Indian rhesus macaques, African baboons and new-world origin common marmosets) and young and old animals, to determine susceptibility to the SARS-CoV-2 virus and the development of COVID-19 disease. Over the course of the study, the macaque and baboon models showed significant promise as animal models for COVID-19 disease studies moving forward. Based on outcomes, the researchers recommended use of the macaque as a model to help develop vaccines, while the baboon showed greater disease development, making it a potential option for evaluating anti-viral therapeutics and co-morbidities, such as understanding the connection between COVID-19 and diabetes or COVID-19 and heart disease.

"Thanks to the support of our community, Texas Biomed was able to launch and complete the most comprehensive animal model study to date (June 2020) that has provides scientists greater understanding of the immune response to SARS-CoV-2 and definitively identifies two possible animal models to help move vaccines and therapeutics forward," said Larry Schlesinger, M.D., Texas Biomed President and CEO. "The speed and completeness to which this team of researchers operated to execute this study is nothing short of heroic. I am very pleased at the progress the Institute is making in our COVID-19 studies and believe this is the first of many discoveries to come."

COVID-19 is the defining pandemic of a generation. Texas Biomed launched this study in late March 2020 because animal models are a critical component of the biomedical pipeline necessary to fast track drug and vaccine development. The study was completed by May 2020.

"The benefit of Texas Biomed's unique research model lies in the expertise to support individual scientific study and contract research on one campus with the animal, biosafety and regulatory proficiency to help shepherd research from basic discovery through preclinical development and on to human clinical trials," explained Joanne Turner, PhD, Vice President for Research at Texas Biomed.

Animal models for infectious diseases, such as COVID-19, are allowing scientists worldwide to determine whether the candidate vaccines and antiviral therapeutics currently under development will be viable as human interventions. Additionally, animal models enable scientists to understand how the disease progresses in people with compromised immune systems to assist in the development of treatments for these individuals.

"Finding the appropriate animal models for COVID-19 allows for these critical discoveries to happen now, and they are an important step in combatting this disease," said Dr. Deepak Kaushal, PhD, Director of the Southwest National Primate Research Center and lead Principal Investigator on the macaque portion of the study. "Without well-documented animal data, the FDA is unlikely to license a vaccine or antiviral therapy for human use, even those currently undergoing human trials, because animal model data assure us that we have a complete picture of the disease and how humans may respond to potential therapies."

The team of 43 researchers reported clinical, viral, imaging, immunological and histopathological (tissue examination) findings during SARS-CoV-2 infection/COVID-19 disease in all three species of NHPs. The study ultimately found that nonhuman primates showed similar progression of SARS-CoV-2 infection to that of humans, with some becoming more ill than others, and signs of the virus in both the upper and lower respiratory tracts and signs of pneumonia.

"Our results tell us that these animal models will provide relevant, quantifiable information moving forward as we delve deeper into understanding the disease and targets for therapeutics and vaccines for human trials," Dr. Kaushal explained.

While previous animal studies showed the macaque to be a viable model for SARS-CoV-2, this was the first time that researchers performed a longitudinal study of three different NHPs (looking at disease progression factors over several days) and in both young and older macaques to determine if age is a factor in disease progression. Moreover, the researchers used the most comprehensive set of evaluations, ranging from bronchoalveolar lavages (lung fluid collection) and nasal swabs to determine virus presence to chest x-rays and CT scans to evaluate lung health after infection.

Results showed that the macaque and baboon models develop strong signs of acute viral infection leading to pneumonia, and the NHP immune system mounts a strong response and clears the infection. Specialized sets of myeloid cells (phagocytes) move from blood to the lungs and secrete high levels of Type I interferons, cytokines or proteins that send chemical messages required for controlling viruses in general and coronaviruses in particular. The appearance of these specialized phagocytes (cells that ingest foreign particles or dying cells in the body) corresponded with a decline in measurable amounts of virus and disease parameters. The longitudinal study of young and old animals showed little difference. However, the virus appears to persist and shed longer in the baboons and create greater pathology in the lungs. The marmoset model did not show any significant signs of disease progression.

This study was also the first report of SARS-CoV-2 infection specifically altering lymphoid cells (T cells) in the lung, which generated a strong and very specific immune response in the macaque, enabling the animals to clear the virus. This finding indicates the NHP model will be useful in understanding the immune response to SARS-CoV-2 and aid in the development of interventions that can create a similar response, as well as help evaluate the safety and effectiveness of vaccines, which require a specific immune response in order to be effective.

"While this study was not the first to indicate the macaque would serve as a good model for SARS-CoV-2, the study provides strong scientific evidence in support of this model, as well as the first evidence of the baboon model via comprehensive, clinically-relevant and well-documented research with controls," Dr. Kaushal said. "We strongly believe macaques and baboons will be very helpful in evaluating interventions that generate the strong immune response seen in these animal models."

The study was funded by philanthropic support from more than 300 donors after a call-to-action campaign was launched in late March. The campaign raised more than $3.5 million in one week, and additional donor support has brought the total raise for COVID-19 research at Texas Biomed to more than $5.7 million.

Concurrently, Texas Biomed investigators are submitting several grant applications to the National Institutes of Health and other federal agencies to further these study findings and develop novel vaccine candidates, diagnostics and therapeutics. Scientists have already begun collaborative immune system and co-morbidity studies, as well as small animal model development studies in rodents and guinea pigs. Additionally, the Institute is collaborating with several pharmaceutical and research and development partners to test vaccine and therapeutic candidates.

Credit: 
Texas Biomedical Research Institute

Drug discovery study identifies promising new compound to open constricted airways

image: Stephen Liggett, MD, of the University of South Florida Morsani College of Medicine (Tampa, FL), led the cross-disciplinary, preclinical study that identified a promising new compound for opening constricted airways.

Image: 
Photo courtesy of of USF Health

TAMPA, Fla (Jan 4, 2021) — Despite the progress made in managing asthma and chronic obstructive pulmonary disease (COPD), poorly controlled symptoms for both respiratory diseases can lead to severe shortness of breath, hospitalizations or even death.

“Only about 50 percent of asthmatics, and an even lower percentage of people with COPD, achieve adequate control of lung inflammation and airway constriction with currently available medications,” said Stephen Liggett, MD, vice dean for research at the University of South Florida Morsani College of Medicine and a USF Health professor of medicine, molecular pharmacology and physiology, and biomedical engineering. “So, we’re clearly missing something from our drug armamentarium to help all these patients.”

Dr. Liggett’s laboratory has discovered several subtypes of bitter taste receptors (TAS2Rs) — G protein-coupled receptors expressed on human smooth airway muscle cells deep inside the lungs. In asthma and COPD, tightening of smooth muscles surrounding bronchial tubes narrows the airway and reduces air flow, and Dr Liggett’s lab found that these taste receptors open the airway when activated. They are now looking for new drugs to treat asthma and other obstructive lung diseases by targeting smooth muscle TAS2Rs to open constricted airways.

A promising bronchodilator agonist rises to the top

In a preclinical study published Nov. 5 in ACS Pharmacology and Translational Science, Dr. Liggett and colleagues identified and characterized 18 new compounds (agonists) that activate bitter taste receptor subtype TAS2R5 to promote relaxation (dilation) of human airway smooth muscle cells. The cross-disciplinary team found 1,10 phenanthroline-5,6-dione (T5-8 for short) to be the most promising of several lead compounds (drug candidates). T5-8 was 1,000 times more potent than some of the other compounds tested, and it demonstrated marked effectiveness in human airway smooth muscle cells grown in the laboratory.

For this drug discovery project, Dr. Liggett’s laboratory collaborated with Jim Leahy, PhD, professor and chair of chemistry at the USF College of Arts and Sciences, and Steven An, PhD, professor of pharmacology at the Rutgers Robert Wood Johnson Medical School.

In an extensive screening conducted previously, another research group identified only one compound that would bind to and specifically activate the TASR5 bitter taste receptor – although apparently with limited effectiveness. Using this particular agonist (called T5-1 in the paper) as a starting point, the team relied on their collective disciplines to devise new activators, aiming for a much better drug profile for administration to humans.

“The two key questions we asked were: ‘Is it possible to find a more potent agonist that activates this receptor?’ and ‘Is it feasible to deliver by inhalation given the potencies that we find?’” said Dr. Liggett, the paper’s senior author. “T5-8 was the bronchodilator agonist that worked best. There were a few others that were very good as well, so we now have multiple potential new drugs to carry out the next steps.”

The researchers developed screening techniques to determine just how potent and effective the 18 compounds were. A biochemical test assessed how well these new agonists activated TAS2R5 in airway smooth muscle cells isolated from non-asthmatic human donor lungs. Then, the researchers validated the effect on airway smooth muscle relaxation using a technique known as magnetic twisting cytometry, pioneered by Dr An.

“Team science” solves a structural problem

“The biggest challenge we faced was not having a 3-D crystal structure of TAS2R5, so we had no idea exactly how agonist T5-1 fit into this mysterious bitter taste receptor,” Dr. Liggett said. “By merging our strength in receptors, pharmacology, physiology, and drug development, our team was able to make the breakthrough.”

T5-8 was superior to all the other bronchodilator agonists screened, exhibiting a maximum relaxation response (50%) substantially greater than that of albuterol (27%). Albuterol belongs to the only class of direct bronchodilators (beta-2 agonists) available to treat wheezing and shortness of breath caused by asthma and COPD. However, this drug or its derivatives, often prescribed as a rescue inhaler, does not work for all patients and overuse has been linked to increased hospitalizations, Dr. Liggett said. “Having two distinct classes of drugs that work in different ways to open the airways would be an important step to help patients optimally control their symptoms.”

The ACS Pharmacology paper highlights the importance of translational research in bridging the gap between laboratory discoveries and new therapies to improve human health, he added. “This study yielded a drug discovery that successfully meets most of the criteria needed to advance the compound toward its first trial as a potential first-in-class bronchodilator targeting airway receptor TAS2R5.”

Credit: 
University of South Florida (USF Health)

Scrambled supersolids

image: Supersolids are fluid and solid at the same time. Physicists from Innsbruck and Geneva have for the first time investigated what happens when such a state is brought out of balance. They discovered a soft form of a solid of high interest for science.

Image: 
IQOQI Innsbruck/Harald Ritsch

Last year, more than fifty years after initial theoretical proposals, researchers in Pisa, Stuttgart and Innsbruck independently succeeded for the first time in creating so-called supersolids using ultracold quantum gases of highly magnetic lanthanide atoms. This state of matter is, in a sense, solid and liquid at the same time. "Due to quantum effects, a very cold gas of atoms can spontaneously develop both a crystalline order of a solid crystal and particle flow like a superfluid quantum liquid, i.e. a fluid able to flow without any friction" explains Francesca Ferlaino from the Institute for Quantum Optics and Quantum Information of the Austrian Academy of Sciences and the Department of Experimental Physics at the University of Innsbruck. "Much simplified, a dipolar supersolid can be imagined as a chain of quantum droplets which communicate with each other via a superfluid background bath," says Thierry Giamarchi, theoretical physicist from the University of Geneva.

Surprisingly reversible

In Nature Physics, the researchers now report how such a supersolid state reacts if the superfluid bath between the droplets is drained by control of the external magnetic field. "We were able to show that without the bath the droplets quickly lose knowledge about each other and start to behave like small independent quantum systems - they dephase. The supersolid turns into a normal solid," says Maximilian Sohmen from Francecsa Ferlaino's team. "This 'solid', however, is still soft, it can wobble and support many collective excitations, called phonons", adds Philipp Ilzhöfer from the Innsbruck team. "This makes this state a very interesting but complex subject of study with strong connections to solid-state physics and other fields."

Maybe surprisingly, the Innsbruck physicists were also able to reverse this dephasing process: When they replenished the background bath, the droplets renewed their communication by particle tunneling and re-established supersolidity.

Credit: 
University of Innsbruck

Parents' finances differently affected by having a child diagnosed with cancer

image: Mattias Öhman, researcher at the Institute for Housing and Urban Research, Uppsala University.

Image: 
Mikael Wallerstedt

Mothers and fathers of children diagnosed with cancer are affected financially in different ways. While mothers' incomes fall in the short term and then rise, the adverse financial repercussions on fathers occur later. Researchers at Uppsala University have investigated the socioeconomic impact on parents of having a child diagnosed with cancer. The study is published in the International Journal of Cancer.

Previous research has shown that when a child falls ill with cancer, the parents are affected financially as well as psychologically. The available literature shows that mothers are more affected than fathers.

"Data from a research project I've worked on since 2005, studying the same parents of children with cancer over a long period, indicate that fathers are affected more, in the long term, than the evidence has previously borne out. In the new study, we've looked into the validity of these data," says Louise von Essen of Uppsala University's Department of Women's and Children's Health.

Using register data from Swedish public agencies, the researchers followed nearly 4,000 fathers and nearly 4,000 mothers of an equal number of children diagnosed with cancer in Sweden when 0-18 years old, five years before and ten years after diagnosis.

The findings show that in Sweden childhood cancer has negative short-term effects on fathers' and mothers' earnings. The long-term effects on earnings are negative for fathers, and positive for mothers. Negative short-term effects on employment were found for fathers and strong negative short-term effects for mothers. The long-term effects on employment are negative for both fathers and mothers.

As for why the fathers' long-term income trend was negative, the researchers will now examine this in detail. One theory they are pursuing is that fathers more often go on working while the children are ill, and therefore receive less support than the mothers from the healthcare services and personal networks alike. Moreover, this happens while the fathers are living under a heavy burden of stress. This might cause a relatively sharp fall in wellbeing among fathers, which may in turn result in adverse financial consequences.

"In our opinion, the findings of the study provide arguments for involving mothers and fathers equally in the care of gravely ill children, and for offering psychological support to all parents of children with cancer. That way, it would be possible to reduce the risk of any group not getting any support and, because of that, suffering from harmful repercussions like a lower income in the long run," says the first author of the study, Mattias Öhman of the Institute for Housing and Urban Research at Uppsala University.

Credit: 
Uppsala University

Innovative battery chemistry revolutionizes zinc-air battery

image: The basis of the innovative battery chemistry for the zinc-air batteryis a non-alkaline, aqueous electrolyte.

Image: 
WWU - MEET (Judith Kraft)

High-performance, eco-friendly, safe and at the same time cost-effective: the zinc-air battery is an attractive energy storage technology of the future. Until now, the conventional zinc-air battery has struggled with a high chemical instability, parasitic reactions which rooted in the usage of alkaline electrolytes lead to electrochemical irreversibility. Based on an innovative, non-alkaline, aqueous electrolyte, an international research team led by scientist Dr. Wei Sun of MEET Battery Research Center at the University of Muenster has developed a new battery chemistry for the zinc-air battery which overcomes the previous technical obstacles. The scientific team has published the detailed results of their research project, involving researchers from Fudan University in Shanghai, the University of Science and Technology in Wuhan, the University of Maryland and the US Army Research Laboratory, in the journal "Science".

Key parameters of the zinc-air battery optimised

"Our innovative, non-alkaline electrolyte brings a previously unknown reversible zinc peroxide (ZnO2)/O2 chemistry into the zinc-air battery", explains Dr. Wei Sun. Compared with the conventionally strong alkaline electrolytes, the newly developed non-alkaline aqueous electrolyte, which is based on the zinc trifluoromethanesulfonate salt, has several decisive advantages: The zinc anode is used more efficiently with a higher chemical stability and electrochemical reversibility. The full zinc-air batteries thus constructed can long-term operate stably for 320 cycles and 1,600 hours under ambient air atmosphere.

The mechanism of this ZnO2/O2 battery chemistry and the role of the hydrophobic trifluoromethanesulfonate anion were systematically revealed using well-designed electrochemical, analytical techniques and multiscale simulations. The identified increased energy density has now the potential to compete with the lithium-ion battery currently dominating the market. "The zinc-air battery provides a potential alternative battery technology with advantages such as environmental friendliness, high safety and low costs", emphasises Sun. "This technology still requires further, intensive research and optimisation before its practical application."

Credit: 
University of Münster

Research shows a few beneficial organisms could play key role in treating type 2 diabetes

PORTLAND, Ore. - Researchers at Oregon State University have found that a few organisms in the gut microbiome play a key role in type 2 diabetes, opening the door to possible probiotic treatments for a serious metabolic disease affecting roughly one in 10 Americans.

"Type 2 diabetes is in fact a global pandemic and the number of diagnoses is expected to keep rising over the next decade," said study co-leader Andrey Morgun, associate professor of pharmaceutical sciences in the OSU College of Pharmacy. "The so-called 'western diet' - high in saturated fats and refined sugars - is one of the primary factors. But gut bacteria have an important role to play in modulating the effects of diet."

Formerly known as adult-onset diabetes, type 2 diabetes is a chronic condition affecting the way the body metabolizes glucose, a sugar that's a key source of energy. For some patients, that means their body resists the effects of insulin - the hormone produced by the pancreas that opens the door for sugar to enter cells. Other patients don't produce enough insulin to maintain normal glucose levels.

In either case, sugar builds up in the bloodstream and if left untreated the effect is impairment to many major organs, sometimes to disabling or life-threatening degrees. A key risk factor for type 2 diabetes is being overweight, often a result of a western diet in combination with low physical activity.

The human gut microbiome features more than 10 trillion microbial cells from about 1,000 different bacterial species. Dysbiosis, or imbalance, in the microbiome is commonly associated with detrimental effects on a person's health.

"Some studies suggest dysbiosis is caused by complex changes resulting from interactions of hundreds of different microbes," said Natalia Shulzhenko, an associate professor of biomedical sciences in OSU's Carlson College of Veterinary Medicine and the study's other co-leader. "However, our study and other studies suggest that individual members of the microbial community, altered by diet, might have a significant impact on the host."

Shulzhenko and Morgun used a new, data-driven, systems-biology approach called transkingdom network analysis to study host-microbe interactions under a western diet. That allowed them to investigate whether individual members of the microbiota played a part in metabolic changes the diet induces in a host.

"The analysis pointed to specific microbes that potentially would affect the way a person metabolizes glucose and lipids," Morgun said. "Even more importantly, it allowed us to make inferences about whether those effects are harmful or beneficial to the host. And we found links between those microbes and obesity."

The scientists identified four operational taxonomic units, or OTUs, that seemed to affect glucose metabolism; OTUs are a means of categorizing bacteria based on gene sequence similarity.

The identified OTUs corresponded to four bacterial species: Lactobacillus johnsonii, Lactobacillus gasseri, Romboutsia ilealis and Ruminococcus gnavus.

"The first two microbes are considered potential 'improvers' to glucose metabolism, the other two potential 'worseners,'" Shulzhenko said. "The overall indication is that individual types of microbes and/or their interactions, and not community-level dysbiosis, are key players in type 2 diabetes."

The researchers fed mice the equivalent of a western diet and then supplemented the rodents' intake with the improver and worsener microbes. The Lactobacilli boosted mitochondrial health in the liver, meaning improvements in how the host metabolizes glucose and lipids, and the mice receiving those Lactobacilli also had a lower fat mass index than those fed only a western diet.

Checking the mouse results against data from an earlier human study, the scientists found correlations between human body mass index and abundance of the four bacteria - more of the improvers meant a better body mass index, more of the worseners was connected to a less healthy BMI.

"We found R. ilealis to be present in more than 80% of obese patients, suggesting the microbe could be a prevalent pathobiont in overweight people," Shulzhenko said.

A pathobiont is an organism that normally has a symbiotic relationship with its host but can become disease-causing under certain circumstances.

"Altogether, our observations support what we saw in the western diet-fed mice," she said. "And in looking at all of the metabolites, we found a few that explain a big part of probiotic effects caused by Lactobacilli treatments."

Lactobacillus is a microbial genus that contains hundreds of different bacterial strains. Its representatives are common among probiotics and frequently found in many types of fermented foods and Lactobacillus-fortified dairy products, such as yogurt.

"Our study reveals potential probiotic strains for treatment of type 2 diabetes and obesity as well as insights into the mechanisms of their action," Morgun said. "That means an opportunity to develop targeted therapies rather than attempting to restore 'healthy' microbiota in general."

Credit: 
Oregon State University

In kefir, microbial teamwork makes the dream work

To make kefir, it takes a team. A team of microbes.

That's the message of new research from EMBL and Cambridge University's Patil group and collaborators, published in Nature Microbiology today. Members of the group study kefir, one of the world's oldest fermented food products and increasingly considered to be a 'superfood' with many purported health benefits, including improved digestion and lower blood pressure and blood glucose levels. After studying 15 kefir samples, the researchers discovered to their surprise that the dominant species of Lactobacillus bacteria found in kefir grains cannot survive on their own in milk - the other key ingredient in kefir. However, when the species work together, feeding on each other's metabolites in the kefir culture, they each provide something another needs.

"Cooperation allows them to do something they couldn't do alone," says Kiran Patil, group leader and corresponding author of the paper. "It is particularly fascinating how L. kefiranofaciens, which dominates the kefir community, uses kefir grains to bind together all other microbes that it needs to survive - much like the ruling ring of the Lord of the Rings. One grain to bind them all."

A model for microbial interactions

Consumption of kefir originally became popular in Eastern Europe, Israel, and areas in and around Russia. It is composed of 'grains' that look like small pieces of cauliflower and have fermented in milk to produce a probiotic drink composed of bacteria and yeasts.

"People were storing milk in sheepskins and noticed these grains that emerged kept their milk from spoiling, so they could store it longer," says Sonja Blasche, a postdoc in the Patil group and joint first author of the paper. "Because milk spoils fairly easily, finding a way to store it longer was of huge value."

To make kefir, you need kefir grains. These can't be artificially made, but must come from another batch of kefir. The grains are added to milk to ferment and grow. Approximately 24 to 48 hours later (or, in the case of this research, 90 hours later), the kefir grains have consumed the nutrients available to them. The grains grow in size and number in this time and the kefir process is complete. The grains are removed and added to fresh milk to begin the process anew.

For scientists, however, kefir provides more than just a healthy beverage: it's an easy-to-culture model microbial community for studying metabolic interactions. And while kefir is quite similar to yogurt in many ways - both are fermented or cultured dairy products full of 'probiotics' - kefir's microbial community is far larger than yogurt's, including not just bacterial cultures but also yeast.

Learning from kefir

While scientists know that microorganisms often live in communities and depend on their fellow community members for survival, mechanistic knowledge of this phenomenon has been quite limited. Laboratory models historically have been limited to two or three microbial species, so Kefir offered - as Kiran describes - a 'Goldilocks zone' of complexity that is not too small (around 40 species), yet not too unwieldy to study in detail.

Sonja started this research by gathering kefir samples from several places. While most samples were obtained in Germany, they're likely to have originated elsewhere, since kefir grains have been passed down over centuries.

"Our first step was to look at how the samples grow. Kefir microbial communities have many member species with individual growth patterns that adapt to their current environment. This means fast- and slow-growing species and some that alter their speed according to nutrient availability," Sonja says. "This is not unique to the kefir community. However, the kefir community had a lot of lead time for co-evolution to bring it to perfection, as they have stuck together for a long time already."

Cooperation is the key

Finding out the extent and the nature of the cooperation between kefir microbes was far from straightforward. To do this, the researchers combined a variety of state-of-the-art methods such as metabolomics (studying metabolites' chemical processes), transcriptomics (studying the genome-produced RNA transcripts), and mathematical modelling. This revealed not only key molecular interaction agents like amino acids, but also the contrasting species dynamics between the grains and the milk part of kefir.

"The kefir grain acts as a base camp for the kefir community, from which community members colonise the milk in a complex yet organised and cooperative manner," Kiran says. "We see this phenomenon in kefir, and then we see it's not limited to kefir. If you look at the whole world of microbiomes, cooperation is also a key to their structure and function."

In fact, in another paper from Kiran's group in collaboration with EMBL's Bork group, out today in Nature Ecology and Evolution, scientists combined data from thousands of microbial communities across the globe - from soil to the human gut - to understand similar cooperative relationships. In this second paper, the researchers used advanced metabolic modelling to show that the co-occurring groups of bacteria, groups that are frequently found together in different habitats, are either highly competitive or highly cooperative. This stark polarisation hasn't been observed before, and sheds light on evolutionary processes that shape microbial ecosystems. While both competitive and cooperative communities are prevalent, the cooperators seem to be more successful in terms of higher abundance and occupying diverse habitats. Stronger together.

Credit: 
European Molecular Biology Laboratory

Fires, flooding before settlement may have formed the Amazon's rare patches of fertility

EUGENE, Ore. -- Jan. 4, 2021 -- Phosphorous, calcium and charcoal in spotty patches of fertile soil in the Amazon rainforest suggest that natural processes such as fires and river flooding, not the ingenuity of indigenous populations, created rare sites suitable for agriculture, according to new research.

The presence of pre-Columbian artifacts and signs of plant domestication uncovered in the region's fertile soil, commonly called Amazonian dark earth, had been thought to mean that agricultural practices, including controlled burning, by indigenous people had boosted soil nutrients.

However, radiocarbon dating of soil at an extensively studied 210-hectare basin near the confluence of the Solimoes and Negro rivers in northwest Brazil tell a different story, said Lucas Silva, a professor of environmental studies at the University of Oregon who led the project.

In a paper that published Jan. 4 in Nature Communications, a 14-member team report that phosphorous and calcium levels at the site, which is home to the Brazilian Agricultural Research Corp., are orders of magnitude higher than in surrounding soil.

Those levels, Silva said, correlate spatially with 16 trace elements that indicate that fertility did not form in place. Combined with other elements in the soil and isotopic ratios of neodymium and strontium, the researchers concluded that pre-settlement river flooding likely delivered nutrients and charcoal from upstream.

"We analyzed carbon and nutrient pools in light of the local anthropological context to estimate the chronology of management and the population density needed to attain the observed gain in Amazonian dark earth fertility compared to the surrounding landscape," Silva said.

Much of the Amazon contains highly weathered oxisols and ultisols, tropical soil types with high acidity and low nutrient levels. Archaeological artifacts have been found in charcoal-rich soil that began forming about 7,600 years ago, about 1,000 years before indigenous people transitioned from nomadic to sedentary populations in patches of land in the notoriously nutrient-poor Amazon environment, the researchers noted.

"Our results show that large sedentary populations would have had to manage soils thousands of years prior to the emergence of agriculture in the region or, more likely, that indigenous peoples used their knowledge to identify and preferentially settle areas of exceptionally high fertility before the onset of soil management in central Amazonia," he said.

Researchers have long theorized that Amazonian dark earth had been formed by controlled burning of forest biomass. That view, Silva said, fueled an entire industry of charcoal production from biosolids, such as biochar, in which such soils are considered a model for sustainable agriculture.

Charcoal and nutrient accumulation, the researchers argue, match that found in sedimentary deposits that can be traced to open vegetation fires upstream from rivers that flooded.

Records of soil content and past monsoon intensity, the researchers said, indicate a climate-driven shift in river dynamics after a long dry period between 8,000 and 4,000 years ago. That shift to flooding, they noted, would have reduced fire disturbance, increased regional tree coverage and "could have caused divergent patterns of carbon and nutrient accumulation in flooded versus non-flooded areas," consistent with the minerals in the dark earth at the research site.

Many areas of central Amazonia today are associated with sediment deposits that reflect flood regimes that were either deactivated during the Holocene or are presently in the process of deactivation, when sedimentary deposits become suitable habitats for grasslands within the rainforest, the researchers wrote.

"Our findings underscore the need for a broader view of landscape evolution as a path towards understanding the formation of Amazonian dark earths and redirecting applications for sustainable land use and conservation," said Silva, who has visited and gathered samples from the site since 2009 when he was a doctoral student.

"If corroborated elsewhere," he said, "our hypothesis would transform our understanding of human influence in Amazonia, opening new frontiers for the sustainable use of tropical landscapes going forward."

Credit: 
University of Oregon

Public mobility, social media attention in response to COVID-19 in Sweden, Denmark

What The Study Did: Denmark was one of the first countries to enforce lockdown to reduce the spread of COVID-19 and subsequent gradual reopening, whereas Sweden has had few restrictions, largely limited to public recommendations. Researchers assessed public mobility and social media attention associated with COVID-19 spread and societal interventions from February to June in Denmark and Sweden.

Authors: Isabell Brikell, Ph.D., of the Karolinska Institutet in  Stockholm, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.33478)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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JAMA Network

Risk of substance use disorder among patients with autism

What The Study Did: Researchers used health insurance data from Taiwan to investigate the risk of substance use disorder among patients with autism spectrum disorder and its associations with risk of death.

Authors: Chih-Sung Liang, M.D., of the National Defense Medical Center, and Mu-Hong Chen, M.D., Ph.D., of the Taipei Veterans General Hospital in Taipei, Taiwan, are the corresponding authors.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamapediatrics.2020.5371)

Editor's Note: The article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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JAMA Network