Culture

Sex, age, and severity of disease may be useful in identifying COVID-19 survivors who are likely to have high levels of antibodies that can protect against the disease, according to a new study co-led by researchers at Johns Hopkins Bloomberg School of Public Health.

The findings suggest that older males who have recovered from COVID-19 after having been hospitalized are strong candidates for donating plasma for treating COVID-19 patients. Doctors have been using infusions of plasma--the part of blood that contains antibodies--from recovered COVID-19 patients to treat COVID-19 patients and also as a possible prophylaxis to prevent COVID-19.

Doctors have used convalescent plasma to treat patients or immunize persons at high risk of virus exposure during outbreaks of measles, mumps, polio, Ebola, and even the 1918 pandemic flu.

Clinical trials of convalescent plasma treatment against COVID-19 are ongoing, and doctors until now haven't had guidance for selecting COVID-19 survivors who are likeliest to have strong antibody responses.

"We propose that sex, age, and severity of disease should be used to guide the selection of donors for convalescent plasma transfer studies because we found that these were significant patient characteristics that not only predicted the amount of antibody but the quality of that antibody," says study lead author Sabra Klein, PhD, professor in the Bloomberg School's Department of Molecular Microbiology and Immunology.

The study, published October 19 in the Journal of Clinical Investigation, was a collaboration with several other research groups including that of Arturo Casadevall, MD, PhD, Bloomberg Distinguished Professor and chair of the Department of Molecular Microbiology and Immunology, and co-corresponding author Aaron Tobian, MD, PhD, professor in the Department of Pathology and director of the Transfusion Medicine Division at the Johns Hopkins School of Medicine.

For their study, the researchers tested the blood of 126 COVID-19 survivors and found high variability in their antibody levels and their antibodies' ability to neutralize the COVID-19-causing coronavirus, SARS-CoV-2. Three factors were associated with stronger antibody responses: having been sick enough with COVID-19 to be hospitalized, being older, and being male.

Initial studies of recovered COVID-19 patients have revealed a significant variability in their antibody responses to the virus--some survivors having very weak responses that would almost certainly be ineffective in helping new patients. The researchers in the new study looked for factors that might help explain some of that variability and guide clinicians to the patients most likely to have high levels of SARS-CoV-2 neutralizing antibodies.

The researchers examined samples of plasma from the 126 recovered patients using several tests. These included tests of the plasma's ability in cell cultures to neutralize cell-to-cell infection with SARS-CoV-2, as well as commercial tests for levels of antibodies to the coronavirus's spike protein--the protein that studs the surface of coronavirus particles and allows the virus to attach to and infiltrate human cells.

Consistent with several prior studies, the researchers found considerable variability among the subjects in their spike-protein antibody levels and plasma coronavirus-neutralization potency. But on average, the plasma of survivors who had been hospitalized with COVID-19 had markedly more anti-spike protein antibodies and neutralized the virus more effectively--suggesting that disease severity prompts a stronger immune response.

"We know that the magnitude of antibody responses correlates with disease severity in other infectious diseases, such as active tuberculosis," Klein says.

Older age and male sex, which prior studies in both China and Europe have shown are associated with more severe COVID-19, were also associated with stronger antibody responses, though these links were weaker than for hospitalization status.

As part of their study, the researchers also tested study participants with commercial test kits and found that recovered COVID-19 patients who have strong neutralizing antibody responses also are very likely to have high levels of coronavirus anti-spike antibodies. This suggests that this type of test kit, which is relatively inexpensive, might be a good tool for identifying suitable plasma donors for clinical trials and treatments.

COLLEGE PARK, Md. - Anxiety, the most common family of mental illnesses in the U.S., has been pushed to epic new heights by the COVID-19 pandemic, with the Centers for Disease Control and Prevention estimating that nearly 1 in 3 U.S. adults and a staggering 41% of people ages 18-29 experienced clinically significant anxiety symptoms in late August. Now, the findings of a recent UMD-led study indicate that some long-accepted thinking about the basic neuroscience of anxiety is wrong.

The report by an international team of researchers led by Alexander Shackman, an associate professor of psychology at UMD, and Juyoen Hur, an assistant professor of psychology at Yonsei University in Seoul, South Korea, provides new evidence that fear and anxiety reflect overlapping brain circuits. The findings run counter to popular scientific accounts, highlighting the need for a major theoretical reckoning. The study was published last week in the Journal of Neuroscience.

"The conceptual distinction between 'fear' and 'anxiety' dates back to the time of Freud, if not the Greek philosophers of antiquity," said Shackman, a core faculty member of UMD's Neuroscience and Cognitive Science Program, and 2018 recipient of a seed grant award from UMD's Brain and Behavior Initiative, "In recent years, brain imagers and clinicians have extended this distinction, arguing that fear and anxiety are orchestrated by distinct neural networks.

However, Shackman says their new study adds to a rapidly growing body of new evidence suggesting that this old mode is wrong. "If anything, fear and anxiety seem to be constructed in the brain using a massively overlapping set of neural building blocks," he said.

Prevailing scientific theory holds that fear and anxiety are distinct, with different triggers and strictly segregated brain circuits. Fear--a fleeting reaction to certain danger--is thought to be controlled by the amygdala, a small almond-shaped region buried beneath the wrinkled convolutions of the cerebral cortex. By contrast, anxiety--a persistent state of heightened apprehension and arousal elicited when threat is uncertain--is thought to be orchestrated by the neighboring bed nucleus of the stria terminalis (BNST). But new evidence from Shackman and his colleagues suggests that both of these brain regions are equally sensitive to certain and uncertain kinds of threats.

Leveraging cutting-edge neuroimaging techniques available at the Maryland Neuroimaging Center, their research team used fMRI to quantify neural activity while participants anticipated receiving a painful shock paired with an unpleasant image and sound--a new task that the researchers dubbed the "Maryland Threat Countdown".

The timing of this "threat" was signaled either by a conventional countdown timer--i.e. "3, 2, 1..."--or by a random string of numbers--e.g. "16, 21, 8." In both conditions, threat anticipation recruited a remarkably similar network of brain regions, including the amygdala and the BNST. Across a range of head-to-head comparisons, the two showed statistically indistinguishable responses.

The team examined the neural circuits engaged while waiting for certain and uncertain threat (i.e. "fear" and "anxiety"). Results demonstrated that both kinds of threat anticipation recruited a common network of core brain regions, including the amygdala and BNST.

These observations raise important questions about the Research Domain Criteria (RDoC) framework that currently guides the U.S. National Institute of Mental Health's quest to discover the brain circuitry underlying anxiety disorders, depression, and other common mental illnesses. "As it is currently written, RDoC embodies the idea that certain and uncertain threat are processed by circuits centered on the amygdala and BNST, respectively. It's very black-and-white thinking," Shackman noted, emphasizing that RDoC's "strict-segregation" model is based on data collected at the turn of the century.

"It's time to update the RDoC so that it reflects the actual state of the science. It's not just our study; in fact, a whole slew of mechanistic studies in rodents and monkeys, and new meta-analyses of the published human imaging literature are all coalescing around the same fundamental scientific lesson: certain and uncertain threat are processed by a shared network of brain regions, a common core," he said.

As the crown jewel of NIMH's strategic plan for psychiatric research in the U.S., the RDoC framework influences a wide range of biomedical stakeholders, from researchers and drug companies to private philanthropic foundations and foreign funding agencies. Shackman noted that the RDoC has an outsized impact on how fear and anxiety research is designed, interpreted, peer reviewed, and funded here in the U.S. and abroad.

"Anxiety disorders impose a substantial and growing burden on global public health and the economy," Shackman said, "While we have made tremendous scientific progress, existing treatments are far from curative for many patients. Our hope is that research like this study can help set the stage for better models of emotion and, ultimately, hasten the development of more effective intervention strategies for the many millions of children and adults around the world who struggle with debilitating anxiety and depression."

PITTSBURGH, Oct. 19, 2020 - Older people who report greater levels of social engagement have more robust gray matter in regions of the brain relevant in dementia, according to new research led by scientists at the University of Pittsburgh Graduate School of Public Health. It is the first to use a particularly sensitive type of brain imaging to conduct such an evaluation.

The findings, reported today in the Journal of Gerontology: Psychological Sciences, suggest that "prescribing" socialization could benefit older adults in warding off dementia, much the way prescribing physical activity can help to prevent diabetes or heart disease.

"Our data were collected before the COVID-19 pandemic, but I believe our findings are particularly important right now, since a one-size-fits-all social isolation of all older adults may place them at risk for conditions such as dementia," said lead author Cynthia Felix, M.D., M.P.H., a geriatrician and a post-doctoral associate in Pitt Public Health's Department of Epidemiology. "Older adults should know it is important for their brain health that they still seek out social engagement in safe and balanced ways during the pandemic."

Felix and her colleagues used information about social engagement from 293 community-dwelling participants from the Health, Aging and Body Composition (Health ABC) study. These participants, who averaged 83 years old, also received a sensitive brain scan called Diffusion Tensor Imaging MRI that measured the cellular integrity of brain cells used for social engagement.

These participants provided detailed information about their social engagement and were scored using a tool Felix developed. High scores were awarded to people who did things like play board games; go to movies; travel long distance; attend classes, lectures or adult education events; participate in church or other community activities; get together with children, friends, relatives or neighbors at least once a week; volunteer or work; be married and live with others.

Felix and colleagues found that greater social engagement is related to better microstructural integrity of brain gray matter in these older adults. Maintaining brain health is of critical importance. Once brain cells die, dementia typically follows.

Social engagement with at least one other relative or friend activates specific brain regions needed to recognize familiar faces and emotions, make decisions and feel rewarded. The good news is that even moderate "doses" seem to be beneficial.

"We need to do more research on the details, but that's the beauty of this--social engagement costs hardly anything, and we do not have to worry about side-effects," Felix said. "There is no cure for dementia, which has tremendous costs in terms of treatment and caregiving. Preventing dementia, therefore, has to be the focus. It's the 'use it or lose it' philosophy when it comes to the brain."

Felix notes that cause-and-effect still need to be disentangled: Does greater social engagement keep these brain regions healthy? Or is it that having a healthy brain results in better social engagement?

Similar to how large public health studies assess the best programs to encourage physical activity to prevent chronic disease in older people, Felix believes her team's findings, coupled with previous research, provides justification for randomized control trials to assess the impact of specific types and amounts of social activities on brain health.

Enriched by her prior public health training at Johns Hopkins University, Felix recognizes the critical role of public health in applying this finding on a large scale.

"It would be good if we develop programs across the U.S. through which structured social activities can be prescribed for community-dwelling older adults, aimed at reducing rates of dementia and the resulting health care costs," Felix said. "Existing platforms providing group physical activities can be a good starting point."

CHAMPAIGN, Ill. -- Researchers studied the effects of a 12-week exercise regimen on 148 active-duty Air Force airmen, half of whom also received a twice-daily nutrient beverage that included protein; the omega-3 fatty acid, DHA; lutein; phospholipids; vitamin D; B vitamins and other micronutrients; along with a muscle-promoting compound known as HMB. Both groups improved in physical and cognitive function, with added gains among those who regularly consumed the nutritional beverage, the team reports.

The findings appear in the journal Scientific Reports.

Participants were randomly assigned to the two groups. The exercise regimen combined strength training and high-intensity interval aerobic fitness challenges. One group received the nutritional beverage and the other consumed a placebo beverage that lacked the added nutrients. Neither the researchers nor the participants knew who received the nutrient-enriched beverage or placebo.

"The exercise intervention alone improved strength and endurance, mobility and stability, and participants also saw increases in several measures of cognitive function. They had better episodic memory and processed information more efficiently at the end of the 12 weeks. And they did better on tests that required them to solve problems they had never encountered before, an aptitude called fluid intelligence," said Aron Barbey, a professor of psychology at the University of Illinois at Urbana-Champaign who led the study with postdoctoral researcher Christopher Zwilling.

"Those who also consumed the nutritional supplement saw all of these improvements and more. For example, they were better able to retain new information in their working memory and had quicker responses on tests of fluid intelligence than those taking the placebo," Barbey said.

Physical power increased in both groups as a result of the physical training, Zwilling said.

"Power is a measure of physical fitness that is based on several factors, such as how fast a participant can pull a heavy sled over a set distance, how far they can toss a weighted ball, and how many pushups, pullups or situps they can perform in a set time period," he said.

The physical training reduced participants' body fat percentage and increased their oxygen-uptake efficiency, or VO2 max. The airmen also performed better than they had initially on several measures of cognitive function. The most notable of these was an increase in the accuracy of their responses to problems designed to measure fluid intelligence.

"But we also wanted to know whether taking the supplement conferred an advantage above and beyond the effect of exercise," Zwilling said. "We saw that it did, for example in relationship to resting heart rate, which went down more in those who took the supplement than in those who didn't."

Participants who consumed the nutritional beverage also saw greater improvements in their ability to retain and process information. And their reaction time on tests of fluid intelligence improved more than their peers who took the placebo, the researchers found.

"Our work motivates the design of novel multimodal interventions that incorporate both aerobic fitness training and nutritional supplementation, and illustrates that their benefits extend beyond improvements in physical fitness to enhance multiple measures of cognitive function," Barbey said.

The U. of I. team conducted the intervention with study co-author Adam Strang, a scientist in the Applied Neuroscience Branch of Wright-Patterson Air Force Base near Dayton, Ohio, along with his colleagues in the Air Force Research Laboratory. The U. of I. team also worked with research fellow and study co-author Tapas Das and his colleagues at Abbott Nutrition, who led the design of the nutritional beverage, which is a mixture of nutrients targeting both muscle and brain. The specially designed beverage provided ingredients that previous studies have shown are associated with improved physical cognitive function.

Transportation is the top source of greenhouse gas emissions in the United States, accounting for almost 30 percent of total emissions. In the national and global effort to reduce emissions and mitigate climate change, electric vehicles (EVs) provide an attractive option. But despite dropping prices and rising popularity, EVs continue to make up a small percentage of the automotive industry's market share.

Are Americans resistant to purchasing these vehicles? And what are some of the biggest barriers--or perceived barriers--to widespread adoption? A new report out from researchers at Stanford University, Resources for the Future, and ReconMR has some answers.

Interviews with 502 American adults from May 28 to August 10, 2020 reveal American perceptions of EVs and illustrate whether those perceptions may lead to purchasing reluctance. The report also identifies sources of hesitation among three subgroups: sex, education, and prior exposure to EVs.

Topline Findings

57% of future car buyers are willing to consider buying an EV.

The most important driver of openness to purchasing an EV is belief that global warming will be a serious problem for the US in the future

The perception that batteries may catch on fire, that maintenance costs are higher, and that EVs have weaker acceleration than gas-powered cars are sources of hesitation among potential buyers.

Perceived difficulty of replacing batteries and lack of mechanics as compared to gas-powered vehicles are also predictors of purchasing reluctance.

65% of respondents have not driven nor know anyone who has driven an EV.

"Purchasing a vehicle is a big decision that consumers don't make lightly, and making a change from familiar gas-powered vehicles to electric vehicles involves venturing into the unknown to some degree. The decision to do so is likely shaped by perceptions of the features of EVs, so understanding those perceptions is a useful way to identify sources of hesitation inhibiting the adoption of this comparatively new technology," report co-author Jon Krosnick said. "Highlighting ways in which public perceptions don't line up with reality can pave pathways for educating people and alleviating concerns, which could lead to increased interest in EVs."

Any Red Sea diver will have encountered colorful triggerfish along coral reefs, and some divers will have experienced the painful bite of their huge teeth if they get too close to their nesting grounds. Now, Ph.D. student Matthew Tietbohl and colleagues at KAUST report a peculiar feeding strategy by a titan triggerfish that highlights their innate ability to learn and adapt.

Tietbohl and his colleagues were on Mar Mar island in the south central Red Sea looking for signs of turtle nesting when they saw a titan triggerfish come up on to the shoreline and attack, and eventually grab, a Red Sea ghost crab. Most interesting was that the triggerfish partially beached itself in shallow water for the first attack, a hunting behavior that has not been previously reported in any fish belonging to the order Tetraodontiformes, which comprises 350 coral reef species, including triggerfish. Several subsequent attacks ensued in very shallow water, without beaching, with the fish slowly approaching the crab and then rushing at it horizontally. The fish finally grabbed the crab in several centimeters of water and dragged it into deeper water, where it was eaten.

"Triggerfish seem to be particularly adept at taking advantage of a wide variety of prey," says Tietbohl. "They will jet water from their mouths to uncover invertebrate food buried in the sand, and flip rocks and break coral to get at prey. Given this diverse range of feeding behaviors, it is not too surprising that they have found a way to take advantage of semiterrestrial prey too."

Tietbohl believes that their discovery highlights the importance of observational studies as a means for investigating marine life. He and his colleagues suggest that triggerfish could serve as model systems for studying learning and cognition in coral reef fish.

All modern life uses energy to reproduce itself. During this process, organisms build and break down larger molecules such as fats and sugars using a remarkably common set of reactive intermediate energy carrier molecules. These intermediate energy carriers (for example ATP) are often not building blocks in and of themselves, but they allow the energy coupling between separate reactions needed to push forward cellular reproduction. One class of these compounds are thioesters, chemical compounds that contain a high-energy carbon-sulfur bond. It has been speculated for some time that thioesters might be among the most ancient versions of such metabolic reactive intermediates, partly because modern organisms still use thioesters to help break down sugars and make proteins from amino acids. Just how reactive intermediate compounds like thioesters could have been formed before life evolved, or as early life was taking its first baby steps, remains shrouded in mystery. New work from researchers at the Earth-Life Science Institute (ELSI) at Tokyo Institute of Technology, shows that a simple compound that can be found in some modern volcanic gases - a thioacid (a compound formed from an organic acid and hydrogen sulfide, which is the compound largely responsible for the "rotten egg" smell of many hot springs) - readily reacts with simple sulfur containing thiol compounds similar to those fundamental to modern metabolism to form reactive thioesters similar to those found in modern biology. This reaction happens readily in water and may have served as a starting point for the evolution of more complex biochemistry. During the research, they found that when they included iron (which is the most abundant element on Earth and comprises about 5% of Earth's surface layer, known as the crust), in their reactions, the reaction product yields increased.

The team suggests this may mean energy coupling between multiple reactions, in which one reaction drives another forward, may have its origins in non-living environmental chemistry. Remarkably, they also found a side product of the reaction they discovered can be used to make a second type of versatile energy-coupling compound required by all living things: FeS (short for iron-sulfur) clusters. These are small aggregates of only a few atoms each of iron and sulfur, which help organisms metabolize as they move electrons from one molecule to another. One important example of such a FeS-cluster-using-pathway is photosynthesis, which transfers electrons from water to CO2 to make sugars and oxygen. This work thus provides a new understanding of how high energy molecules and electron transfer reactions may have been naturally produced as early metabolism was evolving.

Although scientists have been trying to understand the origins of life's building blocks, things like amino acids, nucleotides, peptides, and so on, for some time, little effort has been given to understanding how energy transfer originated in prebiotic chemistry. Understanding this energy exchange could be as important as understanding the origin of building blocks, so the ELSI team decided to search for reactions which could be coupled together energetically. As lead author, Sebastian Sanden notes "We were already studying FeS minerals, and we knew how easy their formation was, so we wanted to see if we could couple this excess wasted energy to another reaction." The thioacid they began their study with contains sulfur, which they knew then only had to be reacted with iron to make the FeS clusters they were already studying.

The experiments and analyses the ELSI researchers performed had to be done in rapid succession to track the progress of the reaction. They developed techniques for doing this, and thus they were able to determine how fast these reactions happened. Their preliminary thioester-making experiments did not proceed as fast as they initially hoped, but by adding a catalyst and increasing the temperature, they found that maximum thioester yields were obtained in less than an hour, as opposed to a few days before making these changes.

The team thinks it is especially fascinating that these kinds of reactions may create "cascade reactions" which make more and more complex molecules: pyruvate decomposes, helping form a thioester, which then allows peptides (smaller cousins of proteins) to form via the newly discovered thioester route. The team hopes to test this experimentally next and to create a system that can increase the number of components it contains and their complexity by itself, perhaps all the way to self-reproduction. Some modern microbes in fact use pyruvate decomposition and thioester formation assisted by FeS clusters in their metabolism, and it is possible that the reactions the team discovered recapitulate how early prebiological or biological evolution discovered them. As the lead investigator on this work, ELSI Associate Professor Shawn McGlynn says, "This work provides new connections between multiple prebiotic reaction components that may have been critical to establishing early energy metabolism on Earth."

While this work may shine new light on how naturally occurring energy exchange reactions may have helped "jump-start" metabolism, it may also be important for the field of "green chemistry," which is concerned with finding the most energetically effective and environmentally friendly methods to make chemical compounds. While toxic heavy metals like cadmium and mercury and solvents like chloroform are often used in industrial organic chemistry, the reactions discovered by this research group are very efficient and work in water using non-toxic iron as a catalyst.

One way CBD appears to reduce the "cytokine storm" that damages the lungs and kills many patients with COVID-19 is by enabling an increase in levels of a natural peptide called apelin, which is known to reduce inflammation and whose levels are dramatically reduced in the face of this storm.

Dental College of Georgia and Medical College of Georgia researchers reported this summer CBD's ability to improve oxygen levels and reduce inflammation as well as physical lung damage in their laboratory model of deadly adult respiratory distress syndrome, or ARDS.

Now they have shown that apelin levels go way down with the viral infection, which has killed 1 million people worldwide, and that CBD quickly helps normalize those levels along with lung function.

"It was dramatic in both directions," says Dr. Babak Baban, DCG immunologist and associate dean for research, of shifting apelin levels in both circulating blood and lung tissue.

Blood levels of the peptide dropped close to zero in their ARDS model and increased 20 times with CBD, they report in the Journal of Cellular and Molecular Medicine.

"CBD almost brought it back to a normal level," Dr. Jack Yu, physician scientist and chief of pediatric plastic surgery at MCG, says of the apparent first connection between CBD and apelin.

Apelin is a pervasive peptide made by cells in the heart, lung, brain, fat tissue and blood, and is an important regulator in bringing both blood pressure and inflammation down, says Baban, the study's corresponding author.

When our blood pressure gets high, for example, apelin levels should go up in the right place, like endothelial cells that line blood vessels, to help bring it down. Apelin should do the same to help normalize the significant increases in inflammation in the lungs and related breathing difficulties associated with ARDS.

"Ideally with ARDS it would increase in areas of the lungs where it's needed to improve blood and oxygen flow to compensate and to protect," Baban says. But when they looked at their ARDS model, apelin didn't do either, and instead decreased in both the lung tissue itself and the general circulation. Until they gave CBD.

They reported this summer in the journal Cannabis and Cannabinoid Research that treatment with CBD reduced excessive lung inflammation, enabling improvements in lung function, heathier oxygen levels, and repair of some of the structural damage to the lungs that are classic with ARDS. The investigators said then more work was needed, including finding how CBD produced the significant changes as well as human trials, before it should be included as part of a treatment regimen for COVID-19.

Now they have correlated those improvements with regulation of apelin. While they don't attribute all CBD's benefits to apelin, they say the peptide clearly has an important role in this scenario. They also don't yet know whether the novel coronavirus, or CBD for that matter, have a direct effect on apelin, or if these are downstream consequences, but they are already pursuing answers to those unknowns.

"It is an association; we don't know yet about causative, but it is a very good indicator of the disease," Baban says of the bottom line impact of the viral infection on apelin levels.

The now familiar spiked virus enters human cells via the also pervasive angiotensin-converting enzyme 2, or ACE2, receptor. "The spike proteins have just the right docking mechanism," says coauthor Yu. And there is plenty of common ground between ACE2 and apelin, including the fact that many cell types and tissues have both, including the lungs.

Apelin and ACE2 also normally work together to control blood pressure, and upregulation of both may be helpful in cardiovascular disease, including heart failure, by decreasing blood pressure while increasing the heart's ability to pump. In fact, apelin and ACE2 work together to regulate a healthy cardiovascular system and they are factors in pretty much any condition, like obesity or hypertension, that hurt the cardiovascular system, Baban says.

Like other disease, the novel coronavirus appears to upset their positive partnership. The virus' binding to the receptor for ACE2 has been shown to decrease ACE2 levels and increase levels of the powerful blood vessel constrictor angiotensin II, because less angiotensin II gets degraded and fewer vasodilators get produced, which worsens the patient's prognosis.

"Instead of ACE2 helping blood vessels relax, it helps the virus get into the host where it makes more virus instead of helping the lungs relax and do their job," says Yu.

While the researchers are still putting the pieces together, reduced levels of ACE2 appear to enable less apelin and less protection.

However it happens, their finding of dramatic reductions in apelin in the face of ARDS, makes levels of the protective peptide a potential early biomarker for ARDS and response to treatment efforts, they say.

The new finding was their first in learning more about how CBD produces the beneficial effects they saw in their model of ARDS. Next steps include better understanding the interaction between CBD, apelin and the novel coronavirus including why apelin goes down in the face of the virus and why CBD brings it up. That includes exploring how eliminating apelin affects ARDS and if CBD produces the same lung benefit without apelin.

Likely the virus suppresses something that suppresses apelin, they say and CBD interferes. But they doubt the apelin-CBD interaction is the only way the compound, the second most prevalent found in the marijuana plant, works in this and other scenarios.

The studies were enabled by the investigators' development of a safe, relatively inexpensive model of ARDS by giving a synthetic analog of double-stranded RNA called POLY (I:C). The novel coronavirus also has double-stranded RNA, while ours is single-stranded, so this analog produced a response similar to the virus, including the extreme lung damage that has led to the need for ventilator and other extreme support measures for patients, and is a major cause of death. Much as with the SARS-CoV-2 infection, the result is the "cytokine storm" that reflects an over-the-top immune response in the lungs, which results in an attack rather than protection.

For these studies, a control group received intranasal saline for three consecutive days while the COVID-19 model received POLY (I:C) intranasally for three days. A third group, the treatment group, received POLY ((I:C) and CBD over the same timeframe.

This time they looked and also found significantly reduced apelin levels in the mice that developed COVID-like symptoms compared to controls. Treatment with CBD normalized the immune response and apelin levels, along with oxygen levels and swelling and scarring in the lungs characteristic of the deadly ARDS.

"The apelinergic system is a very, very ubiquitous signaling system," Yu says. While it has diverse jobs in different places, and levels may rise and fall depending on what is needed, its levels are consistently measurable in the lungs, one of the reasons it should be a good biomarker, and it's also generally considered protective, they say.

Apelin's important, diverse roles include helping ensure the placenta is well supplied with blood and the oxygen and nutrients it carries during a pregnancy. In fact, DCG and MCG investigators decided to look at apelin because of the work of Dr. Évila Lopes Salles, a postdoctoral fellow with Baban in the DCG Department of Oral Biology and the study's first author, who was looking at the peptide's significant impact in gestation and clear anti-inflammatory role, Baban says.

Synthetic agonists that increase apelin levels exist and are showing promise in the laboratory for cardiovascular disease, including slowing the growth rate of weak points in blood vessels called aneurysms. CBD appears to be a natural apelin agonist, the researchers say.

Ants are one of the most successful groups of animals on the planet, occupying anywhere from temperate soil to tropical rainforests, desert dunes and kitchen counters. They're social insects and their team-working abilities have long since been identified as one of the key factors leading to their success. Ants are famously able to lift or drag objects many times their own weight and transport these objects back to their colony. But with previous research having focused on the social aspects of an ant colony, looking at an individual ant has been somewhat neglected.

Now, researchers at the Okinawa Institute of Science and Technology Graduate University (OIST) and Sorbonne University in Paris have investigated why individual worker ants are so strong by taking X-ray images and creating 3D models of their thorax - the central unit of their bodies - to analyze their muscles and internal skeleton. Their study, published in Frontiers in Zoology, examines the hypothesis that loss of flight in worker ants is directly connected to the evolution of greater strength.

"Worker ants evolved from flying insects," said Professor Evan Economo, who leads OIST's Biodiversity and Biocomplexity Unit. "We've always assumed that losing flight helped to optimize their bodies for working on the ground, but we have much to learn about how this is achieved."

Being able to fly might be a common dream amongst people but the reality of flight is that it puts strong constraints on the build of a body. In flying insects, the wing muscles occupy a major part of the thorax - sometimes more than 50%. This means that other muscles, which are used to support and move the head, legs, and abdomen are constrained and squeezed up against the exoskeleton.

But once the constraints of flight are removed, all that space in the thorax is open, which, the researchers surmised, would allow the remaining muscles to expand and reorganize.

Previous research in this area had focused on the external structure of ants but, with the technology available at OIST, the researchers were able to gain a highly detailed picture of what was going on inside the thorax. The aim was to analyze the general features common across all ants, rather than focus on the specialization of certain species. To do this, the researchers did a detailed analysis of two distantly related ant species, including both the wingless workers and the flying queens, and confirmed their findings across a broader sample of species.

They used advanced X-ray technology to scan the internal and external anatomy, like CT scans used in a hospital, but at much higher resolution. From these scans, the researchers mapped all the different muscles and modeled them in 3D. The result was a comprehensive image of the inside of the thorax. They then compared findings from these two species to a range of other ants and wingless insects.

As predicted, the researchers found that loss of flight had allowed for clear-cut reorganization of the thorax. "Within the worker ant's thorax, everything is integrated beautifully in a tiny space," said the late Dr. Christian Peeters, lead author of this paper, who was a research professor at Sorbonne University. "The three muscle groups have all expanded in volume, giving the worker ants more strength and power. There has also been a change in the geometry of the neck muscles, which support and move the head. And the internal attachment of muscles has been modified."

Interestingly, when looking at wingless wasps, the researchers found that these insects had responded to the loss of flight in a completely different way. Wingless wasps are solitary and consume food as they find it. On the other hand, ants are part of a colony. They hunt or scavenge for food that then needs to be carried back to the nest for the queen and younger nestmates, so it makes sense that there was a selection pressure to promote carrying ability.

Ants have been studied for centuries in terms of their behavior, ecology, and genetics but, the researchers emphasized, this story of strength has, so far, been somewhat overlooked. The next step is to develop more detailed biomechanical models of how different muscle groups function, do similar research on the mandible and legs, and explore the diversity seen between ant species.

"We're interested in what makes an ant an ant and understanding the key innovations behind their success" explained Professor Economo. "We know that one factor is the social structure, but this individual strength is another essential factor."

Beijing, China 19 Oct 2020: Elevated birth weight is linked with developing atrial fibrillation later in life, according to research presented at the 31st Great Wall International Congress of Cardiology (GW-ICC).

GW-ICC 2020 is a virtual meeting during 19 to 25 October. Faculty from the European Society of Cardiology (ESC) will participate in joint scientific sessions with the GW-ICC as part of the ESC Global Activities programme.

Study author Dr. Songzan Chen of Zhejiang University, Hangzhou, China said: "Our results suggest that the risk of atrial fibrillation in adulthood may be higher for large newborns (over 4,000 grams or 8 pounds 13 ounces) than those with normal birth weight. Preventing elevated birth weight could be a novel way to avoid atrial fibrillation in offspring - for example with a balanced diet and regular check-ups during pregnancy, particularly for women who are overweight, obese or have diabetes."

He added: "People born with a high weight should adopt a healthy lifestyle to lower their likelihood of developing the heart rhythm disorder."

Atrial fibrillation is the most common heart rhythm disorder, affecting more than 40 million individuals globally.1 People with atrial fibrillation have a five times greater risk of having a stroke. The relationship between birth weight and atrial fibrillation is controversial.2-5 This study investigated the lifetime causal effect of birth weight on the risk of atrial fibrillation.

The researchers conducted a naturally randomised controlled trial - a technique called Mendelian randomisation. First, they used data from 321,223 individuals in a genome-wide association study (GWAS) to identify 132 genetic variants associated with birth weight.6 Next, they identified which of those variants play a role in atrial fibrillation using data from 537,409 participants of the Atrial Fibrillation Consortium (of whom 55,114 had atrial fibrillation and 482,295 did not).7

To conduct the naturally randomised controlled trial, the 132 genetic variants were randomly allocated to the 537,409 participants at conception, giving each individual a birth weight in grams. The investigators then analysed the association between birth weight and atrial fibrillation.

Elevated birth weight was associated with an increased risk of atrial fibrillation later in life. Specifically, participants with a birth weight that was 482 grams (about 1 standard deviation) above the average (3,397 grams) were 30% more likely to develop the heart rhythm disorder (odds ratio = 1.30; 95% confidence interval 1.18-1.44; p=0.0000004).

Dr. Chen said: "A major strength of our study is the methodology, which allows us to conclude that there may be a causal relationship between high birth weight and atrial fibrillation. However, we cannot discount the possibility that adult height and weight may be the reasons for the connection. Birth weight is a robust predictor for adult height, and taller people are more likely to develop atrial fibrillation. Previous research has shown that the link between birth weight and atrial fibrillation was weaker when adult weight was taken into account."2

Professor Guosheng Fu of Sir Run Run Shaw Hospital (SRRSH), affiliated with the Zhejiang University School of Medicine, and one of the Scientific Committee Chairmen of GW-ICC 2020, said: "This study provides genetic evidence for the association between elevated birth weight and the increased risk of atrial fibrillation. From this research, we can see that reducing the number of newborns with elevated birth weight is probably considered as a feasible prevention to ease the burden of atrial fibrillation. Therefore, pregnant women should pay more attention to the diet control and regular check-ups, especially for those with obesity or diabetes. Equally important, people born with a high birth weight should be aware of reducing other risk factors to prevent atrial fibrillation."

Professor Michel Komajda, a Past President of the ESC and Global Affairs regional Ambassador for Asia at GW-ICC 2020, said: "Atrial fibrillation is a devastating illness that causes avoidable strokes if left untreated. We know that people with unhealthy lifestyles are more likely to develop atrial fibrillation, and risk can be lowered through physical activity and keeping body weight under control. This study is a welcome addition to our knowledge about how to prevent atrial fibrillation."

Tokyo, Japan - Researchers from Tokyo Metropolitan University studied the biodiversity of wetland plants over time in rice paddies in the Tone River basin, Japan. They found that paddies which were more likely to have been wetland before agricultural use retained more wetland plant species. On the other hand, land consolidation and agricultural abandonment were both found to negatively impact biodiversity. Their findings may one day inform conservation efforts and promote sustainable agriculture.

The Asian monsoon region is home to a vast number of rice paddies. Not only have they fed its billions of inhabitants for centuries, they are also an important part of the ecosystem, home to a vast array of wetland plant species. But as the population grows and more agricultural land is required, their sheer scale and complexity beg an important question: what is their environmental impact?

A team from Tokyo Metropolitan University led by Associate Professor Takeshi Osawa and their collaborators have been studying how rice paddies affect local plant life. In their most recent work, they investigated the biodiversity of wetland plants in rice paddies around the Tone River basin Japan. The Tone River is Japan's second longest river, and runs through the 170,000 square kilometer expanse of the Kanto plains. Previous studies have looked at how a particular species or group of species fare in different conditions. Instead, the team turned their attention to the range of species that make up the plant community, with a particular focus on the number of wetland and non-wetland species present. Changes were tracked over time using extensive survey data from 2002, 2007 and 2012.

They found that not all rice paddies are equal when it comes to how well they support original wetland species. In fact, there was a correlation between how likely it was that the land was wetland before it was put to agricultural use, and the number of wetland species which were retained over time. Here, the team measured this using flow accumulation values (FAVs) for different plots of land, a simple metric which showed how easily water could accumulate. Importantly, this kind of approach might help us predict how amenable new rice paddies might be to the local wetland flora by calculating a simple number using the local terrain. However, they also found that things like land consolidation and agricultural abandonment could also have a negative impact. The emerging story is that both current human usage and original geographical conditions play an important role in deciding how 'friendly' rice paddies could be for the original wetland ecosystem.

The team believe that the same approach could be applied to different locations such as plantation forests which were (or were not) originally woodland. After all, many nations are turning to large scale tree planting to offset carbon emissions. The ability to systematically 'assign' how new land usage might impact local ecosystems is sure to greatly help restoration and conversation efforts.

Droplets of fat inside our cells are helping the body's own defence system fight back against infection, University of Queensland researchers have discovered.

The international collaboration between UQ Institute for Molecular Bioscience researchers Professor Robert Parton and Professor Matt Sweet, and the University of Barcelona's Professor Albert Pol found that these fat droplets are both a food source and weapon against bacterial invaders.

"It was previously thought that bacteria were merely using the lipid droplets to feed on, but we have discovered these fatty droplets are involved in the battle between the pathogens and our cells," Professor Parton said.

"Fat is part of the cell's arsenal--cells manufacture toxic proteins, package them into the lipid droplets, then fire them at the intruders.

"This is a new way that cells are protecting themselves, using fats as a covert weapon, and giving us new insights into ways of fighting infection."

With antibiotic-resistant superbugs on the rise, researchers are determined to find alternative ways to fight infection.

One possibility is ramping up the body's natural defences.

"We showed that upon infection of white blood cells called macrophages, lipid droplets move to the part of the macrophage where the bacteria are present," Professor Sweet said.

The bacterial infection also changed the way that white blood cells used energy.

"Lipid droplets can be used as a fuel source for mitochondria when there aren't enough other nutrients," Professor Sweet said.

"During an infection, lipid droplets move away from the mitochondria and attack the bacteria instead, altering metabolism of the cell."

Cell biologist Professor Parton was inspired to continue this research after the phenomenon was seen in fruit flies.

"Most people thought the lipid droplets were 'blobs of fat', only useful for energy storage but now we are seeing that they act as metabolic switches in the cell, defend against infection and much more--there are now entire scientific conferences of researchers working on them," he said.

"Our next step is to find out how the lipid droplets target the bacteria.

"By understanding the body's natural defences, we can develop new therapies that don't rely on antibiotics to fight drug-resistant infections."

LA JOLLA--Your pancreas is studded with cell clusters called islets. In most people, special beta cells live snug in the islets, happily making the insulin that the body uses to regulate blood sugar. But in people with type 1 diabetes, the body's T cells mistakenly move into the islets and kill the beta cells.

It's long been thought that having "autoreactive" T cells in the pancreas was a sure sign of type 1 diabetes. Yet a new study led by scientists at La Jolla Institute for Immunology (LJI) shows that even healthy people have these cells lurking in the pancreas--in surprisingly high numbers.

"These T cells are like predators," says LJI Professor Matthias von Herrath, M.D., senior author of the new study, published October 16, 2020, in Science Advances. "And we always thought that beta cells would die if the predator was there. But it turns out the T cells are already there. They just seem to be waiting for a signal to attack."

These "predator" cells are called CD8+ T cells, and they specifically target a molecule called preproinsulin, a precursor to insulin. Previous studies have shown that healthy people do have some of these T cells in their bloodstream. No one knew if these cells would travel to the pancreas though--partly because of the challenge of obtaining pancreas samples.

In work spearheaded by Christine Bender, Ph.D., first author of the study and a postdoctoral fellow in the von Herrath Lab, the researchers used a new staining technique to show where these cells gathered in precious human tissue samples. They were surprised to see that even healthy people had proproinsulin-specific T cells swarming in the pancreas.

It appears that high numbers of these T cells in the pancreas are the default--whether you have type 1 diabetes or not. "We were surprised," says Bender. "Of course, every donor is different, but in general, the numbers are pretty high."

Of course, people with type 1 diabetes had it worse. Their tissue samples showed the T cells very close to--and even infiltrating--the islets.

"We can't say that these are the only culprits in type 1 diabetes," says von Herrath. "But these T cells are the prime suspects."

These results add evidence for the theory that type 1 diabetes is not caused by malfunctioning T cells attacking beta cells. Instead, the body is already making these T cells and something in the pancreas is triggering the attack. Von Herrath thinks this could mean that an effective type 1 diabetes therapy would need to be local to the pancreas.

Going forward, the researchers plan to take a closer look at how the preproinsulin-specific T cells behave. The team also hopes to investigate other proteins in islets that might attract T cell attacks.

"We still have so many questions," says Bender.

New research suggests that conditions such as attention deficit hyperactivity syndrome (ADHD), bipolar disorder, and even aggressive behaviors may be linked with sugar intake, and that it may have an evolutionary basis.

The research, out today from the University of Colorado Anschutz Medical Campus and published in Evolution and Human Behavior, presents a hypothesis supporting a role for fructose, a component of sugar and high fructose corn syrup, and uric acid (a fructose metabolite), in increasing the risk for these behavioral disorders.

"We present evidence that fructose, by lowering energy in cells, triggers a foraging response similar to what occurs in starvation," said lead author Richard Johnson, MD, professor at the University of Colorado School of Medicine on the CU Anschutz Medical Campus.

Johnson outlines research that shows a foraging response stimulates risk taking, impulsivity, novelty seeking, rapid decision making, and aggressiveness to aid the securing of food as a survival response. Overactivation of this process from excess sugar intake may cause impulsive behavior that could range from ADHD, to bipolar disorder or even aggression.

"While the fructose pathway was meant to aid survival, fructose intake has skyrocketed during the last century and may be in overdrive due to the high amounts of sugar that are in the current Western diet," Johnson adds.

The paper looks at how excessive intake of fructose present in refined sugars and high fructose corn syrup may have a contributory role in the pathogenesis of behavioral disorders that are associated with obesity and Western diet.

Johnson notes, "We do not blame aggressive behavior on sugar, but rather note that it may be one contributor."

Johnson recommends further studies to investigate the role of sugar and uric acid, especially with new inhibitors of fructose metabolism on the horizon.

"The identification of fructose as a risk factor does not negate the importance of genetic, familial, physical, emotional and environmental factors that shape mental health," he adds.

RNA interference is a gene regulatory mechanism in which the expression of specific genes is downregulated by endogenous microRNAs or by small interfering RNAs (siRNAs). Although siRNAs have broad potential for gene-silencing therapy, their instability is one of the difficulties to develop siRNA-based agents. To improve their stability, most of the developed siRNA-based drugs are chemically modified in their nucleotides or phosphodiester linkages. However, chemical modification is not a perfect strategy for siRNA stabilisation because extensive modification may interrupt the gene-silencing activity of siRNAs and also induce cytotoxicity.

siRNAs consist of oligonucleotide duplexes of 21-23 bases and form an A-form helix structure in which the major grooves have highly negative potential, therefore cationic molecules that can bind to the major grooves are expected to stabilise the RNA duplexes and protect them against cleavage in the body fluid. Based on this idea, organic chemists at Tokyo University of Science have recently synthesised an artificial cationic oligosaccharide, oligodiaminogalactose 4mer (ODAGal4), that can preferentially bind to the major grooves of RNA duplexes for siRNA stabilisation (Iwata, RI. et al. Org. Biomol. Chem. https://doi.org/10.1039/c6ob02690g (2017)).

Now, Atsushi Irie and his colleague at Tokyo Metropolitan Institute of Medical Science in collaboration with the team at Tokyo University of Science have developed a new strategy for siRNA stabilisation using ODAGal4 combined with phosphorothioate modification of RNAs. In the study published online on 9th September in the Scientific Reports, the researchers have proved that ODAGal4 strongly enhances biological and thermal stability of siRNAs in vitro.

The researchers show that ODAGal4 has several unique characteristics for stabilising siRNAs. Firstly, ODAGal4 can improve stability of various siRNAs independent of nucleotide sequence because ODAGal4 binds to phosphodiester linkages of RNA duplexes but not to nucleobases of the nucleotides. In addition, importantly, ODAGal4 does not compromise gene-silencing activity of any siRNAs. This character of ODAGal4 is in sharp contrast to those of known chemical modifications, which may interrupt gene-silencing activity of siRNAs. ODAGal4, therefore, has great potential for siRNA stabilisation, being widely applicable to various siRNA-based drugs.

Secondly, the effect of ODAGal4 on siRNA stabilisation is further enhanced by chemical modification of the siRNAs; in particularly, ODAGal4 prominently improves stability of RNAs with phosphorothioate linkages. This improvement in siRNA stability is superior to that observed for other chemical modifications (e.g., 2'-O-methyl, locked nucleic acid and 2'-deoxy-2'-fluoro nucleotides) suggesting that ODAGal4 combined with phosphorothioate modification is highly effective for stabilising siRNAs.

Lastly, another striking property of ODAGal4 is its binding specificity to RNA duplexes; ODAGal4 binds to A-form RNA helix but not to B-form DNA helix nor to single-stranded RNA/DNA. Although various gene delivery systems consisting of cationic polymers have been developed to stabilise nucleotides, the molecular structures of the polymers are not designed to specifically bind to nucleotides. The binding of the polymers to nucleotides relies on the ionic interaction between them, and thereby the polycation complexes are prone to induce cytotoxicity due to nonspecific binding of the polymers to other biomolecules. In marked contrast, ODAGal4 escapes from causing cytotoxicity because of its restricted binding with high affinity to RNA duplexes.

"Our goal will be application of ODAGal4 for siRNA-based agents. Although we should study in vivo experiments to confirm and expand our findings, we emphasise that ODAGal4 has a great advantage as improving siRNA stability and has a potential for reducing total dose and frequency of administration of siRNA-based drugs in future application," concludes Atsushi Irie.