Culture

Renewable energy demand and consumption is at an all-time high in the United States.

Shrub willow - a quick-growing woody crop - can be an excellent source of renewable bioenergy. The crop is harvested and turned into wood chips, which can be used for heat, mulch, animal bedding, biochar, and biofuel.

In a new study, researchers grew shrub willow on a semi-commercial scale to better understand the nuances of this bioenergy crop. The research was published in Agronomy Journal, a publication of the American Society of Agronomy.

"We learned and developed key know-hows that we can transfer to industry partners interested in this crop," says Armen Kemanian. Kemanian is a member of the American Society of Agronomy and is the lead author of the study.

Insights include determining which willow varieties to plant and how to best handle planting and harvesting.

"Starting a willow crop can be expensive," says Kemanian. "It also requires a perfectly choreographed operation to keep costs low and yields high."

But shrub willow also offers several advantages as a bioenergy crop.

"Shrub willow thrives in wetter areas with cold winters and mild summers," says Kemanian. That makes the crop well-suited to New England and parts of the upper Midwest.

Other bioenergy crops, such as switchgrass, grow better in areas of the U.S. with warmer summers.

According to Kemanian, "Shrub willow can be part of a geographically diverse combination of bioenergy crops."

One important quality of shrub willow is its ability to store a tremendous amount of carbon. That's beneficial because when there is more carbon stored in plants, there is less carbon in the atmosphere.

When the carbon is in the atmosphere as carbon dioxide, it can be a harmful greenhouse gas. But when the carbon is in the plant, it doesn't pose a risk to the environment.

Shrub willow also has tremendous genetic variability. That's important for breeding key crop characteristics, such as pest resistance.

"The study found that planting a mixture of willow varieties is critically important," says Kemanian.

That's because some highly productive willow varieties attract pests, like the willow leaf beetle. Surrounding these high-yield willow varieties with beetle-resistant varieties can slow down the pests.

"This is a different strategy compared to growing annual crops," explains Kemanian.

Annuals can be replanted every year. In contrast, shrub willow can be harvested every two to four years for more than 20 years. "Growing different varieties together is critical," says Kemanian.

The relatively long lifespan of willow crops also means that planning is vitally important.

"Harvest costs account for a large fraction of total operation cost over the life cycle of willow crops," says Kemanian.

The study established that a well-designed field is easier to harvest. That might seem obvious, but some of the findings are counterintuitive.

For example, while yields are important, seeking the highest possible yield per unit area is not the most critical parameter when planning willow planting schemes.

"Designing fields and plantings so that harvest machinery traffic is efficient is more important," says Kemanian.

However, the study also found that - at least on semi-commercial scales - actual willow yields could be lower than the expected yield potential.

"Willow thrives in productive soils," says Kemanian. "Rocky soils can increase planting and harvest cost and lower yields."

Researchers suggest that when it comes to growing shrub willow, the harvestable crop isn't the only valuable outcome for farmers.

"We should also monetize the ecosystem services that willow provides," says Kemanian.

These services include storing carbon, hosting pollinators, reducing water runoff, and retaining nutrients - such as nitrogen - in the soil.

"Willow can play a significant role in improving our most intensely farmed land," says Kemanian. "We just need to take advantage of the synergies between animal production and crop production."

But quantifying the ecosystems services of willow at a large scale remains complicated. "We can tackle this challenge with computer modeling," says Kemanian. "That's something our team is doing right now."

Other next steps include monitoring for pest outbreaks with unmanned aerial vehicles (UAVs). These UAVs could also be used to detect and control pests efficiently and economically.

"Ultimately, we think willow can play a role in regenerative and climate-smart agriculture," says Kemanian.

SILVER SPRING, Md. - As concern has grown over COVID-19 variants and their implications for how well COVID-19 vaccines will protect against the virus, researchers have proposed a method to examine instances of SARS-COV-2 infections in people who have received a COVID-19 vaccine.

Genomic sieve analysis of these so-called "breakthrough" SARS-CoV-2 infections in COVID vaccine trials is a critical tool to identify viral mutations associated with vaccine failure and to predict how vaccination impacts the virus' evolution.

Dr. Morgane Rolland, Chief of Viral Genetics for the U.S. Military HIV Research Program at the Walter Reed Army Institute of Research, and Dr. Peter Gilbert, biostatistician and professor at the Vaccine and Infectious Disease and Public Health Sciences Divisions at Fred Hutchinson Cancer Research Center, described the strategy in a recent publication in PLOS Pathogens.

"No vaccine is 100 percent effective, so even in clinical trials for the highly effective COVID vaccines being rolled out now, some of the trial volunteers who received the vaccine experienced breakthrough infections," explained Rolland. "Sieve analysis compares those breakthrough viruses to those that infected the placebo group to help pinpoint which variants are evading the vaccine-induced immune response and inform efforts to improve COVID vaccines."

Gilbert added, "Think of the vaccine as a sieve and different variants as pebbles poured into the sieve: the vaccine will block some variants but allow others to pass through, and sieve analysis learns which variants make it through."

Sieve analysis allows scientists to recognize evolutionary patterns that will be key to infer how SARS-CoV-2 might adapt to widely used vaccines and predict how virus evolution could eventually impact vaccine efficacy. The paper's authors note SARS-CoV-2 is relatively slow to mutate, meaning it's unlikely current vaccines will be rendered obsolete soon, but increased vigilance is needed in the months until a majority of the population has been vaccinated to stem spread of concerning variants.

"The variants that emerged in the past two months highlight the need for next generation vaccines," said Rolland. "Conducting sieve analysis of samples obtained through vaccine trials is an efficient way to determine how future vaccines should be designed."

Scientists at Sinai Health say they have discovered a new pathway that controls dangerous overreactions in a body's immune system, including deadly forms of hyper-inflammation.

In new findings out today in the journal Science, researchers at the Lunenfeld-Tanenbaum Research Institute (LTRI) detail how a protein known as WAVE2, a protein expressed in all immune cells, plays a critical role in maintaining immune system balance.

As part of the research, scientists knocked out, or turned off, WAVE2 in a subset of immune cells in mice, which led to severe autoimmunity and inflammation, as well as an inability to mount an immune response to a viral infection.

The study's senior author, Dr. Kathy Siminovitch, said they also found that another protein, known as mTOR, became overly active in the absence of WAVE2, putting the immune system into overdrive and leading to immune cell exhaustion.

"Much like Goldilocks, a proper immune response requires such a delicate balance," said Dr. Siminovitch, senior investigator at the LTRI and Canada Research Chair in the Mechanisms Regulating Immunologic Disease. "You have to get it just right. By developing a mouse strain in which T cells, key players in immunity, lack WAVE2, we have shown that this protein is absolutely required for balanced immune responses."

How to keep the immune system from going into overdrive has been a key question for medical experts as they continue to grapple with the devastating effects of COVID-19 pandemic, particularly on the elderly population.

Patients over the age of 65 are at a higher risk of developing severe COVID-19, partly due to a phenomenon called "cytokine storm" where the immune system overacts and damages organs.

"The pandemic has starkly illuminated the critical importance of immune balance and the severe consequences of disrupting such balance," said Siminovitch. "It has also highlighted the importance of fundamental research, which has taken us where we are today in understanding the virus and having treatment and prevention strategies in hand."

For years, Dr. Siminovitch has been exploring the genetic and molecular mechanisms that regulate and maintain balance across the immune system. In previous work, she helped trace the complex molecular steps that turn a rare gene mutation into Wiskott-Aldrich syndrome, which impairs the immune system of boys, and can lead to death at a very young age.

Dr. Siminovitch said they would like to expand their research to look at how the WAVE2-mTOR pathway may contribute to specific autoimmune, inflammatory and other conditions, such as Alzheimer's disease.

"Understanding how to achieve this kind of control in immunity is really important," said Dr. Siminovitch. "This research opens the door to new ways of restoring that balance through the development of new therapeutics that target the WAVE2- mTOR pathway."

The evolving science of wisdom rests on the idea that wisdom's defined traits correspond to distinct regions of the brain, and that greater wisdom translates into greater happiness and life satisfaction while being less wise results in opposite, negative consequences.

Scientists have found in multiple studies that persons deemed to be wiser are less prone to feel lonely while those who are lonelier also tend to be less wise. In a new study, published in the March 25, 2021 issue of the journal Frontiers in Psychiatry, researchers at University of California San Diego School of Medicine take the connection between wisdom, loneliness and biology further, reporting that wisdom and loneliness appear to influence -- and/or be influenced by -- microbial diversity of the gut.

The human gut microbiota is comprised of trillions of microbes -- bacteria, viruses, fungi -- that reside within the digestive tract. Researchers have known for a while about the "gut-brain axis," which is a complex network that links intestinal function to the emotional and cognitive centers of the brain.

This two-way communication system is regulated by neural activity, hormones and the immune system; alterations can result in disruptions to stress response and behaviors, said the authors, from emotional arousal to higher-order cognitive abilities, such as decision-making.

Past studies have associated gut microbiota with mental health disorders including depression, bipolar disorder and schizophrenia, as well as personality and psychological traits regarded as key, biologically based components of wisdom. Recent research has connected the gut microbiome to social behavior, including findings that people with larger social networks tend to have more diverse gut microbiotas.

The new Frontiers in Psychiatry study involved 187 participants, ages 28 to 97, who completed validated self-report-based measures of loneliness, wisdom, compassion, social support and social engagement. The gut microbiota was analyzed using fecal samples. Microbial gut diversity was measured in two ways: alpha-diversity, referring to the ecological richness of microbial species within each individual and beta-diversity, referring to the differences in the microbial community composition between individuals.

"We found that lower levels of loneliness and higher levels of wisdom, compassion, social support and engagement were associated with greater phylogenetic richness and diversity of the gut microbiome," said first author Tanya T. Nguyen, PhD, assistant professor of psychiatry at UC San Diego School of Medicine.

The authors said that the mechanisms that may link loneliness, compassion and wisdom with gut microbial diversity are not known, but observed that reduced microbial diversity typically represents worse physical and mental health, and is associated with a variety of diseases, including obesity, inflammatory bowel disease and major depressive disorder.

A more diverse gut microbiota may be less susceptible to invasion by outside pathogens, which could contribute to and help promote better resilience and stability of the community.

"It is possible that loneliness may result in decreased stability of the gut microbiome and, consequently, reduced resistance and resilience to stress-related disruptions, leading to downstream physiological effects, such as systemic inflammation," the authors wrote.

"Bacterial communities with low alpha-diversity may not manifest overt disease, but they may be less than optimal for preventing disease. Thus, lonely people may be more susceptible to developing different diseases."

The relationship between loneliness and microbial diversity was particularly strong in older adults, suggesting that older adults may be especially vulnerable to health-related consequences of loneliness, which is consistent with prior research.

Conversely, the researchers said that social support, compassion and wisdom might confer protection against loneliness-related instability of the gut microbiome. Healthy, diverse gut microflora may buffer the negative effects of chronic stress or help shape social behaviors that promote either wisdom or loneliness. They noted that animal studies suggest that gut microbiota may influence social behaviors and interactions, though the hypothesis has not been tested in humans.

The complexity of the topic and study limitations, such as the absence of data about individuals' social networks, diet and degree of objective social isolation versus subjective reports of loneliness, argue for larger, longer studies, wrote the authors.

"Loneliness may lead to changes in the gut microbiome or, reciprocally, alterations of the gut milieu may predispose an individual to become lonely," said Dilip V. Jeste, MD, Distinguished Professor of Psychiatry and Neurosciences at UC San Diego School of Medicine and senior author of the paper. "We need to investigate much more thoroughly to better understand the phenomenon of the gut-brain axis."

An analysis of adult human brain tissue reveals over 900 proteins tied to epilepsy. The brain disorder, estimated to afflict more than 3 million Americans, is mostly known for symptoms of hallucinations, dreamlike states, and uncontrolled, often disabling bodily seizures.

Led by researchers at NYU Grossman School of Medicine, the study examined molecular differences among the brains of 14 epilepsy patients and another group of 14 adults of similar age and gender who did not have the disease.

Study results showed that altered levels of brain proteins predominated in the hippocampus, a structure located deep inside the skull and responsible for memory and learning. However, some 134 proteins were significantly changed in both the hippocampus and frontal cortex, the front third of the brain, which is also responsible for controlling thought and body movements. Most of the changed proteins were tied to genes in charge of protein production and linked to epilepsy in much smaller, earlier studies, but four of the 20 most-altered proteins had never previously been associated with the disorder.

One particular protein, researchers say, stood out as the most significantly depleted across all brain regions. Called G Protein Subunit 1, or GNB1, the protein is known to play an important role in dozens of biological reactions, or pathways, involved in nerve growth and communication throughout the brain, but they say its precise role in epilepsy remains unclear.

Despite decades of research, researchers say, the causes of epilepsy remains unknown. Dozens of drugs are used to control seizures by targeting known protein weaknesses, excesses, or deficiencies, and the "electrical storms" they trigger in the brain, but fail in one-third of patients to do so.

Publishing in the journal Brain Communications online March 9, the new investigation focused on regions of the frontal cortex and hippocampus that previous imaging and neurological studies had identified as most impacted by seizures.

"Our analysis identifies hundreds of potential new treatment targets for epilepsy, focusing on areas of the brain mostly damaged by the disease," says study co-senior investigator Orrin Devinsky, MD, a professor in the departments of Neurology, Neuroscience and Physiology, Neurosurgery, and Psychiatry at NYU Langone Health.

"While our results point to the hippocampus as the brain region most vulnerable in epilepsy, further research is needed to confirm if this region is the primary source of the illness from which damage spreads out across other brain regions, as well as how epilepsy is mutually tied to other disorders, such as dementia and depression," says Devinsky, who also serves as director of the Comprehensive Epilepsy Center at NYU Langone.

"Of particular interest, these findings suggest that the G Protein Subunit 1 brain pathways are a strong target for new epilepsy therapies," says study co-senior author Thomas Wisniewski, MD.

Wisniewski, the Gerald J. and Dorothy R. Friedman Professor in the Department of Neurology and director of the Center for Cognitive Neurology at NYU Langone, says GNB1 pathways are already the target of more than a dozen drugs, such as nabilone and prazosine, used to treat conditions other than epilepsy, including nausea and high blood pressure.

Wisniewski says the NYU Langone team has plans to create a database that depicts "the brain landscape" of epilepsy protein and gene targets. They also plan initial clinical studies to determine how existing GNB1-altering medications may prevent or treat the disorder.

Researchers from Charité - Universitätsmedizin Berlin and the Francis Crick Institute have developed a mass spectrometry-based technique capable of measuring samples containing thousands of proteins within just a few minutes. It is faster and cheaper than a conventional blood count. To demonstrate the technique's potential, the researchers used blood plasma collected from COVID-19 patients. Using the new technology, they identified eleven previously unknown proteins which are markers of disease severity. The work has been published in Nature Biotechnology*.

Thousands of proteins are active inside the human body at any given time, providing its structure and enabling reactions which are essential to life. The body raises and lowers the activity levels of specific proteins as required, including when responding to external factors such as pathogens and drugs. The detailed patterns of the proteins found inside cells, tissues and blood samples can therefore help researchers to better understand diseases or make diagnoses and prognoses. In order to obtain this 'protein fingerprint', researchers use mass spectrometry, a technology known to be both time-consuming and cost-intensive. 'Scanning SWATH', a new mass-spectrometry-based technology, promises to change this. Developed under the leadership of Prof. Dr. Markus Ralser, Director of Charité's Institute of Biochemistry, this technology, which is much faster and cost-effective than previous methods, enables researchers to measure several hundred samples per day.

"In order to speed up this technology, we changed the mass spectrometer's electric fields. The data produced are of such extreme complexity that humans can no longer analyze them," explains Einstein Professor Prof. Ralser, who is also a Group Leader at the Francis Crick Institute in London. He adds: "We therefore developed computer algorithms that are based on neural networks and which use these data to extract the relevant biological information. This enables us to identify thousands of proteins in parallel and greatly reduces measuring timescales. Fortunately, this method is also more precise."

This high-throughput technology has a broad range of potential applications, ranging from basic research and large-scale drug development to the identification of biological markers (biomarkers), which can be used to estimate an individual patient's risk. The technology's suitability for the latter was demonstrated by the researchers' study on COVID-19. As part of this research, the team analyzed blood plasma samples from 30 Charité inpatients with COVID-19 of varying degrees of disease severity, comparing the protein patterns obtained with those of 15 healthy individuals. The actual measurements conducted on individual samples only took a few minutes.

The researchers were able to identify a total of 54 proteins whose serum levels varied according to the severity of COVID-19. While 43 of these proteins had already been linked to disease severity during earlier studies, no such relationship had been established for 11 of the proteins identified. Several of the previously unknown proteins associated with COVID-19 are involved in the body's immune response to pathogens which increases clotting tendency. "In the shortest of timeframes, we discovered protein fingerprints in blood samples which we are now able to use to categorize COVID-19 patients according to severity of disease," says one of the study's lead authors, Dr. Christoph Messner, who is a researcher at Charité's Institute of Biochemistry and the Francis Crick Institute. He continues: "This type of objective assessment can be extremely valuable, as patients will occasionally underestimate the severity of their disease. However, in order to be able to use mass spectrometry analysis for the routine categorization of COVID-19 patients, this technology will need to be refined further and turned into a diagnostic test. It may also become possible to use rapid protein pattern analysis to predict the likely course of a case of COVID-19. While the initial findings we have collected are promising, further studies will be needed before this can be used in routine practice."

Prof. Ralser is convinced that mass spectrometry-based investigations of the blood could one day complement conventional blood count profiles. "Proteome analysis is now cheaper than a complete blood count. By identifying many thousands of proteins at the same time, proteomic analysis also produces far more information. I therefore see enormous potential for widespread use, for instance in the early detection of diseases. We will therefore continue to use our studies to develop proteome technology for this type of application."

Tel-Aviv, ISRAEL - March 25, 2021 - Wild Biotech, a preclinical stage drug discovery & development company emerging out of stealth mode, today announces the publication of its first major paper, which appears in the journal Science. The study mapped the gut microbiota of animals in the wild on an unprecedented scale, adding millions of potentially novel microbiome-based therapeutics for human diseases to the company's already massive database. Wild will use these findings to first tap its database for targets in inflammatory, immune and gastrointestinal diseases.

"For the study, we collected gut microbiota from almost 200 species of animals in the wild, covering diverse classes, feeding behaviors, geographies, and traits," said Neta Raab, Co-founder & Chief Executive Officer at Wild Biotech. "Using de novo metagenome assembly, we constructed and functionally annotated a database of over 5,000 microbial genomes from those animals covering more than 1,200 bacterial species - 75% of which were previously unknown."

Animals in the wild exhibit extraordinary feats of survival. Some, from hyenas and jackals to Tasmanian devils, subsist on rotting, pathogen-infected and toxic food while remaining immune to disease - possible due, in part, to their gut microbiota. While the understanding of the diversity and functions within these ecosystems is poor, the microbial composition, diversity, and functional content of animals' microbiota have known associations with animal taxonomy, diet, activity, social structure and lifespan. "These are clues which we could tap into in order to discover entirely new agents to treat human diseases," Raab said.

The findings reported in Science add 30 million genes - each representing a potentially new therapeutic agent - to Wild's unique database of animal microbiota, which now comprises hundreds of animal species and 100 million genes. "The majority of that genomic material is novel, and our database introduces thousands of previously undescribed species into the bacterial tree of life," Raab said.

Wild applies cutting-edge AI tools to decipher the therapeutic potential of its database and identify proteins, peptides, bacteriophages, and other agents with direct activity on targets in human diseases. The company's database is unique because, unlike microbes found in the ocean or soil, the gut microbiota of animals is the most relevant and directly translatable to human therapeutics.

Wild Biotech's database and AI tools are complemented by high-throughput synthetic biology to validate microbiome-derived agents and accelerate them into preclinical testing, and the high quality of the data extracted from microbial genomes enables the company to directly synthesize and test agents. For example, in the Science study the team synthesized a panel of previously-undescribed enzymes from carrion eater microbiota and showed that they operate on a range of microbial toxins, suggesting a mechanism that detoxifies carrion for its safe consumption by the host animal.

The company has also identified in its database over 2,000 CRISPR/Cas genome editing systems, of which approximately one third does not belong to any known CRISPR/Cas family.

"Intractable diseases require new thinking on intervention. Wild has built a revolutionary approach and the tools to explore its novel data sets, unlike any other company," said Dr. John Baldoni, leading pharmaceutical industry expert and advisor to Wild. "You must have the data in order to do the computational work. Because of their highly evolved and relevant library, they are able to look at millions of interactions quickly, within days, and screen and target logical therapeutic areas. Wild's approach enables a translatable workflow from its microbiome data to molecular mechanisms associated with complex diseases."

"We are balancing innovation and clinical evidence to screen many millions of interactions with specific targets associated with human diseases," said Raab. "We are very excited about the extraordinary potential hidden in this database for identifying entirely novel approaches to treat disease."

Researchers at Baylor College of Medicine, Shandong University in China and other institutions may have found an explanation for dawn phenomenon, an abnormal increase of blood sugar only in the morning, observed in many patients with type 2 diabetes. They report in the journal Nature that mice lacking the circadian clock gene called Rev-erb in the brain show characteristics similar to those of dawn phenomenon.

The researchers then looked at Rev-erb gene expression in patients with type 2 diabetes comparing a group with dawn phenomenon to a group without it and found that the gene's expression followed a different temporal pattern between these two groups. The findings support the idea that an altered daily rhythm of expression of the Rev-erb gene may underlie dawn phenomenon. Future investigations may lead to therapies.

"We began this study to investigate what was the function of Rev-erb in the brain," said co-corresponding author Dr. Zheng Sun, associate professor of medicine-endocrinology, diabetes and metabolism at Baylor. "We are interested in this gene because it is a 'druggable' component of the circadian clock with potential applications in the clinic. Rev-erb is expressed only during the day but not at night. When we started, we did not know where this was going to lead us."

The researchers first developed a mouse model by knocking out the Rev-erb gene in GABA neurons. They chose this approach because the gene's expression is highly enriched in a particular brain area called the suprachiasmatic nucleus that is mainly composed of GABA neurons.

An unexpected finding

"We observed something very interesting in these mice," Sun said. "They were glucose intolerant - that is they had high glucose levels - only in the evening. Mice are nocturnal, meaning that they become active in the evening as people do in the morning."

When the body awakes and takes in food, insulin is secreted from the pancreas to signal the body to lower blood sugar. Insulin is more effective in doing this job upon waking than at other times of the day. This high insulin sensitivity is probably because the body is anticipating feeding behaviors upon waking up. In mice, high insulin sensitivity occurs in the evening, while in people it occurs in the morning.

Sun and his colleagues found that the abnormal higher glucose levels observed in the evening in Rev-erb knockout mice resulted from an insufficient suppression of liver glucose production by insulin. Their data demonstrate an essential role of neural Rev-erb in regulating the hepatic insulin sensitivity rhythm independent of eating behaviors or basal hepatic glucose production.

Next, the researchers looked to understand how defects in Rev-erb gene expression in the brain can result in changes in the ability of the liver to respond to insulin. They discovered that the suprachiasmatic nucleus GABA neurons in Rev-erb knockout mice had a higher firing activity than those neurons of normal mice when the animals woke up, and that this neuronal hyperactivity was sufficient and necessary to cause glucose intolerance in the evening. In normal mice, these GABA neurons drop their firing activity in the evening, lowering sugar blood levels. Interestingly, by re-expressing Rev-erb back in the knockout mice, the researchers found that Rev-erb expression is only needed during the day, but not needed at night, which is in line with the highly oscillatory expression pattern of endogenous Rev-erb in normal condition.

Connecting with dawn phenomenon

Mice having higher glucose levels in the evening reminded Sun and his colleagues of dawn phenomenon observed in people with type 2 diabetes. "Given the similarities of the phenomenon in mice and people, we thought that maybe this gene that we are studying could be linked to the biology of dawn phenomena in diabetic patients," said Sun, a member of Baylor's Dan L Duncan Comprehensive Cancer Center and the Huffington Center on Aging.

In collaboration with Qilu Hospital of Shandong University in China, the researchers followed 27 type2 diabetes patients with continuous glucose monitoring. They found that, although the patients had diabetes with similar severity in terms of their basal glucose levels, obesity and other parameters, about half of the patients had dawn phenomenon while the other half did not.

"We collected the patients' blood at different times of the day and determined the expression of the Rev-erb gene in white blood cells, which has been reported to correlate well with the central clock in the brain," Sun said. "Interestingly, we found that the gene's expression followed a temporal pattern that was different between those with dawn phenomenon and those without," Sun said. "We propose that the altered temporal pattern of expression of this gene may explain dawn phenomena in people. It is possible that, in the future, a drug might be used to regulate this gene to treat the condition."

WASHINGTON (March 25, 2021)--Although demand for COVID-19 vaccines currently seems high, vaccine hesitancy could pose a major threat to public health efforts to end the pandemic, according to an editorial published today in the journal Science.

The authors, including David A. Broniatowski, associate director of the George Washington University Institute for Data, Democracy & Politics, point out that public sentiment towards vaccines are volatile in the face of events such as the recent controversy surrounding the AstraZeneca vaccine clinical trial data. For example, some people could develop safety concerns due to the news reporting about the AstraZeneca vaccine and then turn down the chance to get an approved COVID-19 vaccine--thus putting them at risk.

Vaccine hesitant people may have anxiety over safety concerns, or they might belong to a community that historically has mistrusted the medical establishment, according to the editorial.

Unfortunately, public health officials might not address their concerns. The editorial notes that people who are hesitant about getting the COVID-19 vaccine are often dismissed as anti-science. At the same time, the vaccine hesitant can be influenced by false information posted on social media or the internet by anti-vaxx activists and organized anti-vaxx groups, the authors said.

"Vaccine hesitant people are targeted by anti-vaxxers and ridiculed by some health care providers." Broniatowski said, "They are therefore doubly at risk."

How can vaccine hesitancy be addressed?

Broniatowski co-authored the editorial with Professor Heidi J. Larson, Director of The Vaccine Confidence Project at the London School of Hygiene & Tropical Medicine.

"Messages about vaccines must be delivered in a way that is empathetic to avoid stigmatizing people who have questions about the vaccine. Particularly in the context of Covid-19, with all its uncertainties, people need to be reassured, and feel that their concerns are heard," Larson said. "And, if there is one thing we have learned in all our research, people's concerns can change. Listening needs to be ongoing."

Narcissism is driven by insecurity, and not an inflated sense of self, finds a new study by a team of psychology researchers. Its research, which offers a more detailed understanding of this long-examined phenomenon, may also explain what motivates the self-focused nature of social media activity.

"For a long time, it was unclear why narcissists engage in unpleasant behaviors, such as self-congratulation, as it actually makes others think less of them," explains Pascal Wallisch, a clinical associate professor in New York University's Department of Psychology and the senior author of the paper, which appears in the journal Personality and Individual Differences. "This has become quite prevalent in the age of social media--a behavior that's been coined 'flexing'.

"Our work reveals that these narcissists are not grandiose, but rather insecure, and this is how they seem to cope with their insecurities."

"More specifically, the results suggest that narcissism is better understood as a compensatory adaptation to overcome and cover up low self-worth," adds Mary Kowalchyk, the paper's lead author and an NYU graduate student at the time of the study. "Narcissists are insecure, and they cope with these insecurities by flexing. This makes others like them less in the long run, thus further aggravating their insecurities, which then leads to a vicious cycle of flexing behaviors."

The survey's nearly 300 participants--approximately 60 percent female and 40 percent male--had a median age of 20 and answered 151 questions via computer.

The researchers examined Narcissistic Personality Disorder (NPD), conceptualized as excessive self-love and consisting of two subtypes, known as grandiose and vulnerable narcissism. A related affliction, psychopathy, is also characterized by a grandiose sense of self. They sought to refine the understanding of how these conditions relate.

To do so, they designed a novel measure, called PRISN (Performative Refinement to soothe Insecurities about SophisticatioN), which produced FLEX (perFormative seLf-Elevation indeX). FLEX captures insecurity-driven self-conceptualizations that are manifested as impression management, leading to self-elevating tendencies.

The PRISN scale includes commonly used measures to investigate social desirability ("No matter who I am talking to I am a good listener"), self-esteem ("On the whole, I am satisfied with myself"), and psychopathy ("I tend to lack remorse"). FLEX was shown to be made up of four components: impression management ("I am likely to show off if I get the chance"), the need for social validation ("It matters that I am seen at important events''), self-elevation ("I have exquisite taste"), and social dominance ("I like knowing more than other people").

Overall, the results showed high correlations between FLEX and narcissism--but not with psychopathy. For example, the need for social validation (a FLEX metric) correlated with the reported tendency to engage in performative self-elevation (a characteristic of vulnerable narcissism). By contrast, measures of psychopathy, such as elevated levels of self-esteem, showed low correlation levels with vulnerable narcissism, implying a lack of insecurity. These findings suggest that genuine narcissists are insecure and are best described by the vulnerable narcissism subtype, whereas grandiose narcissism might be better understood as a manifestation of psychopathy.

CHAMPAIGN, Ill. -- Materials that contain special polymer molecules may someday be able to warn us when they are about to fail, researchers said. Engineers at the University of Illinois Urbana-Champaign have improved their previously developed force-sensitive molecules, called mechanophores, to produce reversible, rapid and vibrant color change when a force is applied.

The new study led by postdoctoral researcher Hai Qian, materials science and engineering professor and head Nancy Sottos, and Beckman Institute of Advanced Science and Technology director Jeffrey Moore is published in the journal Chem.

Moore's team has been working with mechanophores for more than a decade, but past efforts have produced molecules that were slow to react and return to their original state, if at all. This inability to produce an on/off-like response has limited their use as molecular probes that continuously report a material's mechanical condition, the study reports.

"The color change is the result of stress applied to the bonds that connect the mechanophores to a polymer chain," Qian said. "We are now bonding the mechanophores to polymer chains using a different arrangement scheme, called an oxazine structure. The new structure allows for an instantaneous and reversible color change, so instead of the polymer slowly becoming darker over time, the color changes quickly when the force is applied and disappears when the force is removed."

See a video demonstrating the new oxazine structure and the older spiropyran structure.

Materials that contain the new mechanophores could be used as stress sensors to enable researchers to study the effects of stress on materials before they fail.

"The rapid response and reversibility will allow engineers to better monitor, quickly detect and respond rapidly to an overstressed structure in the lab and eventually in the field," Sottos said.

A long-standing challenge in materials science has been making observations regarding mechanical load and other stresses in materials at the single-molecule level. Although this advancement cannot do this, Moore says the goal is nearer with the development of this new type of mechanophores.

"There is more work to do, but this advancement opens the door to detailed insight of what's going on at the molecular level in all sorts of materials," Moore said. "In the area of biomechanics, for example, we see this research as a steppingstone toward better monitoring of how our bodies react to external forces from the cellular level and beyond."

Researchers at GMI - Gregor Mendel Institute of Molecular Plant Biology of the Austrian Academy of Sciences, the University of North Carolina at Chapel Hill and The Howard Hughes Medical Institute (HHMI) use two complementary approaches to unveil a co-evolutionary mechanism between bacteria and plants and also explain complex immune response patterns observed in the wild. Together the papers change the way scientists have been thinking about the relationship of a bacterial antigenic component with its plant immune receptor. The two papers are published back to back in the journal Cell Host & Microbe.

Immune responses have developed in virtually all organisms over evolutionary time scales to protect them from foreign invaders. A central aspect of the immune response of higher organisms, i.e., plants and animals, is the use of sensory systems that detect and respond to "non-self" molecular signals. These molecular signals generally determine the survival chances of the pathogen, a factor that prevents them from being eliminated by natural selection as a means to evade host recognition. Their evolutionary conservation is thus due to the functionality of these molecular signals to the foreign invader. However, the negative evolutionary pressure to maintain this functionality is counterbalanced by the positive evolutionary pressure to mediate the pathogen's immune evasion. The dissection of these co-evolutionary forces through synthetic and reverse evolutionary methods is one of the two research approaches that researchers from the Belkhadir lab at GMI and the Dangl lab at UNC- Chapel Hill team up to investigate. In an orthogonal approach, they also inquire into the natural diversity of molecular antigenic determinants (epitopes) in plant-colonizing bacterial communities (commensal communities) and map the complex immune response patterns they trigger in the plants. Jeffery Dangl, John N. Couch Distinguished Professor at UNC-Chapel Hill and an HHMI investigator explains: "To date, most science in this field has used a handful of epitopes. We sampled thousands, derived from synthetic biology and commensal communities. This depth of analysis allowed us to uncover a rich diversity of host response mediated by a single receptor."

Reverse evolution and new insights on co-evolution

The researchers examine how the Arabidopsis immune sensor FLS2 (flagellin sensing 2) influenced the evolution of its interacting epitope on the Pseudomonas flagellin, and how this, in turn, influenced Pseudomonas motility. Using reverse evolutionary methods, Parys et al. uncover a new mechanism of co-evolutionary force between FLS2 and flagellin, and frame it as a molecular form of the scarcely studied theory of antagonistic pleiotropy (AP) in plant immunology. AP is the ability of a gene to induce opposing effects in different contexts, a prevailing theory for the evolutionary origin of aging in humans. The researchers demonstrate that AP fosters stable colonization of Arabidopsis by commensal communities by weighing out bacterial motility against sensor detection. This strategy results in flagellin epitopes that either mildly activate or outright block the receptor (gain in virulence), while losing in motility as a trade-off (loss in virulence). Even more excitingly, they find signatures of these synthetic experiments in naturally occurring commensal communities, suggesting that natural microbiomes might be less dependent on flagella-mediated motility and willing to trade it off against another form of immune evasion in order to stay in harmony with the plant.

Friend or foe?

In the second, natural sampling approach, Colaianni et al. demonstrate that immune evasion mechanisms in plant root commensal communities are rampant and are a determining factor of the community's structure. Moreover, this conceptual breakthrough is accompanied by the corroborating findings of complex immune response fine-tuning mechanisms in Arabidopsis. The diversity of the ligand epitopes is translated in a complexity of the immune responses engaged by the plant, which is capable of detecting threshold variations in its microbiome, and thus, discriminating between "friend and foe."

On immune evasion and plant growth promotion

Asked about possible applications of this joint work, GMI group leader Youssef Belkhadir elaborates: "Sometimes, it is good to know how to turn on an immune response, but we often forget that, sometimes, it might also be good to turn it off. For example, you could help a growth-promoting microbe better colonize the plant by providing it with an additional way to evade the plant's immune response. And here we discovered synthetic antagonistic peptides that could do just that."

Back to the (plant) roots

This collaboration draws on an exchange in expertise between the alternating first authors of the two publications, but also refreshes long-dating, outstanding, scientific contacts. In fact, Nicholas Colaianni, Ph.D. student in the Dangl lab at UNC-Chapel Hill, is a computational expert, whereas the main fields of expertise of Katarzyna Parys (former Ph.D. student in the Belkhadir lab) lie in biochemistry and wet lab genetics. Colaianni also visited the Belkhadir lab at GMI and both he and Parys benefited from hands-on training in each other's field of expertise. In addition, as a third co-first author on both publications, Ho-Seok Lee, postdoctoral fellow in the Belkhadir lab, contributed his skills in microscopy imaging.

After many years of separate research, the two main principal investigators who share seniority and alternate corresponding authorships on the two publications, decided to make a comeback together. The shared seniority also includes Corbin Jones, Biology Professor at UNC-Chapel Hill and Colaianni's co-mentor. Youssef Belkhadir is a UNC-Chapel Hill alumnus who worked with Jeffery Dangl as a Ph.D. student. Referring to the UNC Tar Heels basketball team that Dangl loves, Belkhadir says "17 years after I co-authored my first paper with Jeff, it was a lot of fun to get on the court and 'slam-dunk' it with him once more!". Dangl adds "Just like basketball, science is a team effort and the best teams play fluidly together."

An international consortium

GMI and UNC-Chapel Hill share a deep commitment to international collaboration and the present work rallied an international consortium of scientists spearheaded by Youssef Belkhadir, including the University of Geneva and the University of Lausanne in Switzerland, the Max Perutz Labs of the University of Vienna in Austria and the University of Würzburg in Germany. The researchers also acknowledge the contribution of the Vienna Biocenter member institutes and facilities.

A pediatric heart transplant procedure pioneered by Canadian doctors--once deemed impossible--has been shown to be at least as effective as the traditional approach, according to newly published research in The Lancet Child & Adolescent Health.

ABO-incompatible heart transplantation was developed in the mid-1990s, after a Canadian transplant team led by Lori West realized that infants under the age of two have immature immune systems that would allow them to accept life-saving replacements for their defective hearts from donors with incompatible blood types.

"It's really important to see it has not only helped these very sick babies to get transplants faster, but also to live as long, with no more rejections, and better outcomes with regards to infections, as children who received a matched blood group heart," said principal investigator Simon Urschel, associate professor of pediatrics in the University of Alberta's Faculty of Medicine & Dentistry, director of pediatric cardiac transplantation at the Stollery Children's Hospital and member of the Women and Children's Health Research Institute (WCHRI).

ABO-incompatible heart transplantation is now routinely carried out in Canada and some other countries, but not everywhere. That should change thanks to these new study results, Urschel said.

"For example, Eurotransplant (the agency responsible for transplants in eight European countries) still considers it an inferior option to be used with caution," he said. "That concern will probably be relieved in those last places that were reluctant to do it, now that we have shown it is safe."

About 50 per cent of the population is born with type O blood, while 35 per cent has A type and 15 per cent has B or AB type blood. Organs from a donor with type O blood can be accepted by anyone, but adult type O patients can receive only type O organs. The development of ABO-incompatible pediatric heart transplantation meant that twice as many organs would be available to type O infants born with heart defects.

Urschel and his team analyzed data from more than 2,200 infant transplant recipients in Canada, the United Kingdom and the United States from 1999 to 2018. The records were from the Pediatric Heart Transplant Society registry, an international research collaboration that collects data from 58 transplant centres. This resulted in more than 11,000 cumulative patient-years of observation, by far the largest study of its kind.

Three hundred sixty-four of the babies received ABO-incompatible transplants, while 1,842 received ABO-compatible hearts. "We wanted to compare apples with apples, so the children were matched by characteristics such as their underlying disease and the age at which they underwent surgery," Urschel said.

The researchers found the survival rate was the same between the two groups, as were the rates of acute and chronic organ rejection and the risk of developing leukemia after transplant. They also examined the rates of post-transplant bacterial, viral and fungal infections, which they were concerned might be higher among the ABO-incompatible transplant recipients.

"Interestingly, we found that there were fewer of the infections that we were worried about in the ABO-incompatible patients," Urschel said.

Earlier work by Urschel's research team showed that wait times for these patients were significantly shortened, with the average time to transplant being about 50 per cent shorter thanks to the innovative transplant technique.

"It's easier and faster to find a heart for these patients, which is crucial because they are extremely sick, often on mechanical heart support devices or on ventilators in intensive care units," he said. "This gives them a chance not only to survive, but to stay healthier and be in better condition before and after transplantation."

The pioneering pediatric heart surgeons who started it all in 1996--West and Ivan Rebeyka--refined their method after being recruited to join the U of A faculty, with help from other faculty members such as Urschel. Urschel and West's work has received funding from the Stollery Children's Foundation through WCHRI.

The "rule" requiring ABO-compatible donors was instituted for older patients and had never been revisited from the perspective of the immunologic immaturity of infants, said West, now Canada Research Chair (Tier 1) in Cardiac Transplantation, and director of the Alberta Transplant Institute and the Canadian Donation and Transplantation Research Program.

"This, in combination with an extremely high mortality for infants on our transplant waiting list, is why we instituted the first ABO-incompatible transplant protocol," she said.

"Transplantation has always been about pushing the boundaries of risks in order to offer reasonable options to patients who would otherwise have no options."

Urschel will continue his work to understand the mechanism in infant immune systems that allows them to accept blood type-incompatible hearts, in hopes of being able to one day use what is learned to help older transplant recipients. He is also involved in projects to improve the quality of life of young transplant patients and their families.

"It's a real lesson in the need for scientific vigour to guide our operationalization of clinical protocols, not just the blind adoption of previously accepted regulations," said West.

The fact that heart transplant recipients can now survive with a normal lifespan is a credit to both West and Rebeyka, who has a clinical faculty position with the U of A's Cardiovascular Research Centre, said Urschel, who continues to provide clinical care for teenage and young adult patients who received ABO-incompatible transplants as babies.

"It's just amazing to see them, knowing that at one time they were so sick in the intensive care unit that they might not make it to the next day," Urschel said.

How can we better understand how people move during the pandemic and how they spread COVID-19? New George Mason University's College of Health and Human Services research is one of the first individual-level studies to explore this question.

Dr. Janusz Wojtusiak led the study published in the Journal of Healthcare Informatics Research. Wojtusiak and colleagues tracked symptoms and movements of 175 volunteer individuals on George Mason University's campus. They found that there is no evidence that participants altered their movements based on the symptoms they reported.

"We could not detect any significant change of movement when people should self-quarantine. On the other hand some people almost did not leave home since the beginning of the pandemic, while others move freely around," said Wojtusiak.

Participants used the Mason COVID HealthCheckTM to record symptoms of possible COVID-19 infection and GPS and WiFi data to provide information on how they move during the pandemic. This allows the researchers to model and predict movements during the pandemic and in conjunction with any reported possible COVID-19 symptoms.

"By tracking individual movements and symptoms in our study, our findings could help inform effective public health interventions to reduce COVID-19 infections," explains Wojtusiak.

In addition, Wojtusiak and colleagues analyzed de-identified Mason COVID HealthCheckTM responses and found that a headache was the most frequently reported symptom, and a headache was always listed as a symptom when any other symptoms were reported. Other commonly reported symptoms were coughs and sore throats.

Movement patterns varied among participants, with some only going out for essential trips while others moved about more. As a group, movement was consistent over the study period, which included a period when Virginia was under a stay-at-home order and when it was not. Participants traveled a total average of 139 miles per week, visiting an average of less than six locations per week. This low average mileage and number of sites visited does suggest that COVID-19-related restrictions affected their movement. However, they also found that even when participants reported symptoms of COVID-19 or contact with others with COVID-19, they did not change their movements as recommended by public health guidance.

George Mason University has a very low COVID-19 infection rate, and during the period none of the study participants reported COVID-19 infection, so researchers weren't able to link COVID-19 positive tests and movement. Future analysis will include data from the winter of 2020 so may provide more information on movement after COVID-19 infection. The researchers are also conducting surveys and interviews to provide richer data including reasons for complying or not complying with social distancing.

Opioids are the main driver of fatal drug overdoses in the United States, according to the Centers for Disease Control and Prevention, resulting in 46,802 deaths in 2018, usually because the person stops breathing.

Naloxone -- a Food and Drug Administration-approved medication used to reverse overdoses from opioids, such as heroin, morphine and oxycodone -- works by restoring normal respiration to a person whose breathing has slowed or stopped.

"Opioid overdoses cause the largest number of accidental and avoidable deaths," said Peter Davidson, PhD, associate professor in the Department of Medicine at University of California San Diego School of Medicine. "The human toll of drug addiction is devastating. Using naloxone to prevent opiate overdoses can and has saved many lives."

In a study published in the March 23, 2021 online edition of the International Journal of Drug Policy, Davidson and an international group of researchers, found that opioid users who participate in a 12-step abstinence program and recently stopped using drugs refused to take home naloxone, even if having it on hand might save lives.

For the study, trained interviewers visited areas known for high drug use in three Southern California counties: San Diego, Orange and Ventura. Forty-four participants were asked questions about drug use initiation, overdose experiences, both their own and observed and past treatments.

"In our research, individuals who were newly abstinent from opioid use believed that carrying naloxone symbolically tied them to a drug-use identity that they were trying to leave behind," said first author Jeanette Bowles, DrPH, who is now a postdoctoral fellow with the Centre on Drug Policy Evaluation in Toronto, Canada, but was a UC San Diego School of Medicine postdoctoral fellow at the time of the study.

"Twelve-step programs promote abstinence through social behaviors that include staying away from people, places and things considered to be tied to drug use. Naloxone was seen as an item linked to their drug use and clashing with these sober behaviors and their goal of abstinence."

To reduce the stigma associated with naloxone, researchers suggest reframing the meaning of carrying naloxone to represent a commitment to group safety and the wellbeing of those "who still suffer" and relabeling naloxone training programs in substance use disorder treatment settings as "overdose first aid."

In addition, researchers propose focusing on the lifesaving impact those trained to administer naloxone can have on their peers, and re-targeting naloxone distribution efforts to include persons at any phase of their drug use, including abstinence.

"It is very important that people understand that after periods of abstinence, the body is less tolerant if an individual resumes drug use, making them physiologically more vulnerable to overdose and death," said Davidson, co-corresponding author and principal investigator. "If someone is experiencing an opioid overdose, it is important to recognize the signs and respond quickly to prevent death."

In the United States, laws now allow people to access and use naloxone to respond to overdose with protection from liability.

The Addiction Recovery and Treatment Program at UC San Diego Health provides patients with outpatient behavioral treatment for substance use, such as cannabis, alcohol and opioids.