Culture

Tohoku University scientists have found that human editing enzymes are likely behind a type of mutation in the COVID-19 virus that stimulates the release of pro-inflammatory molecules called cytokines by immune cells in the body. The finding, published in the journal Scientific Reports, is important for understanding how the virus is evolving.

The genetic material of coronaviruses, including the SARS-CoV-2 virus that causes COVID-19 infection, is contained in a single strand of RNA. Coronaviruses have fewer genetic mutations compared to other RNA viruses because they have a kind of RNA-proofreading machinery that protects them. Nevertheless, they still do have some mutations, and scientists would like to understand how they come about and what their effects might be.

Tohoku University immunobiologist Emi Furusawa-Nishii and colleagues investigated the genome sequences of almost 8,000 SARS-CoV-2 viruses from an international database. They specifically looked for 'point mutations', in which a nucleotide base within the virus's RNA is switched to another base.

Their analyses found that virus strains that had evolved from the original one isolated in Wuhan, China had a disproportionate number of cytosine bases that were switched to uracil, in addition to a number of other nucleotide base switches. Further analyses of the nucleotide bases preceding and following these point mutations suggested they were caused by two types of human editing deaminase enzymes, called APOBECs and ADARs.

The scientists then wanted to study the effects of the mutations on macrophages: a type of white blood cell that forms part of the body's first line of defence, or its innate immunity. They tested the production of two pro-inflammatory cytokines, called tumour necrosis factor-alpha and interleukin-6, by human macrophage cell lines. The cells were stimulated with an RNA fragment from Wuhan-type or mutated-type SARS-CoV-2 viruses. Surprisingly, they found that the uracil-rich RNA fragment in the mutated-type SARS-CoV-2 viruses increased the production of the two cytokines.

"Our findings suggest that the point mutations we detected in SARS-CoV-2 viruses were caused by RNA editing as part of the human defence reaction against the infection," says Furusawa-Nishii. "They also show that the virus's evolution is increasing innate immune responses in the host."

The scientists say further studies are needed to determine whether this increased innate immune response helps efficient virus elimination or if it leads to an aggravation of symptoms.

Osaka, Japan -- It's a fact of life that things break down. And when they do, whether it's your car, the roof, or a blocked artery, there are people who we can call to help with the repairs. A lesser known fact of life is that DNA also regularly breaks down and needs to be repaired. Researchers led by Noriyuki Sugo at Osaka University in Japan have been studying natural DNA repairmen in the developing brain. In a new study, they show that an enzyme known as Polβ prevents breaks in the DNA of specific neurons in the brain's hippocampus soon after birth.

Although Polβ was already known to prevent immature cells in the brain from dying by helping to repair DNA in neural stem cells, what it does in mature neurons was unclear. The researchers at Osaka University answered this question by creating mice in which nondividing mature neurons lacked Polβ. They found that these mice had many more breaks in their DNA, specifically in the CA1 and CA3 regions of the hippocampus—a region of the brain critical for learning and memory. The difference in the number of breaks peaked around two weeks after birth and then subsided, indicating that this phenomenon is related to brain development.

Throughout life, gene expression can be modified when certain molecules called methyl groups attach or detach themselves from DNA. During brain development, patterns of DNA methylation and demethylation can affect neurons and how they interact with each other. This in turn can affect future behavior and mental ability. However, this process appears to damage DNA. "We found that double-stranded breaks in the DNA of CA1 hippocampal neurons was related to DNA demethylation," explains Sugo. "When we prevented active demethylation, we no longer saw the increased number of double-stranded breaks, even though Polβ remained absent." On the flip side, purposefully initiating DNA demethylation resulted in more breaks in the DNA, thus confirming the relationship.

The team next focused on what happens to the mice because of all the double-stranded breaks in DNA. Analysis of the affected neurons showed that in addition to altered gene expression, the dendrites—the branch-like parts of neurons that receive input from other neurons—were thinner, shorter, and less complex than those in control mice. Along with these changes in the developing hippocampus, the mice themselves had difficulties forming certain kinds of memories.

"Although our results indicate a role for Polβ in genome maintenance during epigenetic regulation of gene expression during hippocampal development," says Sugo, "it remains unclear why genome maintenance of neurons is needed at this time. We hope to investigate whether this process is related to genome alternations observed in mental illness."

Specialized reflective panels located on top of buildings and deployed widely across a city could significantly improve network coverage, shows a KAUST modeling study.

Next-generation cellular networks (5G and beyond) will provide communication coverage to wider rural areas, while improving data exchange rates to meet rapidly rising demand. In urban areas in particular, obstacles in the form of buildings and other structures can impede wireless communication links, reducing mobile device signals and slowing data exchange.

Research has shown that reconfigurable intelligent surfaces (RISs) hold great promise as a technology for eliminating communication "blind spots" caused by blockages. RISs are specially designed surfaces comprising multiple reflective elements that can modify and redirect incoming signals, allowing for better control and performance over an entire communication network. RISs can be opaque or transparent, and they are well established in terms of their energy efficiency and effectiveness at manipulating signals. An RIS system can use both localization and beam tracking technologies to pinpoint a user's location and to follow their device--even if they are moving in a car at high speed.

"The RIS system and the way it reflects signals has been thoroughly studied in the literature, leading to various useful mathematical models," explains postdoc Mustafa Kishk, who conducted the study with his advisor Mohamed-Slim Alouini. "We used one of these well-established models for RIS behavior in our system setup. Then, using a mathematical tool called stochastic geometry, we created a large-scale system that distributes RISs at random on the faces of buildings. We then analyzed the probable coverage gains under different scenarios."

The results demonstrate that RISs can dramatically improve coverage in areas with blind spots. At a density of 300 blockages per square kilometer, the researchers found that only six RISs would be needed per kilometer to significantly enhance coverage. However, if the blockage density rises to 700 per kilometer, the system becomes inherently far more complex, and an estimated 490 RISs per kilometer would be needed.

"An interesting question still to be answered is whether there is an optimum number of RISs that can be deployed in any one area before they begin to interfere with one another," says Kishk.

"Our model can be used to anticipate the performance of any given large-scale network," adds Alouini. "We believe it will provide accurate, rapid assessments of potential real-world RIS applications. We could see RISs deployed in 6G networks, possibly in a decade."

The action of metformin, the classic drug used to treat diabetes by stabilizing blood sugar, can be blocked by a molecule from the bacteria in our intestines, a University of Gothenburg study shows.

Metformin is the primary treatment option for type 2 diabetes, but there are major variations in how individuals respond to this drug. In some people it lowers blood glucose (sugar) and delays the course of the disease, while in others its effects are less favorable.

An article published in the journal Cell Metabolism now clarifies one underlying factor that explain why metformin action can be blocked. This blocking is preceded by processes in the gut bacteria -- the intestinal microbiota -- in which the molecule imidazole propionate is produced.

The change in gut microbiota associated with type 2 diabetes has been demonstrated in previous research under the leadership of Fredrik Backhed, Professor of Molecular Medicine at Sahlgrenska Academy, University of Gothenburg.

He has also shown that the altered gut microbiota brings about a change in metabolism of the amino acid histidine. This, in turn, leads to an increase in the production of imidazole propionate, a molecule that inhibits the effects of insulin in lowering blood glucose.

The present study shows that, besides blocking the effects of insulin, imidazole propionate also reduces the efficacy of metformin in lowering blood glucose. In type 2 diabetes patients, high imidazole propionate levels proved to be associated with impaired metformin action, and vice versa.

The study also shows that imidazole propionate impairs the glucose-lowering effect of metformin in mice.

"Our study demonstrates clearly that imidazole propionate not only inhibits the effects of insulin but may also reduce the therapeutic action of the metformin," Backhed says.

"Since imidazole propionate has also been linked to inflammation in the gut, and metformin has several side effects in the form of intestinal problems, it's conceivable that imidazole propionate both blocks the treatment effect and contributes to side effects of metformin. But new studies are needed to verify this hypothesis."

How imidazole propionate obstructs the efficacy of metformin in regulating blood glucose has been thoroughly investigated through applied biochemistry and molecular biology. Ara Koh is the first author of the study.

"We found out that imidazole propionate interacts with AMPK, the same molecule as metformin. But instead of activating AMPK, imidazole propionate inhibits metformin-induced AMPK activation," she relates.

By blocking another protein, p38gamma, which is required to enable imidazole propionate to block AMPK (AMP-activated protein kinase), the researchers were able to inhibit the effects of imidazole propionate.

The research group works at the Wallenberg Laboratory for Cardiovascular and Metabolic Research at the University of Gothenburg, and the present study was conducted in collaboration with Sahlgrenska University Hospital.

"The work demonstrates the robustness of the translational research carried out at the Wallenberg Lab. There, observations of patients can be explained in molecular terms, which can give rise to new therapies," Fredrik Backhed concludes.

Naturally occurring compounds in ash leaves could be linked to susceptibility or resistance of individual trees to the fungal disease ash dieback (ADB).

Scientists at the University of Warwick and University of Exeter have identified a group of chemicals present in ash leaves which could be used as biomarkers to look for susceptibility or resistance to ADB.

Identifying resistant trees and breeding from them could help populate the UK with ADB resistant ash.

But, the same chemicals are used by trees to deter herbivorous insects, so selective breeding for ADB resistance could have the unintended consequence of leaving the UK ash population open to attack by invading pests.

Naturally occurring compounds in ash leaves could be linked to susceptibility of individual trees to the fungal disease ash dieback (ADB). But selecting trees with lower levels of these compounds and breeding for resistance could leave the UK ash tree population open to attack from invading insect pests in the future, according to scientists at the University of Warwick.

Secoiridoid glycosides are naturally occurring compounds found in plant leaves. Researchers from Warwick's School of Life Sciences and Department of Chemistry and the School of Biosciences at the University of Exeter looked at the abundance and diversity of secoiridoid glycosides in the leaves of a panel of ash trees known to be resistant and samples from trees known to be susceptible to ADB from both Denmark and the UK.

Previous research had identified five compounds in the secoiridoid glycoside family that were enriched in susceptible Danish trees, but results published today in
Nature Scientific Reports, show UK ash tree leaves produced 27 different individually identifiable chemicals in the group. In the paper entitled Diversity of secoiridoid glycosides in leaves of UK and Danish ash provide new insight for ash dieback management, researchers have identified particular secoiridoid glycoside compounds that could potentially be used as biomarkers for tolerance or susceptibly to ADB.

Lead author, Dr John Sidda, from the School of Life Sciences at Warwick, said: "Ash dieback is an enormous problem for the UK, as ash makes up 5.5% of British woodlands. It is the third most abundant tree species in the UK with numbers exceeding 100 million trees. Ash dieback could be devastating to the British landscape and it is estimated it could cost the UK economy up to £15 billion. Currently there is no treatment for the disease so it is vital we understand all the possible pathways to developing resistance.

"Our work shows that the small molecules in leaves could give a pretty reliable indication of a tree's resistance as well as new insight into possible resistance mechanisms. Work is already underway to validate our results on a much larger panel of UK trees, and to identify other compounds that contribute to ash dieback resistance."

If potential ADB tolerant ash could be identified via a rapid test, they could be selected for breeding to begin repopulating the UK countryside. However, there may be another enemy on the horizon.

The Emerald Ash Borer (EAB) beetle is an insect pest of ash which has devastated the ash tree population in North America. The pest is moving towards Europe and has already been identified in Russia and Ukraine. At the current rate of spread it will reach central Europe in 15-20 years.

Dr Sidda said: "We know that secoiridoid glycosides play a number of roles in plants, and some of these compounds act as a defence mechanism against herbivorous insect pests. In selecting trees with lower levels of these compounds in order to help protect the ash population against ADB, we may run the risk of reducing the UK's ash trees' natural defence against the EAB.

"However, our results indicate that there may be higher concentrations of secoiridoid glycosides in UK ash compared to Danish ash, so UK trees might be better protected against future herbivore threats such as EAB. There is also much more structural diversity of secoiridoid glycosides in the UK and Danish trees than we first thought.

"Researching and understanding these chemical compounds further will help us plan for protecting the UK ash population over the next few decades."

Professor Murray Grant, Elizabeth Creak Chair in Food Security at the University of Warwick and report co-author said: "These results are exciting as they reveal an unexpected diversity in this class of chemical compounds between ADB susceptible and tolerant UK trees, and also between Danish and UK ash. These may act as a potential reservoir of protective compounds that contribute to tree health.

"Our ongoing research is focussed on better understanding the biology of these compounds. We are grateful to funding from UKRI that allows us to expand this study to identify other chemical markers that discriminate tolerant and susceptible trees with the goal of developing a screen for ADB tolerant ash."

Researchers from HEC Montreal and York University published a new paper in the Journal of Marketing that examines how people who attain "prestigious" posts in high-profile organizations can manage their professional brands to promote career mobility.

The study, forthcoming in the Journal of Marketing, is titled "Working It: Managing Professional Brands in Prestigious Posts" and is authored by Marie-Agnès Parmentier and Eileen Fischer.

Job insecurity is pervasive. There are no guarantees of continued employment, even for those who are extremely successful in their field. This research addresses two primary questions: (1) for individuals managing their professional brands, what tensions are triggered while working in a prestigious post? and (2) what practices are conducive to mitigating these tensions and enhancing professional brand equity in a way that promotes career mobility?

The research team analyzed interviews with creative directors who have had one or more prestigious posts at top high fashion heritage brands, including Balenciaga, Chanel, Dior, Gucci, and Saint Laurent Paris. This context is well suited to the research questions given the frequent turnover among creative directors, which has been characterized by the media as akin to a game of musical chairs.

The analysis highlights that working a prestigious post in contexts such as heritage fashion triggers two types of tensions for an individual managing his/her professional brand: resource-related and identity-related. Resource-related tensions arise because prestigious posts both contribute resources and deplete resources critical to an individual's professional brand. Identity-related tensions arise because prestigious posts tend both to enhance a person's professional brand's identity and dilute that identity.

The researchers identified several practices that can mitigate these tensions. One practice that is largely internally oriented consists of "transporting teams" to support the professional brand. This means continuously surrounding oneself with trusted individuals who can help the professional brand perform effectively in a manner that is consistent over time and across organizational settings. A second practice that is both internally and externally oriented is "out-conforming to commercial logics." This means working to exceed expectations related to the commercial logics that are valorized along with artistic logics in fields such as heritage fashion. A third mitigating practice is "selectively neglecting local normative expectations." Of course, professional brands will be contractually obliged to perform in specific ways that reflect the institutionalized expectations of the organizations for which they are working. However, there are likely to be more tacit expectations of which they are aware, but which they choose to neglect in order to protect or promote their professional brand. A final mitigating practice involves "materializing the professional brand in the broader market." This means creating and publicly circulating digital or material artefacts that instantiate the individual's professional brand, but that are not sponsored by the organization that employs the individual.

Unlike prior studies on person branding, this research considers the perspective of professionals who hold prestigious jobs in organizations embedded in highly institutionalized fields. It highlights that external stakeholders' evaluations of an individual's professional brand influence who might offer that individual the next post or provide the resources to establish his/her own enterprise. Parmentier elaborates that "The unique focus of this study leads to surfacing hitherto neglected factors that may fuel, if not disloyalty to an employer, at least some efforts to limit the extent to which the professional brand allows his/her identity to become conflated with that of the organization."

Fischer adds, "The paper sends a clear message to individuals trying to manage their professional brands while holding prestigious posts: strive to strike a balance between benefiting from the affiliation while at the same time maintaining your professional independence." The paper also calls on organizations who employ professionals in prestigious posts to approach the relationship in a way that works to the mutual benefit of the employer and the employee. Organizations may wish to regard their relationships with key personnel who hold prestigious posts as akin to a co-branding alliance where both parties to the alliance benefit from it, even if the alliance is not permanent.

Philadelphia, November 11, 2020 - Sleep is crucial for consolidating our memories, and sleep deprivation has long been known to interfere with learning and memory. Now a new study shows that getting only half a night's sleep - as many medical workers and military personnel often do - hijacks the brain's ability to unlearn fear-related memories. That might put people at greater risk of conditions such as anxiety or posttraumatic stress disorder.

The study appears in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier.

"This study provides us with new insights into how sleep deprivation affects brain function to disrupt fear extinction," said Cameron Carter, MD, Editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.

The researchers, led by Anne Germain, PhD, at the University of Pittsburgh and Edward Pace-Schott, PhD, at Harvard Medical School and Massachusetts General Hospital, studied 150 healthy adults in the sleep laboratory. One third of subjects got normal sleep, one third were sleep restricted, so they slept only the first half the night, and one third were sleep deprived, so they got no sleep at all. In the morning, all the subjects underwent fear conditioning.

"Our team used a three-phase experimental model for the acquisition and overcoming of fearful memories while their brains were scanned using functional magnetic resonance imaging," said Dr. Pace-Schott. In the conditioning paradigm, subjects were presented with three colors, two of which were paired with a mild electric shock. Following this fear conditioning, the subjects underwent fear extinction, in which one of the colors was presented without any shocks to learn that it was now "safe." That evening, subjects were tested for their reactivity to the three colors, a measure of their fear extinction recall, or how well they had "unlearned" the threat.

Brain imaging recorded during the tasks showed activation in brain areas associated with emotional regulation, such as the prefrontal cortex, in people who got normal sleep. But the brain activity looked very different in people with restricted sleep, said Dr. Pace-Schott. "We found that among the three groups, those who had only gotten half a night's sleep showed the most activity in brain regions associated with fear and the least activity in areas associated with control of emotion."

Surprisingly, people who got no sleep lacked the brain activation in fear-related areas during fear conditioning and extinction. During the extinction recall 12 hours later, their brain activity looked more similar to those with normal sleep, suggesting that a limited night of sleep may be worse than none at all.

The researchers hypothesize that sleeping only half the night results in a loss of rapid eye movement (REM) sleep, which has been shown to be important for memory consolidation and usually happens toward the end of a normal sleep period.

Dr. Carter said the study used "noninvasive brain imaging to give us a novel window into how sleep deprivation disrupts the normal fear extinction mechanisms and potentially increases vulnerability to posttraumatic stress symptoms."

"Medical workers and soldiers often have curtailed or interrupted sleep rather than missing an entire night's sleep," Dr. Pace-Schott said. "Our findings suggest that such partially sleep-deprived individuals might be especially vulnerable to fear-related conditions such as posttraumatic stress disorder."

High doses of vitamin C under study for treating COVID-19 may benefit some populations, but investigators exploring its potential in aging say key factors in effectiveness include levels of the natural transporter needed to get the vitamin inside cells.

Age, race, gender, as well as expression levels and genetic variations of those vitamin C transporters that make them less efficient, all may be factors in the effectiveness of vitamin C therapy against COVID-19 and other maladies, investigators at the Medical College of Georgia Center for Healthy Aging report in a commentary in the journal Aging and Disease.

The investigators recommend that those factors be considered in the design and execution of clinical trials, and when trial results are analyzed, for COVID-19 as well as other conditions, says Dr. Sadanand Fulzele, aging researcher and the article's corresponding author.

The novel nature and lack of immunity against the coronavirus has prompted a worldwide pursuit of effective treatments for COVID-19, they write. That includes repurposing drugs with known safety profiles, including Vitamin C, an established immune system booster and antioxidant, which made it a logical choice to explore in COVID-19. Both strategies are needed in response to infection with the novel coronavirus to ensure a strong immune response to stop the virus from replicating in the body, and to avoid the over-the-top, destructive immune response the virus itself can generate if it does.

There are at least 30 clinical trials underway in which vitamin C, alone or in combination with other treatments, is being evaluated against COVID-19, some with doses up to 10 times the recommended 65 to 90 milligrams daily of vitamin C.

Factors like whether or not vitamin C can get inside the cell, likely are an issue in the effectiveness the therapies ultimately show, says Dr. Carlos M. Isales, co-director of the MCG Center for Healthy Aging and chief of the MCG Division of Endocrinology, Diabetes and Metabolism.

In fact, without adequate transporters on a cell's surface to get the water-soluble vitamin past the lipid layer of cell membranes, particularly large doses may enable the vitamin to cluster around the outside of cells where it actually starts producing oxidants, like damaging reactive oxygen species, rather than helping eliminate them, says Isales, a study coauthor.

"We think it's important to look at transporter expression," Fulzele says.

They suspect low transporter expression is a factor in the mixed results from vitamin C's use in a variety of other conditions. Clinical trials in osteoarthritis, for example, an autoimmune disease where a misdirected immune system is attacking the joints, has gotten mixed results, Fulzele says. However its usage in other viral-induced problems, like potentially deadly sepsis, has shown benefit in reducing organ failure and improving lung function in acute respiratory distress syndrome, which is also a major cause of sickness and death with COVID-19.

At the time their Aging and Disease paper was published, there were not yet published studies of the efficacies of high-dose, intravenous vitamin studies underway for COVID-19.

Fulzele, who works on vitamin C in aging, and others have shown that some conditions, like osteoarthritis and even normal aging, are associated with significant downregulation of at least one subtype of vitamin C transporter.

In fact, part of the paradox and concern with COVID-19 is that those most at risk mostly have both lower levels of vitamin C before they get sick and fewer transporters to enable the vitamin to be of benefit if they get more, Fulzele says.

Many of those most at risk from COVID-19, including individuals who are older, Black, male and with chronic medical conditions like osteoarthritis, hypertension and diabetes, tend to have lower levels of vitamin C, another reason vitamin C therapy would be considered a reasonable treatment, Isales says. The investigators also note that patients may develop a vitamin C deficiency over the course of their COVID-19 illness since, during an active infection, vitamin C is consumed at a more rapid rate. Insufficient levels can augment the damage done by an overzealous immune response.

While not routinely done, transporter expression can be measured today using PCR technology, a method also used for novel coronavirus as well as influenza testing. While increasing transporter expression is not yet doable in humans, one of Fulzele's many research goals is to find a drug or other method to directly increase expression, which should improve the health of older individuals as well as those with other medical conditions that compromise those levels.

He notes that reduced transporter levels that occur naturally with age are a factor in the reduced immune function that also typically accompanies aging. That means that even when a 60-year-old and 20-year-old both have a healthy diet in which they consume similar, sufficient amounts of vitamin C, the vitamin is not as effective at boosting the older individual's immune response. Reduced immune function in older individuals is known to put them at increased risk for problems like cancer and COVID-19.

Low vitamin C levels also have been correlated with higher mortality in older individuals from causes like cardiovascular disease. High oxidative stress, a major factor in conditions like cardiovascular disease as well as aging and now COVID-19, also is associated with significantly reduced expression of the vitamin C transporter.

Isales and Fulzele doubt that taking a lot of vitamin C is a good preventive strategy against COVID-19, except in those individuals with a known deficiency.

Vitamin C is an essential vitamin, which means people have to consume it in their food or supplements. Foods naturally high in vitamin C include oranges, potatoes, tomatoes, broccoli and Brussels sprouts. The vitamin's diverse roles in the body also include formation of blood vessels, collagen and cartilage.

WEST LAFAYETTE, Ind. - A new treatment option for lung fibrosis is being developed by Purdue University scientists. Lung fibrosis has been a concern for COVID-19 patients.

People with idiopathic pulmonary fibrosis (IPF) have a life expectancy of less than five years. Fibrotic diseases cause organ failure that lead to about 45% of all deaths in the United States. Existing therapies do little to slow progression.

Now, Philip S. Low, the Purdue Ralph C. Corley Distinguished Professor of Chemistry and Presidential Scholar for Drug Discovery, has led a team to develop two targeted therapies for people with IPF. The two different therapeutic approaches are published in Science Translational Medicine and EMBO Molecular Medicine.

"This is a horrible disease that claimed the lives of my next-door neighbor and a good friend's wife," Low said. "We developed two targeted therapies that allow us to use powerful drugs with high toxicities because we specifically deliver them to diseased cells without harming healthy ones."

The first of the Purdue team's novel targeted molecules is designed to slow fibrosis and extend life. The second IPF therapy suppresses fibrosis-inducing cytokine production.

The two therapies will be moving into human clinical trials within the next several months. The developments come as a number of people with COVID-19 or who have recovered from COVID-19 experience lung fibrosis or other related conditions.

A survey of over 5,000 people in Chinese cities affected by COVID-19 in early 2020 suggests that people who quarantined for a longer period of time generally experienced poorer well-being--but that experiencing the mental state of flow reduced or eliminated that link. Kate Sweeny and colleagues at the University of California, Riverside, U.S., Central China Normal University, China and Nanjing University, China and colleagues present these findings in the open-access journal PLOS ONE on November 11, 2020.

A person experiences flow when they become so absorbed in an enjoyable activity that they lose track of their external surroundings. Previous studies have found that flow is associated with greater well-being in a variety of stressful settings.

Sweeny and colleagues hypothesized that flow could be associated with greater well-being for people who experienced the stressful uncertainty of the rise of COVID-19 in China in early 2020. They also hypothesized that greater well-being might be associated with mindfulness, in which a person is also absorbed in the present moment, but in contrast to flow, they maintain awareness of their external surroundings.

In February 2020, the researchers tested these hypotheses by conducting an online survey of 5,115 people in Wuhan and other large cities in China that were affected by COVID-19. The survey evaluated self-reported levels of flow, mindfulness, and well-being.

Statistical analysis of the survey data showed that both flow and mindfulness were linked to better well-being of several types, such as less loneliness and more positive emotion. Additionally, people who experienced a longer period of quarantine reported poorer well-being of several types. However, the link between longer quarantine and poorer well-being was significantly weaker or disappeared entirely for people who experienced high levels of flow--but not mindfulness.

The study could not test the causal relationship between flow and well-being, though future research could investigate whether engaging in activities that induce flow directly helps to ease the negative impact of quarantining. Research could also explore which flow-inducing activities are most effective for which people.

The authors add: "In a sample collected via social media in February 2020 in China, experiencing flow and mindfulness was associated with better well-being. More interestingly, whether people were in quarantine was irrelevant for well-being among people who experienced a lot of flow in the previous week, but the same was not true for mindfulness."

The environment provided by the mother during embryo development has major consequences on later-life health and lifespan. This can arise through effects on cellular ageing which is often estimated with the length of telomeres. Telomeres are the protective end caps of chromosomes and their length is a marker of 'biological age'.

While telomeres normally shorten with age, short telomeres at a given age predict higher disease and mortality risks. Prenatal exposure to maternal stress hormones as well as instability during embryo development have previously been found to result in short telomeres, i.e. accelerated cellular ageing.

A new study funded by the Academy of Finland and the Turku Collegium for Science and Medicine manipulated prenatal exposure to maternal thyroid hormones using egg injection in an avian model.

"The telomere biology of humans is closer to the telomere biology of birds than those of traditional laboratory models. In both human and birds, telomere length is measured in a minimally-invasive way from small blood samples," says Collegium Researcher Antoine Stier from the University of Turku (Finland), the main author of the research article.

While authors of the study had reasons to expect shorter telomeres in chicks born from eggs injected with thyroid hormones, they were quite surprised to find that those chicks actually exhibited longer telomeres right after birth.

"Based on the natural decline of telomere length observed with age in the same collared flycatcher population, we estimated that chicks hatching from thyroid hormones injected eggs were approximately 4 years 'younger at birth' than chicks hatched from control eggs," adds Collegium Researcher Suvi Ruuskanen.

Although the molecular mechanisms underlying such effects remain to be discovered, the new findings suggest that prenatal thyroid hormones might have a role in setting the 'biological age' at birth.

"Considering the interest and controversies surrounding gene therapy trials in humans to elongate telomeres as an anti-ageing therapy, this discovery opens potential avenues to better understand the influence of telomere elongation in animal models," Stier says.

The study was conducted on a long-term monitored population of wild collared flycatcher breeding in Gotland island, and relied on extensive collaborations with the University of Uppsala (Sweden), Lyon, Glasgow and Aberdeen.

UNIVERSITY PARK, Pa. -- Gold foil, ornate labels and an intriguing backstory are product characteristics highly desired by premium chocolate consumers, according to research conducted by food scientists in Penn State's College of Agricultural Sciences.

The study is one of the first to thoroughly research what American premium chocolate consumers find to be desirable attributes in their chocolate bars. An additional focus was on these consumers' perceptions of craft chocolate, which is made from scratch -- bean to bar -- by small companies using fine flavor cocoa beans.

Much like craft beer and specialty coffee, craft chocolate is gaining popularity among consumers who are seeking a unique experience, noted lead researcher Allison Brown, food science doctoral candidate in the college's International Agriculture and Development dual-title degree program.

She added that study outcomes, which were published in the journal PLOS ONE, will aid craft chocolate companies when making decisions about product development and marketing.

"The U.S. craft chocolate market is estimated to be worth $100 million and growing," Brown said. "However, many companies are small startups with few employees. They do not have marketing teams to guide their brand strategies. Our findings will help them make decisions that could have a large impact on their businesses."

Brown -- joined by Helene Hopfer, assistant professor of food science, and Alyssa Bakke, sensory scientist in the Sensory Evaluation Center at Penn State -- conducted the mixed-method study, which involved a "projective mapping" activity and focus groups.

Projective mapping, Brown explained, is a technique in which consumers group products on a sheet of paper based upon similarities and differences in the products. They also may add words to explain their groupings.

For this study, participants mapped 47 different chocolate product stickers on a piece of paper and brought these maps to the focus groups, where they discussed their reasons for putting the chocolates into categories they named "artisan," "Halloween candy" or "special occasion," among others.

In the second half of the focus groups, participants tasted five chocolate bars in three categories: mainstream (Hershey's Milk Chocolate Bar), premium (a Lindt Cocoa Dark Chocolate Bar, a Green and Black's Organic Dark Chocolate Bar, and an Endangered Species Dark Chocolate with Sea Salt and Almonds); and craft (Dandelion Chocolate 70% Ambanja, Madagascar).

They gave their opinions on flavor, packaging, sustainability labels and other aspects that they found to be appealing and unappealing. These discussions were coded to determine themes, which fell into three main categories of attributes: search, reflected by segmentation, price, availability and packaging; credence, or the degree to which the consumer trusted the product; and experience, such as feeling joy when consuming the chocolate or the use of chocolate as a gift.

Overall, participants responded favorably to every sample because, as Brown pointed out, "It's hard to make chocolate undesirable." However, they focused more on extrinsic cues, such as packaging, rather than intrinsic cues, such as flavor, to judge product quality.

For example, almost all consumers found the craft chocolate sample to be novel and exciting, likening it to coffee and wine in terms of flavor and packaging elements. They were wowed by the product's intricate label design and thick gold foil, with one consumer saying it was "like getting a golden ticket from Willy Wonka."

Consumers also associated high-quality chocolate with the presence of the percentage of cocoa on the label and additional ingredients such as sea salt, almonds or fruit.

Products with higher price tags -- and those available only at specialty stores or online -- also were deemed to be top notch. "These are more sophisticated, so my brain just thinks they must taste better, so they must be high quality," said a participant. "Also, they're more expensive."

Sustainability labels, such as "Organic" and "Fair Trade," piqued some participants' interest, while others distrusted their presence on the chocolate bar. These attitudes were reflected in participants' willingness to pay for products with certifications -- some participants indicated they would spend more for these products, while others would not pay more for chocolate with sustainability labels.

Meaning was another selling point, with the consumers placing a higher value on chocolate bars made by companies that had an interesting backstory, supported a cause or featured a person's name. For example, the Endangered Species bar was a hit because its label indicates that proceeds support wildlife conservation. "Participants viewed it as a guilt-free indulgence," Brown said.

Consumers cited positive childhood experiences as the origin of many of the attributes they look for in chocolate products. Chocolate flavors or packaging reminiscent of holidays, campfires or gift giving were highly sought after.

The findings clearly outline how craft chocolates are perceived differently from premium and mainstream chocolates, noted Hopfer.

"Consumers picked up on the exclusive and specialty nature of these products," she said. "The findings highlight the importance of a story behind the product and show that consumers derive a purpose and joy from chocolate. We also determined the importance of availability, price and packaging as proxies for perceived chocolate quality."

Liberalism and conservatism are associated with qualitatively different psychological concerns, notably those linked to morality, shows a new study that explores how political ideology and moral values are connected to motivated social cognition. The findings, which appear in the journal PLOS ONE, offer deeper psychological insights into the nature of political division in the United States.

"Psychological research on the different motives underlying support for liberal versus conservative leaders and agendas, such as those separating Biden and Trump supporters, can help to explain why, for instance, one group is much more focused on promoting equality and social justice than the other," explains John Jost, a professor of psychology, politics, and data science at New York University and the study's senior author.

The work centered on the concept of "moral foundations" and its connection to political ideology. In this, and similar research, social scientists have sought to determine how important matters such as "whether or not someone conformed to the traditions of society" or "whether or not someone cared for someone weak or vulnerable" are to morality.

Previously, some have argued that liberals have an impoverished sense of morality, emphasizing only issues of fairness and harm avoidance, which they see as individualistic, whereas conservatives have a broader "moral palette" that values ingroup loyalty, obedience to authority, and the enforcement of purity sanctions, which they view as "binding foundations."

In the PLOS ONE article, however, the researchers found something important that previous studies have failed to consider.

Specifically, the studies by Jost and his colleagues, including Michael Strupp-Levitsky, who conducted the work as an NYU undergraduate and is now a doctoral candidate at Long Island University-Brooklyn, showed that those moral foundations known to be more appealing to liberals than conservatives--specifically, fairness and harm avoidance--are linked to empathic motivation, whereas the moral foundations that are more appealing to conservatives than to liberals --such as ingroup loyalty and deference to authority--are not.

In fact, the "binding foundations" cited by previous studies as evidence of a broad "moral palette" are associated with authoritarianism, social dominance, and economic system justification--matters quite apart from morality. Moreover, they are also associated with psychological motives to reduce uncertainty and threat, consistent with a theory of political ideology as motivated social cognition that Jost and other collaborators proposed in 2003.

"All of this may help to explain why the endorsement of 'binding foundations' is associated with prejudice, outgroup hostility, and other antisocial outcomes, whereas the endorsement of 'individualizing foundations' is negatively associated with prejudice, outgroup hostility, and other antisocial outcomes," explains Jost.

To explore these matters in the PLOS ONE work, the researchers conducted two studies.

They asked American participants a series of questions that sought to capture different motivations (e.g., "I have an intense fear of death" and "I only think as hard as I have to"), empathies (e.g., "After being with a friend who is sad about something, I usually feel sad"), and moral intuitions (e.g., "Respect for authority is something all children need to learn") as well as beliefs about system justification (i.e., the legitimacy of the existing social, economic, and political order) and political orientation (e.g., conservative, liberal) on social and economic issues. Here, the researchers sought to illuminate the relationship between political ideology and motivated social cognition.

Their results showed that liberalism and conservatism were indeed associated with qualitatively different psychological concerns, as suggested in previous research.

The motivational basis of conservative preferences for "binding" intuitions has for years been assumed to be independent of needs to reduce uncertainty and threat and to represent a broad, prosocial sense of morality. However, the new findings in PLOS ONE indicate that the endorsement of "binding foundations" is linked to the very same motives associated with many other conservative preferences, including authoritarianism, social dominance, system justification, and underlying psychological needs to reduce uncertainty and threat.

Scientists have compiled the first comprehensive review of plant natural products that play a role in antibacterial activity, to serve as a guide in the search for new drugs to combat antibiotic-resistant pathogens.

Chemical Reviews published the work by researchers at Emory University, which includes 459 plant natural products that met rigorous criteria for demonstrating antibacterial activity. The review is also deposited on the Shared Platform for Antibiotic Research and Knowledge (SPARK), sponsored by Pew Charitable Trusts.

"We hope that chemists and pharmacology researchers will use our review as a guide to dig deeper into the promising potential of many plant compounds," says Cassandra Quave, senior author of the review and associate professor in Emory's Center for the Study of Human Health and Emory School of Medicine's Department of Dermatology. Quave is also a member of the Emory Antibiotic Resistance Center.

In the United States, at least 2.8 million people get antibiotic-resistant infections each year and more than 35,000 people die from them, according to the Centers for Disease Control and Prevention.

"If ever there was a time to cultivate our knowledge and tap into the chemical power of plants, this is it," Quave says. "We're seeing a rise in antimicrobial resistance across the globe. And, at the same time, we're also losing vast amounts of plant biodiversity."

Two in five plants are currently estimated to be threatened with extinction, according to the State of the World's Plants and Fungi Report, published in 2020 by the Royal Botanic Gardens, Kew.

Quave is a leader in the field of medical ethnobotany, studying how Indigenous people incorporate plants in healing practices to uncover promising candidates for new drugs. The Quave lab has identified compounds from plants such as the Brazilian peppertree, the American beautyberry and the European chestnut that inhibit dangerous antibiotic-resistant bacteria.

Her lab found, for instance, that triterpenoid acids from the Brazilian peppertree "disarm" methicillin-resistant Staphylococcus aureus, known as MRSA, by blocking its ability to produce toxins.

The first antibiotic, penicillin, was derived from microbes in mold that kill bacteria. Since then, scientists have found other microorganisms that live in soil that are easy to grow in a laboratory setting and can kill pathogens resistant to some drugs. The ability of bacteria to continue to evolve resistance, however, is outpacing the ability to generate effective drugs from these sources.

"One obstacle to plant natural products making it into the new drug pipeline is the complexity of the discovery process," Quave says. "You have to identify a promising plant candidate, tease through the hundreds of chemicals contained within a particular plant to identify the active compound, and then isolate enough of this compound to do experiments on it. It's not nearly as easy as sequencing a soil microbe and growing up a big vat of it to conduct experiments."

Tapping the knowledge of traditional people who have used plants for centuries to treat infections offers valuable clues for where to focus research, she adds.

"In recent decades, interest has grown in investigating plants as potential drug candidates," Quave says. "Technologies have improved to more easily access and study bioactive molecules within plants. And more papers are being published that follow standardized procedures for evaluation of antimicrobial activities among plant compounds."

For the current review, the Quave lab looked at nearly 200 papers published between 2012 and 2019 that met strict standardization criteria for authenticating plant-derived compounds that significantly inhibited antibacterial activity. The co-authors spanned undergraduates who conducted the initial literature reviews to graduate students and scientists specialized in biology, chemistry, pharmacology and/or botany.

The 459 compounds included in the review encompass a diverse range of species -- including those from commonly known plant families such as citrus, daisies, beans and mint. The compounds fall into three major classes of chemicals: About half are phenolic derivatives, around 25 percent are terpenoids, nearly 6 percent are alkaloids and the remainder are classified as other metabolites.

The review authors selected 183 of the compounds and provided further discussion of their antibacterial activity, biosynthesis, chemical structure, mechanism of action and their potential as antibiotics.

"These are all compounds as they appear in nature, not synthesized or derivatized by chemists," Quave explains. "We wanted to provide a systematic overview that brings promising drug candidates to the forefront, opening up new chemical space for discovery. Our review can serve as a starting point for chemists to consider whether they could possibly optimize any of these compounds to become scaffolds for antibiotics treatments."

During the COVID-19 pandemic, many people have become accustomed to wearing cotton face masks in public places. However, viruses and bacteria that stick to the mask could be transferred elsewhere when the wearer removes or touches it. Now, researchers reporting in ACS Applied Materials & Interfaces have developed a special type of cotton face mask that kills up to 99.9999% of bacteria and viruses within 60 minutes of daylight exposure.

Face masks made of various cloth materials can filter nanoscale aerosol particles -- such as those released by a cough or sneeze -- potentially helping to reduce the spread of diseases, including COVID-19. But live bacteria and viruses on the surface of the mask could still be contagious. Peixin Tang, Gang Sun, Nitin Nitin and colleagues wanted to develop a new cotton fabric that would release reactive oxygen species (ROS) when exposed to daylight, killing microbes attached to the fabric's surfaces while being washable, reusable and safe for the wearer. Then, a person could disinfect their cloth mask during their lunch hour outside in the sun, or by spending a longer period of time under office or building lights, which are much less intense than sunlight.

The researchers made their antimicrobial fabrics by attaching positively charged chains of 2-diethylaminoethyl chloride (DEAE-Cl) to ordinary cotton. Then, they dyed the modified cotton in a solution of a negatively charged photosensitizer (a compound that releases ROS upon exposure to light), which attached to the DEAE chains by strong electrostatic interactions. The team found that a fabric made with a dye called rose Bengal as the photosensitizer killed 99.9999% of bacteria added to the fabric within 60 minutes of daylight exposure and inactivated 99.9999% of T7 bacteriophage -- a virus thought to be more resistant to ROS than some coronaviruses -- within 30 minutes. Further testing showed that the material could be handwashed at least 10 times and constantly exposed to daylight for at least 7 days without losing its antimicrobial activity. The fabric shows promise for making reusable, antibacterial/antiviral cloth face masks and protective suits, the researchers say.