Culture

Metformin is a widely prescribed blood sugar-lowering drug. It is often used as an early therapy (in combination with diet and lifestyle changes) for type 2 diabetes, which afflicts more than 34 million Americans.

Metformin works by lowering glucose production in the liver, reducing blood sugar levels that, in turn, improve the body's response to insulin. But scientists have also noted that metformin possesses anti-inflammatory properties, though the basis for this activity was not known.

In a study published online June 8, 2021 in the journal Immunity, a multi-institution team led by researchers at University of California San Diego School of Medicine identified the molecular mechanism for the anti-inflammatory activity of metformin and, in mouse studies, found that metformin prevents pulmonary or lung inflammation in animals infected with SARS-CoV-2, the virus that causes COVID-19.

Over the past year, several retrospective clinical studies had reported that metformin use by diabetic and obese patients prior to hospital admission for COVID-19 correlated to reduced severity and mortality. Both diabetes and obesity are recognized risk factors for COVID-19, and are linked to more severe outcomes. Notably, other drugs used to control blood sugar levels do not appear to produce a similar effect.

But while these clinical studies suggested metformin's anti-inflammatory activity, rather than lowering of blood glucose, could be responsible for reduced COVID-19 severity and mortality, none of the studies offered an explanation or prompted large, randomized clinical trials needed for obtaining conclusive answers.

"The clinical studies were plagued by confounders that made conclusions hard to reach. There was some skepticism in their findings," said corresponding study author Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology and Ben and Wanda Hildyard Chair for Mitochondrial and Metabolic Diseases at UC San Diego School of Medicine. "And because metformin is an out-of-patent, low-cost drug, there is little impetus to conduct large-scale trials, which are quite expensive."

Karin, with co-senior author Elsa Sanchez-Lopez, PhD, an assistant professor at the Department of Orthopedic Surgery, postdoctoral fellow Hongxu Xian, PhD, and others, turned their focus to a mouse model of acute respiratory distress syndrome (ARDS), a life-threatening condition in which fluids leak into the lungs, making breathing difficult and restricting oxygen supply to essential organs.

ARDS is triggered by trauma and by bacterial or viral infections. It is a frequent cause of death in patients hospitalized with COVID-19. The researchers found that metformin administered to mice prior to or after exposure to bacterial endotoxin, a surrogate for bacterial pneumonia, resulted in the inhibition of ARDS onset and lessening of its symptoms. Metformin also produced a marked reduction in mortality in endotoxin-challenged mice and inhibited IL-1β production and inflammasome assembly within alveolar macrophages -- immune cells found in the lungs.

IL-1β, along with IL-6, are small proteins called cytokines that cause inflammation as an early immune response. Their amounts are often highly elevated in persons infected by SARS-CoV-2, creating "cytokine storms" in which the body starts attacking its own cells and tissues. They are signs of an acute immune response gone awry.

Production of IL-1β depends on a large protein complex called the inflammasome, whose presence in lung tissue is found to be highly increased in deceased COVID-19 patients, a discovery made by co-authors Moshe Arditi, MD, and Timothy R. Crother, PhD, at Cedars-Sinai Medical Center in Los Angeles.

Working with colleagues at The Scripps Research Institute, the UC San Diego researchers confirmed that metformin inhibited inflammasome activation and prevented SARS-CoV-2-induced pulmonary inflammation in mice.

Cell culture studies using macrophages revealed the underlying mechanism by which metformin exerts its anti-inflammatory activity: reduced production of ATP by mitochondria. ATP is the molecule that mitochondria use to store chemical energy for cells. It is essential to all cellular processes, but blunted ATP production in liver cells is responsible for the glucose lowering effect of metformin.

Lower amounts of ATP in macrophages led to inhibition of mitochondrial DNA synthesis, which had been previously identified by Karin's lab as a critical step in NLRP3 inflammasome activation. Subsequent research found that clearing away damaged mitochondria reduced NLRP3 inflammasome activity and reduced inflammation.

UC San Diego researchers also confirmed that specific interference with mitochondrial DNA synthesis in macrophages caused by removal of the enzyme CMPK2 (cytidine monophosphate kinase 2) inhibited IL-1β (but not IL-6) production and prevented ARDS onset.

"These experiments strongly suggest that improved delivery of metformin or CMPK2 inhibitors into lung macrophages can provide new treatments for severe COVID-19 and other forms of ARDS," said Sanchez Lopez.

The authors said the findings suggest metformin may have therapeutic potential for treating a variety of neurodegenerative and cardiovascular diseases in which NLRP3 inflammasome activation is a factor. "Inhibition of inflammasome activation may also account for the poorly explained anti-aging effect of metformin," said Karin.

Married men who don't help out around the house tend to bring home bigger paychecks than husbands who play a bigger role on the domestic chores front.

New research from the University of Notre Dame shows that "disagreeable" men in opposite-sex marriages are less helpful with domestic work, allowing them to devote greater resources to their jobs, which results in higher pay.

In contemporary psychology, "agreeableness" is one of the "Big Five" dimensions used to describe human personality. It generally refers to someone who is warm, sympathetic, kind and cooperative. Disagreeable people do not tend to exhibit these characteristics, and they tend to be more self-interested and competitive.

"Why Disagreeableness (in Married Men) Leads to Earning More: A Theory and Test of Social Exchange at Home" is forthcoming in Personnel Psychology from lead author Brittany Solomon and Cindy Muir (Zapata), management professors at Notre Dame's Mendoza College of Business, along with Matthew Hall, the David A. Potenziani Memorial College Professor of Constitutional Studies and concurrent law professor at Notre Dame, and Elizabeth Campbell from the University of Minnesota.

"Across two studies, we find evidence that disagreeable men tend to earn more money relative to their more agreeable male counterparts because they are more self-interested and less helpful to their wives at home, which allows for greater job involvement and, ultimately, higher pay," Solomon said. "This effect is even stronger among disagreeable men with more traditional gender role attitudes and when their wives are highly conscientious, presumably because in these cases their wives take on more household management and more seamlessly carry out the responsibilities."

The concept may bring to mind the '50s and '60s sitcom "Leave it to Beaver," where Ward Cleaver always arrived home in time for dinner and June Cleaver wore dresses and pearls to clean floors. Did they have advanced understanding of their respective roles?

The study suggests that because these men are able to preserve more time and energy at home, they can invest these resources into their work and earn more. However, the team found that disagreeableness does not predict career success for more egalitarian men, those whose wives are less conscientious or any men outside opposite-sex marriages.

"While disagreeableness in the workplace may lead some employees to success, those hoping to attain higher pay should at least hesitate before leaning into a disagreeable workplace persona," Solomon cautioned. "Indeed, if self-interested and less communal work behavior was the only key to higher pay, then disagreeable men would tend to earn more, regardless of whether they were married, how they viewed gender roles or to whom they were married."

Prior research has shown that disagreeableness predicts financial success (especially for men), and this association is attributed to workplace behavior. However, this effect remains puzzling given that disagreeableness is negatively associated with valued workplace behaviors, such as cooperation and prosocial behavior. In contrast, the team theorizes the male disagreeableness premium can be further understood by considering imbalanced social exchanges at home, specifically with one's spouse. 

"Our findings build on the conventional wisdom that organizations seem to reward disagreeable workplace behaviors and highlight the importance of social exchange at home for success at work," Solomon said. "Our research suggests that organizations acknowledge the role that spousal exchange plays in individual success and points to the potential for organizations to refocus efforts to fuel job involvement on lightening the burden of at-home responsibilities. Doing so could allow employees to preserve resources that could then be invested in their jobs.

"Presumably, this type of initiative would be especially beneficial to those who do not have the persona and gender that, we found, naturally drives individually advantageous spousal exchange -- that is, everyone other than disagreeable, married men," she said. "To help those who do not have the built-in at-home arrangement that enhances job involvement and pay, organizations may consider investing in infrastructure that helps establish more level career-related playing fields."

These may include providing non-work resources, such as lists of reputable providers for home services and maintenance, establishing child care programs, pre-vetting caregivers or having couriers on retainer, which Solomon speculates may enhance job involvement even more than traditional work-focused incentives like bonuses.

"Practices that situate employees more equitably outside of work may offer more employees the opportunity to succeed," Solomon said. "Also, some research shows that men are stigmatized for taking advantage of flex work policies. Changing the organizational culture, in addition to implementing such policies, may influence calculations within a marriage or partnership about whose career should take priority and who should do more at home. Consequently, organizations may also help support initiatives aimed to promote gender diversity and inclusion, especially efforts to reduce male dominance in high-income positions."

The study also carries implications for career self-management. Most notably, the findings may influence how employees view other people's roles in their own success, beyond their boss and other organizational members, and help improve the understanding of how one's choice of romantic partner and social exchange at home can have substantial implications for one's career success.

"Professionals often publicly thank their spouses when receiving achievement awards or earning promotion," Solomon said. "And, at least for disagreeable men, our findings quantify the truth behind this sentiment."

Have you ever been cut off in traffic by another driver, leaving you still seething miles later? Or been interrupted by a colleague in a meeting, and found yourself replaying the event in your head even after you've left work for the day? Minor rude events like this happen frequently, and you may be surprised by the magnitude of the effects they have on our decision-making and functioning. In fact, recent research co-authored by management professor Trevor Foulk at the University of Maryland's Robert H. Smith School of Business suggests that in certain situations, incidental rudeness like this can be deadly.

In "Trapped by A First Hypothesis: How Rudeness Leads to Anchoring" forthcoming in the Journal of Applied Psychology, Foulk and co-authors Binyamin Cooper of Carnegie Mellon University, Christopher R. Giordano and Amir Erez of the University of Florida, Heather Reed of Envision Physician Services, and Kent B. Berg of Thomas Jefferson University Hospital looked at how experiencing rudeness amplifies the "anchoring bias." The anchoring bias is the tendency to get fixated on one piece of information when making a decision (even if that piece of information is irrelevant).

For example, if someone asks, "Do you think the Mississippi River is shorter or longer than 500 miles?," that suggestion of 500 miles can become an anchor that can influence how long you think the Mississippi River is. When it happens, it's difficult to stray very far from that initial suggestion, says Foulk.

The anchoring bias can happen in a lot of different situations, but it's very common in medical diagnoses and negotiations. "If you go into the doctor and say 'I think I'm having a heart attack,' that can become an anchor and the doctor may get fixated on that diagnosis, even if you're just having indigestion," Foulk explains. "If doctors don't move off anchors enough, they'll start treating the wrong thing."

Because anchoring can happen in many scenarios, Foulk and his co-authors wanted to study more about the phenomenon and what factors exacerbate or mitigate it. They have been studying rudeness in the workplace for years and knew from previous studies that when people experience rudeness, it takes up a lot of their psychological resources and narrows their mindset. They suspected this might play a role in the anchoring effect.

To test their theory, the researchers ran a medical simulation with anesthesiology residents. The residents had to diagnose and treat the patient, and right before the simulation started, the participants were given an (incorrect) suggestion about the patient's condition. This suggestion served as the anchor, but then throughout the exercise, the simulator provided feedback that the ailment was not the suggested diagnosis, but instead something else.

In some iterations, before the simulation started, the researchers had one doctor enter the room and act rudely toward another doctor in front of the residents.

"What we find is that when they experienced rudeness prior to the simulation starting, they kept on treating the wrong thing, even in the presence of consistent information that it was actually something else," says Foulk. "They kept treating the anchor, even though they had plenty of reason to understand that the anchor diagnosis was not what the patient was suffering from."

This effect was replicated across a variety of other tasks, including negotiations as well as general knowledge tasks. Across the different studies, the results were consistent - experiencing rudeness makes it more likely that a person will get anchored to the first suggestion they hear.

"Across the four studies, we find that both witnessed and directly-experienced rudeness seemed to have a similar effect," says Foulk. "Basically, what we're observing is a narrowing effect. Rudeness narrows your perspective, and that narrowed perspective makes anchoring more likely."

In general, the anchoring tendency is usually not a big deal, says Foulk. "But when you're in these important, critical decision-making domains - like medical diagnoses or big negotiations - interpersonal interactions really matter a lot. Minor things can stay on top of us in a way that we don't realize."

To provide additional insights into this phenomenon, the researchers also explored ways to counteract it. Rudeness makes you more likely to anchor because it narrows your perspective, so the researchers explored two tasks that have been shown to expand your perspective - perspective-taking and information elaboration.

Perspective-taking helps you expand your perspective by seeing the world from another person's point of view, and information elaboration helps you see the situation from a wider perspective by thinking about it more broadly. Across their studies, the researchers found that both behaviors could counteract the effect of rudeness on anchoring.

While these interventions can help make rudeness less likely to anchor people, Foulk says these should be a last resort. The best remedy for the rudeness problem?

"In important domains, where people are making critical decisions, we really need to rethink the way we treat people," he says. "We never really did allow aggressive behavior at work. But we're fine with rudeness, and now we're learning more and more that small insults are equally impactful on people's performance."

And it needs to stop, he says.

"We tend to underestimate the performance implications of interpersonal treatment. We hear 'If you can't stand the heat, get out of the kitchen.' It's almost like being able to tolerate people's treatment of you is like a badge of honor. But the reality is that this bad treatment is having really deleterious effects on performance in domains that we care about - like medicine. It matters."

This is the fourth paper in a string of Foulk's research showing that rudeness negatively impacts medical performance, where the impacts can be much bigger - and much more dire - than the insults, he says.

"In simulations, we're finding that mortality is increased by rudeness. People could be dying because somebody insulted the surgeon before they started operating."

HOUSTON - (June 10, 2021) - Leaders who encourage their employees to learn on the job and speak up with ideas and suggestions for change have teams that are more effective and resilient in the face of unexpected situations, according to new research from Rice University and the University of Windsor.

"A Resource Model of Team Resilience Capacity and Learning" will appear in a special issue of Group & Organization Management. Authors Kyle Brykman, an assistant professor at the Odette School of Business at the University of Windsor, and Danielle King, an assistant professor of psychological sciences at Rice, studied what makes employees more resilient and fosters learning in the workplace. The researchers specifically examined the interactions of 48 teams from five Canadian technology startups.

"Understanding what organizations can do to help employees become more resilient is the focus our work in my WorKing Resilience Research Laboratory," King said. "This research project offered an opportunity to uncover the important role of leadership and employee voice in the resilience process."

Brykman and King found that teams that were more effective and resilient if their bosses encourage employees to take risks, make suggestions and learn from the process. Creating a work environment centered around learning and open communication is helpful as teams grow and take on new tasks, King said. Leaders must reinforce this workplace culture with positive language that signals openness and a focus on their development, she said.

"Knowing that you have a leader who is focused on learning and not just on performance outcomes is critical," King said. "It's also important for them to be intentional about communicating this regularly to employees, as it can make all the difference in building more resilient teams. Leaders need to verbally reward a learning mindset. For example, when a boss responds to an employee who makes an on-the-job error by saying, 'Great, now you can learn from this experience,' rather than berating them for making a mistake, it makes a big difference."

To request a copy of the study, contact Amy McCaig, senior media relations specialist at Rice, at 713-348-6777 or amym@rice.edu.

DALLAS - June 9, 2021 - A phenomenon in which an RNA named NORAD drives a protein named Pumilio to form liquid droplets in cells, much like oil in water, appears to tightly regulate the activity of Pumilio. A new study led by UT Southwestern scientists suggests that such RNA-driven "phase separation," in turn, protects against genome instability, premature aging, and neurodegenerative diseases, and may represent a previously unrecognized way for RNAs to regulate cellular processes.

"It's becoming more and more clear that phase separation is an important organizing principle in cells," says Joshua Mendell, M.D., Ph.D., professor of molecular biology and a Howard Hughes Medical Institute investigator at UTSW who led the study published online today in Nature.

Other scientists at UTSW, including Michael Rosen, Ph.D., chair of biophysics, a member of the National Academy of Sciences (NAS), and a Howard Hughes Medical Institute investigator, and Steven McKnight, Ph.D., professor of biochemistry and a member of NAS and the National Academy of Medicine, have previously found that phase separation participates in many cellular pathways. "Our work," says Mendell, "builds upon their findings, uncovering how phase separation enables some RNAs to regulate the activity of proteins that they interact with."

Mendell and Mahmoud Elguindy, a student in UTSW's Medical Scientist Training Program, uncovered this role for phase separation by studying an RNA known as "non-coding RNA activated by DNA damage," or NORAD. Although NORAD isn't directly responsible for generating proteins, it binds and inhibits Pumilio, a protein that represses the expression of hundreds of other messenger RNAs that encode proteins involved in cell division.

Previous work from the Mendell lab showed that human cells and lab animals genetically engineered to lack NORAD have too much active Pumilio, which prevents them from maintaining consistent numbers of chromosomes during cell division and causes them to prematurely age. On the flip side, mutations that lead to too little Pumilio have been linked to neurodegenerative diseases in humans.

But a fundamental question remained as to how NORAD regulates Pumilio to prevent disease. Because NORAD is only one RNA of hundreds in the cell that is bound by Pumilio, it was unclear how NORAD is able to outcompete these other RNAs to control levels of active Pumilio.

To answer this question, Mendell and Elguindy used microscopy to locate NORAD-Pumilio complexes in cells. They found that these complexes dotted the cells' interiors, forming their own oil droplet-like structures separate from the cytoplasm, which they named "NORAD-Pumilio bodies."

Further investigation showed that about half the Pumilio in cells was sequestered in NORAD-Pumilio bodies, and that phase separation was critical for concentrating Pumilio in these structures. Not only did Pumilio bind to numerous sites on each NORAD molecule, but interactions between Pumilio molecules also played a central role in droplet formation. This combination of attraction between the RNA and protein molecules provides a strong driving force that separates Pumilio proteins from the surrounding cellular environment, Elguindy says, preventing them from interacting with other RNAs.

When the researchers used techniques to disrupt this phase separation, NORAD was no longer able to sequester enough Pumilio, leading to chromosomal abnormalities.

"While phase separation has been observed in many different settings in cells, the scientific community has debated which cellular activities require this process," says Elguindy. "Our study showed that in this instance, when you perturb phase separation, there are real consequences."

Mendell adds that better understanding the NORAD-Pumilio system could lead to new ways to counter symptoms associated with aging and to treat neurodegenerative diseases. In addition, looking for more examples of phase separation by other RNA molecules could shed light on how cells regulate other key processes.

Young clownfish living closest to shore are dying faster than those further offshore because they are being exposed to artificial lighting, says an international research team.

Working on the reefs around Moorea in French Polynesia, scientists from France, the United Kingdom, Chile and Australia found that nearshore juvenile clownfish living in anemones under lights had higher mortality than juveniles in anemones not exposed to artificial light.

The scientists also found that the surviving clownfish grew 44 per cent more slowly than clownfish under natural lighting conditions.

Professor Stephen Swearer, a marine ecologist, from the University of Melbourne, said the team exposed 42 clownfish in their host anemones to either artificial light at night (ALAN) or natural light in the lagoon.

The clownfish were monitored over nearly two years, individually identified as survivors, and captured to measure their growth.

"The impacts of light pollution found here are probably underestimated and mitigation measures and policy changes are urgently required," said Professor Swearer.

Lead author, Jules Schligler, from the École Pratique des Hautes Études PSL Université Paris (EPHE) and the Centre of Island Research and Environmental Observatory (CRIOBE), said clownfish can live in shallow coastal waters and are highly sedentary living in anemones, which means they can be easily impacted by light at night coming from streetlights, piers or ports.

"As with many other reef fish, clownfish feed, reproduce, defend their territories and interact with other fish during the day and reset whilst sleeping at night. However, 36 per cent of the clownfish exposed to light pollution were more likely to die than fish under natural light cycles," he said.

"Like humans, fish need a period of inactivity, which is crucial for their well-being."

In the research paper "Longterm exposure to artificial light at night in the wild decreases survival and growth of a coral reef fish" published in Royal Society B, the scientists say "even those fish that survived didn't entirely escape the effects of artificial light at night as they grew less than fish from the control group."

"This is the first time that the impacts of ALAN have been tested on a coral reef fish in the wild and over such a long time," said Daphne Cortese, a former EPHE and CRIOBE student, who is now post-doctoral fellow at the University of Glasgow.

"As 12 per cent of all coral reef fish live in close association with another sedentary species, such as a coral or anemone, light pollution could already be having severe negative impacts on a fifth of fringing reef fish populations," she said.

The international team hope the research will help raise awareness of the impacts of ALAN on coastal marine ecosystems.

"Many marine protected areas are impacted by light pollution at night, and authorities are not taking this pollution into account," said Ricardo Beldade, Associate Professor at the Pontificia Universidad Católica de Chile. "We hope that policy makers take this threat much more seriously for future management strategies."

New Curtin research has shown how a readily available, cheap and safe-to-use product found in the medicine cabinet of most homes could be the key to better ecological restoration practices with major benefits for the environment and agriculture.

The study revealed that aspirin, which naturally occurs in the bark of the willow tree and other plants, can improve the survival of grass species important for ecological restoration and sustainable pasture when applied in a seed coating.

Lead researcher Dr Simone Pedrini from the ARC Centre for Mine Site Restoration in Curtin's School of Molecular and Life Sciences, said salicylic acid has been used for its medicinal properties for more than 4000 years and its modern synthetic version, acetylsalicylic acid, or aspirin, is one of the most widely used medications in the world.

"Our research found that aspirin can do more than just ease a headache; it can also help restore degraded land and ecosystems and establish sustainable pastures through improving plant growth and survival," Dr Pedrini said.

"This study was performed on native perennial grasses and showed that applying very low concentrations of salicylic acid to the seed can improve plant survival and therefore its effectiveness in reaching restoration goals.

"Salicylic acid was already known for its ability to improve stress resistance for plants such as tomatoes, making it useful for the agricultural industry, but its effect on native species and potential to aid landscape restoration was still unknown."

Research team member and Director of the ARC Centre for Mine Site Restoration, John Curtin Distinguished Professor Kingsley Dixon said salicylic acid was applied to the seeds of the native grass species using a technology called seed coating, perfected by Curtin University researchers, that allows seed shape and size to be modified, improving seeding efficiency, and can be used to carry growth benefiting compounds.

"This is the first study to deliver aspirin via coating on native species which means the technology can be scaled up for improving restoration targets such as the UN Decade on Ecosystem Restoration to be launched on 5 June 2021," Professor Dixon said.

"Further research is now needed to test salicylic acid as a coating in other wild species to improve native plant resistance to drought, extreme temperatures, salinity, pathogens, and herbicides.

"Moreover, coating with salicylic acid in combination with other beneficial compounds should be tested on a broader array of plant species used in restoration, as their combined impact on seed germination, emergence, growth and plant establishment could improve the successful deployment of native seed onto degraded landscapes, ultimately allowing for a more efficient seed-based restoration."

The full paper, 'Seed encrusting with salicylic acid: a novel approach to improve establishment of grass species in ecological restoration' will be published in PLOS ONE.

Scientists have leapt over the emerging problem of publication bias within genetic research by performing a meta-analysis of publicly available databases of 'transcriptomes', or the full range of messenger RNA molecules produced by an organism. Researchers from Hiroshima University applied the technique to their own field--the study of the genes that are activated when an organism experiences low-oxygen conditions--but it should also be applicable in any other fields that make use of the transcriptome, providing a powerful weapon against the threat posed by publication bias.

The meta-analysis technique was published in a paper appearing in the journal Biomedicines in May 2021.

Scientists are often held up as the pinnacle of objective, disinterested observation and investigation. But in recent years, the danger of what is called publication bias, or sometimes the 'file-drawer problem' is being recognized right across the natural sciences. It describes the bias of researchers and of scientific journals toward the publication of results that support the hypotheses of researchers or otherwise show a significant finding. Both researchers and journals are frequently not very excited about experiments that do not support their hypotheses, and so the findings are left 'in the researcher's file drawer.' There may be no malevolent intention behind such exclusion, but the lack of publication of these 'boring' results does skew, or bias, what exists across the published scientific literature. Ironically, the more well studied the field, the greater the effect of such publication bias.

The Hiroshima University researchers had noticed that there were some 600,000 publications in scientific journals that described around 20,000 human genes that code for the building of a specific protein (as opposed to 'non-coding' genes that perform other functions but do not code for a protein). Across this enormous number of publications, there were a whopping 9,000 articles that discussed the p53 gene, but some 600 genes were not mentioned at all.

Within their own field, they found that this sort of publication bias had led to a great focus on genes that are already well known to be activated during conditions of hypoxia, or low-oxygen conditions.

Under hypoxic conditions, hypoxia-inducible transcription factors, or HIFs, are produced. Transcription factors are proteins that control the rate of transcription (copying a segment of DNA into RNA in order for the RNA to then be translated into a protein). When human cells are deprived of sufficient oxygen, there is a response system governed by the HIFs that attempts to ameliorate the effects of hypoxia by preventing cells from differentiating and by promoting the formation of blood vessels. And HIFs are known to be activated by certain genes.

"But are there other genes that are activated during hypoxia that all researchers have up till now somehow missed due to this publication bias?" asked lead author Hidemasa Bono, professor in the Graduate School of Integrated Sciences for Life at Hiroshima University.

As transcriptome researchers, Bono and his team knew that, unlike with scientific articles in journals, all transcriptome data have to be archived in public databases, not just the interesting transcriptome data.

"So we thought that if we performed a meta-analysis--or an analysis of analyses--on these transcriptome data, we might be able to identify novel hypoxia-inducible genes that had been buried by publication bias," Bono added.

They searched publicly available transcriptome databases to obtain hypoxia-related experimental data, retrieved the metadata, and then manually curated it. They then selected all the genes that are expressed during hypoxic stimulation, and evaluated their relevance in hypoxia by performing gene enrichment analyses. This latter method allows the statistical identification of groups of genes that are over-represented in a large set of genes, and so may be associated with a particular condition.

Alongside this, the researchers performed a bibliometric analysis, a statistical method of analyzing the occurrence of particular words or phrases commonly used in library and information science. The bibliometric analysis in this case was used on the gene2pubmed--a gene literature data source that describes which genes have been discussed where in the scientific literature--to identify genes that have not been well studied in relation to hypoxia. This is a new type of analysis that within biomedical research is called the 'bibliome'.

By combining the transcriptomic meta-analysis and the bibliome, the researchers were indeed able to find four genes that were not previously known to be associated with hypoxia.

The results have encouraged the researchers to keep going with their meta-analysis technique. They plan to keep using public databases to discover similar new findings, in particular to investigate gene activation (expression) of non-coding RNAs, or RNA molecules that are not translated into proteins, during hypoxic stress.

A research collaboration based in Kumamoto University, Japan has revealed the DNA methylation status of gene transcriptional regulatory regions in the frontal lobes of patients with bipolar disorder (BD). The regions with altered DNA methylation status were significantly enriched in genomic regions which were reported to be genetically related to BD. These findings are expected to advance the understanding of the pathogenesis of BD and the development of therapeutic drugs targeting epigenetic conditions.

BD is a mental disorder that affects about 1% of the population and requires long-term treatment. Epidemiological studies have suggested that the onset of the disease is related to a complex interaction of genetic and environmental factors. Epigenetic changes in the genome, particularly in the repression of gene expression through DNA methylation, are thought to be deeply involved in the pathogenesis of various diseases, including mental disorders.

Previous studies analyzed DNA methylation using peripheral blood and saliva samples to identify genes with altered DNA methylation and use them as biomarkers. Since mental disorders are diseases of the nervous system, research using brain tissue is particularly important. However, in addition to the scarcity of samples, brain tissue is a mixture of various cell types, such as neurons and glial cells, and is affected by differences in the ratio of cell types contained in the tissue, making accurate analysis difficult.

The researchers used neuronal nuclear markers to fractionate frontal lobe samples from 34 BD patients and 35 healthy subjects into neuronal and non-neuronal cell nuclei. Genomic DNA extracted from each of these samples was then used to examine the DNA methylation status of the regulatory regions of gene transcription using an array method. They found that many genes in both neurons and non-neurons were hypomethylated in BD patients compared to healthy subjects. On the other hand, genes important for psychiatric and neurological functions were found to be hypermethylated in neurons.

To investigate the effects of mood stabilizers—drugs used to treat BD—the researchers cultured human neuroblastoma cells in the presence of mood stabilizers (lithium, valproate and carbamazepine) in effective blood concentration ranges and measured DNA methylation status. They found that about 30% of the regions with altered DNA methylation status in BD patients overlapped with mood stabilizers-induced DNA methylation changes. Most of the DNA methylation changes were in the opposite direction of those in the postmortem brain, which the researchers thought reflected the effects of the treatment. They also measured the expression levels of 10 genes associated with DNA methylation changes and found that the DNMT3B gene, a DNA methyltransferase, was elevated in BD patients, suggesting that it may be associated with neuron-specific DNA methylation changes.

Finally, the researchers compared the genomic regions associated with mental disorders as identified in genome-wide association studies (GWAS) with regions having an altered DNA methylation status. Significant accumulation was observed in the genomic regions reported in the GWAS for BD, while no accumulation was observed in the genomic regions reported for depression and schizophrenia.

"The clarification of neuron-specific DNA methylation changes and characteristics is expected to greatly advance our understanding of the pathogenesis of bipolar disorder," said Professor Kazuya Iwamoto, who led this study. "We also expect that this will help in the development of therapeutic drugs targeting epigenetic conditions."

This research was posted online in Molecular Psychiatry on 20 April 2021.

RUDN University chemist with his colleagues from Portugal has developed two types of coating based on new coordination polymers with silver. Both compounds were successfully tested against four common pathogens. The results are published in ACS Publications (ACS Appl. Mater. Interfaces).

Due to the rapid mutation, harmful microorganisms constantly adapt to new antibiotics and antiseptics. It is especially difficult to destroy bacteria when they form a biofilm. They stick together and create a community ready to fight antimicrobial agents back. Coordination polymers (scaffolds made of metal ions and organic ligands) can solve this problem. They prevent pathogens from forming biofilms and replicating on the surfaces. RUDN University chemists have created two coordination polymers with silver ions with almost 100% antibacterial activity.

"We developed a synthesis protocol and described the characteristics and structural features of two new silver-based bioactive coordination polymers. We immobilized these compounds acrylated epoxidized soybean oil and created a hybrid material for antimicrobial use", Alexander Kirillov, PhD, an associate of the Joint Institute for Chemical Studies at RUDN.

Coordination polymers consist of cyclic structures. Their central element is an atom or an ion. Scientists used silver nitrate and pyromellitic or trimesic acid to synthetise silver-based polymers. The polymers were obtained by self-assembly, it means that cyclic components themselves interacted to form a pattern which was then added to the substrate made of soybean oil. Chemists have created three types of films with different concentrations of the coordination polymer-0.05%, 0.1% and 0.5%.

RUDN chemists have tested whether the bacteria can form biofilms on surfaces that are coated with new polymers. For the experiment, they used four pathogens that can form biofilms in the human body and cause diseases. Staphylococcus epidermidis causes sepsis, endocarditis, conjunctivitis, Staphylococcus aureus causes purulent inflammatory processes in almost all organs and tissues, Pseudomonas aeruginosa is the agent of nosocomial infections in humans, and the mostly harmless Escherichia coli can sometimes cause severe food poisoning. The new polymers appeared to be active against all four bacteria. The effectiveness of protection depended on the concentration. One of the coatings proved to be more promising -- a film with 0.05% of the active polymer destroyed 99.99% of the bacteria of all four species.

"Our work opens up antibiofilm applications of CP-doped biopolymers, providing new perspectives and very promising results for the design of functional biomaterials", Alexander Kirillov, PhD, an associate of the Joint Institute for Chemical Studies at RUDN.

Tokyo, Japan - Incoming sensory information can affect the brain's structure, which may in turn affect the body's motor output. However, the specifics of this process are not always well understood. In a recent study published in Scientific Reports, researchers from Tokyo Medical and Dental University (TMDU) found that when young rats were fed a diet of either soft or regular food, these different sensory inputs led to differences in muscle control and electrical activity of the jaw when a specific chewing-related brain region was stimulated.

Chewing is mainly controlled by the brainstem, a brain region that controls many automatic activities such as breathing and swallowing. For chewing, the brainstem is also influenced by signaling that comes from higher brain regions, including the cortical masticatory area (CMA), which can be split into the front (anterior) and back (posterior) parts. When the anterior CMA is stimulated, signals travel through the brainstem and reach the jaw muscles, causing chewing to occur. However, it remains unknown whether incoming sensory information affects chewing under the control of the anterior CMA, something researchers at Tokyo Medical and Dental University (TMDU) decided to address.

"In the developing brain, changes in sensory information can greatly affect the brain's structure," says senior author of the study Takashi Ono. "We fed 2-week-old rats either a soft diet or a regular diet, and then investigated a range of different neuromuscular outcomes in response to stimulation of the anterior CMA."

After rats had been fed the soft or regular diet for 3 to 9 weeks, electrodes were used to stimulate the anterior CMA while the rats' jaw movements were measured, along with the electrical activity of the jaw muscles. In response to anterior CMA stimulation, rats in the soft diet group had altered movement and electrical activity in the jaw muscles compared with the regular diet group.

"Our findings suggest that the anterior CMA strongly influences the regulation of chewing, and is affected by sensory inputs during development. As such, reduced chewing function during growth should be corrected as soon as possible to avoid any potential adverse effects on jaw muscle development and chewing ability," says Ono.

Given the importance of chewing for obtaining nutrients, the results of this study could be vital for monitoring and improving chewing ability in young children with chewing difficulties, as well as in adults after trauma or disease. The results of this study suggest that the brain's control of chewing may be influenced by simply increasing chewing difficulty.

Indigenous Māori people may have set eyes on Antarctic waters and perhaps the continent as early as the 7th century, new research published in the peer-reviewed Journal of the Royal Society of New Zealand shows.

Over the last 200 years, narratives about the Antarctic have been of those carried out by predominantly European male explorers.

However, this new study uncovers the story of the deep-rooted connections of Māori (and Polynesian) people with Antarctica dating back as far as the seventh century and continuing into the present day.

"We found connections to Antarctica and its waters have been occurring since the earliest traditional voyaging, and later through participation in European-led voyaging and exploration, contemporary scientific research, fishing, and more for centuries," explains lead author Dr Priscilla Wehi, from Manaaki Whenua Landcare Research the organisation which led the project, alongside researchers from Te R?nanga o Ngāi Tahu.

"Our exploration begins to construct a richer and more inclusive picture of Antarctica's relationship with humanity and builds a platform on which much wider conversations about New Zealand relationships with Antarctica can be furthered."

The study was compiled by a team of researchers who scanned literature and integrated this with oral histories. The outcome is a compiled record of Māori presence in, and perspectives of, Antarctic narratives and exploration, which - the team states - "plays an important role" to fill knowledge gaps about both Māori and Antarctic exploration.

And these stories start as far back as 1,320 years ago.

"We find Polynesian narratives of voyaging between the islands include voyaging into Antarctic waters by Hui Te Rangiora (also known as ?i Te Rangiora) and his crew on the vessel Te Ivi o Atea, likely in the early seventh century," Wehi says.

"These navigational accomplishments are widely acknowledged; and Māori navigators are described as traversing the Pacific much as Western explorers might a lake.

"In some narratives, Hui Te Rangiora and his crew continued south. A long way south. In so doing, they likely set eyes on Antarctic waters and perhaps the continent."

Other evidence gathered includes Māori carvings, which depict both voyagers and navigational and astronomical knowledge.

"As well," Wehi says, "a 'pou whakairo' (translating as carved post), represents Tamarereti as protector of the southern oceans stands on the southernmost tip of the South Island of New Zealand at Bluff. Ngāi Tahu, the largest tribal group in the South Island, and other tribal groups or iwi also cherish other oral repositories of knowledge in relation to these early explorers and voyagers."

These Māori narratives of connections with Antarctic were not limited to these early voyages either. Rather, voyaging and expedition was shown to continue to the present day; "but is rarely acknowledged or highlighted," Wehi says.

And this research, she hopes, will begin more on the path to ensure inclusion of Māori in future relationships with Antarctica.

"Taking account of responsibilities to under-represented groups, and particularly Māori as Treaty partners, is important for both contemporary and future programmes of Antarctic research, as well as for future exploration of New Zealand's obligations within the Antarctic Treaty System."

Concluding, she says: "Growing more Māori Antarctic scientists and incorporating Māori perspectives will add depth to New Zealand's research programmes and ultimately the protection and management of Antarctica."

Further evidence of Māori exploration is likely to enter the public domain in future as tribal researchers partner with iwi to share these narratives, and Māori leadership in Antarctic research grows more visible, including that of the Kāhui Māori in the Antarctic Science Platform.

RUDN University professor and her colleagues from France proved that higher intake of magnesium and vitamin B6 helps to cope with the consequences of magnesium deficiency during pregnancy and in hormone-related conditions in women. Within four weeks, the painful symptoms become less severe, the quality of life improves, and the risks of miscarriage are reduced. The results of the study are published in Scientific Reports.

Magnesium is involved in important processes in the human body -- from protein synthesis to respiration. The most common causes of magnesium imbalance are a lack of this element in the diet, diabetes, and hypertension. The problem of magnesium deficiency is more acute for woman, because magnesium is in higher demand during pregnancy. The lack of magnesium also leads to conditions associated with hormonal disorders -- endometriosis or polycystic ovary syndrome.

"Our study was aimed to assess the effectiveness of magnesium-vitamin B6 intake in achieving normalization of total serum Mg for patients with different starting levels of deficiency. It was also important to determine at what Mg level the painful symptoms are eliminated, and the patients notice changes and quality of life", said Svetlana Orlova, Doctor of Medicine, Head of the Laboratory of Molecular Nutrition of RUDN University.

The study involved 869 pregnant women, with a median age of 28, and 957 women with hormone-related conditions. The median age in this group was higher -- 44 years. The participants were residents of varying size cities in Russia. Laboratory tests showed that they had a lower level of magnesium in the serum (less than the 0.8 mmol per liter). Pregnant women have experienced symptoms associated with the risk of miscarriage, such as high blood pressure and excessive activity of the uterine muscles. Patients in the group with hormone-related conditions, along with the main symptoms were concerned about osteoporosis, premenstrual and menopausal syndromes.

Participants received magnesium and vitamin B6 supplementation in the standard dosage for their gender, age, and weight for four weeks. During this time, for most women (73.8% in the group of pregnant women and 58.9% in the group with hormone-related conditions) Mg level increased to 0.8 mmol / L and higher. In most of the others, it was in the between 0.66 to 0.8 mmol / L, which is considered as a moderate magnesium deficiency. At the same time, the total number of complaints about painful symptoms both during pregnancy and in the group of women with hormone-related conditions decreased by an average of 1.

"Along with the physiological state, we monitored the quality of life of the patients. World Health Organization quality of life questionnaire assessed such aspects as physical health, psychological health, social relationships, and environment. During the study, the scores increased, and the most noticeable effect was among the group of women who reached normal Mg level starting from a moderate deficiency. Thus, we have shown that the consequences of a minor magnesium deficiency can be eliminated by receiving supplementation. For more ssevere deficiency below 0.5 mmol / L, treatment must target the cause of the Mg deficiency", said Svetlana Orlova, Doctor of Medicine, Head of the Laboratory of Molecular Nutrition of RUDN University.

The research team led by Prof. GUO Guangcan from the University of Science and Technology of China (USTC) of the Chinese Academy of Sciences (CAS), together with Prof. Adam Gali from Wigner Research Centre for Physics, realized robust coherent control of solid-state spin qubits using anti-Strokes (AS) excitation, broadening the boundary of quantum information processing and quantum sensing. This study was published in Nature Communications.

Solid-state color center spin qubits play an important role in quantum computing, quantum networks and high-sensitivity quantum sensing. Considered as the basis of quantum technology application, optically detected magnetic resonance (ODMR) technology offers a readout approach to detect the spin state. Conventional ODMR detection of solid-state spin states is almost all under Strokes excitation, which requires that the excitation laser has higher energy than emitted photons.

To extend the scope of solid-state quantum technologies, the researchers first realized the AS excited ODMR detection of silicon vacancy defect spin in silicon carbide (SiC), where the energy of exciting laser is lower than that of the emission photons.

By investigating the dependence of laser power and temperature on AS excited ODMR signals, the researchers proved that the AS photoluminescence (PL) was induced by phonon-assisted single photon absorption process, and was applicable to all-optical high-temperature temperature sensing.

On the basis of this, they found that AS and Strokes excited ODMR followed similar behavior facing the change of laser power, microwave (MW) power and temperature, while the AS ODMR contrast remained approximately three times larger than the Strokes one.

Furthermore, the researchers realized the coherent manipulation of solid-state spin states in SiC under AS excitation. The results showed that the AS excitation method increased the signal contrast by around three times, enabling the potential applications of AS excited ODMR approach to quantum information processing and quantum sensing.

This study improves any ODMR-based measurement. This AS demonstration can be used in yet unforeseen development.

A research team led by Professor Jianping Huang from Lanzhou University has launched a Global Prediction System for COVID-19 pandemic. Their recent work explored the periodicity and mutability in the evolutionary history of the COVID-19 pandemic and investigated the principle mechanisms behind them. They attributed the periodic oscillations of COVID-19 daily cases to seasonal modulations and reporting bias, and identified the unrestricted mass gatherings as the main culprit of the COVID-19 disaster.

Their findings, entitled "The oscillation-outbreaks characteristic of the COVID-19 pandemic", were published in National Science Review.

In this study, the influence of human interventions and environmental influence were isolated based on statistical analysis and model simulations. They have decomposed the time series of COVID-19 daily cases into the oscillations over weekly and seasonal timescales. Weekly oscillations are mainly attributable to reporting bias, while seasonal oscillations are likely caused by variations in the meteorological and environmental factors due to seasonality. The seasonal components indicate higher infectivity and mortality in colder climates for both hemispheres. "Though accurate quantification of the environmental influence on the COVID-19 dynamic remains a challenge, what is certain is that the seasonal oscillations with limited amplitude are not able to reverse the long-term growing trend of the cases," said Prof. Huang. The authors concluded that beneficial climate conditions (e.g. onset of higher temperatures during the warm seasons) should not be used as a criterion to decide on relaxing control measures.

The evolution of COVID-19 cases is also strongly regulated by some rapid growth periods. Model simulations indicate that these abrupt shifts are mainly attributable to changes in the governmental response and public adherence, as well as the unexpected natural and socio-economic crisis. The government response, public adherence, and the unexpected natural and socio-economic crisis would ultimately influence the frequency and size of gathering activities. Higher risk of mass gathering would then give rise to multiple super-spreading events and the subsequent COVID-19 disaster. Prof. Huang further pointed out, "We identify mass gatherings as the main culprit of the COVID-19 disaster. Environmental factors do influence the transmission, but their limited impact is not able to reverse the growth of cases."

Additionally, this work highlights the decisive role of Non-pharmacological interventions (NPIs). "Though vaccination has streamed into the community, we still can't let down our guard." Prof. Huang said, "Before high levels of vaccine-mediated protection can be achieved across the world, NPIs remain the most effective measure to control the epidemic in the foreseeable future."