Culture

Washington and Chicago, January 28, 2021--The American Educational Research Association (AERA) and the Spencer Foundation have released a report, Voices from the Field: The Impact of COVID-19 on Early Career Scholars and Doctoral Students, that shares findings from focus groups conducted in spring 2020. The report, available on the AERA and Spencer websites, is part of an ongoing initiative by the two organizations to assess the pressing needs facing scholars and doctoral students during the pandemic and ways to address these needs.

"The realities of the COVID-19 pandemic and the ensuing impact on social institutions like school, work, and the family have created challenging conditions that are taking their toll on research and academic careers," said AERA Executive Director Felice J. Levine, who served as co-principal investigator of the study. "Such conditions also exacerbate the inequities that can have lasting effects on future generations of education researchers and the production of education research."

"It is critical to learn from those with the most at stake in order to identify and provide opportunities for institutions and leaders to support this generation of researchers who will have gone through an experience unprecedented in recent time," said Spencer Foundation President and AERA President-elect Na'ilah Suad Nasir, study co-principal investigator. "While the findings and recommendations we present in the report are suggestive, and not conclusive, they provide important lessons."

Findings from the focus groups centered on seven themes: (1) Research Impact: Disruptions, Delays, and Adaptations; (2) Impact on Teaching: The Need to Be Inventive, Inclusive, and Intentional; (3) Balancing Acts: Negotiating Family, Home, Community, and Professional Life; (4) The Emergence of a Dual Pandemic and Confronting Racism; (5) Employment Trajectories, Uncertainties, and Deferments; (6) Institutional (In)Capacity to Respond and Support; and (7) Emerging and Lost Connections, Communities, and Communication.

For each theme, the report presents findings drawing upon the voices of focus group participants. The report concludes with recommendations to institutions and the field that can address the circumstances faced by early career scholars and doctoral students as a consequence of COVID-19 and more broadly encourage changes that can lead to more equitable and enriching places for them to work and thrive.

Along with Levine and Nasir, study authors included Cecilia Rios-Aguilar (University of California, Los Angeles), Ryan E. Gildersleeve (University of Denver), Katherine J. Rosich (AERA), Megan Bang (Spencer Foundation, Northwestern University), Nathan E. Bell (AERA), and Matthew Holsapple (iMentor).

AERA and Spencer plan to release a second report later in 2021 that focuses on findings from a major national survey on the experiences and concerns of early career scholars and doctoral students in education research. The two organizations will hold a forum on this work at the AERA 2021 Virtual Annual Meeting, which will be held April 8-12.

After analyzing the genomes of more than one-quarter of a million military veterans, a team of scientists, led by researchers at University of California San Diego, Veterans Affairs San Diego Healthcare System (VASDHS), Yale University and West Haven VA, have identified 18 specific, fixed positions on chromosomes (known as loci) that appear associated with post-traumatic stress disorder (PTSD).

The findings validate the underlying biology of PTSD, its relationship to comorbid anxiety and depressive disorders and provide potential new targets for treatment, write the authors in the January 28, 2021 online issue of Nature Genetics.

"We're very intrigued by the findings of this study, for example, as they pertain to the genetic relationships between different kinds of PTSD symptoms," said co-principal investigator Murray Stein, MD, MPH, Distinguished Professor of Psychiatry and Family Medicine and Public Health at UC San Diego School of Medicine and a psychiatrist at VASDHS. "It also shows the huge value of the Million Veteran Program in facilitating research important to the care of our military veterans."

The research team conducted genome-wide association studies (GWAS) of more than 250,000 persons of European and African ancestry participating in the Million Veteran Program. GWAS involve rapidly scanning markers across complete sets of DNA, or genomes, of many people to find genetic variations associated with a particular disease. Launched in 2011, the Million Veteran Program is a U.S. Veteran Affairs-sponsored research effort to learn how genes, lifestyle and military exposures affect health and illness. More than 825,000 U.S. veterans have joined.

The scientists surveyed veterans' electronic health records for diagnosed cases of PTSD and for quantitative symptoms, such as recurrent intrusive memories of traumatic events, severe emotional distress or physical reactions to reminders of traumatic events, self-destructive behaviors and difficulty sleeping.

PTSD is a serious mental disorder that can occur after exposure to extreme, life-threatening stress. It's estimated that half to more than three-quarters of Americans experience traumatic events over a lifetime, but most do not develop PTSD. Lifetime prevalence for PTSD is approximately 7 percent (but much higher among veterans), which suggests people have varying degrees of resilience to stress and vulnerability to the disorder.

Susceptibility to PTSD has long been known to be heritable. Like other mental disorders, it is an extremely complex phenotype, or set of observable characteristics, that is influenced by multiple genes. Indeed, current diagnostic guidelines permit up to 163,120 unique conformations of symptoms for the disorder.

The study directly compared the heritability of diagnostic PTSD cases with continuous, symptom-based phenotypes of PTSD. Though symptoms of PTSD are extremely diverse, their genetic overlap is high -- an important insight into the disorder's underlying biology.

The researchers identified multiple genes that were repeatedly implicated in different PTSD phenotypes, indicating both that the genes were key players in development of the disorder and that they might be suitable targets for therapeutic drugs.

"These findings give us new insights into the biological basis of PTSD," said co-principal investigator Joel Gelernter, MD, professor of psychiatry, genetics and neuroscience at Yale School of Medicine and VA Connecticut Healthcare System, "and point to some possible next steps for testing new treatments."

HOUSTON - (Jan. 28, 2021) - Like a wrench that gums up the gears, a common anesthetic keeps the motor proteins in your cells from making their rounds.

This is not necessarily a bad thing, but how it works has been a mystery until now.

Researchers at Rice's Center for Theoretical Biological Physics (CTBP) detail the mechanism that allows propofol -- the general anesthetic injected to knock you out before surgery -- to halt the movement of kinesin proteins that deliver cargoes along microtubules to the far reaches of cells.

The drug's effect on kinesin was known, said Rice physicist and CTBP co-director José Onuchic, but the mechanism was not. Computational simulations of the protein in the presence of propofol clearly show where it binds to kinesin and how that disrupts kinesin's function.

"A lot of things in the cell are regulated by microtubules and motor proteins, including mitosis and the trafficking of organelles and vesicles, so any insight into how they work is important," said Onuchic, who led the study with former Rice postdoctoral researcher Biman Jana, now an associate professor of chemical sciences at the Indian Association for the Cultivation of Science, Jadavpur, and Susan Gilbert, a professor of biological sciences at Rensselaer Polytechnic Institute.

Understanding the mechanism suggests those same binding pockets could be used in other therapies, Jana suggested. "This study opens up immense possibilities for therapeutics in kinesin motor protein-related disease," he said.

"As we now know with better confidence about the important regions of kinesin, we can look for more small-molecule binders in those regions," Jana said. "It will help to discover better anesthetic agents and also treat several diseases related to kinesin."

The research appears in the Proceedings of the National Academy of Sciences.

Researchers know propofol affects many proteins in the body as it induces anesthesia, and they suspect kinesin inhibition may contribute to the anesthetic's effects on memory and consciousness.

Kinesins were first observed in squid in 1985, but now there are 45 known kinesins in humans, 38 of them in the brain and as many as 20 that regulate transport in cells.
These literally take about 100 steps along the microtubules. Their protein heads (which function as feet) are powered by the chemical energy from ATP that, when it binds to the leading head, powers the trailing head forward. As the trailing head advances, it becomes the leading head, releases ADP and grabs the microtubule.

When both heads are on the microtubule, a normal stage in the walking cycle, it is important that ATP does not remain bound to the leading head, Onuchic said. If this happens, ATP can be hydrolyzed in both heads, prompting the kinesin to be released from the microtubule, stopping its motion. Propofol binding shortens this "run length" by up to 60%.

"Like us, they always have to have at least one foot on the ground," Onuchic said. "When both heads unbind, that disrupts the process."

The simulations showed propofol molecules interfere by binding to the leading head in one of two places, either near the neck linker that regulates communication between the walking heads or to a site near where it binds to the microtubule. This weakens its grip and the strain on the neck linker, prompting the leading head to bind ATP while both heads are bound to the microtubule. ATP bound to both heads may cause hydrolysis of both, followed by the kinesin's release.

The researchers found in their simulations that propofol had no direct effect on kinesin's normal operation upon binding to the trailing head. They also traded the model of propofol to fropofol, a derivative molecule with a fluoride in place of a hydroxyl group, and found it did not affect kinesin function, suggesting the significance of the hydrogen bond in propofol.

"From our previous experience in working with kinesin related to neurodegenerative diseases, we knew about the important regions and interactions of kinesin for its reliable functionality," Jana said. "However, finding propofol binding pockets in exactly the same regions was a pleasant surprise as it strengthened our propositions."

WACO, Texas (Jan. 28, 2021) - An organization that projects an ethical face but whose managers fail to respond to internal ethical situations sends mixed messages to its employees, which can lead to a lack of employees' moral courage and an increase in unethical behavior, according to a study led by a Baylor University researcher.

The study, "Management Without Morals: Construct Development and Initial Testing of Amoral Management," is published in the journal Human Relations. The research comprises three survey-based studies of 1,034 full- and part-time workers to answer the question of, "What happens when leaders do not respond to the ethical components of business situations?".

"I believe the key surprise finding is that in an ethical environment - or one that is thought to be ethical - amoral management is even more problematic for employees," said the study's lead researcher Matthew J. Quade, Ph.D., associate professor of management in Baylor University's Hankamer School of Business. "The amoral manager's lack of an ethical message is particularly ambiguous in an environment that is otherwise offering clear messages about ethical expectations for organizational members."

The study was split into sample groups in which the participants took surveys indicating their assessment of amoral management in their workplace. Study results revealed that "amoral management had a significant effect when ethical environment was high but had a weaker effect on moral courage when ethical environment was low."

"Despite being problematic, amoral management is believed to be quite common in organizations," Quade said. "The ill effects of amoral managers are made even worse when they operate in organizations that are thought to be ethical from the perspective of employees."

Defining Amoral Management

Although an amoral manager can be unethical, Quade said the researchers define an "amoral manager" as different from an "unethical manager."

"Amoral management - which is when a leader consistently does not respond to ethical situations - has a detrimental influence on employees," Quade said. "Employees who work for amoral managers have less moral courage, which results in their engaging in higher levels of unethical behavior.

Moral courage, he said, is needed when the person recognizes there is an objective danger in acting morally and it helps him/her to endure through the danger.

Examples of moral courage include a willingness to correct co-workers; adherence to policies or procedures, even in the face of peer pressure to do otherwise; and a willingness to do the right thing, even at a personal cost.

Lack of moral courage can lead to unethical behaviors such as employees discussing confidential information with unauthorized people, falsifying receipts to get greater reimbursements, damaging work property, taking property from work without permission, misusing company assets and resources; and saying or doing hurtful things to others purposefully.

"Itis imperative for managers to be vocal about their expectations when it comes to ethics," Quade said." When they fail to engage in situations that have ethical implications, employees suffer."

Preventing Amoral Management in the Workplace

Amoral management could have damaging long-term effects on an otherwise ethical workplace environment. The study indicates that organizations can prevent amoral management by being proactive in their ethical training and setting of expectations for employees.

Key steps in preventing amoral management include:

Organizations should realize that ethical environments alone do not prevent employees from behaving unethically. They need to be supported with leaders who engage when circumstances with ethical implications arise.

When it comes to ethics, employees need consistent messages from their direct supervisors and the broader organization.

Organizations should train supervisors to consistently and clearly engage employees regarding the ethical expectations of the organization and to address circumstances that have ethical implications.

The researchers conclude that "by introducing an amoral management measure, future research will be able to test the theoretical assumptions made by previous researchers and help managers recognize why leaders may default to amoral management and whether this leadership approach is effective or ineffective."

The emergence of SARS-CoV-2 virus variants that are adding twists in the battle against COVID-19 highlight the need for better genomic monitoring of the virus, says Katia Koelle, associate professor of biology at Emory University.

"Improved genomic surveillance of SARS-CoV-2 across states would really help us to better understand how the virus causing the pandemic is evolving and spreading in the United States," Koelle says. "More federal funding is needed, along with centralized standards for sample collection and genetic sequencing. Researchers need access to such metadata to better track how the virus is spreading geographically, and to identify any new variants that may make it harder to control, so that health officials can respond more quickly and effectively."

Koelle studies the interplay between viral evolution and the epidemiological spread of viral infectious diseases. She is senior author of a "Viewpoint" article just published in the journal Science on the importance of SARS-CoV-2 sequencing to control the COVID-19 pandemic.

Michael Martin, a PhD student in Emory's Population, Biology and Ecology Program and a member of Koelle's lab, is first author of the Science article. David VanInsberghe, a post-doctoral fellow in Koelle's lab, is co-author.

"Research into SARS-CoV-2 has been going at lightning speed," Martin says. "This acceleration has provided us with one of the largest datasets ever so quickly assembled for a disease. We've learned a lot so far about how this virus spreads and adapts, but we still have many blind spots that need to be addressed."

The article summarizes key insights about SARS-CoV-2 that have already been gained by sequencing of its genome from individual patient samples. It also cites challenges that remain, including the collection and integration of metadata into genetic analyses and the need for the development of more efficient and scalable computational methods to apply to hundreds of thousands of genomes.

A genome is an organism's genetic material. Human genomes are made up of double-stranded DNA, coded in four different nucleotide base letters. A single human genome consists of more than 3 billion base pairs. In contrast, the genome of coronaviruses, including SARS-CoV-2, are made of RNA, which can have a simpler structure than DNA. The SARS-CoV-2 genome, for instance, consists of a single RNA strand that is only 30,000 letters long. Sequencing is a technique that provides a read-out of these letters.

If the SARS-CoV-2 virus is found in a sample swabbed from someone's nose or mouth, it confirms the likelihood that the person is carrying the virus, whether they have symptoms of COVID-19 or not. The virus in the sample can also be sequenced.

"Sequencing the virus is like fingerprinting it," Koelle explains. "And based on how close the fingerprints match between samples -- that is, how close they are genetically -- you can at times learn who is infecting whom. Analyzing sequences from samples taken from infected individuals in a given region over time can provide even more information."

Analyses of SARS-CoV-2 sequencing data have enabled researchers to estimate the timing of SARS-CoV-2 spillover into humans; identify some of the transmission routes in its global spread; determine infection rates and how they change within a region; and identify the emergence of some new variants of concern.

Viral genomes can mutate during replication, changing letters as they spread to new people. Most of these random mutations will likely not affect the transmissibility or virulence of a virus -- but a few may make it even more difficult to fight. Early evidence, for instance, suggests that a SARS-CoV-2 variant that recently emerged in the UK may be more easily transmitted and potentially more severe. A South African variant shows signs that it may reduce the efficacy of existing vaccines, while a variant first detected in Brazil also contains mutations that health officials worry may make the virus spread more quickly.

"It can be difficult to identify which variants actually change how the virus replicates, spreads and causes disease because of confounding factors," Martin explains. "If a variant spreads more quickly, for instance, you have to tease apart whether that was due to it becoming more transmissible or if someone who was infected with it attended a large gathering."

The better data researchers have, the faster they can solve such puzzles, he adds.

Technological advances during recent years have made it more efficient and less costly to generate sequencing data. Barely a year after it emerged, more than 400,000 sequences of SARS-CoV-2 are now available in public databases, such as the GISAID platform which was launched in 2008 to share information among National Influenza Centers for the WHO Global Influenza Surveillance and Response System.

"A large chunk of the public sequencing data for SARS-CoV-2 has come out of the UK," Koelle notes. "That's because the British government has an initiative to do high-density sampling of the SARS-CoV-2 genome."

The rich data set from the UK helped identify the emergence of the variant in Britain that is spreading rapidly. "There might be other variants of concern emerging in other places around the world besides the ones already identified, but we just don't know because we don't have as good of surveillance in those locations," Koelle says.

"While the United States has been slow in efforts to sequence SARS-CoV-2 from samples across the nation, there are several excellent viral sequencing efforts and phylogenetic analyses, primarily driven by academic researchers, that have helped to understand SARS-CoV-2 transmission more locally," Koelle says. "We have the expertise in the U.S., but the effort is more piecemeal."

"We need a coordinated, nationally standardized program to do widespread sequencing of SARS-CoV-2 in the United States," Martin says. "Much of the data collected now just has a state identifier but we need greater resolution while also protecting patient privacy. More county-level identifiers, for instance, would be one way to greatly improve the quality and the depth of the data."

Once the COVID-19 pandemic ebbs, it's important to continue to build the national infrastructure and systems for infectious disease surveillance -- including viral sequencing -- and to keep it in place, both researchers stress.

"There will be more infectious disease pandemics, and we need to be better prepared," Martin says.

Housing instability and homelessness are widely understood to have an impact on health, and certain housing problems have been linked to specific childhood health conditions, such as mold with asthma. But it has not been clear how overall housing quality may affect children--especially those who are at risk from other social determinants of health such as food insecurity or poverty.

A new nationally representative study in the Journal of Child Health Care, led by researchers at Nationwide Children's Hospital, has found poor-quality housing is independently associated with poorer pediatric health, and suggests ways health care providers and housing programs may address those findings.

"We are really trying to pick apart the social determinants of health. What happens to a child's health if the child is hungry? What happens if a parent can't pay rent?" said Kelly Kelleher, MD, senior author of the study and vice president of Community Health at Nationwide Children's. "What we found in this study is that when housing quality is a problem, children suffer. And children are suffering now."

The authors based the study on the 2014 U.S. Census Survey of Income and Program Participation, ultimately considering 12,964 children 2-14 years of age across the country. As part of the survey, parents were asked about their children's overall health, number of medical visits and number of hospitalizations. They were also asked about the quality of their housing in four specific categories: holes or cracks in walls or ceilings; holes in the floor "big enough to catch your foot on"; plumbing features (including hot water heaters and toilets) that do not work; and problems with pests such as mice and roaches.

The study found each additional housing problem was associated with 43% greater odds of having a poorer health status.

"It was important, however, to account for other factors that are understood to impact health, and so the study used a modeling strategy that went beyond housing quality alone," said Samantha Boch, PhD, RN, the lead author of the study who completed it as a post-doctoral fellow in Nationwide Children's Patient-Centered Pediatric Research Program. She is now an assistant professor at the University of Cincinnati College of Nursing and an affiliate faculty member of the James M. Anderson Center for Health Systems Excellence at Cincinnati Children's Hospital Medical Center.

"Even when you adjust for demographic factors like race, ethnicity and disability, and housing-related issues like inability to pay rent or neighborhood safety, poor housing quality has an independent association with poorer health and higher health care use," said Dr. Boch.

When demographic factors were considered, each additional housing problem was associated with 18% greater odds of poorer health; when other housing issues were considered, there were 16% greater odds.

The authors also found poor housing quality was independently associated with a greater number of medical visits for children (as were inability to pay utilities, rent or mortgage and living in a nonmetropolitan home).

Dr. Kelleher says these findings reinforce the need for social determinants of health screening, and suggest housing quality, not just homelessness or housing insecurity, should be part of those screens. The study also puts a national lens on the convergence of health and housing Nationwide Children's has long seen locally through its Healthy Neighborhoods Healthy Families initiative, which has now built or helped improve approximately 400 homes in traditionally disadvantaged Columbus neighborhoods.

"We know anecdotally, from our experience in our own backyard, that housing quality impacts health," said Dr. Kelleher. "We can now say it's true nationally, and new housing isn't the only thing that matters--improving existing housing may be just as important."

As states and municipalities begin to roll out mass vaccination campaigns, some people have dared to ask: When will it be safe to resume "normal" activities again? For those in most parts of the United States, the risk of COVID-19 infection remains extremely high.

People now have access to better real-time information about infection rates and transmission at the county or city level, but they still need a framework to help them decide what is safe to do. Social distancing and shutting businesses have reduced the number of cases, but there is mounting pressure to reopen businesses and classrooms.

Life is likely to continue in this limbo for some time. A new model co-authored by a Washington University in St. Louis mathematician helps to contend with the uncertainty.

"People need a way to decide whether an activity is worth undertaking," said John E. McCarthy, the Spencer T. Olin Professor of Mathematics in Arts & Sciences and chair of the Department of Mathematics and Statistics at Washington University.

"We provide a model to estimate the relative infection risks of different activities," he said. "That information can allow decision-makers in industry and government to rank activities according to their relative risk of infection.

"In combination with an understanding of the benefits and costs of those activities, decision-makers can then make informed choices about whether, and if so how, to allow participation in previously forbidden activities."

McCarthy wrote the model, published Jan. 28 in the journal PLOS ONE, along with Barry D. Dewitt at Carnegie Mellon University, Bob A. Dumas at Omnium LLC and Myles T. McCarthy at the University of Illinois at Urbana-Champaign.

The researchers present several example calculations, analyzing the risks of idealized versions of airplane travel, attending a sporting event, sitting in a classroom, going to a restaurant and attending a religious service.

Crucially, the new model breaks up the component parts of such in-person activities -- walking through a turnstile at a stadium, for example, or sitting in one's seat in the stands -- and adds up their contributions to relative risk. This makes the model easy to use and allows the user to quantify the effect of any proposed mitigation strategy.

McCarthy has already been using a version of this formula to help sports franchises to keep the fan experience at stadiums and arenas the safest it can be. In describing this effort, McCarthy said: "We learned pretty quickly two big takeaways: The single most important risk factor in a fan experience is seating; and, with mitigation, the risk in everything else is relatively small."

In the PLOS ONE paper, the mathematicians describe how the model they share is a good approximation of a more refined model in which assumed infections come from a series of independent risks. A linearity assumption governing several potentially modifiable risk factors -- such as duration of the activity, density of participants and infectiousness of the attendees -- makes interpreting and using the model straightforward. The researchers argue that it does so without significantly diminishing the reliability of the model.

This type of decision-making tool will be relevant for months or possibly years ahead, even after the COVID-19 vaccines become more widely available.

"Our approach could be modified to account for estimates of the percent vaccinated of the population of potential participants in an activity," McCarthy said.

"To be a useful decision-making tool, a model must be robust and quantitative," he said. "All activities outside one's home have some risk. To make an informed decision on what activities to engage in and which ones to avoid, we need some way to estimate the relative risks of different activities and of different ways of managing a given activity."

A University of Otago study explored factors which influence Americans' levels of concern over climate change, providing discussion on how those factors could impact mitigation efforts.

A key thread of the research examined the ability of people to visualize the future. Results showed that while 74 per cent of respondents were concerned about climate change, only 29 per cent discussed lower carbon options when asked to describe travel in the year 2050.

"This suggests actively envisioning a sustainable future was less prevalent than climate change concern. So while the majority were concerned, there was a disconnect with expectations of what the future might hold," says lead author Jean Fletcher, who completed the study as part of her PhD in Otago's Centre for Science Communication.

The study discusses how mitigation efforts such as greater adoption of low carbon systems could be more widely accepted and happen sooner if expectations of a low carbon future were more prevalent.

"For example, if people expect vehicles will, rather than might, switch from petrol to electric, the uptake of electric car purchasing would likely increase sooner," Miss Fletcher says.

The study also describes how the abstract nature of 'the future' may inspire procrastination as people wait for more information before making a decision.

"This has important implications for climate change. The cumulative nature of carbon emissions means the longer we wait to reduce emissions, the more drastic the emission reduction needs to be," Miss Fletcher adds.

Study supervisor, Professor Nancy Longnecker of Otago's Centre for Science Communication, says that the study's finding of a link between technological optimism and climate change concern suggests that individuals are hoping for technological fixes rather than making personal lifestyle changes. She notes that individual action, collective action and policy are all necessary components in global response to climate change.

"For policy makers, knowing drivers behind people's thinking can help communicate measures to mitigate climate change in ways that lead to action, instead of people either seeing the problem too far away to worry about, too difficult to fix, or being someone else's responsibility," Professor Longnecker says.

Scientists are opening new windows into understanding more about the constantly shifting evolutionary arms race between viruses and the hosts they seek to infect. Host organisms and pathogens are in a perennial chess match to exploit each other's weaknesses.

Such research holds tantalizing clues for human health since the immune system is on constant alert to deploy counter measures against new viral attacks. But unleashing too much of a defensive response can lead to self-inflicted tissue damage and disease.

A new study published in the journal eLife by biologists at the University of California San Diego has revealed insights on the intricate, adaptive mechanisms of a protective system employed by the cells of mammalian immune systems. Through a multidisciplinary approach that combined bioinformatics, biochemistry and virology, Biological Sciences graduate students Brian Tsu, Chris Beierschmitt and Andy Ryan, Assistant Professor Matt Daugherty and their collaborators at UC Berkeley found surprising defensive functions coordinated by a protein called NLRP1, which serves as a sensor for invasive pathogens.

The study involved Picornaviridae family viruses, which generate proteases, or molecular "scissors," that can cleave and activate NLRP1. These viruses include human pathogens such as poliovirus, coxsackievirus (responsible for hand, foot and mouth disease) and rhinovirus (one of the most frequent causes of the common cold). The analysis revealed that NLRP1 has recently evolved to "sense" these viral proteases through a type of trap that sets off an immune response in reaction to being cut by the viral proteases. Interestingly, NLRP1 has evolved to do this by mimicking natural sites that the viral protease normally needs to cut in order for the virus to replicate, making it difficult for the virus to avoid cleaving NLRP1 while maintaining its ability to survive.

"In our paper we're showing that NLRP1 acts to bait viral protease cleavage and set off a sort of alarm, or tripwire, in the organism," said Tsu, the lead author of the study. "This is like an Achilles heel to the virus. This allows the host organism to evolve ways to take advantage of this evolutionarily constrained cleavage."

Daugherty said the results offer an interesting switch of conventional beliefs about virus-host dynamics.

"We often think of viruses taking advantage of the fact that hosts evolve slowly, but we're seeing that the hosts have turned the tables and used the fact that the viruses are really stuck here to their advantage, and therefore they use this constraint to activate an immune response."

While evolution is often considered to occur one step after another, the viruses analyzed in this study would need to simultaneously alter numerous regions within their viral proteins to evolve around the tripwire defense, which would be extremely difficult.

The research was derived in cells but lays the groundwork for potential future clinical applications in which the tripwire function could be employed in immune defenses in human systems such as the lungs, brain and other areas. Based on the study's results in individual cells, new research avenues are opening to investigate how the tripwire operates across entire organisms.

"I'm particularly excited about looking for more of these cases because this is an evolutionarily elegant way of detecting and responding to viral infection," said Daugherty.

Scientists have created a new way to detect the proteins that make up the pandemic coronavirus, as well as antibodies against it. They designed protein-based biosensors that glow when mixed with components of the virus or specific COVID-19 antibodies. This breakthrough could enable faster and more widespread testing in the near future. The research appears in Nature.

To diagnose coronavirus infection today, most medical laboratories rely on a technique called RT-PCR, which amplifies genetic material from the virus so that it can be seen. This technique requires specialized staff and equipment. It also consumes lab supplies that are now in high demand all over the world. Supply-chain shortfalls have slowed COVID-19 test results in the United States and beyond.

In an effort to directly detect coronavirus in patient samples without the need for genetic amplification, a team of researchers led by David Baker, professor of biochemistry and director of the Institute for Protein Design at UW Medicine, used computers to design new biosensors. These protein-based devices recognize specific molecules on the surface of the virus, bind to them, then emit light through a biochemical reaction.

Antibody testing can reveal whether a person has had COVID-19 in the past. It is being used to track the spread of the pandemic, but it ,too, requires complex laboratory supplies and equipment.

The same team of UW researchers also created biosensors that glow when mixed with COVID-19 antibodies. They showed that these sensors do not react to other antibodies that might also be in the blood, including those that target other viruses. This sensitivity is important for avoiding false-positive test results.

"We have shown in the lab that these new sensors can readily detect virus proteins or antibodies in simulated nasal fluid or donated serum, said Baker. "Our next goal is to ensure they can be used reliably in a diagnostic setting. This work illustrates the power of de novo protein design to create molecular devices from scratch with new and useful functions."

Beyond COVID-19, the team also showed that similar biosensors could be designed to detect medically relevant human proteins such as Her2 (a biomarker and therapy target for some forms of breast cancer) and Bcl-2 (which has clinical significance in lymphoma and some other cancers), as well as a bacterial toxin and antibodies that target Hepatitis B virus.

A fifth basic flavour has crept into our conceptualisation of foods in recent years--umami. In Japanese, umami translates roughly to 'savoury deliciousness'.

It is often associated with the earthy flavours of meat, mushrooms, broths and vine-ripened tomatoes. It enhances saltiness and sweetness, while reducing bitterness, which is why most people love it.

But does umami exist in beverages? And if so, which fermented beverage has the most umami potential: wine, beer, sake or champagne? And, what happens to flavours when these beverages are paired with foods?

Three researchers from the University of Copenhagen's Department of Food Science have published this first of a kind study in the journal Food Chemistry.

"We investigated the average umami flavour content in a range of wines, champagnes, beers and sakes. Our analyses demonstrate that it is in sake (Japanese rice wine), where umami reigns supreme on the umami scale, far ahead of beer, followed by champagne and finally wine. However, we studied slightly fewer beers than the other beverages, so that class of beverage may have been difficult to score precisely," reports postdoctoral researcher Charlotte Vinther Schmidt, one of the study's authors.

Higher potential when paired with food

Determining the umami flavour content of a drink involves finding out how much of an amino acid known as glutamic acid there is in it.

Umami flavour reaches us by way of glutamate as it lands on the specialised "umami" taste receptors of our tongues.

"Our results suggest that the longer a beverage's fermentation time, the higher its glutamate content--which leads to more umami flavour. This is probably why sake leads the pack by so much in terms of umami, as it is typically fermented using both yeast and a mold culture called koji," explains Charlotte Vinther Schmidt.

But even if other beverages can't match sake's umami flavor on their own, UCPH's savoury-deliciousness experts assert that the flavour can be provoked by pairing.

"We already know about food combinations which pair happily--like ham and cheese, for example. Therefore, we calculated the effects of pairing shellfish like oysters, shrimp and scallops with the various beverages, so as to investigate which combinations would synergize and provoke an emergence of umami. Here, we conclude that each of the beverage classes studied elicit an umami flavour when paired with oysters and tuna. Furthermore, sake, certain aged wines and champagne can also exhibit umami flavour when paired with scallops," explains CharlotteVinther Schmidt.

According to the researchers, this is because pairing high-content glutamate drinks with foods high in ribonucleotides (RNA's building blocks), catalyzes a synergistic flavour magic through which the best qualities of both drink and food emerge.

"If one takes a drink with glutamate and a food with just as many ribonucleotides, the umami flavour can generally be multiplied by eight," explains Charlotte Vinther Schmidt.

Useful knowledge for sustainable eating

Knowing how to enhance umami is useful when it comes to a more sustainable diet, as Charlotte Vinther Schmidt explains:

"If we can understand which vegetables, that together with selected beverages, provide the best taste--that umami contributes to--we could probably get far more people to consume vegetables, which is healthy for us humans, as well as for our planet."

So, there is good reason to consider the rapport between a meal's food and drink, as Charlotte Vinther Schmidt concludes:

"Although there are other factors contribute to taste experiences, like mouthfeel and smell, it might be a good idea to buy beverages with a high concentration of umami, as they improve the chance of enhancing taste in high-ribonucleotide foods, thus resulting in the delightful savoury-deliciousness of umami."

FACTS:

Average umami flavour content in selected beverages:

The researchers studied 8 sakes, 9 types of white, rosé and sparkling wines, 9 champagnes and 5 types of beer. Here is the average umami content for each beverage class:

Sake = 20,1

Beer = 5,7

Champagne = 4,2

Wines = 3.5

Researchers from the Hong Kong University of Science and Technology (HKSUST) and the University of Hong Kong (HKU) recently demonstrated that the selectivity determinant of Origin Recognition Complex (ORC) for DNA binding lies in a 19-amino acid insertion helix in the Orc4 subunit, which is present in yeast but absent in human. Removal of this motif from Orc4 transforms the yeast ORC, which selects origins based on base-specific binding at defined locations, into one whose selectivity is dictated by chromatin landscape (genomic nucleosome profile), a characteristic feature shared by human ORC.

Further understanding of the preferred DNA shapes and nucleosome positioning requirements will provide new insights for the plasticity of the human ORC in selecting replication initiation sites during programmed development and disease transformation, and also help identify potential targets for anti-cancer drug screening and therapy design.

All living creatures, from simple unicellular yeast to complex multicellular human being, propagate through cell divisions. Each division requires the exact replication of the genome DNA, which is the blueprint of the identity of every organism. Over-replication may lead to cancers and under-replication may lead to developmental defects such as Meier-Gorlin syndrome. DNA replication is initiated at replication origins by ORC and other protein complexes assembled at these sites.

Interestingly, ORC is highly conserved in protein structure and function from yeast to human, but targets DNA sites that bear no obvious common features in these two systems. What causes this difference? This question had puzzled the scientists for decades.

"Structure informs function," said Prof. Bik TYE, lead researcher and Senior Member of the Institute for Advanced Study, HKUST. "In 2018, we solved a high-resolution structure of the yeast ORC using cryo-electron microscopy. When we compared the structures between yeast and human, we found one important difference between them, which lies in one subunit of ORC--Orc4."

"The yeast Orc4 has an additional 19-amino acid motif which makes specific contacts with origin DNA and is not present in human," said Prof. Tye. "We immediately realized that this short motif of Orc4 might be a critical factor that causes the different behaviors of ORC in DNA binding between yeast and human. We then deleted this motif in yeast cells to test if it could convert the yeast ORC into one that behaves with human-like properties. Indeed, the engineered ORC in yeast behaves more like a human ORC, or as we call it, a humanized ORC."

DNA replication is one of the most fundamental processes in living cells. It is catalyzed by a similar set of replication machineries from yeast to human. In yeast cells, DNA replication starts from a set of sites, termed as replication origins. These sites share a specific DNA sequence, which can be recognized by a six-subunit protein complex known as origin recognition complex (ORC), Orc1-6. ORC binds to origin DNA, then serving as a platform to recruit Mcm2-7 helicase onto DNA. Mcm2-7 helicase is the machine responsible for separating double-stranded DNA to provide templates for DNA replication.

"The activities of each origin are tightly regulated to ensure genome integrity," said Prof. ZHAI Yuanliang, collaborator of the study and Assistant Professor at the School of Biological Sciences, Faculty of Science at HKU. "Mis-regulation of replication initiation can cause either under- or over-replication of chromosomal DNA, which will induce DNA strand breaks, gross chromosomal rearrangements, and genome instability, a characteristic of almost all human cancers."

Inhibition of replication initiation is considered as an effective anti-cancer strategy for the selective killing of cancer cells through apoptosis while normal human cells arrest in G1 state (growth) or withdraw from the cell cycle into G0 state (inactive).

"Our studies lay a solid foundation to identify pairs of interactions, that are critical for origin recognition and helicase loading, with the potential as targets for anticancer drug screening and design," Prof. Zhai noted.

"This study demonstrates the power of multi-disciplinary approaches to answer fundamental questions in life sciences." commented Prof. Danny LEUNG, Assistant Professor at the Division of Life Science, HKUST, and Director of HKUST's Center for Epigenomics Research. Prof. Leung's team was responsible for the epigenomics and bioinformatic analyses of this study. The Center coordinates the efforts of the Hong Kong Epigenomics Project and facilitates regional researchers in carrying out epigenomic studies.

"It began with the atomic model of the yeast ORC bound to origin DNA and the discovery that a single motif in one of the subunits is responsible for the base-specific recognition of DNA by ORC. We conducted genome-wide assays and biochemical experiments to define binding characteristics, which led to the model that removal of this motif is the basis for the behavior of the human ORC, culminating in an insight for the evolution of ORC as eukaryotes adopt more complex genomic and epigenomic structures. This insight also bears critical information on disease transformation that is often associated with the plasticity of DNA replication," Prof. Leung observed.

Researchers have discovered a novel and druggable insulin inhibitory receptor, named inceptor. The latest study from Helmholtz Zentrum Muenchen, the Technical University of Munich and the German Center for Diabetes Research is a significant milestone for diabetes research as the scientific community celebrates 100 years of insulin and 50 years of insulin receptor discovery. The blocking of inceptor function leads to an increased sensitisation of the insulin signaling pathway in pancreatic beta cells. This might allow protection and regeneration of beta cells for diabetes remission.

Diabetes mellitus is a complex disease characterized by the loss or dysfunction of insulin-producing beta cells in the islets of Langerhans, a specialist "micro-organ" in the pancreas that controls systemic blood sugar levels. Diabetes complications, such as chronic high blood sugar, systemic metabolic failure and, in the long-term, multi-organ damage, create enormous medical and social burdens and leads to premature death. Currently no pharmacological treatment can stop or reverse disease progression. Previous studies have demonstrated that intensive insulin therapy has the potential for improved blood sugar control and diabetes remission but also leads to unintended weight gain and even more severe side effects, such as an increased risk of deep drop in blood sugar causing unawareness.

Heiko Lickert's* research focuses on the development of regenerative approaches to treat diabetes complementary and alternative to the classical immunological and metabolic therapies. "Insulin resistance in pancreatic beta cells causes diabetes. Therapies that sensitize those cells to insulin may protect patients with diabetes against beta cell loss and failure", says Lickert. With the discovery of the insulin inhibitory receptor, his research group has found a promising molecular target for beta cell protection and regeneration therapy that does not carry the unintended side effects of intensive insulin therapy.

In experiments with mice, the researchers showed that the function of inceptor is to shield the insulin-producing beta cells from constitutive insulin pathway activation. Remarkably, inceptor is upregulated in diabetes and by blocking insulin signaling it might contribute to insulin resistance.

What happens if the function of inceptor is inhibited genetically or pharmacologically? The group explored this question by knocking out inceptor in beta cells and by blocking its function using monoclonal antibodies. "The result was exactly what we were hoping for: Insulin signaling and the functional beta cell mass was increased. This makes inceptor a very promising target to treat the root cause of diabetes, the loss and dysfunction of beta cells," says Ansarullah, one of the first-authors of the study published in Nature and diabetes researcher at Helmholtz Zentrum München.

"Frederick Banting noted already in his Nobel Prize lecture for the discovery of the life-saving drug insulin a hundred years ago that 'Insulin is not a cure for diabetes, but a treatment of the symptoms'. This has not changed in the last century. Our goal for future research is to leverage on the discovery of inceptor and develop drugs for beta cell regeneration. This could be beneficial for patients with type 1 and 2 diabetes and ultimately lead to diabetes remission", states Lickert.

"A hundred years ago, the discovery of insulin has transformed a deadly illness into a manageable disease. Our discovery of the insulin inhibitory receptor now is another important step to finally get rid of the disease," says Matthias Tschöp, CEO at Helmholtz Zentrum München. "While the COVID-19 pandemic represents an immediate threat we will overcome, we must not forget that diabetes remains one of the biggest and fastest growing killers on our planet. With a series of recent breakthroughs, now including the discovery of inceptor, our Helmholtz Diabetes Center is doubling down on its mission that is a world without diabetes."

Scientists have calculated the mass range for Dark Matter - and it's tighter than the science world thought.

Their findings - due to be published in Physics Letters B in March - radically narrow the range of potential masses for Dark Matter particles, and help to focus the search for future Dark Matter-hunters. The University of Sussex researchers used the established fact that gravity acts on Dark Matter just as it acts on the visible universe to work out the lower and upper limits of Dark Matter's mass.

The results show that Dark Matter cannot be either 'ultra-light' or 'super-heavy', as some have theorised, unless an as-yet undiscovered force also acts upon it.

The team used the assumption that the only force acting on Dark Matter is gravity, and calculated that Dark Matter particles must have a mass between 10-3 eV and 107 eV. That's a much tighter range than the 10-24 eV - 1019 GeV spectrum which is generally theorised.

What makes the discovery even more significant is that if it turns out that the mass of Dark Matter is outside of the range predicted by the Sussex team, then it will also prove that an additional force - as well as gravity - acts on Dark Matter.

Professor Xavier Calmet from the School of Mathematical and Physical Sciences at the University of Sussex, said:

"This is the first time that anyone has thought to use what we know about quantum gravity as a way to calculate the mass range for Dark Matter. We were surprised when we realised no-one had done it before - as were the fellow scientists reviewing our paper.

"What we've done shows that Dark Matter cannot be either 'ultra-light' or 'super-heavy' as some theorise - unless there is an as-yet unknown additional force acting on it. This piece of research helps physicists in two ways: it focuses the search area for Dark Matter, and it will potentially also help reveal whether or not there is a mysterious unknown additional force in the universe."

Folkert Kuipers, a PhD student working with Professor Calmet, at the University of Sussex, said:

"As a PhD student, it's great to be able to work on research as exciting and impactful as this. Our findings are very good news for experimentalists as it will help them to get closer to discovering the true nature of Dark Matter."

The visible universe - such as ourselves, the planets and stars - accounts for 25 per cent of all mass in the universe. The remaining 75 per cent is comprised of Dark Matter.

It is known that gravity acts on Dark Matter because that's what accounts for the shape of galaxies.

A new study has shown that, while there is limited evidence for overall increased mortality in patients with atopic eczema, those with severe atopic eczema may have a greater risk of dying from several health issues compared with those without eczema, according to a new study in the Journal of Allergy and Clinical Immunology.

The research team, led by the London School of Hygiene & Tropical Medicine (LSHTM) and funded by the Wellcome Trust, compared the risk of dying in over 500,000 adults with atopic eczema with more than 2.5 million without eczema. Patients with severe atopic eczema had a 62% higher risk of dying compared to individuals without atopic eczema, due to several causes - the strongest links of which were seen for infections, lung problems and kidney or bladder disorders.

There was limited evidence of increased 'all-cause' mortality in patients with non-severe atopic eczema, and the absolute risk of death was modest, with low overall mortality rates (1435 per 100,000 people per year in those without atopic eczema, and 1496 per 100,000 people per year in those with atopic eczema).

The researchers did not set out to find the reasons behind the increases in risk of death in severe or predominantly active atopic eczema. Previous studies have suggested that the elevated risk may be linked to reduced physical activity and reduced sleep quality, as well as immunological dysfunction due to the disease itself or the drug treatments the patients might be on. They urge for more research into the causes to help develop intervention strategies.

The research was conducted in collaboration with Health Data Research UK, Aarhus University Hospital, Nottingham Support Group for Carers of Children with Eczema and the University of California San Francisco School of Medicine.

Atopic eczema affects up to 10% of adults and is becoming more common globally. The disease is characterised by itch, sleeplessness and adverse effects on quality of life. Around 30% of people with atopic eczema have moderate to severe disease.

Sinéad Langan, Professor of Clinical Epidemiology at LSHTM, said: "Recent evidence has led to a paradigm shift in how atopic eczema is perceived, from focusing on skin symptoms and associated allergic diseases, to understanding that the disease may be associated with a range of important medical outcomes. Recently, we found atopic eczema to be associated with an increased risk of myocardial infarction, ischemic stroke, angina and heart failure.

"However, few studies have assessed if atopic eczema increases the risk of death, a research question we aimed to address in this study."

This new research used the healthcare records from UK general practices alongside hospitalisation records and mortality data from the Office for National Statistics spanning 1998 to 2016. More than 500,000 people with atopic eczema, of which nearly 35,000 were classified as having severe atopic eczema, were matched with up to five individuals without eczema, based on their age (within 15 years), sex and general practice. This resulted in more than three million individuals were successfully matched, with a median age of 41.8 years.

The researchers found that patients with atopic eczema had 8% to 14% increased risk of death due to infectious, digestive and genitourinary causes.

Crucially, they noted that increased mortality risk was mainly in those with the most severe or more active atopic eczema. Patients with severe atopic eczema had 62% higher overall risk of death. These findings are consistent with previous studies.

Long-standing patient collaborator, Amanda Roberts, said: "Forewarned is fore-armed. Now we eczema patients can be more aware of potential harms and complications associated with lungs, kidneys or bladder. This research team is adding so much to our understanding of eczema."

Professor Langan added: "Although the absolute risk of death from severe eczema is low, our findings suggest that those with severe or more active forms of the disease do face a higher risk of dying from associated health issues. We hope that this new information will help inform further research to better understand this pattern and the underlying mechanisms of these associations, and subsequently inform and improve treatment processes for those with severe eczema."

The researchers acknowledge the limitations of this study, including a lack of standardised measures of disease severity. Severity had to be identified based on hospital referral or receiving of specific therapies, prevent the researchers from disentangling the effects of treatment and severity.