Thursday, May 21, 2020

Scientists identify chemicals in noxious weed that 'disarm' deadly bacteria

"Nature is the best chemist, hands down," says Emory ethnobotanist Cassandra Quave, shown with berries from the Brazilian peppertree. The plant is native to South America where traditional healers in the Amazon have used it as a treatment for skin infections. 

By Carol Clark

Scientists have identified specific compounds from the Brazilian peppertree — a weedy, invasive shrub in Florida — that reduce the virulence of antibiotic-resistant staph bacteria. Scientific Reports published the research, demonstrating that triterpenoid acids in the red berries of the plant “disarm” dangerous staph bacteria by blocking its ability to produce toxins.

The work was led by the lab of Cassandra Quave, an assistant professor in Emory University’s Center for the Study of Human Health and the Emory School of Medicine’s Department of Dermatology. The researchers’ laboratory experiments provide the first evidence that triterpenoid acids pack a punch against methicillin-resistant Staphylococcus aureus, known as MRSA.

The Brazilian peppertree (Schinus terebinthifolia), native to South America, is also abundant in Florida, where it forms dense thickets that crowd out native species. “It is a noxious weed that many people in Florida hate, for good reason,” Quave says. “But, at the same time, there is this rich lore about the Brazilian Peppertree in the Amazon, where traditional healers have used the plant for centuries to treat skin and soft tissue infections.”

Brazilian peppertree
Quave, a leader in the field of medical ethnobotany and a member of the Emory Antibiotic Resistance Center, studies how indigenous people incorporate plants in healing practices to uncover promising candidates for new drugs.

The Centers for Disease Control and Prevention calls antibiotic resistance “one of the biggest public health challenges of our time.” Each year in the U.S., at least 2.8 million people get antibiotic-resistant infections, leading to more than 35,000 deaths.

“Even in the midst of the current viral pandemic of COVID-19, we can’t forget about the issue of antibiotic resistance,” Quave says. She notes that many COVID-19 patients are receiving antibiotics to deal with secondary infections brought on by their weakened conditions, raising concerns about a later surge in antibiotic-resistant infections.

In 2017, the Quave lab published the finding that a refined, flavone-rich mix of 27 compounds extracted from the berries of the Brazilian peppertree inhibits formation of skin lesions in mice infected with MRSA. The extract works not by killing the MRSA bacteria, but by repressing a gene that allows the bacteria cells to communicate with one another. Blocking that communication prevents the cells from taking collective action, which essentially disarms the bacteria by preventing it from excreting the toxins it uses to damage tissues. The body’s immune system then stands a better chance of healing a wound.

That approach is different from the typical treatment of blasting deadly bacteria with drugs designed to kill them, which can help fuel the problem of antibiotic resistance. Some of the stronger bacteria may survive these drug onslaughts and proliferate, passing on their genes to offspring and leading to the evolution of deadly “super bugs.”

For the current paper, the researchers wanted to narrow down the scope of 27 major compounds from the berries to isolate the specific chemicals involved in disarming MRSA. They painstakingly refined the original compounds, testing each new iteration for its potency on the bacteria. They also used a series of analytical chemistry techniques, including mass spectrometry, nuclear magnetic resonance spectroscopy and X-ray crystallography to gain a clear picture of the chemicals involved in the anti-virulence mechanism.

The results showed that three triterpenoid acids worked equally well at inhibiting MRSA from forming toxins in a petri dish, without harming human skin cells. And one of the triterpenoid acids worked particularly well at inhibiting the ability of MRSA to form lesions on the skin of mice. The researchers also demonstrated that the triterpenoid acids repressed not just one gene that MRSA uses to excrete toxins, but two genes involved in that process.

“Nature is the best chemist, hands down,” Quave says. She adds that weeds, in particular, tend to have interesting chemical arsenals that they may use to protect them from diseases so they can more easily spread in new environments.

The research team plans to do further studies to test the triterpenoid acids as treatments for MRSA infections in animal models. If those studies are promising, the next step would be to work with medicinal chemists to optimize the compounds for efficacy, delivery and safety before testing on humans.

“Plants are so incredibly complex chemically that identifying and isolating particular extracts is like picking needles out of haystacks,” Quave says. “When you’re able to pluck out molecules with medicinal properties from these complex natural mixtures, that’s a big step forward to understanding how some traditional medicines may work, and for advancing science towards a potential drug development pathway.”

First authors of the current paper are Huaqiao Tang — a former visiting scholar at Emory and a veterinarian at Sichuan Agricultural University in China — and Gina Porras, an Emory post-doctoral fellow. In addition to senior author Quave, co-authors include Francois Chassagne and James Lyles, who are both members of the Quave lab; John Basca, director of Emory’s X-ray Crystallography Center; and Alexander Horswill and Morgan Brown from the University of Colorado School of Medicine.

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Tuesday, May 5, 2020

Global experts call for mental health science to combat pandemic's impacts

Emory anthropologist Carol Worthman is among 25 mental health experts who issued a call for global action on mental health science surrounding the COVID-19 pandemic.

By Carol Clark

The outbreak of severe acute respiratory syndrome (SARS) in 2003 infected about 8,000 people and killed hundreds. Although SARS was stamped out relatively quickly, and before it could spread globally, it left a lingering impact. One study found that most SARS survivors in two major hospitals had high levels of psychological distress a year after the outbreak.

“Just surviving the pandemic was not the end of the story,” says Carol Worthman, professor of anthropology at Emory University. “And the COVID-19 pandemic is much more pervasive than SARS. It affects everybody, worldwide. Even those who do not get COVID-19 will have to live with the fallout.”

Worthman is among 25 mental health experts who issued a call for global action on mental health science surrounding the COVID-19 pandemic, recently published by The Lancet Psychiatry. In a position paper, they stress the immediate need for creating neuro-psychological databases concerning the pandemic’s impacts on brain health, mental health and overall well-being. These databases are needed to support evidence-based responses to the pandemic and to develop longer-term strategies to promote mental health and well-being.

Even as nations mobilize to treat patients, develop drugs and vaccines, and salvage economies, coordinated efforts on a similar scale are needed for mental health, Worthman says. Her research focuses on how cultural and social factors interact with human health, for better or for worse.

“We’re used to thinking about physical diseases and mental illnesses as two separate things,” Worthman says, “but the two actually go hand-in-hand. Mental illness doesn’t just affect the lives of individuals, but of those around them. And like a virus, mental illness is invisible, in a way, and can be even harder to test and screen for.” Before the pandemic, depression already ranked in the top 10 causes of poor health worldwide and had climbed to the top four health problems related to healthy years of life lost.

The impacts of the lockdowns and social isolation on the mental health of vulnerable people are among the key questions that need to be tackled in an international response to COVID-19, the experts write. Their paper also stresses the need to research the best ways to move people to follow the advice of public health messages without unduly increasing stress and anxiety.

“People are especially hurting right now, they’re suffering, and they’re looking for ways to feel better,” Worthman says. “If we don’t develop pro-social ways to help people cope now and, in the future, we’re going to be living with the consequences for a long time.”

She points out that the 1918 flu pandemic, following on top of the first world war, helped set the stage for the social disruption and sense of hopelessness that fueled political movements and nationalism leading to the second world war.

One critical need is to gather data and develop strategies to support people currently working in high-intensity, high-risk settings during the pandemic, such as healthcare workers. “Burnout and higher suicide rates among healthcare providers had already been a growing problem for years,” Worthman says.

She cites the mental health effects of massive unemployment as another critical area. “Work is a huge part of peoples’ identities, not to mention their livelihoods,” she says. “Depression, anxiety, stress and lack of control are all things that undermine resilience. What can we do to help people stay resilient when they’re losing their sense of dignity and self-worth and predictability for their futures?”

Youth and adolescent mental health is another vital area to consider, Worthman says. “Young people are having to watch a remapping of the social-economic political world and try to find their way through it. Their future is our future and they need to be part of the solution. How do we mobilize youth to help them make their future as great as possible? Do we make supporting youth as important as saving airlines and other industries?”

COVID-19 is revealing and widening existing fault lines in social, economic and political systems. “We now have the challenge and opportunity to heal those ruptures even as we seek to heal ourselves of COVID-19,” Worthman says.

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Wednesday, April 29, 2020

How family stories help children weather hard times

Stories of family members — who persevered by simply putting one foot in front of the other and by maintaining loving bonds — reassure children that their family will also find a way to get through a situation, says Emory psychologist Robyn Fivush. (Getty Images)

By Carol Clark

In times of great stress, stories sustain us, says Robyn Fivush, director of the Family Narratives Lab in Emory’s Department of Psychology.

Family reminiscing is especially important, says Fivush, who is also director of Emory’s Institute for the Liberal Arts. When children learn family stories it creates a shared history, strengthens emotional bonds and helps them make sense of their experiences when something senseless happens — like the current global pandemic.

“When we don’t know what to do, we look for stories about how people have coped in the past,” Fivush says. “You can see that happening in the media now, in articles comparing today to historical events, like the 1918 flu pandemic and 9/11.”

She sums up the 9/11 narrative in the United States: “A horrific event happened; we were attacked. But we came together as a nation, persevered and rose back up together.”

Such narratives help build a shared capacity for resilience. “That’s true for nations and it’s true for families,” Fivush says.

Over decades of research, Fivush and Emory psychologist Marshall Duke developed a scale to measure how much children know about their family histories. Using this scale, they conducted a study that began just before 9/11 and continued for two years. “We found that in families that talked in more coherent and emotionally open ways about challenging family events with 10- to 12-year-olds, the children coped better over the two-year period than in families telling less emotionally expressive and coherent stories about their challenges,” Fivush says.

The families in the study were all comparable, middle-class, two-parent households.

Standardized measures showed that children in the families that told the more coherent family narratives had better self-esteem, higher levels of social competence, higher quality friendships, and less anxiety and stress. They also had fewer behavioral problems, as reported by parents.

Tips for telling family stories 

For families under quarantine together, opportunities abound to weave family stories into conversation, Fivush says. The stories need to be tailored to different ages, she adds, so that children are emotionally and cognitively able to understand them.

Elementary school children, for example, are not ready to digest complex family stories. “With younger kids, it’s really more about helping them structure their own experiences into stories that help them process their feelings,” Fivush says. “You want to start by asking them non-judgmental, open-ended questions like: ‘Why do you think you were upset yesterday? What could you have done to make yourself feel better? What can we do about this?'"

She uses an example of a little girl who left her favorite storybook at her school and was worried that it wasn’t going to be there when she went back. A mother could tell a story about how she left a favorite toy somewhere when she was little but later her father took her back and they found it.

“Tell them a story from your own life that provides a model for how everybody forgets things, but you can get them back,” Fivush says. “Or, ‘My brother used to tease me a lot, too. But now he’s your Uncle Bill and we love each other.’ Parents are identity figures. Little kids are fascinated by stories about their parents when they were little.”

Ultimately, the goal is to help children construct a coherent story that validates their feelings while helping them think of resolutions.

“Particularly with very young kids, don’t make assumptions about what they may be upset or sad about,” Fivush says. “You may be surprised. Stay open to what your children of all ages may be experiencing.”

Middle school children are starting to have more of an ability to understand the bigger picture. “By the age of 10, children are thinking in the abstract and because of that, they are likely to be anxious about the future,” Fivush says.

By this stage, children begin to understand stories on a deeper level. It’s not that every story needs a happy ending or a silver lining, Fivush stresses. “You can explain to your child, ‘We don’t know yet how this story is going to end but let me tell you about some challenging times I got through, or your grandparents got through.’”

Examples of family members — who persevered by simply putting one foot in front of the other and by maintaining loving bonds — reassure children that their family will also find a way to get through a situation.

When they reach adolescence, children are especially vulnerable. “High school is a time when children start to really think about themselves as a person and what their life is going to be like,” Fivush says. “They are mulling big questions, like ‘Who am I? What are my passions?’ And now the pandemic has pulled the rug out from under them.”

By the age of 16, parents can start talking to a teen-ager about their own vulnerabilities as people and as parents. “Emphasize how you can build strength together, as a family,” Fivush says. She suggests finding ways of giving teen-agers a role in supporting younger children in positive ways.

“Human beings are really altruistic and empathetic. We feel good when we help other people, particularly people that we love,” Fivush says. “That’s going to make every family member feel better about themselves and about each other.”

Silly, funny family stories are also valuable, along with small touchpoints about the past that emerge spontaneously, Fivush says. “When you’re cooking together with your children it’s a perfect time to say, ‘When I was a little girl, my mother taught me how to cook this dish. We used to have pot roast every Friday and I would peel the carrots.’”

Adolescents are especially hungry for these kinds of stories, she adds. “If they roll their eyes, so be it, they’re still listening,” Fivush says. “It’s the really mundane, everyday stories that reassure them that life is stable. It provides a sense of continuity, of enduring relationships and values. They need to know that they come from a long line of people who are strong, who are resilient, who are brave. And who can cook. The definition of who they are is not just something independent and autonomous, spun from nowhere. It’s embedded in a long, intergenerational family story.”

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Psychologists document the age our earliest memories fade

Wednesday, April 22, 2020

Bat ecology in the era of pandemics

The International Union for Conservation of Nature recently appointed Emory graduate student Amanda Vicente to its Bat Specialist Group — global recognition for her expertise. (Photo by Neto Villalobos)

Bats are primarily creatures of the night. Their cape-like wings, alien faces and strange behaviors drive human fascination and fear.

“People have so many misconceptions,” says Amanda Vicente, who studies the disease ecology of bats as an Emory University doctoral candidate. “Bats are associated with dark things, like Dracula. They have never had a good reputation.”

Evidence linking viruses carried by bats to disease outbreaks, from the ongoing COVID-19 pandemic to SARS, Marburg, MERS, Nipah, Hendra and Ebola, is not helping their image.

“It’s important for people to know that our enemies are not the bats, but the pathogens,” Vicente says. “And in order to better fight these pathogens, we need to understand their evolutionary relationship with bats, and how that relationship is being altered by human behaviors.”

Read more about the work of Vicente, who is leading a team of Emory students to study cave bats in her native Costa Rica.

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Tuesday, April 21, 2020

Mathematicians unite faculty, students and countries to fight COVID-19

Emory math professor Alessandro Veneziani, left, visited his hometown of Bergamo, Italy, last year with his former student Alexander Viguerie, who received his PhD in math in 2018. Bergamo became ground zero in Italy for COVID-19.

By Carol Clark

Alessandro Veneziani loves numbers and he loves people. A professor in Emory’s Department of Mathematics and Department of Computer Science, he uses numerical analysis and computing for real-world applications — such as modeling blood flow through the vascular system to determine risks for an aneurysm or a stroke.

The pandemic shifted the focus of Veneziani — a native of Italy, one of the hardest hit countries — onto the rising number of new COVID-19 cases and the people affected by them. After the campus closed, Veneziani and colleagues launched an Emory student contest to create mathematical models that might yield useful data for controlling the pandemic. More than 90 students jumped in to form teams and take on the challenge.

“The students want to help, and this is a way they can use what they’re learning,” Veneziani says. “They are part of the Emory community and when you work as a community you have more power to make bigger contributions to the world.”

On February 19, only two cases had been detected in Italy, and COVID-19 still seemed a distant problem in the country. On that day, about 45,000 soccer fans from the region of Veneziani’s hometown, Bergamo, traveled to Milan to watch their elite team, Atalanta, beat the Spanish challenger in a Champions League match. They returned home to celebrate.

On February 20, in his adopted hometown of Atlanta, Veneziani celebrated the birth of a daughter, Eleonora, with his wife, Manuela Manetta. Manetta is also Italian, from Abruzzo near Rome, and is a lecturer in Emory’s Department of Mathematics.

On March 19, which is Father's Day in Italy, Veneziani celebrated at his home in Atlanta with his newborn daughter, Eleonora.

By March 19, Italy had become the country with the highest number of COVID-19 deaths in the world. And ground zero was Bergamo, a UNESCO World Heritage Site.

Members of Veneziani’s family still live in the town. They are quarantined in separate homes where he stays in touch with them through Skype. His brother takes his mother meals and leaves them outside her door. “I’m mostly worried about my mom,” Veneziani says, “because she’s 78 and the most vulnerable.”

Veneziani felt frustrated being so far away as Bergamo struggled. “I was awake late at night, my wife was feeding our baby, and I was thinking and thinking,” he recalls. That’s when he got the idea for the math modeling contest.

“The spirit of the initiative is that it is less a competition than a collaboration,” Veneziani says. “We are coming together to fight a common enemy, a virus. And our weapons are differential equations.”

Jim Nagy, chair of the Department of Mathematics, supported the idea and three faculty immediately volunteered to help manage the initiative: Manetta, Longmei Shu, a visiting faculty member, and Maja Taskovic, an assistant professor. They are pulling together other faculty from related disciplines across campus to select the top three student groups in May. Veneziani also enlisted entrepreneur Russell Medford as a judge. A former physician at Emory, Medford is now chair of the board of the Center for Global Health Innovation in Atlanta and is always on the lookout for a fresh perspective.

Students from all majors were welcomed into the initiative, from first years on up.

The sun rises over the ancient, fortified city of Bergamo, in the Lombardy region of northern Italy. (Photo by Sven Manguard)

Veneziani tells stories of hope and resilience from Bergamo to inspire the students, who are all dealing with their own concerns surrounding the pandemic. Bergarmo is situated on a hill and surrounded by stone fortress walls dating to 1500. “Bergarmo is very beautiful and very old,” Veneziani says. “Its people are tough. And they are also generous.”

Bergarmo is known for skilled builders from a range of construction trades. As the existing medical facilities reached peak capacity, people from the region adopted the slogan “Bergarmo, don’t give up” and came together to build a new hospital. “Bergamo was under a storm and people volunteered to help. They built a hospital in just six days,” Veneziani says. “That’s incredible. That’s what a community can do when it comes together.”

Now the pandemic curve is showing signs of flattening in Bergamo and across Italy. On April 11, the United States surpassed Italy as the country with the most deaths from COVID-19.

The Emory student teams are finishing up their projects, including 20-page papers. Students were given free rein to pursue any kind of mathematical modeling project to help understand the spread of the pandemic and make useful predictions.

“The main aim of this initiative is educational,” Veneziani says. “I want students to understand that developing a mathematical model is a creative process. You come up with an idea, introduce some assumptions and then check them with reality to see if you’re on the right track. You have to keep refining your model, keeping it as simple as possible but complex enough to learn something useful.”

Veneziani celebrates with Alexander Viguerie as Viguerie receives his PhD at Emory Commencement in 2018.

“I’ve loved math since I was very young,” says Sanne Glastra, a sophomore majoring in qualitative theories and methods who is involved in the contest. “This is a chance to apply data science to a real problem that everyone is facing right now.”

Her team is modeling COVID-19 through the lens of nursing homes. “I’m learning a lot about how to collect data on health and demographics and work with a team to figure out what’s relevant,” says Glastra, who is quarantining with her family in Boston.

“The students have fresh energy and fresh minds,” Veneziani says. “They may come up with new ideas that deserve further exploration after the competition ends.”

Veneziani also has a math modeling project for COVID-19 underway with one of his former students, Alexander Viguerie, who is now a post-doctoral fellow at the University of Pavia, near Milan. Viguerie, a native of Atlanta, began his academic career at Oxford College before coming to the Emory campus for his undergraduate degree and his PhD in math, which he received in 2018.

Viguerie still has collaborations with Veneziani. He flew into Atlanta on February 20 so the two could work on a project, unrelated to COVID-19, that was expected to last a few weeks. It was the day Veneziani’s daughter was born and the news reported a confirmed COVID-19 case in Italy not related to travel, meaning the virus was on the loose in the country.

“It was surreal, the timing of everything,” Viguerie says.

A simulated outbreak in Georgia using artificial data. Viguerie is leading a team that's attempting to model COVID-19 transmission using Georgia as a framework. The work is still in the preliminary stages.

He and Veneziani soon scrapped their planned collaboration and began to work on modeling COVID-19 transmission. From his parents’ home in Georgia, where he is spending quarantine, Viguerie pulled together an international team for the project. Members include an expert in supercomputing in Germany; an expert in disease modeling from the University of Texas; students from the University of Pavia; and three undergraduates from Emory: Glastra, Kasey Cervantes and Shreya Rana.

“Everyone jumped right in to help,” Viguerie says.

“We’re really pumped about this project,” says Cervantes, a junior majoring in biology and minoring in computer science who is quarantined with his family in Chicago. Cervantes previously worked on a Centers for Disease Control and Prevention project to model malaria transmission and plans a career in computational biology or epidemiology.

Rena is a sophomore, majoring in neuroscience and behavioral biology and minoring in computer informatics. She is quarantined with her family in the San Francisco Bay area. “The more information we have on how a virus spreads through a community, the more prepared we can be in the future,” she says.

The researchers are modeling the spatial-temporal spread of COVID-19. The team chose the state of Georgia as the framework for their model, which they hope could eventually be applied elsewhere.

Health data is collected at the county level, Viguerie explains. Georgia happens to have a high number of counties that are relatively small compared to other states, or to Italian provinces, which yields a greater level of spatial precision for the modelers.

“This is a long-term project, not intended for decision-making today,” Viguerie stresses. “We want to create a tool for down the road. We might learn something useful, for instance, that could help in the case of later waves of the outbreak.”

Georgia happens to have a high number of counties that are relatively small, making it easier for the researchers to generate rich special resolution as the basis for their model.

The researchers created a digital map of Georgia and broke it into a mosaic of 100,000 individual points in space. They wrote differential equations for variables related to COVID-19 transmission and created a computer program including all the equations. They are now running preliminary simulations to test various scenarios and see if the model works.

“You start with a simple model and progressively make it more and more complex,” Viguerie explains. “Our model seeks to describe the spread of COVID-19 across time and space. And from there, we can hopefully use the model to learn some mechanistic natures of the spread.”

By comparing the data on symptomatic spread to actual new cases, they can make assumptions to test. “Certain things, like asymptomatic cases, are difficult to measure but possible to simulate using a model,” Viguerie says. “Good models and simulations are crucial with a disease like COVID-19.”

For Veneziani, who officially became a U.S. citizen in February, the Emory student competition and the international project with his former student are both “emergency” measures and business as usual. He has long used math to tackle healthcare problems and to forge bonds between people and countries.

Emory has many specialists working on various aspects of COVID-19, from nurses and medical doctors to researchers specialized in biology, chemistry, epidemiology, virology, infectious diseases and vaccine development, as well as experts in social, historical, cultural, mental well-being, legal and ethical aspects of disease.

“Math is a common language that joins all these forces so we can all communicate,” Veneziani says. “The enormous problem of this pandemic is truly interdisciplinary. Emory is working together, and the whole world needs to come together. We will fight this virus together and we will win. Like in Bergarmo, at Emory we don’t give up.”

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