Monday, March 20, 2017

Primate-parasite network analyses show how germs jump from host to host

A juvenile bonobo leaps from a branch. The bonobo, a threatened species of great ape found in the Congo Basin, is the closest existing relative to humans, along with the chimpanzee.

By Carol Clark

An extensive review of research on wild primate social networks and parasites underscores the importance of super-spreaders, or central individuals that play an outsized role in transmission of a pathogen.

Trends in Parasitology published the review, the first comprehensive synthesis of environmental and theoretical studies of disease dynamics in wild primate species — most of which are now threatened with extinction.

“This review gives critical insights that are applicable not just to conservation, but to our understanding of emerging infectious diseases and human health,” says Thomas Gillespie, lead author of the review and a primate disease ecologist at Emory University. “We hope it helps jump-start a new way of approaching research into disease transmission – one that integrates ecology, behavior and evolution on a grand scale.”

About 60 percent of the more than 500 known primate species face an extinction threat and more than three-fourths of them are on the decline, due to loss of habitat, hunting and disease. Large chunks of the world’s forests are succumbing to agriculture, mining and logging, bringing people, primates, pets and livestock into closer proximity. That juxtaposition sets the stage for more pathogens to jump between humans and our closest relatives. More than 20 percent of wild primate species harbor parasites capable of spilling over into humans. HIV, Ebola, yellow fever and respiratory viruses are examples of viruses shared by humans and wild primates.

“How an emerging pathogen spreads through a species tends to be ‘a black box’ until it causes an outbreak among people,” Gillespie says. The Zika virus, for instance, was first identified in monkeys in Uganda in 1947 but was not widely studied until recently, after it started sweeping through human populations.

Wild chimpanzees in Uganda's Kibale National Park. Chimpanzees, another threatened species of great ape, share 96 percent of human DNA. (Photo by Julie Rushmore)

Traditional infectious disease models generally assume that all individuals within a population have an equal probability of receiving or giving an infection, but more powerful analytical tools are showing that is not the case.

“Especially during the last decade,” Gillespie says, “it’s become much clearer that, just as everything in natural systems is heterogeneous, so is disease transmission.”

The so-called 80-20 rule – 80 percent of disease transmission events in an epidemic are caused by 20 percent of individuals – is now a well-established phenomenon. What’s not yet as well-understood are all of the variations within a disease system, and how these variations can combine to make an individual a super-spreader.

“Primate-parasite networks are an ideal model system for studying these questions,” Gillespie says, “because primate species are so varied and they have sophisticated social structures. We also have behavioral data for many primates – detailing the hierarchical ranking of individuals, and whom those individuals are related to and whom they interact with – collected over decades of observational studies.”

Combining knowledge of behaviors by individual species with data on their parasites can help researchers sort out high-risk traits and identify super-spreaders that contribute to transmission in a predictable way. Such patterns can help researchers to develop targeted interventions.

The review cites the example of a vaccine under development for Ebola virus, which is designed to replicate and spread immunity from a few individuals to others in a population. Targeting the most central individuals in an ape group with such a vaccine may be an effective way to mitigate future Ebola-related ape die-offs and spillover events into human populations.

The review also lays out a vision for the next decade of research into pathogen transmission, one that integrates ecology, behavior and evolution for studies of wild primates, other wildlife and humans.

“In addition to looking at how sociality influences infection, this review highlights the need to understand more about the flip side of that question: How do pathogens affect behavior and shape sociality?” Gillespie says. “We want to get people thinking about questions like this, in parallel networks of species.”

Co-authors of the review include Julie Rushmore of Oregon State University and the University of Georgia, and Donal Bisanzio of the University of Oxford.

Experts warn of impending extinction of many of the world's primates
Zeroing in on super-spreaders, and other hidden patterns of epidemics

Tuesday, March 7, 2017

Brain scans of service-dog trainees help sort weaker recruits from the pack

Some of the service dog trainees that were involved in the study pose with an fMRI scanner. (Photo by Gregory Berns.)

By Carol Clark

Brain scans of canine candidates to assist people with disabilities can help predict which dogs will fail a rigorous service training program, a study by Emory University finds.

The journal Scientific Reports published the results of the study, involving 43 dogs who underwent service training at Canine Companions for Independence (CCI) in Santa Rosa, California.

“Data from functional magnetic resonance imaging (fMRI) provided a modest, but significant, improvement in the ability to identify dogs that were poor candidates,” says Emory neuroscientist Gregory Berns, who led the research. “What the brain imaging tells us is not just which dogs are more likely to fail, but why.”

All of the dogs in the study underwent a battery of behavioral tests showing that they had a calm temperament before being selected for training. Despite calm exteriors, however, some of the dogs showed higher activity in the amygdala – an area of the brain associated with excitability. These dogs were more likely to fail the training program.

“The brain scans may be like taking a dog’s mental temperature,” Berns says. “You could think of it as a medical test with a normal range for a service dog. And the heightened neural activity that we see in the amygdala of some dogs may be outside of that range, indicating an abnormal value for a successful service dog.”

The findings are important, he adds, since the cost of training a service dog ranges from $20,000 to $50,000. As many as 70 percent of the animals that start a six-to-nine-month training program have to be released for behavioral reasons.

“There are long waiting lists for service dogs, and the training is lengthy and expensive,” Berns says. “So the goal is to find more accurate ways to eliminate unsuitable dogs earlier in the process.

The study found that fMRI boosted the ability to identify dogs that would ultimately fail to 67 percent, up from about 47 percent without the use of fMRI.

“This type of approach is not going to be feasible for individual trainers and their dogs because of the expense of fMRI,” Berns says. “It would only be practical for organizations that train large numbers of dogs every year.”

CCI is a non-profit that breeds, raises and trains dogs to assist human partners. Its service dog program, designed for disabled people, provides dogs to do tasks such as turn on lights, pick up dropped keys, open a door and pull a manual wheelchair.

Golden retrievers, Labradors — or crosses between the two — are the usual CCI service dog breeds, due to their generally calm and affable natures. After the puppies are weaned, they are adopted by volunteer puppy raisers for 15 months, before returning to CCI to undergo behavioral tests. Those that pass begin training.

For the Scientific Reports paper, the researchers taught the dogs how to remain still while undergoing an fMRI at the start of the training program.

The Berns lab was the first to conduct fMRI experiments on awake, unrestrained dogs, as part of an ongoing project to understand canine cognition and inter-species communication. In an early experiment, dogs were trained to respond to hand signals. One signal meant the dog would receive a food treat, and another signal meant that the dog would not receive one. The caudate region of the brain, associated with rewards in humans, showed activation when the dogs saw the signal for the treat, but not for the non-treat signal.

The researchers adapted this experiment for the current study — the largest yet involving dogs undergoing fMRI. The dogs were taught hand signals for “treat” and “no treat,” but sometimes the signals were given by the dog’s trainer and other times by a stranger.

The results found that dogs with stronger activity in the caudate in response to the treat signal – regardless of who gave the signal – were slightly more likely to successfully complete the service dog training program. However, if a dog had relatively more activity in the amygdala in response to the treat signal – particularly if the signal was given by a stranger – that increased the likelihood that the dog would fail.

“The ideal service dog is one that is highly motivated, but also doesn’t get excessively excited or nervous,” Berns says. “The two neural regions that we focused on – the caudate and the amygdala – seem to distinguish those two traits. Our findings suggest that we may be able to pick up variations in these internal mental states before they get to the level of overt behaviors.”

Berns hopes that the technology may become more refined and have applications for a broader range of working dogs, such as those used to assist the military and police forces.

Co-authors of the study include Andrew Brooks and Mark Spivak from Dog Star Technologies in Sandy Springs, Georgia, and Kerinne Levy from CCI.

What is your dog thinking? Brain scans unleash canine secrets
Dogs process faces in specialized brain area, study reveals

Monday, March 6, 2017

Atlanta Science Festival celebrates 'frontiers of the unknown'

Participants in the Zombie Outbreak Game scoured Peavine Creek on the Emory campus in 2016 for clues to the cause of a mock epidemic. The popular game returns this year on Sunday, March 19.

By Carol Clark

Watch for an astronaut, zombies, a hovercraft and liquid nitrogen ice cream to pop up on the Emory campus during the Atlanta Science Festival, March 14 to March 25. Thousands of science enthusiasts, of all ages, are also expected to appear for the fourth annual event – which includes lab tours, talks, a planetarium show, movie screenings, science-themed dance and games and lots more interactive fun.

The festival blasts off at Emory this year with a talk by NASA astronaut Mark Kelly. Tickets are going fast in the countdown to the event, set for 7 pm on Tuesday, March 14 at Glenn Memorial United Methodist Church.

“Emory University is proud to be a founder and strong supporter of the Atlanta Science Festival, which is just one example of the university’s engagement with our city and region,” says Emory President Claire E. Sterk. “We welcome the local community to our campus for the launch of the 2017 festival and to hear astronaut Captain Mark Kelly. Captain Kelly is an inspiration to all of us who are seeking to push the frontiers of the unknown.”

Name the ASF mascot
The title of Kelly’s talk is “Endeavor to Succeed.” He will give an insider’s perspective on space travel and the year-long NASA experiment he is participating in with his twin brother, also an astronaut, on how space affects the human body.

The public is invited to enter a contest to name the festival's new astronaut mascot. Entries are due by Friday, March 10 at 5 pm, and the winner will receive four VIP tickets to Kelly's talk.

Following are highlights of other festival events set at Emory.

“STEM Gems: Giving Girls Role Models in STEM Careers,” brings together women leaders from business, academia, NASA and more for a panel discussion on Thursday, March 16. They will offer advice aimed at girls ages 10 and up, who are interested in careers involving science, technology engineering or math.

The “Zombie Outbreak Game” returns to campus this year, on Sunday, March 19, giving participants ages 12 and up a chance to investigate a mock zombie disease outbreak, using real-world tools employed by scientists at Emory and the Centers for Disease Control and Prevention. Actors from Out of Hand Theater will play the patients as participants don masks and gowns and follow a trail of clues through streams, woods and labs across campus.

A dance performance, “Creating a New Normal: Race, Identity, Health and Activism,” will explore the themes involved in working towards an AIDS free generation, on the afternoon of Monday, March 20. The performance will be followed by a conversation with scientists and public health researchers — hosted by the Emory Center for Ethics — on the past, present and future of viral diseases.

“Investigating Our Human Past,” the evening of Monday, March 20, will allow visitors to examine the Emory Anthropology Department’s cast collection of fossilized skulls of our ancestors. Scientists will be on hand to discuss recent advances in our understanding of how the human brain evolved.

The Mathematics and Computer Science Department will present “Unveiling the Internet,” geared for teens, on the evening of Thursday, March 23. Participants will meet in a computer lab to tinker with code and learn concepts like how Snapchat snaps move through space.
Physics Live! set for Friday, March 24

The ever-popular “Physics Live!” returns to the Emory Math and Science Center on Friday, March 24. Children will be entertained with giant soap bubbles, a hovercraft and liquid nitrogen ice cream, among other activities. This year, the physics fun will be joined by a “Chemistry Carnival” at the Atwood Science Center. Chemists will turn into midway barkers, awarding prizes to visitors who play games like Peptide Jenga and Bacterial Telepathy, based on ongoing research in Emory labs.

The Oxford Campus will host a “Critter Crawl” through Oxford Forest on Sunday, March 19, to learn about wildlife native to Georgia. And on Sunday, March 21, an event called “It’s About Time” will bring guests and local researchers together to share scientific and social concepts of time.

In addition to on-campus events, members of the Emory community will be featured in Atlanta Science Festival activities happening throughout metro Atlanta:

“Science and Spirituality” will explore the intersections of physics and faith, biology and belief. The panel of local scientists and theologians will include Arri Eisen, a biologist from Emory’s Center for Ethics. On Thursday, March 16 at First Christian Church of Decatur.

“The Science Behind Tremors, the Movie,” features Emory paleontologist Tony Martin who will provide a lively discussion about real animals that inspired giant fictional worms. On Sunday, March 19 at Fernbank Science Center.

A live show and podcast called “You’re the Expert” will bring together a panel of comedians and podcast host Chuck Bryant, who will good-naturedly grill Emory chemist Cora McBeth about her work. On Tuesday, March 21 at 7 Stages Theatre.

The Exploration Expo, the culminating event of the festival, will include scientists from Emory biology, chemistry, environmental sciences, the Emory Herbarium and the Emory Center for the Study of Human Health. They will be among the hosts of 100 booths offering science-themed activities for families during the culminating event of the festival, set for Centennial Park on Saturday, March 25.

Monday, February 27, 2017

How protein misfolding may kickstart chemical evolution

The origami of disease, and of life: Research into the abnormal folding of proteins related to neurodegenerative conditions is providing insights into how life may emerge from a chemical system.

By Carol Clark

Alzheimer’s disease, and other neurodegenerative conditions involving abnormal folding of proteins, may help explain the emergence of life – and how to create it.

Researchers at Emory University and Georgia Tech demonstrated this connection in two new papers published by Nature Chemistry: “Design of multi-phase dynamic chemical networks” and “Catalytic diversity in self-propagating peptide assemblies.”

“In the first paper we showed that you can create tension between a chemical and physical system to give rise to more complex systems. And in the second paper, we showed that these complex systems can have remarkable and unexpected functions,” says David Lynn, a systems chemist in Emory’s Department of Chemistry who led the research. “The work was inspired by our current understanding of Darwinian selection of protein misfolding in neurodegenerative diseases.”

The Lynn lab is exploring ways to potentially control and direct the processes of these proteins – known as prions – adding to knowledge that might one day help to prevent disease, as well as open new realms of synthetic biology. For the current papers, Emory collaborated with the research group of Martha Grover, a professor in the Georgia Tech School of Chemical & Biomolecular Engineering, to develop molecular models for the processes.

“Modeling requires us to formulate our hypotheses in the language of mathematics, and then we use the models to design further experiments to test the hypotheses,” Grover says.

Darwin’s theory of evolution by natural selection is well-established – organisms adapt over time in response to environmental changes. But theories about how life emerges – the movement through a pre-Darwinian world to the Darwinian threshold – remain murkier.

The researchers started with single peptides and engineered in the capacity to spontaneously form small proteins, or short polymers. “These protein polymers can fold into a seemingly endless array of forms, and sometimes behave like origami,” Lynn explains. “They can stack into assemblies that carry new functions, like prions that move from cell-to-cell, causing disease.”

This protein misfolding provided the model for how physical changes could carry information with function, a critical component for evolution. To try to kickstart that evolution, the researchers engineered a chemical system of peptides and coupled it to the physical system of protein misfolding. The combination results in a system that generates step-by-step, progressive changes, through self-driven environmental changes.

“The folding events, or phase changes, drive the chemistry and the chemistry drives the replication of the protein molecules,” Lynn says. “The simple system we designed requires only the initial intervention from us to achieve progressive growth in molecular order. The challenge now becomes the discovery of positive feedback mechanisms that allow the system to continue to grow.”

The research was funded by the McDonnell Foundation, the National Science Foundation’s Materials Science Directorate, Emory University’s Alzheimer’s Disease Research Center, the National Science Foundation’s Center for Chemical Evolution and the Office of Basic Energy Sciences of the U.S. Department of Energy.

Additional co-authors of the papers include: Toluople Omosun, Seth Childers, Dibyendu Das and Anil Mehta (Emory Departments of Chemistry and Biology); Ming-Chien Hsieh (Georgia Tech School of Chemical and Biomolecular Engineering); and Neil Anthony and Keith Berland (Emory Department of Physics).

Peptides may hold 'missing link' to life

Monday, February 20, 2017

Contact tracing, with indoor spraying, can curb dengue outbreak

A traditional Queenslander home in Cairns, Australia, is open to breezes, as well as to disease-bearing mosquitoes. (Photo via James Cook University.)

By Carol Clark

Contact tracing, combined with targeted, indoor residual spraying of insecticide, can greatly reduce the spread of the mosquito-borne dengue virus, finds a study led by Emory University.

In fact, this novel approach for the surveillance and control of dengue fever – spread by the same mosquito species that infects people with the Zika virus – was between 86 and 96 percent effective during one outbreak, the research shows. By comparison, vaccines for the dengue virus are only 30-to-70-percent effective, depending on the serotype of the virus.

Science Advances published the findings, which were based on analyses from a 2009 outbreak of dengue in Cairns, Australia.

“We’ve provided evidence for a method that is highly effective at preventing transmission of diseases carried by the Aedes aegypti mosquito in a developed, urban setting,” says the study’s lead author, Gonzalo Vazquez-Prokopec, a disease ecologist in Emory’s Department of Environmental Sciences. “We’ve also shown the importance of human movement when conducting surveillance of these diseases.”

“The United States is facing continual threats from dengue, chikungunya and Zika viruses,” says Sam Scheiner, director of the National Science Foundation’s Ecology and Evolution of Infectious Diseases Program, which funded the research. “For now, the response is to intensively spray insecticides. This research shows that a more targeted approach can be more effective.”

While the method would likely not be applicable everywhere, Vazquez-Prokopec says that it may be viable to control Aedes-borne diseases in places with established health systems and similar environmental characteristics to Cairns, such as South Florida or other U.S. states at risk of virus introduction.

“The widespread transmission of dengue viruses, coupled with the birth defects associated with Zika virus, shows the dire need for as many weapons as possible in our arsenal to fight diseases spread by these mosquitos,” he says. “Interventions need to be context dependent and evaluated carefully and periodically.”

A public health worker collects Aedes mosquito larvae from water that has pooled on a tarp at a residence in Cairns, Australia.

During the dengue outbreak in Cairns, public health officials traced recent contacts of people with a confirmed infection – a surveillance method known as contact tracing. This method is commonly used for directly transmitted pathogens like Ebola or HIV, but rarely for outbreaks spread by mosquitos or other vectors.

Using mobility data from the known cases, public health workers targeted residences for indoor residual spraying, or IRS. Walls of the homes – from top to bottom – and dark, humid places were Aedes mosquitos might rest, were sprayed with an insecticide that lasts for months.

The method is time-consuming and labor intensive, and health officials were not able to reach all of the residences that were connected to the infected persons.

The researchers found that performing IRS in potential exposure locations reduced the probability of dengue transmission by at least 86 percent in those areas, in comparison to areas of potential exposures that did not have indoor spraying.

“The findings are important,” Vazquez-Prokopec says, “because they demonstrate one of the few measures that we have for the effectiveness of an intervention to reduce the transmission of dengue.”

Many times, he says, in the face of a dengue outbreak public health officials end up using trucks to spray insecticide – despite the lack of scientific evidence for the effectiveness of fogging from the streets to control Aedes aegypti mosquitos.

Quantifying the effectiveness of existing methods, and the context within which they work, can strengthen the vector-control arsenal. “We need to develop plans for outbreak containment that are context-specific,” Vazquez-Prokopec says.

He is researching ways to scale up this intervention. While it now takes approximately half-an-hour to conduct indoor residual spraying in a single house, he would like to cut that time to as little as 10 minutes.

“We are evaluating how we can scale up and improve IRS for 21st-century urban areas,” Vazquez-Prokopec says.

Co-authors of the study include researchers from Queensland Health, the Rollins School of Public Health and James Cook University, Cairns.

Zeroing in on 'super spreaders' and other hidden patterns of epidemics
Human mobility data may help curb urban epidemics