Friday, January 26, 2018

Chimpanzee studies highlight disease risk to all endangered wildlife

Famed primatologist Jane Goodall with Emory disease ecologist Thomas Gillespie, who is working with the Jane Goodall Institute to study the health of chimpanzees in Tanzania's Gombe National Park.

The American Journal of Primatology just published a special edition bringing together experts who have contributed to the understanding of chimpanzee health at Gombe National Park in Tanzania and beyond. Gombe is the site where Jane Goodall pioneered her behavioral research of chimpanzees. Goodall’s work at Gombe began in 1960, and continues today through the Jane Goodall Institute, making it the longest field study of any animal.

Thomas Gillespie, associate professor in Emory’s Department of Environmental Sciences, was a guest editor of the special journal edition, along with fellow scientists Dominic Travis and Elizabeth Lonsdorf. Gillespie works at the interface of biodiversity conservation and global health. Much of his research examines how and why anthropogenic influences within tropical forests alter disease dynamics and place wild primates, people and other animals in such ecosystems at increased risk of pathogen exchange.

Following is an interview with Gillespie about the special journal issue and why research on chimpanzee health is important.

What is the current status of chimpanzees?

Both the common chimpanzee and the bonobo, the two chimpanzee subspecies, are endangered. Chimpanzees are the most closely related species to humans and we see them declining precipitously due to habitat loss and poaching. Typical estimates for the chimpanzee population are in the hundreds of thousands. That’s far less than the number of people in Atlanta for the entire chimpanzee species spread across all of Africa. There is a real risk of chimpanzees going locally extinct in core parts of their habitat. Chimpanzee communities in West Africa, for instance, have very little habitat left. They’re often found living in scraps of habitat between villages.

How important is health to conservation? 

Wildlife health is a critical conservation issue, but that’s something that’s only recently been recognized. Wildlife populations already dealing with poaching and habitat loss are more vulnerable to being knocked out by disease. It becomes even more difficult when they are exposed to new pathogens, from humans or domesticated animals.

On top of that, primates are dealing with shifts in the dynamics of pathogens like Ebola. Ebola’s been around for a long time in natural systems but now we’re seeing big mortality events in wild chimpanzees and other apes. The Lowland Gorillas are actually listed as critically endangered due to Ebola.

How did you become involved with Gombe and the Jane Goodall Institute?

Fifteen years ago, as evidence mounted that disease was playing an important role in the population declines observed in Gombe chimpanzees in Tanzania, Dominic Travis and Elizabeth Lonsdorf developed a prospective health monitoring system. They began to collect specific behavioral data on signs of respiratory and gastrointestinal illnesses, combined with body condition scoring on a monthly basis for the chimpanzee communities at Gombe, that paralleled efforts by the Mountain Gorilla Veterinary Project in Rwanda and Uganda.

When I met Dom and Elizabeth at a workshop in Germany in 2004, I was six years into efforts to understand how logging and forest fragmentation in and around Kibale National Park, Uganda, affected disease dynamics in resident primates. My findings in Uganda highlighted that some forms of anthropogenic disturbance can alter the dynamics of natural pathogens in wildlife, such as a legacy of selective logging. It also revealed that other forms of disturbance, such as active forest fragmentation, can lead to opportunities for pathogens to jump between species, including the introduction of pathogens from people and domesticated animals to wild primates.

Dom and Elizabeth asked me to join their effort and expand the scope of their project to a One Health approach. I initiated diagnostic surveillance linked to geographical indicators of species overlap for Gombe’s chimpanzees and baboons, as well as the people and domesticated animals within the Greater Gombe Ecosystems. It serves as a map of all the places these species are interacting, for a greater sense of how transmission may be occurring. Integration of these new data streams, along with the ongoing observational health data and in-depth post-mortem necropsies, have allowed us to establish baselines of health indicators to inform outbreak contingency plans.

Dom, Elizabeth and I now co-direct this effort, which is known as the Gombe Ecosystem Health Project.

How does Gombe fit into the bigger picture of wildlife conservation? 

As a result of Jane Goodall’s initial observations of disease outbreaks impacting Gombe’s chimpanzees, it became apparent that infectious diseases have the capacity to threaten the conservation of endangered species.

Some people call Gombe “a living laboratory.” It’s unique in the sense that it’s a place where there has been long-term data collection on the behavior patterns of chimpanzees, and for the past 15 years we’ve been collecting all this data on their health.

Methods have been developed at Gombe that allow us to monitor chimpanzee health non-invasively, through fecal sampling, so that we don’t have to dart the animals and tranquilize them to take blood samples. Many of the tools and approaches developed at Gombe have the capacity to manage disease-related threats to other wildlife populations globally.

Ashley Sullivan from the Jane Goodall Institute contributed to this report.

Related:
Disease poses risk to chimpanzee conservation, Gombe study finds
Sanctuary chimps show high rates of drug-resistant staph

Thursday, January 25, 2018

Studying how genetic differences contribute to addiction

Psychology professor Rohan Palmer has earned a $2.4 million grant to examine why some people become addicted to alcohol or drugs, while others don't. Emory Photo/Video

By April Hunt
Emory Report

Rohan Palmer, an assistant professor of psychology in Emory College, started on the path to becoming a researcher as an undergraduate, when he worked in a lab studying whether female mice could overcome their anxiety to leave the safety of the nest to retrieve babies that he and other researchers had moved away.

Intriguingly, the work showed that some strains of mice performed very differently than others in overcoming their emotions to perform their motherly duties. Moreover, females exposed to more testosterone in the uterus performed worst at this and other maternal tasks.

“It was understanding behavior at its core,” says Palmer, now an expert in the field of behavioral genetics. “What helps us understand what makes us individuals better than looking at the environment and the biology?”

Palmer now runs his own behavioral genetics lab at Emory that turns that question to one of today’s most pressing issues: What makes some people addicted to drugs or alcohol, and not others?

His highly innovative approach, to find and characterize the layer of biology that combines with factors such as environment to find an answer, has earned him a 2017 Avenir Award for Genetics or Epigenetics of Substance Abuse Disorders (DP1) from the National Institutes of Health Director’s Pioneer Award program.

The five-year, $2.34 million award is among a handful of grants given to recognize “highly creative” scientists from the nation’s top universities and to encourage high-impact approaches to the broad area of biomedical and behavioral science.

“This is a special award, more so because very few beginning investigators receive this honor,” says Ronald Calabrese, the College’s senior associate dean for research.

Read more in Emory Report.

Thursday, January 4, 2018

Aversion to holes driven by disgust, not fear, study finds

Clusters of holes, such as those of a lotus seed pod, may be evolutionarily indicative of contamination and disease — visual cues for rotten or moldy food or skin marred by an infection. (Photo by Peripitus/Wikipedia Commons.)

By Carol Clark

Trypophobia, commonly known as “fear of holes,” is linked to a physiological response more associated with disgust than fear, finds a new study published in PeerJ.

Trypophobia is not officially recognized in the American Psychiatric Association’s Diagnostic and Statistical Manuel of Mental Disorders (DSM). Many people, however, report feeling an aversion to clusters of holes — such as those of a honeycomb, a lotus seed pod or even aerated chocolate.

“Some people are so intensely bothered by the sight of these objects that they can’t stand to be around them,” says Stella Lourenco, a psychologist at Emory University whose lab conducted the study. “The phenomenon, which likely has an evolutionary basis, may be more common than we realize.”

Previous research linked trypophobic reactions to some of the same visual spectral properties shared by images of evolutionarily threatening animals, such as snakes and spiders. The repeating pattern of high contrast seen in clusters of holes, for example, is similar to the pattern on the skin of many snakes and the pattern made by a spider’s dark legs against a lighter background.

“We’re an incredibly visual species,” says Vladislav Ayzenberg, a graduate student in the Lourenco lab and lead author of the PeerJ study. “Low-level visual properties can convey a lot of meaningful information. These visual cues allow us to make immediate inferences — whether we see part of a snake in the grass or a whole snake — and react quickly to potential danger.”

It is well-established that viewing images of threatening animals generally elicits a fear reaction in viewers, associated with the sympathetic nervous system. The heart and breathing rate goes up and the pupils dilate. This hyperarousal to potential danger is known as the fight-or-flight response.

The researchers wanted to test whether this same physiological response was associated with seemingly innocuous images of holes.

They used eye-tracking technology that measured changes in pupil size to differentiate the responses of study subjects to images of clusters of holes, images of threatening animals and neutral images.

Unlike images of snakes and spiders, images of holes elicited greater constriction of the pupils — a response associated with the parasympathetic nervous system and feelings of disgust.

“On the surface, images of threatening animals and clusters of holes both elicit an aversive reaction,” Ayzenberg says. “Our findings, however, suggest that the physiological underpinnings for these reactions are different, even though the general aversion may be rooted in shared visual-spectral properties.”

In contrast to a fight-or-flight response, gearing the body up for action, a parasympathetic response slows heart rate and breathing and constricts the pupils. “These visual cues signal the body to be cautious, while also closing off the body, as if to limit its exposure to something that could be harmful,” Ayzenberg says.

The authors theorize that clusters of holes may be evolutionarily indicative of contamination and disease — visual cues for rotten or moldy food or skin marred by an infection.

The subjects involved in the experiments were college students who did not report having trypophobia. “The fact that we found effects in this population suggests a quite primitive and pervasive visual mechanism underlying an aversion to holes,” Lourenco says.

Since the time of Darwin, scientists have debated the relation between fear and disgust. The current paper adds to the growing evidence that — while the two emotions are on continuums and occasionally overlap — they have distinct neural and physiological underpinnings.

“Our findings not only enhance our understanding of the visual system but also how visual processing may contribute to a range of other phobic reactions,” Ayzenberg says.

A third co-author of the study is Meghan Hickey. She worked on the experiments as an undergraduate psychology major, through the Scholarly Inquiry and Research at Emory (SIRE) program, and is now a medical student at the University of Massachusetts.

Related:
How fear skews our spatial perception
Psychologists closing in on claustrophobia

Monday, December 18, 2017

New methods reveal the biomechanics of blood clotting

An electron micrograph shows a red blood cell, an activated platelet (in yellow) and a white blood cell. The ability to map the magnitude and orientation of forces on a cell provides a new tool for investigating not just blood clotting but a range of biomechanical processes. (NCI photo)

By Carol Clark

Platelets are cells in the blood whose job is to stop bleeding by sticking together to form clots and plug up a wound. Now, for the first time, scientists have measured and mapped the key molecular forces on platelets that trigger this process.

The extensive results are published in two separate studies, in the Proceedings of the National Academy of Sciences (PNAS) and in Nature Methods. “We show conclusively that, in order to activate clotting, the cell needs a targeted force of a magnitude of just a few piconewtons — or a force about a billion times less than the weight of a staple,” says Khalid Salaita, associate professor in Emory University’s Department of Chemistry and the lead author of the studies. “The real surprise we found is that platelets care about the direction of that force and that it has to be lateral. They’re very picky. But they should be picky because otherwise they might accidentally create a clot. That’s what causes strokes.”

Fibrinogen, the third most abundant protein in blood, acts like glue to stick platelets together as a clot forms. Each platelet has about 70,000 copies of a receptor for fibrinogen on its surface. These receptors can work like grappling hooks to latch onto fibrinogen.

“What was puzzling,” Salaita explains, “is that platelets, despite having all these receptors, do not normally latch onto the abundant fibrinogen. They keep flowing past it until you have an injury and fibrinogen becomes anchored. Then the platelets rapidly bind to fibrinogen allowing platelets to aggregate and for clotting to proceed.”



The Salaita lab is a leader in visualizing and mapping the mechanical forces applied by cells. In order to explore the biomechanics of blood clotting, the lab teamed up with physician and biomedical engineer Wilbur Lam, an expert in hematology at Emory’s School of Medicine. Both Salaita and Lam are also affiliated with Emory’s Winship Cancer Institute and the Wallace H. Coulter Department of Biomedical Engineering at Emory and Georgia Tech.

In initial experiments, for the PNAS paper, the Salaita lab anchored fibrinogen ligands onto a lipid membrane. On this surface, the ligands could slip and slide laterally, but resisted motion perpendicular to the surface — similar to the way a hockey puck slides easily over the surface of an ice rink but is harder to lift off of the plane of ice. The researchers then introduced platelets to this surface and experiments showed that the platelets failed to activate and stick together.

In contrast, when the fibrinogen ligands were anchored to a glass slide and unable to move laterally, the platelets rapidly activated. Using tension-imaging technology it developed, the Salaita lab showed that the platelets applied forces between five and 20 piconewtons to initiate activation.

“Platelets have to walk this tightrope between stopping bleeding quickly and accurately during an injury but avoiding unnecessary clotting. Mistakes could be fatal,” Salaita says. “We think they use this lateral force signal like a safety lock to prevent unnecessary clotting.”

Blood vessels are lined with endothelial cells and an injury exposes the fibrous matrix underneath these cells, Salaita explains. Platelets and fibrinogen in the blood can then stick to the injury site.

Salaita theorizes that when a platelet encounters stuck fibrinogen molecules, the platelet tugs on this fibrinogen as a way to test it. The resulting force generates a potent signal to activate platelets and that allows them to grab the fibrinogen from the blood, driving the process of clumping with other platelets.

The abnormal clotting that leads to strokes, and the uncontrollable bleeding of hemophilia, may be related to malfunctions in this biomechanical mechanism, he adds.

In 2011, the Salaita lab developed a fluorescence-sensor method for mapping cell mechanics. Alexa Mattheyses, a cell biologist at Emory’s School of Medicine and Winship Cancer Institute, teamed with the lab to test whether fluorescence polarization could be applied to map the direction of cell forces and provide further insights into the biomechanics of blood clotting.

The results, published in the Nature Methods paper, showed that they could.

Mattheyses “is a guru of fluorescence polarization,” Salaita says. She built a dedicated microscope that allowed mapping force direction at piconewton resolution. She also worked with Joshua Brockman and Aaron Blanchard, graduate students in the Salaita lab, to develop the new imaging technology.

The technique uses DNA molecules as force probes, which behave like molecular ropes and extend in the direction that a cellular force pulls. A series of microscopy images captures the orientation of the DNA, which can then be used to calculate the orientation of piconewton cell forces.

“We got really good at measuring and mapping magnitude, using fluorescence to see how stretched a polymer was,” Salaita says. “Now we can also see which direction a polymer is pointing, in three dimensions.”

Experiments revealed that as platelets begin sticking together to form a clot they contract toward a line, or central axis, in each cell. They do not, however, pull together toward a shared central axis. “It’s similar to having a group of people in a room that are all facing different directions,” Salaita explains. “When they join hands and everybody pulls inward you still get a cluster but the direction that each person is pulling is randomly oriented.”

The ability to map both the magnitude and orientation of forces on a cell provides a powerful tool for investigating not just blood clotting but a range of biomechanical processes, from immune cell activation and embryo development to the replication and spread of cancer cells.

“We’ve developed a completely new way to see things that were not visible before,” Salaita says. “It’s a basic tool with broad applications to help understand why cells are doing things and maybe predict what they’re going to do next.”

Related:
T cells use 'handshakes' to sort friends from foes
Chemists reveal the force within you
Molecular beacon shines light on how cells crawl

Tuesday, December 5, 2017

Goldwater Rule 'gagging' psychiatrists no longer relevant, analysis finds

The Goldwater Rule takes its name from a 1964 incident during the failed presidential bid of Barry Goldwater. An article in a now defunct magazine declared, "1,189 Psychiatrists Say Goldwater is Psychologically Unfit to be President."

By Carol Clark

The rationale for the Goldwater Rule — which prohibits psychiatrists from publicly commenting on the mental health of public figures they have not examined in person — does not hold up to current scientific scrutiny, a new analysis finds.

Perspectives on Psychological Science is publishing the analysis, which concludes that the Goldwater Rule is not well-supported scientifically and is outdated in today’s media-saturated environment. A preprint of the article is available online.

“We reviewed a large body of published scientific literature and it clearly showed that examining someone directly is often not necessary if you compile other valid sources of information,” says Scott Lilienfeld, lead author of the analysis and a professor of psychology at Emory University.

As examples of those sources, the authors cite interviews with family members, friends and others who know a person well, and extensive public records such as media interviews, biographies, YouTube videos, social media accounts and other material that may reveal a person’s longstanding behavioral patterns. The authors also report that direct interviews are subject to a host of biasing factors that are difficult to eliminate, including efforts on the part of interviewees to create positive impressions.

“Even though it is often possible to make a reasonably valid psychiatric diagnosis at a distance, that doesn’t necessarily mean that a mental health professional should,” Lilienfeld cautions. “Such a diagnosis should only be made with great discretion and after a thorough investigation.”

The Goldwater Rule, implemented in 1973 by the American Psychiatric Association (APA), gained new attention after Donald Trump entered the political arena. Some mental health professionals have expressed serious concerns about Trump’s mental health, most notably in the new book “The Dangerous Case of Donald Trump: 27 Psychiatrists and Mental Health Experts Assess a President.” 

The Goldwater Rule takes its name from an incident during the failed presidential bid of Barry Goldwater. A 1964 article in a now defunct magazine declared, “1,189 Psychiatrists say Goldwater is Psychologically Unfit to be President.” Many of the psychiatrists described the candidate in terms such as “emotionally unstable,” “cowardly,” “grossly psychotic,” “paranoid,” “delusional” and a “dangerous lunatic.” Some of the psychiatrists went so far as to offer diagnoses of Goldwater, including schizophrenia and obsessive-compulsive disorder.

Goldwater lost the election to Lyndon B. Johnson, but went on to successfully sue the magazine for libel.

“Many psychiatrists who commented on Goldwater in that article crossed an ethical line,” Lilienfeld says. “A lot of unfair statements were made about him that were poorly supported or unwarranted.” 

The APA later responded by passing what came to be known as the Goldwater Rule, in part to protect public figures from humiliation and in part to safeguard the integrity of the psychiatric profession.

The Goldwater Rule may have been more defensible at the time it was implemented, Lilienfeld says, because much less information was available on public figures.

Times have changed, however, particularly with the advent of the Internet and social media.

“If someone is running for the most powerful position in the world, behavioral professionals should be able to speak out if they take the time to properly investigate a candidate,” Lilienfeld says. “There should be a high threshold for doing so, but psychologists and psychiatrists should not feel gagged if they want to contribute to a national conversation about a presidential candidate or current president.”

While the authors of the analysis recommend abandoning the Goldwater Rule, they add that mental health professionals should avoid making diagnoses of celebrities in general, simply for the sake of prurient interest.

Lilienfeld’s co-authors are Joshua Miller from the University of Georgia and Donald Lynam from Purdue University.