Duke Research Blog

Following the people and events that make up the research community at Duke.

Author: Anne Littlewood

The Importance of Moms

Emily Bray, Ph.D., might have the best job ever. Since earning her bachelor’s at Duke in 2012, she has been researching cognitive development in puppies, which basically means she’s spent the last seven years playing with dogs. If that’s not success, I don’t know what is.

Last Friday marked the 10th birthday of Duke’s Canine Cognition Center, and the 210th birthday of Charles Darwin. To celebrate, Brian Hare, Ph.D., invited former student Bray back to campus to share her latest research with a new generation of Duke undergraduates. The room was riveted — both by her compelling findings and by the darling photos of labs and golden retrievers that accompanied each slide.

Dr. Emily Bray shows photos of her study participants

During her Ph.D. program at the University of Pennsylvania, Bray worked with Robert Seyfarth, Dorothy Cheney, and James Serpell to investigate the effects of mothering on puppy development. For her dissertation, she studied a population of dog moms and their puppies at The Seeing Eye, Inc. The Seeing Eye is one of the oldest and largest guide dog schools in the U.S. They have been successfully raising and training service dogs for the blind since 1929, but like most things, it is still an imperfect science. Approximately half of the puppies bred at The Seeing Eye fail out of program. A dog that completes service training at The Seeing Eye represents two years of intensive training and care, and investing so much time and money into a dog that might eventually fail is problematic. Being able to predict the outcomes of puppies would save a lot of wasted time and energy, and Emily Bray has been doing just this.

What makes a good dog mom? (Photo from Dirk Vorderstraße, from Wikimedia Commons)

Through her work at The Seeing Eye, Bray found that, similar to humans, dogs have several types of mothering styles. She discovered that dog moms tend to fall somewhere on the spectrum from low to high maternal involvement. Some of the moms were very involved with their puppies, and seldom left their side. These hovering moms had high levels of cortisol, and became quite stressed when separated briefly from a puppy. They coddled their children, and often nursed from a laying down position, doing everything they could to make life easy for their babies. On the other side of the spectrum, Bray also observed moms that displayed much more relaxed mothering. They often took personal time, and let their puppies fend for themselves. They were more likely to nurse while sitting or standing up, which made their children work harder to feed. They were less stressed when separated from a puppy, and also just had generally lower levels of cortisol. Sound like bad parenting? Believe it or not, this tough love actually resulted in more successful puppies.

Duke’s very own assistance dogs in training!

As the puppies matured, Bray conducted a series of cognitive and temperament tests to determine if maternal style was associated with a certain way of thinking in the puppies. Turns out, dogs who experienced high maternal care actually performed much worse on the tests than dogs who were shown tough love when they were young. At The Seeing Eye graduation, it was also determined that high maternal care and ventral nursing was associated with failure. Puppies that were over-mothered were more likely to fail as service dogs.

Her theory is that tough love raises more resilient puppies. When mom is always around, the puppies don’t get the chance to experience small stressors and learn how to deal with challenge. The more relaxed moms actually did their kids a favor by not being so overbearing, and allowed for much more independent development.

Bray is now doing post-doctoral research at the University of Arizona, where she is working with Canine Companions for Independence (CCI) to determine if maternal style has similar effects on the outcomes of dogs that will be trained to assist people with a wide range of disabilities. She is also now doing cognition and temperament tests on moms pre-pregnancy to determine if maternal behavior can be predicted before the dogs have puppies. Knowing this could be a game changer, as this information could be used for selective breeding of better moms.

Me snuggling Ashton, one of the Puppy Kindergarten dogs

If you got the chance to hang out with puppies Ashton, Aiden, or Dune last semester, you have an idea of how awesome Bray’s day-to-day work is. These pups were bred at CCI, and sent to Duke to be enrolled in Duke Puppy Kindergarten, a new program on campus run through Duke’s Canine Cognition Center. Which of these three will make it to graduation? I’ve got money on Ashton, but I guess we’ll have to wait and see.

The bottom line according to Bray? “Mothering matters, but in moderation.”

Using Genetic Clues to Reform Cardiac Care

Experiencing cardiac arrest can be compared to being in a hot air balloon in a room that is rapidly filling with water. You are trapped, desperately aware of the danger you are in, and running out of time.

Andrew Landstrom, PHD, MD, shared this metaphor with his audience in the Duke Medicine Pavilion last Thursday, and a wave of empathy flooded through his listeners. He works as an Assistant Professor of Pediatrics in Duke University’s School of Medicine, and devotes his time and energy to studying the genetic and molecular causes of sudden cardiac death in the young.

Andrew Landstrom, PHD, MD (Photo from Duke Center for Applied Genomics and Precision Medicine)

For families of children who have died suddenly and unexpectedly, the worst thing of all is hearing their doctors say, “we have no idea why.” A third of sudden death cases in children have negative autopsies, which means these children die with no explanation.

When faced with an inconclusive autopsy, everyone wants answers. Why did these children die? How do we know it’s a problem with the heart? What can be done about it? What does it mean for the siblings of the child who died?

It has since been discovered that many of these unexplained deaths are actually the result of cardiac channelopathies, which are DNA mutations that cause ion channel defects in heart cell proteins. These mutations can mess up the electrical activity of the heart and cause a heart to beat in an irregular rhythm, which can have fatal consequences. Since this is a molecular problem, and not a structural one, it cannot be identified with a conventional autopsy, and requires a deeper level of genetic and molecular analysis to be found.

One type of channelopathy is a condition known as CPVT, which is short for catecholaminergic polymorphic ventricular tachycardia. This potentially life-threatening genetic disorder is the result of a point mutation in the genome, which means that one tiny nucleotide being changed in the DNA can lead to the single most fatal arrhythmia (irregular heart rhythm) known to man.

Sixty percent of children suffering from CPVT have a mutation in their RYR2 gene. This gene encodes for a protein that is found in cardiac muscle, and is a key player in how calcium is processed in heart cells. The mutated version of this gene results in proteins that let way too much calcium flood the cell, which can cause fatal changes in heart rhythm.

Dr. Landstrom has been using genome research to identify and explain sudden cardiac death in children, but the human genome doesn’t always provide straightforward answers. The problem is, a mutation in the RYR2 gene doesn’t always mean a person will have CPVT, and having an incidental RYR2 gene is much more common than being diagnosed with CPVT. Dr. Landstrom is studying this gene to try to figure out which variants are pathologic, and which are physiological.

“The human genome is a lot more confusing than I think I gave it credit for, and we’re just learning to deal with that confusion now,” he admitted to his audience last Thursday.

The Components of the Human Genome (photo from NHS National Genetics and Genomics Education Centre)

If a variant is falsely identified as pathologic, a patient will be given incorrect therapies, and suffer through unnecessary procedures. However, if a variant is falsely identified as physiological, and the patient isn’t given the necessary treatment, there will be no mitigation of the patient’s life threatening disease. Neither of these are good outcomes, so it’s very important to get it right. The current models for predicting pathogenicity are poor, and Dr. Landstrom is looking to design new model that will be able to avoid the personal, subjective opinions of human doctors and determine if a variant is pathologic or not.

Could serotonin levels be used to predict an infant’s vulnerability to SIDS? (photo from Elmedir, Wikimedia Commons)

Another area that is of interest to Dr. Landstrom is the problem of Sudden Infant Death Syndrome (SIDS), which affects ~6 in every 10,000 infants, and cannot currently be diagnosed before death. He is on the search for a biomarker that would be able to predict an infant’s vulnerability to SIDS, and thinks that these deaths may be related to elevated levels of serotonin. Finding a marker like this would allow doctors to save many healthy infants from unexplained death. Dr. Landstrom knows its not easy research and admitted “we have to fail — we are meant to fail,” on the path to success. He is very aware of both the ethical complexity and the exciting implications of genome research at Duke, and committed to converting his research into patient care.

Post by Anne Littlewood

HIV Can Be Treated, But Stigma Kills

Three decades ago, receiving an HIV diagnosis was comparable to being handed a death sentence. But today, this is no longer the case.

Advances in HIV research have led to treatments that can make the virus undetectable and untransmittable in less than six months, a fact that goes overlooked by many. Treatments today can make HIV entirely manageable for individuals.

However, thousands of Americans are still dying of HIV-related causes each year, regardless of the fact that HIV treatments are accessible and effective. So where is the disconnect coming from?

On the 30th anniversary of World AIDS Day, The Center for Sexual and Gender Diversity at Duke University hosted a series of events surrounding around this year’s international theme: “Know Your Status.”

One of these events was a panel discussion featuring three prominent HIV/AIDS treatment advocates on campus, Dr. Mehri McKellar, Dr. Carolyn McAllaster, and Dr. Kent Weinhold, who answered questions regarding local policy and current research at Duke.

From left to right: Kent Weinhold, Carolyn McAllaster, Mehri McKellar and moderator Jesse Mangold in Duke’s Center for Sexual and Gender Diversity

The reason HIV continues to spread and kill, Dr. McKellar explained, is less about accessibility, and more about stigma. Research has shown that stigma shame leads to poor health outcomes in HIV patients, and unfortunately, stigma shame is a huge problem in communities across the US.

Especially in the South, she said, there is very little funding for initiatives to reduce stigma surrounding HIV/AIDS, and people are suffering as a result.

In 2016, the CDC reported that the South was responsible for 52 percent of all new HIV diagnoses and 47 percent of all HIV-related deaths in the US.

If people living with HIV don’t feel supported by their community and comfortable in their environment, it makes it very difficult for them to obtain proper treatment. Dr. McKellar’s patients have told her that they don’t feel comfortable getting their medications locally because they know the local pharmacist, and they’re ashamed to be picking up HIV medications from a familiar face.

 

HIV/AIDS Diagnoses and Deaths in the US 1981-2007 (photo from the CDC)

In North Carolina, the law previously required HIV-positive individuals to disclose their status and use a condom with sexual partners, even if they had received treatment and could no longer transmit the virus. Violating this law resulted in prosecution and a prison sentence for many individuals, which only enforced the negative stigma surrounding HIV. Earlier this year, Dr. McAllaster helped efforts to create and pass a new version of the law, which will make life a lot easier for people living with HIV in North Carolina.

So what is Duke doing to help the cause? Well, In 2005, Duke opened the Center for AIDS Research (also known as CFAR), which is now directed by Dr. Kent Weinhold. In the last decade, they have focused their efforts mainly on improving the efficacy of the HIV vaccine. The search for a successful vaccine has been long and frustrating for CFAR and the Duke Human Vaccine Institute, but Dr. Weinhold is optimistic that they will be able to reach the realistic goal of 60 percent effectiveness in the future, although he shied away from predicting any sort of timeline for this outcome.

Pre-exposure prophylaxis or PrEP (photo from NIAID)

Duke also opened a PrEP Clinic in 2016 to provide preventative treatment for individuals who might be at risk of getting HIV. PrEP stands for pre-exposure prophylaxis, and it is a medication that is taken before exposure to HIV to prevent transmission of the virus. Put into widespread use, this treatment is another way to reduce negative HIV stigma.

The problem persists, however, that the people who most need PrEP aren’t getting it. The group that has the highest incidence of HIV is males who are young, black and gay. But the group most commonly receiving PrEP is older, white, gay men. Primary care doctors, especially in the South, often won’t prescribe PrEP either. Not because they can’t, but because they don’t support it, or don’t know enough about it.

And herein lies the problem, the panelists said: Discrimination and bias are often the results of inadequate education. The more educated people are about the truth of living with HIV, and the effectiveness of current treatments, the more empathetic they will be towards HIV-positive individuals.

There’s no reason for the toxic shame that exists nationwide, and attitudes need to change. It’s important for us to realize that in today’s world, HIV can be treated, but stigma kills.

Post by Anne Littlewood

Math on the Basketball Court

Boston Celtics data analyst David Sparks, Ph.D, really knew his audience Thursday, November 8, when he gave a presentation centered around the two most important themes at Duke: basketball and academics. He gave the crowd hope that you don’t have to be a Marvin Bagley III to make a career out of basketball — in fact, you don’t have to be an athlete at all; you can be a mathematician.

David Sparks (photo from Duke Political Science)

Sparks loves basketball, and he spends every day watching games and practices for his job. What career fits this description, you might ask? After graduating from Duke in 2012 with a Ph.D. in Political Science, Sparks went to work for the Boston Celtics, as the Director of Basketball Analytics. His job entails analyzing basketball data and building statistical models to ensure that the team will win.

The most important statistic when looking at basketball data is offensive / defensive efficiency, Sparks told the audience gathered for the “Data Dialogue” series hosted by the Information Initiative at Duke. Offensive efficiency translates to the number of points per possession while defensive efficiency measures how poorly the team forced the other offense to perform. These are measured with four factors: effective field goal percentage (shots made/ shots taken), turnover rate, successful rebound percentage, and foul rate. By looking at these four factors for both offensive and defensive efficiency, Sparks can figure out which of these areas are lacking, and share with the coach where there is room for improvement. “We all agree that we want to win, and the way you win is through efficiency,” Sparks said.

Since there is not a lot of room for improvement in the short windows between games during the regular season, a large component of Sparks’ job involves informing the draft and how the team should run practices during preseason.

David Sparks wins over his audience by showing Duke basketball clips to illustrate a point. Sparks spoke as part of the “Data Dialogue” series hosted by the Information Initiative at Duke.

Data collection these days is done by computer software. Synergy Sports Technology, the dominant data provider in professional basketball, has installed cameras in all 29 NBA arenas. These cameras are constantly watching and coding plays during games, tracking the locations of each player and the movements of the ball. They can analyze the amount of times the ball was touched and determine how long it was possessed each time, or recognize screens and calculate the height at which rebounds are grabbed. This software has revolutionized basketball analytics, because the implication of computer coding is that data scientists like Sparks can go back and look for new things later.

The room leaned in eagerly as Sparks finished his presentation, intrigued by the profession that is interdisciplinary at its core — an unlikely combination of sports and applied math. If math explains basketball, maybe we can all find a way to connect our random passions in the professional sphere.

The Importance of Evidence in Environmental Conservation

What counts as good evidence?

In medical research, a professional might answer this question as you would expect: evidence can be trusted if it is the result of a randomized, controlled, double-blind experiment, meaning the evidence is only as strong as the experiment design. And in medicine, it’s possible (and important) to procure this kind of strong evidence.

But when it comes to conservation, it’s a whole different story.

Dr. David Gill (photo from The Nicholas School)

The natural world is complicated, and far beyond our control. When studying the implications of conservation, it’s not so easy to design the kind of experiment that will produce “good” evidence.

David Gill, a professor in Duke’s Nicholas School for the Environment, recently led a study featured in the journal Nature that needed to  define what constitutes good evidence in the realm of marine conservation. Last Wednesday, he made a guest appearance in my Bass Connections meeting to share his work and a perspective on the importance of quality evidence.

Gill’s research has been centered around evaluating the effectiveness of Marine Protected Areas (or MPAs) as a way of protecting marine life. Seven percent of the world’s oceans are currently designated as MPAs, and by 2020, the goal is to increase this number to 10 percent. MPAs arguably have massive effects on ecosystem health and coastal community functioning, but where is the evidence for this claim?

Although past investigations have provided support for creating MPAs,  Gill and his team were concerned with the quality of this evidence, and the link between how MPAs are managed and how well they work. There have historically been acute gaps in study design when researching the effects of MPAs. Few experiments have included pre-MPA conditions or an attempt to control for other factors. Most of these studies have been done in hindsight, and have looked only at the ecological effects within the boundaries of MPAs, without any useful baseline data or control sites to compare them to.

As a result of these limitations, the evidence base is weak. Generating good evidence is a massive undertaking when you are attempting to validate a claim by counting several thousand moving fish.

Gill’s measure of ecosystem health includes counting fish. (Photo from Avoini)

So is there no way to understand the impacts of MPAs? Should conservation scientists just give up? The answer is no, absolutely not.

To produce better evidence, Gill and his team needed to design a study that would isolate the effects of MPAs. To do this, they needed to account for location biases and other confounding variables such as the biophysical conditions of the environment, the population density of nearby human communities, and the national regulations in each place.

The solution they came up with was to compare observations of current conditions within MPAs to “counterfactual” evidence, which is defined as what would have happened had the MPA not been there. Using statistical matching of MPAs to nearby non-MPA and pre-MPA sites, they were able to obtain high-quality results.

A happy sea turtle pictured in a marine protected area (photo from English Foreign and Commonwealth Office.)

The research showed that across 16,000 sampled sites, MPAs had positive ecological impacts on fish biomass in 71 percent of sites. They also discovered that MPAs with adequate staffing had far greater ecological impacts than those without, which is a pretty interesting piece of feedback when it comes to future development. It’s probably not worth it to create MPAs before there is sufficient funding in place to maintain them.

Gill doesn’t claim that his evidence is flawless; he fully admits to the shortcomings in this study, such as the fact that there is very little data on temperate, coldwater regions — mostly because there are few MPAs in these regions.

The field is ripe for improvement, and he suggests that future research look into the social impacts of MPAs and the implications of these interventions for different species. As the evidence continues to improve, it will be increasingly possible to maximize the win-wins when designing MPAs.

Conservation science isn’t perfect, but neither is medicine. We’ll get there.

Sean Carroll on the Evolution of Snake Venom

What’s in a snake bite?

According to University of Wisconsin-Madison evolutionary biologist Sean Carroll who visited Duke and Durham last week, a snake bite contains a full index of clues.

In his recent research, Carroll has been studying the adaptations of novelties in animal form, such as snake venom. Rattlesnakes, he explains, are the picture of novelty. With traits such as a limbless body, fangs, infrared pits, patterned skin, venom, and the iconic rattle, they represent an amazing incarnation of evolution at work.

Rattlesnakes: the picture of novelty (Photo from USGS)

Snake venoms contain a complex mixture of proteins. This mixture can differ in several ways, but the most interesting difference to Carroll is the presence or absence of neurotoxins. Neurotoxic venom has proven to be a very useful trait, because neurotoxins destroy the nervous tissue of prey, effectively paralyzing the animal’s respiratory system.

Some of today’s rattlesnake species have neurotoxic venom, but some don’t. So how did this happen? That’s what Carroll was wondering too.

Some genes within genomes, such as HOX genes, evolve very slowly from their original position among the chromosomes, and see very few changes in the sequence in millions of years.

But snake venom Pla2 genes are quite the opposite. In recent history, there has been a massive expansion of these genes in the snake genome, Carroll said. When animals evolve new functions or forms, the question always arises: are these changes the result of brand new genes or old genes taking on new functions?

Another important consideration is the concept of regulatory versus structural genes. Regulatory genes control the activity of other genes, such as structural genes, and because of this, duplicates of regulatory genes are generally not going to be a favorable adaptation. In contrast, structural gene activity doesn’t affect other genes, and duplicates are often a positive change. This means it is easier for a new structural gene to evolve than a regulatory one. Carroll explained.

Evolutionary Biologist Sean Carroll (Photo from seanbcarroll.com)

Carroll examined neurotoxic and non-neurotoxic snakes living in overlapping environments. His research showed that the most recent common ancestor of these species was a snake with neurotoxic venom. When comparing the genetic code of neurotoxic snakes to non-neurotoxic ones, he found that the two differed by the presence or absence of 16 genes in the metalloproteinase gene complex. He said this meant that non-neurotoxic venom could not evolve from neurotoxic venom.

So what is the mechanism behind this change? What could be the evolutionary explanation?

When Carroll’s lab compared another pair of neurotoxic and non-neurotoxic species in a different region of the US, they found that the two species differed in exactly the same way, with the same set of genes deleted as had been observed in the first discovery. With this new information, Carroll realized that the differences must have occurred through the mechanism of hybridization, or the interbreeding of neurotoxic and non-neurotoxic species.

Carroll’s lab is now doing the structural work to study if the genes that result in neurotoxic and  non-neurotoxic protein complexes are old genes carrying out new functions or entirely new genes. They are using venom gland organoids to look into the regulatory processes of these genes.

In addition to his research studying the evolution of novelties, Carroll teaches molecular biology and genetics at Madison and has devoted a large portion of his career to  storytelling and science education.

Meet New Blogger Anne Littlewood – Working on Biology and Puppies

My name is Anne Littlewood and I am a sophomore here at Duke. I grew up in San Francisco, spent a brief moment living on the island of Kauai, and finished high school in Pebble Beach, California. I am studying the intersection of biology and psychology here at Duke, in an effort to understand how biological mechanisms inform our interactions with the environment.

Snuggles in Puppy Kindergarten!

Outside the classroom, I can be found frequenting Duke’s beloved Puppy Kindergarten, where I work as a volunteer. Recently, I’ve become an Associate Editor for Duke’s literary magazine, The Archive. I love writing creatively, and it’s been so great to find a community of my literature- loving peers. I’m also participating in a Bass Connections project this year, and working on a team to evaluate the outcomes of different conservation interventions through the synthesis of an evidence gap map for World Wildlife fund.

Me and Cricket on Carmel Beach

Most of all I love to spend time outdoors, whether it’s exploring the mountains of North Carolina on a backpacking trip, lying in my hammock at Eno Quarry, or walking through the gardens each day on my way to class. I’m a huge animal lover, and I’m way too obsessed with my dog, a 12-pound cavalier King Charles spaniel named Cricket.

I’ve always been into science, but I think I really fell in love with Biology my freshman year of high school, when my all time favorite teacher, Mr. Cinti helped me extract my DNA one afternoon, just for fun. Writing is my passion, and I’m excited to explore my skills in a variety of genres this year. This blog is my first ever attempt at journalism/ science writing, and I’m excited to give it a try!

Creating a Gender Inclusive Campus: Reflecting on “Becoming Johanna”

Following Duke’s Oct. 4 screening of the 2016 documentary, “Becoming Johanna,” students, faculty, staff and community members in the audience were eager to ask questions of the panel, which included the film’s director/producer, Jonathan Skurnik, and even the film’s transgender subject, Johanna Clearwater herself.

Johanna Clearwater pictured with the film’s director/producer Jonathan Skurnik

The film showcases the heart-wrenching and empowering story of a latina transgender teenager growing up in Los Angeles. After beginning her transition at age 16, Johanna faced the rejection of her mother and intense opposition from school authorities. Soon after, she was abandoned by her family and entered the foster care system, where she was lucky to find a much more supportive family environment. After changing schools, she connected on a personal level with her school principal, Deb, who helped Johanna find a community where she felt understood and supported. This success story of self-advocacy and resilience in the face of abandonment and exclusion highlights the daily struggles of many transgender teenagers. For these individuals, becoming comfortable in their own skin is the end of a long and demanding journey, often made even more difficult by the ignorance and cruelty of society. Finding and following the path to authentic expression takes a huge amount of courage, as this route is often layered with adversity.

Before the screening, Duke clinical social worker Kristin Russel put the film in context for the audience, inviting our reflection with her words: “A well told story… is really what can help us bridge the unfortunate distance that can remain uncrossed and misunderstood if such stories are silenced.” Chief Diversity Officer for the School of Medicine Judy Seidenstein then introduced the film and facilitated the panel discussion.

After the film, the audience was invited to join the conversation. Questions came from every demographic of the crowd, and provided a nice sampling of opinions. Many audience members pointed out how important these conversations are, especially in a conservative state like North Carolina that has so recently struggled with the protection of LGBTQ rights with last year’s ‘Bathroom Bill.’ Specifically, the questions and comments from hospital staff and faculty from the School of Medicine gave a nice insight into the direction of support on campus for sexual and gender diversity.

Audience members reflect on the film with those nearby

Cheryl Brewer, the Associate Vice President of Nursing, told the room about the inclusion work that she is leading in the School of Nursing. They have developed a new core curriculum to promote acceptance and support of gender and sexual diversity through situational trainings. She noted that there have been some people that struggle with implicit biases more than others, but that the program has been a success overall.

Russell spoke briefly about her work with transgender and gender diverse youth in the clinical setting and emphasized the importance of having family support. Legally and psychologically, maintaining family involvement and support of patients is essential for treatment.

Events like this one reflect ongoing efforts to support sexual and gender diversity within and beyond Duke, by promoting conversation and increasing empathy through storytelling. Duke is well on the way to becoming a much more inclusive community, where everyone can feel a sense of belonging.

Guest post by Anne Littlewood

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