A Person’s Race Influences Question Asking as Much as Their Stroke History

DURHAM, NC — Strokes that occur on the right side of the brain can sometimes subtly impair social communication, which can be difficult for clinicians to assess.

But these impairments are a lot less subtle for the patients and their families, who often have their lives and livelihood upended, leading to significant life changes such as job loss and divorce.

Clinical researchers have developed a few diagnostic tools for right side, (right hemisphere) stroke survivors, but the tools have been largely based on data from White patients.

And that’s a problem, according to Duke speech pathologist and assistant professor Jamila Minga, Ph.D., CCC-SLP, because the few diagnostic tools available may be biased against the people most affected by stroke. Black men and women are twice as likely to have a stroke compared to White adults, and a person’s linguistic tendencies can vary based on their race and gender.

A new study from Duke and North Carolina Central University (NCCU) that Minga led verifies the suspicion that race changes how communication impairments present themselves.

Minga has found that some right brain stroke survivors ask fewer questions. But this new study also found that a person’s race – independent of brain injury – affects their inclination to ask questions.

The research appears on January 10 in the Journal of Speech, Language, and Hearing Research.

While a stroke is just as likely to occur within the left or right side of the brain, research on stroke-related communication deficits has mostly focused on people who have survived a left hemisphere stroke.

“That's largely because communication impairments after a left hemisphere stroke are more overt,” said Minga, who recently joined Duke as an assistant professor in the department of head and neck surgery & communication sciences.

Instead, right hemisphere stroke survivors have what clinicians call apragmatism — a difficulty understanding and producing language that is appropriate for different settings and situation. For example, Minga recalled the time she visited a patient’s room for a speech assessment and while his wife sat in a chair beside him, the patient asked Minga to join him in his hospital bed. He wasn’t joking or being deliberately crass.

“He could produce language. He was completely intelligible. His sentence structure, grammar and morphology were all fine,” Minga said. “The appropriateness? Not so much.”

It’s this subtlety in speech and social conventions that makes communication impairments so hard to pinpoint in right hemisphere stroke survivors, which leaves many undiagnosed and without assistance, Minga said.

Another study by Minga found that right hemisphere stroke participants asked fewer questions when getting to know a new person, inspiring her and others to measure the quantity and quality of question asking as a potential diagnostic tool.

“Everyone recognizes what a question is, no matter what language you speak,” Minga said. “It’s easily quantifiable. And questions are used to initiate, maintain and dissolve relationships. They're key to social communication.”

To address whether race affected a stroke survivor’s question-asking habits, Minga analyzed five-minute snippets of conversation from 32 women who had participated in a prior study and measured how many questions they asked while getting to know someone new. The participant pool consisted of an equal number of Black and White women, half of whom had sustained a right hemisphere stroke.

As Minga had found before, right hemisphere stroke participants asked fewer questions than their non-stroke counterparts no matter their race during the get-to-know-you chat with an unfamiliar person (a female speech pathology graduate student).

However, when Minga and her team analyzed the results by race, they discovered that no matter the stroke condition, Black women asked half as many questions as White participants, about 20 on average.

“White participants without stroke had the highest frequency of question-asking, followed by White participants who had a right hemisphere stroke,” Minga said. “Then the Black participants who did not have a stroke, and the lowest numbers seen were with Black participants who had experienced a right hemisphere stroke.”

The results highlight how diagnosing communication impairments resulting from a right hemisphere stroke may need to be adjusted based on race.

The research team is following up on this study to see whether pairing Black participants with a Black conversation partner changes the nature of question asking. (The vast majority of speech pathologists are White; only 4% identify as Black).

Minga hopes this work motivates clinicians to consider providing more information to patients rather than assuming someone’s reservedness is due to a lack of curiosity. Especially for Black women.

“For Black women who survive a stroke, the functional consequences of a communication impairment are significant,” Minga and her team write in their report. “It can impact financial stability, child rearing and daily socializing, which are all important for good health and well-being.”

Support for the research came from the U.S. National Institute on Deafness and Other Communication Disorders (3R01-DC008524-11S1, L60 DC019755), the U.S. National Institutes of Health Office of Research on Women’s Health (2K12-HD043446-16), the U.S. National Institute on Minority Health and Health Disparities (5U54MD012392-03), and the Duke University School of Medicine.

CITATION: “Intersectionality of Race and Question-Asking in Women After Right Hemisphere Brain Damage,” Danai K. Fannin, Jada Elleby, Maria Tackett, Jamila Minga. Journal of Speech, Language and Hearing Research, Jan. 10, 2023. DOI: 10.1044/2022_JSLHR-22-00327.

Designing With DNA

DURHAM, N.C. — Marvel at the tiny nanoscale structures emerging from research labs at Duke University and Arizona State University, and it’s easy to imagine you’re browsing a catalog of the world’s smallest pottery.

A new paper reveals some of the teams’ creations: itty-bitty vases, bowls, and hollow spheres, one hidden inside the other, like housewares for a Russian nesting doll.

But instead of making them from wood or clay, the researchers designed these objects out of threadlike molecules of DNA, bent and folded into complex three-dimensional objects with nanometer precision.

These creations demonstrate the possibilities of a new open-source software program developed by Duke Ph.D. student Dan Fu with his adviser John Reif. Described December 23 in the journal Science Advances, the software lets users take drawings or digital models of rounded shapes and turn them into 3D structures made of DNA.

The DNA nanostructures were assembled and imaged by co-authors Raghu Pradeep Narayanan and Abhay Prasad in professor Hao Yan’s lab at Arizona State. Each tiny hollow object is no more than two millionths of an inch across. More than 50,000 of them could fit on the head of a pin.

But the researchers say these are more than mere nano-sculptures. The software could allow researchers to create tiny containers to deliver drugs, or molds for casting metal nanoparticles with specific shapes for solar cells, medical imaging and other applications.

To most people, DNA is the blueprint of life; the genetic instructions for all living things, from penguins to poplar trees. But to teams like Reif’s and Yan’s, DNA is more than a carrier of genetic information — it’s source code and construction material.

There are four “letters,” or bases, in the genetic code of DNA, which pair up in a predictable way in our cells to form the rungs of the DNA ladder. It’s these strict base-pairing properties of DNA — A with T, and C with G — that the researchers have co-opted. By designing DNA strands with specific sequences, they can “program” the strands to piece themselves together into different shapes.

The method involves folding one or a few long pieces of single-stranded DNA, thousands of bases long, with help from a few hundred short DNA strands that bind to complementary sequences on the long strands and “staple” them in place.

Researchers have been experimenting with DNA as a construction material since the 1980s. The first 3D shapes were simple cubes, pyramids, soccer balls — geometric shapes with coarse and blocky surfaces. But designing structures with curved surfaces more akin to those found in nature has been tricky. The team’s aim is to expand the range of shapes that are possible with this method.

To do that, Fu developed software called DNAxiS. The software relies on a way to build with DNA described in 2011 by Yan, who was a postdoc with Reif at Duke 20 years ago before joining the faculty at Arizona State. It works by coiling a long DNA double helix into concentric rings that stack on each other to form the contours of the object, like using coils of clay to make a pot. To make the structures stronger, the team also made it possible to reinforce them with additional layers for increased stability.

Fu shows off the variety of forms they can make: cones, gourds, clover leaf shapes. DNAxiS is the first software tool that lets users design such shapes automatically, using algorithms to determine where to place the short DNA “staples” to join the longer DNA rings together and hold the shape in place.

“If there are too few, or if they're in the wrong position, the structure won't form correctly,” Fu said. “Before our software, the curvature of the shapes made this an especially difficult problem.”

Given a model of a mushroom shape, for example, the computer spits out a list of DNA strands that would self-assemble into the right configuration. Once the strands are synthesized and mixed in a test tube, the rest takes care of itself: by heating and cooling the DNA mixture, within as little as 12 hours “it sort of magically folds up into the DNA nanostructure,” Reif said.

Practical applications of their DNA design software in the lab or clinic may still be years away, the researchers said. But “it's a big step forward in terms of automated design of novel three dimensional structures,” Reif said.

This research was supported by the National Science Foundation (1909848, 2113941, 2004250, 1931487).

CITATION: "Automated Design of 3D DNA Origami With Non-Rasterized 2D Curvature," Daniel Fu, Raghu Pradeep Narayanan, Abhay Prasad, Fei Zhang, Dewight Williams, John S. Schreck, Hao Yan, John Reif. Science Advances, Dec. 23, 2022. DOI: 10.1126/sciadv.ade4455

 

Former Duke Senior Administrator and Durham Neighborhood Advocate John Burness Dies













Gene Therapy for Heart Attacks in Mice Just Got More Precise

DURHAM, N.C. — If humans are ever going to be able to regrow damaged tissues the way lizards and fish routinely do, it will require the precise control of gene expression in time and place – otherwise you might end up with random cells growing everywhere or a new body part that never quits growing. That is, stopping the process just as important as starting it.

A team of Duke scientists studying how other animals regrow damaged tissues has made an important step toward controlling at least one part of the regenerative machinery with that kind of precision. They used the mechanisms zebrafish rely on to repair damage to their hearts combined with viral vectors used for gene therapy in humans.

In a new paper appearing online Dec. 13 in Cell Stem Cell, the researchers demonstrate the ability to control gene activity in response to injury, limiting it to a specific region of tissue and during a defined time window, rather than being continuously active in the entire organ.

They borrowed a segment of fish DNA that they call a TREE, tissue regeneration enhancer element. TREEs are a family of gene enhancers included in the genome that are responsible for sensing an injury and orchestrating the activity of repair-related genes for reconstruction in a specific place. These enhancers also can shut off gene activity as healing is completed. These regulatory elements have been found in fruit flies, worms, and mice as well as the zebrafish.

“We probably have them too,” said Ken Poss, Ph.D, the James B. Duke Distinguished Professor of Regenerative Biology in the Duke School of Medicine, who discovered heart regeneration in zebrafish two decades ago and has been studying it since. “But it’s just easier for us to find them in zebrafish and ask if they work in mammals.”

About 1,000 nucleotides long, these enhancer sequences are bristling with recognition sites for different factors and stimuli to attach and change gene activity. “We don’t fully understand how they do this and what they’re truly responding to,” Poss said.

Different cell types within an animal also have different types of these enhancers, Poss said. “Some of them are responsive in multiple tissues — those are the ones we use here. But when we profile regenerating spinal cord or fins in fish, we get different sequences.” There may be tens of thousands of these types of enhancers in the human genome, he added.

As a first step in this 6-year research project, the researchers incorporated several different kinds of zebrafish TREEs into the genomes of embryonic mice. Using a visible marker to indicate gene activity, they found that about half of the enhancers worked as intended and turned tissue blue when and where they sensed tissue injury in the transgenic mammals.

Then they wanted to know if they could selectively incorporate the enhancer elements into an adult mouse using adeno-associated virus, a familiar gene therapy tool for introducing gene sequences into cells. The virus introduced DNA containing an enhancer to all tissues, but the hope was that the TREEs would only become active in response to an injury.

A series of experiments in heart attack models of mice showed that viruses containing a TREE could be infused a week before injury and then the enhancer would jump into action when it detected injury. But they found it also worked when introduced to the animal a day or two after the heart attack. “All three TREEs that we tested could be effective if delivered one day or sometimes longer after the injury — they could still target expression to the injury,” Poss said.

“Is this method of delivering a TREE and a gene going to allow us to deliver a molecular cargo to the right place at the right time? We found that it does in mice,” Poss said.

They also virally delivered a TREE and a fluorescent marker gene in pigs, which have a much larger heart with a more human-like heart rate. They infused viruses into the pig hearts through the coronary arteries either before or after a heart attack and again, the marker only glowed at the site of the injury.

Then, to see if this system could actually repair damage, rather than just sensing damage and turning on a gene that lights up tissue, they delivered a hyperactivated form of YAP, a powerful tissue growth gene that is implicated in cancer. The key question was whether this “really potent hammer” that can make cell division run amok could be lassoed into working only in the right time and place.

They used a mutated YAP controlled by a TREE to see whether they could have safe growth of muscle after a heart attack in mice. “The TREE turned on a mutated YAP for a few weeks, just in the injury site, and then it naturally shut down expression,” Poss said. The treatment caused muscle cells to begin to divide and the mouse’s heart returned to near normal function after several weeks, though not without some scarring.

“You really wouldn’t want to express YAP at full blast, that can cause problems like excessive growth, but what we found is that we could direct it,” Poss said. “The whole animal gets the gene therapy, but the YAP cargo only gets expressed at measurable levels when and where you injure the heart,” Poss said. “We think we can use these methods to control genes in a certain time and certain space, and that includes shutting them off.”

The next task for the researchers will be understanding better what molecules bind to the enhancers, what controls their functions, and where they are located in the human genome, in addition to improving their targeting abilities.

“These control elements are what’s important,” Poss said. “Zebrafish have largely the same genes that we do, but their ability to regenerate the heart is a function of how they control those genes after a massive injury.”

“And what about other injury models?” Poss wonders. “Can this work for traumatic brain injury or spinal cord injury?”

Ruorong Yan and Valentina Cigliola were the lead authors for this research, which was supported by Translating Duke Health; the National Institutes of Health (F31-HL162460, R01-HL151522, P30-AG028716, R21-AG067245, R01-HL157277, U01-AI146356, UM1-HG013053, RM1-HG011123, R33-DA041878, U01-HL134764, R01-HL126524, R01-HL146366, R01-DK119621, R35-HL150713, R01-HL136182); National Science Foundation (EFMA-1830957); American Heart Association (AHA) (17POST33660087, 903369, AHA16SDG30020001, AHA117SDG33660922); Swiss National Science Foundation (P2GEP3_175016, P400PM_186709); and Fondation Leducq.

CITATION: “An Enhancer-Based Gene Therapy Strategy for Spatiotemporal Control of Cargoes During Tissue Repair,” Ruorong Yan, Valentina Cigliola, Kelsey A. Oonk, Zachary Petrover, Sophia DeLuca, David W. Wolfson, Andrew Vekstein, Michelle A. Mendiola, Garth Devlin, Muath Bishawi, Matthew P. Gemberling, Tanvi Sinha, Michelle A. Sargent, Allen J. York, Avraham Shakked, Paige DeBenedittis, David C. Wendell, Jianhong Ou, Junsu Kang, Joseph A. Goldman, Gurpreet S. Baht, Ravi Karra, Adam R. Williams, Dawn E. Bowles, Aravind Asokan, Eldad Tzahor, Charles A. Gersbach, Jeffery D. Molkentin, Nenad Bursac, Brian L. Black, and Kenneth D. Poss. Cell Stem Cell, Jan. 5, 2023. (Online Dec. 13, 2022)  DOI: 10.1016/j.stem.2022.11.012

Three From Duke Named to National Academy of Inventors

Duke chemist Matthew L. Becker and biomedical engineers Charles Gersbach and Warren M. Grill have been elected Fellows of the National Academy of Inventors (NAI) class of 2022. They are among 169 distinguished new fellows this year and join 20 other Duke faculty who have been recognized by the 12-year-old organization since 2014.

Matthew L. Becker is the Hugo L. Blomquist Distinguished Professor of Chemistry and Professor of Mechanical Engineering and Material Science and Biomedical Engineering.

Charles Gersbach is the John W. Strohbehn Distinguished Professor of Biomedical Engineering and Associate Professor of Surgery, Orthopaedic Surgery and Cell Biology.

Warren M. Grill is the Edmund T. Pratt, Jr. School Distinguished Professor of Biomedical Engineering and Professor of Neurobiology, Neurosurgery and Electrical and Computer Engineering.

The National Academy of Inventors (NAI) is a professional organization that was founded in 2010 to recognize and promote the contributions of inventors to society. The NAI is made up of over 4,000 members, including leading academic inventors from around the world, who have been recognized for their contributions to technology, innovation and creativity.

New Associate VP Named to Oversee Social Sciences, Humanities and the Arts

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New Associate VP Named to Oversee Social Sciences, Humanities and the Arts

Mary Frances Luce will help the Office for Research & Innovation guide Duke scholarship

Mary Frances Luce, Ph.D., Robert A. Ingram Professor of Business Administration, Interim Exectuive Vice Chancellor for Duke Kunshan University and Associate Vice President for Research & Innovation

Mary Frances Luce, Ph.D., Robert A. Ingram Professor of Business Administration, Interim Exectuive Vice Chancellor for Duke Kunshan University and Associate Vice President for Research & Innovation

Mary Frances Luce, Ph.D. <a href="https://www.fuqua.duke.edu/faculty/mary-frances-luce&quot; target=”_blank”>Mary Frances Luce, a Duke alumna and distinguished professor of business administration, has been appointed associate vice president for Research & Innovation to support social and behavioral sciences, humanities and the arts, Vice President for Research & Innovation Jennifer Lodge announced Monday.

Luce, who serves as interim executive vice chancellor for Duke Kunshan University in China, will begin her role February 1, 2023.

“Mary Frances demonstrates the qualities, perspectives and skills required to support research in the social and behavioral sciences, humanities and arts in this newly-created position,” Lodge said. “Her continued commitment to collaboration, integrity and Duke’s shared values will advance the research mission across the university.”

As associate vice president for Research & Innovation, Luce will work with the <a href="https://research.duke.edu/office&quot; target=”_blank”>Office for Research & Innovation leadership to ensure the delivery of excellent service and support for all Duke’s researchers and scholars, including faculty, trainees and staff.

“Mary Frances is an accomplished scholar and administrator whom I am delighted to welcome to this new role,” said Provost Sally Kornbluth. “I am confident she will be an excellent partner to Duke’s faculty in support of world-class scholarship in the social and behavioral sciences, and arts and humanities.” 

Luce will also serve as a liaison between the Office for Research & Innovation and key leaders in relevant schools, university-wide institutes, initiatives, centers, libraries and administrative offices.

“Creating a supportive environment that elevates and works for all investigators and scholars is one of my essential priorities,” said Luce. “I look forward to enabling our faculty’s research efforts to advance the frontiers of knowledge and contributing to the international community of scholarship within a responsible conduct of research framework.”

Luce previously served six years as associate and senior associate dean for faculty at the Fuqua School of Business, she served one term on the Duke Faculty Appointments, Promotion and Tenure (APT) committee and held multiple key leadership roles such as president of the Association for Consumer Research and co-editor of behavioral marketing’s flagship journal, the Journal of Consumer Research.

Luce earned her Ph.D. in business administration from Duke and graduated cum laude with bachelor’s degrees in economics and marketing from Ball State University.

Parents Talk More To Toddlers Who Talk Back

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Parents Talk More To Toddlers Who Talk Back

Girls babble their way to bigger vocabularies sooner than boys, but it’s not because parents talk to them more

A participant in Dailey and Bergelson’s study dons a dual-camera headset to capture video and audio once a month. Credit - Elika Bergelson, Duke

A participant in Dailey and Bergelson’s study dons a dual-camera headset to capture video and audio once a month. Credit – Elika Bergelson, Duke

DURHAM, N.C. — Hummus. Chewbacca. Tofu. Belly button.

These are just a few of the thousands of words scientists at Duke painstakingly decoded from over 2,000 hours of infants’ daily lives. They recently used these data to determine if the amount of language kids hear might explain why girls have bigger vocabularies early in life than boys.

It doesn’t.

Instead, Shannon”>https://scholars.duke.edu/person/shannon.dailey”>Shannon Dailey, Ph.D., a Duke University postdoctoral scholar and lead author of the new study, found that rather than caregivers talking more to their young daughters, they appear to talk more to young children who themselves are already talking, regardless of their gender. This offers an important insight for language development.

 “This study provides evidence that children actively influence their own language environments as they grow,” Dailey said.

The new findings from Dailey come from her time as a graduate student in the lab of co-author and Duke psychology & neuroscience professor Elika”>https://scholars.duke.edu/person/elika.bergelson”>Elika Bergelson, Ph.D.

The paper appears in the journal Child Development on Dec. 1.

“People have long noted that there are sometimes differences between girls and boys for different language skills,” Bergelson said. “Language delays and deficits, for example, are more common in boys than and girls, so that raises the question of why.”

Dailey and Bergelson reasoned that girls’ typical (and temporary) vocabulary advantage might be due to them receiving more “language input” from their parents than boys.

To test that hunch, the team and a cadre of research assistants counted the utterances that 44 kids (21 girls and 23 boys) heard and produced for an entire year, starting when the tots were only six months old. This age range is ideal because they can track what kids are hearing at six months, which is well before they start talking, all the way through when most kids have started talking at 18 months, Dailey explained.

Girls have a lexical leg up over boys around the time of their first birthday, but their early-life language advantage isn’t because they hear more chatter from mom or dad. Credit – Elika Bergelson Babies were outfitted once a month with a colorful vest that covertly housed a pocket-sized audio recorder to capture a day’s worth (~16 hours) of conversation. They also wore a small camera-embedded cap on their noggin on a separate day once a month to record video, from which the team extracted audio for analysis.

All told, Bergelson amassed a whopping 8,976 hours of sound.

“If it’s fully transcribed by the time I retire, I’ll be happy,” Bergelson said.

That’s because it can take up to eight hours to transcribe just a single hour of recorded audio with a “fine grain of detail,” Bergelson said. To help save time, the team focused on the chattiest few hours per recording, amounting to 2,112 hours of sound to unpack.

Still, with 48 hours of audio from each of the 44 kids, a researcher working nonstop starting January 1 wouldn’t finish transcribing it until December 5 the following year (appropriately, that happens to be National”>https://nationaltoday.com/national-communicate-with-your-kids-days/”>Na… Communicate With Your Kids Day).

Unfortunately, Siri and its peers aren’t smart enough to automatically transcribe baby talk (or even everyday caretaker talk), so Bergelson relies on research assistants in her lab to annotate everything by ear.

The team’s hard work paid off with their latest batch of findings from their massive “corpus,” or finely detailed set of spoken words.

Dailey and Bergelson found, as others have before, that girls have bigger vocabularies than boys, and they grow their vocabularies faster across early life. In this case, Dailey and Bergelson approximated vocabulary size by counting the number of unique nouns kids uttered.

“Most of what kids under 18 months say is nouns,” Bergelson said. “So it’s a nice proxy for language development and vocabulary.”

The team then went down the line trying to figure out what might account for girls’ larger lexicon.

Dispelling antiquated beliefs, Dailey and Bergelson found that girls aren’t more talkative – girls and boys spoke the same amount, a finding that others have found persists into adulthood, Bergelson said. That made it less likely that more conversational practice might lead to a bigger vocabulary.

The girls’ bigger vocabs also weren’t due to them speaking earlier per se. While girls typically warbled their first words around the time of their first birthday, boys were right behind them, and tended to start talking just a month later at 13 months of age.

In the end, the team couldn’t account for girls’ bigger vocabularies based on what they heard before they uttered their first words. Rather, they found that parents talked more to their kids once they started talking, regardless of gender.

“It turns out that girls have a larger vocabulary by 18 months,” Bergelson said. “And so that could’ve meant caretakers talk to girls more, but really they just talk to talkers more.”

Support for the research came from the U.S. National Institutes for Health (NIH DP5 OD019812).

CITATION: “Talking To Talkers: Infants’ Talk Status, But Not Their Gender, Is Related To Language Input,” Shannon Dailey, Elika Bergelson. Child Development, Dec. 1, 2022. DOI: 10.1111/cdev.13872

Corporations Are Making Promises on Plastic Pollution, But Are They Keeping Them?

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Corporations Are Making Promises on Plastic Pollution, But Are They Keeping Them?

A Mother’s High Fat Diet May Rewire Male and Female Babies Brains Differently, Research Suggests

A Mother’s High Fat Diet May Rewire Male and Female Babies Brains Differently, Research Suggests

Quotes postdoctoral researcher Alexis Ceasrine

Aravind Asokan to Lead Partnership with Danaher Corporation to Accelerate Gene Therapy Breakthroughs