Culture

Molecular stress indicator not observed in survivors of child sexual abuse

UNIVERSITY PARK, Pa. -- Researchers and medical experts have long known that child sexual abuse has profoundly negative effects on the health of survivors; however, an international team of researchers was not able to find a link between the abuse and telomere length, considered an indicator of cellular aging and health.

Telomeres -- molecular complexes that cap the ends of chromosomes -- naturally decline in length as a person ages. But past research suggests that telomeres can shorten prematurely in response to stress, said Laura Etzel, a doctoral candidate in biobehavioral health at Penn State and lead author of the study. The researchers, who reported their findings in Psychoneuroendocrinology, available online now, hypothesized that signs of sexual abuse could show up in shortened lengths of a survivor's telomeres.

"Essentially, when we look across different tissues, we find that in many cases shorter telomere lengths are associated with earlier onset aging-related phenotype and diseases. So, for example shorter telomere lengths in the blood or in the heart tissues are associated with earlier and more severe cardiovascular events," said Etzel. "Contrary to our hypothesis, in this cohort, child sexual abuse in the mothers we studied was not associated with differences in telomere lengths at age 36."

Because telomere length is often passed on to offspring, the researchers also checked the telomeres of the women's children and did not find any association between the abuse and telomere length in the children either.

The results are already prompting the team to consider a few different routes for future research, particularly in addressing some of the limitations of the study, said Etzel. For example, she added that investigating the effects of variables -- such as the differing impact of abuse severity, or the length of the abuse -- may be critical, albeit difficult, next step in the research.

"It's important to note that we found no evidence in this cohort of differential telomere lengths between women who were sexually abused as children and those who were not sexually abused as children," she said. "Within both groups of women, however, we have women who were exposed to extreme poverty, to violence, to emotional abuse and physical abuse. So, we didn't compare someone who reported no abuse with someone who only reported sexual abuse. In this research area, it's difficult to tease apart those various forms of abuse because these types of abuse tend to manifest together."

She added that because there was a 20-year gap between when the abuse occurred and when the measurement of the telomeres, there is a possibility that other influences negated the effects of the sexual abuse in the telomeres.

Telomere science is complex, said Etzel and the researchers conducted several checks to verify their findings. For example, they examined telomeres drawn from multiple tissues. Finding similar results in different tissues diminishes the likelihood that the results could be due to mainly random effects, according to the team.

"In the mothers, specifically, we had enough participants to do a cross-tissue look at it, so we included telomeres from their buccal tissue -- the inside of their cheek -- as well as their leukocytes -- or blood -- and we found a strong correlation between those two tissues, as well, " said Etzel.

Although the findings ran counter to what the researchers originally hypothesized, studies like this are important for better understanding the long-term effects of childhood abuse, neglect and other forms of adversity, said Jennie Noll, professor of Human Development and Family Studies, Penn State and director of the Child Maltreatment Solutions Network. Noll is the principal investigator of the Female Growth and Development Study, the study from which the data for this work are drawn.

"Longitudinal, intergenerational cohort studies are extremely rare yet necessary to a nuanced understanding of the transmission of the effects of early life adversities across generations," said Noll. "This analysis is not only important in adding to the literature on intergenerational continuity, but is also an important null finding regarding the impact of early life stress on telomere length later in adulthood."

Noll is also an affiliate of Penn State's Institute for Computational and Data Sciences.

According to Idan Shalev, associate professor of biobehavioral health, Penn State, telomere science is an emerging field that holds great promise for understanding how psychological and environmental exposures influence health and aging over the life course.

"The results of this study were surprising to us, but it also shows that more work is needed to understand the context of specific exposures and other factors that may influence telomere biology," said Shalev. "This study also adds important information to what degree telomere length is correlated between different cells in the body and between mothers and children. This is a theme that our lab continues to investigate together with other leaders in the field as part of the Telomere Research Network."

This investigation used data from the Female Growth and Development Study, which began in 1987. Female subjects with substantiated sexual abuse were referred to the study by Child Protective Services (CPS) agencies in the Washington, D.C., metropolitan area. Control subjects were recruited from the same communities.

Since the study began, the researchers have held five follow-up assessments. Of the 132 females who took part in the study, 108, or 82%, completed blood collection for DNA extraction and TL measurement. The researchers controlled for socioeconomic status, smoking and waist-to-height ratio because of these variables' known associations with telomere length. The researchers also measured anxiety and depression levels in the participants.

Credit: 
Penn State

Study reveals how two sex chromosomes communicate during female embryo development

Researchers at Massachusetts General Hospital (MGH) have solved a mystery that has long puzzled scientists: How do the bodies of female humans and all other mammals decide which of the two X chromosomes it carries in each cell should be active and which one should be silent?

In a breakthrough study published in Nature Cell Biology, the MGH team discovered the role of a critical enzyme in the phenomenon known as X chromosome inactivation (XCI), which is essential for normal female development and also sets the stage for genetic disorders known as X-linked diseases (such as Rett Syndrome) to occur.

Scientists have known for over a half century that female mammals undergo XCI during embryo formation. Females have two copies of the X chromosome, and each carries many genes. Having genes expressed on both X chromosomes would be toxic to the cell, as would having both X chromosomes inactivated. To avoid these fates, females evolved with a mechanism that inactivates, or silences, one of the chromosomes.

Over the years, investigators have made strides in understanding how XCI occurs. In 2006, a team led by Jeannie Lee, MD, PhD, of the Department of Molecular Biology at MGH reported that during embryo development the two X chromosomes briefly come together, or pair.

She and her colleagues have since uncovered conclusive evidence that pairing is necessary for the body to decide which X chromosome to inactivate. "But until now, no one knew what one X chromosome was saying to the other to make the decision," says Lee, who is senior author of the Nature Cell Biology paper.

To find out, Lee and her colleagues had to develop sophisticated molecular tools that allow them to study key proteins involved in XCI, which were previously difficult to measure. It was already known that, prior to pairing, both X chromosomes are identical, or "symmetrical," meaning that they express the same genes.

Importantly, both express a form of noncoding RNA called Xist, which plays a vital role in inactivating the X chromosome. However, both X chromosomes also express another form of RNA, Tsix, which blocks Xist and prevents XCI.

In the Nature Cell Biology paper, Lee and her team show that an enzyme called DCP1A randomly chooses one X chromosome to bind to, and in doing so it cuts off, or "decaps," Tsix's protective cover, making the RNA unstable. However, because DCP1A exists in tiny quantities, there is only enough to bind to one X chromosome. "DCP1A flips the switch that starts the entire cascade of X chromosome inactivation," says Lee.

As a result, a protein called CTCF--the "glue" that holds X chromosomes together during pairing--binds to the unstable Tsix RNA and causes it to shut down permanently. Xist is then able to complete the silencing of that X chromosome.

"DCP1A allows the two X chromosomes to have a fateful 'conversation'," says Lee, noting that there are many other instances where the body must choose which copy of a gene to express in order to maintain a healthy state. "This discovery," says Lee, "will help scientists understand how other molecular conversations take place in the cell."

Jeannie Lee, MD, PhD, of the Department of Molecular Biology at MGH, is also director of the Lee Laboratory and a professor of Genetics at Harvard Medical School. The lead author of the Nature Cell Biology Paper is Eric Aeby, PhD, a research fellow in the Lee Laboratory.

Credit: 
Massachusetts General Hospital

Researchers develop new detection method to protect Army networks

Army researchers developed a novel algorithm to protect networks by allowing for the detection of adversarial actions that can be missed by current analytical methods.

The main idea of this research is to build a higher-order network to look for subtle changes in a stream of data that could point to suspicious activity.

Most analytics build up first order networks, where edges represent a movement between two nodes. For instance, airports connected by direct flights. The history of multi-hop travel by people is lost in such networks. Higher-order networks include additional nodes to also represent the dominant (multi-hop) flows in the data.

The research focuses on harvesting social signals to detect emerging phenomena by looking beyond first-order Markov patterns over network data.

The work developed a representation that embeds higher-order dependencies into the network such that it reflects real-world phenomena and scales for big data and existing network analysis tools. It uses the representation to perform network analytics to identify influential nodes, detect anomalies and predict co-evolution of multi-genre networks.

"We developed a scalable and parameter-free algorithm for higher-order network representation, BuildHON+, building on our prior work," said Dr. Lance Kaplan, researcher with the U.S. Army Combat Capabilities Development Command's Army Research Laboratory. "We demonstrate the efficiency of BuildHON+ through comprehensive complexity and performance analysis on global ship movement data, which is known to exhibit dependencies beyond the fifth order, meaning, for example, we predict the next port based upon more than the past five ports that the shipment has passed through."

This work is the result of a collaboration under the laboratory's now concluded Network Science Collaborative Technology Alliance between Kaplan, Mandana Saebi, Jian Xu, and Nitesh Chawla from the University of Notre Dame, and Bruno Ribeiro from Purdue University. They were able to showcase the performance of BuildHON+ in the task of network-based anomaly detection on both real-world and synthetic taxi trajectory datasets.

To do this, the collaborators created a synthetic dataset of origins and destinations for taxi cabs. In the real world data set, there was only one abnormal day that could be detected. The synthetic data set enabled a more systematic comparison of the BuildHON+ against first order network approaches.

"Using a large-scale synthetic taxi movement data with 11 billion taxi movements, we show how multiple existing anomaly detection methods that depend on first-order network collectively fail to capture anomalous navigation behaviors beyond first-order, and how BuildHON+ can solve the problem," Kaplan said.

According to Kaplan, most analysis of streams over network data assume first-order Markov evolution, i.e., the probability that a ship or taxi visits a port/location depends solely on its current location in the network. The ability to represent higher-order dependencies enables one to distinguish more subtle traffic patterns.

The higher-order network representation results in a more accurate representation of the underlying trends and patterns in the behavior of a complex system, and is the correct way of constructing the network to not miss any important dependencies or signals, he said. This is especially relevant when the data is noisy and has sequential dependencies within indirect pathways.

Another way to describe this method is to look at shipment traffic.

"Consider ships traveling from port to port," Kaplan said. "Each port is a node in the network. A first order network is where an edge between ports B and A represents the non-zero probability of a shipment from port B to port A. Higher order networks consider edges where the shipment at port B has already traveled through specific ports in specific order. The algorithm uses the data stream to build such higher order networks by using specialized statistical tests to progressively determine which next higher order edge is necessary or not to explore."

By building up higher-order networks from the data streams at adjacent time intervals, he said, one can detect subtle changes in the data streams that traditional first-order networks would miss.

For instance, consider a small port E where all of a sudden there is a relatively large shipment of goods from port E to port D to port C to port B to Port A, but because port E is small, and most packages from port E go to port D anyway, the changes in the data stream would not change the structure of the first order network at all. However, Kaplan said, the higher order network method can potentially detect such changes.

In this example, the subtle change was because of a shipment of explosives to be used by a peer adversary in a region of conflict serviced by port A.

"This shows how subtle changes in a data stream of some supply/logistical network can provide intelligence of potentially nefarious activities," Kaplan said.

This research has numerous applications, ranging from information flow to human interaction activity on a website to transportation to invasive species management to drug and human tracking, Kaplan said. For Soldiers, it could be applied to a supply/chain network used both by Soldiers and Civilians within an area of interest.

"The higher-order network analysis can find weak signals in a logistics network of adversarial actions that would be missed by first-order network representations," Kaplan said. "This can include preparations by non-state actors to launch an attack in support of a peer adversary."

Moving forward with this research, there are still a number of scientific questions that the team, and the scientific community at large, will continue to pursue.

"The concept of higher order networks opens up many different interesting avenues of investigation within network science to better predict the coevolution of networks and detect weak signals of adversarial behaviors," Kaplan said.

For instance, he said, a potential research direction would be to generalize the notion of nodes into other network elements such as subgraphs or motifs so that one can better understand how social norms within the general population can evolve.

A second extension is to explore higher order networks in multi-layer networks representing different social groups or different modes of communication to increase the contextual fidelity to find weak anomalous signals. A related question is how to make the analysis robust to deception, where the streaming network data might be manipulated at a subset of the nodes.

Researchers said further testing and exploration will mature this technology for future Soldiers, keeping them safer and more prepared for the missions that lie ahead.

Credit: 
U.S. Army Research Laboratory

NASA looks at water vapor in remnants of tropical depression 10E

image: NASA's Terra satellite passed over 10E's remnants on Aug. 17 at 1:35 a.m. EDT (0535 UTC) in the Eastern Pacific Ocean. Terra found a small area of storms with highest concentrations of water vapor (brown) and coldest cloud top temperatures.

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Credits: NASA/NRL

Tropical Depression 10E weakened to a remnant low-pressure area in the Eastern Pacific Ocean. NASA's Terra satellite observed the water vapor content in the storm.

At 5 p.m. EDT on Sunday, Aug. 16, NOAA's National Hurricane Center noted that the depression had been devoid of organized deep convection for the previous 24 hours at at that time and lacked any convection. NHC therefore classified 10E as a post-tropical as a non-convective remnant low-pressure area.

Water vapor analysis of tropical cyclones tells forecasters how much potential a storm has to develop. Water vapor releases latent heat as it condenses into liquid. That liquid becomes clouds and thunderstorms that make up a tropical cyclone. Temperature is important when trying to understand how strong storms can be. The higher the cloud tops, the colder and stronger the storms.

NASA's Terra satellite passed over 10E's remnants on Aug. 17 at 1:35 a.m. EDT (0535 UTC) and the Moderate Resolution Imaging Spectroradiometer or MODIS instrument gathered water vapor content and temperature information. MODIS data showed a small area of coldest cloud top temperature, that were as cold as or colder than minus 63 degrees Fahrenheit (minus 53 degrees Celsius).

On Aug. 17 at 11 a.m. EDT, the National Hurricane Center (NHC) noted that there was a small area of showers and thunderstorms over the far southwestern portion of the Eastern Pacific basin that are associated with the remnant low pressure area formerly known as Tropical Depression 10E.  Environmental conditions do not appear conducive for significant development and regeneration of this system is not expected while it moves slowly westward.

NASA Researches Tropical Cyclones

Hurricanes/tropical cyclones are the most powerful weather events on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

For more than five decades, NASA has used the vantage point of space to understand and explore our home planet, improve lives and safeguard our future. NASA brings together technology, science, and unique global Earth observations to provide societal benefits and strengthen our nation. Advancing knowledge of our home planet contributes directly to America's leadership in space and scientific exploration.

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NASA/Goddard Space Flight Center

Society perceives the poor as less affected by distress than those with more means

image: The poor are perceived to be "hardened" by negative events and therefore less harmed by them than those with more means, even when this is patently false, according to a series of studies published by Princeton University.

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Egan Jimenez, Princeton University

PRINCETON, N.J.--Negative life events can cause crippling distress, significant hardships, and even lifelong trauma. The poor are perceived to be "hardened" by these events and therefore less harmed by them than those with more means, even when this is patently false, according to a series of studies published by Princeton University.

The researchers found this "thick-skin bias" persisted when looking at poverty in both childhood and adulthood, as well as across White, Black, LatinX, and Asian groups. The researchers also found strong evidence for the bias in a nationally representative U.S. sample, as well as people working in customer service, mental health, and education.

The findings, published in the journal Behavioral Public Policy, have profound implications. According to the authors, the assumption that lower-socioeconomic individuals are better equipped to handle distress than their higher-socioeconomic counterparts is persistent, often wrong, and could lead to institutional and interpersonal neglect of those most in need, further exacerbating cycles of poverty.

"If people in poverty are perceived as happy with less -- less distressed when things go badly and more pleased when little things go well -- they may receive less courtesy, less care, and less attention, along with greater neglect and disrespect," said Eldar Shafir, Class of 1987 Professor in Behavioral Science and Public Policy and professor of psychology and public affairs at the School of Public and International Affairs. "The thick-skin bias risks focusing attention, effort, and other resources on those who overwhelmingly receive them, while exacerbating and justifying the failure to support those most in need -- even when such treatment is neither strategic nor profitable, nor even intentional."

Shafir and co-author Nathan Cheek, a Ph.D. candidate in psychology at Princeton, theorized that a thick-skin bias might influence how people perceive the hardships of the poor. They decided to investigate this across a series of studies that looked at various negative life circumstances, from major to minor. Participants in the first few studies were recruited primarily through Amazon's Mechanical Turk, a crowdsourcing website, as well as other online platforms.

In the first four studies, participants were asked to rate the extent to which they thought individuals of different races would be affected by various negative life events. These ranged from minor inconveniences, like being served an overcooked meal, to more serious experiences like being wrongly accused of shoplifting by a police officer. Participants were presented with a photo and short "story" about each person -- all of whom were described as "born and raised in a large city in the U.S." and identified as either low or high socioeconomic status. Independent of race, individuals of lower socioeconomic status were perceived as significantly less harmed by the negative events that those of higher socioeconomic status.

In the next set of studies, the researchers evaluated poverty in childhood versus adulthood. Participants rated the extent to which a number of negative life events would affect an adult who was described as either having grown up in poverty or affluence or having experienced poverty or affluence in the last 10 years. In follow-up studies, the procedure was the same, though the person was said to have lived in poverty or affluence in the last year instead of 10 years. Other studies in this set followed this approach, differing slightly on details.

These studies found that both past and present socioeconomic status can drive the thick- skin bias. The researchers also observed that people believe the formerly rich are more easily toughened by poverty than the formerly poor are weakened by abundance.

In the last set of studies, the researchers evaluated the thick-skin bias in the judgments of professionals. They recruited chefs, social workers, teachers, and graduate students training to be therapists to be part of the study.

These professionals read about a person who had either a lower or higher socioeconomic background, and had experienced a series of negative events in their field. The chefs, for example, read about people experiencing an overcooked and badly prepared meal, or waiting an exceedingly long time to be served. The teachers read about a child who was scolded by a teacher. These professionals consistently rated the protagonists of lower socioeconomic status to be less affected than those of higher socioeconomic status by the same negative experiences.

Finally, the researchers conducted a representative survey across the U.S. population; 772 participants were analyzed and given a similar test. Participants judged the effect of 10 negative events on a low-socioeconomic or a high- socioeconomic person; sex and race differed, as well as the severity of the events.

Across all studies and scenarios, the thick-skin bias persisted: Participants generally perceived people of lesser means to be less affected by the same negative events than their higher socioeconomic counterparts. This was not driven simply by perceptions of the rich, either. While people thought the absence of hardship left the rich more vulnerable, they clearly felt that hardships hardened the poor. And, the researchers explain, this is often false: "Chronic stress and repeated adverse life experiences of the kind often encountered by those in poverty...do not buffer against future such negative events. On the contrary, they can exacerbate their impact," Shafir said.

The findings held true regardless of expectation, age, or profession. Whether the traumatic event was "to be expected" in the lives of the poor, or was equally surprising for poor and rich, people generally perceived those of lower socioeconomic status to be less distressed by it. Those who were presumed to grow up in poverty were also seen as being less affected by distress than those who grew up in higher socioeconomic contexts. Importantly, professionals working in a variety of fields displayed the thick-skin bias, which could affect how people of lower socioeconomic status are treated in restaurants, schools, and other settings.

This pattern of results, the researchers said, should be concerning. Policymakers themselves are likely to exhibit the thick-skin bias, which is likely to shape their judgments of urgency and need, and can fuel institutional inequality. This is also true for other practitioners like those in finance, housing, law, philanthropy, or the criminal courts. Perhaps most consequential, the researchers conclude, are the implications of the thick-skin bias for the levels of concern and civility shown in everyday life.

"During a global pandemic and recession, it is perhaps more important than ever to ensure that people in poverty receive the resources and support they need," said Cheek. "But it is hard to imagine achieving that if the thick-skin bias prevents us from fully seeing people's experiences -- their distress and their pain -- in the first place."

Credit: 
Princeton School of Public and International Affairs

Potential drug target revealed to help more children survive a lethal heart defect

image: The image on the right shows more robust cardiac muscle fiber development when the gene FN1 is active. The fibers show clear, evenly spaced bands called sarcomeres. Typically, HLHS-affected hearts lack FN1 activity, resulting in fibers with indistinct, disorganized sarcomeres (left).

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Cincinnati Children's

When children are born with hypoplastic left heart syndrome (HLHS), they require a series of major surgical procedures to survive. But even with a repaired heart, as many as one in four children die from complications before age 25.

Now, a study published by a new faculty member at Cincinnati Children's reports a potential therapeutic target that might promote heart cell regeneration even before birth.

Details were published online Aug. 17, 2020, in Cell Stem Cell.

ATLAS PROVIDES DEEP LOOK AT EARLY HEART DEVELOPMENT

Mingxia Gu, MD, PhD, formerly of Stanford University, joined the Center for Stem Cell & Organoid Medicine (CuSTOM) and the Division of Pulmonary Biology at Cincinnati Children's earlier this year. She has been working for several years to find ways to prompt healing in damaged heart tissues.

In this study, a team led by Gu and co-first authors Yifei Miao, PhD, and Lei Tian, PhD, used advanced single-cell transcriptomic analysis to develop a human heart "atlas" that tracks the full chorus of signals that endocardial cells send to each other as the heart develops during pregnancy.

Comparing this atlas of healthy heart development to data from lab-created induced pluripotent stem cells featuring HLHS defects revealed a collection of abnormalities in endocardial cells that disrupt healthy heart formation. Endocardial cells play several pivotal roles in heart development and disease. They can sense blood flow in the heart, interact with surrounding muscle cells, and give rise to key structures of the heart including atrioventricular valves and atrial and membranous ventricular septa.

Tracing HLHS-related disruptions to these cells represents a change in thinking compared to efforts that had been focused on myocardial cells, which form the beating muscle of the heart.

The hopeful news: the team found a potential therapeutic target that could be drugged to improve endocardial function, thus regenerating the cardiac valves, septum, and coronary vessels, and eventually increasing heart chamber size, which could reduce the need for multiple surgeries after birth.

WHAT IS HLHS?

Hypoplastic left heart syndrome results in infants born with a severely malformed cardiac left ventricle, the heart's main pumping chamber. HLHS accounts for about 3% of all congenital heart defects, with a prevalence rate of 1 to 1.5 cases per 5,000 live births in the United States.

Treatment requires three surgeries to reroute blood flow so that the right ventricle can support all the work the heart must perform.

The unusual amount of pressure the repaired heart endures, plus other factors, can lead to heart failure that requires organ transplantation to treat.

For several years, scientists have tried various ways to use a person's own stem cells to help damaged hearts heal. Most early efforts have had little success, especially for adults. In children, however, heart tissues continue to grow, which makes scientists more hopeful that stem cell therapies or other treatments might help improve daily health and life expectancy.

TREATMENT TARGET: FN1

Gu and colleagues found that the gene fibronectin (FN1) was significantly downregulated in HLHS endocardium. Various genetic abnormalities combined to impede FN1, leading to impaired valve formation and poor cardiomyocyte growth and maturation.

"Our discoveries provide a new facet to the pathogenesis of HLHS and an alternative angle for early intervention and cardiac regeneration in HLHS," Gu says.

Given that fetal gene editing is not an option for human infants, more research is needed to determine whether a treatment to replace the missing functions of FN1 in HLHS can be developed for use after a child is born.

"The significance of this finding is that by discovering this gene's role, we now have a target for future study," Gu says.

Credit: 
Cincinnati Children's Hospital Medical Center

Drexel study: Measuring social networks of young adults with autism

As many have recently discovered, social connections are vital to a person’s wellbeing. While social isolation is a core challenge associated with autism, researchers from Drexel University’s A.J. Drexel Autism Institute have laid the groundwork to show how interpersonal relationships, and the resources they provide, could impact autistic youth’s adult outcomes.

“Many autistic young adults are disconnected from people, communities and organizations that could provide them with valuable social resources to support their transition to adulthood,” said Elizabeth McGhee Hassrick, PhD, assistant professor in the Autism Institute and lead author of the study.

The study demonstrated how social network analysis can be adapted for the field of autism, by measuring the social networks of autistic adults and the resources gained from the social connections.

Researchers had 17 autistic adults during post-high school transition (ages 19 to 27) complete an online survey about their social connections and the different types of support they gain from those connections. Parents of three of the autistic adults were also surveyed to provide information about the social connections they rely on to help their autistic young adults transition successfully.

“Interpersonal relationships and the resources and support embedded in the social networks of autistic young adults could impact key adult outcomes, including quality of life, mental health, employment and independence,” said McGhee Hassrick.

According to the researchers, there is currently very little known about the social networks of young adults on the autism spectrum and no studies measuring the social capital of youth and their parents together.

This project produced new and useful ways of collecting social network data from young autistic adults that will produce knowledge about how to help young adults on the autism spectrum build networks that will produce social resources needed to support positive outcomes in adulthood.

The study does have limitations, as it was only designed to test the feasibility of the social network measure and does not provide information about how networks might impact outcomes. There is also the possibility of under-reporting the actual size and makeup of autistic young adult networks, due to the social network measure only allowing participants to identify five people.

“Future studies using our social network measure might provide valuable information about possible interventions that could help autistic youth acquire the social resources needed for successful adult outcomes,” said McGhee Hassrick.

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Drexel University

Penguins are Aussies. Or are they Kiwis?

image: Juliana Vianna of the Pontifical Catholic University of Chile among a group of rockhopper penguins.

Image: 
Photo courtesy of Juliana Vianna

From the four-foot-tall emperor penguin to the aptly named foot-long little penguin, these unique flightless birds have invaded habitats from Antarctica to the equator, not to mention the hearts of the public.

A comparison of the full genomes of 18 recognized species of penguins provides clues to how they achieved this success -- though not their adorability -- over tens of millions of years, through warm and cold climate swings. It also cautions that today's rapidly changing climate may be too much for them.

"We are able to show how penguins have been able to diversify to occupy the incredibly different thermal environments they live in today, going from 9 degrees Celsius (48 F) in the waters around Australia and New Zealand, down to negative temperatures in Antarctica and up to 26 degrees (79 F) in the Galápagos Islands," said Rauri Bowie, professor of integrative biology at the University of California, Berkeley, and curator in the Museum of Vertebrate Zoology (MVZ) at Berkeley. "But we want to make the point that it has taken millions of years for penguins to be able to occupy such diverse habitats, and at the rate that oceans are warming, penguins are not going to be able to adapt fast enough to keep up with changing climate."

The researchers established conclusively that penguins arose in the cool coastal regions of Australia and New Zealand, not frigid Antarctica, as many scientists thought, and they pinpoint the origin of penguins at about 22 million years ago.

Despite their success in spreading widely throughout the Southern Hemisphere, many penguin populations are now threatened. Breeding colonies of emperor penguins in Antarctica have had to relocate because of receding sea ice, while last year saw mass mortality of Adélie penguin chicks on the continent. Galápagos penguin populations are declining as warm El Niño events become more common. In New Zealand, populations of little and yellow-eyed penguins must be fenced off to protect them from the depredations of feral cats, while African penguin populations are declining drastically as the waters off southern Africa warm.

"We saw, over millions of years, that the diversification of penguins decreased with increasing temperature, but that was over a longtime scale," said Juliana Vianna, associate professor of ecosystems and environment at the Pontifical Catholic University of Chile in Santiago. "Right now, changes in the climate and environment are going too fast for some species to respond to the climate change."

Vianna is first author of a paper with Bowie and other colleagues describing their findings that will be published online this week in the journal Proceedings of the National Academy of Sciences.

Where did penguins come from?

For the study, Vianna, Bowie and colleagues at museums and universities around the world gathered blood and tissue samples from 22 penguins representing 18 species and then sequenced and analyzed their whole genomes to chart penguin movement and diversification over the millennia.

Their conclusions resolve several long-standing questions: in particular, where penguins originated -- along the coasts of Australia, New Zealand and nearby islands of the South Pacific -- and when -- 22 million years ago. The genetic evidence indicates that the ancestors of the king and emperor penguins, the two largest species, soon split off from the other penguins and moved to sub-Antarctic and Antarctic waters, respectively, presumably to take advantage of abundant food resources. This scenario is consistent with the contested hypothesis that the emperor and king penguins -- the only two species in the genus Aptenodytes -- are the sister group to all other penguin lineages.

"It was very satisfying to be able to resolve the phylogeny, which has been debated for a long time," Bowie said. "The debate hinged on where, exactly, the emperor and king penguins were placed in the family tree, whether they are nested inside the tree closer to other lineages of penguins or whether they are sisters to all the other penguins, which is what our phylogeny showed and some other previous studies had suggested. And it fits with the rich fossil history of penguins."

The other penguins diversified and spread widely across the southern oceans, after the Drake's Passage between Antarctica and the southern tip of South America fully opened about 12 million years ago. The opening revved up the clockwise-moving Antarctic Circumpolar Current allowed these flightless birds to swim with the ocean currents throughout the southern ocean, populating both the cold sub-Antarctic islands and the warmer coastal areas of South America and Africa, where they populated to coastlines and remote islands with cold, upwelling, nutrient-rich water.

Today, penguins are found in Australia and New Zealand (yellow-eyed, little and other crested penguins), Antarctica (emperor, Adélie, gentoo and chinstrap), the tropical west coast of South America (Galápagos and Humboldt), the southern coasts of South America (Magellanic and southern rockhopper), the South Atlantic (Magellanic and Macaroni), southern Africa (African) and some in the sub-Antarctic (king, gentoo and Macaroni), Indian Ocean islands (eastern rockhopper) and sub-tropical regions (northern rockhopper).

Using powerful analysis techniques, some developed recently to analyze historical interactions among humans and our Neanderthal and Denisovan relatives, the researchers were able to determine that several groups of penguins have interbred over the course of their evolutionary history. Through exchange of genetic material, penguins may have shared genetic traits that facilitated the diversification of penguins across the steep thermal and salinity gradients encountered in the southern oceans. The most hybridized are the rockhopper penguins and their close relatives, which experienced at least four introgressions, or transfers of genetic information, over the course of millions of years.

The team also pinpointed genetic adaptions that allowed penguins to thrive in new and challenging environments, including changes in genes responsible for regulating body temperature, which allowed them to adapt to subzero Antarctic temperatures, as well as tropical temperatures near the equator; oxygen consumption that permitted deeper dives; and osmoregulation, so they could survive on seawater without the need to find fresh water.

New analytical tools helped the researchers to infer the sizes of ancient penguin populations going back about 1 million years. Most penguin species, they found, increased to their greatest numbers as the world cooled 40,000 to 70,000 years ago during the last glaciation -- many species prefer to breed on snow and ice -- and some had a bump in population during the previous glaciation period 140,000 years ago.

Two species -- the gentoo and the Galápagos -- seem to have been declining in populations for at least the past 1 million years.

DNA from the most isolated birds on Earth

Vianna has long-running research projects on penguins in Chile and Antarctica and, for this study, obtained blood samples from many species in those areas. Colleagues in France, Norway, Brazil, Australia, the United States and South Africa supplied blood from some remote species -- Norwegian colleagues provided blood from the chinstrap penguin of the Bouvet islands, for example -- while Vianna and Bowie obtained blood samples from an African penguin in a colony at the California Academy of Sciences in San Francisco.

But some species were harder to locate. The researchers were forced to rely on tissue from a preserved specimen of the yellow-eyed penguin in UC Berkeley's MVZ, while the American Museum of Natural History in New York supplied tissue from preserved erect-crested and Fiordland penguins.

Each genome was sequenced 30 times by Illumina shotgun sequencing, which produced tiny pieces -- about 150 base pairs long -- of the entire genome. Vianna, who at the time was working with Bowie at UC Berkeley on a sabbatical, painstakingly aligned each piece along a reference genome that had previously been sequenced -- that of the emperor penguin -- as a scaffold.

"Having a reference genome is like using the cover of a puzzle box to assemble a jigsaw puzzle: You can take all your super little pieces and align them to that reference genome," Bowie said. "We did that with each of these penguin genomes."

The genome comparisons told them that penguins arose between 21 million and 22 million years ago, narrowing down the 10-to-40-million-year window determined previously from fossil penguins.

They also disproved a paper published last year that suggested that the closely related king and emperor penguins were a sister group to the gentoo and Adélie penguins. Instead, they found that the king and emperor penguins are the sister group to all other penguins.

Vianna and Bowie now have genome sequences of 300 individual penguins and are diving more deeply into the genetic variations within and among disparate penguin populations. They recently discovered a new lineage of penguin that awaits scientific description.

"Penguins are very charismatic, certainly," Vianna said. "But I hope these studies also lead to better conservation."

Credit: 
University of California - Berkeley

Study hopes to encourage use of new technology to reduce errors in DNA testing

image: "We used a realistic model to estimate that tens of thousands of cases could be wrongly interpreted over the past two decades," Dr. Ge said.

Image: 
The University of North Texas Health Science Center at Fort Worth

Today's DNA testing is highly accurate, but errors still occur due to the limited genetic information accessible with current technologies. These errors can have serious impact on people's lives.

New technology has been shown to reduce the chances of false associations and should be more widely used, said Jianye Ge, PhD., Associate Professor and Associate Director of the Center for Human Identification at The University of North Texas Health Science Center at Fort Worth. In a study titled "How Many Familial Relationship Testing Results Could Be Wrong?" Dr. Ge reviewed worldwide practices to assess the potential of errors. Co-author of the study is Dr. Bruce Budowle, Director and Professor for the Center for Human Identification.

"Millions of cases have been tested globally," Dr. Ge said. "Of those, tens of thousands of cases could have been falsely interpreted."

The paper published in PLOS Genetics points out that existing problems of paternity testing have occurred over many years. Those errors are namely unrelated individuals being falsely concluded as biological relatives and biological relatives being falsely concluded as not related, such as a biological father concluded as unrelated to a child in paternity testing cases.

"We used a realistic model to estimate that tens of thousands of cases could be wrongly interpreted over the past two decades," Dr. Ge said. "The problem is the current technology has limitations and thus improvements are needed."

Testing via short tandem repeat or STR-based technology has long been the gold standard of familial relationship testing, such as civil and criminal paternity tests, missing persons identification, and kinship verification with international migration. It is the same tool used in forensics worldwide to distinguish who may or may not have been the donor of biological evidence found at the crime scenes.

Since the STR markers for DNA typing was introduced in the late 1990s, there has not been dramatic improvements in testing.

"In the beginning, only a few STRs were used," Dr. Ge said. "That improved to 20 to 23, which is what is used now."

"The chance of a mistake with that technology is small, but because of the sheer magnitude of testing - millions of cases - errors are not uncommon." he said.

Advances in technology over the last decade allow typing of hundreds of thousands or millions of single nucleotide polymorphisms, or SNPs.

"With the high density SNP-based technology, the chance of making a mistake is substantially less likely," Dr. Ge said.

Although UNTHSC stopped providing civil paternity testing services years ago, it still uses the STR technology and information in the context of missing person cases and criminal paternity cases. Nationwide the center does about 1,000 missing persons cases a year.

"We do lots of relationship testing to determine if a missing person belongs to a family," Dr. Ge said. "We need to continue to reduce the chance of making a false conclusion."

The purpose of the study was to encourage the community to move forward to this new generation of testing. "We need to move forward so that mistakes in kinship relationship testing are less of a possibility," he said.

Credit: 
University of North Texas Health Science Center

Desire to be in a group leads to harsher judgment of others

DURHAM, N.C. --If you're reluctant to identify as a Democrat or Republican even though you are staunchly liberal or conservative, you're probably also less prone to bias in other ways.

In a time where political affiliations can feel like they're leading to tribal warfare, a research team from Duke University's Trinity College of Arts & Sciences has found that the desire to be part of a group is what makes some of us more likely to discriminate against people outside our groups, even in non-political settings.

"It's not the political group that matters, it's whether an individual just generally seems to like being in a group," said Rachel Kranton. She is an economist who conducted the research with Scott Huettel, a psychologist and neuroscientist.

"Some people are 'groupy' - they join a political party, for example," Kranton said. "And if you put those people in any arbitrary setting, they'll act in a more biased way than somebody who has the same political opinions, but doesn't join a political party."

The research appears this week in the Proceedings of the National Academy of Sciences. Kranton and Huettel worked with Seth Sanders, formerly of Duke and now at Cornell, and Matthew Pease, a 2010 Duke graduate now at the University of Pittsburgh Medical Center.

The team tested what they call "groupiness" with 141 participants, using in-person research.

Participants were asked to allocate money to themselves and someone in their group, or to themselves and someone outside their group. They did this in different settings.

For one test, the participants were divided into groups according to their self-declared political leanings. In another setting, the groups were organized more neutrally, based on their preferences among similar poems and paintings. In a third test, the other recipients of the money were chosen at random.

The researchers expected to find the stronger people's opinions were within their group, the more they would discriminate against people outside the group.

But that wasn't the case.

What they found instead was that being more attached to the group itself made participants more biased against people outside their groups, regardless of the context, compared to people with similar political beliefs but who didn't identify as Democrat or Republican.

"There is this very specific distinction between the self-declared partisans and politically similar independents," Huettel said. "They don't differ in their political positions, but they do behave differently toward people who are outside their groups."

A third of the participants were not swayed at all by group membership when allocating their money. Those participants were more likely to be politically independent, the researchers found.

"People who say they're politically independent are much less likely to show bias in a non-political setting," Kranton said.

They also found less group-minded people made decisions faster.

"We don't know if non-groupy people are faster generally," Kranton said. "It could be they're making decisions faster because they're not paying attention to whether somebody is in their group or not each time they have to make a decision."

What makes people groupy? The researchers don't know, but they did rule out some possibilities. It doesn't relate to gender or ethnicity, for example.

"There's some feature of a person that causes them to be sensitive to these group divisions and use them in their behavior across at least two very different contexts," Huettel said. "We didn't test every possible way in which people differentiate themselves; we can't show you that all group-minded identities behave this way. But this is a compelling first step."

Credit: 
Duke University

Negative side effects of opioids could be coming from users' own immune systems

WASHINGTON, Aug. 17, 2020 -- In addition to possibly developing opioid use disorder, those who take opioids long term, including patients who have been prescribed the drugs for pain relief, can develop chronic inflammation and heightened pain sensitivity. Scientists now report in a pilot study that some of those side effects might be influenced by the body's own immune system, which can make antibodies against the drugs.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

A brand-new video on the research is available at http://www.acs.org/fall2020-opioids.

"Extrapolating from previous work on opioid vaccines, we started thinking that the patient's own immune system could be responsible for some of the negative effects of long-term opioid use," says Cody J. Wenthur, Pharm.D., Ph.D., who led the study. "We thought the body could be mounting an immune response and making antibodies against the drugs."

The researchers, who are at the University of Wisconsin-Madison School of Pharmacy, Scripps Research and Scripps Clinic, realized that one issue with this hypothesis is that commonly prescribed opioids for back pain, such as hydrocodone or oxycodone, are not large enough molecules for the immune system to recognize as antigens. From their past studies, however, they knew that an immune response could be triggered if something larger were bound to the drugs. This could happen in the body when a protein in the bloodstream reacts with the opioid to create a larger molecule in a process called haptenization.

To find out whether long-term opioid users produced antibodies against the drugs, the team performed an enzyme-linked immunosorbent assay (ELISA). Blood samples were obtained from 19 patients who used either hydrocodone or oxycodone for chronic back pain and from three control patients who used over-the-counter remedies (OTCs) or non-pharmacologic approaches. Jillian Kyzer, Ph.D., a postdoc in Wenthur's lab, along with Hyeri Park, Ph.D., a postdoc in the laboratory of Kim Janda, Ph.D., developed new techniques to synthesize hydrocodone and oxycodone haptens, linking them with a common blood protein to form bioconjugates. These bioconjugates were then coated on the surface of ELISA plates, and the patients' blood samples were added. If antibodies against the haptens were present in the patients' blood, they would stick to the surface of the plate and would be detected by another antibody that binds and creates a colorful dye through an enzyme-linked reaction.

Anti-opioid antibodies were found in the plasma of 10 people who regularly took prescription opioids for chronic lower back pain and almost none were found in those who used OTCs. The larger the dose of opioid, the larger the antibody response. "This was surprising," Kyzer says. "We saw antibody responses in people who were taking large doses for as little as 6 months."

The scientists are now working on isolating the key opioid antigenic intermediates in the body that prompt the generation of antibodies. One possibility is that the intermediates are modified proteins known as advanced glycation end products (AGEs), which could form when hydrocodone or oxycodone metabolites react with a carbohydrate. AGEs have been implicated in diseases such as atherosclerosis, cancer and Alzheimer's disease, and they might help explain chronic inflammation in long-term opioid users. The researchers have observed preliminary signals of hydrocodone-associated AGE formation under conditions relevant to those found in the human body, and they are planning to validate these results soon.

Wenthur says the findings support undertaking a broader study to determine the prevalence of antibodies in people based on race, age and sex. "The research could also be helpful in identifying efficacy biomarkers for opioid vaccines that are entering clinical trials," Kyzer says. "If our findings hold up in subsequent research, you would expect individuals with higher levels of these antibodies to be poor candidates for anti-opioid vaccine therapy."

Credit: 
American Chemical Society

Immunotherapy extends survival in mouse model of hard-to-treat breast cancer

image: Illustration of a spherical nucleic acid containing tumor cell lysate, with targeted cancer cells in the background (not to scale).

Image: 
Cassandra Callmann

WASHINGTON, Aug. 17, 2020 -- Immunotherapies for cancer -- treatments that prime the immune system to attack tumors -- are valuable weapons in the anti-cancer arsenal. But some cancers are more difficult to target with this strategy than others. Today, scientists report a new type of immunotherapy that dramatically extends the survival of mice that have triple negative breast tumors, a difficult-to-treat form of cancer.

The researchers will present their results at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

A brand-new video on the research is available at http://www.acs.org/fall2020-breast-cancer.

"From an immunotherapy standpoint, one of the biggest problems with triple negative breast cancer is that it doesn't produce any known antigens, or molecules recognized by the immune system, that are unique to the tumor," says Cassandra Callmann, Ph.D., who is presenting the work. "If you don't have a known tumor-specific antigen, it's hard to train your immune system to go after the tumor while ignoring healthy cells."

According to the Triple Negative Breast Cancer Foundation, this disease accounts for 15-20% of all breast cancers. The tumor gets its name from the fact that it tests negative for the estrogen receptor, the progesterone receptor and excess HER2 protein -- three proteins commonly produced in large amounts by other types of breast cancer. Because triple negative breast cancer lacks these markers, many commonly used breast cancer drugs aren't effective. This is one reason triple negative breast cancer has a poorer prognosis than other forms of the disease, according to the American Cancer Society.

To develop a new type of treatment, Callmann, a postdoctoral fellow in the lab of Chad Mirkin, Ph.D., at Northwestern University, needed to take a different approach from conventional immunotherapies that target a tumor-specific antigen. "The idea was to take tumor cells, chop them up, feed them to the immune system and let it figure out what to go after on its own," Callmann says. Other researchers have tried this approach for different cancers, but they typically administer both the chopped-up tumor cells (called a lysate) and a molecule that stimulates the immune system, known as an adjuvant, as a mixture. Instead, the team packaged the lysate and the adjuvant together in a single nanoparticle. The nanoparticle, called a spherical nucleic acid (SNA), contained the lysate inside its core and many copies of a DNA adjuvant radiating from its lipid membrane shell.

When the team injected SNAs under the skin of mice, the SNAs traveled to the lymph nodes. There, SNAs entered the cells, released their cargo and stimulated the cells to mount an immune response against antigens in the lysate. Interestingly, a stronger immune response occurred when the researchers incorporated oxidized tumor cell lysates from stressed tumor cells into SNAs.

The researchers tested the treatment on mice in which mouse triple negative breast cancer tumors were implanted. Two-thirds of mice receiving SNAs with oxidized lysates experienced complete tumor remission for at least 90 days, whereas all untreated animals died by day 30. None of the treated mice had obvious side effects or autoimmune responses.

The therapy is not yet ready for clinical trials, Callmann says. One of the next steps will be to investigate why the oxidized lysates work better than regular lysates. The team has begun to identify subsets of the lysates that are more immunogenic than others. She notes that a stressed cell could be producing different proteins, or perhaps the oxidizing agent is changing chemical groups on proteins. To get a clearer picture, Callmann plans to conduct a proteomic analysis to identify proteins that differ between oxidized and non-oxidized lysates.

The oxidized lysate/SNA approach might prove useful for treating other tumors, as well. "We have demonstrated that the overall structural presentation of a cancer vaccine or immunotherapeutic, as opposed to simply the identity of the active chemical components, dictates its potency, and this finding is opening doors in the field," Mirkin says.

Credit: 
American Chemical Society

Micro- and nanoplastics detectable in human tissues

Clarification: The researchers involved with the work highlighted in this release analyzed 47 human tissue samples by mass spectrometry, and these samples were found to have monomers, or plastic constituents, in them. These samples were not spiked with plastics. In separate experiments, the researchers spiked tissue samples with polymers (plastic beads), and found they could use flow cytometry to detect the polymer plastics that they introduced in tissues. In future work, these methods will be used to see if nanoplastics can be detected in human tissues. Edits have been made in the press release to clarify this information.

Updated on Oct. 21, 2020

WASHINGTON, Aug. 17, 2020 — Plastic pollution of land, water and air is a global problem. Even when plastic bags or water bottles break down to the point at which they are no longer an eyesore, tiny fragments can still contaminate the environment. Animals and humans can ingest the particles, with uncertain health consequences. Now, scientists report that they are among the first to develop analytical methods and reporting strategies for examining plastic monomers, micro- and nanoplastics in mammalian tissues, including human organs and tissues.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

“You can find plastics contaminating the environment at virtually every location on the globe, and in a few short decades, we’ve gone from seeing plastic as a wonderful benefit to considering it a threat,” says Charles Rolsky, Ph.D., who is presenting the work at the meeting. “There’s evidence that plastic is making its way into our bodies, but very few studies have looked for it there. And at this point, we don’t know whether this plastic is just a nuisance or whether it represents a human health hazard.”

Scientists define microplastics as plastic fragments less than 5 mm, or about 0.2 inches, in diameter. Nanoplastics are even smaller, with diameters less than 0.050 mm. Research in wildlife and animal models has linked micro- and nanoplastic exposure to infertility, inflammation and cancer, but health outcomes in people are currently unknown. Previous studies have shown that plastics can pass through the human gastrointestinal tract, but Rolsky and Varun Kelkar, who is also presenting the research at the meeting, are studying if the tiny particles accumulate in mammalian and human organs and how to detect them. Rolsky is a postdoctoral scholar and Kelkar is a graduate student in the lab of Rolf Halden, Ph.D., at Arizona State University.

To find out, the researchers collaborated with Diego Mastroeni, Ph.D., to obtain samples from a large repository of brain and body tissues that was established to study neurodegenerative diseases, such as Alzheimer’s. Samples were taken from human and animal lungs, liver, adipose tissue, spleen and kidneys –– mammalian organs likely to be exposed to, filter or collect plastic monomers and microplastics. To develop a method and test it, the team spiked nano/microplastic beads into a sample set mammalian tissues. Then, they analyzed the sample with flow cytometry. With this procedure, the researchers showed that they could detect the beads that they introduced into these samples. The researchers also created a computer program that converted information on plastic particle count into units of mass and surface area. They plan to share the tool online so that other researchers can report their results in a standardized manner. “This shared resource will help build a plastic exposure database so that we can compare exposures in organs and groups of people over time and geographic space,” Halden says. The flow cytometry method allowed the researchers to show that they can detect nano/microplastics in mammalian tissues to which these had been added. The researchers also demonstrated the use of μ-Raman spectrometry to study environmental contamination with microplastics, including polycarbonate (PC), polyethylene terephthalate (PET) and polyethylene (PE).

In addition, the researchers used another method called mass spectrometry to analyze 47 human liver and fat tissue samples. No materials were spiked into these samples. The team found plastic contamination in the form of monomers, or plastic building blocks, in every sample. Bisphenol A (BPA), still used in many food containers despite health concerns, was found in all 47 human samples.

Taken together, to the researchers’ knowledge, their study is the first to provide an array of methods for examining monomer, nano- and microplastic occurrence in human organs from individuals with a known history of environmental exposure. “The tissue donors provided detailed information on their lifestyle, diet and occupational exposures,” Halden says. “Because these donors have such well-defined histories, our study provides the first clues on potential plastic exposure sources and routes.”

Should people be concerned about the high detection frequency of plastic components (i.e., monomers) in human tissues? “We never want to be alarmist, but it is concerning that these non-biodegradable materials that are present everywhere can enter and accumulate in human tissues, and we don’t know the possible health effects,” Kelkar says. “Once we get a better idea of what’s in the tissues, we can conduct epidemiological studies to assess human health outcomes. That way, we can start to understand the potential health risks, if any.”

Credit: 
American Chemical Society

'Cyborg' technology could enable new diagnostics, merger of humans and AI

image: Molecular model of PEDOT with maleimide; carbon atoms are grey, oxygens red, nitrogens blue, sulfurs yellow and hydrogens white.

Image: 
David Martin

WASHINGTON, Aug. 17, 2020 -- Although true "cyborgs" -- part human, part robotic beings -- are science fiction, researchers are taking steps toward integrating electronics with the body. Such devices could monitor for tumor development or stand in for damaged tissues. But connecting electronics directly to human tissues in the body is a huge challenge. Now, a team is reporting new coatings for components that could help them more easily fit into this environment.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

"We got the idea for this project because we were trying to interface rigid, inorganic microelectrodes with the brain, but brains are made out of organic, salty, live materials," says David Martin, Ph.D., who led the study. "It wasn't working well, so we thought there must be a better way."

Traditional microelectronic materials, such as silicon, gold, stainless steel and iridium, cause scarring when implanted. For applications in muscle or brain tissue, electrical signals need to flow for them to operate properly, but scars interrupt this activity. The researchers reasoned that a coating could help.

"We started looking at organic electronic materials like conjugated polymers that were being used in non-biological devices," says Martin, who is at the University of Delaware. "We found a chemically stable example that was sold commercially as an antistatic coating for electronic displays." After testing, the researchers found that the polymer had the properties necessary for interfacing hardware and human tissue.

"These conjugated polymers are electrically active, but they are also ionically active," Martin says. "Counter ions give them the charge they need so when they are in operation, both electrons and ions are moving around." The polymer, known as poly(3,4-ethylenedioxythiophene) or PEDOT, dramatically improved the performance of medical implants by lowering their impedance two to three orders of magnitude, thus increasing signal quality and battery lifetime in patients.

Martin has since determined how to specialize the polymer, putting different functional groups on PEDOT. Adding a carboxylic acid, aldehyde or maleimide substituent to the ethylenedioxythiophene (EDOT) monomer gives the researchers the versatility to create polymers with a variety of functions.

"The maleimide is particularly powerful because we can do click chemistry substitutions to make functionalized polymers and biopolymers," Martin says. Mixing unsubstituted monomer with the maleimide-substituted version results in a material with many locations where the team can attach peptides, antibodies or DNA. "Name your favorite biomolecule, and you can in principle make a PEDOT film that has whatever biofunctional group you might be interested in," he says.

Most recently, Martin's group created a PEDOT film with an antibody for vascular endothelial growth factor (VEGF) attached. VEGF stimulates blood vessel growth after injury, and tumors hijack this protein to increase their blood supply. The polymer that the team developed could act as a sensor to detect overexpression of VEGF and thus early stages of disease, among other potential applications.

Other functionalized polymers have neurotransmitters on them, and these films could help sense or treat brain or nervous system disorders. So far, the team has made a polymer with dopamine, which plays a role in addictive behaviors, as well as dopamine-functionalized variants of the EDOT monomer. Martin says these biological-synthetic hybrid materials might someday be useful in merging artificial intelligence with the human brain.

Ultimately, Martin says, his dream is to be able to tailor how these materials deposit on a surface and then to put them in tissue in a living organism. "The ability to do the polymerization in a controlled way inside a living organism would be fascinating."

Credit: 
American Chemical Society

Safer, more comfortable soldier uniforms are in the works

image: In a test, untreated fabric (left-hand panel) burns completely after a flame is removed, whereas fabric treated with phytic acid (right panels) is self-extinguishing in seconds after the ignition source is removed.

Image: 
Sourabh Kulkarni

WASHINGTON, Aug. 17, 2020 -- Uniforms of U.S. Army soldiers must meet a long list of challenging requirements. They need to feel comfortable in all climates, be durable through multiple washings, resist fires and ward off insects, among other things. Existing fabrics don't check all of these boxes, so scientists have come up with a novel way of creating a flame-retardant, insect-repellent fabric that uses nontoxic substances.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

"The Army presented to us this interesting and challenging requirement for multifunctionality," says study leader Ramaswamy Nagarajan, Ph.D. "There are flame-resistant Army combat uniforms made of various materials that meet flame retardant requirements. But they are expensive, and there are problems with dyeing the fabrics. Also, some of the raw materials are not produced in the U.S. So, our goal was to find an existing material that we could modify to make it flame retardant and insect repellent, yet still have a fabric that a soldier would want to wear."

Because Nagarajan's research group focuses on sustainable green chemistry, the team sought nontoxic chemicals and processes for this study. They chose to modify a commercially available 50-50 nylon-cotton blend, a relatively inexpensive, durable and comfortable fabric produced in the U.S. The material is used in a wide range of civilian and military applications because the nylon is strong and resistant to abrasion, whereas the cotton is comfortable to wear. But this type of textile doesn't inherently repel bugs and is associated with a high fire risk.

"We started with making the fabric fire retardant, focusing on the cotton part of the blend," explains Sourabh Kulkarni, a Ph.D. student who works with Nagarajan at the University of Massachusetts Lowell Center for Advanced Materials. "Cotton has a lot of hydroxyl groups (oxygen and hydrogen bonded together) on its surface, which can be activated by readily available chemicals to link with phosphorus-containing compounds that impart flame retardancy." For their phosphorus-containing compound, they chose phytic acid, an abundant, nontoxic substance found in seeds, nuts and grains.

Next, the researchers tackled the issue of making the material repel insects so that soldiers wouldn't have to spray themselves repeatedly or carry an additional item in their packs. The team took permethrin, an everyday nontoxic insect repellent, and attached it to the fabric using plasma-assisted deposition in collaboration with a local company, LaunchBay. Through trial and error, the researchers eventually got both the phytic acid and permethrin to link to the fabric's surface molecules.

Using methods to measure heat release capacity and total heat release, as well as a vertical flame test, they found that the modified material performed at least 20% better than the untreated material. They also used a standard insect repellency test with live mosquitoes and found that the efficacy was greater than 98%. Finally, the fabric remained "breathable" after treatment as determined by air permeability studies.

"We are very excited," Nagarajan says, "because we've shown we can modify this fabric to be flame retardant and insect repellent -- and still be fairly durable and comfortable. We'd like to use a substance other than phytic acid that would contain more phosphorous and therefore impart a greater level of flame retardancy, better durability and still be nontoxic to a soldier's skin. Having shown that we can modify the fabric, we would also like to see if we can attach antimicrobials to prevent infections from bacteria, as well as dyes that remain durable."

Credit: 
American Chemical Society