Culture

KANSAS CITY, MO - It can be hard to dispute the common adage 'survival of the fittest'. After all, "most of the genes in the genome are there because they're doing something good," says Sarah Zanders, PhD, assistant investigator at the Stowers Institute for Medical Research. But, she says, "others are just there because they've figured out a way to be there."

The conventional understanding of evolution is that genes encoding a beneficial function are the most frequently transmitted, which ensures that the fittest organisms - the ones that have traits most favorable for their environment - survive. Less known is the fact that there exist parasitic gene elements within an organism that are doing just the opposite.

"The way one could think of it is that the genome is like a society," explains Zanders. "Within that society, there are individuals who derive their living from doing good things and making valuable contributions. But there are others who don't contribute in beneficial ways and are actually harmful to society," explains Zanders.

The Zanders Lab studies parasitic genes in Schizosaccharomyces pombe, a species of fission yeast sometimes found in the popular fermented tea drink kombucha. Because of its simplicity and fast generation times, S. pombe is a highly tractable system for studying parasitic gene elements, particularly a class known as meiotic drivers. Instead of conferring a benefit to their host, meiotic drivers confer distinct disadvantages to their host, in order to bias their own perpetuation. One method of doing so, employed by the wtf meiotic drive genes, is through selective poisoning of cells in meiosis.

Meiosis is the process of cell division through which sexually-reproducing organisms form gametes - such as egg and sperm cells in humans, or spores in yeast - to propagate the next generation. Normally, this process results in gametes that inherit one of two copies of each chromosome carried by the parent cell, and each copy is transmitted to gametes at an equal rate. Meiotic drivers, however, short-circuit this law of Mendelian segregation.

"Usually all the alleles - or variants of a particular gene - get a fair chance, and natural selection can pick the best ones," explains Zanders. "But alleles that are meiotic drivers select themselves even if they're not the best option. And they're never the best option."

In a paper published online August 13, 2020, in eLife, members of the Zanders lab explain how it could be possible that meiotic drivers persist in the population, even as they kill off many would-be hosts. It turns out that S. pombe can employ variants of other genes to help suppress the negative effect of meiotic drivers, albeit at a cost to fitness.

Usually, to propagate laboratory strains of S. pombe, they are inbred. "When you outcross two isolates that are almost identical, they produce almost no progeny," explains first author María Angélica Bravo Núñez, PhD, who was involved in the identification of the wtf genes, and who did this work in the Zanders Lab as a predoctoral researcher at the Graduate School of the Stowers Institute. "This suggested there might be some type of competition at play." Bravo Núñez and colleagues used this reasoning to seek out genes that could be in conflict in similar, but non-identical, genomes of S. pombe. The central experimental design of the current work involved outcrossing of S. pombe isolates that are over 99% identical.

"Outcrossing can have many advantages," says Bravo Núñez, such as providing a normal allele of a gene to rescue the effect of a mutant allele. "But the meiotic drive genes that we study actually exert their deleterious effect in the heterozygous scenario, where the alleles of a gene are not the same."

One illuminating experiment they did was to compare outcomes of inbred and outcrossed S. pombe isolates in a genetic background containing a mutation in rec12, which is a gene that promotes proper chromosome segregation.

"Rec12 usually promotes fertility," says Bravo Núñez. "When we removed rec12 function, the numbers of viable spores decreased, but only in the inbred scenario. The relative numbers of viable spores didn't really decrease in the outcrossed scenario." Moreover, of the viable spores, they found that survival was biased towards atypical gamete products, resulting from mis-segregation and unequal crossover of paired chromosomes. In other words, surviving spores contained the maximal number of meiotic drivers, sometimes due to inheriting an extra chromosome. This finding was surprising because extra chromosomes are usually considered very harmful. In humans, for instance, extra or missing chromosomes can lead to inviable gametes, severe birth defects, or infertility.

"When you have heterozygosity of wtf genes, making a mutation in the rec12 gene is relatively good for the organism, because that's just what has to happen in order to not kill all the progeny," says Bravo Núñez.

"We think of rec12 as this gene that's really important for fertility," explains Zanders. "But the situation is totally different when there is outcrossing. Having rec12 doesn't actually help at all, because the yeast is better off making gametes that do not result from proper chromosome segregation. This is just one example of the power of meiotic drivers to change the landscape of meiosis. Fundamentally, what is 'good' for the organism has changed."

"Having that extra chromosome is not good, and the yeast colonies look unusual, small, and irregular. But after they continue to grow for a while, the cells lose that extra chromosome and then they can thrive as haploids. So, this step is actually just temporary," says Bravo Núñez.

Precisely because meiotic drivers exert their influence in a heterozygous scenario, they are easy to miss. "There are many flavors of meiotic drive. Some forms of meiotic drive are hard to measure experimentally because the bias is so subtle," says Zanders. "We're not the first to study meiotic drivers in depth. We just have a better model system now, so we can make more progress faster."

"Drive systems tend to be repetitive, and you can usually find them in various copies in genomes," says Bravo Núñez. "They have, in many cases, already been found in other systems, such as fungi, mice, and fruit flies, but are not yet fully characterized." The study of meiotic drivers in S. pombe "will hopefully guide future research to understand other drive systems."

"Humans certainly have meiotic drive genes. Whether or not they have meiotic drive genes of the gamete-killing type is unclear," says Zanders. "Meiotic drive has likely affected the evolution of human centromeres, which are regions of chromosomes that are very important for proper chromosome segregation. Certain chromosome fusions exhibit meiotic drive in humans, as do sequences that are involved in DNA recombination. We're going to continue focusing on these and other parasitic gene elements, their strategies, and their effects."

Other coauthors of this work include Ibrahim M. Sabbarini and Lauren E. Eide from the Stowers Institute and Robert L. Unckless, PhD, from the University of Kansas.

This work was funded in part by the Stowers Institute for Medical Research, March of Dimes Foundation Basil O'Connor Starter Scholar Research Award (5-FY18-58 to SEZ), Searle Scholar Award (to SEZ), and National Institutes of Health (National Institute of General Medical Sciences awards R00GM114436 and DP2GM132936 to SEZ and National Cancer Institute award F99CA234523 to MABN). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Lay Summary of Findings

A new study published online August 13, 2020, in eLife from the laboratory of Sarah Zanders, PhD, at the Stowers Institute for Medical Research describes a strategy that the S. pombe fission yeast genome can use to mitigate some of the worst effects conferred by parasitic gene elements known as meiotic drivers.

The meiotic drivers analyzed in the study are able to short-circuit the conventional law of Mendelian segregation, which usually ensures that each gamete (reproductive cell) receives one of two copies of each chromosome from the parent cell with equal transmission. Meiotic drivers instead can poison gametes that do not contain their genetic sequence, thereby swinging the transmission rate in their favor.

As a way of enabling the survival of some gametes that would otherwise die, the S. pombegenome can employ variants of other genes to create a situation that "protects" them, even if it comes at a cost to fitness. For example, a mutation in rec12, a gene responsible for proper chromosome segregation, can lead to gametes having extra chromosomes. While extra chromosomes are usually undesirable, in this scenario they actually enable more gametes to survive. This surprising insight into meiotic drivers and how they can be suppressed could help researchers better understand the forces that shape the evolution of gamete formation, as well as those underlying human infertility.

Although Live Oak trees are common in South Florida today, Ken Feeley, a University of Miami biology professor, said their time here may be fleeting. With climate change pushing up temperatures, the oaks, which favor cooler conditions, could soon decline in the region and be replaced with more tropical, heat-loving species such as Gumbo Limbo or Mahogany trees.

"Live Oaks occur throughout the southeast and all the way up to coastal Virginia, so down here we are in one of the very hottest places in its range," said Feeley, who is also the University's Smathers Chair of Tropical Tree Biology. "As temperatures increase, it may simply get too hot in Miami for oaks and other temperate species."

Likewise, in Canada, as temperatures increase, sugar maple trees--which are used to produce maple syrup--are losing their habitats. And in New York City, trees that are more typical of the balmy South, such as Magnolias, are increasing in abundance and blooming earlier each year, news reports indicate.

These are just a few examples of a larger trend happening across the Americas--from Hudson Bay to Tierra del Fuego--as plant communities shift their ranges and respond to changing climates, Feeley pointed out. In his newest study, published in Nature Climate Change, Feeley, along with three of his graduate students and a visiting graduate student from the Nacional University of Colombia, analyzed more than 20 million records of more than 17,000 plant species from throughout the Western Hemisphere. They found that since the 1970s, entire plant ecosystems have changed directionally over time to include more and more of the species that prefer warmer climates. This process is called thermophilization.

"Almost anywhere you go, the types of species that you encounter now are different than what you would have found in that same spot 40 years ago, and we believe that this pattern is the direct result of rising temperatures and climate change," Feeley said.

The research of Feeley and his students demonstrates that entire ecosystems are consistently losing the plant species that favor cold temperatures, and that those plants are being replaced by more heat-tolerant species that can withstand the warming climate. Plants favoring cool temperatures are either moving to higher elevations and latitudes, or some species may even be going locally extinct. Feeley and his students are now exploring key focal species that may offer more insight into these processes.

"Some of these changes can be so dramatic that we are shifting entire habitat types from forests to grasslands or vice versa--by looking at all types of plants over long periods of time and over huge areas, we were able to observe those changes," he explained.

In addition to the effects of rising temperatures, the researchers also looked at how plant communities are being affected by changes in rainfall during the past four decades. Feeley and his team observed shifts in the amounts of drought-tolerant versus drought-sensitive plant species. But in many cases, the observed changes were not connected to the changes in rainfall. In fact, in many areas that are getting drier, the drought-sensitive species have become more common during the past decades. According to Feeley, this may be because of a connection between the species' heat tolerances and their water demands. Heat tolerant species are typically less drought-tolerant, so as rising temperatures favor the increase of heat-tolerant species, it may also indirectly prompt a rise in water-demanding species. Feeley stressed that this can create dangerous situations in some areas where the plant communities are pushed out of equilibrium with their climate.

"When drought hits, it will be doubly bad for these ecosystems that have lost their tolerance to drought," he said, adding that "for places where droughts are becoming more severe and frequent--like in California--this could make things a lot worse."

But the implications of thermophilization go far beyond just the loss of certain plants, according to Feeley. Plants are at the base of the food chain and provide sustenance and habitat for wildlife--so if the plant communities transform, so will the animals that need them.

"All animals--including humans--depend on the plants around them," Feeley said. "If we lose some plants, we may also lose the insects, birds, and many other forms of wildlife that we are used to seeing in our communities and that are critical to our ways of life. When people think of climate change, they need to realize that it's not just about losing ice in Antarctica or rising sea levels--climate change affects almost every natural system in every part of the planet."

CLEVELAND--Researchers at Case Western Reserve University have added to the growing body of understanding about how hydroxychloroquine (HCQ) is not a possible defense against COVID-19.

Specifically, they found that HCQ is not effective in preventing COVID-19 in patients with lupus and rheumatoid arthritis (RA), suggesting a broader interpretation of HCQ as ineffective preventive medicine for the general population. Their findings were recently published in the Annals of the Rheumatic Diseases.

Many researchers have focused on patients with systemic lupus erythematosus (SLE) and RA because HCQ is frequently taken by these patients. Anecdotal reports in the early stages of the pandemic showed these patients were not getting COVID-19. Earlier researchers then explored HCQ in the lab and found it effective against the virus, in addition to its already established anti-inflammatory properties, so testing in people for prevention or treatment at first held some promise. Since those early tests, various more recent studies have shown that HCQ is not effective in treating moderate-to-severe hospitalized cases. Treatment with HCQ early in the disease or for mild cases is still under review.

"Our study shows, with a large degree of confidence, that HCQ is ineffective as a preventive antiviral in people with SLE and/or RA taking drugs that suppress their immune system, putting them at greater risk," said Mendel Singer, PhD, MPH, lead author and associate professor and vice chair for education in the Department of Population & Quantitative Health Sciences at the Case Western Reserve School of Medicine. "Given how the study was structured, one can make an educated extension that it is not effective in preventing COVID-19 in people without those conditions. It is not uncommon for something to show promise in the lab, and then prove ineffective in the more complex biological landscape of humans."

The Case Western Reserve team drew on a large national database, pulling de-identified patient data from 36 health systems, to compile a much larger study than previous work, looking at patients with SLE and/or RA and their health outcomes related to their use of HCQ. Prior studies had fewer than 20 COVID-19 patients with SLE and/or RA; this study had 159. This study showed that patients with SLE and/or RA who contracted COVID-19 were just as likely to be taking HCQ as SLE and/or RA patients who did not get COVID-19.

"By drawing on data from a relatively large patient population with lupus and/or RA, we can offer a higher level of confidence in our findings," said Singer. "We see from this large retrospective review that this drug is ineffective in preventing COVID-19 in these patients who have been taking HCQ. If HCQ were effective in prevention, we would have seen fewer HCQ-taking SLE/RA patients with COVID-19, but did not. This likely means that HCQ is not active against the SARS-CoV-2 virus in humans--versus in the lab--and is unlikely to be an effective preventive antiviral for anyone."

ORLANDO, Aug. 17, 2020 - An international team of researchers using data from Arecibo Observatory and the Fermi Space Telescope have discovered what they call a "gamma-ray heartbeat" coming from a cosmic gas cloud.

The cloud is in the constellation Aquilla and "beats" in rhythm with a black hole 100 light years away in a microquasar system known as SS 433. The results were published today in the journal Nature Astronomy.

"This result challenges obvious interpretations and is unexpected from previously published theoretical models," says Jian Li, a Humboldt Fellow with the Deutsches Elektronen-Synchrotron in Zeuthen, Germany, and study co-author. "It provides us with a chance to unveil the particle transport from SS 433 and to probe the structure of the magnetic field in its vicinity."

In the SS 433 system, a black hole orbits a giant star, 30 times the mass of Earth's sun. The black hole sucks matter from the giant star while orbiting it, forming a swirling accretion disc that drains into the black hole, like water into a bathtub drain.

Some of the matter doesn't fall into the hole though, but rather jets out in high speed spirals from the disc's center in both directions, top and bottom, like pegs on a wheel.

The researchers made the discovery by analyzing more than a decade of data from NASA's Fermi Large Area Space Telescope and from Galactic ALFA HI survey data collected with the Arecibo Observatory's 1,000-foot-wide radio telescope. The observatory was recently damaged and is currently offline, but scientists continue to have access to data previously collected. Engineers are assessing what caused a cable to break and plans for repairs.

The researchers found that the precession, or wobble, of the black hole's jets matched with a gamma-ray signal emitted from a gas cloud. The researchers have labeled the position in the gas cloud Fermi J1913+0515. The position was revealed using Arecibo Observatory's telescope, and Fermi provided data about the SS 433 system.

"The consistent periods indicate the gas cloud's emission is powered by the micro quasar," Li says.

Scientists still do not fully know how the jets overcome the black hole's pull and are emitted from the disc, and the current study presents a new question - How does the black hole power the gas cloud's heartbeat?

The study's researchers say further observations and theoretical work are needed, but one suggestion is that the cloud's gamma-ray emissions are caused by the injection of the nuclei of hydrogen atoms, known as fast protons, that are produced at the end of the jets, or near the black hole.

"SS 433 continues to amaze observers at all frequencies and theoreticians alike," Li says. "And it is certain to provide a testbed for our ideas on cosmic-ray production and propagation near microquasars for years to come."

Study co-authors also included Diego Torres with the Institute of Space Sciences, Barcelona, Spain, the Institució Catalana de Recerca i Estudis Avançats in Barcelona, and the Institut d'Estudis Espacials de Catalunya in Barcelona; Ruo-Yu Liu with the School of Astronomy and Space Science, at Nanjing University in China and the Key Laboratory of Modern Astronomy and Astrophysics at Nanjing University, Ministry of Education, in China; Matthew Kerr with the Space Science Division of the Naval Research Laboratory in Washington, D.C.; Emma de Oña Wilhelmi with Deutsches Elektronen-Synchrotron in Zeuthen, Germany, and the Institute of Space Sciences in Barcelona, Spain; and Yang Su with Purple Mountain Observatory and Key Laboratory of Radio Astronomy in the Chinese Academy of Sciences in Nanjing, China.

UCF manages the National Science Foundation's Arecibo Observatory under a cooperative agreement with Universidad Ana G. Méndez and Yang Enterprises Inc. The facility, which is home to one of the most powerful telescopes on the planet, is used by scientists around the world to conduct research in the areas of atmospheric sciences, space weather research, planetary sciences, radio astronomy and radar astronomy.

Adolescents transitioning into high school encounter a large number of unfamiliar peers, who they quickly label into groups by using an individual's appearance as their guide.

But how do visible queues of high school cliques correlate with what youth say about themselves?

Are adolescents that are stereotyped by peers as jocks actually more sports-oriented, populars more well-liked, and loners more lonely than the average high schooler?

A new study led by University of Illinois Chicago researcher Rachel Gordon, in collaboration with colleagues from the University of Texas at Austin, examines the accuracy of these peer group classifications based on similar values, behaviors, and interests.

The study, which is published in Social Psychology Quarterly, shows that peer crowd classification predicts aspects of unknown peers' mental health, academic achievement, extracurricular involvement, social status, and risk-taking behaviors.

"This study offers insights into the link between perceptions and reality and the social-psychological shortcuts that can, on the one hand, make youths' lives easier and, on the other hand, pigeonhole others into categories different from their true selves," said Gordon, professor of sociology and a fellow of the Institute for Health Research and Policy at UIC.

The researchers, who build on their earlier work on modern-day adolescent experiences, used video and survey data from a subgroup of U.S. youth who were born in 1991 and attended high school in the mid- to late- 2000s. These children were recruited at birth for the National Institute of Child Health and Human Development's Study of Early Child Care and Youth Development.

To determine relevant peer crowds, the researchers assembled 10 focus groups totaling 61 approximate same-age peers as the youth in the previous study. Participants were asked to describe crowds they encountered in high school and their feedback led to the identification of nine peer crowds used in the study - "populars," "jocks," "smarts," "fine arts," druggies/stoners," "emo/goths," "anime/mangas," "troublemakers," and "loners."

Participants were also asked to view seven-second video clips of 15-year-olds and classify them into one of the groups. Ratings based on the short video clips were compared to what the depicted youth actually said about themselves.

For each outcome of the students' self-assessment, the researchers placed crowds into sets predicted by the focus group members to fall into low, middle, and high levels. The hypothesized low mental health group reported more depressive symptoms and loneliness than the middle group, as predicted. In terms of sports participation, the hypothesized high group was more involved in sports than both the middle and low groups. Lastly, the hypothesized high risk-taking group reported engaging in a higher average number of risks compared to the middle group.

"In many cases, these associations were consistent with expectations, based on what same-age focus groups predicted would be the hallmarks of various crowds," said Gordon, who chairs the Institute of Government and Public Affairs' working group on education and learning.

Other notable findings include:

-Focus groups did not consider "smarts" to be part of the low mental health group, despite "smarts" reporting greater loneliness than other crowds.

-Both the "fine arts and "anime/mangas" were assumed by focus groups as having middle levels of achievement. Members of the "fine arts" group had relatively high achievement in terms of their GPAs and advanced English enrollment. "Anime/mangas" had high GPAs but were among the crowds with the lowest enrollment in advanced English courses.

-"Smarts" had unexpectedly low sports participation compared to other crowds although focus group members viewed them as all-around engaged in extra-curricular activities.

-Despite being placed by focus groups in the middle, "jocks" had lower arts participation than almost all other crowds.

-"Smarts and "anime/mangas" engaged in less risk-taking than other crowd members, although focus groups expected them to fall in the middle.

Mild cases of coronavirus disease 2019 (COVID-19) can trigger robust memory T cell responses, even in the absence of detectable virus-specific antibody responses, researchers report August 14 in the journal Cell. The authors say that memory T cell responses generated by natural exposure to or infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)--the virus that causes COVID-19--may be a significant immune component to prevent recurrent episodes of severe disease.

"We are currently facing the biggest global health emergency in decades," says senior author Marcus Buggert (@marcus_buggert) of the Karolinska Institutet. "In the absence of a protective vaccine, it is critical to determine if exposed or infected people, especially those with asymptomatic or very mild forms of the disease who likely act inadvertently as the major transmitters, develop robust adaptive immune responses against SARS-CoV-2."

To date, there is limited evidence of reinfection in humans with previously documented COVID-19. Most studies of immune protection against SARS-CoV-2 in humans have focused on the induction of neutralizing antibodies. But antibody responses tend to wane and are not detectable in all patients, especially those with less severe forms of COVID-19. Research in mice has shown that vaccine-induced memory T cell responses, which can persist for many years, protect against the related virus SARS-CoV-1, even in the absence of detectable antibodies. Until now, it was not clear how SARS-CoV-2-specific T cell responses relate to antibody responses or to the clinical course of COVID-19 in humans.

To address this gap in knowledge, Buggert and his collaborators assessed SARS-CoV-2-specific T cell and antibody responses in more than 200 individuals from Sweden across the full spectrum of exposure, infection, and disease. During the acute phase of infection, the T cell responses were associated with various clinical markers of disease severity. After recovery from COVID-19, SARS-CoV-2-specific memory T cell responses were detectable. The strongest T cell responses were present in individuals who recovered from severe COVID-19. Meanwhile, progressively lower T cell responses were observed in individuals who recovered from very mild COVID-19, and family members exposed to the virus.

In line with expectations, all 23 individuals who recovered from severe COVID-19 developed both SARS-CoV-2-specific antibody and T cell responses. But surprisingly, SARS-CoV-2-specific memory T cell responses were detected months after infection in exposed family members and in most individuals with a history of very mild COVID-19, sometimes in the absence of SARS-CoV-2-specific antibodies. Among the 28 exposed family members, only 17 (a few more than half) had detectable antibody responses, whereas nearly all (26/28) showed T cell responses. Among the 31 individuals who recovered from mild COVID-19, almost all had detectable antibody responses (27/31) and developed T cell responses (30/31).

"Our findings suggest that the reliance on antibody responses may underestimate the extent of population-level immunity against SARS-CoV-2," Buggert says. "The obvious next step is to determine whether robust memory T cell responses in the absence of detectable antibodies can protect against COVID-19 in the long-term."

In her role as the American Association of Critical-Care Nurses (AACN) 2020 Distinguished Research Lecturer, Karen Giuliano, a University of Massachusetts Amherst associate professor, has examined her "unconventional journey" from caring for patients at the bedside to challenging precedent in critical care to medical device design and innovation.

Giuliano's paper, published in the American Journal of Critical Care, describes her 35-year nursing career, leading to her current joint position with the College of Nursing and the Institute for Applied Life Sciences (IALS), where she heads up a product development laboratory.

"My goal is to share lessons learned and to help participants to see the many different ways that critical care nursing knowledge can be used to improve patient care," Giuliano writes.

In addition to publishing her paper, the journal posted a video interview with Giuliano discussing her experiences and perspective in critical-care nursing.

She writes, "My nursing practice has always included a propensity to play with ideas and do things differently, and my practice and clinical research interests are largely driven by a passionate desire to improve the delivery of care for nurses and the experience of care for patients and their families."

Giuliano emphasizes the importance of developing medical products in cooperation with bedside caregivers. "Nurses, especially critical care nurses, are in a unique position to identify and address everyday health care issues, challenge assumptions and the status quo, address unrecognized and unarticulated needs, and ensure that clinical outcomes research serves as the foundation for validating the effectiveness of medical product innovation," she writes.

After 15 years as a critical care nurse, Giuliano spent 13 years with Philips Healthcare, focusing on developing multiparameter patient monitors. In her academic role at UMass Amherst, "My hope is to cultivate productive and fun interdisciplinary collaborations, especially with business and engineering colleagues, deepen and share my passion and ability to contribute to person-centered, humanistic patient care, and expand my capacity to develop and mentor the next generation of nurses."

Giuliano is also collaborating with an Indiana-based startup, Recovery Force, to lead the clinical testing of a portable active-compression system designed to improve patient mobility and prevent deep vein thrombosis. The research is funded by a $1.8 million National Institutes of Health Phase 2 Small Business Innovation Research grant.

HOUSTON -- (Aug. 17, 2020) -- Meals are typically family affairs for zebras, gazelles, cape buffalo and other grazing species in the African Serengeti, but in one of the first studies of its kind, ecologists have found grazing species can be more willing to share meals in areas frequented by lions.

The study, which is available online this week in the journal Ecology, was conducted by a team from Rice University, Princeton University, Wake Forest University and the University of Minnesota. They analyzed more than 115,000 camera-trap photos to see where, when and how often six of the Serengeti's most abundant grazing species -- cape buffalo, gazelle, hartebeest, topi, wildebeest and zebra -- formed mixed-species groups.

"The mixed-species groups occur near places where lions like to hunt, which suggests the grazers are trying to reduce their chances of being killed by predators," said Rice lead-author Lydia Beaudrot.

Mixed-species groups of grazers were found in 1.9% of the camera-trap photos, which were collected between 2010-2015 in Tanzania's Serengeti National Park and processed by volunteers for the citizen science website snapshotserengeti.org. Camera-trap findings were combined with information from long-term GPS collar monitoring by the Serengeti Lion Project and satellite imagery that showed both the location of hunting areas favored by lions and where and when food was plentiful or scarce for grazers.

"Mixed-species groups were most likely in 'risky' places, like woodland habitats and near rocky outcroppings that lions use as viewsheds," said Beaudrot, an assistant professor of biosciences.

But the threat from lions apparently isn't the only thing grazers have to consider.

"One of the most interesting results is that grazers in mixed-species groups appear to be making a tradeoff between the risk of being eaten and the need to eat," Beaudrot said.

Mixed-species groups were less likely to form when plant productivity was low, she said, which suggests there is a foraging cost associated with mixed-species grazing, said study co-author Meredith Palmer, a behavioral ecologist and postdoctoral fellow at Princeton.

"These animals face a trade-off," Palmer said. "When different species group together, each individual is less likely to be eaten by a lion than it would be if it were alone or even possibly with its own species. But each individual is also foraging, and if they get further apart they don't have to compete as much for food. As forage becomes more scarce, these animals have to decide whether the extra food they would get from grazing alone is worth the increased danger from lions."

The study focuses on a longstanding idea in ecology called the 'stress gradient hypothesis,' which holds that species are more likely to compete with one another when times are good and more likely to benefit each other when they're under stress, Beaudrot said.

"The hypothesis is supported by the findings from more than 700 plant studies, but it's rarely been applied to animals because mixed-species behavior is rare and there typically aren't enough data about it to draw statistically significant conclusions," she said.

The collaboration began when Beaudrot heard Palmer describe the Snapshot Serengeti database in a talk at the 2018 Gordon Research Conference on Predator-Prey Interactions. While mixed-species groups had previously been documented in animals, including primates, cetaceans, ungulates, fish and birds, Palmer and Beaudrot realized that the size of the Snapshot Serengeti camera-trap database would allow them a rare opportunity to not simply observe mixed-species groups but to examine the ecological context within which they occur.

"Our findings partially support the hypothesis," Beaudrot said. "On the one hand, we found mixed-species groups were more likely to occur when stress was high because of predators, but we also found that mixed-species groups were less likely to form when stress from food scarcity was high, which suggests that stress can also lead to increased competition."

She and Palmer said there are also plenty of questions to address with follow-up research, including how mixed-species groups better protects grazers from lions.

"The larger groups could provide more warning of lions because there are more eyes for vigilance, or that individual species in the group benefit from the behavior of other species in a way that they wouldn't if they had grazed on their own," Palmer said. "Or it could simply be that the odds of any one individual being eaten go down if it's part of a larger group. Our study can't differentiate between any of those mechanisms."

Opioid use, particularly in high doses, can cause deafness, according to Rutgers researchers.

The study, published in The Journal of Medical Toxicology, reviewed records from the New Jersey Poison Control Center, based at Rutgers New Jersey Medical School, from 1999 to 2018 to determine the association between opioid use and degrees of hearing loss.

Researchers identified 41 people with opioid exposure who experienced full or partial hearing loss or tinnitus, likely caused by toxicity to the ear. More than half had used heroin, followed by oxycodone, methadone and tramadol; 88 percent had only one known exposure.
Most people reported the condition affecting both ears, with 12 people experiencing deafness, 15 partial or total loss of hearing acuity, 10 tinnitus and four a mix of symptoms.

While some people may regain their hearing, the loss could be permanent with others -- 21 percent of those reporting the condition had no improvement in hearing when they were discharged from the hospital.
"The delicate structures of the inner ear are very susceptible to injury if oxygen supply is insufficient, as well as to the direct effect of toxins like opioids," said co-author Lewis Nelson, chair of the Department of Emergency Medicine.

"Although the study found a link with heroin, toxicity to the ear can occur with every opioid," said Diane Calello, executive and medical director of the New Jersey Poison Control Center. "This study supports what has been found in animal studies, which is that any opioid can cause hearing loss," she said. "This might be because we already have built-in opioid receptors, or binding sites, in the inner ear. Activating them may trigger this injury in some patients."

The researchers said health care providers should be aware of the association with opioid use when evaluating a patient with hearing loss.

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.

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.

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.

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.

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."

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.