Culture

Millions of people around the world experience serious blood sugar problems which can cause diabetes, but a world first study is revealing how gut bacteria impact the normally feel good hormone serotonin to negatively influence blood sugar levels.

Serotonin, a neurotransmitter in the brain, is nicknamed the 'happy hormone' and is normally linked with regulating sleep, well-being and metabolism. But the gut actually produces 95 percent of it, and not in the happy form like we know about in the brain.

In a study published in the leading international journal Proceedings of the National Academicy of Sciences (PNAS) today, researchers from Flinders, SAHMRI, and McMaster University in Canada show exactly how bacteria living in the guts of mice, the microbiome, communicate with cells producing serotonin to influence blood sugar levels in the host body.

Professor Damien Keating, Head of Molecular and Cellular Physiology at Flinders University and Deputy Director of the Flinders Health and Mecical Research Institute, says this study sheds light on the unanswered question about exactly how bacteria in the microbiome communicate to control glucose levels in the metabolism.

"We found that the microbiome worsens our metabolism by signalling to cells in the gut that produce serotonin. They drive up serotonin levels, which we previously showed to be increased in obese humans, and this rise in blood serotonin causes significant metabolic problems."

"The next step will be to understand exactly which bacteria do this, and how, in the hope that this could lead to new approaches to regulating blood sugar levels in humans." says Professor Keating

This study is the first to show how the microbiome, the bacteria that lives in the gut, effectively communicate with an organism to impact the hosts metabolism.

If researchers can better understand which bacteria cause the signals to produce serotonin in the gut, treatments could one day be developed to reduce blood sugar levels, and this is a first step towards better understanding this process.

"This is an exciting revelation that can one day have direct implications for human health disorders such as diabetes, but much more research like this is required in the years to come."

DURHAM, N.C. -- Anyone who says females are the 'gentle sex' has never met a lemur. Lady lemurs get first dibs on food, steal their mates' favorite sleeping spots and even attack males, swatting or biting those that annoy them.

What gives these female primates the urge and ability to reign supreme while the meeker males give in or get out of the way? New research suggests that female lemurs' bullying behavior may get programmed early, before birth.

A Duke University study shows that a mother lemur's hormone levels during pregnancy can have long-term effects on her daughters. Female fetuses that are naturally exposed to higher doses of a sex hormone called androstenedione while still in the womb grow up to be more aggressive as adults, researchers report.

Understanding female domination in lemurs has been a puzzle, said lead author Nicholas Grebe, a postdoctoral associate working with Duke professor Christine Drea. Female lemurs are no bigger or brawnier than their male counterparts. Nor are they better armed with horns or tusks like some male animals.

Testosterone levels are significantly lower in females than males too. If the "aggression hormone" doesn't explain females' drive to run the show, the researchers wondered, could other hormonal pathways shape their behavior in some way?

For the study, Grebe, Drea and colleagues followed 24 young lemurs from three to 30 months of age, collecting blood and observing their behavior from infancy to adulthood at the Duke Lemur Center.

The researchers watched the lemurs play for 20 minutes at a time, noting every time they chased or wrestled with a playmate; who instigated and who was on the receiving end; but also when their horseplay crossed a line from play fighting to real fighting.

The researchers also had blood samples collected from the lemur moms during each trimester of pregnancy.

Blood hormone test results confirmed that lemur males have much more testosterone than females: 17 times as much. Yet when it comes to being rough and rowdy, girl lemurs play-fight about as often as boys. And once they reach puberty, females but not males quickly cross a line from play to abuse.

The team found no link between a lemur's hormone levels while they were growing up, and whether they were more likely to be on the giving or the receiving end of aggression. But hormone exposure before birth was a different story.

The researchers found strong links between hormones circulating in a mother's bloodstream during late pregnancy and aggressive behavior in her offspring later on, particularly in females.

While in the womb, developing lemurs are bathed in high doses of the hormone androstenedione, known to increase in lemur moms during pregnancy. Female fetuses that were exposed to higher doses of androstenedione in utero were less likely to be bullied while growing up.

The findings suggest that prenatal exposure to the hormone has lasting effects on their development, permanently programming their bodies and brains in a more aggressive direction.

"The prenatal hormonal soup that lemurs were swimming in before they were born predicted their behavior later on in life," Grebe said.

Early rice growers unwittingly gave barnyard grass a big hand, helping to give root to a rice imitator that is now considered one of the world's worst agricultural weeds.

New research from Zhejiang University, the Chinese Academy of Sciences and Washington University in St. Louis provides genomic evidence that barnyard grass (Echinochloa crus-galli) benefited from human cultivation practices, including continuous hand weeding, as it spread from the Yangtze River region about 1,000 years ago.

Barnyard grass is a globally common invasive weed of cultivated row crops and cereals. The new study was published Sept. 16 in the journal Nature Ecology & Evolution.

"In Asia, rice farmers have traditionally planted and weeded their paddies by hand. Any weeds that stick out are easily detected and removed," said Kenneth Olsen, professor of biology in Arts & Sciences. "Over hundreds of generations, this has selected for some strains of barnyard grass that specialize on rice fields and very closely mimic rice plants. This allows them to escape detection."

Olsen collaborated on data analyses and interpretation for the new study. He is working with the study's corresponding author, Longjiang Fan of Zhejiang University, on other research related to rice evolutionary genomics and agricultural weed evolution.

This study sequenced the genomes of rice-mimic and non-mimic forms of the weed as a step towards understanding how this process has occurred.

This form of mimicry, called Vavilovian mimicry, is an adaptation of weeds to mimic domesticated plants. In the case of barnyard grass, the rice mimics grow upright like a rice plant instead of sprawling along the ground like most barnyard grass. They also have green stems like rice plants instead of the red stems more commonly found in the weed.

"With the advent of agriculture about 10,000 years ago, humans all over the planet began creating a wonderful habitat for naturally weedy plant species to exploit," Olsen said. "The most successful and aggressive agricultural weeds were those that evolved traits allowing them to escape detection and proliferate in this fertile new environment."

The researchers estimate that the mimic version of E. crus-galli emerged at about the same time that Chinese historical records indicate that the regional economic center was shifting from the Yellow River basin to the Yangtze River basin. During this period of the Song Dynasty, human populations were growing rapidly, demand for rice as the staple grain was paramount. This is also the time when a quick-maturing, drought-resistant variety of rice called Champa rice was introduced to the Yangtze basin from Southeast Asia -- to allow two harvests in a year. Weed management in paddies might have been intensified in the context of these conditions.

Traditional farming preserves diversity of Thai purple rice

However, while common barnyard grass is a major agricultural weed in the U.S., the rice mimic form has never become widespread in the main rice growing region -- the southern Mississippi valley.

Olsen speculates that this is because U.S. rice farmers rely on mechanized farming instead of hand labor.

"Without farmers out in the fields planting and weeding by hand, there's not such strong selection for weeds to visually blend in with the rice crop," he said.

Bicuspid aortic valve (BAV) is the most common heart valve birth defect and one of the most common birth defects of any type, affecting around 70 million people worldwide. A healthy aortic valve has three leaflets; in BAV disease, two of the leaflets are fused together, impairing the function of the valve. In many individuals with BAV, the valves eventually will have to be replaced or repaired through heart surgery.

A team of researchers at the Medical University of South Carolina (MUSC) have discovered that a mutation in a gene controlling the production of cilia, tiny antennae protruding from the cell surface, are linked to the development of BAV.

In an article published online August 7, 2019 in the journal Circulation, the team used animal models and human data to reveal that BAV disease and aortic valve narrowing are caused by disruption of the exocyst, a shuttling complex that moves cilia cargo to the cell membrane and allows for the development of cilia, and defects in cilia production.

Most cells have cilia, which help them "sense" their surroundings.

"You can think of cilia like tiny antennae that cells use to transmit information to each other," said Diana Fulmer, Ph.D. candidate at MUSC and lead author of the manuscript. "In heart valves, cilia function as signaling hubs during development to coordinate how cells and extracellular matrix arrange to form mature tissue."

Only recently has the medical community begun to realize how cilia are involved in human health and disease.

"Up until 20 years ago, people were writing that cilia were vestigial organelles and had no function," said Joshua H. Lipschutz, M.D., professor of medicine and director of the Division of Nephrology at MUSC and co-senior author of the article. "Now, there's a whole field of ciliopathies."

Russell A. Norris, Ph.D., associate professor of medicine in the Department of Regenerative Medicine and Cell Biology at MUSC and an expert in heart valve biology and genetics, is co-senior author of the manuscript. Norris first started to suspect that cilia were involved in BAV disease when he noticed that patients with certain ciliopathies, or cilia diseases, also had BAV disease. This observation led to a collaboration with Lipschutz, who studies autosomal dominant polycystic kidney disease, or ADPKD, which is a cilia disease affecting the kidney.

"We knew that ADPKD patients have a much higher incidence of heart defects, including bicuspid aortic valve disease," said Lipschutz. "So, there was a very strong clinical association."

Norris and Lipschutz wrote a collaborative grant with Simon Body, M.D., director of the Bicuspid Aortic Valve Consortium and an associate professor of anaesthesia at Harvard Medical School, to find out how cilia contribute to BAV disease. "It was really a true collaboration," said Lipschutz. The grant was funded through the American Heart Association.

The investigators first compared the genomes of healthy adults and adults with BAV disease. In a genome-wide association study, the most associated differences in genomes were found in or near genes that are important in regulating ciliogenesis through the exocyst.

Animal models were then used to determine whether mutations in a central exocyst protein, Exoc5, caused disease in other organisms. Knocking out or "disabling" the gene for Exoc5 in zebrafish severely obstructed blood flow from the heart, leading to poor cardiac function and early death. The zebrafish also showed signs of other ciliopathies.

Remarkably, injecting the correct gene sequence for Exoc5 into the zebrafish prevented them from developing heart defects, proving that the mutation was causing the disease.

The investigators then disabled the Exoc5 gene in mice, specifically in the cells that make up the cardiac valves. Mice with both copies of the disabled gene died early during development. Mice with only one copy of the disabled gene were born but had a high rate of BAV disease and problems with cilia production.

Humans with BAV disease often develop calcification on their aortic valve, leading to stenosis, or narrowing, of the valve opening. This can cause severe functional defects within the heart and is a major indication for surgery.

Interestingly, mice with the disabled exocyst gene also developed calcified aortic valves and had significantly larger aortic roots.

"We saw the same thing we see in people," said Lipschutz. "This gives us a good animal model for the disease."

This study provides novel insight into the origin of BAV disease.

"We showed that the cause of a very common, potentially lethal, genetic defect in people was due to cilia and the exocyst," Lipschutz said.

Knowledge gained from the study should accelerate the development of new therapies.

"Finding the cause for disease is the first step to finding a cure," said Lipschutz. "Now that we know what's causing it, we can come up with ways to treat it without surgery."

CHAMPAIGN, Ill. -- Researchers have developed soft robotic devices driven by neuromuscular tissue that triggers when stimulated by light - bringing mechanical engineering one step closer to developing autonomous biobots.

In 2014, research teams led by mechanical science and engineering professor Taher Saif and bioengineering professor Rashid Bashir at the University of Illinois worked together to developed the first self-propelled biohybrid swimming and walking biobots powered by beating cardiac muscle cells derived from rats.

"Our first swimmer study successfully demonstrated that the bots, modeled after sperm cells, could in fact swim," Saif said. "That generation of singled-tailed bots utilized cardiac tissue that beats on its own, but they could not sense the environment or make any decisions."

In a new study published in the Proceedings of the National Academy of Sciences and led by Saif, the researchers demonstrate a new generation of two-tailed bots powered by skeletal muscle tissue stimulated by on-board motor neurons. The neurons have optogenetic properties: Upon exposure to light, the neurons will fire to actuate the muscles.

"We applied an optogenetic neuron cell culture, derived from mouse stem cells, adjacent to the muscle tissue," Saif said. "The neurons advanced towards the muscle and formed neuromuscular junctions, and the swimmer assembled on its own."

After confirming that the neuromuscular tissue was compatible with their synthetic biobot skeletons, the team worked to optimize the swimmer's abilities.

"We used computational models, led by mechanical science and engineering professor Mattia Gazzola, to determine which physical attributes would lead to the fastest and most efficient swimming," Saif said. "For example, we looked at variations in the number of tails and tail lengths for most efficient design of the biohybrid swimmer."

"Given the fact that biological actuators, or biobots, are not as mature as other technologies, they are unable to produce large forces. This makes their movement hard to control," Gazzola said. "It is very important to carefully design the scaffold the biobots grow around and interact with to make the most out of technology and achieve locomotive functions. The computer simulations we run play a critical role in this task as we can span a number of possible designs and select only the most promising ones for testing in real life."

"The ability to drive muscle activity with neurons paves the way for further integration of neural units within biohybrid systems," Saif said. "Given our understanding of neural control in animals, it may be possible to move forward with biohybrid neuromuscular design by using a hierarchical organization of neural networks."

Saif said he and his team envision this advance leading to the development of multicellular engineered living systems with the ability to respond intelligently to environmental cues for applications in bioengineering, medicine and self-healing materials technologies.

However, the team acknowledges that - like living organisms - no two biohybrid machines will develop to be exactly the same.

"Just like twins are not truly identical, two machines designed to perform the same function will not be the same," Saif said. "One may move faster or heal from damage differently from the other - a unique attribute of living machines."

MIT and Dartmouth College researchers have demonstrated, for the first time, a tool that detects new characteristics of environmental "noise" that can destroy the fragile quantum state of qubits, the fundamental components of quantum computers. The advance may provide insights into microscopic noise mechanisms to help engineer new ways of protecting qubits.

Qubits can represent the two states corresponding to the classic binary bits, a 0 or 1. But, they can also maintain a "quantum superposition" of both states simultaneously, enabling quantum computers to solve complex problems that are practically impossible for classical computers.

But a qubit's quantum "coherence" -- meaning its ability to maintain the superposition state -- can fall apart due to noise coming from environment around the qubit. Noise can arise from control electronics, heat, or impurities in the qubit material itself, and can also cause serious computing errors that may be difficult to correct.

Researchers have developed statistics-based models to estimate the impact of unwanted noise sources surrounding qubits to create new ways to protect them, and to gain insights into the noise mechanisms themselves. But, those tools generally capture simplistic "Gaussian noise," essentially the collection of random disruptions from a large number of sources. In short, it's like white noise coming from the murmuring of a large crowd, where there's no specific disruptive pattern that stands out, so the qubit isn't particularly affected by any one particular source. In this type of model, the probability distribution of the noise would form a standard symmetrical bell curve, regardless of the statistical significance of individual contributors.

In a paper published today in the journal Nature Communications, the researchers describe a new tool that, for the first time, measures "non-Gaussian noise" affecting a qubit. This noise features distinctive patterns that generally stem from a few particularly strong noise sources.

The researchers designed techniques to separate that noise from the background Gaussian noise, and then used signal-processing techniques to reconstruct highly detailed information about those noise signals. Those reconstructions can help researchers build more realistic noise models, which may enable more robust methods to protect qubits from specific noise types. There is now a need for such tools, the researchers say: Qubits are being fabricated with fewer and fewer defects, which could increase the presence of non-Gaussian noise.

"It's like being in a crowded room. If everyone speaks with the same volume, there is a lot of background noise, but I can still maintain my own conversation. However, if a few people are talking particularly loudly, I can't help but lock on to their conversation. It can be very distracting," says William Oliver, an associate professor of electrical engineering and computer science, professor of the practice of physics, MIT Lincoln Laboratory Fellow, and associate director of the Research Laboratory for Electronics (RLE). "For qubits with many defects, there is noise that decoheres, but we generally know how to handle that type of aggregate, usually Gaussian noise. However, as qubits improve and there are fewer defects, the individuals start to stand out, and the noise may no longer be simply of a Gaussian nature. We can find ways to handle that, too, but we first need to know the specific type of non-Gaussian noise and its statistics."

"It is not common for theoretical physicists to be able to conceive of an idea and also find an experimental platform and experimental colleagues willing to invest in seeing it through," says co-author Lorenza Viola, a professor of physics at Dartmouth. "It was great to be able to come to such an important result with the MIT team."

Joining Oliver and Viola on the paper are: first author Youngkyu Sung, Fei Yan, Jack Y. Qiu, Uwe von Lüpke, Terry P. Orlando, and Simon Gustavsson, all of RLE; David K. Kim and Jonilyn L. Yoder of the Lincoln Laboratory; and Félix Beaudoin and Leigh M. Norris of Dartmouth.

Pulse filters

For their work, the researchers leveraged the fact that superconducting qubits are good sensors for detecting their own noise. Specifically, they use a "flux" qubit, which consists of a superconducting loop that is capable of detecting a particular type of disruptive noise, called magnetic flux, from its surrounding environment.

In the experiments, they induced non-Gaussian "dephasing" noise by injecting engineered flux noise that disturbs the qubit and makes it lose coherence, which in turn is then used as a measuring tool. "Usually, we want to avoid decoherence, but in this case, how the qubit decoheres tells us something about the noise in its environment," Oliver says.

Specifically, they shot 110 "pi-pulses" -- which are used to flip the states of qubits -- in specific sequences over tens of microseconds. Each pulse sequence effectively created a narrow frequency "filter" which masks out much of the noise, except in a particular band of frequency. By measuring the response of a qubit sensor to the bandpass-filtered noise, they extracted the noise power in that frequency band.

By modifying the pulse sequences, they could move filters up and down to sample the noise at different frequencies. Notably, in doing so, they tracked how the non-Gaussian noise distinctly causes the qubit to decohere, which provided a high-dimensional spectrum of the non-Gaussian noise.

Error suppression and correction

The key innovation behind the work is carefully engineering the pulses to act as specific filters that extract properties of the "bispectrum," a two-dimension representation that gives information about distinctive time correlations of non-Gaussian noise.

Essentially, by reconstructing the bispectrum, they could find properties of non-Gaussian noise signals impinging on the qubit over time -- ones that don't exist in Gaussian noise signals. The general idea is that, for Gaussian noise, there will be only correlation between two points in time, which is referred to as a "second-order time correlation." But, for non-Gaussian noise, the properties at one point in time will directly correlate to properties at multiple future points. Such "higher-order" correlations are the hallmark of non-Gaussian noise. In this work, the authors were able to extract noise with correlations between three points in time.

This information can help programmers validate and tailor dynamical error suppression and error-correcting codes for qubits, which fixes noise-induced errors and ensures accurate computation.

Such protocols use information from the noise model to make implementations that are more efficient for practical quantum computers. But, because the details of noise aren't yet well-understood, today's error-correcting codes are designed with that standard bell curve in mind. With the researchers' tool, programmers can either gauge how their code will work effectively in realistic scenarios or start to zero in on non-Gaussian noise.

Keeping with the crowded-room analogy, Oliver says: "If you know there's only one loud person in the room, then you'll design a code that effectively muffles that one person, rather than trying to address every possible scenario."

DALLAS - Sept. 16, 2019 - Cardiologists know that when patients use a blood pressure cuff at home, they have a significant head start on managing their heart health risk. Now, researchers have learned the added value for African Americans.

According to the American Heart Association, African Americans have the highest rates of disability and death related to high blood pressure of any group in the United States. Researchers at UT Southwestern Medical Center studied data from the Dallas Heart Study and learned that at-home measurements are more accurate, less expensive, and easier to obtain than blood pressure screenings done in medical settings. Patients' readings tend to be higher in the clinic due to stress or anxiety.

"Our study shows that African American men and women who are taking medications to control their hypertension should monitor their blood pressure at home on a regular basis. These home-taken readings are a more accurate measure of how healthy the heart is than clinic readings when compared to other ethnic groups," said Dr. Wanpen Vongpatanasin, Professor of Internal Medicine, at UT Southwestern and Director of the Hypertension Section and its Hypertension Fellowship Program. Checking blood pressure in the clinic alone may miss the opportunity to prevent heart disease, especially in high-risk hypertensive black patients, she added.

The risks are substantial. Having hypertension can potentially lead to heart failure, stroke, kidney failure, and premature death.

"The debate among cardiologists has been whether measuring blood pressure in the clinic can lead to under-treatment or over-treatment of hypertension," said Dr. Vongpatanasin. "We wanted to see if measuring blood pressure at home would give us a more accurate picture of heart health."

The research team assessed 1,262 black and 927 white participants ages 30-64 years. At-home blood pressure measurements were found to be more likely to predict potentially dangerous thickening of the left heart chamber than blood pressure taken at the doctor's office.

The study, published in the journal Hypertension, is one of the few to examine an at-home approach to blood pressure monitoring in African Americans. It was led by prominent hypertension expert and former UT Southwestern Cardiologist Dr. Ron Victor, who lost his battle with pancreatic cancer in 2018. Dr. Victor was a co-founder of the Dallas Heart Study who became widely known for his heart disease outreach to African American men through community barbershop visits. Both Dr. Vongpatanasin and Dr. Robert W. Haley, Professor of Internal Medicine and Director of the Division of Epidemiology, helped design the Dallas Heart Study in the late 1990s. They considered Dr. Victor to be a mentor and close colleague.

"The Dallas Heart Study is one of the nation's first major population studies designed to focus on the specific heart disease issues of African Americans," Dr. Haley said. "The idea arose from Dr. Victor's concerns over the disproportionate numbers of young black men and women with advanced heart disease that he treated over the years. Although long recognized, he felt the causes and solutions of their disease were not being addressed."

BOSTON -Major physical changes occurred in the human heart as people shifted from hunting and foraging to farming and modern life. As a result, human hearts are now less "ape-like" and better suited to endurance types of activity. But that also means those who lead sedentary lives are at greater risk for heart disease. Those are the main conclusions from a unique study led by Aaron L. Baggish, MD, director of the Massachusetts General Hospital (MGH) Cardiovascular Performance Program. Baggish and his collaborators examined how ape hearts differ from those of humans, why those differences exist and what that means to human health.

They measured and compared heart function in apes and four groups of humans (ranging from sedentary through to elite runners, and including indigenous subsistence farmers). Their research is presented in the Sept. 2019 issue of Proceedings of the National Academy of Sciences of the United States of America (PNAS). Baggish's collaborators on this paper included Robert E. Shave, PhD, School of Health and Exercise Sciences, University of British Columbia; and Daniel E. Lieberman, PhD, Department of Human Evolutionary Biology, Harvard University.

Chimpanzees are humans' closest known relatives, based on genetics and evolutionary studies. There are, of course, some stark differences between these species. For example, in terms of exertion, chimpanzees mainly engage in short bursts of activity, such as climbing and fighting, which put intense pressure on the heart but only for a limited time. In contrast, it's believed that, up until the industrial revolution, humans were active for longer bouts of time in order to hunt and farm. Survival of pre-industrial humans, it is thought, depended on moderate-intensity, endurance-like activity (e.g. hunting, gathering, and then farming).

It is also well established that some physical features of the heart change in response to certain physical challenges. Walking and running, for example, require more blood to be pumped to deliver fuel to active muscles. In contrast, brief but intense exertion from activities such as climbing or fighting, create pressure in heart, which over time can makes the heart chambers develop stiffer and thicker walls.

"The heart remodels in response to two main forces: pressure and volume," says Baggish. As a result, "Humans have longer, thinner- and more flexible-walled hearts, while chimps have smaller hearts with thicker walls." What Baggish and his collaborators wanted to know was: Could those differences have evolved in response to humans' new activity levels? And if so, what implications does that have on human health today?

Using a group of more than 160 study participants, the researchers carried out detailed heart function studies, including measuring blood pressure and using ultrasound to examine the heart's structure and function during many different activities. Their subjects were fairly evenly divided into elite runners, American football players, indigenous Mexican subsistence farmers and people who engage in little physical activity. They made similar measurements in about 40 semi-wild chimpanzees and five gorillas.

"The goal was to compare heart structure and function in each "type" - whether the subject was very active, to barely active," Baggish says. In addition, the investigators sought to determine if adaptation to either pressure or volume comes at the expense of the ability to handle the alternative form of stress. This was done by giving pressure adapted (football linemen) and volume adapted (long distance runners) both a "volume challenge," by giving them a large intravenous saline infusion and a "pressure challenge," by sustained, forceful handgrip, and simultaneously measuring heart function. The goal was to see if there is a tradeoff between having a heart that is adapted for endurance versus having one that performs better for short bursts of intense activity. Or could the heart adapt for both?

Baggish and his collaborators found that indeed, human hearts appear to have evolved to be better at handling endurance type activity, as opposed to short intense bouts. The researchers also confirmed that people who train specifically for endurance sports have hearts with longer, larger, and more elastic left ventricles, which is the part of the heart that pumps the blood out to the body. Those features, and others, make the heart better able to cope with pumping higher volumes of blood over a sustained time. In contrast, sedentary people, even at a relatively young age, have hearts that appear more "ape-like" that are better suited to cope with short bursts of high activity.

These findings help answer that question about the heart's evolution. "The human heart has evolved over hundreds of thousands of years as our activity levels gradually became more sustained," Baggish says. "We now understand that the human heart, coupled with changes in the musculoskeletal and thermoregulatory system, evolved to facilitate extended endurance activity rather than spurts of intense exertion." This study has important implications for understanding heart health today. For example, people who live a sedentary lifestyle appear to develop more ape-like hearts and are more prone to hypertension. That disease process then causes further changes and a negative feedback loop that raises risk of disease.

This study was unique for several reasons, Baggish says. "Not only were we able to study heart function in three types of primates, but we also had the opportunity to work with people who are among the last groups of truly subsistence-based farmers, the Tarahumara in Mexico's Copper Canyons." The research team also included a cardiologist (Baggish), an expert in exercise physiology (Shave) and an evolutionary biologist (Lieberman).

Ecologists have long tried to understand and anticipate the compositional change of plant species, especially now, as climate and land usage disrupts the way in which plants colonize and expand their communities. Called plant succession, the study of predicting plant communities through time is one of ecology's oldest pursuits.

In 2016, Brian Buma, PhD, assistant professor of integrative biology at the University of Colorado Denver, assembled a team of researchers to hunt down and then expand eight long-forgotten, 103-year-old succession plots with a grant from National Geographic. The team discovered the plots and with the new data, revived the longest running succession study in the world.

The researchers found that the initial, random assortment of plants spent a few decades fighting for dominance and sunlight, before settling into a stable and nearly unchanging community for the next 50 years, upending the classic model of thought about succession.

The findings were published in the journal Ecology.

Hunting for quadrats

In 1916, William S. Cooper, an early president of the Ecological Society of America, measured out six one-square meter plots, called quadrats, on the edge of a glacier in Alaska's remote Glacier Bay National Park to study how an ecosystem develops from scratch. Cooper visited the quadrats every five to 10 years until the 1940s, when it was taken over by his student who maintained the record until his death in 1988. Unfortunately, his student never published the results, and so for over 75 years Cooper's plots were forgotten and buried in layers of soil and vegetation in the Alaskan bush.

Luckily, the famed ecologist kept a detailed journal of his observations of the life within the small quadrats, along with maps and directions to them, but finding them wouldn't be easy.

To begin, Cooper's north isn't Buma's north. In the century since Cooper first cataloged the locations of his plots, the Earth's magnetic pole has shifted about 12 degrees. Other land markings have also changed: a large inlet has since shrunk to a small indentation on the coastline, Cooper's open fields are now impassable with vegetation, and one of the quadrats became a victim to erosion and fell, quite literally, into the sea.

Cooper drove in steel nails or rebar to mark the corners and piled small rock cairns around them to denote their location. He marked the quadrat locations by pacing out the distance from big boulders, anywhere from 30 to 50 paces, and at varying degrees from North. Notes like "Go 12 paces from the large rock, 27 degrees from north to a small cairn" were common.

Unearthing 75 years of missing data

Armed with laminated photographs of the plots and surrounding areas, Cooper's original handwritten journals, a metal detector and a bit of luck, researchers spent eight days tracking down the plots, finding the final one within hours of having to leave. Through extensive fieldwork, historical archives, remote sensing and dendrochronological methods, they were able to fill in the data for the missing 75 years.

"Nowhere in the world can you look through data and maps and pictures from one hundred years ago and have the detail required for this type of scientific study," said Buma.

Upending chronosequence models

Before now, most ecologists have relied on chronosequence studies to study long time periods, in which researchers compare old sites to young sites as representative of the passage of time to study how communities have evolved. But that makes a huge assumption about how those sites differ because the old site may have looked nothing like the young site a hundred years ago, said Buma.

As a result, chronosequence studies have churned out results that predict plants interact with each other over time to form predictable, successional trajectories. Cooper's Glacier Bay quadrats show the opposite.

Instead of a succession of plants as chronosequence models suggested, the 103-year-old communities remained relatively the same. No other plants came in and the existing plants reproduced asexually.

"It undermines a lot of the normal succession papers because it turns out that space really is important," said Buma. "There are a lot of random things that happen early in the plot history - where seeds landed, for example - that still influence what we see today. It's like standing at the edge of a cliff and kicking a rock off of the top. As it falls, the rock may bounce off one way or the other, and you could get hundreds of different paths, even though the rocks started from more or less the same spot."

In addition to monitoring Cooper's original quadrats, Buma's team have expanded the plot sizes, added new baseline biogeochemical data and spatial mapping for future researchers. Their goal is to observe whether or not the conclusions from Cooper's plot reflects the broader reality now.

"The plots could all end up looking the same in one thousand years," said Buma. "But right now, in the first one hundred years, we can say that each is very different."

WASHINGTON (Sept. 16, 2019) -- The American College of Cardiology today published its first health policy statement on cardiologist compensation and opportunity equity, recognizing that both are critical to the health and future of the cardiovascular workforce and achieving ACC's mission to transform cardiovascular care and improve heart health. The document is the first in a new series of ACC workforce health policy documents and will serve as guidance for clinicians and administrators to advance the profession toward the goals of fairness, including minimizing and reducing disparities, and improved patient care.

"With this policy statement, the ACC intends to provide a clear set of principles related to equity in compensation and opportunity in the professional cardiovascular workplace along with the associated underlying considerations," said Pamela S. Douglas, MD, the Ursula Geller Professor for Research in Cardiovascular Diseases at Duke University and chair of the writing committee. "The ACC has developed 17 principles for achieving equity in compensation and opportunity, beginning with the firm declaration that the College believes that cardiologist compensation should be equitable and fair for equivalent work."

Despite laws prohibiting discrimination in compensation, the medical field, including cardiology, continues to struggle with equitable compensation and opportunity. Women and underrepresented minorities are often paid less than their white, male counterparts in almost every industry, and the annual salary gap between female and male cardiologists amounts to more than $1 million over the course of a career.

Inequities in compensation and opportunity are often cited as causes of burnout, a common problem among physicians that can lead to problems with the quality of patient care. The College has recently recognized a need to develop a more strongly inclusive culture to address the lack of diversity among cardiologists, and lack of equal compensation has also been noted as contributing to the low number of female medical graduates pursuing careers in cardiology. Increasing the number of underrepresented minority health professionals in the field is an important step in improving the cultural competence of the health care system.

According to these ACC principles, cardiologist compensation should be objectively determined by a modeled systems approach that is prospectively developed and based on consensus principles, which in turn are fully aligned with an organization's or practice's business strategy, mission and core values. These principles may be used by organizations and practices of any size and are adaptable to a range of strategic goals.

Equity cannot be fully ensured without considering other factors that may affect compensation directly or indirectly, including career advancement; quality and quantity of clinical, administrative and research support; clinic/lab/procedure space and time; work environment; and access to resources. The document groups these factors broadly under "opportunity" and considers them prerequisites to ensuring compensation equity.

"Compensation and opportunity equity are critical components of a fair and professional work environment, Douglas said. "No compensation plan can provide fairness unless there is also equal opportunity to maximize performance and advancement. The ACC believes that adherence to these principles will improve the performance and satisfaction of the cardiovascular workforce, enhance team-based care and ultimately benefit patient and population health."

Washington, DC - September 16, 2019 - Researchers have engineered a plasmid to remove an antibiotic resistance gene from the Enterococcus faecalis bacterium, an accomplishment that could lead to new methods for combating antibiotic resistance. The research is published this week in Antimicrobial Agents and Chemotherapy, a journal of the American Society for Microbiology.

In vitro, and in mouse models, the engineered plasmid removed the antibiotic resistance gene from E. faecalis. In mouse models, it reduced the abundance of the resistance gene threefold..

"Our concern with organisms that cause hospital-acquired infections that are resistant to many clinical antibiotic therapies motivated the research," said co-senior author Breck A. Duerkop, PhD, Assistant Professor of Immunology and Microbiology, University of Colorado School of Medicine, Anschutz Medical Center, Aurora.

E. faecalis is part of the normal, benign intestinal flora, but when antibiotics kill off beneficial intestinal flora, E. faecalis can become pathogenic. As such, it can also acquire single or multidrug resistance. Antibiotic resistant E. faecalis infections are a major problem in hospitals.

The mechanism used to remove antibiotic resistance genes is the specialized protein, CRISPR-Cas9. It can make cuts just about anywhere in DNA.

Along with CRISPR-Cas9, RNA sequences homologous to DNA within the antibiotic resistance gene have been added to the engineered plasmid. These RNAs guide the CRISPR-Cas9 to make the cuts in the right places.

Previous work in animal models by co-senior investigator Kelli L. Palmer, PhD, found that CRISPR-Cas9 could prevent intestinal E. faecalis from acquiring resistance genes. Dr. Palmer is Fellow, Cecil H. and Ida Green Chair in Systems Biology Science, Associate Professor of Biological Sciences, University of Texas, Dallas.

The delivery vehicle for the engineered plasmid is a particular strain of E. faecalis, which conjugates with E. faecalis of various different strains. Conjugation is the process whereby bacteria come together to transfer genetic material from one to the other via direct cell to cell contact.

"E. faecalis strains used to deliver these plasmids to drug resistant strains [of E. faecalis] are immune to acquiring drug resistant traits carried by the target cells," said Dr. Duerkop. "The engineered plasmid can significantly reduce the occurrence of antibiotic resistance in the target bacterial population rendering it more susceptible to antibiotics. We envision that this type of system could be used to re-sensitize antibiotic resistant E. faecalis to antibiotics," he said.

Nonetheless, Dr. Duerkop cautioned that it remained possible that E. faecalis could still circumvent the engineered plasmid. Some bacteria have anti-CRISPR systems that can block CRISPR-Cas9 function, and some others have systems that can degrade foreign DNA. "Future studies will need to be done to address such an issue as E. faecalis avoiding the targeting system and under what conditions this may happen," said Dr. Duerkop.

Female mice housed alone during adolescence show atypical development of the prefrontal cortex and resort to habitual behavior in adulthood, according to new research published in eNeuro. These findings show how social isolation could lead to an over-reliance on habit-like behaviors that are associated with addiction and obesity.

The adult brain is largely shaped during adolescence, when some connections between brain cells are solidified and others are eliminated. Prior research has established an important role for social experience in this development.

To investigate the long-term, neurobehavioral consequences of social isolation, Hinton et al. raised mice alone during adolescence and reintroduced them to a social environment in adulthood. The researchers identified a critical period during which social isolation impaired the adult brain and behavior and linked these effects to dendritic spine excess. Therapeutic interventions targeting the refinement of the brain during adolescence may therefore represent a promising direction for future research.

URBANA, Ill. - Corn, soybean, and cotton farmers shudder at the thought of Palmer amaranth invading their fields. The aggressive cousin of waterhemp - itself a formidable adversary - grows extremely rapidly, produces hundreds of thousands of seeds per plant, and is resistant to multiple classes of herbicides, including glyphosate.

Palmer's resistance to PPO-inhibiting herbicides, a group of chemicals that disrupt chlorophyll synthesis, is especially problematic with glyphosate out of the picture. Farmers had been turning to PPO-inhibitors as an effective alternative, until resistance was discovered in waterhemp in 2001 and in Palmer in 2011.

Pat Tranel from the University of Illinois has been working to understand the mechanisms of resistance to PPO-inhibitors for years, and was the first to discover key mutations in both weed species. Now, in two new studies, he goes farther to explain Palmer's evil genius.

"We knew Palmer had the same molecular mechanism as waterhemp to resist PPO-inhibitors, a genetic mutation known as the gly-210 deletion, and at least one more. Now we know that it evolved the gly-210 deletion independently, rather than picking it up through hybridization with waterhemp," says Tranel, associate head and professor of molecular weed science in the Department of Crop Sciences at U of I.

This is important in two ways. It's good news that scientists aren't finding evidence of hybridization between the two superweeds, at least not so far. But the fact that Palmer evolved the same mutation independently, and at least one more to boot, shows just how wily the weed is.

Tranel and his team determined the evolutionary origins of the gly-210 mutation by looking at the genetics of resistant plants of both species that were growing together in a Kentucky field. Being in close proximity for several years should have provided opportunity for hybridization, if it was going to happen.

"We know from lab experiments that they are capable of hybridizing, so the fact that it's not happening in the field is a good thing. The more they can and do hybridize, the more concerns we'd have," Tranel says.

Only about a third of the Palmer plants in the Kentucky field had the gly-210 deletion. The rest were using a different mutation - an arginine substitution - to ward off PPO-inhibitor damage.

"The finding that this population of Palmer has two different mutations is a concern because if you look forward in the future, Palmer is well positioned to deal with future PPO chemistries. It can use whichever is more effective against a new PPO.

"It's also well positioned to combine the two mutations to create a double mutant, with both mutations on the same copy of the chromosome. Chemistry designed to kill plants with the gly-210 deletion won't be able to kill double mutants," Tranel says. "In my opinion, it's just a matter of time until we see double mutants in the field."

Tranel's second new study explains why Palmer amaranth took a decade longer than waterhemp to develop the gly-210 deletion, and reveals another diabolical truth about the species: Palmer amaranth appears to be naturally tolerant to post-emergence PPO-inhibitor application.

It has long been recognized that the timing of post-emergence PPO application is especially critical for Palmer amaranth, relative to waterhemp. If Palmer plants aren't sprayed before they reach about 4 inches, it's all over.

"If you wait too long, you miss 'em. And too long can be a matter of a single day because Palmer grows so fast. It can go from a 4-inch plant where you could control it to a 6-inch plant literally in a day," Tranel says.

For Tranel, the pattern suggests a natural tolerance to post-emergence PPO-inhibitors. Tolerance describes the ability of a species to handle a substance, in this case PPO herbicides. Resistance, on the other hand, happens at the population level; localized populations of the species evolve mutations in response to repeated exposure to the substance. For example, corn is tolerant to atrazine. It can handle being sprayed and doesn't need to evolve a mutation to handle it in a particular population.

The idea is that Palmer amaranth has a natural tolerance to PPO inhibitors and didn't need to develop resistance. That's why it took longer to evolve the gly-210 mutation. But, until now, no one had specifically studied Palmer's tolerance to the chemistry before.

Tranel confirmed it by growing Palmer and waterhemp plants with and without the gly-210 mutation side-by-side and applying different formulations of pre-emergence and post-emergence PPO-inhibitors. The post-emergence applications were done early (smaller than 4 inches) or late (taller than 4 inches).

"We found that 'sensitive' Palmer plants without the mutation survived just as well as resistant waterhemp when sprayed post-emergence," Tranel says.

On the other hand, the research team found that pre-emergence formulations effectively controlled both species.

"The difference in tolerance between Palmer and waterhemp goes away at the pre-emergence stage," Tranel says. "Ultimately, that's the take-home message here. If you're dealing with these weeds, especially Palmer amaranth, and you want to incorporate a PPO-inhibitor as an alternative effective mode of action, you'll have much better luck if you use it in a pre-emergence application."

How people behave in one situation often tells us how they will act in others. A shy introvert in one place, for example, isn't likely to be the gregarious life of the party in another.

Such is personality -- patterns of behavior within individuals that are reasonably stable over time and contexts. But what creates those patterns of behavior, and why do they persist?

Different behaviors tend to covary, or present together. Gregarious people, for example, are also likely to be assertive. But this covariation in behavioral tendencies is neither random nor easily explained by genes. The social and ecological environments in which we develop, scientists say, have a lot to do with how we develop.

Socioecological niches and navigating daily life

New work by researchers at UC Santa Barbara, UC Merced, California State University Fullerton and the University of Richmond suggests that societies differ in the personality profiles of their members because societies vary in the number and richness of their socioecological niches -- the shorthand for all the occupational, social and other ways of navigating successfully through daily life. Their findings are published in the journal Nature Human Behaviour.

"We developed a computational model to create a world in which we can vary how many niches are in the environment," said Michael Gurven, a professor of anthropology at UC Santa Barbara and the paper's senior author. The researchers wanted to discover whether increasing the number of niches in a particular environment resulted in the kinds of shifts in personality structure that coincide with their theory. Their idea is that more complex societies (i.e. those having more niches) will show a greater diversity of personality types.

"Each niche has an ideal personality profile to fit it," Gurven continued. "People in the environment are born with some initial personality picked at random. And then we let people sort across the landscape in ways that might best suit their personality -- if you're a loner, for example, maybe you don't want to live in the middle of New York City; if you love mountains and snow, you probably don't want to live in Phoenix, Arizona."

The researchers also varied the extent to which individuals can adjust their personalities to better fit the environments in which they find themselves.

Societal complexity in populations

As it turned out, it didn't matter whether they were working with a population of a hundred individuals or a thousand. Increasing the number of niches made personality traits tend to look more like those in the Big Five. This separable quintet of dimensions that psychologists have long believed universally define the structure of human personality include openness, conscientiousness, extraversion, agreeableness and neuroticism. "Increasing the number of niches in a population results in lower correlations among personality traits, so you need a larger number of higher-level Big Five-like factors to best explain personality," Gurven said.

The crux of their argument rests on the degree of societal complexity in a population -- i.e. specialization in all areas of life, including jobs, clubs and hobbies. "Simpler" societies have fewer niches, while more "complex" societies have many. "You can think about it like a five-band equalizer on a stereo. The more bands you have, the more combinations and nuances of sound you can create," said Gurven, "Imagine if all you have is one volume control. The only thing you can change is loudness."

"The socioecological environment shapes who we are," said lead author Paul Smaldino, an assistant professor of cognitive and information sciences at UC Merced. "Within a socioecological niche, particular behavioral characteristics may contribute to more or less success and be more or less reinforced."

An unexpected prediction

Their model results demonstrate how differences in the diversity of niches can explain the interesting empirical patterns. The team had earlier shown that across 55 nations where the Big Five were measured using the same methods, greater complexity (measured as a combination of urbanization, development and a country's product diversity portfolio) was associated with lower correlations among Big Five personality traits. The researchers' new model helps explain this result, and also yields an unexpected prediction: Personality traits should exhibit more internal variation in more complex societies.

Re-examining their 55-nation dataset, the researchers found support for their prediction: Indeed, personality factor variance correlates with socioecological complexity.

What's behind the Big Five

The social complexity and personality project was borne of a confluence of coincidences. Gurven, co-director of the Tsimane Health and Life History Project, had begun collecting personality data among the Tsimane, an isolated indigenous population in the Bolivian Amazon, to assess health and fitness costs and benefits associated with different personality types. When he and Christopher von Rueden, formerly a graduate student in anthropology at UC Santa Barbara and now an associate professor at Jepson School of Leadership Studies and a co-author of the paper, began analyzing the data using all the standard tools of the trade, they realized they couldn't replicate the Big Five personality structure.

What's more, they were struck by the fact that there is no theory in personality psychology that can explain the Big Five structure from first principles. Why do certain traits -- like trust and sympathy, impulsivity and anxiety -- bundle together the way they do? There are many possibilities for what personality structure might look like, so why does something like the Big Five appear in so many places? How can the Big Five be a human universal, yet scientists have little understanding about why trait covariation takes this exact form over another?

Gurven's previous work with the Tsimane revealed a Big Two (prosociality and industriousness), as opposed to Five, among that population and led the researchers to contemplate the role of societal structure, divisions of labor and specialization. Together with Aaron Lukaszewski, who completed his Ph.D. in evolutionary psychology at UC Santa Barbara and is now an assistant professor of psychology at CSU Fullerton and also a co-author of the paper, the group developed a verbal theory of how personality traits might emerge in response to societal complexity. They tested this with the personality data from 55 nations.

At the same time, Smaldino had been developing a theory of social identity signaling and social complexity that involved similar arguments. "I found my theory difficult to model as social identity doesn't have well-established, cross-culturally validated measurement paradigms, and was looking for a way to make progress," he said. "Personality data fit the bill and was a way to show how social complexity can shape the emergence of psychological features."

A new model

The model developed by the researchers is intentionally a simple one that ignores a number of features that spring to mind when considering this topic, like social networks and social influence, developmental processes and competition. "We initially designed and build a much more complicated model that included many of those things, as well as frequency-dependency payoffs within niches, membership in multiple niches and competing drives for similarity and differentiation," Smaldino explained. "But this model had so many parameters that analyzing it was complicated and not particularly informative. We were forced to ask ourselves: What is the essence of our theory?"

Only when they simplified their model by building it around only the essentials of their theory were they able to make progress

(BOSTON) -- The high-profile case of Jeffrey Epstein has shined a light on the reality that minors are being commercially sexually exploited, and that sexual exploitation can happen in any neighborhood, city, state, or country.

But a new study conducted by researchers at Boston University School of Public Health and Northeastern University, funded by the National Institute of Justice, says there may be a way to prevent this sex trafficking. The study is the first to evaluate the potential impact of a child CSE prevention program in the US.

Published in the Journal of Interpersonal Violence, the study found that young teenagers who completed the Boston-based My Life My Choice Exploitation Prevention Curriculum showed signs of being less at risk for commercial sexual exploitation (CSE) afterward, including reporting half as many episodes of sexually explicit behavior. They were also 24 percent less likely to have experienced dating abuse, and 40 percent more likely to give CSE-related information and help to their friends.

"What is so exciting about the My Life My Choice model is that they are bringing education and support to girls who are believed to be at high risk before they are exploited," said Emily Rothman, professor of community health sciences at Boston University School of Public Health, and corresponding author of the study.

The My Life My Choice Prevention Groups work to prevent harm and connect young people who are at risk with supportive services, said Amy Farrell, associate professor of criminology and criminal justice at Northeastern University's School of Criminology and Criminal Justice, and a co-author of the study.

"As communities increasingly seek strategies to meet the needs of young people who are at risk of commercial sexual exploitation, it is critical to have models to guide these responses that have been tested empirically," Farrell said. "The model has been recognized nationally as a best practice and we now have evidence to support the idea that is has a positive impact."

My Life My Choice is a survivor-led pioneer program fighting to end the commercial sexual exploitation of children. Trained facilitators run MLMC Prevention Groups in 33 states and Canada. Child protection workers, teachers, social workers, juvenile probation officers, and others refer young people who might be at particularly high risk to an MLMC Prevention Group (groups are restricted to young people who identify as female and/or were assigned female at birth). Previous research has identified child CSE risk factors including neglect and abuse, involvement with the child welfare system, substance use, running away from home, being homeless (and particularly being homeless and LGBTQ), and having a lack of family support and education/employment opportunities.

"Our model is unique because it has been informed, created and delivered by survivors of the commercial sex industry," said Lisa Goldblatt Grace, co-founder and Executive Director of

My Life My Choice. "We have paired this authentic, powerful perspective with public health innovation to develop our curriculum. We are thrilled to see this evaluation reflect what we experience every day: prevention can make a difference."

In the 10-week MLMC curriculum, group facilitators (usually a clinician and/or a CSE survivor) provide information designed to increase participants' knowledge about the commercial sex industry and individuals who sexually exploit others and shift their attitudes about the commercial sex industry. The curriculum also acknowledges barriers to making behavioral and safety-oriented changes, and teaches participants about risk factors for CSE, as well as helping participants develop media literacy skills and build self-esteem, resilience, and personal empowerment. Each participant keeps a journal during the curriculum and shares it only with the facilitator, giving the facilitator an opportunity to adapt the curriculum and giving participants a way to privately communicate possible threats to their safety and/or risky behavior.

The group participants assess their own vulnerability to exploitation, and the curriculum also encourages them to share what they have learned with other young people who may be at risk.

For the study, Rothman and her colleagues focused on about 300 participants in

My Life My Choice groups in Boston, Connecticut, New Jersey, and Florida, most of them around 14 years old. These participants filled out a survey before their first group, then responded to the same questions when they completed the curriculum and three months later. The surveys collected information about the demographics and lived experiences of the participants. They also measured behavior change and shifts in knowledge and attitudes about CSE and its harmful impact on youth (including questions about the recruitment tactics that pimps use, myths/facts about the commercial sex industry, healthy relationships, and drug and alcohol use as it pertains to CSE).

Both immediately after the curriculum and three months later, the researchers found that the participants reported half as many episodes of sexually explicit and potentially CSE-related behavior than they had before the curriculum. These behaviors ranged from taking naked selfies to exchanging sex for money, food, a place to stay, drugs, gifts, or favors.

At the three-month follow up, participants were two times less likely to report dating abuse victimization than before the curriculum. They also demonstrated increased knowledge and awareness of CSE and its harms and 100% of youth gave CSE-related help to a friend.

My Life My Choice's Survivor Mentoring model was also studied. For more information, including results of both parts of this study, visit http://www.mylifemychoice.org.