Category Archives: University of Chicago

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How HIV ‘hacks’ cells to spread itself

Using a computer model, researchers have uncovered previously unknown details about how HIV “hacks” cells to make them spread the virus to other cells. Their findings may offer a new avenue for drugs to combat the virus.

A key part of HIV’s success is a nasty little trick to propagate itself inside the body. Once HIV has infected a cell, it forces the cell to make a little capsule out of its own membrane, filled with the virus.

The capsule pinches off—a process called “budding”—and floats away to infect more cells. Once inside another unsuspecting cell, the capsule coating falls apart, and the HIV RNA gets to work.

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Scientists modeled how the HIV protein Gag is involved in forcing a victim’s cell to make a capsule of HIV to infect other cells, a process called “budding.” (Credit: Gregory Voth/U. Chicago)

Scientists knew that budding involves an HIV protein complex called Gag protein, but the details of the molecular process were murky.

“For a while now we have had an idea of what the final assembled structure looks like, but all the details in between remained largely unknown,” says Gregory Voth, professor of chemistry at the University of Chicago and corresponding author of the paper.

Since it’s been difficult to get a good molecular-level snapshot of the protein complex with imaging techniques, Voth and his team built a computer model to simulate Gag in action.

Simulations allowed them to tweak the model until they arrived at the most likely configurations for the molecular process, which experiments in the laboratory of Jennifer Lippincott-Schwartz at the National Institutes of Health and the Howard Hughes Medical Institute Janelia Research Campus then validated.

Potential HIV vaccine works in a new way

They built a model of missing parts of the Gag protein complex, and tweaked it until they could see how the proteins assemble by taking advantage of cellular infrastructure in preparation for the budding process.

“It really demonstrates the power of modern computing for simulating viruses,” Voth says.

“The hope is that once you have an Achilles’ heel, you can make a drug to stop Gag accumulation and hopefully arrest the virus’s progression.”

The team plans next to study the structures of the Gag proteins in the HIV virus capsule after budding, he says.

Is HIV cured or still lurking? New test can say

The researchers report their findings in the Proceedings of the National Academy of Sciences.

Source: University of Chicago

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‘Fireworks’ fly when cold bosons collide

Researchers have discovered a new kind of quantum behavior—and saw some fireworks in the process.

“This is a very fundamental behavior that we have never seen before; it was a great surprise to us,” says Cheng Chin, study author and professor of physics at the University of Chicago.

The research details a curious phenomenon—seen in what was thought to be a well-understood system—that may someday be useful in quantum technology applications.

Chin’s lab studies what happens to particles called bosons in a special state called a Bose-Einstein condensate. When cooled down to temperatures near absolute zero, bosons will all condense into the same quantum state.

Researchers applied a magnetic field, jostling the atoms, and they began to collide—sending some flying out of the condensate. But rather than a uniform field of random ejections, they saw bright jets of atoms shooting together from the rim of the disk, like miniature fireworks.

“If you’d asked almost anyone to predict what would happen, they would have said that these collisions would just send atoms flying off in random directions,” says postdoctoral fellow Logan Clark, the first author of the study; he and a coauthor, postdoctoral fellow Anita Gaj, were the first to see the phenomenon. “But what we see instead are thousands of bosons bunching together to leave in the same direction.”

“It’s like people forming a consensus and leaving in groups,” Chin says.

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Jets of atoms shoot off together like fireworks from a central disc in a new quantum phenomenon (color added for illustration). (Credit: Cheng et al./U. Chicago)

The tiny jets may show up in other systems, the researchers say—and understanding them may help shed light on the underlying physics of other quantum systems.

Moreover, the jets, like other new quantum behaviors, may be of interest in technology.

“For example, if you sent a particular atom in one direction, then a bunch more would follow in that same direction, which would help you amplify small signals in the microscopic world,” Clark says.

Since they delivered energy to the system and the particles are not at their ground states, the authors say the new behavior falls under the category of a particularly hot area of quantum engineering research called “driven” quantum systems. The physics of systems in these quantum states is not well understood, but essential for engineering useful technologies.

To create a better clock, apply this quantum ‘magic trick’

However, Bose-Einstein condensates are a generally well-studied area, so the researchers were excited to see a never-before-documented behavior, the scientists say.

“If you see something crazy in this simple experiment, it makes you wonder what else is out there,” says graduate student Lei Feng, also a study coauthor.

The researchers report their findings in the journal Nature.

The US Army Research Office, National Science Foundation, Grainger and Kadanoff-Rice fellowships, and University of Chicago Materials Research Science and Engineering Center funded the research.

Source: University of Chicago

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Microbiome database spans 7 continents, 27,000 samples

Researchers have created the first database of the bacteria colonizing the planet. Called the Earth Microbiome Project, the work involves over 27,000 samples from environments around the world.

“There are large swathes of microbial diversity left to catalogue…”

Researchers analyzed the collections of microbes, or microbiomes, in each sample to generate the database. The project, founded in 2010, will continue to grow and improve as new data are added.

“The potential applications for this database and the types of research questions we can now ask are almost limitless,” says Rob Knight, project cofounder and professor and director of the Center for Microbiome Innovation at University of California, San Diego.

“Here’s just one example—we can now identify what kind of environment a sample came from in more than 90 percent of cases, just by knowing its microbiome, or the types and relative quantities of microbes living in it. That could be useful forensic information at a crime scene,” he says.

Goals and methods

The goal of the Earth Microbiome Project is to sample as many of the Earth’s microbial communities as possible in order to advance scientific understanding of microbes and their relationships with their environments, including plants, animals, and humans.

So far the project has spanned seven continents and 43 countries, from the Arctic to the Antarctic, and more than 500 researchers have contributed to the sample and data collection. Project members are using this information as part of approximately 100 studies, half of which have appeared in peer-reviewed journals.

Project members analyze bacterial diversity among various environments, geographies, and chemistries by sequencing the 16S rRNA gene, a genetic marker specific for bacteria and their relatives, archaea. The 16S rRNA sequences serve as “barcodes” to identify different types of bacteria, allowing researchers to track them across samples from around the world.

Earth Microbiome Project researchers also use a new method to remove sequencing errors in the data, allowing them to get a more accurate picture of the number of unique sequences in the microbiomes.

Within this first release of data, the Earth Microbiome Project team identified around 300,000 unique microbial 16S rRNA sequences, almost 90 percent of which don’t have exact matches in pre-existing databases.

Pre-existing 16S rRNA sequences are limited because they were not designed to allow researchers to add data in a way that’s useful for the future.

“Before, you had to write in to get your sequence listed,” says project coauthor Jon Sanders, “and the listing would contain very little information about where the sequence came from or what other sequences it was found with. Now, we have a framework that supports all that additional context, and which can grow organically to support new kinds of questions and insights.”

Could tree microbiomes cut fertilizer on crops?

“There are large swathes of microbial diversity left to catalogue,” says Gilbert. “And yet we’ve ‘recaptured’ about half of all known bacterial sequences. With this information, patterns in the distribution of the Earth’s microbes are already emerging.”

Surprising findings

According to Gilbert, one of the most surprising observations is that unique 16S sequences are far more specific to individual environments than are the typical units of species used by scientists. The diversity of environments sampled by the Earth Microbiome Project helps demonstrate just how much local environment shapes the microbiome.

For example, the skin microbiomes of cetaceans (whales and dolphins) and fish are more similar to each other than they are to the water they swim in; conversely, the salt in saltwater microbiomes makes them distinct from freshwater, but they are still more similar to each other than to aquatic animal skin. Overall, the microbiomes of a host, such as a human or animal, were quite distinct from free-living microbiomes, such as those found in water and soil.

“These global ecological patterns offer just a glimpse of what is possible with coordinated and cumulative sampling,” Jansson says. “More sampling is needed to account for factors such as latitude and elevation, and to track environmental changes over time. The Earth Microbiome Project provides both a resource for the exploration of myriad questions and a starting point for the guided acquisition of new data to answer them.”

Wasps don’t live as long with ‘borrowed’ microbiomes

More than 300 researchers at more than 160 intuitions around the world, including researchers at the University of Chicago; Argonne National Laboratory; University of California, San Diego; and Pacific Northwest National Laboratory worked on the paper describing this effort, which appears in Nature.

Source: University of Chicago

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Certain proteins stay ‘relaxed’ while floating inside cells

New research may answer a long-standing question about how proteins act inside cells.

For many years, scientists thought that all proteins must fold into complicated shapes to fulfill their functions, looking like thousands of sets of custom-tailored locks and keys. But over the past two decades, scientists have begun to realize other proteins—including those involved in many essential cellular functions—remain fully or partially unfolded for parts of their lives.

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A new study suggests many proteins remain expanded in the cell, rather than contracting into tight folded shapes. (Credit: Micayla Bowman/U. Chicago)

Out of this realization has come a debate: how such proteins spend their time when floating in the cell. Since they’re not folded into their precise shapes, do they contract into balls, or remain expanded, like a rope?

Different methods have yielded different results. Scattering using X-rays suggested they remained expanded, but fluorescent methods observed the opposite behavior. The answer would affect how we envision the movement of a protein through its life—essential for understanding how proteins fold, what goes wrong during disorders and disease, and how to model their behavior.

“The results are very clear, but contradict the current consensus…”

Now, a team of researchers have used simulations and X-rays to tackle the question. They conclude that these proteins remain unfolded and expanded as they float loose in the cytoplasm of a cell.

“What we need to determine is how ‘sticky’ they are,” says coauthor Tobin Sosnick, chair of the biochemistry & molecular biology department at the University of Chicago, as well as director of the graduate program in biophysical sciences. “For survival, you want a protein to ‘stick’ only in the right conformation, and with the right other pieces or partners at the right times.” This stickiness is determined by the protein’s chemistry and physics.

Sosnick’s team came up with a way to analyze a single X-ray measurement to determine stickiness, finding that the proteins are generally much less sticky than expected. Their chemistry is set up to prefer to interact with water, rather than itself or other proteins.

Supercomputer peeks into cell to observe proteins

“The results are very clear, but contradict the current consensus,” Sosnick says. “It’s possible that proteins can avoid unwanted interactions by being expanded.” This reduces the chances of them sticking to other proteins by accident, causing dysfunction or disease.

The researchers report their work in the journal Science.

Additional researchers who contributed to the work are from the University of Chicago and the University of Notre Dame. The researchers conducted the X-rays measurements at the nearby Advanced Photon Source, a powerful synchrotron at Argonne National Laboratory.

The National Institutes for Health, the National Science Foundation, and the US Department of Energy for the Advanced Photon Source funded the research.

Source: University of Chicago

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100 years ago, air pollution stained birds gray

The dirty feathers of birds in some museum collections are giving scientists clues as to the level of carbon in the air over the years.

Horned larks are songbirds with white bellies and yellow chins—at least, now they are. But 100 years ago, at the height of urban smoke pollution in the United States, soot in the atmosphere stained their pale feathers dark gray.

A new paper in the Proceedings of the National Academy of Sciences shows that the discoloration of these birds can be used to trace the amount of black carbon in the air over time and measure the effects of environmental policy on pollution.

“…when you look at pictures of Beijing and Delhi, you get a sense for what US cities like Chicago and Pittsburgh were once like.”

“The soot on these birds’ feathers allowed us to trace the amount of black carbon in the air over time,” says author Shane DuBay, a graduate student in the Committee on Evolutionary Biology at the University of Chicago and The Field Museum. “We found that the air at the turn of the century was even more polluted than scientists previously thought.”

DuBay and coauthor Carl Fuldner, a graduate student in the art history department, analyzed more than a thousand birds collected over the last 135 years to determine and quantify the effects of soot in the air over cities in the Rust Belt.

“If you look at Chicago today, the skies are blue. But when you look at pictures of Beijing and Delhi, you get a sense for what US cities like Chicago and Pittsburgh were once like,” DuBay says. “Using museum collections, we were able to reconstruct that history.”

Flying air filters

Ornithologists at The Field Museum have long known that bird specimens in the collection from the early 1900s were visibly darker than expected, and atmospheric soot was the suspected cause.

During the Great Depression, there’s a sharp drop in black carbon on the birds.

“When you touch these birds, you get traces of soot on your hands. We’d wear white gloves while handling them, and the gloves would come away stained, like when you get ink on your fingertips reading a newspaper,” DuBay says, because the soot in the air clung to the birds like dust to a feather duster. “These birds were acting as air filters moving through the environment.”

Birds were also ideal candidates for the study because they molted and grew new sets of feathers every year, meaning that the soot on them had been accumulating only for the past year when they were collected. And there was an apparent trend: old birds were dirtier, and new birds were cleaner.

To measure the changes in sootiness over the years, researchers turned to a new approach: photographing birds and measuring the light reflected off of them. Fuldner, a photo historian who focuses on images of the environment, worked with DuBay to develop a method for analyzing the birds using photography.

Researchers photographed more than 1,000 birds for the study from all five species that bred in the Manufacturing Belt. They all have lots of white feathers that show off soot. The images, depicting the contrast between the soiled gray birds and the clean white ones, are dramatic.

“The photographs give the project a visceral dimension—you make a connection to the images,” Fuldner says.

“The fact that the more recent birds are cleaner doesn’t mean we’re in the clear.”

The researchers plotted the amount of light bouncing off the feathers according to the year the birds were collected. To make sense of their findings, they then delved into the social history of urban air pollution.

“The changes in the birds reflect efforts, first at the city level but eventually growing into a national movement, to address the smoke problem,” Fuldner says. “We are actually able to go back and see how effective certain policy approaches were.”

“We were surprised by the precision we were able to achieve,” DuBay says. “The soot on the birds closely tracks the use of coal over time. During the Great Depression, there’s a sharp drop in black carbon on the birds because coal consumption dropped—once we saw that, it clicked.”

The amount of soot on the birds rebounded around World War II, when wartime manufacturing drove up coal use. Then it dropped off quickly after the war, around when people in the Rust Belt began heating their homes with natural gas piped in from the West rather than with coal.

Less visible pollution

“The fact that the more recent birds are cleaner doesn’t mean we’re in the clear,” DuBay says. “While the US releases far less black carbon into the atmosphere than we used to, we continue to pump less-conspicuous pollutants into our atmosphere—those pollutants just aren’t as visible as soot. Plus, many people around the world still experience soot-choked air in their cities.”

Analysis of atmospheric black carbon might help scientists who study climate change. “We know black carbon is a powerful agent of climate change, and at the turn of the century, black carbon levels were worse than previously thought,” DuBay says.

“I hope that these results will help climate and atmospheric scientists better understand the effects of black carbon on climate.”

People of color breathe more air pollution

“As a historian, one of the questions I always ask is, ‘What is the point of this research to the way we live now?’ In this case the answer quickly became clear,” Fuldner says. “Filling in a blank space in the historical record of something as large as air pollution in American cities, and being able to share that with atmospheric scientists who study the effects of black carbon on the climate, is extraordinary.”

“This study shows a tipping point when we moved away from burning dirty coal, and today, we’re at a similar pivotal moment with fossil fuels,” DuBay says. “In the middle of the 20th century, we made an investment in infrastructure and regulated fuel sources—hopefully, we can take that lesson and make a similar transition now to more sustainable, renewable energy sources that are more efficient and less harmful to our environment.”

Researchers used collections from The Field Museum in Chicago, the Carnegie Museum of Natural History in Pittsburgh, and the University of Michigan Museum of Zoology in Ann Arbor in the work.

Source: University of Chicago

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Tracing titanium revises Earth’s ancient history

Researchers are revising their understanding of early Earth—including how the planet came to support multi-cellular life—by tracing the metallic element titanium through the planet’s crust through time.

The new research, which appears in the journal Science, suggests significant tectonic action was already taking place 3.5 billion years ago—about half a billion years earlier than currently thought.

The crust was once made of uniformly dark, magnesium- and iron-rich mafic minerals. But today the crust looks very different between land and ocean: The crust on land is now a lighter-colored felsic, rich in silicon and aluminum. The point at which these two diverged is important, since the composition of minerals affects the flow of nutrients available to the fledgling life struggling to survive on Earth.

granite peaks, an example of felsic rock
These granite peaks are an example of felsic rock, created via plate tectonics.(Credit: Basil Greber/U. Chicago)

“This question has been discussed since geologists first started thinking about rocks,” says lead author Nicolas Dauphas, professor and head of the Origins Laboratory in the geophysical sciences department and the Enrico Fermi Institute at the University of Chicago. “This result is a surprise and certainly an upheaval in that discussion.”

To reconstruct the crust changing over time, geologists often look at a particular kind of rock called shales, made up of tiny bits of other rocks and minerals that water carries into mud deposits and compressed into rock. The only problem is that scientists have to adjust the numbers to account for different rates of weathering and transport. “There are many things that can foul you up,” Dauphas says.

To avoid this issue, Dauphas and his team looked at titanium in the shales over time. This element doesn’t dissolve in water and isn’t taken up by plants in nutrient cycles, so they thought the data would have fewer biases with which to contend.

They crushed samples of shale rocks of different ages from around the world and checked in what form its titanium appeared. The proportions of titanium isotopes present should shift as the rock changes from mafic to felsic. Instead, they saw little change over three and a half billion years, suggesting that the transition must have occurred before then.

This also would mark the beginning of plate tectonics, since that process is believed to be needed to create felsic rock.

“With a null response like that, seeing no change, it’s difficult to imagine an alternate explanation,” says Matouš Ptáček, a graduate student and coauthor of the study.

“Our results can also be used to track the average composition of the continental crust through time, allowing us to investigate the supply of nutrients to the oceans going back 3.5 billion years ago,” says Nicolas Greber, the first author of the paper, then a postdoctoral researcher at the University of Chicago and now with the University of Geneva.

Bubbles in lava could change our view of early Earth

The question about nutrients is important for our understanding of the circumstances around a mysterious but crucial turning point called the great oxygenation event. This is when oxygen started to emerge as an important constituent of Earth’s atmosphere, wreaking a massive change on the planet—and making it possible for multi-celled beings to evolve.

The flood of oxygen came from a surge of photosynthetic microorganisms; and in turn their work was fostered by a surge of nutrients to the oceans, particularly phosphorus.

“Phosphorus is the most important limiting nutrient in the modern ocean. If you fertilize the ocean with phosphorus, life will bloom,” Dauphas says.

The titanium timeline suggests that the primary trigger of the surge of phosphorus was the change in the makeup of mafic rock over time. As the Earth cooled, the mafic rock coming out of volcanoes and underground melts became richer in phosphorus.

“We’ve known for a long time that mafic rock changed over time, but what we didn’t know was that their contribution to the crust has stayed rather consistent,” Ptáček says.

Methane from microbes kept early Earth warm

Additional researchers contributing to the work are from University of California, Riverside; University of Oregon-Eugene; and the University of Johannesburg.

The National Science Foundation, NASA, Swiss National Science Foundation, and the Natural Sciences and Engineering Research Council of Canada provided funding for the research.

Source: University of Chicago

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Atoms-thick semiconductor layers stick like Post-its

Scientists have figured out how to make tiny individual films—each just a few atoms high—and stack them for use in new kinds of electronics.

Over the past half-century, scientists have shaved silicon films down to just a wisp of atoms in pursuit of smaller, faster electronics. For the next set of breakthroughs, though, they’ll need new ways to build even tinier and more powerful devices.

In a study that appears in Nature, researchers describe an innovative method to make stacks of thin, uniform layers of semiconductors just a few atoms thick which could expand capabilities for devices like solar cells and cell phones.

“When the material itself is just atoms thick, every little stray atom is a problem.”

Stacking thin layers of materials offers a range of possibilities for making electronic devices with unique properties. But manufacturing them is a delicate process, with little room for error, researchers say.

“The scale of the problem we’re looking at is, imagine trying to lay down a flat sheet of plastic wrap the size of Chicago without getting any air bubbles in it,” says Jiwoong Park, a professor of chemistry at the University of Chicago and at the Institute for Molecular Engineering and the James Franck Institute. “When the material itself is just atoms thick, every little stray atom is a problem.”

Today, these layers are “grown” instead of stacking them on top of one another. But that means the bottom layers are subjected to harsh growth conditions such as high temperatures while the new ones are added—a process that limits the materials with which to make them.

For the new process, Park’s team did something different. They made the films individually, then put them into a vacuum, peeled them off, and stuck them to one another, like Post-it notes.

This allowed scientists to make films that were connected with weak bonds instead of stronger covalent bonds—interfering less with the perfect surfaces between the layers.

“The films, vertically controlled at the atomic-level, are exceptionally high-quality over entire wafers,” says postdoctoral associate Kibum Kang, the study’s first author.

Graduate student Kan-Heng Lee, a co-first author of the study, then tested the films’ electrical properties by making them into devices and showed that their functions can be designed on the atomic scale, which could allow them to serve as the essential ingredient for future computer chips.

‘Rusty’ semiconductor circuits can be thinner than silicon

The method opens up a myriad of possibilities for such films. They can be made on top of water or plastics; they can be made to detach by dipping them into water; and they can be carved or patterned with an ion beam.

Researchers are exploring the full range of what can be done with the method, which they said is simple and cost-effective.

“We expect this new method to accelerate the discovery of novel materials, as well as enabling large-scale manufacturing,” Park says.

Researchers from Cornell University are coauthors of the study. The US Air Force, the National Science Foundation, and the National Research Foundation of Korea funded the work.

Source: University of Chicago

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Molecular ‘time machine’ shows chance’s role in evolution

By studying a massive set of genetic variants of an ancient protein, scientists have been able to examine the myriad other ways that evolution could have turned out. Their work reveals the key role random chance plays in the history of evolution.

The study is the first to subject reconstructed ancestral proteins to deep mutational scanning—a state-of-the-art technique for characterizing massive libraries of protein variants. The strategy allowed them to compare the path that evolution actually took in the deep past to the millions of alternative routes that could have been taken, but were not.

Starting with a resurrected version of an ancient protein that evolved a new function some 500 million years ago—a function critical to human biology today—the researchers synthesized a massive library of genetic variants and used deep mutational scanning to analyze their functions. They found more than 800 different ways that the protein could have evolved to carry out the new function as well, or better than, the one that evolved historically.

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Tyler Starr holds a vial of yeast cells engineered with a library of proteins comprising millions of possible evolutionary paths from our ancient ancestor to its modern function. (Credit: Matt Wood/U. Chicago)

The researchers showed that chance mutations early in the protein’s history played a key role in determining which ones could occur later. As a result, the specific outcome of evolution depended critically on the way a serial chain of chance events unfolded.

“By comparing what happened in history to all the other paths that could have produced the same result, we saw how idiosyncratic evolution is,” says Tyler Starr, a graduate student in biochemistry and molecular biology at the University of Chicago, who performed the paper’s experiments.

“People often assume that everything in biology is perfectly adapted for its function. We found that what evolved was just one possibility out of many that were just as good, or even better, functionally than what we happened to end up with today,” he explains.

Back through time

Over the last 15 years, Thornton, senior author on the new study and a professor in ecology and evolution and human genetics at the university, led research that pioneered “molecular time travel” using ancestral protein reconstruction.

In 2013, his team resurrected and analyzed the functions of the ancestors of a family of proteins called steroid hormone receptors, which mediate the effects of hormones like testosterone and estrogen on sexual reproduction, development, physiology, and cancer. The body’s various receptors recognize different hormones and, in turn, activate the expression of different target genes, which they accomplish by binding specifically to DNA sequences called response elements near those targets.

“There’s nothing special about the history that happened, except that a few chance steps brought us to this singular chance outcome.”

Thornton’s group inferred the genetic sequences of ancient receptor proteins by statistically working their way back down the tree of life from a database of hundreds of present-day receptor sequences. They synthesized genes corresponding to these ancient proteins, expressed them in the lab, and measured their functions.

They found that the ancestor of the family behaved like an estrogen receptor—recognizing only estrogens and binding to estrogen response elements—but during one specific interval of history, they evolved into a descendant group capable of recognizing other steroid hormones and binding to a new class of response elements. The researchers found that three key mutations before the emergence of vertebrate animals caused the ancestral receptor to evolve its ability to bind to the new target sequences.

Evolution pop quiz: How much do you know?

That work set the stage for the current study. Knowing precisely how evolution played out in the past, Thornton’s group asked: Was this the only evolutionary path to evolving the new function? Was it the most effective one, or the easiest to achieve? Or was it simply one of many possibilities?

Paths not taken

Starr began working on the project during his first year as a graduate student, developing the technique to assess massive numbers of variants of the ancestral receptor for their ability to bind the new response element.

First, he engineered strains of yeast in which the ancestral or new response elements drive expression of a fluorescent reporter gene. He then synthesized a library of ancestral proteins containing all possible combinations of amino acids at the four key sites in the receptor that recognize DNA—160,000 in all, comprising all possible evolutionary paths that this critical part of the protein could have followed—and introduced this library into the engineered yeast.

He sorted hundreds of millions of yeast cells by their fluorescence using a laser-driven device, and then used high-throughput sequencing to associate each receptor variant with its ability to carry out the ancestral function and the new function.

Most of the variants failed to function at all, and some maintained the ancestral function. But Starr found 828 new versions of the protein that could carry out the new function as well, or better than, the one that evolved during history. Remarkably, evolution could have accessed many of these even more easily than the historical “solution,” but it happened not to, apparently wandering around the space of possible mutations until it arrived at the version of the protein in our bodies today.

“We all share the same gene sequence for this protein, so it might seem like evolutionary destiny, as if we’ve arrived at the best possible version. But there are hundreds of other directions that evolution could just as well have taken,” Thornton says. “There’s nothing special about the history that happened, except that a few chance steps brought us to this singular chance outcome.”

Evolution’s winning groups have these 3 traits

Thornton says that deep mutational scanning will be a powerful tool for evolutionary biologists, geneticists and biochemists, and he looks forward to using the approach on successive ancestors at different points in history to see how the set of possible outcomes changed through time.

“We have a molecular time machine to go back to the past, and once we’re there, we can simultaneously follow every alternate history that could possibly have played out,” Thornton says. “It’s a molecular version of every evolutionary biologist’s dream.”

The study appears in the journal Nature.

Source: University of Chicago

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In northern China, air pollution cuts years off life expectancy

People in northern China have a reduced life expectancy when compared with people living in the south due to higher concentrations of air pollution, a new study suggests.

The study also outlines a new method researchers developed to calculate the impact of air pollution on life expectancy.

There are currently an estimated 4.5 billion people around the world exposed to levels of particulate air pollution that are at least twice what the World Health Organization considers safe. Yet the impact of sustained exposure to pollution on a person’s life expectancy has largely remained a vexingly unanswered question.

“…the impact on life expectancy in many parts of the world [is] similar to the effects of every man, woman, and child smoking cigarettes for several decades…”

The study finds that a Chinese policy is unintentionally causing people in northern China to live 3.1 years less than people in the south. The study found that this was due to air pollution concentrations that are 46 percent higher in the north than in the south.

The new findings imply that every additional 10 micrograms per cubic meter of particulate matter pollution reduces life expectancy by 0.6 years. The elevated mortality is entirely due to an increase in cardiorespiratory deaths, indicating that air pollution is the cause of reduced life expectancies to the north.

“These results greatly strengthen the case that long-term exposure to particulates air pollution causes substantial reductions in life expectancy. They indicate that particulates are the greatest current environmental risk to human health, with the impact on life expectancy in many parts of the world similar to the effects of every man, woman, and child smoking cigarettes for several decades,” says study coauthor Michael Greenstone, director of the Energy Policy Institute at the University of Chicago and a professor in economics.

“The histories of the United States, parts of Europe, Japan, and a handful of other countries teach us that air pollution can be reduced, but it requires robust policy and enforcement,” Greenstone says.

Free coal

The study exploits China’s Huai River policy, which provided free coal to power boilers for winter heating to people living north of the river and provided almost no resources toward heating south of the river. The policy’s partial provision of heating occurred because China did not have enough resources to provide free coal nationwide.

“Unveiling this important information helps build the case for policies that ultimately serve to improve the lives of the Chinese people…”

Additionally, since migration was greatly restricted, people exposed to pollution were generally not able to migrate to less polluted areas. Together, the discrete change in policy at the river’s edge and the migration restrictions provide the basis for a powerful natural experiment that offers an opportunity to isolate the impact of sustained exposure to particulates air pollution from other factors that affect health.

“Unveiling this important information helps build the case for policies that ultimately serve to improve the lives of the Chinese people and the lives of those globally who suffer from high levels of air pollution,” says study coauthor Maigeng Zhou, deputy director of the National Center for Chronic and Noncommunicable Disease Control and Prevention in the Chinese Center for Disease Control and Prevention.

Overall, the study provides solutions to several challenges that have plagued previous research. In particular, prior studies rely on research designs that may be unlikely to isolate the causal effects of air pollution; measure the effect of pollution exposure for relatively short periods of time (e.g., weekly or annually), failing to shed light on the effect of sustained exposure; examine settings with much lower pollution concentrations than those currently faced by billions of people in countries, including China and India, leaving questions about their applicability unanswered; measure effects on mortality rates but leave the full loss of life expectancy unanswered.

“The study’s unique design provides solutions to several challenges that have been difficult to solve,” says coauthor Maoyong Fan, an associate professor at Ball State University. “The Huai River policy also provides a research design that can be used to explore a variety of other questions about the long-run consequences of exposure to high levels of pollution.”

The study follows on an earlier study, conducted by some of the same researchers, which also utilized the unique Huai River design. Despite using data from two separate time periods, both studies revealed the same basic relationship between pollution and life expectancy.

The new study’s more recent data, however, cover a population eight times greater than the previous one. It also provides direct evidence on smaller pollution particles that are more often the subject of environmental regulations.

Complaints on Weibo predict Chinese air pollution

“This new study provides an important opportunity to assess the validity of our previous findings. The striking finding is that both studies produced remarkably similar results, increasing our confidence that we have uncovered the causal relationship between particulates air pollution and life expectancy,” says Avraham Ebenstein, a lecturer in the environmental economics and management department at Hebrew University of Jerusalem and an author of both studies.

Since the earlier paper, China has increased its efforts to confront its air pollution challenge. China is switching its primary source of heating from coal-fired boilers to gas-fired or electric units, and it has shut down many polluting plants. The consequence is that particulate air pollution in some of China’s most polluted cities, such as Beijing, has improved significantly.

“Our findings show that these changes will bring about significant health benefits for the Chinese people in the long run,” says coauthor Guojun He, an assistant professor at the Hong Kong University of Science and Technology. “If all of China were brought into compliance with its Class I standards for PM10 (40), more than 3.7 billion life-years will be saved.”

The Air Quality-Life Index

Importantly, the results from this paper can be generalized to quantify the number of years that air pollution reduces lifespans around the globe—not just in China. Specifically, Greenstone and his colleagues at EPIC used the finding that an additional 10 micrograms per cubic meter of PM10 reduces life expectancy by 0.6 years to develop a new pollution index, the Air Quality-Life Index.

The index allows users to better understand the impact of air pollution on their lives by calculating how much longer they would live if the pollution in the air they breathe were brought into compliance with national or WHO standards. It also serves as an important complement to the frequently used Air Quality Index, which is a complicated function of air pollution concentrations and does not map directly to long-term human health.

Rats gain weight after breathing Beijing’s air for 3 weeks

“The AQLI uses the critical data and information gathered from our China research and applies it to every country, allowing the billions of people around the world who are exposed to high air pollution levels to estimate how much longer they would live if they breathed cleaner air,” said Greenstone.

The study appears in the Proceedings of the National Academy of Sciences.

Source: Vicki Ekstrom High for University of Chicago

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Empathy doesn’t always decline during med school

A new study challenges the idea that medical students’ empathy declines during their time at medical school.

Previous studies that reported an erosion of empathy during medical training relied on one self-reported assessment of cognitive empathy.

Some studies have documented troubling declines in empathy during medical training—the steepest of which are believed to occur between the second and third years of medical school, when students begin clinical training and empathetic communication is critical, but this new study may refute those findings.

The relationship between a doctor and patient relies heavily on the physician’s capacity to empathize with or be sensitive to a patient’s emotional state. Empathy has been associated with patients’ increased adherence to treatment, fewer malpractice complaints, improved patient satisfaction, and favorable health outcomes.

The authors of the new study point to the interaction of two facets of empathy: cognitive and affective.

“Cognitive empathy is the ability to recognize and understand another person’s experience, to communicate and confirm that understanding, and to act in an appropriate and helpful manner without necessarily sharing his or her emotions,” says Jean Decety, a professor of psychology and psychiatry, and lead author of the new study. “Affective, or emotional, empathy is being attuned to someone else’s emotions, feeling what he or she feels.”

Previous studies that reported an erosion of empathy during medical training relied on one self-reported assessment of cognitive empathy. Often emphasized as most important in a clinical setting, it enables physicians to understand how their patients feel without having an emotional attunement. Affective empathy has long been thought to impede a physician’s effectiveness in diagnosing and treating patients.

Decety and colleagues contend that both components are important in patient-physician interactions, as doctors must be able to both accurately perceive and respond to their patients’ emotional states.

In this study, a variety of subjective and objective measures helped provide a more complete understanding of the mechanisms that contribute to changes in empathetic capacity over the course of medical school. It also shed light on current discrepancies and inconsistencies within medical empathy literature.

Researchers designed a study that followed 129 medical students from Loyola University, Northwestern University, and the University of Chicago during their first three years of medical school. At the beginning and end of each year, students completed a series of online surveys and behavioral tasks designed to objectively assess different components of empathy.

The first survey was the Jefferson Scale of Physician Empathy, one of the most common self-assessment questionnaires in the field and thought to primarily evaluate the cognitive aspects of empathy.

“We sought to replicate the results of previous studies that used this self-report measure,” says Decety. “We did, in fact, see declines in assessment scores over the course of student training, which is in line with other studies that used this method.”

New way to test empathy uses painful images

The research team was interested in more than just a self-report on cognitive empathy, however. They wanted to tease out how the individual components of empathy changed over time, so they also administered the Questionnaire of Cognitive and Affective Empathy. This assessment is designed to reliably distinguish between the two facets of empathy, based on the social cognitive neuroscience literature on empathy and its underlying brain mechanisms.

At each appointment, students also were asked to complete a set of computerized tasks aimed at objectively evaluating their ability to recognize different mental and emotional states and sensitivity to the pain of others.

In contrast to the results of the Jefferson Scale questionnaire, student scores on the Questionnaire of Cognitive and Affective Empathy improved over time. Specifically, they found that both affective empathy and cognitive empathy increased during medical training. Similarly, medical students showed both greater sensitivity to facial expressions of pain and progress in their ability to quickly and accurately recognize others’ emotional states.

The study challenges the view of an overall decline of empathy during medical training. The authors write: “We found that changes in empathy during medical training are not necessarily negative—the narrative appears to be much more complicated than we initially thought and illustrates how problematic it is to rely on a single, subjective measure to evaluate a complex psychological construct.”

‘Walk in their shoes’ isn’t the best way to empathize

The facets of empathy that improved, including perspective-taking and understanding others’ emotions, are thought to be most important to physician empathy—and the most susceptible to change through teaching. Given the importance of empathy in the clinical setting, characterizing and understanding changes in student empathy has important implications for future teaching interventions, the authors contend.

Observed changes also may be the result of a curriculum that focuses on understanding the patient’s perspective and conveying that to the patient. Many medical schools, including those included in this work, have explicit empathy curricula aimed at developing these skills, and the findings in this study could indicate these programs create positive changes.

The study appears in the journal Medical Education.

Source: Tina Cormier for University of Chicago

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