Imaging system tracks brain activity of a freely moving worm

TO EXPLORE HOW THE BRAIN controls behavior, researchers have for the first time captured the whole-brain activity of a freely moving animal, in this case a nematode worm called Caenorhabditis elegans.

Using an imaging system they designed, Andrew Leifer, a Lewis-Sigler Fellow, and Joshua Shaevitz, an associate professor of physics and the Lewis-Sigler Institute for Integrative Genomics, measured the activity of 78 of the worm brain’s 125-plus neurons, which they engineered to turn green when active.

The setup consists of cameras that monitor the worm’s position and a motorized stage that adjusts to track the worm as it roams freely. The researchers were able to show significant correlations between neuron activity patterns and behaviors such as moving backward or forward, and turning. The team included Jeffrey Nguyen, a postdoctoral research associate and first author on the study, and colleagues at the Lewis-Sigler Institute and the Princeton Neuroscience Institute.

The study was posted on the preprint server and was funded by Princeton’s Dean for Research Innovation Fund for New Ideas in the Natural Sciences, the Simons Foundation and the National Institutes of Health.

–By Catherine Zandonella

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Nobel Prize in economics goes to Angus Deaton

Angus Deaton

Angus Deaton, the Dwight D. Eisenhower Professor of International Affairs and a professor of economics and international affairs in Princeton’s Woodrow Wilson School of Public and International Affairs, was awarded the 2015 Nobel Prize in economics for his contributions to understanding consumption at the individual level and in aggregate. PHOTO BY DENISE APPLEWHITE






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Student identifies difference between the dinosaur sexes

THE DISCOVERY OF A SINGLE ANATOMICAL DIFFERENCE between males and females of a species of Stegosaurus provides some of the most conclusive evidence that some dinosaurs looked different based on sex, according to research published in PLoS One and conducted by Evan Saitta while he was an undergraduate at Princeton.

The study found that the back plates of the species Stegosaurus mjosi came in two varieties that indicated the animal’s sex — short and wide, and tall and narrow. Females had one type of plate and males the other. The lack of a particular female-specific bone tissue found in birds and some dinosaurs, however, made it difficult to determine which sex had which plate type.

Saitta, who graduated from Princeton in 2014 and conducted the research for his senior thesis project, drew from existing animals, particularly horned animals, to suggest that the distinct shape of male and female S. mjosi plates indicated two different functions. He supposes that the tall, narrow plates belonged to females, who would have needed the pointier plates to defend themselves against predators. The wide plates, which were 45 percent larger in surface area, likely served as “billboard” displays males used to attract females, similar to the plumes of the male peacock.

Beyond the implications for Stegosaurus, the research establishes that sexual dimorphism — in which males and females of a species have distinct physical forms — could exist in non-avian dinosaurs, a group that includes iconic reptiles such as Tyrannosaurus and Brontosaurus, Saitta said. Existing work on sexual dimorphism in non-avian dinosaurs had been inconclusive. Saitta is now a graduate student at the University of Bristol in the United Kingdom.

Andrew Farke, the Augustyn Family Curator of Paleontology at the Raymond M. Alf Museum of Paleontology in Claremont, California, said that the work provides a potential foothold for other researchers wanting to explore sexual dimorphism in Stegosaurus and possibly other non-avian dinosaurs.

“This is very species specific, so there’s a lot of work that needs to be done to extend this to other animals,” said Farke, who is familiar with the study but had no role in it. “It’s not the end of the road, but I think it will stimulate people to look at this issue in Stegosaurus.”

–By Morgan Kelly

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Energy boost: Study sheds light on mitochondrial disease

Ileana Cristea


INSIDE OUR CELLS, TINY FACTORIES convert nutrients from food into a form of energy that cells can use. Failure of these factories, known as mitochondria, can lead to metabolic disorders that are difficult to diagnose and even harder to treat.

Now researchers have identified an important regulator of cellular energy production that could aid in the diagnosis and treatment of a range of conditions. In a study published on Dec. 18, 2014, in the journal Cell, the researchers demonstrated that an enzyme known as Sirtuin 4 acts as a guardian of cellular energy production.

“The finding has broad implications in human health,” said Ileana Cristea, associate professor of molecular biology, who led the study. “Stress, nutritional deficiencies and viral infections can impact Sirtuin 4 functions and trigger dysfunction in energy metabolism,” Cristea said. “With this knowledge, we now have a new regulatory point that can be targeted in therapeutic interventions.”

Cristea’s team discovered that Sirtuin 4 turns off energy production by removing certain protein modifications, called lipoylation, from a key part of the energy-making machinery, called the pyruvate dehydrogenase complex.

The research team included former Postdoctoral Researcher Rommel Mathias and Associate Research Scholar Todd Greco in the Cristea laboratory, as well as collaborators Thomas Shenk, the James A. Elkins Jr. Professor in the Life Sciences, and Yibin Kang, the Warner-Lambert/Parke-Davis Professor of Molecular Biology.

Cristea’s research is supported by the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Disease, the National Institute of General Medical Sciences, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

–By Catherine Zandonella

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Life among strangers: Exile in the Middle Ages


IN THE 1300s, A ROVING GANG OF THUGS went on a crime spree in France that included robbery, homicide and burial — possibly alive — of a body in a public privy. One of the gang’s members was Philip “Little Phil” Cavillon, an Englishman who’d been sentenced to exile in France.

The lives of Little Phil and other exiled English subjects in the late Middle Ages are the focus of a new book by historian William Chester Jordan, the Dayton-Stockton Professor of History. By studying English judicial documents, petitions to the king for pardon and surviving French records, Jordan pieced together the stories of these forsaken individuals in the scholarly work From England to France: Felony and Exile in the High Middle Ages (2015, Princeton University Press).

Not all of the exiles were murderers, but most had committed a serious crime, such as arson or theft, and then sought refuge in a church where they confessed their sins. Protected from execution by the church, the offenders were condemned to exile.

Between 1180 and 1350, thousands of men and the occasional woman went into exile, or “abjured the realm,” boarding ships in the port of Dover and arriving, often penniless and desperate, in the village of Wissant in a Dutch-speaking region of France. Some sought work as farm laborers, servants or prostitutes, while others, like Little Phil, resumed their lawless behaviors.

Jordan’s stories of these exiles bring to life what it was like to live at the height of the Middle Ages, an era that was prosperous by medieval standards but was close enough to subsistence level that theft was a threat to survival and punishable by death.

The practice of sentencing of criminals to exile probably arose as a backlash to the harsh punishments — notably hanging — allowed by medieval English law, Jordan said, drawing comparisons to the use of exile by France, which transferred felons to French Guiana, and Russia, which shipped political prisoners to Siberia.

“When society realizes that too many people are being executed,” Jordan said, “you begin to see the rise of alternatives such as exile, which itself contributed to many deaths, but far out of sight of the authorities.”

–By Catherine Zandonella

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Hero explores Vietnam War experiences

FOR HIS SENIOR THESIS, Eamon Foley combined indie rock music, dance, aerial choreography and ethnographic research to create an original theater-dance piece titled Hero, which tells the story of a young man transformed by his experiences in the Vietnam War.

The senior thesis is a major research or creative work required of all Princeton undergraduates. Foley’s thesis, featuring a cast of fellow Princeton students, was performed April 25 through May 1, 2015, at the Lewis Center for the Arts’ Matthews Acting Studio, the Program in Theater’s black box theater.

The script is based on Foley’s interviews with Vietnam veterans and other research, including his visit to Vietnam in summer 2014. “I spent a lot of time studying ethnography — the idea of gathering information through interview,” said Foley, who graduated in 2015 with an anthropology degree and a theater certificate. “I thought this would be a great way to look at where anthropology and theater meet.”

A documentary about the experience of creating Hero, by Danielle Alio and Jamie Saxon, takes viewers through Foley’s 10-month creative journey, from early fall 2014 when he had no script, no choreography and no cast — just “a lot of great ideas bouncing around in my head” — through opening night.

-By Danielle Alio and Jamie Saxon

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Taming the network: Finding relationships in complex data sets

WHAT BRINGS PEOPLE TOGETHER IN ONLINE NETWORKS? Researchers (and advertisers) would like to know, but without access to personal profiles, the question is not easy. Finding previously undetected relationships in networks and complex data sets is one of the major challenges in the age of “big data.”

Now Assistant Professor Emmanuel Abbe and his collaborators have come up with a new way of thinking about networks to accomplish this task. Not limited to exploring social communities, the technique can tackle significant challenges such as determining which genes work together to increase your cancer risk or how to identify objects — such as chairs or puppies — in a collection of digital images.

The method involves examining whether members of a network are connected by looking at how many common “friends” they have, how many common friends those friends have, and so on. Using this information, the researchers construct a set of statistics that can predict who is in the same sphere.

The approach extracts the “signals” of communities amid a background of “noisy” connections. Abbe’s method is analogous to work by Claude Shannon, sometimes called the father of information theory, who showed that noise imposes a limit to the rate at which data can be transmitted with almost zero error. Abbe has shown that there is an analogous limit to the problem of recovering communities from large data sets.

“Once we understood that there is a fundamental limit to this problem, there was a clear line of sight for how to solve it,” said Abbe, a member of Princeton’s Department of Electrical Engineering and Program in Applied and Computational Mathematics. Abbe and Colin Sandon, a graduate student in the Department of Mathematics, put the method to the test by examining political blogs, some right-leaning and others left-leaning, that sprung up prior to the 2004 presidential election. They asked, if you knew which blogs were referring to each other, but had zero information about the content of the blog, could you figure out which blogs are run by Republicans and which ones by Democrats? “We were able to identify 95 percent of the blogs that we looked at as left- or right-leaning,” Abbe said.

The work was published in the Proceedings of the Annual Symposium on Foundations of Computer Science in 2015. Abbe received the prestigious Bell Labs Prize in 2014 for his research contributions.

–By Catherine Zandonella

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Baby steps: Inside the developing brain

AT ONE OF PRINCETON’S NEWEST RESEARCH LABS, the T-shirts only go up to 4T, the art on the walls is done in crayon and the books on the shelves include The Little Mermaid.

Researchers at the Princeton Baby Lab study how babies and young children learn to see, talk and understand the world. The lab, located in the Department of Psychology’s Peretsman Scully Hall, opened this summer and is co-directed by two new additions to the Princeton faculty, assistant professors of psychology Lauren Emberson and Casey Lew-Williams.

Emberson investigates how experience supports learning and early development. She focuses on the development of perceptual abilities such as vision, hearing and multisensory perception. She often uses neuroimaging techniques that let researchers see infants’ brains change as they learn and develop.

“How infants are using their experiences to develop is a huge mystery,” Emberson said. “We’re examining how babies are developing expectations about the world and shape their neural activity almost in real time.”

Lew-Williams examines how babies and young children learn language. His research subjects include children growing up in poverty and children with communication disorders. His studies often involve children listening to language, looking at pictures and watching short videos as researchers track their eye movements.

“The most fundamental, basic science questions I’m interested in are what is learning, how does it happen and how does it happen differently for different children?” Lew-Williams said. “To me, language is a great way to investigate this because language is such an important skill. How does language learning get off the ground in infancy?”

–By Michael Hotchkiss

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Listening in on bacterial communications

Leah Bushin and Mohammad Syedsayamdost

While an undergraduate, Leah Bushin (left) co-authored an article on the structure of a signaling molecule involved in bacterial communication with co-first author Kelsey Schramma and adviser Mohammad Seyedsayamdost (right), assistant professor of chemistry, PHOTO BY C. TODD REICHART

BACTERIA SPEAK TO ONE ANOTHER using a soundless language known as quorum sensing. In a step toward translating bacterial communications, researchers have revealed the structure and biosynthesis of streptide, a signaling molecule involved in the quorum sensing system common to many diseasecausing streptococci bacteria.

The research team included undergraduate Leah Bushin, who was the co-first author on an article published on April 20, 2015, in Nature Chemistry. Bushin helped determine the structure of streptide as part of her undergraduate senior thesis project.

To explore how bacteria communicate, first she had to grow them, a challenging process in which oxygen had to be rigorously excluded. Next, she isolated the streptide and analyzed it using two-dimensional nuclear magnetic resonance (NMR) spectroscopy, a technique that allows scientists to deduce the connections between atoms.

The experiments revealed that streptide contains an unprecedented crosslink between two unactivated carbons on the amino acids lysine and tryptophan. To figure out how this novel bond was being formed, the researchers took a closer look at the gene cluster that produces streptide. Within the gene cluster, they suspected that a radical S-adenosyl methionine (SAM) enzyme, which they dubbed StrB, could be responsible for this unusual modification.

“Radical SAM enzymes catalyze absolutely amazing chemistries,” said Kelsey Schramma, a graduate student and the other co-first author on the article. The team showed that one of the iron-sulfur clusters reductively activated one molecule of SAM, kicking off a chain of one-electron (radical) reactions that gave rise to the novel carbon-carbon bond.

Kelsey Schramma is a graduate student in chemistry working on a project to study bacterial communication. Disrupting communication could lead to novel strategies to fight infections. PHOTO CREDIT: C. TODD REICHART

Kelsey Schramma is a graduate student in chemistry working on a project to study bacterial communication. Disrupting communication could lead to novel strategies to fight infections. PHOTO CREDIT: C. TODD REICHART

“The synergy between Leah and Kelsey was great,” said Mohammad Seyedsayamdost, an assistant professor of chemistry who led the research, which was supported by the National Institutes of Health. “They expressed interest in complementary aspects of the project, and the whole ended up being greater than the sum of its parts,” he said.

Future work will target streptide’s biological function — its meaning in the bacterial language — as well as confirming its production by other streptococcal bacteria strains.

–By Tien Nguyen

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Unconscious bias: Research helps break down barriers

Stacey Sinclair

Unconscious bias: Research helps break down barriers, PHOTO BY SAMEER A. KHAN/FOTOBUDDY

STACEY SINCLAIR WAS AWARE OF INEQUALITY AT A YOUNG AGE. ”On some level I was always interested in injustice,” said Sinclair, an associate professor of psychology and African American studies. “As a 7-year-old, I wanted to be the first black female to do everything.”

Today, Sinclair uses the tools of science to peel back the human psyche in search of the causes of racial inequality. In a recent study, she and Drew Jacoby-Senghor, who earned his doctorate in 2014, explored how implicit prejudices affected people’s interactions. Since people tend to group together based on shared characteristics, Sinclair and Jacoby-Senghor wondered if people with the same levels of implicit prejudice — also called unconscious bias — end up in the same circles.

The researchers found that whites with stronger implicit anti-black bias were less motivated to affiliate with whites who have black friends than with whites who have white friends. In other words, people likely to have similar levels of implicit prejudice gravitated toward each other, even if they weren’t consciously aware of it. The study was published in the September 2015 issue of the Journal of Personality and Social Psychology.

For the study, the researchers recruited white participants via an online platform and showed them pairs of faces, one white and the other either white or black. In each case, subjects were asked to rate the friendliness of the white face by answering questions such as, “To what extent do you think you would want to become friends with this person?” Additionally, the subjects’ perceived similarity between themselves and the person on the screen was measured by asking how strongly they agreed with statements such as, “This person and I probably see things in much the same way.”

Sinclair and her collaborators found that white participants with higher implicit bias exhibited higher perceived similarity to the white faces paired with a white friend. This perceived similarity in turn was related to a stronger desire for friendship.

Sinclair’s previous research shows that people adjust their implicit-prejudice level to match the views of the people with whom they interact, a principle called social tuning. This research, which Sinclair outlined in a 2014 review article in the journal Policy Insights from the Behavioral and Brain Sciences, suggests that egalitarian views can be catching.

Sinclair offers some practical advice based on her research. To make use of social tuning, she advises: “Literally wear your egalitarianism on your sleeve. In policy, what this means is make it clear that this is an environment that truly appreciates diversity, that equality is a value that the individuals in this environment hold. Our research suggests that people’s attitudes will change to be in line with these values relatively effortlessly on their part.”

In awareness of their tendency to seek similarity, Sinclair suggests that people step out of their comfort zone. “When you’re networking, or when you’re at a party, and you’re deciding who to walk up to, if your impulse tells you to go one way, go the other way. If we all did that, it could really change what our networks look like.”

–By Takim Williams

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