The most common cause of death from breast cancer is not the primary tumor, but metastatic disease, when the cancer travels and takes root in the brain. About 1 in 5 women with metastatic breast cancer will contract a brain lesion, and median survival for those patients is less than a year after diagnosis. Yet physicians currently have few tests to predict which breast tumors will eventually involve the brain and which will not. As it becomes more accepted that no two patients’ cancers are alike, physicians recognize that they need more “biomarkers” that can both reliably predict how the disease will progress and suggest the best method of treatment.

Just as successfully treating cancer often requires the cooperation of different disciplines, finding sufficiently predictive cancer biomarkers needs to be a collaborative effort. An ongoing University of Chicago Medicine search for a factor that can help physicians calculate the risk of brain metastasis in breast cancer patients has united researchers from neurosurgery, oncology, pathology, and Health Studies. The first fruit of that large collaboration, published late last year in the journal Cancer, discovered a promising biomarker with an innocuous name: KISS1.

The interest in brain metastases started in the laboratory of Maciej Lesniak, professor of surgery and neurology and director of neurological oncology. Lesniak, who often treats patients with these types of brain tumors, said that there is a gap in knowledge about what predisposes some women to this serious complication of breast cancer.

“If you have breast cancer, does this automatically mean that you will develop a brain metastasis? We don’t know,”  Lesniak said. “Are there any risk factors or biological phenomena behind this form of the disease? That was the question that we set out to answer.”

Fortunately, the means to test that question were available through the Specialized Program of Research Excellence (SPORE) in Breast Cancer at the University of Chicago Comprehensive Cancer Center, led by medical oncologist and Walter L. Palmer Distinguished Service Professor Olufunmilayo Olopade. The Breast Cancer SPORE maintains a bank of tissue and tumor samples that researchers could use to look for potential biomarkers. Working with Peter Pytel, assistant professor of pathology, the research team developed an assay to test levels of target proteins in tissue from metastatic and non-metastatic breast cancer patients.

For the first potential biomarker, the research team led by Ilya Ulasov chose KISS1, levels of which were previously associated with the progression of bladder, ovarian, and other cancer types. Using antibody staining techniques, the researchers measured KISS1 levels in breast tissue from patients with cancer, non-cancerous breast tissue, and brain lesions from metastatic cancer patients. The comparison found lower levels of KISS1 protein in the brain metastases relative to breast tumors, suggesting that a reduction of this protein is associated with increased spread of cancer to the brain. Another analysis correlated KISS1 levels in the patient’s tissue samples with their clinical outcome, finding that those with higher levels of KISS1 expression exhibited slower disease progression and reduced chance of developing brain metastases.

Interestingly, the relationship between brain metastasis and KISS1 expression was not correlated with previously established breast cancer subtypes that use the estrogen receptor, progesterone receptor, and HER2 gene as biomarkers.

“KISS1 is an interesting protein that seems to at least play a role which subset of patients go on to develop brain metastases from breast cancer,” Lesniak said. “The beauty of this paper is that it carries across different subtypes of tumors.”

However promising the data, the authors caution that their study is only the first step toward establishing KISS1 as a valid biomarker for predicting the course of metastatic breast cancer. Until the biological link between KISS1 expression and cancer progression can be determined, the relationship can’t be considered more than a correlation. But if a mechanism is discovered, Lesniak speculated that KISS1 may hold clues to a way to stop or slow brain metastases from occurring.

“The question is how can you modulate KISS1 expression for the benefit of patients,” Lesniak said. “One approach would be to restore KISS1 expression in patients with advanced metastatic breast cancer, and see whether it makes the tumor less aggressive or less prone to metastatic disease. It’s an interesting thought, but it’s probably too premature to know whether that would hold true.”

read more

In the aftermath of a mass extinction, nature tends to get creative. Those lucky species that survive often explode with Seussian abandon into a diverse array of shapes, sizes, and behaviors, capitalizing upon the ecological opportunities left available by their less fortunate peers. Usually, the oddities produced by these “adaptive radiations” are whittled down by natural selection to only a few surviving forms. But evolutionary biologists are interested in the course these radiations take — the dynamics that result when nature hits the “randomize” button.

Scientists have tried to understand the order underlying this chaos by studying modern animals that have established broad diversity, such as the immense cichlid family of fishes (which encompasses over 1,000 documented species) or Darwin’s finches of the Galapagos islands. But these studies can only work backwards from the species that exist today. To watch an adaptive radiation unfold, a better source is the fossil record, as the University of Chicago’s Lauren Sallan and the University of Oxford’s Matt Friedman discovered in a recent journal article for Proceedings of the Royal Society B.

Sallan and Friedman used fossil databases from two prehistoric mass extinction events: the Hangenberg event, of roughly 359 million years ago, and the end-Cretaceous extinction, which ended the age of dinosaurs. By measuring how surviving fish species changed body shape and size after these ecological disturbances, the researchers could test two common theories of adaptive radiation inspired by studying surviving species. One model proposed a free-for-all “burst” of divergence followed by a long period of relative stability. Another, sometimes known as the “general vertebrate model,” introduced the idea of staged divergences, with habitat-driven changes in body type preceding diversification of head types.

“There hadn’t been any tests of these things using fossils,” said Sallan, a graduate student in the Department of Organismal Biology and Anatomy. “You have all these analyses of diversification, yet not one of them goes back to the fossil record and says what’s happening at this time period, and the next time period, and the one after that.”

When Sallan and Friedman looked carefully at their data, they didn’t find evidence for either of the pre-existing theories. Instead, they saw a staged radiation that started not tail-first, but head-first, with surviving species initially trying out a wide range of head shapes attached to similar bodies. The driver of this diversity may have been a simple factor: food. Faced with far less competition, the surviving fish evolved new types of teeth, jaws, and heads to take advantage of the expanded menu suddenly available. Later, once head shapes stabilized, different body types from broad and flat to thin and eel-like appeared as new species adapted to their surroundings.

“It seems like resources, feeding and diet are the most important factors at the initial stage,” said Sallan, who works in the laboratory of University of Chicago Professor Michael Coates.

read more

By Matt Wood

Joseph Kirsner, MD, continues to report to work after 76 years as a gastroenterologist at the University of Chicago Medical Center. At 102, he must be doing something right. Sure, he keeps his mind and body active by keeping up with research and coming into the office. But how much of longevity is attributable to a healthy lifestyle and good genes, and how much is due to luck?

Two researchers at the Center on Aging at the University of Chicago have found that luck plays a significant role in living to 100. In a new study published in The Journal of Aging Research, they found that people born in September, October or November had higher odds to crack the century mark than those born in the spring.

Leonid Gavrilov, PhD, and his colleague and wife, Natalia Gavrilova, PhD, look for clues to longevity at the Center on Aging, which is part of NORC at the University of Chicago. They study potential predictors and determinants of human longevity, such as family background and environment. “It’s a way to get insights into mechanisms of aging and longevity, and hopefully to find new approaches to extend healthy human life,” Leonid Gavrilov said.

In past studies they found that chances for exceptional longevity are higher for U.S. citizens who were born to young mothers, had a slender or medium body build at age 30 and were farmers or spent their childhood on a farm. Studying pooled data about longevity for large populations can be tricky though.

“People from families with different ethnic, educational and income background may have somewhat different chances for long life,” Natalia Gavrilova said. “Also, different families may have slightly different seasonal patterns of births, because of religious and cultural traditions, holidays and vacation preferences.”

To control for unobserved differences between families in their latest study, they used a “within-family” approach by studying differences in life span between siblings within the same families, with the same parents and family background. They also studied spouses in the same families who lived together and shared their living conditions at adult age.

read more

In baseball, much is made of the half-second or less a batter is given to swing or not swing at each 100-mph fastball. But another important snap decision is made by the home plate umpire, who must pinpoint the position of the ball as it crosses the plate and immediately decide whether it counted as a ball or a strike. To complicate matters, the strike zone changes size depending on the hitter, pitchers throw balls at varying speeds and with knee-buckling spin, and a good number of pitches fall into a gray zone on the “corners” of the strike zone. Given the hundreds of ejections each year resulting from players arguing balls and strikes with the umpire, the competitive stakes for this task is incredibly high.

Fortunately, the human brain is quite accomplished at rapidly sorting visual information into categories. Even if you’ve never stood behind home plate to call a game, you have experienced this ability. Imagine you are crossing a street, and from the corner of your eye you see a quickly moving object heading your way. From even the most basic of visual features, your brain can quickly categorize a four-wheeled vehicle of any make and model as a “car”…or “thing that will cause me serious harm if I don’t jump out of the way.” Nobody is born with the innate ability to recognize an automobile, but the collected experience of life reinforces the rules of what is a car and what isn’t — as well as complicated sub-categories such as sportscars and SUVs — and keeps them in the brain for rapid retrieval.

The laboratory of David Freedman, assistant professor of neurobiology at the University of Chicago, is interested in where exactly these categories are stored in the brain. For over a decade, Freedman has conducted experiments looking for the brain area that is the earliest responder when an individual must quickly categorize a stimulus.

“Making effective decisions and evaluating every situation that you’re in moment by moment is critical for successful behavior,” Freedman said. “We’re really interested in what changes occur in the brain to allow you to recognize not just the features of a stimulus, but what it is and what it means.”

Typically, these studies are done using monkeys who are taught to play a simple video game while researchers record brain activity from different regions looking for the signals that underlie decision-making, called category signals. In a study published in Science in 2001, Freedman and colleagues at MIT found the first evidence for brain category signals in a region called the prefrontal cortex (PFC). The site made sense, as the PFC (an area that is especially large in humans) has long been associated with complex, cognitive functions such as memory, planning, and decision-making.

However, the trail didn’t end with that finding. Freedman moved on to study another part of the brain, called the parietal cortex, which is located on the sides of the brain and thought to be involved in processing sensory information. By happy accident, Freedman discovered that the parietal cortex also responded while the monkeys played the categorization task, and the signals looked as though they might be even stronger than those seen previously in the PFC. But to determine which of the two brain areas was the original source of category signals, a direct comparison was needed.

That comparison, published this week in Nature Neuroscience by Freedman and graduate student Sruthi Swaminathan, offers the best evidence to date that the parietal cortex is the primary residence for visual categories in the brain. As monkeys played their categorization game, deciding whether two groups of moving dots fell into the same category or different categories, a sub-region of parietal cortex known as the lateral intraparietal areas (LIP) reacted faster and more strongly.

“This is as close as we’ve come to the source of these abstract signals,” Freedman said. “The relative timing of signals in the two brain areas gives us an important clue about their roles in solving the categorization task. Since category information appeared earlier in parietal cortex than prefrontal cortex, it suggests that parietal cortex might be more involved in the visual categorization process, at least during this task,” Freedman said.

read more

By Matt Wood

Parents of young children know the drill for childproofing a home: covers on electrical outlets, gates at the top and bottom of stairs, cabinets and drawers locked, fragile knickknacks placed safely out of reach of little hands. But how many parents worry about toddlers using a microwave oven?

As you probably know from reheating leftovers or whipping up a batch of ramen noodles, microwaves can heat food to extremely high temperatures very quickly. It’s hard enough for adults to avoid singeing fingers while pulling a hot bowl of soup out of the microwave; imagine the danger posed to kids. A new study by researchers at the University of Chicago Medical Center found that children as young as 17 months old can turn on a microwave, open the door and remove items, putting them at significant risk for scald injuries.

Scalds are the leading cause of burn-related injury to children living in the United States. In 2009 an estimated 1,230 children younger than 5 years old were treated in emergency rooms for burns related to microwave ovens. Marla Robinson, assistant director of Inpatient Therapy Services at the Medical Center and lead author on the study, said that over the past four years the emergency department has treated an increasing number of young children for burns related to taking items out of a microwave. “These young children were getting very significant burns causing disfiguring scars and putting them at risk for contractures and deformity,” she said. “They can push the button and take something out, and it spills down their face, neck, chest and arms.”

read more

By Dianna Douglas

Imagine your doctor says he plans to increase your oral medication to control your diabetes. You do not like taking pills. Should you:
A. Not rock the boat with your doctor and agree to take the increased dosage?
B. Agree, but keep taking the same number of pills?
C. Try to discuss another option with your doctor?

Monica Peek, MD, assistant professor of internal medicine at the University of Chicago, believes the best answer for long-term health and happiness is C. But she knows that low-income African Americans with diabetes will often, for a variety of reasons, agree with the doctor and then ignore the advice. Peek has spent hours leading classes with patients from this vulnerable group. They role-play talking to their doctor, critique each other as they practice, and give a debriefing on whether they could ever truly feel comfortable taking an active approach with a physician.

The classes are part of a new program to chip away at the disparities in diabetes among low-income African Americans. The gap is huge. The prevalence of diabetes on the South Side is 19.3 percent, compared with an average prevalence in Chicago of about 7 percent. African American neighborhoods in Chicago have five times the rate of diabetes-related leg amputations as primarily white neighborhoods do.

Three years ago, about 40 people at the University of Chicago Medical Center with expertise in nutrition, cultural tailoring, communication, quality improvement, and even community organizing launched an effort to close this gap. They were prepared to tackle multiple factors that exacerbate diabetes outcomes on the South Side. Among them are unhealthy eating habits, limited safe places to exercise, food insecurity and less access to health care.

Their first move was to get out of the hospital.

The group created teams at six community health clinics to focus on improving diabetes care. They led patients on field trips to local grocery stores to practice making smart food choices. The physicians were constantly on the radio, at health fairs, in churches and high school gymnasiums, educating South Siders about diabetes. Still, the Medical Center team ran into challenges from all sides.

“The economic factors of people choosing between food and medications don’t account for all of the disparities,” Peek said. “There is racial and cultural baggage that creeps into clinical encounters between doctors and poor African American patients.” As an example of this long history of bias, Peek cites a famous 1999 study from Georgetown University in which cardiologists were found to offer better care to men over women who complained of heart problems, and to white patients over black patients.

“People who have had bad interactions with the health care system may delay treatment until their condition is dire,” Peek said. Some say they are afraid of being experimented on, that they don’t trust doctors to do right by them, or that they dislike the perceived power imbalance of being in a doctor’s office.

Peek said she was surprised to learn how some low-income African Americans view the doctor-patient relationship. A woman told her that she gets agitated when she goes to a doctor’s office and hears, “What brings you here today?” — she thinks the doctor is saying, “Why are you sitting in front of me when I’m so busy?” read more

In books and movies, time travel is typically fraught with negative consequences. Any attempt to change the past — say, stopping the JFK assassination, or taking your mom to the Enchantment Under the Sea dance — is bound to produce ripples of change that alter the future. But what if you could safely contain a trip back in time within the boundaries of a test tube? In a new paper published in Nature, a University of Chicago geneticist used a form of “molecular time travel” to observe a crucial event in the evolutionary history of life on Earth…and extinguish a favorite argument of intelligent design advocates.

The concept of “irreducible complexity” is a favorite talking point of the forces against evolution, both today and historically. As the argument goes, the complex structures found within modern organisms — from the eye to the microscopic protein machines that conduct business in cells — are far too complicated to be the result of the random genetic mutations and selective forces at the core of Darwin’s grand theory. The argument is so old that Darwin himself addressed it in On the Origin of Species, speculating on how an accumulation of small changes could lead from a simple photoreceptor to the wondrous eye shared by many organisms today.

The best way to demonstrate how the minute changes of evolution could produce great complexity is to capture that process in action. But to happen upon such a leap live would be a biological needle in an enormous haystack. A better strategy would be to pick a historic leap in complexity from the evolutionary past, and then go back and observe how it happened. Easy, right?

To accomplish this task, Joe Thornton, a new faculty member in the Departments of Human Genetics and Ecology & Evolution, developed the method of “molecular time travel.” Instead of a Delorean, Thornton’s method uses a computational analysis of the genes from modern-day species to resurrect the genes of ancestral species that lived hundreds of millions of years ago. For the new paper, Thornton and colleagues at the University of Oregon decided to “travel” back to look at a complex molecular machine found in various species of fungus.

“Our strategy was to use ‘molecular time travel’ to reconstruct and experimentally characterize all the proteins in this molecular machine just before and after it increased in complexity,” said Thornton, professor of human genetics and evolution & ecology at the University of Chicago, professor of biology at the University of Oregon, and an Early Career Scientist of the Howard Hughes Medical Institute. “By reconstructing the machine’s components as they existed in the deep past,” Thornton said, “we were able to establish exactly how each protein’s function changed over time and identify the specific genetic mutations that caused the machine to become more elaborate.”

Their target was a molecular machine called the V-ATPase proton pump, which helps maintain the proper acidity of compartments within cells. In modern Fungi, this pump contains a six-part ring made up of three separate proteins, but that wasn’t always the case. Some 800 million years ago, that same ring was made from only two proteins, meaning some kind of event occurred around then to increase the complexity of this machine.

Thornton’s group calculated the genetic sequence of the ring proteins from that ancient ancestor using the sequences of 139 modern Fungi family members, computationally tracing their common elements back up the Tree of Life to their ancient predecessor. The researchers could then reproduce the protein before the split (called Anc.3-11) and the two proteins that came after the split (Anc.3 and Anc.11), and see how they functioned in the proton pump’s ring.

Surprisingly, the “newer” proteins were less versatile than the ancestral Anc.3-11, which could substitute for either of its descendants when transplanted into modern Fungi. The result suggests that the pump’s increase in complexity resulted not from the evolution of a new, “better-designed” function, but from an initial loss of versatility.

“It’s counter-intuitive but simple: complexity increased because protein functions were lost, not gained,” Thornton said. “Just as in society, complexity increases when individuals and institutions forget how to be generalists and come to depend on specialists with increasingly narrow capacities.”

read more

By Matt Wood

In the field of pediatric eating disorder studies, you might think that the one thing on which researchers could agree would be how to determine the appropriate body weight for a child. An exact determination of expected body weight for adolescents based on age, height and gender is critical for diagnosis and management of eating disorders such as anorexia nervosa and bulimia. Surprisingly, however, there are no clear guidelines regarding the appropriate method for calculating this weight in children with such disorders.

In a study published this week in Pediatrics, researchers from the University of Chicago, the Harvard School of Public Health and the University of Rochester Medical Center tackled this problem. “It may seem perfectly straightforward to an outsider to the field: How can we not have figured this out yet? And yet we haven’t,” said study author Daniel Le Grange, PhD, professor of psychiatry and Director of the Eating Disorders Program at the University of Chicago. He and his colleagues compared three common methods for calculating expected body weight of adolescents with eating disorders and found that one in particular, the body mass index (BMI) percentile method, is recommended for clinical and research purposes.

“There are no clear guidelines in the adolescent field,” said Le Grange. “We set out to do something that is relatively straightforward that hasn’t been done before, and that is look at some of the most frequently used methods of calculating weight in the pediatric and adolescent eating disorder populations, and see whether we can come up with a gold standard for clinical as well as for research purposes.”

read more

As the weather finally starts to get seriously cold, we thought this would be a good time to revisit our conversation with Dr. Ginard Henry on Cold Hands Syndrome. While it seems like your frozen fingertips could be fixed by simply wearing a good pair of gloves, Cold Hands Syndrome is a real medical condition caused by a range of different diseases that restrict blood flow to extremities. It can strike at any time, not just the dark days of winter.

For more, check out our four-part video Q&A with Dr. Henry:

read more

As another year comes to a close we’d like to look back at the fascinating research breakthroughs and inspiring patient stories from 2011. ScienceLife ran 168 posts this year, and while we wish we could highlight all of them, here are a handful of our favorites from each month.

January

Patrick Wilson found out that the H1N1 virus could end up helping us fight all types of flu. Stephen Pruett-Jones studied how some male birds mimic the sounds of predators to pick up the ladies (with an audio clip). We interviewed David Gozal about his study on the link between childhood obesity and lack of sleep, and took a look at NCAA regulations mandating sickle cell testing for athletes.

February

Harold Pollack gave a lecture on why violent crime in urban, minority communities should be considered a public health epidemic. Siri Atma Greeley studied the actual medical benefit of widespread genetic testing. Stacy Lindau wanted to know why so few women get help for sexual problems after surviving cancer. We talked to Bana Jabri about the causes of celiac disease, and Sliman Bensmaïa showed us how the brain processes the basic elements of touch very much like it handles visual information.

March

Sola Olopade educated women in Nigeria about using clean-burning stoves to prevent indoor pollution. Stefano Allesina and Jonathan Levine looked at how rock-paper-scissors helps explain evolution. Joshua Miller went to Yellowstone Park to see what stories the ghostly bones of animals can tell, and Scott Eggener questioned the wisdom of indiscriminate prostate cancer screening.

Photo by Gerald Waddell

Andrea King studied the wide range of responses to drinking alcohol, and why it can be fun for some people and a bummer for others. Cheryl Reed took a ride in a helicopter with our UCAN nurses. Kamal Sharma looked at the genes that control animals’ gait, and Ningqi Hou studied how urban environments can dictate how much exercise people get.

May

Daniel McGehee looked at the long-term effects of nicotine on the brain. Habibul Ahsan went to Bangladesh to study the health impacts of accidental exposure to arsenic in drinking water. The brain’s overlooked supporting cells got their due at a conference on neuroscience, and we remembered a landmark discovery about a once popular drug taken during pregnancy that we now know can cause cancer.

June

As we headed into summer, Diana Lauderdale used Google to track MRSA. We learned about an extraordinary transplant where a man received a new heart, liver AND kidney. Daniel Geynisman gave us the rundown on whether or not cell phones are killing us (they’re not, as long as you don’t use them in the car), and some UChicago undergrads studied what happens to gorillas on the birth control pill.

July

We spoke to Donald Jensen and Andrew Aronsohn about the new outlook for patients with hepatitis C. Igor Schneider made a time machine to find the genetic switch for limb development. Farr Curlin led a study about the benefits of addressing spiritual needs alongside medical care, and Adam Cifu looked at the phenomenon of scientific study reversals.

August

Stefano Allesina dug into the long, shady history of nepotism in academia in Italy. John Schneider talked about his work addressing sexual health and stigma in India. Michael Becker discovered a new treatment for the Royal Disease, and we had the rare chance to name check a Spiderman villain in a post.

September

Martha McClintock and Suzanne Conzen studied the connection between social isolation, stress and breast cancer. Gallego Romero traveled to India to search for the origins of lactose intolerance. Stephanie Dulawa developed a mouse model for OCD, and Paul Vezina looked at a different kind of obsession, compulsive gambling.

October

Arshiya Baig started a pilot project to help people learn about life with diabetes through pictures. Manyuan Long found that some of the youngest genes are in the brain. Jens Ludwig and Stacy Lindau published a landmark study about the connection between neighborhood poverty and health, and Issam Awad studied a rare brain disease that soon could be treated with a drug instead of surgery.

November

Cathy Pfister and Tim Wootton figured out how to use seashells to track climate change over the years. Lianne Kurina found a link between loneliness and sleep quality. Shantanu Nundy, Monica Peek and Marshall Chin developed a program to send text message reminders to people with diabetes, and Pan Chen looked at the links between childhood abuse and aggressive behavior in adults.

December

Inbal Ben-Ami Bartal, Jean Decety and Peggy Mason discovered that rats can show empathy for their fellow rats in distress. Maciej Lesniak performed a scary but amazing brain surgery on a patient who was awake. Cathryn Nagler searched for the source of food allergies within our bodies, while Stafano Guandalini uncovered the challenges in educating doctors about one of those allergies, celiac disease.

Whew. Hope you were able to click through at least a few of those. We look forward to another great year of research in 2012. We’re taking a break next week, but we’ll be back on January 5. Happy holidays!

By John Easton

Molecular markers found in cancer cells that have spread from a primary tumor to a limited number of distant sites can help physicians predict which patients with metastatic cancer will benefit from aggressive, targeted radiation therapy.

In a study published online Dec. 13, 2011, in the journal PloS One, researchers from the University of Chicago and the University of Illinois at Chicago show that if cells from metastatic tumors have high levels of a particular type of microRNA — a tool cells use to silence certain genes– not even aggressive treatment of those tumors would help. But if the cells have lower levels of that biological marker, then focused local treatment could be effective, even curative.

“We previously demonstrated that we could provide lasting disease-free survival to a percentage of patients with metastatic disease,” said study author Ralph Weichselbaum, MD, professor and chair of radiation and cellular oncology and Director of the Ludwig Center for Metastasis Research at the University of Chicago. “This finding means we can have a pretty good sense in advance of which patients we can help. Patients unlikely to benefit from focused, local therapy can receive systemic treatment immediately.”

Yves Lussier, MD, professor of medicine at the University of Illinois at Chicago and co-senior author of the study, added that “the biological differences between locally curable metastases or potentially fatal widespread metastases can also be targeted for drug development.”

read more

By Matt Wood

Each day people make decisions about how much effort they’re willing to put into various tasks. The decision about how much effort to invest in an activity is influenced by the reward for doing something and the probability of actually getting it. You might be willing to work hard at your job because the reward—a paycheck—is both valuable and fairly certain. But you might not be willing to try a complicated new recipe for dinner, even though it sounds delicious, because of the chance that it won’t turn out well.

Animal studies suggest that the neurotransmitter dopamine plays an important role in this type of decision-making, especially the decision to expend effort. In rats, dopamine levels influence tolerance for effort and probability costs. Rats with higher levels of dopamine are more willing to press levers and climb over barriers to reach better food, whereas those with lower levels will settle for food that’s less tasty but within easy reach.

Little is known about how dopamine affects effort-based decision-making processes in humans. But a new study published in The Journal of Neuroscience by Margaret Wardle, a post doctoral researcher in the Department of Psychiatry and Behavioral Neuroscience at the University of Chicago, her mentor Harriet de Wit, Professor and Director of the Human Behavioral Pharmacology Laboratory, and colleagues at Vanderbilt University shows for the first time that people behave in much the same way. Their research, sponsored by the National Institute on Drug Abuse, not only sheds light on how dopamine influences decision-making in humans, but also points toward possible treatment for psychiatric disorders like depression.

read more

By Rob Mitchum

A surgical procedure is a daunting experience for any patient, though thanks to general anesthesia, it’s not typically a memorable one. That’s not the case for patients who go through an awake craniotomy — a unique procedure that allows surgeons to react based on feedback from the patient during removal of a brain tumor.

“I remember them waking me up using a flashlight and talking to me,” Anna Litchfield, a 49-year-old patient who was operated on by Maciej Lesniak, MD, Professor of Surgery and Neurology, said in August. “I remember Dr. Lesniak saying ‘Anna, are you OK?’ and I remember saying ‘Great, Dr. L!’ out of nowhere. I never thought I’d call him Dr. L! In retrospect, I feel like my brain was thrilled that he was there operating.”

Awake craniotomies are unique, complex procedures typically used to remove tumors nestled close to functional areas of the brain. Though the macabre nature of the surgery might induce shudders, the benefits for the patient are great. As the tumor is carefully removed by the surgeon, a neurologist can continuously monitor the patient’s language, motor and sensory function to make sure critical parts of the brain suffer minimal damage.

“When tumors are in what we call eloquent, functional areas, the margin of error is a millimeter,” Lesniak said. “You have to ask yourself whether you feel comfortable with a patient being asleep, potentially missing that millimeter while taking out the tumor and having them wake up devastated, or minimizing that risk.”

Lesniak and his team at the University of Chicago Medical Center perform more awake craniotomies than any other group in the Chicago area — more than 30 each year. Each surgery utilizes a truly interdisciplinary and experienced team of neurosurgeons, neurologists, anesthesiologists and operating room nurses who must collaborate to ensure the unusual surgery’s success. Often, craniotomy candidates are referred to Lesniak from hospitals around the area and country, as the surgery can be performed only by individuals with significant expertise and experience.

read more

All of the animal life on Earth, including human beings, can be traced back to a unicellular ancestor somewhat similar to the modern-day protozoa. In one sense, the hundreds of millions of years of evolution is the story of how organisms became more and more complex, growing from a single cell to trillions of highly specialized cells forming different organs and tissues in a single body. Yet while you could easily tell a protozoa from a human in a police lineup, cells from the two species are made up of many of the same proteins, performing similar jobs. What changed to produce these profound differences in complexity?

One potential area where this complexity may have bloomed is tyrosine phosphorylation, a key cellular signal for pathways that control cell growth, proliferation, and structure. Enzymes called tyrosine kinases add a phosphate group to a wide range of cellular targets, which can act like a light switch, turning their function on or off. The phosphorylated proteins are recognized by another group of proteins with a special “sensor” called the SH2 domain. Because tyrosine kinases will promiscuously phosphorylate many targets in the cell, the very picky SH2 domain proteins are responsible for sorting out the noise.

“Tyrosine kinases tend to be not that selective,” said Piers Nash, assistant professor in the Ben May Department of Cancer Research at the University of Chicago who studies this system. “They’ll phosphorylate a lot of things, and that creates all of these docking sites for SH2-domain-containing proteins. It’s really up to the SH2 domains to interpret those signals and convert them into downstream signaling pathways.”

The more complex the cell, the more unique types of SH2 domains that are needed to perform this important sorting function. In the unicellular cousins of animals, organisms can get by with just a single SH2 domain. But in humans, some 121 SH2 domains are known to exist, managing many different pathways in many different cells. In two recent papers, Nash’s laboratory studied how these SH2 domains manage their impressive selectivity and the evolutionary pathway that they took from simple protozoa to complicated human.

It’s essential that SH2 domains only bind to the right phosphorylated protein — repeatedly screwing up and activating the wrong pathway could lead to diabetes, cancer, or worse. But scientists have struggled to figure out how SH2 domains choose their appropriate target, with some even concluding that they aren’t so selective at all, merely in the right part of the cell at the right time to only bind the correct protein. However, that wasn’t what a research team led Bernard Liu from Nash’s laboratory found when they looked at how SH2 domains bind actual cell targets such as the insulin receptor.

“It turned out that the SH2 domains were exquisitely selective, much more selective than the general motifs for the SH2 domains that had previously been mapped,” Nash said. “So it was clear there was additional information encoded in the peptide that the SH2 domain makes use of.”

The researchers then deduced that the SH2 domains select their target through a kind of language, looking for the exact sequence of amino acids - or “word” - that marks the appropriate match. Because each amino acid (akin to the letters of the word) will either attract a particular SH2 domain or reject its peers, changing only one amino acid can completely change the meaning, like altering the word “light” to “fight.”

“For SH2 domains, that makes all the difference in the world. They can sense incredibly subtle differences,” Nash said. “It’s looking at the entire peptide and seeing both the permissive and the non-permissive residues, integrating that and making this collective decision about what to bind.”

read more

If you called someone a rat, they probably wouldn’t take it as a compliment. But in a clever new study published today in Science, a team of University of Chicago neurobiologists show that rodents could serve as role models for how humans should behave. Rats were given a difficult choice between heart and stomach: either open a container of chocolate chips and enjoy the feast, or free a companion and share the chocolate chip bounty. The results argue that humans aren’t the only species to feel empathy for the distress of another and act upon it, suggesting a deep evolutionary basis for helping your fellow creature.

When Inbal Ben-Ami Bartal was a master’s student in Israel researching immunosuppression after surgery, she noticed a strange phenomenon in her laboratory rats. When rats were brought to the room where she regularly conducted surgical procedures, they grew extremely agitated.

“It was very obvious that rats could sense what was going on with other rats,” Bartal said. “They freaked out and were affected by the emotional state of the other rats once they were removed from the cages.”

Other researchers had previously noticed this phenomenon in both humans and animals and gave it the name “emotional contagion,” describing when the distress or pain of one individual spreads to others. In 2006, Jeffrey Mogil of McGill University found evidence of this effect in mice, observing that when one mouse is given a mildly painful stimulus, a second mouse viewing the first mouse’s pain will exhibit increased sensitivity to pain. When that paper was published, it was considered by some to be the first evidence for empathy in a rodent. But Bartal, having started as a graduate student advised by Jean Decety, Irving B. Harris Professor of Psychology and Psychiatry at the University of Chicago, wanted to find more definite proof of rat compassion.

Collaborating with the laboratory of Peggy Mason, professor of neurobiology, Bartal designed a test to see whether emotional contagion could actually drive a rat to take action. Two rats who live together in the same cage were placed in a special arena, with one held in a transparent, tube-shaped restrainer and one allowed to roam free. The restrainer’s door could be opened by a nudge from the outside, though the free rat - at least initially - didn’t know that. But after several sessions where the free rat was visibly agitated by his trapped companion’s distress, he figured out how to pop open the restrainer. As you can see in this video from Science, once the free rat learned this trick, he would take action almost immediately upon being placed in the arena during subsequent sessions.

“We are not training these rats in any way,” Bartal said. “These rats are learning because they are motivated by something internal. We’re not showing them how to open the door, they don’t get any previous exposure on opening the door, and it’s hard to open the door. But they keep trying and trying, and it eventually works.”

Proving that the free rat’s actions were motivated by empathy required more experimental conditions. When the restrainer was left empty, or when researchers put a stuffed toy rat in the tube, the free rat showed no interest in opening the restrainer door. He did, however, when the arena was rigged so that opening the restrainer released the trapped rat into a separate compartment from the free rat, showing that the free rat was not motivated by the “reward” of social interaction. The experiments left behavior motivated by empathy as the simplest explanation for the rats’ behavior.

read more