By Meghan Sullivan

On her visit to the University of Chicago earlier this month, Megan Urry gave two very different talks, both backed with empirical evidence and arriving at clear, well-supported conclusions. However, while her afternoon talk to the astronomy department focused on her research of Active Galactic Nuclei, Urry’s earlier talk was on a subject more universal to academia: why are there so few women in science?

Expressing a sentiment that is common among young female scientists, Urry, Israel Munson Professor of Physics & Astronomy and Chair of Physics at Yale University, started out by admitting that as a student it was hard to imagine that the blatant discrimination of the 1950s and 60s could possibly affect her career in the 1980s. Harder still was the dawning realization that many of the obstacles were based more on gender than merit, though the symptoms of bias were more subtle than they had been in the past.

“It turns out that we scientists are a species that are of great interest to [sociologists],” Urry said, describing her research into the sociological literature on gender in the STEM sciences (science, technology, engineering, and math). “Sociologists understand very well why there are so few women in science.”

The fact that there are fewer women in science is beyond doubt. Data has repeatedly shown that women’s academic careers progress more slowly and they are less likely to be hired into academic positions, where they are then less likely to get tenured. Such trends become obvious when the numbers of PhDs awarded to women and the number of female faculty members hired are compared; women are lost between each level (described previously by Nancy Hopkins as the “Leaky Pipeline”).

“Our scientific fields are not fully utilizing the talent that is out there,” Urry pointed out. “We are basically dipping deeper into the talent pool of men instead of finding the outstanding women that are out there…if we hire a smaller fraction of women as professors than there are women with PhDs we have basically thrown away talent.”

To address why women were underrepresented in these fields, Urry debunked several myths surrounding women in science, key among them being family status.

“Family is the number one hypothesis that people come up with when I talk with them about these issues,” Urry admitted with some frustration. “But the truth is this cannot be the explanation.”

Considering that 70 percent of American women with children under the age of two work, it seems unlikely that having children would uniquely affect women in science. A well-known study by Mason & Goulden titled “Do Babies Matter?” is often interpreted as concluding that if women have children, they will fall behind. In fact, women who have children are more likely to become part-time employees. This, Urry said, certainly affects women’s progress in academia. However, among women who stay full time, those without children are not more successful than women with children, indicating family status cannot define how women succeed.

“Having a family is hard, but it’s so much easier to do it as a grad student, a post doc, a tenured professor than it is - for instance - to do it as an employee at Walmart,” Urry said. “Grad students at Yale make more than your average Walmart employee. You have control of your hours, work, and you can get help pretty easily.”

Since family status is an unsupported explanation for the gender imbalance, the issue of scientific aptitude often arises. A study published by the National Academy Press entitled “Beyond Bias and Barriers” reported findings on women’s ability, persistence in science, evaluation by peers, and reviewed strategies that effectively kept women in science. By almost all measures there was no difference in ability, the one exception being rotation of 3D objects in space, which seems to be more attributable to childhood play than inborn aptitude.

“There are no measured differences between the abilities of men and women that could possibly explain the large gender gap seen in science professions,” Urry stated.

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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.”

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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.

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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.

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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.

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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.”

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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.”

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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.”

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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:

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