A novel method developed at the National Institute for Mathematical and Biological Synthesis at UT helps determine which patients will benefit from transplantation.

The topic of the underreported dangers of overdosing on acetaminophen has received ample attention following recent in-depth investigation by the radio program “This American Life” and public-interest journalism organization ProPublica.

There is a chemical antidote to acetaminophen poisoning, but it is effective only if administered within eight hours of an overdose. If liver damage is severe enough and the antidote is not administered early enough, the only lifesaving treatment is liver transplantation.

However, determining which patients need a transplant and which will recover is a major challenge in treating patients with acetaminophen overdose.

Chris Remien, a postdoctoral researcher at NIMBioS, and his research partners have developed a novel method to determine which patients will benefit from liver transplant in these instances. Rather than relying on purely statistical methods, Remien’s method is based on a dynamic model of acetaminophen metabolism and cellular damage.

In addition to making predictions on the need for a transplant, the model also defines a limit to how much acetaminophen someone can take over time before it causes liver damage.

“There is a simple threshold in the model because of how the liver processes acetaminophen, so that there is either very little liver damage or rapid damage, which may explain why patients who chronically overuse acetaminophen can eventually develop rapid liver damage,” Remien said.

The model has shown promise in a set of fifty-three patients from the University of Utah, but it still needs to be validated in a larger multicenter study before it can be used by physicians.

“We are currently collecting more data and collaborating with other groups in order to validate our method,” Remien said.

Collaborating on the project are Norman Sussman, associate professor of surgery at Baylor College of Medicine, and Fred Adler, professor of mathematics and biology at the University of Utah.

For more information about Remien’s model, view a video of his seminar talk at bit.ly/186aQbr.

The National Institute for Mathematical and Biological Synthesis brings together researchers from around the world to collaborate across disciplinary boundaries to investigate solutions to basic and applied problems in the life sciences.

To learn more, visit nimbios.org.

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CONTACT:

Catherine Crawley (865-974-9350, ccrawley@nimbios.org)

Whitney Heins (865-974-5460, wheins@utk.edu)

To read more about the research, visit the NIMBioS website.

To view an animation of the distribution, visit tiny.utk.edu/polities.

The LA Times, Popular Mechanics, Huffington Post, and Wired are among the outlets featuring the research.

Hayes Griffin (left) and Dalton Chaffee (right) present their award-winning research at the international meeting of the Society for Mathematical Biology. Photo credit: NIMBioS

Dalton Chaffee and Hayes Griffin worked with mentor R. Tucker Gilman, a former postdoctoral research fellow at the National Institute for Mathematical and Biological Synthesis (NIMBioS) at UT to study mate choice.

Their work was published this week in the journal Evolution.

The students began their research between their junior and senior years at Bearden High School in Knoxville. They wanted to know why individuals choose the mates they choose.

Using a combination of analytical models and mathematical simulations, Chaffee and Griffin made several important discoveries that shed new light on how mate choice is influenced by “sexual imprinting,” a process whereby individuals express preference for mates with traits similar to their mothers, to their fathers or to other adult members in their population. It is known from field studies that females of many species are choosier about mating partners than males are.

“Sexual imprinting is common in nature, but different species do it different ways, and how it evolves is poorly understood,” said Gilman. “Dalton and Hayes wanted to know why different species would evolve to imprint on different individuals.”

The research showed that if the apparatus females use to identify and select their preferred mates requires a lot of evolutionary effort to maintain—for example, if they must have special cells in their eyes to see male colors—then sexual imprinting will not evolve. This suggests that a complex apparatus used for sexual imprinting must evolve initially for some other reason, such as to avoid predators.

When imprinting does evolve, females will choose mates like their fathers—which increases the likelihood of viable offspring and sons that are sexually attractive to females, as the fathers were to the mothers.

In situations where the father is absent, females can evolve to imprint on their mothers or on randomly selected adult males. This kind of imprinting allows females to select mates that will give them viable offspring, but it doesn’t guarantee that these offspring, particularly sons, will be sexually attractive like the females’ fathers were to the mothers.

Chaffee said that he and Griffin spent about twenty hours each week on the project, including reading reams of biological studies about sexual imprinting and learning how to use sophisticated computer programming to run their simulations.

“Just reading was extremely difficult, as much of the jargon and format were completely unfamiliar and very complex,” he said.

Gilman said he was impressed with the students’ drive and initiative.

“Dalton and Hayes needed very little guidance and demonstrated a great deal of commitment to the project,” said Gilman, now a faculty member at the University of Manchester, UK. “Their results explain something completely new about the way mate choice and sexual selection work, and will motivate future work in these fields. That is quite an achievement for scientists at any level.”

The research won a regional finalist award last year in the nationwide Siemens Competition in Math, Science and Technology and was also presented at the international meeting of the Society for Mathematical Biology in 2012. For more information about the study, visit www.nimbios.org/press/FS_highschool.

This fall, Chaffee will be a freshman at Purdue University and Griffin will be a freshman at Duke University.

The National Institute for Mathematical and Biological Synthesis (NIMBioS) brings together researchers from around the world to collaborate across disciplinary boundaries to investigate solutions to basic and applied problems in the life sciences.

To learn more, visit www.nimbios.org.

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CONTACT:

Whitney Heins (865-974-5460, wheins@utk.edu)

Catherine Crawley (865-974-9350, ccrawley@nimbios.org)

Chronic harvesting of a tropical tree that many local communities in Western Africa depend on can alter the tree’s reproduction and drastically curtail fruit and seed yields over the tree’s lifetime, according to a new study from the National Institute for Mathematical and Biological Synthesis (NIMBioS) at UT. The study, which appears this week in the Journal of Ecology, is the first of its kind to use what’s called “age-from-stage” mathematical modeling. To read the full article about the study, visit the NIMBioS website.

The award covers the next five years and renews the work of the institute, which was initially funded by a five-year $16 million NSF award in 2008. NIMBioS is also supported by UT.

Chancellor Jimmy G. Cheek said NIMBioS’ track record for success has raised UT’s profile for cross-disciplinary science.

“We are proud to host a critical NSF center where researchers from a wide range of disciplines come to work together and tackle the world’s toughest science questions,” said Chancellor Jimmy G. Cheek. “This allows their important work to continue finding solutions to everything from controlling infectious diseases to predicting climate change effects.”

Since NIMBioS was established in 2008, more than 3,500 researchers from every state in the United States, Washington, D.C., Puerto Rico, and more than fifty-five countries have participated in NIMBioS’ scientific activities, which include workshops, smaller working group meetings, tutorials, postdoctoral and sabbatical fellowships, short-term visits, and a wide variety of educational and outreach events for elementary school-aged children up to postgraduate students.

“Since many of today’s significant scientific challenges require the convergence of multiple fields to find creative solutions, the scientific activities that NIMBioS has fostered have been highly interdisciplinary and have involved collaborations between researchers from vastly diverse backgrounds,” said NIMBioS Director Louis Gross, who founded the institute.

Participants have included anthropologists and psychologists, game theorists and economists, biophysicists and statisticians, experts on partial differential equations and control theory, and experts from all areas of biology.

Research activities have led to more than 270 scientific publications, many in high-impact academic journals, across a vast array of different areas of science and education.

One area of particular emphasis at NIMBioS has been modeling animal infectious diseases, such as white-nose syndrome in bats, pseudo-rabies virus in feral swine, Toxoplasma gondii in cats, and malaria from mosquitoes. As a leading international center for animal infectious disease modeling, NIMBioS has contributed significantly to global needs in analyzing the potential spread, impact, and control of diseases that can move from animals to humans, such as West Nile virus, anthrax, swine flu, and mad cow disease.

The renewal award continues NIMBioS’ efforts in animal infectious disease but will expand activities in other areas including biological engineering, molecular biology, cell biology, and microbiology, as well as offer new opportunities for graduate students to conduct research and train at NIMBioS.

“NIMBioS is pleased to be able to continue to build new collaborations among diverse researchers and educate future leaders of interdisciplinary science,” said Gross.

NIMBioS has also had a positive economic impact on the region through the employment of twenty-seven full-time employees with more than $2 million in annual pay and benefits. In addition, the institute has brought more than 12,000 lodging nights to the region and more than 21,000 meals provided through restaurants and caterers.

To view a graphic about NIMBioS’s activities over the past five years, visit www.nimbios.org/about/#infographic. To learn more about NIMBioS, visit www.nimbios.org.

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C O N T A C T:

Whitney Heins (865-974-5460, wheins@utk.edu)

Catherine Crawley (865-974-9350, ccrawley@nimbios.org)

The event is 8-10 a.m., Thursday, June 27, at the Seven Islands Wildlife Refuge, 2809 Kelly Lane, Kodak, Tennessee.

The Great Smoky Mountains National Park is home to a large number of rare bird species, but finding where they live and how many there are is difficult. Students will record bird songs, develop signal processing algorithms to detect and identify the calls automatically, and then test these algorithms on unattended 24-hour recordings from the park. Automated equipment that can detect and identify the birds’ calls and songs would allow park staff to quantify and localize the presence of rare birds and plan management accordingly.

The students are participating in the Research Experience for Undergraduates (REU) program organized by NIMBioS.

These students join a highly select group of nineteen undergraduates total conducting research as a part of NIMBioS’ Research Experience for Undergraduates (REU) program from June 10 to August 2. The participants live on campus and work in teams with NIMBioS postdoctoral researchers and UT professors on various mathematical biology research projects. The organizer, NIMBioS, is located on the UT campus and fosters new collaborative efforts to investigate biological questions using mathematical and computational methods. More information on REU is available at www.nimbios.org/reu.

Samuel Estes, a mathematics major; Brittany Hale, a biochemistry and mathematics major; and Jacob Lambert, a mathematics and computer science major, are among the nineteen undergraduates participating from across the country.

The 2013 NIMBioS REU program runs for eight weeks, from June 10 to August 2.

During the program, participants live on campus and work in teams with NIMBioS postdoctoral researchers and UT faculty. tackling research at the interface of mathematics and biology.

Research projects for the 2013 program include mathematical modeling of fetal electrocardiograms, modeling animal disease from coronavirus, automatic detection of rare birds from audio recording, modeling the environmental transmission of E.coli in cattle, modeling protein translation and genome evolution, and modeling animal social network dynamics. More information about the REU program, a list of participants and further details about the projects can be found on the NIMBioS website. Follow the REU experience at the REU blog.

NIMBioS is a National Science Foundation-sponsored initiative to foster interdisciplinary research at the interface between mathematical and biological sciences. Additional NIMBioS sponsors include the US Department of Homeland Security and the US Department of Agriculture.

• US News and World Report: Scientists May Have Finally Unlocked Puzzle of Why People Are Gay
• Knoxville News Sentinel/AP: UT Experts: Can Homosexuality Be Inherited?
• Fox News: Homosexuality Ultimately a Result of Gene Regulation, Researchers Find
• World Science: “Epigenetics” Proposed to Underlie Homosexuality
• Salon.com: There is No Gay Gene
• Cosmos Magazine: Homosexuality Starts in the Womb
• Examiner: “Gay Gene” Believed Altered in Womb by Epi-Marks
• TIME: New Insight into the (Epi)Genetic Roots of Homosexuality
• Popular Science: Could Scientists Have Found a Gay Switch?
• VOXXI: Homosexuality Switch, Not Gene, Passed From Parent to Child
• CNN’s AC360: Study: Homosexuality Can Be Passed Down
• Itar-Tass, the main news agency in Russia

Now researchers at UT say they’ve found a clue that may unlock the mystery. It lies in something called epi-genetics—how gene expression is regulated by temporary switches.

A working group at the National Institute for Mathematical and Biological Synthesis (NIMBioS), based at UT, used mathematical modeling that found the transmission of sex-specific epi-marks may signal homosexuality.

According to the study, published online today in The Quarterly Review of Biology, sex-specific epi-marks, which are “erased” and thus normally do not pass between generations, can lead to homosexuality when they escape erasure and are transmitted from father to daughter or mother to son.

“Previous studies have shown that homosexuality runs in families, leading most researchers to presume a genetic underpinning of sexual preference,” said Sergey Gavrilets, paper co-author, joint professor of math and ecology and evolutionary biology and NIMBioS’s associate director for scientific activities. “However, no major gene for homosexuality has been found despite numerous studies searching for a genetic connection.”

Epi-marks may be the trigger they’ve been searching for.

Epi-marks constitute an extra layer of information attached to our genes’ backbones that regulates their expression. While genes hold the instructions, epi-marks direct how those instructions are carried out. They are usually produced anew each generation, but recent evidence demonstrates that they sometimes carry over between generations.

Sex-specific epi-marks produced in early fetal development protect each sex from the substantial natural variation in testosterone that occurs during later fetal development.

Different epi-marks protect different sex-specific traits from being masculinized or feminized.

The researchers found homosexuality can occur in opposite-sex offspring when the sex-specific epi-marks are carried on to another generation.

“We discovered when these epi-marks are transmitted across generations from fathers to daughters or mothers to sons, they may cause reversed effects, such as the feminization of some traits in sons, such as sexual preference, and similarly a partial masculinization of daughters,” said Gavrilets.

The study may solve the evolutionary riddle of homosexuality, finding that “sexually antagonistic” epi-marks, which normally protect parents from natural variation in sex hormone levels during fetal development, sometimes carryover across generations and cause homosexuality in opposite-sex offspring.

The mathematical modeling demonstrates that gene coding for these epi-marks can easily spread in the population because they always increase the fitness of the parent but only rarely escape erasure and reduce fitness in offspring.

“Transmission of sexually antagonistic epi-marks between generations is the most plausible evolutionary mechanism of the phenomenon of human homosexuality,” said Gavrilets.

The paper is co-authored with William Rice, a professor at the University of California, Santa Barbara, and Urban Friberg, a professor at Uppsala University in Sweden.

NIMBioS brings together researchers from around the world to collaborate across disciplinary boundaries to investigate solutions to basic and applied problems in the life sciences. It is sponsored by the National Science Foundation, the US Department of Homeland Security, and the US Department of Agriculture, with additional support from UT. For more information, visit nimbios.org.

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C O N T A C T :

Catherine Crawley (865-974-9350, ccrawley@utk.edu)

Whitney Heins (865-974-5460, wheins@utk.edu)