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Archive - Aug 16, 2013


Female Tree Frogs Prefer Males Who Can Multitask

From frogs to humans, selecting a mate is complicated. Females of many species judge suitors based on many indicators of health or parenting potential. But it can be difficult for males to produce multiple signals that demonstrate these qualities simultaneously. In a study of Cope’s grey tree frogs, a team of University of Minnesota researchers discovered that females prefer males whose calls reflect the ability to multitask effectively. In this species (Hyla chrysoscelis), males produce "trilled" mating calls that consist of a string of pulses. Typical calls can range in duration from 20-40 pulses per call and occur at the rate of between 5-15 calls per minute. Males face a trade-off between call duration and call rate, but females preferred calls that are longer and more frequent, which is no simple task. The findings were published in the August 2013 issue of Animal Behaviour. "It’s kind of like singing and dancing at the same time," says Dr. Jessica Ward, a postdoctoral researcher who is lead author for the study. Dr. Ward works in the laboratory of Dr. Mark Bee, a professor in the College of Biological Sciences’ Department of Ecology, Evolution and Behavior. The study supports the multitasking hypothesis, which suggests that females prefer males who can do two or more hard-to-do things at the same time because these are especially good-quality males, Dr. Ward says. The hypothesis, which explores how multiple signals produced by males influence female behavior, is a new area of interest in animal behavior research. By listening to recordings of 1,000 calls, Dr. Ward and colleagues learned that males are indeed forced to trade off call duration and call rate. That is, males that produce relatively longer calls only do so at relatively slower rates.

Supercomputers Shed Light on How DNA Repair Helps Prevent Cancer

The biological information that makes us unique is encoded in our DNA. DNA damage is a natural biological occurrence that happens every time cells divide and multiply. External factors such as overexposure to sunlight can also damage DNA. Understanding how the human body recognizes damaged DNA and initiates repair fascinates Dr. Michael Feig, professor of biochemistry and molecular biology at Michigan State University. Dr. Feig studies the proteins MutS and MSH2-MSH6, which recognize defective DNA and initiate DNA repair. Natural DNA repair occurs when proteins like MutS (the primary protein responsible for recognizing a variety of DNA mismatches) scan the DNA, identify a defect, and recruit other enzymes to carry out the actual repair. "The key here is to understand how these defects are recognized," Dr. Feig explained. "DNA damage occurs frequently and if you couldn't repair your DNA, then you wouldn’t live for very long." This is because damaged DNA, if left unrepaired, can compromise cells and lead to diseases such as cancer. Dr. Feig, who has used national supercomputing resources since he was a graduate student in 1998, applied large-scale computer simulations to gain a detailed understanding of the cellular recognition process. Numerical simulations provide a very detailed view down to the atomistic level of how MutS and MSH2-MSH6 scan DNA and identify which DNA needs to be repaired. Because the systems are complex, the research requires large amounts of computer resources, on the order of tens of millions of CPU core hours over many years. "We need high-level atomic resolution simulations to get insights into the answers we are searching for and we cannot run them on ordinary desktops," Dr. Feig said.

Exome Sequencing Reveals Two New Genes, 25 De Novo Mutations in Severe Childhood Epilepsies

A genetic study of childhood epilepsies has linked two new genes to severe forms of disease and provides a novel strategy for identifying therapy targets. This study used exome sequencing to search for new mutations that are not inherited. The results suggest that this may be a highly effective way to find and confirm many disease-causing gene mutations. "It appears that the time for using this approach to understand complex neurological disorders has arrived," said David Goldstein, Ph.D., director of the Human Genome Variation Center at Duke University Medical Center, Durham, North Carolina, and a leader of the study. "This moderately-sized study identified an unusually large number of disease-causing mutations and provides a wealth of new information for the epilepsy research community to explore." The study is part of a worldwide, $25 million project, largely funded by the National Institutes of Health, called Epilepsy 4000 (Epi4K). Epi4K's mission is to use the latest genetic techniques to sequence and analyze DNA from 4000 epilepsy patients and their relatives. To do this, the researchers and NIH staff involved organized a team of international research institutions devoted to the mission, called the Epilepsy Centers without Walls. This approach facilitates the sharing and analysis of DNA sequences and patient information among the dozens of institutions participating in the project. The study, published online on August 11, 2013 in Nature by the Epi4K and Epilepsy Phenome/Genome Project (EPGP) Investigators, found as many as 25 epilepsy-causing mutations in new and previously identified genes.

Treatment-Resistant Lymphomas “Reprogrammed” to Respond to Cancer Drugs

A phase I clinical trial showed diffuse, large B-cell lymphomas (DLBCLs) resistant to chemotherapy can be reprogrammed to respond to treatment using the drug azacitidine, according to a study published online on August 16, 2013 in Cancer Discovery, a journal of the American Association for Cancer Research (AACR). Patients whose lymphomas recur after initial chemotherapy are treated with a combination of approaches, including high-dose chemotherapy followed by a stem cell transplant. However, some patients have tumors that do not respond to these extensive second treatments, and many of these patients die within two years of diagnosis. "When lymphomas are formed, they shut down the cellular programs that sense that something is wrong in the cells. Once these fail-safe mechanisms that trigger cell death are shut down, it becomes difficult to kill the tumor with chemotherapy," said senior author Leandro Cerchietti, M.D., assistant professor at the Hematology and Oncology Division of Weill Cornell Medical College in New York. "Our study showed that using low concentrations of the DNA methyltransferase inhibitors decitabine or azacitidine, these fail-safe mechanisms can slowly be awakened to induce lymphoma cell death when chemotherapy is administered." Dr. Cerchietti and an international group of colleagues conducted a phase I trial in patients with newly diagnosed DLBCL. Eleven of the 12 patients enrolled were more than 60 years old when diagnosed, which meant that they were at high risk for tumor recurrence after initial treatment. The patients were treated with azacitidine, in escalating doses, eight days prior to initiation of six cycles of standard chemotherapy. Side effects from pretreatment with azacitidine were minimal.