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Archive - Jan 15, 2015

Rattlesnake Venom Can Change Significantly with Snake Location; Huge Impact on Anti-Venom Design and Use

If you're one of the unfortunate few to be bitten by a venomous snake, having access to effective anti-venom to combat the swelling, pain, and tissue damage to these bites is critical. But new research by a team of biologists at Florida State University (FSU) has revealed that creating anti-venom is a bit tricky. That's because the type of venom a snake produces can change according to where it lives. Mark Marges, an FSU doctoral student in Professor Darin Rokyta's laboratory, led a research study that examined the venom of 65 eastern diamondback rattlesnakes (image) and 49 eastern coral snakes from all over the state of Florida to determine whether snake venoms varied by geography. In the rattlesnakes, geography mattered. The venom from an eastern diamondback rattlesnake in the Florida panhandle is very different from the venom from an eastern diamondback rattlesnake 500 miles south in the Everglades, and this has huge implications for snakebite treatment. "So if you use just southern venoms when making the antivenom, it would be ineffective against some of the more common toxins found in northern diamondback rattlesnakes," said Mr. Margres. This research was published online on November 11, 2014 in the journal Genetics. In the eastern diamondback rattlesnakes, the scientists found significant venom variation linked to geography. But, in the eastern coral snakes, they found the venom to be identical no matter where the snakes were found. "This can tell us a bit of the history and evolutionary patterns of the snakes," said Dr. Kenny Wray, a post-doctoral research associate in Dr. Rokyta's lab. "This suggests that the coral snakes may be recent invaders to the region and haven't had time to evolve different venoms in different areas."

Coenzyme A Regulates Nitric Oxide Activity; New Class of Metabolic Enzymes Discovered

Case Western Reserve and University Hospitals (UH) Case Medical Center researchers and physicians have discovered that the molecule known as coenzyme A plays a key role in cell metabolism by regulating the actions of nitric oxide (image). Cell metabolism is the ongoing process of chemical transformations within the body's cells that sustains life, and alterations in metabolism are a common cause of human disease, including cancer and heart disease. Their findings about the mechanisms of action for coenzyme A, as well as the discovery of a new class of enzymes that regulate coenzyme A-based reactions, are described in an article published online on December 15, 2015 in PNAS. "The governing role of coenzyme A in nitric oxide function was completely unknown and unanticipated before this study," said senior author Jonathan Stamler, M.D., Professor of Medicine, Case Western Reserve University (CWRU) School of Medicine, and Director, Harrington Discovery Institute at UH Case Medical Center. "Nitric oxide operates in every cell and tissue of the body to influence cell function. We are trying to work through the basic control of nitric oxide biology to elucidate the machinery underlying its mechanisms of action." Coenzyme A sets into motion a process known as protein nitrosylation, which unleashes nitric oxide to alter the shape and function of proteins within cells to modify cell behavior. The purpose of manipulating the behavior of cells is to tailor their actions to accommodate the ever-changing needs of the body's metabolism. In addition, Case Western Reserve and UH investigators identified hundreds of proteins regulated by coenzyme A-driven protein nitrosylation. Many of the newly discovered targets of nitrosylation were noted to influence cellular energy production.

Next-Gen Sequencing ID’s Genetic Clues to Rare Breast Tumor Type

A new study from researchers at the University of Michigan Comprehensive Cancer Center characterizes the genetic underpinnings of a rare type of breast tumor called phyllodes tumors, offering the first comprehensive analysis of the molecular alterations at work in these tumors. The analysis uses next-generation sequencing techniques that allow researchers to identify alterations in more than 100 genes from archived tissue samples. "We know little about the biology of phyllodes tumors. In part, they have not been studied much because it's difficult to accumulate a large number of samples. Using these new sequencing techniques, we were able to study archived tissue samples, which allowed us to identify enough samples to perform a meaningful analysis," says study author Scott A. Tomlins, M.D., Ph.D., Assistant Professor of Pathology and Urology at the University of Michigan Medical School. Phyllodes tumors represent about 1 percent of all types of breast tumors. Most are benign, but they do have the potential to become metastatic. Currently, there are no good ways to reliably predict which tumors are likely to recur or spread after initial treatment. Once phyllodes tumors become metastatic, there are few effective treatments. Researchers looked at 15 samples of phyllodes tumors, culled from archived tissue samples at the University of Michigan. The samples were equally divided according to their classification, with five considered benign, five borderline, and five malignant. While still a small sample, it can be sufficient with a rare tumor to identify genetic clues to the tumor's biology. The researchers sequenced the samples against a panel of genes known to have some function or role in cancer. They found two genes, EGFR and IGF1R, that were amplified in multiple malignant phyllodes tumors.