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Archive - Aug 1, 2014

Study Tells Butterfly Evolutionary History Using Large-Scale, Next-Gen Sequencing

By tracing nearly 3,000 genes to the earliest common ancestor of butterflies and moths, University of Florida (UF) scientists have created an extensive “Tree of Lepidoptera” in the first study to use large-scale, next-generation DNA sequencing. Among the study’s more surprising findings: Butterflies are more closely related to small moths than to large ones, which completely changes scientists’ understanding of how butterflies evolved. The study also found that some insects once classified as moths are actually butterflies, increasing the number of butterfly species higher than previously thought. “This project advances biodiversity research by providing an evolutionary foundation for a very diverse group of insects, with nearly 160,000 described species,” said Dr. Akito Kawahara, lead author and assistant curator of Lepidoptera at the Florida Museum of Natural History on the UF campus. “With a tree, we can now understand how the majority of butterfly and moth species evolved.” Available online and to be published in the August print edition of the Proceedings of the Royal Society B: Biological Sciences, the study builds the evolutionary framework for future ecological and genetics research of insects, Dr. Kawahara said. “There is a DNA revolution taking place,” Dr. Kawahara said. "This is an important time in the history of science when we can use DNA sequencing on a very large scale.” Dr. Kawahara said the year-long study is one of the first to utilize a massive amount of genetic data to answer questions about the history of butterflies and moths. The analysis reveals monumental discoveries about the lineage of Lepidoptera, including strongly contradicting the traditional placement of butterflies in evolutionary history, Dr. Kawahara said.

Strict Genomic Partitioning by Biological Clock Separates Key Metabolic Functions

Much of the liver’s metabolic function is governed by circadian rhythms – our own body clock – and UC Irvine (UCI) researchers have now found two independent mechanisms by which this occurs. The study, published online today July 31, 2014 in Cell, reveals new information about the body clock’s sway over metabolism and points the way to more focused drug treatments for liver disease and such metabolic disorders as obesity and diabetes. Dr. Paolo Sassone-Corsi, UCI’s Donald Bren Professor of Biological Chemistry, and postdoctoral scholar Dr. Selma Masri report that two of these circadian-linked proteins, SIRT1 and SIRT6, manage important liver processes – lipid storage and energy usage in liver cells – separately and distinctly from each other. This surprising discovery of genomic partitioning, Dr. Masri noted, reveals how strictly regulated circadian control of metabolism can be. “The ability of the genome and epigenome to cross-talk with metabolic pathways is critical for cellular and organismal functions. What’s remarkable is that the circadian clock is intimately involved in this dialogue,” she said. Circadian rhythms of 24 hours govern fundamental physiological functions in virtually all organisms. The circadian clocks are intrinsic time-tracking systems in our bodies that anticipate environmental changes and adapt themselves to the appropriate time of day. Changes to these rhythms can profoundly influence human health. Up to 15 percent of people’s genes are regulated by the day-night pattern of circadian rhythms; nearly 50 percent of those involved with metabolic pathways in the liver are influenced by these rhythms.

Oldest Beetle in Omaliini Tribe Found in Amber

An international team of scientists from Spain, France, and the U.S. has discovered and described a rove beetle that is the oldest definitive member of the tribe Omaliini that has ever been found in amber. The discovery and description were made possible through the use of the propagation phase-contrast X-ray synchrotron imaging technique, which allows the detailed study of otherwise invisible specimens in opaque amber. The new species is described in the journal Annals of the Entomological Society of America in an article called "Oldest Omaliini (Coleoptera: Staphylinidae: Omaliinae) Discovered in the Opaque Cretaceous Amber of Charentes." The tribe Omaliini belongs to the subfamily Omaliinae, which belongs to the family Staphylinidae, the largest of all of the beetle families, with more than 60,000 described species. Two specimens of the “new” species, called Duocalcar geminum, were found in a single piece of opaque amber, along with other arthropods that were embedded in the same piece of amber. The genus name, Duocalcar, means “two spurs” in Latin, “alluding to the two distinctive projections on each hind leg, at the trochanteral apex and near the tibial apex.” The specific epithet, geminum, is a Latin adjective meaning “twin-born,” in reference to the discovery of both specimens in the same piece of amber.“ D. geminum is the first Omaliinae described from any amber, increasing the minimum age of Omaliini to ≈100 million years, from Eocene to latest Albian,” the authors wrote. [Press release] [Annals of the Entomological Society of America abstract]

Molecular Gate That Could Keep Cancer Cells Locked Up

In a study published ton August 1, 2014 in Genes & Development, Dr Christian Speck from the MRC Clinical Sciences Centre's DNA Replication group, in collaboration with Brookhaven National Laboratory (BNL), New York, reveals the intricate mechanisms involved in the enzyme that governs DNA duplication during cell division. By developing a sophisticated system using synthetic, chemical and structural biology approaches, the study reveals how a key enzyme involved in duplicating genetic information embraces DNA through a gated system, which opens up at precise positions allowing for a highly regulated replication process. This work enhances current understanding of an essential biological process and suggests a route for stopping cell division in disease such as cancer. When a cell divides, genetic information is duplicated in a process known as DNA replication. For this to occur, a 'replication machine' is assembled on top of the DNA prior to duplication. A protein complex known as ORC that recognises the DNA replication origin initiates the whole process. Next, an enzyme, MCM2-7 helicase, whose role is to unwind and separate the two strands of the DNA helix, is loaded onto the DNA by the machine system ORC. The helicase is a ring-shaped enzyme composed of six subunits (hexamer), though how the ring structure opens and encircles the DNA has, until now, remained a mystery. Initial theories within the field assumed the helicase to exist in an open ring conformation. Dr. Speck's team argued that this would undoubtedly lead to poorly regulated DNA replication with no control or specificity. To examine the helicase activity in more detail, Jingchuan Sun at BNL used an electron microscope and revealed, contrary to initial theories, the helicase actually existed as a closed ring conformation.

How DNA Avoids Damage from UV Light

In the same week that the U.S. surgeon general issued a 101-page report about the dangers of skin cancer, researchers at Montana State University (MSU) published a paper breaking new ground on how DNA – the genetic code in every cell – responds when exposed to ultraviolet (UV) light. The findings advance fundamental understanding of DNA damage by the UV rays found in sunlight. This damage can lead to skin cancer, aging, and some degenerative eye diseases. "Our paper advances foundational knowledge about how DNA responds to UV radiation. In our experiments, we observe the earliest events immediately after DNA is energized by UV radiation. These events determine whether or not DNA is damaged," said one of the paper's co-authors, Dr. Bern Kohler, an MSU professor in the Department of Chemistry and Biochemistry. DNA is built like a staircase and carries genetic instructions that are unique to each person. It's very hardy and generally able to stand up to ultraviolet rays, but UV rays sometimes cause mutations. UV exposure is a major cause of skin cancer, and while there are nearly 5 million cases of skin cancer each year in the U.S. alone – and 9,000 related deaths – the numbers would be far worse if DNA were more easily damaged. "UV is actually very damaging, yet our DNA is damaged less than expected," Dr. Kohler said. "In the early evolution of life on Earth when there was no ozone layer, the amount of UV would have been far higher and yet life, and the DNA that is central to life, survived. We've been trying to understand the molecular mechanisms that make DNA resist UV damage." In a paper published July 28, 2014 in the online version of the scientific journal PNAS, Dr.

Scientists Discover Biochemical Mechanisms Contributing to Fibromuscular Dysplasia

An important step has been made to help better identify and treat those with fibromuscular dysplasia (FMD). FMD causes both an abnormal narrowing and enlarging of medium-sized arteries in the body, which can restrict blood flow to the kidneys and other organs causing damage. In a new report appearing in the August 2014 issue of The FASEB Journal, scientists provide evidence that that FMD may not be limited to the arteries as currently believed. In addition, the scientists show a connection to abnormalities of bones and joints, as well as evidence that inflammation may be driving the vascular disease in FMD patients. "Having medical treatment options for FMD, or for people who may be susceptible to FMD, will improve their quality of life by preventing vascular complications," said Nazli B. McDonnell, M.D., Ph.D., a researcher involved in the work from the National Institute on Aging at the National Institutes of Health in Baltimore, Maryland. "Recognizing the additional features of FMD, namely those involving the joints and bones, may help us to design better treatments for these ancillary symptoms that were previously thought to be independent of FMD." To make this discovery, Dr. Nazli and colleagues recruited patients with FMD and performed physical exams. Vascular imaging and bone density studies were also conducted. Researchers measured specific proteins in the blood that indicated inflammation activation of the transforming growth factor-beta (or TGF-beta) pathway. Patient skin biopsies also were collected to grow dermal fibroblast cell lines, which were studied for TGF-beta pathway and inflammatory biomarkers and were compared to age-, sex-, and BMI-matched controls that did not have FMD. "FMD is a serious blood vessel disease for which we know little," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal.

Potential Basis for the Treatment and Prevention of Parkinson’s Disease

Parkinson’s disease affects neurons in the substantia nigra brain region – their mitochondrial activity ceases and the cells die. In an open-access article published online on August 1, 2014 in The Company of Biologists/Biology Open, researchers at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, show that supplying D-lactate or glycolate, two products of the gene DJ-1, can stop and even counteract this process: Adding the substances to cultured HeLa cells and to cells of the nematode C. elegans restored the activity of mitochondria and prevented the degeneration of neurons. Thee team also showed that the two substances rescued the toxic effects of the weed killer Paraquat. Cells that had been treated with this herbicide, which is known to cause a Parkinson's-like harm of mitochondria, recovered after the addition of the two substances. Both glycolic and D-lactic acids occur naturally in unripe fruits and certain kinds of yoghurt. Drs. Teymuras Kurzchalia and Tony Hyman both have labs at the Max Planck Institute of Molecular Cell Biology and Genetics with rather different research programs – but both happened to stumble upon the gene DJ-1 and joined forces. This gene, originally thought of as an oncogene, has been linked to Parkinson’s disease since 2003. Recent studies showed that DJ-1 belongs to a novel glyxolase family. The major function of these genes is assumed to be the detoxification of aggressive aldehyde by-products from mitochondrial metabolism. The Dresden research team has now shown that the products of DJ-1, D-lactate and glycolate, are actually required to maintain the high mitochondrial potential and thus can prevent the degeneration of neurons implicated in Parkinson’s disease.