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Archive - Nov 8, 2013

Reduced Mitochondrial DNA May Lead to Breast Cancer Metastasis

For years, scientists have observed that tumor cells from certain breast cancer patients with aggressive forms of the disease contained low levels of mitochondrial DNA. But, until recently, no one was able to explain how this characteristic influenced disease progression. Now, University of Pennsylvania researchers have revealed how a reduction in mitochondrial DNA content leads human breast cancer cells to take on aggressive, metastatic properties. The work, published online on November 4, 2013, in the journal Oncogene, breaks new ground in understanding why some cancers progress and spread faster than others and may offer clinicians a biomarker that would distinguish patients with particularly aggressive forms of disease, helping personalize treatment approaches. The study was led by the Penn School of Veterinary Medicine’s Dr. Manti Guha, a senior research investigator, and Dr. Narayan Avadhani, Harriet Ellison Woodward Professor of Biochemistry in the Department of Animal Biology. Additional Penn Vet collaborators included Drs. Satish Srinivasan, Gordon Ruthel, Anna K. Kashina, and Thomas Van Winkle. They teamed with Dr. Russ P. Carstens of Penn’s Perelman School of Medicine and Drs. Arnulfo Mendoza and Chand Khanna of the National Cancer Institute. Mitochondria, the so-called “powerhouses” of mammalian cells, are also a signaling hub. They are heavily involved in cellular metabolism as well as in apoptosis, the process of programmed cell death by which potentially cancerous cells can be killed before they multiply and spread. In addition, mitochondria contain their own genomes, which code for specific proteins and are expressed in coordination with nuclear DNA to regulate the provision of energy to cells.

New Species of Scorpion Discovered in Turkey

Scientists have discovered and described a new species of scorpion, Euscorpius lycius, coming from the area of ancient Lycia, nowadays the regions of the Muğla and Antalya Provinces in Southwestern Turkey. With the new discovery, the scorpions from this genus found in the country go up to a total of five known species. The study was published in the open-access journal ZooKeys and featured on the cover of the August 8, 2013 print issue. Euscorpius is a genus of scorpions, commonly called small wood-scorpions. As their name suggests, these scorpions don't impress with a large size, the biggest representative being ony approximately 5 cm long. The group is widespread in North Africa and across Europe. Euscorpius scorpions are relatively harmless, with poison that has effects similar to a mosquito bite. The new species is named after the historical region of Ancient Lycia, which is referenced in Egyptian and Ancient Greek myths. Like the mystical history of the region, the new species is rather secretive and can be found mainly in pine forests at night hidden away in pine forests, crawling on rocks or sitting on stone garden walls. All localities where the species was found were humid and cool, with calcareous stones covered with moss. The new scorpion is a relatively small representative, reaching a size ranging between two and two-and-a-half centimeters. The color of the adult representatives is pale, between brown and reddish, with pedipalps, or claws, usually darker than the rest of the body. "A total of 26 specimens belonging to the new species were collected from Antalya and Muğla Province, in the south-west of Turkey." explains Dr. Ersen Yağmur, the lead author of the study.

Cost-Effective Method Accurately Orders DNA Sequencing along Entire Chromosomes

A new computational method has been shown to quickly assign, order, and orient DNA sequencing information along entire chromosomes. The method may help overcome a major obstacle that has delayed progress in designing rapid, low-cost -- but still accurate -- ways to assemble genomes from scratch. Data gleaned through this new method can also validate certain types of chromosomal abnormalities in cancer, research findings indicate. The advance was reported online on November 3, 2013 in Nature Biotechnology by several University of Washington scientists led by Dr. Jay Shendure, associate professor of genome sciences. Existing technologies can quickly produce billions of "short reads" of segments of DNA at very low cost. Various approaches are currently used to put the pieces together to see how DNA segments line up to form larger stretches of the genetic code. However, current methods produce a highly fragmented genome assembly, lacking long-range information about what sequences are near what other sequences, making further biological analysis difficult. "Genome science has remained remarkably distant from routinely assembling genomes to the standards set by the Human Genome Project," said the researchers. They noted that the Human Genome Project tapped into many different techniques to achieve its end result. Many of these are too expensive, technically difficult, and impractical for large-scale initiatives such as the Genome 10K Project, which aims to sequence and assemble the genomes of 10,000 vertebrate species. Members of the Shendure lab that developed what they hope will be a more scalable strategy were Drs. Joshua N. Burton, Andrew Adey, Rupali P. Patwardhan, Ruolan Qiu, and Jacob O. Kitzman.

Unique Change in Protein Structure Guides Production of RNA from DNA

One of biology's most fundamental processes is something called transcription. It is just one step of many required to build proteins—and without it life would not exist. However, many aspects of transcription remain shrouded in mystery. But now, scientists at the Gladstone Institutes in San Francisco are shedding light on key aspects of transcription, and in so doing are coming even closer to understanding the importance of this process in the growth and development of cells—as well as what happens when this process goes awry. In the November 7, 2013 issue of Molecular Cell, researchers in the laboratory of Gladstone Investigator Melanie Ott, M.D., Ph.D., describe the intriguing behavior of a protein called RNA polymerase II (RNAPII) (see image). The RNAPII protein is an enzyme, a catalyst that guides the transcription process by copying DNA into RNA, which forms a disposable blueprint for making proteins. Scientists have long known that RNAPII appears to stall or "pause" at specific genes early in transcription. But they were not sure as to why. "This so-called 'polymerase pausing' occurs when RNAPII literally stops soon after beginning transcription for a short period before starting up again," explained Dr. Ott, who is also a professor of medicine at the University of California, San Francisco, with which Gladstone is affiliated. "All we knew was that this behavior was important for the precise transcription of DNA into RNA, so we set out to understand how, when, and—most importantly—why." The research team focused its efforts on a segment of RNAPII called the C-terminal domain, or CTD. This section is most intimately involved with transcription regulation. Previous research had found that CTD's chemical structure is modified before and during transcription.