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Archive - Oct 2011

October 22nd

Coupling of Two Proteins Promotes Glioblastoma Development

Two previously unassociated proteins known to be overly active in a variety of cancers bind together to ignite and sustain malignant brain tumors, a research team led by scientists at The University of Texas MD Anderson Cancer Center reports in the cover story of the October 18, 2011 issue of Cancer Cell. This research is the first to connect FoxM1 to a molecular signaling cascade that regulates normal neural stem cells, said senior author, Dr. Suyun Huang, associate professor in MD Anderson's Department of Neurosurgery. "When FoxM1 binds to beta-catenin, we found that it also supports the self-renewal and differentiation of glioma- initiating cells, cancer stem cells thought to drive glioblastoma multiforme," Dr. Huang said. Glioblastoma multiforme is the most common and lethal form of brain tumor. Glioma- initiating cells are prime suspects in the disease's resistance to treatment and ability to reoccur. The scientists established the relationship between FoxM1 and beta-catenin in a series of cell line experiments and then confirmed their findings in mouse models of human glioblastoma and in an analysis of human tumors. FoxM1 and beta-catenin separately have so far largely evaded targeting by drugs. Dr. Huang and her team are focusing on the details of the connection between the two proteins in search of small molecules that might block their binding. "Our study might lead to the development of a new class of small-molecule anti-cancer drugs, including but not necessarily limited to glioblastoma multiforme," Dr. Huang said. Much preclinical work remains to be done before such a drug can be identified and brought to clinical trial. FoxM1 was previously known solely as a transcription factor – a protein that binds to the DNA in a gene's promoter region to prompt the gene's expression of messenger RNA that is processed into a protein.

Common 3-Drug Regimen for Idiopathic Pulmonary Fibrosis Found Harmful

The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, has stopped one arm of a three-arm multi-center, clinical trial studying treatments for the lung-scarring disease idiopathic pulmonary fibrosis (IPF) for safety concerns. The trial found that people with IPF receiving a currently used triple-drug therapy consisting of prednisone, azathioprine, and N-acetylcysteine (NAC) had worse outcomes than those who received placebos, or inactive substances. "These findings underscore why treatments must be evaluated in a rigorous manner," said Dr. Susan B. Shurin, acting director of the NHLBI. "This combination therapy is widely used in patients with IPF, but has not previously been studied in direct comparison to a placebo for all three drugs." The interim results from this study showed that compared to placebo, those assigned to triple therapy had greater mortality (11 percent versus 1 percent), more hospitalizations (29 percent versus 8 percent), and more serious adverse events (31 percent versus 9 percent) and also had no difference in lung function test changes. Participants randomly assigned to the triple- therapy arm also remained on their assigned treatment at a much lower rate (78 percent adherence versus 98 percent adherence). "Anyone on some combination of these medications with questions or concerns should consult with their health care provider and not simply stop taking the drugs," said Dr. Ganesh Raghu, professor of medicine at the University of Washington, Seattle, and a co-chair of this IPF study.

CK1 Enzyme May Be New Target for the Treatment of Cancer

Researchers from the New York University (NYU) Cancer Institute, a National Cancer Institute (NCI)-designated cancer center at NYU Langone Medical Center, and collaborators have identified a cell cycle-regulated mechanism behind the transformation of normal cells into cancerous cells. The study shows the significant role that protein networks can play in a cell leading to the development of cancer. The study results, published in the October 21, 2011 issue of the journal Molecular Cell, suggest that inhibition of the CK1 (casein kinase 1) enzyme may be a new therapeutic target for the treatment of cancer cells formed as a result of a malfunction in the cell's mTOR signaling pathway. In the study, NYU Cancer Institute researchers examined certain multi-protein complexes and protein regulators in cancer cells. Researchers identified a major role for the multi-protein complex called SCFβTrCP . This complex assists in the removal from cancer cells of the recently discovered protein DEPTOR, an inhibitor of the mTOR (mammalian Target of Rapamycin) pathway. SCF (Skp1, Cullin1, F-box protein) ubiquitin ligase complexes are responsible for the removal of unnecessary proteins from a cell. This degradation of proteins by the cell's ubiquitin system controls cell growth and prevents malignant cell transformation. Researchers show that inhibiting the ability of SCFβTrCP to degrade DEPTOR in cells can result in blocking the proliferation of cancer cells. In addition, researchers discovered that the activity of CK1, a protein that regulates signaling pathways in most cells, is needed for SCFβTrCP to successfully promote the degradation of DEPTOR. "Low levels of DEPTOR and high levels of mTOR activity are found in many cancers, including cancers of the breast, prostate, and lung," said senior study author Dr.

October 21st

Small Molecule Work Advances Progress Toward More Tailored Drugs

Research led by St. Jude Children's Research Hospital scientists advances a strategy for reducing the side effects and enhancing the therapeutic benefits of steroids and other medications that work by disrupting the activity of certain hormones. The approach relies on a small molecule developed at St. Jude. In this study, scientists showed that a compound known as SJ-AK selectively blocked the activity of genes in a cell signaling pathway regulated by thyroid hormone. Investigators showed that SJ-AK also affected cells growing in the laboratory, reducing cell proliferation as well as the production and secretion of a growth hormone regulated by thyroid hormone. The research appears in the October 21, 2011 issue of the scientific journal ACS Chemical Biology. The findings raise hope that compounds like SJ-AK will lead to drugs with more tailored effects by selectively controlling signaling pathways that switch genes on and off. This research focused on a pathway controlled by a thyroid hormone. Investigators said, however, the approach also could potentially be used to target pathways regulated by glucocorticoid, estrogen, androgen, and other hormones that are widely used to treat cancer and other conditions, but that also have serious side effects. "This study offers the first evidence it is possible to shut down a portion of the signaling network activated by a particular hormone," said Dr. R. Kiplin Guy, chair of the St. Jude Chemical Biology and Therapeutics Department. Dr. Guy is the senior author of the paper. The first author is Dr. Prabodh Sadana, a former St. Jude postdoctoral fellow who now works in the Department of Pharmaceutical Sciences at Northeastern Ohio Universities College of Medicine and Pharmacy.

First Complete 3-D Structure of a Bacterial Chromosome

A team of researchers at the University of Massachusetts Medical School, Harvard Medical School, Stanford University, and the Prince Felipe Research Centre in Spain have deciphered the complete three-dimensional (3-D) structure of the bacterium Caulobacter crescentus's chromosome. Analysis of the resulting structure —published this week in the October 21, 2011 issue of Molecular Cell — has revealed new insights into the function of genetic sequences responsible for the shape and structure of this genome. Scientists know that the 3-D shape of a cell's chromosome plays a role in how genetic sequences and genes are regulated. However, technical challenges have limited genome-wide analysis of a chromosome's architecture that would allow for simultaneous identification of the elements involved in shaping it and analysis of specific features of the structure. In this study, researchers used high-throughput chromatin interaction detection; next-generation DNA sequencing; computational modeling; and fluorescent microscopy to build the first 3-D model of the architecture of the bacterium's chromosome and analyze the resulting structures. This new experimental approach revealed novel characteristics of a specific genetic sequence called the parS site, which helps to define the chromosome's shape. "What we've shown is that it's possible to combine molecular biology with 3-D modeling technology to perform studies that tell us novel things about how genomes fold and identify the genetic sequences that are responsible," said Dr. Job Dekker, a pioneer in chromosome interaction detection technologies, professor of biochemistry & molecular pharmacology at the University of Massachusetts Medical School, and one of the authors of the study. Dr.

October 20th

Robins Are “Super-Spreaders” of West Nile Virus

After its initial appearance in New York in 1999, West Nile virus spread across the United States in just a few years and is now well established throughout North and South America. Both the mosquitoes that transmit it and the birds that are important hosts for the virus are abundant in areas that have been modified by human activities. As a result, transmission of West Nile virus is highest in urbanized and agricultural habitats. "The virus has had an important impact on human health in the United States partly because it took advantage of species that do well around people," said Dr. Marm Kilpatrick, a biologist at the University of California, Santa Cruz, who studies the ecology of infectious diseases. West Nile virus can infect a wide range of animals, including more than 300 species of birds and 60 species of mosquitoes. It also infects mammals, reptiles, and even amphibians. But researchers have found that in most places only a few key species of bird "hosts" and mosquito "vectors" are important in transmission of the virus. "We now know that in any given location, only one or two species of mosquitoes play a big role, and only a handful of birds appear to be important in overall transmission rates," said Dr. Kilpatrick, who reviewed a decade of research on the ecology and evolution of West Nile virus in a paper published in the October 21, 2011 issue of the journal Science. According to Dr. Kilpatrick, the familiar American robin plays a key role in the transmission of West Nile virus across much of North America. It is such an important host species that Kilpatrick calls robins "super-spreaders" of West Nile virus. The reason is not so much the abundance of robins, but rather the feeding patterns of the mosquitoes that transmit the virus.

NGS Aids Determination of Family Tree for Hawaiian Honeycreepers

Using one of the largest DNA data sets for a group of birds and employing next-generation sequencing (NGS) methods, Smithsonian scientists and collaborators have determined the evolutionary family tree for one of the most strikingly diverse and endangered bird families in the world, the Hawaiian honeycreepers. Not only have the researchers determined the types of finches that the honeycreeper family originally evolved from, but they have also linked the timing of that rapid evolution to the formation of the four main Hawaiian Islands. The findings were published online on October 20, 2011 in Current Biology. "There were once more than 55 species of these colorful songbirds, and they are so diverse that historically it wasn't even entirely clear that they were all part of the same group," said Dr. Heather Lerner, who was a postdoctoral researcher at the Smithsonian Conservation Biology Institute's (SCBI’s) Center for Conservation and Evolutionary Genetics when she conducted this research, and is currently an assistant professor of biology at Earlham College and Joseph Moore Museum director. "Some eat seeds, some eat fruit, some eat snails, some eat nectar. Some have the bills of parrots, others of warblers, while some are finch-like and others have straight, thin bills. So the question that we started with was how did this incredible diversity evolve over time," Dr. Lerner said. The answer is unique to the Hawaiian Islands, which are part of a conveyor belt of island formation, with new islands popping up as the conveyor belt moves northwest. Each island that forms represents a blank slate for evolution, so as one honeycreeper species moves from one island to a new island, those birds encounter new habitat and ecological niches that may force them to adapt and branch off into distinct species.

October 19th

Efficacy of Vaccine for Non-Hodgkin’s Lymphoma Demonstrated in Dogs

An experimental vaccine developed by researchers at the University of Pennsylvania’s schools of Medicine and Veterinary Medicine is the first veterinary cancer vaccine of its kind that shows an increase in survival time for dogs with spontaneous non-Hodgkin’s lymphoma (NHL). The work shows for the first time the feasibility and therapeutic efficacy of this alternative cell-based vaccine, which could be employed in the treatment of a number of different cancer types. The research was conducted by Dr. Nicola Mason, assistant professor of medicine at Penn Vet; Dr. Robert H. Vonderheide, associate professor of hematology and oncology at the Perelman School of Medicine; and Dr. Karin U. Sorenmo, associate professor of oncology at Penn Vet. Drs. Erika Krick, Beth Overley and Thomas P. Gregor of Penn Vet and Dr. Christina M. Coughlin of the School of Medicine also contributed to the research. Their work was published on August 31, 2011 in the open access journal PLoS ONE. The team recruited dogs that were brought to Penn’s Matthew J. Ryan Veterinary Hospital with newly diagnosed NHL to receive the experimental vaccine following standard induction chemotherapy and confirmation of clinical remission. The goal of the study was to determine whether the vaccine would prevent or prolong time to a relapse, a common scenario in both humans and dogs with NHL. “We vaccinated dogs, which were in clinical remission following chemotherapy, three times,” Dr. Mason said. “We then tracked them over several years to see if the vaccine would prevent relapse and would prolong overall survival.

Unusual Plant Found Near Mississippi Gravesite of Gypsy Queen

A U.S. Department of Agriculture (USDA) scientist has confirmed the identity of a strange grass-like sedge discovered in a Mississippi graveyard, and believes the appearance of the potentially invasive plant is linked to the final resting places of several members of a royal Gypsy family. Agricultural Research Service (ARS) botanist Dr. Charles Bryson was asked by Mississippi State University graduate student Lucas Majure to help classify a plant Majure had found in Rose Hill Cemetery in Meridian, Mississippi. Dr. Bryson works at the ARS Crop Production Systems Research Unit in Stoneville, Mississippi. ARS is USDA's chief intramural scientific research agency. After several months of searching, Dr. Bryson identified the plant as blue sedge (Carex breviculmis), a native of Asia and Australia and previously unknown in North America. He also found it growing along railroad tracks, campgrounds used by transients, and in or around four cemeteries in Meridian, including Rose Hill Cemetery. Visitors from all over the world come to Rose Hill Cemetery to pay their respects at the gravesite of Kelly Mitchell, the Queen of the Gypsies, who was buried there in 1915. Her husband and other family members were also laid to rest in the cemetery. Given the plant's restricted and distinctive distribution in the region, Bryson thinks that global travelers introduced the sedge to Mississippi, possibly via seeds trapped in clothing or by leaving plants or soil at the gravesites of the Gypsy royalty. Then cemetery caretakers may have spread plant material from the first introduction site to the other cemeteries via contaminated clothing and lawn care equipment. At two sites where it is now established, the plant exhibits weedy characteristics and reproduces and spreads profusely. To Dr.

October 18th

Two New Bee Species May Shed Light on Panama’s History

Smithsonian scientists have discovered two new, closely related bee species: one from Coiba Island in Panama and another from northern Colombia. Both descended from of a group of stingless bees that originated in the Amazon and moved into Central America, the ancestors of Mayan honeybees. The presence of one of these new species on Coiba and Rancheria Islands, and its absence from the nearby mainland, is a mystery that may ultimately shed light on Panama's history and abundant biodiversity. The new findings were published online on September 8, 2011 in Systematic Entomology. At almost 200 square miles, Coiba Island is the largest offshore island along the Pacific coast of Latin America. Rancheria Island is a much smaller neighbor. The species name, insularis, of the new bee from Coiba, Melipona insularis, means "island." This is the first species in its group to be found on islands near the mainland. "These forest bees have a small range over which they can establish new nests and colonies," says Dr. David Roubik, staff scientist at the Smithsonian Tropical Research Institute. "They can't establish a new nest across more than a short stretch of open water because workers from the original nest have to build and supply the new nest before the new queen moves in." Either several entire tree-cavity nests arrived on Coiba and Rancheria in floating mats of vegetation or a land connection existed between the island and the mainland before the bees disappeared from the mainland. Sea level has risen and fallen dramatically in the past. During ice ages, when much of the Earth's water is locked up in polar caps and glaciers, sea level drops in Panama.