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Archive - Dec 2011

Date

December 5th

Rarest US Bumblebee Rediscovered

A team of scientists from the University of California (UC), Riverside, recently rediscovered the rarest species of bumblebee in the United States (last seen in 1956) living in the White Mountains of south-central New Mexico. Known as "Cockerell's Bumblebee," the bee was originally described in 1913 from six specimens collected along the Rio Ruidoso, with another 16 specimens collected near the town of Cloudcroft, and one more from Ruidoso, the most recent being in 1956. No other specimens had been recorded until three more were collected on weeds along a highway north of Cloudcroft on Aug. 31, 2011. "Most bumblebees in the US are known from dozens to thousands of specimens, but not this species," said Dr. Douglas Yanega, senior museum scientist at UC Riverside. "The area it occurs in is infrequently visited by entomologists, and the species has long been ignored because it was thought that it was not actually a genuine species, but only a regional color variant of another well-known species." Dr. Yanega pointed out that there are nearly 50 species of native US bumblebees, including a few on the verge of extinction, such as the species known as "Franklin's Bumblebee," which has been seen only once since 2003. That species, as rare as it is, is known from a distribution covering some 13,000 square miles, whereas Cockerell's Bumblebee is known from an area of less than 300 square miles, giving it the most limited range of any bumblebee species in the world. "There is much concern lately about declines in our native bumblebee species, and as we now have tools at our disposal to assess their genetic makeup, these new specimens give fairly conclusive evidence that Cockerell's Bumblebee is a genuine species," he said. "With appropriate comparative research, we hope to be able to determine which other species is its closest living relative.

Progress Made Toward Vaccine for Ebola Virus

On August 26, 1976, a time bomb exploded in Yambuku, a remote village in Zaire (now the Democratic Republic of the Congo). A threadlike virus known as Ebola had emerged, soon earning grim distinction as one of the most lethal, naturally occurring pathogens on earth, killing up to 90 percent of its victims, and producing a terrifying constellation of symptoms known as hemorrhagic fever. Now, Dr. Charles Arntzen, a researcher at the Biodesign Institute® at Arizona State University (ASU), along with colleagues from ASU, the University of Arizona College of Medicine-Phoenix, and the United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, have made progress toward a vaccine against the deadly virus. The group's research results appear online on December 5, 2011 in the Proceedings of the National Academy of Science, along with a companion paper by their collaborators at Mapp Pharmaceuticals in San Diego, California, led by Dr. Larry Zeitlin. Dr. Arntzen's group demonstrated that a plant-derived vaccine for Ebola provided strong immunological protection in a mouse model. If early efforts bear fruit, an Ebola vaccine could be stockpiled for use in the United States, should the country fall victim to a natural outbreak or a bioterrorism event in which a weaponized strain of the virus were unleashed on soldiers or the public. To date, Ebola outbreaks have been mercifully rare. For researchers like Dr. Arntzen however, this presents a challenge: "With other lethal viruses like HIV, there is a common pattern of occurrence, allowing for vaccine testing. For example, an AIDS vaccine study is now underway at two locations in Thailand, which were chosen because of a current high incidence of the disease." By contrast, Ebola events are fleeting, episodic, and largely unpredictable. For this reason, Dr.

Streamlined Approach for Reconstructing Accurate DNA Sequence

Researchers at the Genome Institute of Singapore (GIS) have, for the very first time, developed a computational tool that comes with a guarantee on its reliability when reconstructing the DNA sequence of organisms, thus enabling a more streamlined process for reconstructing and studying genomic sequences. The work, lead by Dr. Niranjan Nagarajan, Assistant Director of Computational and Mathematical Biology at the GIS, was reported in the November 10, 2011 issue of the Journal of Computational Biology. The genomic study of life (plants and animals alike) is based on computational tools that can first piece together the DNA sequence of these organisms, a process called genome assembly, that is similar to solving a giant puzzle or putting together the words in a book from a shredded copy. Due to the sheer scale of this challenge, existing approaches for genome assembly rely on heuristics and often result in incorrect reconstructions of the genome. The work reported here represents the first algorithmic solution for genome assembly that provides a quality guarantee and scales to large datasets. A new and improved implementation for this algorithm called Opera is now freely available at http://sourceforge.net/projects/operasf/ and has been used at the GIS for successfully assembling large plant and animal genomes. The assembled genome of an organism forms the basis for a range of downstream biological investigations and serves as a critical resource for the research community. The draft human genome, for example, was obtained at the expense of billions of dollars, serves as a fundamental resource for biomedical research and is, in fact, still being refined.

Orphan Experiences Alter Genome Function

Children who experience the stress of separation at birth from biological parents and are brought up in orphanages undergo biological consequences such as changes in their genome functioning, Yale School of Medicine researchers report in a new study. Published online on November 29, 2011 in Development and Psychopathology, the study reports differences in DNA methylation, one of the main regulatory mechanisms of gene expression, or genome functioning. The investigators compared two cohorts: 14 children raised since birth in institutional care and 14 children raised by their biological parents. Senior author Dr. Elena Grigorenko, associate professor at the Yale Child Study Center, and her colleagues took blood samples from children aged 7 to 10 living in orphanages and children growing up in typical families in the northwest region of the Russian Federation. The researchers then profiled the genomes of all the children to identify which biological processes and pathways might be affected by deprivation of parental attention and care. The team found that in the institutionalized group, there was a greater number of changes in the genetic regulation of the systems controlling immune response and inter-cellular interactions, including a number of important mechanisms in the development and function of the brain. "Our study shows that the early stress of separation from a biological parent impacts long-term programming of genome function; this might explain why adopted children may be particularly vulnerable to harsh parenting in terms of their physical and mental health," said Dr. Grigorenko.

December 4th

Inhibitors of Ras Oncoprotein Identified by Genentech Researchers

A drug discovery team at Genentech, Inc., has uncovered a chink in the molecular armor of Ras, the most commonly occurring oncogene, which is a gene that when mutated has the potential of causing cancer in humans. The chink, a binding pocket of "functional significance" on the Ras oncoprotein, could provide the long-sought attack point for a therapeutic agent, making the previously "undruggable" Ras oncogene "druggable," the researchers reported on December 4, 2011 at the American Society for Cell Biology's 51st Annual Meeting in Denver, Colorado. The first human oncogene to be identified, Ras is mutated in about 25% of all human tumors. For cancer patients, the presence of an activated Ras oncogene is a marker for poor prognosis. Ras has a molecular on-off switch, activated by the energy transfer molecule GTP. In the "on" position, the oncogene activates critical cell signaling pathways involving cell proliferation, cell migration, and cell differentiation, all of which are in hyper-drive in tumors. To develop a drug that would switch Ras off, scientists needed a binding site, an opening in the Ras oncoprotein to which the docking mechanism of a therapeutic molecule could attach. At the ASCB meeting, Drs. Joachim Rudolph, Weiru Wang, and Guowei Fang, of Genentech, a member of the Roche Group, reported that they identified such a binding pocket by fragment-based lead discovery, a screening process that sorted through 3,300 small molecule compounds. Nuclear magnetic resonance (NMR) spectroscopy was used to pinpoint molecules with even a weak affinity for binding to Ras oncoproteins. The researchers identified 25 compounds, none of which knocked out the oncoprotein. However, NMR spectroscopy revealed that the 25 compounds were binding to the same location on the Ras oncoprotein.

December 3rd

Small Molecule Shows Activity Against Many Sarcomas

MK 1775, a small, selective inhibitor molecule, has been found to be active against many sarcomas when tested by researchers at Moffitt Cancer Center in Tampa, Florida. Their findings, appearing online on November 14, 2011 in Molecular Cancer Therapeutics, published by the American Association for Cancer Research, suggest that a badly needed new agent against sarcomas - especially sarcomas affecting children - may be at hand. According to corresponding author Dr. Soner Altiok, sarcomas are rare forms of cancers and comprise more than 70 types. Approximately 10 percent of children with cancer are diagnosed with sarcomas, compared to eight percent of young adults and one percent of adults. While chemotherapy and radiation play a role in treating some sarcoma patients, escalations of treatment are unlikely to be tolerable, nor will they prolong survival, said the researchers. "There is a great need for new agents to treat sarcomas and improve patient outcomes," said Dr. Altiok. "Toxicity from radiation and chemotherapy is high and response rates for patients with sarcomas are modest, with improvement and survival negligible." Sarcomas are cancers that result from transformed cells in one of a number of tissues that develop from embryonic mesoderm. Sarcomas include tumors of bone, cartilage, fat, muscle, vascular and hematopoetic tissues. Sarcomas are different from carcinomas that originate in epithelial cells and result in more common cancers, such as breast, colon, and lung cancers. Researchers from Moffitt's Experimental Therapeutics Program and the Sarcoma Program collaborated in testing MK1775's ability to inhibit Wee1, a nuclear kinase known to be a regulator of cell size and an initiator of cell division, or mitosis. Wee1 is known to play a role in determining the timepoint at which mitosis begins.

December 1st

New Insights into Causes of Fatal Lung Disease (IPF)

Tracking individual cells within the lung as they move around and multiply has given Duke University researchers new insights into the causes of idiopathic pulmonary fibrosis (IPF) a disease that can only be treated now by lung transplantation. IPF fills the delicate gas exchange region of the lung with scar tissue, progressively restricting breathing. The Duke University Medical Center researchers have discovered that some commonly held ideas about the origins of the scar-forming (fibrotic) cells are oversimplified, if not wrong. “We are the first to show that pericytes, a population of cells previously described to play a role in the development of fibrosis in other organs, are present in fibrotic lung tissue,” said Dr. Christina Barkauskas, a pulmonary fellow in the Duke Division of Pulmonary, Allergy, and Critical Care Medicine. The team found that pericytes move from blood vessels into fibrotic regions, and were in the damaged lungs of both humans and mice. In mice, they also showed that the epithelial cells, which make up the lacy sacs called alveoli, could divide and repair the damage in the gas-exchange location, but these cells were not the source of scarring. IPF affects about 100,000 people in the U.S. each year and leads to death within three years of diagnosis. The study was published online on November 28, 2011 in PNAS. “We don’t know yet whether the pericytes make the scar matrix itself or just release signals that stimulate the scarring process, but either way, they are a potential target for new therapies,” said Dr. Brigid Hogan, senior author and chair of the Duke Department of Cell Biology. The researchers used genetic lineage tracing to study the origin of cells that gathered in fibrotic areas. They gave several different cell types an indelible fluorescent tag and then followed the cells over time.