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March 16th, 2011

Bacteria More Likely to Adopt “Loner” Genes

A new study of more than three dozen bacteria species — including the microbes responsible for pneumonia, meningitis, stomach ulcers and plague — settles a longstanding debate about why bacteria are more likely to steal some genes than others. While most organisms get their genes from their parents just as people do, bacteria and other single-celled creatures also regularly pick up genes from more distant relatives. This ability to 'steal' snippets of DNA from other species — known as lateral gene transfer — is responsible for the rapid spread of drug resistance among disease-causing bacteria. "By understanding why some genes are more likely to spread from one species to the next, we can better understand how new virulent bacterial strains emerge," said co-author Dr. Tal Pupko, a visiting scientist at the National Evolutionary Synthesis Center in Durham, North Carolina. Scientists have proposed several theories to explain why some bacterial genes are more likely to jump into other genomes. One theory, Dr. Pupko explained, is that it depends on what the gene does in the cell. Genes involved in core functions, like converting RNA into protein, are much less likely to make the leap. "If a species already has the basic molecular machinery for transcription and translation, there's no advantage to taking in another set of genes that do the same thing," Pupko said. Other studies suggest it's not what the gene does that matters, but how many proteins it interacts with – a network researchers have dubbed the 'interactome.' Genes involved in transcription and translation, for example, must work in concert with many partners to do their job.

March 16th

Using Light to Move Molecules in Living Cells

Using a light-triggered chemical tool, Johns Hopkins scientists report that they have refined a means of moving individual molecules around inside living cells and sending them to exact locations at precise times. This new tool, they say, gives scientists greater command than ever in manipulating single molecules, allowing them to see how molecules in certain cell locations can influence cell behavior and to determine whether cells will grow, die, move or divide. A report on the work was published in the January 12, 2011 issue of the Journal of the American Chemical Society. Studying how just one signaling molecule communicates in various parts of a living cell has posed a challenge for scientists investigating how different interactions influence cell behavior, such as the decision to move, change shape or divide. "By using one magical chemical set off by light, we modified our previous technique for moving molecules around and gained much more control," said Dr. Takanari Inoue, assistant professor of cell biology and member of the Center for Cell Dynamics in the Institute for Basic Biomedical Sciences. "The advantage of using light is that it is very controllable, and by confining the light, we can manipulate communication of molecules in only a tiny region of the cell," he said. Specifically, the Hopkins team designed a way to initiate and spatially restrict the molecular interactions to a small portion of the cell by attaching a light-triggered chemical to a bulky molecule, the bond between which would break when researchers shined a defined beam of ultraviolet light on it. This enabled the chemical to enter the cell and force two different and specific proteins in that cell to mingle when they otherwise wouldn't.

Nanopolymer Used to Screen for Kinase Inhibitors

A Purdue University scientist's nanopolymer would make it easier and cheaper for drug developers to test the effectiveness of a widely used class of cancer inhibitors (kinase inhibitors). Dr. W. Andy Tao, an associate professor of biochemistry analytical chemistry and a member of the Purdue Center for Cancer Research team, created the Purdue-patented pIMAGO nanopolymer that can be used to determine whether cancer drugs have been effective against biochemical processes that can lead to cancer cell formation. The nanopolymers would attach themselves to target proteins that would later be detected by a relatively simple laboratory procedure called chemiluminescence. Tymora Analytical, a company Tao started in the Purdue Research Park, will manufacture the pIMAGO nanopolymers. The 'p' stands for phosphor, and the IMAGO comes from the Greek word for image. Tao's pIMAGO nanopolymers are coated in titanium ions and would attract and bond with phosphorylated proteins, ones in which a phosphate group has been added to a protein activating an enzyme called kinase. Kinase, when overactive, is known to cause cancer cell formation, and many cancer drugs are aimed at inhibiting kinase activity. “It is universal. You can detect any kind of phosphorylation in a protein," said Tao, whose findings were reported online on March 11, 2011, in the journal Analytical Chemistry. "It is also cheaper and would be more widely available." The nanopolymers would be added to a solution of proteins, a chemical agent to start phosphorylation and a drug to inhibit kinase activity. Phosphorylated proteins would only be present if the drug is ineffective. Avidin-HRP - the protein Avidin bound with the enzyme horseradish peroxidase - would be added. Avidin would bind with a vitamin B acid called biotin that is also on the nanopolymers' surfaces.

Some Blind “See” with Their Ears

Dr. Olivier Collignon of the University of Montreal's Saint-Justine Hospital Research Centre compared the brain activity of people who can see and people who were born blind, and discovered that the part of the brain that normally works with our eyes to process vision and space perception can actually rewire itself to process sound information instead. The research was undertaken in collaboration with Dr Franco Lepore of the Centre for Research in Neuropsychology and Cognition and was published in the March 15, 2011 issue of PNAS. The research builds on other studies which show that the blind have a heightened ability to process sounds as part of their space perception. "Although several studies have shown occipital regions of people who were born blind to be involved in nonvisual processing, whether the functional organization of the visual cortex observed in sighted individuals is maintained in the rewired occipital regions of the blind has only been recently investigated," Dr. Collignon said. The visual cortex is responsible for processing sight. The right and left hemisphere of the brain have one each. They are located at the back of the brain, which is called the occipital lobe. "Our study reveals that some regions of the right dorsal occipital stream do not require visual experience to develop a specialization for the processing of spatial information and are functionally integrated in the preexisting brain network dedicated to this ability." The researchers worked with 11 individuals who were born blind and 11 who were not. Their brain activity was analyzed via MRI scanning while they were subjected to a series of tones. "The results demonstrate the brain's amazing plasticity," Dr. Collignon said.

March 14th

Jagged2 Binding Drives Metastasis in Lung Cancer Study

Researchers have discovered a new, key component in the spread of lung cancer as well as a likely way to block it with drugs now in clinical trial. The study was published on March 14, 2011, in the Journal of Clinical Investigation. A team led by scientists at The University of Texas MD Anderson Cancer Center found a way to identify metastasis-prone lung cancer cells and then uncovered a mechanism that shifts primary tumor cells into a more deadly type of cell with the capacity to move elsewhere in the body. "We think tumors have to learn how to metastasize because they can't do it initially," said paper senior author Dr. Jonathan Kurie, professor in MD Anderson's Department of Thoracic/Head and Neck Medical Oncology. "Cells change in response to cues from their external environment." About 90 percent of all cancer deaths are caused by metastasis - the spread to, and invasion of, other organs. Lung cancer is the leading cause of cancer-related death in the United States, accounting for more than 157,000 deaths annually. The median five-year survival rate is 3.5%. The researchers found that when a protein called Jagged2 binds externally to Notch, a membrane protein that sticks out through the surface of a cell, it suppresses a microRNA that thwarts metastasis inside the cell. "Jagged2 suppresses miR-200 and drives metastasis as a consequence." Dr. Kurie said. "It's been known for some time that Notch is involved in cancer, but no one really knew how." Two Notch inhibitors are in clinical trial at MD Anderson. "These drugs might suppress the ability of primary tumors to metastasize," Dr. Kurie said. "One question is who is supposed to get these drugs," Dr. Kurie said.

Orchid Lures Prey with Scent of Death

Research led by Dr. Timotheüs van der Niet at the University of KwaZulu-Natal in South Africa shows that the South African orchid Satyrium pumilum lures flies into its flowers by mimicking the smell of rotting flesh. A new study comparing the scent of the orchids with that of roadkill was published online on March 13, 2011, in the Annals of Botany. The orchid S. pumilum is found in sandy, moist conditions near small streams across the Cape floral kingdom of South Africa. The flowers are a puzzle. They don't carry any nectar and even if they did, the spurs that would hold it are the wrong shape to feed any visitors. So how do they attract insects to pollinate their flowers? Dr. Van der Niet said: "We know it's common for orchids to deceive insects into pollinating them. We also know that some plant species can mimic carrion to attract flies. What we didn't know was how successful this was. Mimicry is often a very poor way to pollinate a plant. So we set out to observe the plants in the wild and see if we could work out how they were attracting flies." The team staked out a region of farmland with many of the orchids on it. They then went about finding carrion for a comparison. Dr. Van der Niet said: "We didn't kill creatures to entice the flies. Instead we used dassies (rock hyraxes). They're small animals and they look a little like a guinea pig. You can find them almost anywhere in South Africa, and that means you can also find them as roadkill. So we examined the flies visiting the dead dassies, and compared them to the flies visiting the orchids. Because of the high density of orchids we didn't see many flies visiting the flowers, but on the nearby dassie carcass we caught a lot of flies carrying orchid pollen, providing ample 'smoking gun' evidence of how common this interaction was.

Taking Tamoxifen to Prevent Breast Cancer Can Save Lives

Tamoxifen, taken by certain women as a preventive measure against breast cancer, saves lives and reduces medical costs. That is the conclusion of a new study published online on March 14, 2011, in Cancer, a peer-reviewed journal of the American Cancer Society. The study's results suggest that the benefits of tamoxifen to prevent cancer can sufficiently compensate for its side effects in post-menopausal women under age 55 years who have an increased risk of developing breast cancer. Research has shown that tamoxifen can protect against breast cancer for years after treatment ends, but identifying the group of women who can most benefit from the drug as a cancer preventive agent, without experiencing serious side effects, is a challenge. Side effects of the drug can include pulmonary embolism, endometrial cancer, deep vein thrombosis, and cataracts, as well as hot flashes and early menopause. To investigate those women who would benefit the most from taking tamoxifen as a cancer preventive drug, Dr. Peter Alperin, of Archimedes, Inc., in San Francisco, and his colleagues used a mathematical model to simulate a post-menopausal population under age 55 years in a virtual clinical trial comparing tamoxifen treatment with no treatment. The investigators modeled tamoxifen therapy based on an analysis of four randomized, placebo-controlled cancer prevention trials, and they assessed the effects that tamoxifen would have on women's breast cancer risk for 10 years following the end of treatment. Cancer incidences and survival information were taken from the Surveillance Epidemiology and End Results cancer registry, while factors such as non-cancer disease incidences, quality of life, and costs were taken from the medical literature.

March 13th

Single Cell Sequencing Suggests Tumors Evolve in Staccato-Like Bursts

A new method of analyzing cancerous tumors developed by scientists at Cold Spring Harbor Laboratory (CSHL) suggests that tumors may not evolve gradually, but rather in punctuated or staccato-like bursts. It is a finding that has already shed new light on the process of tumor growth and metastasis, and may help in the development of new methods to clinically evaluate tumors. The new analytic method, devised by CSHL Professor Michael Wigler and colleagues, features a process called single cell sequencing (SNS), which enables accurate quantification of genomic copy number within a single cell nucleus. In cancer, portions of the genome are amplified or deleted, giving rise to extra or missing copies of key genes and interfering with mechanisms that normally control cell growth. In a study published online on March 13, 2011, in the journal Nature, "we demonstrated that we can obtain accurate and high-resolution copy number profiles by sequencing a single cell from a cancerous tumor," said Dr. Wigler, "and that by examining multiple cells from the same cancer, we can make inferences about how the cancer evolved and spread." The CSHL team also included Professor W. Richard McCombie, Assistant Professor Alex Krasnitz and Research Professor James Hicks. Nicholas Navin, the paper's first author, was a graduate student while pursuing the research at CSHL and is now Assistant Professor at the MD Anderson Cancer Center in Texas. It has been very difficult for scientists to translate their growing ability to classify tumors at the molecular level into methods and tests that can be used in the clinic to analyze tumors in actual patients.

Major Breakthrough in Materials Design for Hydrogen Storage

Since the 1970s, hydrogen has been touted as a promising alternative to fossil fuels due to its clean combustion —unlike hydrocarbon-based fuels, which spew greenhouse gases and harmful pollutants, hydrogen's only combustion by-product is water. Compared to gasoline, hydrogen is lightweight, can provide a higher energy density, and is readily available. But there's a reason we're not already living in a hydrogen economy: to replace gasoline as a fuel, hydrogen must be safely and densely stored, yet easily accessed. Limited by materials unable to leap these conflicting hurdles, hydrogen storage technology has lagged behind other clean energy candidates. In recent years, researchers have attempted to tackle both issues by locking hydrogen into solids, packing larger quantities into smaller volumes with low reactivity—a necessity in keeping this volatile gas stable. However, most of these solids can only absorb a small amount of hydrogen and require extreme heating or cooling to boost their overall energy efficiency. Now, scientists with the U.S. Department of Energy (DOE) Lawrence Berkeley National Laboratory (Berkeley Lab) have designed a new composite material for hydrogen storage consisting of nanoparticles of magnesium metal sprinkled through a matrix of polymethyl methacrylate, a polymer related to Plexiglas. This pliable nanocomposite rapidly absorbs and releases hydrogen at modest temperatures without oxidizing the metal after cycling—a major breakthrough in materials design for hydrogen storage, batteries, and fuel cells. "This work showcases our ability to design composite nanoscale materials that overcome fundamental thermodynamic and kinetic barriers to realize a materials combination that has been very elusive historically," said Dr.

Rhodopsin May Also Be Involved in Temperature Sensation

New research from the Mount Sinai School of Medicine has revealed that rhodopsin, a pigment of the retina that is responsible for the first events in the perception of light, may also be involved in temperature sensation. This detection had not been revealed in previous studies. The work emerged from a collaboration between the laboratory of Dr. Andrew Chess, Professor in the Departments of Neuroscience, Developmental and Regenerative Biology and Genetics and Genomic Sciences at Mount Sinai, and the laboratory of Dr. Craig Montell, Professor of Biological Chemistry at Johns Hopkins School of Medicine. Their paper is published in the March 11 issue of Science. The research focused on rhodopsin in Drosophila larvae. The temperature-detection function of rhodopsin allows the Drosophila larvae to move to their preferred temperature of 18 degrees Celsius (64.4 degrees Fahrenheit). This ability depends on a thermosensory signaling pathway that includes a heterotrimeric guanine nucleotide-binding protein, or G-protein. "It is very surprising that rhodopsin has a role in temperature sensation, as it was thought to be completely devoted to its well-known role as a light sensor," said Dr. Chess. "This function of rhodopsin allows temperature discrimination in the comfortable range." This new role for rhodopsin emerged from studies of the process that results in the activation of a temperature-sensor protein known as a TRPA1, which Dr. Montell's group has been studying. The researchers released about 75 larvae onto a plate with two temperature zones. Half of the plate was kept at 18 degrees Celsius and the other half ranged from 14 to 32 degrees Celsius. After ten minutes, the larvae lacking rhodopsin could not discriminate temperatures in comfortable range, just like the larvae lacking TRPA1.