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Odorants May Have Potential in Early Detection of Lung Cancer

Small-molecule volatile organic compounds (odorants) in urine may be useful in diagnosing lung cancer at an early stage, according to results of a mouse study by scientists at the Monell Chemical Senses Center, the Panasonic Corporation, and the University of Pennsylvania. These molecules, which can be perceived as odors (especially by animals), have been shown to function as “signatures” that convey social, emotional, and health information to other members of the species. The results of other studies support the hypothesis that odorants can be detected in the breath of lung cancer patients by smell (dogs were trained to do this, for example) or through bioanalytical techniques such as solid-phase microextraction followed by gas chromatography. Analysis of breath samples, however, is cumbersome and technically challenging, thus limiting its applicability. Lung cancer is the leading cause of cancer-related deaths throughout much of the world, and the only treatment with a high rate of cure is surgical resection of early disease (before metastatic spread occurs). Because only about 25 percent of cases are diagnosed at this early stage, effective early diagnostic techniques are urgently needed. In the current study, the scientists demonstrated that mice can be trained to discriminate between urinary odors of mice with and without experimental lung tumors, demonstrating that odorants are sufficient to identify tumor-bearing mice. Consistent with this result, chemical analyses of urinary odorants demonstrated that the amounts of several compounds were dramatically different between tumor and control mice. These chemical analyses were carried out using solid-phase microextraction followed by gas chromatography combined with mass spectrometry.

Scientists Discover Switch That Turns On Metastasis

A specific protein called disabled-2 (Dab2) switches on the process that releases cancer cells from the original tumor and allows the cells to spread and develop into new tumors in other parts of the body, according to a report by scientists from the Cleveland Clinic, Case Western Reserve University, and collaborating institutions. The process called epithelial-mesenchymal transdifferentiation (EMT) has been known to play a role in releasing cells (epithelial cells) on the surface of a solid tumor and transforming them into transient mesenchymal cells, i.e., cells with the ability to migrate and start to grow a new tumor. This is often the fatal process in breast, ovarian, pancreatic, and colorectal cancers. The researchers knew that transforming growth factor beta (TGF-beta) induces EMT, but they did not know how. In their research, they found that TGF-beta triggers the formation of the Dab2 protein and that it is the Dab2 protein that activates the EMT process. Among the group’s findings was that if Dab2 was knocked out in animal models, EMT did not occur. "If we can understand the signaling pathway for modulating EMT, then we can design drugs to delay or halt EMT cells and control tumor progression," said Dr. Gi Jin, one of the authors of the report. This work was published online on February 14, 2010 in Nature Cell Biology. [Press release] [Nature Cell Biology abstract]

Bacteria-Killing Proteins Address Immune Blind Spot to Blood Type Antigens

A set of proteins found in the human intestine can recognize and kill bacteria that have human blood group antigens on their surfaces, according to collaborating scientists from the Emory University School of Medicine in the United States and the University of Sao Paulo in Brazil. "It's like having a platoon in an army whose sole purpose is to track down enemy soldiers that are wearing the home country's uniforms,” said Emory’s Dr. Richard Cummings, senior author of the report. The potential problem is that the human body’s adaptive immunity system, as a self-protective mechanism, eliminates any of its immune cells that recognize the body’s own blood group antigen type (A, AB, or B). That means that the adaptive immune system is potentially vulnerable to attack by bacteria that express a human blood group antigen on their surfaces. The scientists investigated how humans cope with this potentially dangerous vulnerability. Emory graduate students Connie Arthur and Dr. Sean Sowell identified two particular intestinal proteins (galectin-4 and galectin-8) that kill strains of E. coli that express human blood group antigens on their surfaces. The proteins do not kill E. coli strains that do not express these antigens on their surfaces. The researches further found that the killing activity of both galectin-4 and galectin-8 is mediated by their C-terminal domains, occurs rapidly, takes place independently of complement, and is accompanied by disruption of membrane integrity. "These proteins are separate from antibodies and other parts of the immune system," Dr. Cummings said. "They kill bacteria like E. coli O86 all by themselves within a couple of minutes." The E. coli O86 strain has molecules on its surface like those in humans with blood type B.

Pathway-Targeted Drug Meliorates Cystic Fibrosis in Mice

In a study that could lead to new therapeutic targets for patients with cystic fibrosis (CF), a research team from the University of California-San Diego (UCSD) School of Medicine has identified a defective signaling pathway that contributes to disease severity. The researchers reported that defective signaling for a protein called peroxisome proliferator-activated receptor-γ (PPAR-γ) accounts for a portion of disease symptoms in CF, and that correction of the defective pathway with a PPAR-γ activating drug (rosiglitazone) reduces symptoms of the disease in CF mice. The scientists also showed, in both CF mice and cells from patients with CF, that the defect in signaling for PPAR-γ results from reduced levels of prostaglandins that normally activate the receptor. "The finding of the reduced PPAR-γ activating prostaglandins in CF is exciting since it could serve as a marker to identify which patients might benefit from treatment with PPAR-γ activating drugs," said Dr. Christopher Glass, senior author of the study. CF is reportedly the most common, potentially lethal genetic disease among whites, occurring in one in 3,000 births. The disease is a multisystem condition that leads to progressive lung failure, pancreatic failure, and gastrointestinal obstruction, or blockage. Exactly how the disease process occurs has been a matter of intense scientific investigation; yet despite numerous therapeutic advances, individuals with the disease continue to endure shortened lifespans. "Someone born in the 1990s with CF is expected to live to an age of around 40," said Dr Gregory Harmon, the lead author of the current study. Former NFL quarterback Boomer Esiason (photo) has a son with CF and Mr. Esiason has been very supportive of efforts to treat and cure the disease.

Duck-Tolling Retrievers Yield Genetic Clues to Autoimmune Disease

Genome-wide association studies (GWAS) of DNA from Nova Scotia duck-tolling retrievers (NSDTRs) have identified five genetic loci that predispose this breed to an autoimmune disease similar to systemic lupus erythematosis (SLE) in humans. "We know that SLE in humans is caused by many genes and were therefore not surprised to find several risk factors that contribute to the disease in dogs," said Maria Wilbe, a doctoral candidate at the Swedish University of Agricultural Sciences in Uppsala and lead author of the article. The results provide clues as to where researchers might look for corresponding SLE-related disease genes in humans. The results also demonstrate why dogs can serve as highly useful and efficient models for identifying genes for multigenic diseases and related pathways in humans. "Our results indicate that the homogeneity of strong genetic risk factors within dog breeds allows multigenic disorders to be mapped with fewer than 100 cases and 100 controls, making dogs an excellent model in which to identify pathways involved in human complex diseases," said Dr. Hannes Lohi, of the University of Helsinki and Folkhälsan Research Center in Finland, a co-leader of the project. As the result of two genetic bottlenecks—domestication from the wolf and breed formation--the members of any particular dog breed tend to share much longer stretches of DNA with each other than do members of heterogeneous human populations or even members of relatively homogeneous human sub-populations.

Electron Tunneling-Based DNA Reader Developed

An electron tunneling-based technology for accurately reading the base sequence of DNA molecules has been developed by an Arizona State University (ASU) research team headed by Dr. Stuart Lindsay. This is the first tunneling-based DNA reader that can discriminate among DNA's four bases in one tunnel gap. If the technology can be perfected, DNA sequencing could be performed much more quickly than by current technologies, and at a fraction of the cost. The ASU work was supported, in part, by funding from the National Human Genome Research Institute’s “$1000 Genome” initiative, which is intended to make DNA genome sequencing as widespread as a routine medical checkup, thus helping to usher in the era of “personalized medicine.” The new technology relies on a scanning tunneling microscope and an atomic force microscope, to make its measurements. The microscopes have a delicate electrode tip that is held very close to the DNA sample. In its current innovation over earlier versions, Dr. Lindsay's team made two gold electrodes, one on the end of the microscope probe, and another on the surface, that had their tiny ends chemically modified to attract and catch the DNA between a gap, like a pair of chemical tweezers. The gap between these functionalized electrodes had to be adjusted to find the hydrogen-bonding sweet spot, so that when a single chemical base of DNA passed through a tiny, 2.5-nanometer opening between the two electrodes, it momentarily sticks to the electrodes and a small increase in the current is detected. Any smaller, and the molecules would be able to bind in many configurations, confusing the readout; any larger and smaller bases would not be detected. "What we did was to narrow the number of types of bound configurations to just one per DNA base," said Dr. Lindsay.

First Genes for Stuttering Discovered

Scientists have identified the first three genes ever associated with the phenomenon of stuttering. All three genes are involved in the day-to-day process by which cellular components in key regions of the brain are broken down and recycled by processing in a cell structure called the lysosome. "For hundreds of years, the cause of stuttering has remained a mystery for researchers and health care professionals alike, not to mention people who stutter and their families," said Dr. James F. Battey, Jr., director of the NIH’s National Institute on Deafness and Other Communication Disorders (NIDCD), who was not directly involved in the research. "This is the first study to pinpoint specific gene mutations as the potential cause of stuttering, a disorder that affects three million Americans, and by doing so, might lead to a dramatic expansion in our options for treatment." Stuttering is a speech disorder in which a person repeats or prolongs sounds, syllables, or words, disrupting the normal flow of speech. It can severely hinder communication and a person's quality of life. Most children who stutter will outgrow the problem, although many do not; roughly 1 percent of adults stutter worldwide. Current therapies for adults who stutter have focused on such strategies as reducing anxiety, regulating breathing and rate of speech, and using electronic devices to help improve fluency. Former college and NBA basketball star Bill Walton (photo) suffered from a stuttering problem that he largely overcame and he has subsequently gone on to become a successful TV announcer. Stuttering tends to run in families, and researchers have long suspected a genetic component. Previous studies of stuttering in a group of families from Pakistan have been performed by Dr.

Genome of Ancient Human Is Sequenced

Using sophisticated DNA sequencing technology and powerful data analysis tools, an international team has succeeded in sequencing approximately 80 percent of the genome of a 4,000-year-old sample from a man who lived in Greenland and belonged to an extinct culture (Saqqaq) that was the first to settle in the New World Arctic. The sequencing was achieved using DNA obtained from a permafrost-preserved tuft of hair. According to the research team, led by Dr. Eske Willerslev and his graduate student Morten Rasmussen at the University of Copenhagen’s Centre of Excellence in GeoGenetics, this marks the first time that a detailed reconstructed genome of an ancient human has been published. The scientists have named the ancient human "Inuk," which means "man" or "human" in Greenlandic. The genome sequence serves as a blueprint that scientists can use to give a description of how the pre-historic Greenlander looked--including his tendency to baldness, dry earwax, brown eyes, dark skin, the blood type A+, shovel-shaped front teeth, and that he was genetically adapted to cold temperatures, and to what extent he was predisposed to certain illnesses. This is important as, aside from four small pieces of bone and hair, no human remains have been found of the first people that settled the New World Arctic. Dr. Willerslev's team was also able to determine that Inuk's ancestors crossed into the New World from north-eastern Siberia between 4,400 and 6,400 years ago in a migration wave that was independent of those of Native Americans and Inuit ancestors. Thus, Inuk and his people left no dependents behind among contemporary indigenous people of the New World. “Our findings can be of significant help to archaeologists and others as they seek to determine what happened to people from extinct cultures,” Dr. Willerslev said.

Owls Chattier on Moonlit Nights

An international team of scientists from Spain, Finland, and Portugal recently discovered that eagle owls (Bubo bubo) communicate with each other using a patch of white throat plumage that is repeatedly exposed during each call and is only visible during vocal displays. The scientists found that the owls use moonlight to increase the conspicuousness of this visual signal during their call displays. Call displays were found to be directly influenced by the amount of moonlight, with silent nights being more frequent during periods with no moonlight versus those with moonlight. Furthermore, high numbers of calling bouts were more frequent at moonlight. Finally, call posts were located on higher positions on moonlit nights. The researches said that their results support the idea that moon phase affects the visual signaling behavior of this species, and provide a starting point for examination of this method of communication by nocturnal species. This work was reported on January 20, 2010, in PLoS ONE. [PLoS ONE article]

Bees Prefer Nicotine and Caffeine in Nectar

Bees prefer nectar with small amounts of nicotine and caffeine over nectar that does not contain these substances at all, according to results of a recent study from the University of Haifa in Israel. “This could be an evolutionary development intended, as in humans, to make the bee addicted,” stated Dr. Ido Izhaki, one of the researchers who conducted the study. The researchers emphasized, however, that their study has proved a preference, not an addiction, and they are currently conducting additional studies to determine if bees do indeed become addicted to nicotine and caffeine. Flower nectar is primarily composed of sugars, which provide energy for the potential pollinators. But the floral nectar of some plant species also includes small quantities of substances known to be toxic, such as caffeine and nicotine. Nicotine is found naturally in floral nectar at a concentration of up to 2.5 milligrams per liter, primarily in various types of tobacco trees. Caffeine is found at concentration levels of 11-17.5 milligrams per liter, mostly in citrus flowers. In the nectar of grapefruit flowers, however, caffeine is present in much higher concentrations, reaching 94.2 milligrams per liter. In order to examine whether bees prefer the nectar containing caffeine and nicotine, the researchers offered artificial nectar that contained various natural sugar levels and various levels of caffeine and nicotine, alongside “clean” nectar that included sugar alone. The caffeine and nicotine concentrations ranged from the natural levels in floral nectar up to much higher concentrations than found in nature. The results showed that bees clearly prefer nectar containing nicotine and caffeine over the “clean” nectar. The preferred nicotine concentration was 1 milligram per liter, similar to that found in nature.

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