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Archive - 2012

August 31st

Possible Therapy for Tamoxifen-Resistant Breast Cancer Identified

A study by researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) has discovered how tamoxifen-resistant breast-cancer cells grow and proliferate. It also suggests that an experimental agent might offer a novel targeted therapy for tamoxifen-resistant breast cancer. Like a second door that opens after the first door closes, a signaling pathway called hedgehog (Hhg) can promote the growth of breast-cancer cells after tamoxifen shuts down the pathway activated by the hormone estrogen. A second signaling pathway, called PI3K/AKT, is also involved. Activation of the Hhg pathway renders tamoxifen treatment ineffective and enables the tumor to resume its growth and progression. As part of the study, the researchers analyzed over 300 human tumors and found that the tumors with an activated Hhg pathway had a worse prognosis. Finally, the researchers showed that an experimental drug called vismodegib, which blocks the Hhg pathway, inhibits the growth of tamoxifen-resistant human breast tumors in an animal model. The drug is currently in clinical trials testing for other types of cancer. Currently, chemotherapy is used to treat hormone-resistant breast cancers, but this is associated with significant side effects. This study has identified targeted therapies that could be an alternative to chemotherapy for these resistant tumors. The study was published online on August 8, 2012 in Cancer Research. “Our findings suggest that we can target this pathway in patients with estrogen-receptor breast cancers who have failed tamoxifen therapy,” says first author Dr. Bhuvaneswari Ramaswamy, a medical oncologist specializing in breast cancer at the OSUCCC – James.

August 30th

Bacteria in Hyena Scent Glands Key to Group-Specific Social Odors

The results, published online on August 30, 2012 in Scientific Reports, a Nature publication, show a clear relationship between the diversity of hyena clans and the distinct microbial communities that reside in their scent glands, said Dr. Kevin Theis, the paper’s lead author and a Michigan State University (MSU) postdoctoral researcher. “A critical component of every animal’s behavioral repertoire is an effective communication system,” said Dr. Theis, who co-authored the study with Dr. Kay Holekamp, an MSU zoologist. “It is possible that without their bacteria, many animals couldn’t ‘say’ much at all.” This is the first time that scientists have shown that different social groups of mammals possess different odor-producing bacterial communities. These communities produce unique chemical signatures, and the hyenas can distinguish among them by using their noses. Past research has demonstrated important roles played by microbes in digestion and other bodily functions. It’s also widely known that most mammals use scent to signal a wide range of traits, including sex, age, reproductive status, and group membership. This study details bacteria living in a mutually beneficial relationship with their hyena hosts. It also highlights the contribution of new DNA sequencing technologies showcasing the role good, symbiotic bacteria play in animal behavior. On the grassy Kenyan plains, Dr. Theis gathered information about the bacterial types present in samples of paste, a sour-smelling secretion that hyenas deposit on grass stalks. Field samples were collected from hyenas’ scent pouches and analyzed using next-generation sequence (NGS) technology back at MSU labs. The samples revealed a high degree of similarities, microbial speaking, between deposits left by members of the same clans.

Protein Linked to Increased Risk of Heart Failure/Death in Older Adults

A protein known as galectin-3 can identify people at higher risk of heart failure, according to new research supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. This research is based on work from the NHLBI's Framingham Heart Study, which began in 1948 and has been the leading source of research findings about heart disease risk factors. The article was published online on August 29, 2012 in the Journal of the American College of Cardiology and will also be published in the October 2, 2012 print issue of the same journal. Heart failure occurs when the heart cannot fill with enough blood and/or pump enough blood to meet the body's needs. Galectin-3 has recently been associated with cardiac fibrosis, a condition in which scar tissue replaces heart muscle, and cardiac fibrosis plays an important role in the development of heart failure. Heart failure carries enormous risk for death or a lifetime of disability and often there are few warning signs of impending heart failure. Measuring levels of galectin-3 in the blood may offer a way to identify high-risk individuals who could benefit from treatments to prevent debilitating heart failure and death. Early identification of predisposed individuals would allow treatment to begin long before heart failure develops and could help people at high risk for heart failure to live longer, more active lives. Galectin-3 levels were measured in 1996-1998 as part of a routine examination of 3,353 participants enrolled in the Offspring Cohort of the Framingham Heart Study. At the time of measurement, the average age of the participants was 59 years old. During an average follow-up of 11 years, 166 participants (5.1 percent) had a first heart failure event.

Max Planck Researchers Describe Ancient Denisovan Genome

The analyses of an international team of researchers led by Dr. Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, show that the genetic variation of Denisovans was extremely low, suggesting that although they were present in large parts of Asia, their population was never large for long periods of time. In addition, a comprehensive list documents the genetic changes that set modern humans apart from their archaic relatives. Some of these changes concern genes that are associated with brain function or nervous system development. In 2010, Dr. Pääbo and his colleagues sequenced DNA that they isolated from a finger bone fragment discovered in the Denisova Cave in southern Siberia. They found that it belonged to a young girl of a previously unknown group of archaic humans that they called “Denisovans.” Thanks to a novel technique which splits the DNA double helix so that each of its two strands can be used for sequencing, the team was able to sequence every position in the Denisovan genome about 30 times over. The thus-generated genome sequence shows a quality similar to genomes that have been determined from present-day humans. In a new study, which was published online on August 30, 2012 in Science, Dr. Pääbo and his colleagues compare the Denisovan genome with those of the Neandertals and eleven modern humans from around the world. Their findings confirm a previous study according to which modern populations from the islands of southeastern Asia share genes with the Denisovans.

August 27th

Over 40 Plant-Based Compounds Found That Slow Metastasis

More than 40 plant-based compounds can turn on genes that slow the spread of cancer, according to a first-of-its-kind study by a Washington State University (WSU) researcher. Dr. Gary Meadows, WSU professor and associate dean for graduate education and scholarship in the College of Pharmacy, says he is encouraged by his findings because the spread of cancer is most often what makes the disease fatal. Moreover, says Dr. Meadows, diet, nutrients, and plant-based chemicals appear to be opening many avenues of attack. "We're always looking for a magic bullet," he says. "Well, there are lots of magic bullets out there in what we eat and associated with our lifestyle. We just need to take advantage of those. And they can work together." Dr. Meadows started the study, published in the June 2012 issue of Cancer and Metastasis Reviews, with some simple logic: Most research focuses on the prevention of cancer or the treatment of the original cancer tumor, but it's usually the cancer's spread to nearby organs that kills you. So rather than attack the tumor, said Dr. Meadows, let's control its spread, or metastasis. He focused in particular on genes that suppress metastasis. As search engine terms go, it took him down many a wormhole in the PubMed research database, as the concept of nutrients and metastasis suppressor genes is rarely identified by journals. It's even an afterthought of some of the researchers who find the genes. "People for the most part did not set out in their research goals to study metastasis suppressor genes," says Dr. Meadows. "It was just a gene that was among many other genes that they had looked at in their study." But Dr. Meadows took the studies and looked to see when metastasis suppressor genes were on or off, even if original authors didn't make the connection.

August 17th

Test Vaccine Protects Monkeys from Nipah Virus

Researchers have successfully tested in monkeys a vaccine against Nipah virus, a human pathogen that emerged in 1998 during a large outbreak of infection and disease among pigs and pig farmers in Southeast Asia. This latest advance builds upon earlier work by the scientists, who found that the same vaccine can protect cats from Nipah virus and ferrets and horses from the closely related Hendra virus. The latest work was published online on Agust 8, 2012 in Science Translational Medicine. Both viruses have a high fatality rate in humans—more than 75 percent for Nipah and 60 percent for Hendra. Infections by these viruses target the lungs and brain, and disease outbreaks have occurred regularly in the past decade. Nipah outbreaks have occurred in Malaysia, Singapore, Bangladesh, and India. Hendra outbreaks have remained confined to Australia since its emergence there in horses and humans in 1994. Certain fruit bats, also known as flying foxes, spread the viruses; so far, only Nipah is known to spread from person-to-person. The research group developed a vaccine based on a Hendra virus surface protein, the G glycoprotein, a known target for triggering a protective host immune response. In this study, they used the recently developed African green monkey model of Nipah disease to test three different doses of the vaccine in combination with an adjuvant. All nine vaccinated animals survived a lethal Nipah virus challenge given 42 days after the initial vaccination. Christopher Broder, Ph.D., of the Uniformed Services University of the Health Sciences (USU) and Katharine Bossart, Ph.D., a former USU graduate student now at Boston University, developed the vaccine.

August 14th

Artificial Retina with Neural Code Restores Sight to Blind Mice

Two researchers at Weill Cornell Medical College in New York City have deciphered a mouse's retina's neural code and coupled this information to a novel prosthetic device to restore sight to blind mice. The researchers say they have also cracked the code for a monkey retina — which is essentially identical to that of a human —and hope to quickly design and test a device that blind humans can use. The breakthrough, reported online on August 13, 2012 in PNAS, signals a remarkable advance in longstanding efforts to restore vision. Current prosthetics provide blind users with spots and edges of light to help them navigate. This novel device provides the code to restore normal vision. The code is so accurate that it can allow facial features to be discerned and allow animals to track moving images. The lead researcher, Dr. Sheila Nirenberg, a computational neuroscientist at Weill Cornell, envisions a day when the blind can choose to wear a visor, similar to the one used on the television show Star Trek. The visor's camera will take in light and use a computer chip to turn it into a code that the brain can translate into an image. "It's an exciting time. We can make blind mouse retinas see, and we're moving as fast as we can to do the same in humans," says Dr. Nirenberg, a professor in the Department of Physiology and Biophysics and in the Institute for Computational Biomedicine at Weill Cornell. The study's co-author is Dr. Chethan Pandarinath, who was a graduate student with Dr. Nirenberg and is currently a postdoctoral researcher at Stanford University. This new approach provides hope for the 25 million people worldwide who suffer from blindness due to diseases of the retina. Because drug therapies help only a small fraction of this population, prosthetic devices are their best option for future sight.

July 18th

Stanford Study Identifies Potential Target for Treating Major Symptom of Depression

Stanford University School of Medicine scientists have laid bare a novel molecular mechanism responsible for the most important symptom of major depression: anhedonia, the loss of the ability to experience pleasure. While the study was conducted in mice, the brain circuit involved in this newly elucidated pathway is largely identical between rodents and humans, increasing the odds that the findings point toward new therapies for depression and other disorders. Additionally, opinion leaders hailed the study's inventive methodology, saying it may offer a much sounder approach to testing new antidepressants than the methods now routinely used by drug developers. While as many as one in six Americans are likely to suffer a major depression in their lifetimes, current medications either are inadequate or eventually stop working in as many as 50 percent of those for whom they're prescribed. "This may be because all current medications for depression work via the same mechanisms," said Robert Malenka, M.D., Ph.D., the Nancy Friend Pritzker Professor in Psychiatry and Behavioral Sciences at Stanford. "They increase levels of one or another of two small molecules that some nerve cells in the brain use to signal one another. To get better treatments, there's a great need to understand in greater detail the brain biology that underlies depression's symptoms." The study's first author is Byung Kook Lim, Ph.D., a postdoctoral scholar in Dr. Malenka's laboratory. Dr. Malenka is the senior author of the new study, published online on July 11, 2012 in Nature, which reveals a novel drug target by showing how a hormone known to affect appetite turns off the brain's ability to experience pleasure when an animal is stressed.

July 16th

New Gene Mutations Linked to Lou Gehrig’s Disease

Researchers have linked newly discovered gene mutations in a particular gene to some cases of the progressive fatal neurological disease amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Shedding light on how ALS destroys the cells and leads to paralysis, the researchers found that mutations in this gene affect the structure and growth of nerve cells. The results were published online on July 15, 2012 in Nature. ALS attacks motor neurons, the nerve cells responsible for controlling muscles. People with ALS experience such early symptoms as limb weakness or swallowing difficulties. In most people, the disease leads to death three to five years after symptoms develop, usually as a result of respiratory failure. Scientists at the University of Massachusetts Medical School, Worcester, collaborated with international ALS researchers to search for gene mutations in two large families with an inherited form of ALS. The researchers used a technique known as exome sequencing to decode only the protein-encoding portions of DNA, known as the exome, allowing an efficient yet thorough search of the DNA regions most likely to contain disease-causing mutations. This deep sequencing of the exome led to the identification of several different mutations in the gene for profilin (PFN1) which were present only in the family members that developed ALS. Further investigations of 272 other familial ALS cases across the world showed that profilin mutations were also found in a small subset (about 1 to 2 percent) of the familial ALS cases studied. The protein profilin plays a key role in the creation and remodeling of a nerve cell's scaffolding or cytoskeleton. In fly models, disrupting profilin stunts the growth of axons – the long cell projections used to relay signals from one neuron to the next or from motor neurons to muscle cells.

July 12th

Salt Cress Genome Yields New Clues to Salt Tolerance

An international team, led by the Institute of Genetics and Developmental Biology, the Chinese Academy of Science, and BGI, the world's largest genomics organization, has completed the genomic sequence and analysis of salt cress (Thellungiella salsuginea), a wild salt-tolerant plant. The salt cress genome serves as a useful tool for exploring mechanisms of adaptive evolution and sheds new light on understanding the genetic characteristics underlying plant abiotic stress tolerance. The study was published online on July 9, 2012 in PNAS. Salt cress is a typical halophyte with high resistance to cold, drought, oxidative stresses, and salinity. Due to its small plant size, short life cycle, copious seed production, small genome size, and an efficient transformation, salt cress could serve as an important genetic model system for botanists, geneticists, and breeders to better explore the genetic mechanisms of abiotic stress tolerance. In the study, researchers sequenced the genome of salt cress (Shandong ecotype) using the paired-end Solexa sequencing technology. The genomic data yielded a draft sequence of salt cress with about 134-fold coverage. The final length of the assembled sequences amounted to about 233.7 Mb, covering about 90% of the estimated size (~260 Mb). A total of 28,457 protein-coding regions were predicted in the sequenced salt cress genome. Researchers found that the average exon length of salt cress and A. thaliana genes was similar, whereas the average intron length of salt cress was about 30% larger than that of A. thaliana. The evolutionary analysis indicated that salt cress and its close relative- Arabidopsis thaliana- diverged from approximately 7-12 million years ago. When tracing the differences between salt cress and A.