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Archive - 2011 - Story

November 2nd

Nicotine Primes Brain for Cocaine Use; A Gateway Drug Mechanism Explained

Cigarettes and alcohol serve as gateway drugs, which people use before progressing to the use of marijuana and then to cocaine and other illicit substances; this progression is called the "gateway sequence" of drug use. An article in the November 2, 2011 issue of Science Translational Medicine by Drs. Amir Levine, Denise Kandel, and Eric Kandel, and colleagues at Columbia University Medical Center provides the first molecular explanation for the gateway sequence. They show that nicotine causes specific changes in the brain that make it more vulnerable to cocaine addiction -- a discovery made by using a novel mouse model. Alternate orders of exposure to nicotine and cocaine were examined. [Referential web site: http://www.dependency.net/]The authors found that pretreatment with nicotine greatly alters the response to cocaine in terms of addiction-related behavior and synaptic plasticity (changes in synaptic strength) in the striatum, a brain region critical for addiction-related rewards. On a molecular level, nicotine also primes the response to cocaine by inhibiting the activity of an enzyme―histone deacetylase―in the striatum. This inhibition enhances cocaine's ability to activate a gene called FosB gene, which promotes addiction. The relationship between nicotine and cocaine was found to be unidirectional: nicotine dramatically enhances the response to cocaine, but there is no effect of cocaine on the response to nicotine. Nicotine's ability to inhibit histone deacetylase thus provides a molecular mechanism for the gateway sequence of drug use. Nicotine enhances the effects of cocaine only when it is administered for several days prior to cocaine treatment and is given concurrently with cocaine.

Nature Study Addresses Causes of Ice Age Extinctions

Did climate change or humans cause the extinctions of the large-bodied Ice Age mammals (commonly called megafauna) such as the woolly rhinoceros and woolly mammoth? Scientists have for years debated the reasons behind the Ice Age mass extinctions, which caused the loss of a third of the large mammals in Eurasia and two-thirds of the large mammals in North America, and now, an inter-disciplinary team from more than 40 universities around the world led by Professor Eske Willerslev and his group from the Centre for GeoGenetics, University of Copenhagen, has tried to answer the contentious question in one of the biggest studies of its kind ever. The study by the team, which includes two Texas A&M University professors, is published online on November 2, 2011 in the journal Nature and reveals dramatically different responses of Ice Age species to climate change and human impact. Using ancient DNA, species distribution models, and the human fossil record, the findings indicate that neither climate nor humans alone can account for the Ice Age mass extinctions. "Our findings put a final end to the single-cause theories of these extinctions," says Dr. Willserslev. "Our data suggest care should be taken in making generalizations regarding past and present species extinctions; the relative impacts of climate change and human encroachment on species extinctions really depend on which species we're looking at." The study reports that climate alone caused extinctions of woolly rhinoceros and musk ox in Eurasia, but a combination of climate and humans played a part in the loss of bison in Siberia and of wild horse. While the reindeer remain relatively unaffected by any of these factors, the reasons behind causes of the extinction of the mammoth remain unresolved.

Towards an Epstein-Barr Virus Vaccine That Prevents Associated Disease, Cancers

Epstein-Barr virus (EBV) infects nine out of ten people worldwide at some point during their lifetimes. Infections in early childhood often cause no disease symptoms, but people infected during adolescence or young adulthood may develop infectious mononucleosis, a disease characterized by swollen lymph nodes, fever, and severe fatigue. EBV also is associated with several kinds of cancer, including Hodgkin lymphoma and stomach and nasal cancers. Organ transplant recipients and people infected with HIV (who become infected with or who already are infected with EBV) also may develop EBV-associated cancers. There is no vaccine to prevent EBV infection and no way for doctors to predict whether an EBV-infected person will develop virus-associated cancer. In a new article from the National Institutes of Health (NIH) and published in the November 2, 2011 issue of Science Translational Medicine, Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), and Dr. Harold Varmus, director of the National Cancer Institute (NCI), join Dr. Gary Nabel, director of NIAID's Vaccine Research Center, and Dr. Jeffrey Cohen, chief of NIAID's Laboratory of Infectious Diseases, in summarizing a recent meeting of experts who gathered to map directions toward an EBV vaccine. Although it may not be possible to create a vaccine that completely prevents EBV infection, the authors note, clinical observations and results from clinical trials of an experimental EBV vaccine suggest that it may be possible to create an EBV vaccine capable of preventing the diseases that sometimes follow EBV infection.

Boosting PGC-1 Activity May Increase Lifespan, Fly Study Shows

One of the few reliable ways to extend an organism's lifespan, be it a fruit fly or a mouse, is to restrict calorie intake. Now, a new study in fruit flies is helping to explain why such minimal diets are linked to longevity and offering clues to the effects of aging on stem cell behavior. Scientists at the Salk Institute for Biological Studies and their collaborators found that tweaking a gene known as PGC-1, which is also found in human DNA, in the intestinal stem cells of fruit flies delayed the aging of their intestines and extended their lifespans by as much as 50 percent. "Fruit flies and humans have a lot more in common than most people think," says Dr. Leanne Jones, an associate professor in Salk's Laboratory of Genetics and a lead scientist on the project. "There is a tremendous amount of similarity between a human small intestine and the fruit fly intestine." The findings of the study, which was a collaboration among researchers at the Salk Institute for Biological Studies and the University of California, Los Angeles, were published in the November 2, 2011 issue of Cell Metabolism. Scientists have long known that calorie restriction, the practice of limiting daily food intake, can extend the healthy lifespan of a range of animals. In some studies, animals on restricted diets lived more than twice as long on average as those on non-restricted diets. While little is known about the biological mechanisms underlying this phenomenon, studies have shown that the cells of calorie-restricted animals have greater numbers of energy-generating structures known as mitochondria. In mammals and flies, the PGC-1 gene regulates the number of these cellular power plants, which convert sugars and fats from food into the energy for cellular functions. This chain of connections between the mitochondria and longevity inspired Dr.

November 1st

New Drug Targeting B-Cells Shows Promise for Multiple Sclerosis

An experimental drug called Ocrelizumab has shown promise in a Phase 2 clinical trial involving 220 people with multiple sclerosis (MS), an often debilitating, chronic autoimmune disease that affects an increasing number of people in North America. It usually strikes young adults and is more common in women than in men. The study, carried out by researchers at the University of California, San Francisco (UCSF) Medical Center, and involving hospitals in the United States, Canada, and Europe, was published online on November 1, 2011 in the British medical journal Lancet. The study involved patients with relapsing-remitting MS, a form of the disease marked by the accumulation of lesions in the brain and spinal cord and periodic “attacks” of neurological impairment. The 220 patients were randomly enrolled into four groups – two that received injections of the monoclonal antibody Ocrelizumab at two different doses, one that received the standard multiple sclerosis drug interferon-beta, and one “control” group that was given a placebo. The doctors gauged the effectiveness of each treatment by performing monthly magnetic resonance imaging (MRI) brain scans of the patients and counting the number of visible marks that indicate inflamed lesions, a hallmark of the disease. They also compared the severity and frequency of neurological “attacks” that cause loss of vision, incoordination, weakness and numbness, among other symptoms. The results of this trial showed that patients who received the drug generally fared well and showed fewer signs of the disease than patients who receive a placebo or the standard interferon treatment. Overall, the trial found that Ocrelizumab led to a 89 percent reduction in the formation of brain lesions, and it also reduced the number of new MS attacks over 24 weeks.

How Homologous Chromosomes Find Each Other at Meiosis

After more than a century of study, mysteries still remain about the process of meiosis—a special type of cell division that helps ensure genetic diversity in sexually-reproducing organisms. Now, researchers at Stowers Institute for Medical Research, in Kansas City, Missouri, shed light on an early and critical step in meiosis. The research, published online on October 27, 2011 in Current Biology, clarifies the role of key chromosomal regions called centromeres in the formation of a structure known as the synaptonemal complex (SC). "Understanding this and other mechanisms involved in meiosis is important because of the crucial role meiosis plays in normal reproduction—and the dire consequences of meiosis gone awry," says Dr. R. Scott Hawley, who led the research at Stowers. "Failure of the meiotic division is probably the most common cause of spontaneous abortion and causes a number of birth defects such Down syndrome," Dr. Hawley says. Meiosis reduces the number of chromosomes carried by an individual's regular cells by half, allocating precisely one copy of each chromosome to each egg or sperm cell and thus ensuring that the proper number of chromosomes is passed from parent to offspring. And because chromosomes come in pairs—23 sets in humans—the chromosomes must be properly matched up before they can be divided up. "Chromosome 1 from your dad has to be paired with chromosome 1 from your mom, chromosome 2 from your dad with chromosome 2 from your mom, and so on," Dr. Hawley explains, "and that's a real trick. There's no room for error; the first step of pairing is the most critical part of the meiotic process. You get that part wrong, and everything else is going to fail." The task is something like trying to find your mate in a big box store.

Study Illuminates Mechanism of Polyploidy

An international team of scientists, including biologists from the University of North Carolina (UNC) at Chapel Hill, may have pinpointed for the first time the mechanism responsible for cell polyploidy, a state in which cells contain more than two paired sets of chromosomes. When it comes to human chromosomes and the genes they carry, our tissue cells prefer matched pairs. Bundled within the nucleus of our cells are 46 chromosomes, one set of 23 inherited from each of our parents. Thus, we are known from a cellular standpoint as "diploid" creatures. But a cellular chromosome situation common in plants and in many insects is polyploidy, in which there are more – sometimes many more – than two sets of chromosomes. Here, growth occurs through an increase in cell size versus an increase in cell number via cell division (mitosis). This allows more DNA to be crammed into the cell nucleus. Polyploidy also appears in some tissues of otherwise diploid animals, including people – for example, in specialized organ tissue such as muscle, placenta, and liver. These biologically highly active tissues also produce large polyploid cells. An intriguing slice of discovery science led by geneticist Dr. Bruce Edgar, of the University of Heidelberg, Germany, was published online on Oct 30, 2011 in the journal Nature. The research team may have identified for the first time the regulatory mechanism responsible for cell polyploidy. Study co-author Dr. Robert J.

Scientists Discover How Cancer-Causing Bacterium Causes Cell Death

Researchers report they have figured out how the cancer-causing bacterium Helicobacter pylori attacks a cell's energy infrastructure, sparking a series of events in the cell that ultimately lead it to self-destruct. H. pylori are the only bacteria known to survive in the human stomach. Infection with H. pylori is associated with an increased risk of gastric cancer, the second-leading cause of cancer-related deaths worldwide. "More than half the world's population is currently infected with H. pylori," said University of Illinois microbiology professor Dr. Steven Blanke, who led the study. "And we've known for a long time that the host doesn't respond appropriately to clear the infection from the stomach, allowing the bacterium to persist as a risk factor for cancer." The new study, published in the September 20, 2011 issue of the Proceedings of the National Academy of Sciences, is the first to show how a bacterial toxin can disrupt a cell's mitochondria – its energy-generation and distribution system – to disable the cell and spur apoptosis (programmed cell death). "One of the hallmarks of long-term infection with H. pylori is an increase in apoptotic cells," Dr. Blanke said. "This may contribute to the development of cancer in several ways." Apoptosis can damage the epithelial cells that line the stomach, he said, "and chronic damage to any tissue is a risk factor for cancer." An increase in apoptotic cells may also spur the hyper-proliferation of stem cells in an attempt to repair the damaged tissue, increasing the chance of mutations that can lead to cancer. Previous studies had shown that VacA, a protein toxin produced by H. pylori, induces host cell death, Dr.

October 31st

Evidence of Massive Global Network of Recent Gene Exchange Among Bacteria

Much as people can exchange information instantaneously in the digital age, bacteria associated with humans and their livestock appear to freely and rapidly exchange genetic material related to human disease and antibiotic resistance through a mechanism called horizontal gene transfer (HGT). In a paper appearing in Nature online on October 30, 2011, researchers — led by Dr. Eric Alm of MIT's Department of Civil and Environmental Engineering and Department of Biological Engineering — say they've found evidence of a massive network of recent gene exchange connecting bacteria from around the world: 10,000 unique genes flowing via HGT among 2,235 bacterial genomes. HGT is an ancient method for bacteria from different lineages to acquire and share useful genetic information they didn't inherit from their parents. Scientists have long known about HGT and known that when a transferred gene confers a desirable trait, such as antibiotic resistance or pathogenicity, that gene may undergo positive selection and be passed on to a bacterium's own progeny, sometimes to the detriment of humans. For example, the proliferation of antibiotic-resistant strains of bacteria is a very real threat, as seen in the rise of so-called "superbugs." But until now, scientists didn't know just how much of this information was being exchanged, or how rapidly. The MIT team's work illustrates the vast scale and rapid speed with which genes can proliferate across bacterial lineages. "We are finding [completely] identical genes in bacteria that are as divergent from each other as a human is to a yeast," says Dr. Alm, the Karl Van Tassel Associate Professor.

Fungus Confirmed As Cause of Bat Epidemic

Bats in North America have been under attack. Since 2006, more than a million have been killed. Little has been done to save them, because there has not been enough evidence to implicate the suspect—until now. A new study has discovered that the fungus Geomyces destructans is the causal agent of White-Nose Syndrome (WNS), the fungal disease decimating the bat population. The study is coauthored by Dr. Justin Boyles, a post-doctoral research associate in ecology and evolutionary biology at the University of Tennessee, Knoxville, and a team led by Dr. David Blehert at the U.S. Geological Survey (USGS) National Wildlife Health Center together with Jeffrey Lorch, a graduate student at the University of Wisconsin, Madison. WNS is so dubbed because affected bats develop halos of white fungus around their muzzles. The symptoms of WNS include loss of body fat, unusual winter behavior, lesions to the wing membranes, and death. The findings were published online on October 26, 2011 in Nature. G. destructans has been thought to be the likely culprit, because the skin lesions characteristic of the disease are associated with colonization of the fungus. Still, the role of G. destructans in WNS has remained controversial, because evidence proving the fungus as the primary cause of the disease was lacking. "Many assumed that fungal infections in mammals only occur if some other pathogen has already weakened the immune system," said Dr. Boyles. "Additionally, the recent discovery that G. destructans commonly colonizes the skin of bats in Europe with no major die-offs generated speculation that other unidentified factors are the primary cause of WNS." To put the speculation to rest, the researchers set up an experiment to see if G. destructans causes WNS.