Varicose veins, sometimes referred to as "varices" in medical jargon, are usually just a cosmetic problem if they occur as spider veins. In their advanced stage, however, they pose a real health threat. In people with this widespread disorder, the blood is no longer transported to the heart unhindered, but instead pools in the veins of the leg. This is because the vessel walls or venous valves no longer function adequately. Dr. Thomas Korff and his group at the Division of Cardiovascular Physiology (Director: Professor Markus Hecker) of Heidelberg University's Institute of Physiology and Pathophysiology have now shown that the pathological remodeling processes causing varicose veins are mediated by a single protein (AP-1). As a response to increased stretching of the vessel wall, this protein triggers the production of several molecules promoting changes in wall architecture. The paper, published in the October 2011 issue of The FASEB Journal, may offer a possibility for using drugs to decelerate the formation of, or even prevent, new varicose veins. Previously, no suitable experimental systems existed for studying the way in which these changes in the cells of the blood vessels are controlled. For their studies, Dr. Korff and his team took advantage of the fact that blood vessels in the mouse ear are clearly visible and are also easily accessible for minor surgical procedures. In order to artificially set off processes that are similar to the formation of varicose veins, they tied off a vein with a thin thread. The elevated pressure in the vessels caused by the pooled blood led to the recognizable remodeling characteristic of varicose veins. In addition, in the affected veins, the cell proliferation rate and the production of MMP-2 increased.
A novel study involving fruit flies and mice has allowed biologists to identify two critical genes responsible for congenital heart defects in individuals with Down syndrome, a major cause of infant mortality and death in people born with this genetic disorder. In a paper published on November 3, 2011 in the open-access journal PLoS Genetics, researchers from the University of California (UC)-San Diego, the Sanford-Burnham Medical Research Institute in La Jolla, California, and the University of Utah report the identification of two genes that, when produced at elevated levels, work together to disrupt cardiac development and function. Down syndrome, the most common genetic cause of cognitive impairment, is a disorder that occurs in one in 700 births when individuals have three, instead of the usual two, copies of human chromosome 21. “Chromosome 21 is the shortest human chromosome and intensive genetic mapping studies in people with Down syndrome have identified a small region of this chromosome that plays a critical role in causing congenital heart defects,” said Dr. Ethan Bier, a biology professor at UC-San Diego and one of the principal authors of the study. “This Down syndrome region for congenital heart disease, called the ‘DS-CHD critical region,’ contains several genes that are active in the heart which our collaborator, Julie Korenberg, had suspected of interacting with each other to disrupt cardiac development or function when present in three copies. But exactly which of these half dozen or so genes are the culprits? Identifying the genes within the DS-CHD critical region contributing to congenital heart defects is challenging to address using traditional mammalian experimental models, such as mice,” added Dr.
For decades, scientists and farmers have attempted to understand how a bacterial pathogen continues to damage tomatoes despite numerous agricultural attempts to control its spread. Pseudomonas syringae pv. tomato is the causative agent of bacterial speck disease of tomato (Solanum lycopersicum), a disease that occurs worldwide and causes severe reduction in fruit yield and quality, particularly during cold and wet springs. In the spring of 2010, for example, an outbreak in Florida and California devastated the harvest in those areas. "There is not much that can be done from a farming standpoint," said Dr. Boris Vinatzer, associate professor of plant pathology, physiology and weed science, and an affiliated faculty member with the Fralin Life Science Institute at Virginia Tech. "First, farmers try to use seed that is free of the pathogen to prevent disease outbreaks. Then, there are some disease-resistant tomato cultivars, but the pathogen has overcome this resistance by losing the gene that allowed these resistant plants to recognize it and defend themselves. For the rest, there are pesticides, but the pathogen has become resistant against them." So how exactly has the pathogen evolved to consistently evade eradication efforts? This is where science steps in, and a copy of the bacterial pathogen's game plan is crucial. Thanks to the collaborative work of Dr. Vinatzer, Virginia Bioinformatics Institute computer scientist Dr. Joao Setubal, assistant professor of statistics Dr. Scotland Leman, and their students, the genomes of several Pseudomonas syrinage pv. tomato isolates have been sequenced in order to track the bacterial pathogen's ability to overcome plant defenses and to develop methods to prevent further spread.
Bright light arouses us. Bright light makes it easier to stay awake. Very bright light not only arouses us, but is known to have antidepressant effects. Conversely, dark rooms can make us sleepy. It's the reason some people use masks to make sure light doesn't wake them while they sleep. Now researchers at UCLA have identified the group of neurons that mediates whether light arouses us — or not. Dr. Jerome Siegel, a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA, and colleagues report in the October 26, 2011 edition of the Journal of Neuroscience that the cells necessary for a light-induced arousal response are located in the hypothalamus, an area at the base of the brain responsible for, among other things, control of the autonomic nervous system, body temperature, hunger, thirst, fatigue — and sleep. These cells release a neurotransmitter called hypocretin, Dr. Siegel said. The researchers compared mice with and without hypocretin and found that those that didn't have it were unable to stay awake in the light, while those who had it showed intense activation of these cells in the light but not while they were awake in the dark. This same UCLA research group earlier determined that the loss of hypocretin was responsible for narcolepsy and the sleepiness associated with Parkinson's disease. But the neurotransmitter's role in normal behavior was, until now, unclear. "This current finding explains prior work in humans that found that narcoleptics lack the arousing response to light, unlike other equally sleepy individuals, and that both narcoleptics and Parkinson's patients have an increased tendency to be depressed compared to others with chronic illnesses," said Dr.
Scientists of the German Cancer Research Center have discovered an alternative mechanism for the extension of the telomere repeat sequence by DNA repair enzymes. The ends of the chromosomes, the telomeres, are repetitive DNA sequences that shorten every time a cell divides during the process of duplicating its genome. Once the telomeres become very short the cell stops dividing. Thus, telomeres work like a cellular clock that keeps an eye on the number of cell divisions. And once the cell's time is over it can no longer divide. Circumventing this control mechanism is crucial for tumor cells in order to proliferate without limits. In the majority of tumors this is accomplished by reactivating telomerase, an enzyme that normally extends the telomeres only in embryonic cells, and thus resets the cellular clock during development. However, a 10-15% fraction of tumors keeps on dividing without telomerase by making use of what is called the ALT-mechanism for "Alternative Lengthening of Telomeres". The hallmark of ALT cancer cells is a special type of complexes of promyelocytic leukemia (PML) protein at the telomeres that are termed ALT-associated PML nuclear bodies or APBs. ALT-tumors can be identified by the presence of APBs on fluorescence microscopy images since normal cells do not have these structures. However, the function of APBs has remained mysterious. In a recent study, Dr. Inn Chung and Dr. Karsten Rippe from the German Cancer Research Center, together with Dr. Heinrich Leonhard from the LMU in Munich, applied a novel approach to study APBs. They succeeded in artificially making APBs in living cells by tethering PML and other APB proteins to the telomeres.
A new study has confirmed that the drug, ivacaftor, significantly improves lung function in some people with cystic fibrosis (CF). The results of the phase III clinical trial study, "A CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation," led by Dr. Bonnie W. Ramsey of Seattle Children's Research Institute and the University of Washington, were published in the November 3, 2011 issue of the New England Journal of Medicine. Ivacaftor, also known as VX-770, was developed by Vertex Pharmaceuticals with financial support from the Cystic Fibrosis Foundation. The oral medicine targets the defective protein produced by the gene mutation called G551D that can cause CF. Researchers found that CF patients carrying the G551D mutation – approximately four per cent of all CF patients – who were treated with VX-770 showed a 17 per cent relative improvement in lung function that was sustained over the course of 48 weeks. Additionally, patients with G551D treated with VX-770 showed improvements in other areas critically important to the health of people with CF. Study participants experienced significant reductions in sweat chloride levels indicating an improvement in the body's ability to carry salt in and out of cells – a process, which when defective, leads to CF. They also experienced decreased respiratory distress symptoms and improved weight gain. Those who received VX-770 gained on average seven pounds compared to those in the placebo group who gained approximately one pound. This is significant because many people with CF have difficulty gaining and maintaining weight due to reduced lung function and chronic infection. "Our study shows that we are now able to improve the quality of life for cystic fibrosis patients with the G551D mutation with the administration of VX-770," said Dr.
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.
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.
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.
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.