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News 18 march 2009

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Dioxin alters ability to fight infection, mouse study finds

Researchers find for the first time that mice exposed to the contaminant dioxin during development or while nursing have a diminished capacity to fight a flu infection later in life. Mouse pups born to pregnant mice that were exposed to a small amount of the ubiquitous and persistent pollutants had fewer white blood cells that normally kill the flu virus and more of a different kind that increases lung inflammation. The increased inflammation can make the disease more severe and recovery more difficult.

Computer learning, electrical stimulation offer hope for paralyzed

Trainers have used it for decades to help athletes build muscle. Late-night TV commercials hawk it as an effortless flab buster. But a University of Florida engineering researcher says electrical stimulation — a simple, decades-old technique to prompt muscles to contract — can be combined with sophisticated computer learning technology to help people regain more precise, more life-like control of paralyzed limbs.
Although his research is still exploring the fundamentals, his progress so far suggests computer-adapted electrical stimulation could one day help the estimated 700,000 Americans who suffer from strokes and the 11,000 who suffer from cord injuries annually. “It’s an adaptive scheme to do electrical stimulation more efficiently, with less fatigue and more accuracy,” said Warren Dixon, an associate professor of mechanical and aerospace engineering, explaining that existing techniques do little more than apply a set current to a designated muscle. Stroke victims may be among the first to benefit. Dixon said stroke sufferers who work at regaining the ability to walk often unconsciously drag their toes, causing them to stumble. He said his goal is to develop techniques for a wearable, pacemaker-sized device. The device would deliver just the right stimulation to the calf at just the right moment in a person’s gait, lifting the toe just enough to avoid a stumble and walk naturally.

Lab-on-a-Chip Homes in on How Cancer Cells Break Free

Johns Hopkins engineers have invented a method that could be used to help figure out how cancer cells break free from neighboring tissue, an "escape" that can spread the disease to other parts of the body. The new lab-on-a-chip, described in the March issue of the journal Nature Methods, could lead to better cancer therapies. "Studying cell detachment at the subcellular level is critical to understanding the way cancer cells metastasize," says principal investigator Peter Searson, Reynolds Professor of Materials Science and Engineering. "Development of scientific methods to study cell detachment may guide us to prevent, limit or slow down the deadly spreading of cancer cells." His team's research focuses on a missing puzzle piece in the common but unfortunate events that can occur in cancer patients. For example, cancer that starts in the breast sometimes spreads to the lungs. That's because tumor cells detach and travel through the bloodstream to settle in other tissues. Scientists have learned much about how cancer cells attach to these surfaces, but they know little about how these insidious cells detach because no one had created a simple way to study the process.

Study finds how brain remembers single events

Single events account for many of our most vivid memories – a marriage proposal, a wedding toast, a baby’s birth. Until a recent UC Irvine discovery, however, scientists knew little about what happens inside the brain that allows you to remember such events. In a study with rats, neuroscientist John Guzowski and colleagues found that a single brief experience was as effective at activating neurons and genes associated with memory as more repetitive activities. Knowing how the brain remembers one-time events can help scientists design better therapies for diseases such as Alzheimer’s in which the ability to form such memories is impaired. “Most experiences in life are encounters defined by places, people, things and times. They are specific, and they happen once,” says Guzowski, UCI neurobiology and behavior assistant professor. “This type of memory is what makes each person unique.

Penn Researchers Identify New Protein Important in Breast Cancer Gene’s Role in DNA Repair

For years, researchers have known that under normal conditions, the breast cancer protein BRCA1 orchestrates the repair of damaged DNA, but the details of just how BRCA1 moves to the damaged site and recruits the right nuclear repairmen for DNA restoration remains a mystery. Now, a new study from the University of Pennsylvania School of Medicine has identified genes associated with the BRCA1 protein and their involvement in the DNA repair pathway, helping to clear the way for researchers to better understand what goes wrong when the BRCA1 gene is mutated and the repair pathway goes haywire. Identifying patients with mutations in these BRCA1-associated genes may help better fight breast cancer.

Study finds biological clue in brain tumour development

Scientists at The University of Nottingham have uncovered a vital new biological clue that could lead to more effective treatments for a children’s brain tumour that currently kills more than 60 per cent of young sufferers. Clinician –scientists at the University’s Children’s Brain Tumour Research Centre, working on behalf of the Children’s Cancer and Leukaemia Group (CCLG), have studied the role of the WNT biological pathway in central nervous system primitive neuroectodermal tumours (CNS PNET), a type of brain tumour that predominantly occurs in children and presently has a very poor prognosis.
In a paper published in the British Journal of Cancer, they have shown that in over one-third of cases, the pathway is ‘activated’, suggesting that it plays a role in tumour development. The research also highlighted a link between WNT pathway activation and patient survival — patients who had a CNS PNET tumour that was activated survived for longer than those without pathway activation.

Vitamin D may not be the answer to feeling SAD

A lack of Vitamin D, due to reduced sunlight, has been linked to depression and the symptoms of Seasonal Affective Disorder (SAD), but research by the University of Warwick shows there is no clear link between the levels of vitamin D in the blood and depression. Exposure to sunlight stimulates vitamin D in the skin and a shortage of sunlight in the winter has been put forward as one possible cause of SAD. However Warwick Medical School researchers, led by Dr Oscar Franco, have discovered low levels of vitamin D in the blood may not be connected to depression. In a study published in the Journal of Affective Disorders, the team recruited more than 3,000 people and tested levels of vitamin D (25-hydroxyvitamin D) in the blood. They then carried out a questionnaire with the participants to assess the prevalence of depressive symptoms.
Vitamin D deficiency exists when the concentration of 25-hydroxy-vitamin D (25-OH-D) in the blood serum occurs at 12ng/ml (nanograms/millilitre) or less. The normal concentration of 25-hydroxy-vitamin D in the blood serum is 25-50ng/ml. The researchers found there was no clear association between depressive symptoms and the concentration of vitamin D in the blood.

Fish Health Claims May Cause More Environmental Harm than Good

The health benefits of fish consumption have been over-dramatized and have put increased pressure on wild fish, according to a new research published today in the Canadian Medical Association Journal (CMAJ). In an innovative collaboration, medical scientists from St. Michael’s Hospital and the University of Toronto have teamed up with researchers from the University of British Columbia’s Fisheries Centre and author Farley Mowat to closely examine the effects of health claims with regard to seafood. For years, international agencies concerned with health and nutrition have promoted seafood consumption. “Our concern is that fish stocks are under extreme pressure globally and that studies are still urgently required to define precisely who will benefit from fish oil,” says Dr. David J. A. Jenkins, a doctor at St. Michael’s Hospital and a professor at the University of Toronto Faculty of Medicine’s Department of Nutritional Sciences. “Further, if we decide that fish oil supplementation is necessary for good health, then unicellular sources of ‘fish oil’ like algae, yeasts, etc, should now be used, as they are in infant formula,” adds Dr. Jenkins. While many studies show healthy benefits of consuming omega-3 fatty acids, found in fish oils, some other studies fail to show significant benefits. But these negative studies are often ignored and the result is that there is increasing demand for seafood by consumers in the developed world, often at the expense of food security in developing nations.

Depressed People Have Trouble Learning 'Good Things In Life'

While depression is often linked to negative thoughts and emotions, a new study suggests the real problem may be a failure to appreciate positive experiences. Researchers at Ohio State University found that depressed and non-depressed people were about equal in their ability to learn negative information that was presented to them.
But depressed people weren’t nearly as successful at learning positive information as were their non-depressed counterparts. “Since depression is characterized by negative thinking, it is easy to assume that depressed people learn the negative lessons of life better than non-depressed people – but that’s not true,” said Laren Conklin, co-author of the study and a graduate student in psychology at Ohio State.

Regular exercise reduces depressive symptoms, improves self esteem in overweight children

Less than an hour of daily exercise reduces depressive symptoms and improves self esteem in overweight children, Medical College of Georgia researchers say. The study included 207 overweight, typically sedentary children ages 7-11 randomly assigned to either continue their sedentary lifestyle or exercise for 20 or 40 minutes every day after school for an average of 13 weeks. The 40-minute group sustained the most psychological benefit, according to research published online in the Journal of Pediatric Psychology. The MCG researchers were the first to demonstrate this dose response benefit of exercise – meaning the more the better – on depressive symptoms and self worth in these children. Benefits came despite the fact that the children's weight did not change much over the three months. "Just by getting up and doing something aerobic, they were changing how they felt about themselves," says the study's first author, Dr. Karen Petty, postdoctoral fellow in psychology at MCG's Georgia Prevention Institute. "Hopefully these children are taking home the idea: Hey, when we do this stuff, we feel better."

Liking sweets makes sense for kids

As any parent knows, children love sweet-tasting foods. Now, new research from the University of Washington and the Monell Center indicates that this heightened liking for sweetness has a biological basis and is related to children's high growth rate. "The relationship between sweet preference and growth makes intuitive sense because when growth is rapid, caloric demands increase. Children are programmed to like sweet taste because it fills a biological need by pushing them towards energy sources," said Monell geneticist Danielle Reed, PhD, one of the study authors. Across cultures, children prefer higher levels of sweetness in their foods as compared to adults, a pattern that declines during adolescence. To explore the biological underpinnings of this shift, Reed and University of Washington researcher Susan Coldwell, PhD, looked at sweet preference and biological measures of growth and physical maturation in 143 children between the ages of 11 and 15. The findings, reported in the journal Physiology & Behavior, suggest that children's heightened liking for sweet taste is related to their high growth rate and that sweet preferences decline as children's physical growth slows and eventually stops.
Based on the results of sensory taste tests, children were classified according to their sweet taste preference into a 'high preference' or 'low preference' group. Children in the 'low preference' group also had lower levels of a biomarker (type I collagen cross-linked N-teleopeptides; NTx) associated with bone growth in children and adolescents.

Unique nerve-stimulation device proves effective against epilepsy

Epilepsy is a common medical condition characterized by convulsions and short periods of confusion. It affects more than 50 million people worldwide. But intractable epilepsy, which affects more than 1 million Americans and is often resistant to drug treatment and surgery, is arguably worse. But in a just completed clinical trial, a unique nerve-stimulation treatment for intractable epilepsy reduced the number of seizures by more than 50 percent. In the March edition of the journal Neurology, UCLA neurology professor Christopher M. DeGiorgio and colleagues report the results of the long-term pilot trial, which demonstrated the effectiveness of the new treatment, called trigeminal nerve stimulation (TNS). The results, though preliminary, are very encouraging, DeGiorgio said. Those participating in the trial for three months saw a 66 percent reduction in the number of seizures, those participating for six months saw a 56 percent reduction and those who completed one year saw a 59 percent reduction in seizures. One of the subjects who participated for a full year had a 90-percent reduction in seizures. The trigeminal nerve extends into the brain from the face and forehead and is known to play a role in seizure inhibition. The stimulator, about the size of a large cell phone, attaches to a belt or can slip into a pocket. Two wires from the stimulator are passed under the clothing and connected to electrodes attached to the forehead by adhesive. The electrodes, which can be covered by a cap or scarf, transmit an electrical current to the nerve. "People with intractable epilepsy who have continuing seizures are often drug-resistant," DeGiorgio said. "In addition, anti-seizure drugs can have significant side effects on thinking and alertness."

Researchers identify genetic markers for aggressive head and neck cancer

Scientists at Albert Einstein College of Medicine of Yeshiva University have identified genetic markers that signal poor outcomes for patients with head and neck cancer. These findings could one day lead to a genetic test that could help select or predict successful treatment options for patients with this type of cancer. The results were published in the American Journal of Pathology. Head and neck cancer refers to tumors in the mouth, throat or larynx (voice box). Each year, about 40,000 men and women in the U.S. develop head and neck cancer, making it the sixth most common cancer in the U.S. Surgery, chemotherapy and/or radiation are the main treatment options but cause serious side effects: surgery may involve removing large areas of the tongue, throat, or neck and can affect appearance, and any type of therapy can cause swallowing or speech problems that can significantly affect quality of life. Despite curative treatment attempts, on average only about half of patients survive beyond five years after treatment. This is greatly affected by the size and location of the tumor. The Einstein study focuses on microRNAs, a recently identified class of short RNA molecules that play key roles in regulating gene expression. Abnormal microRNA levels have been associated with all types of cancer yet examined. In previous research, the Einstein scientists and other groups reported that approximately 50 specific microRNAs were expressed at higher or lower levels in head and neck tumor cell lines compared with normal cells. In this study, the Einstein researchers, for the first time, have linked levels of specific microRNAs with tumor recurrence and poorer survival in head and neck cancer. The Einstein team analyzed samples from 104 head and neck cancer patients from Montefiore Medical Center, The University Hospital and Academic Medical Center for Einstein. The patients were treated and followed over five years. At the time of cancer diagnosis and before any therapy, researchers removed samples tumor tissue from patients, as well as normal tissue adjacent to their tumor, and measured microRNA levels in the two types of tissue.
Patients who fared worst had the lowest levels of two particular microRNAs?miR-205 and let-7d?in their tumor tissue. Specifically, these patients were four times more likely to have an earlier metastasis or local-regional recurrence of their cancer than patients with higher levels of miR-205 and let-7d in tumor tissue.

Einstein Researchers Develop Novel Antibiotics That Don't Trigger Resistance

Bacterial resistance to antibiotics is one of medicine's most vexing challenges. In a study described in Nature Chemical Biology, researchers from Albert Einstein College of Medicine of Yeshiva University are developing a new generation of antibiotic compounds that do not provoke bacterial resistance. The compounds work against two notorious microbes: Vibrio cholerae, which causes cholera; and E. coli 0157:H7, the food contaminant that each year in the U.S. causes approximately 110,000 illnesses and 50 deaths. Most antibiotics initially work extremely well, killing more than 99.9% of microbes they target. But through mutation and the selection pressure exerted by the antibiotic, a few bacterial cells inevitably manage to survive, repopulate the bacterial community, and flourish as antibiotic-resistant strains.Vern L. Schramm, Ph.D., professor and Ruth Merns Chair of Biochemistry at Einstein and senior author of the paper, hypothesized that antibiotics that could reduce the infective functions of bacteria, but not kill them, would minimize the risk that resistance would later develop. Dr. Schramm's collaborators at Industrial Research Ltd. earlier reported transition state analogues of an enzyme that interferes with "quorum sensing" — the process by which bacteria communicate with each other by producing and detecting signaling molecules known as autoinducers. These autoinducers coordinate bacterial gene expression and regulate processes — including virulence — that benefit the microbial community. Previous studies had shown that bacterial strains defective in quorum sensing cause less-serious infections.

New Jefferson Research Suggests Common Anti-Seizure Medications May Increase Risk of Cardiovascular Problems

An important clinical repercussion in the treatment of epilepsy has been discovered by a research team led by Scott Mintzer, M.D., assistant professor in the Department of Neurology at Jefferson Medical College of Thomas Jefferson University. The team has determined that two of the most commonly prescribed anti-seizure medications may lead to significantly increased levels of cholesterol, C-reactive protein and other markers of cardiovascular disease risk. The finding – set to appear in the April issue of Annals of Neurology – may help doctors manage the care of patients with seizures more effectively by prescribing different anti-seizure medications that will not adversely affect cardiovascular health. The study involved two of the most widely-prescribed anticonvulsants – phenytoin (DilantinŽ) and carbamazepine (TegretolŽ, CarbatrolŽ) – which have potent effects on many enzymes in the body involved in different areas of metabolism. The researchers recruited 34 epilepsy patients taking either one of those two drugs who were being switched over to one of two newer anti-seizure drugs which do not widely affect enzymes – lamotrigine (LamictalŽ) or levetiracetam (KeppraŽ). The goal was to determine if the change affected the patients’ cholesterol levels and other key markers of cardiovascular disease. Just 6 weeks after the patients’ drugs were switched, there were significant declines in total cholesterol, non-high-density lipoprotein (commonly referred to as ‘bad’) cholesterol, triglycerides and C-reactive protein, suggesting the older, commonly-used drugs might substantially increase the risk of cardiovascular disease.

Mechanism of Alzheimer's suggests combination therapy needed

Researchers at the University of Illinois at Chicago College of Medicine have discovered a mode of action for mysterious but diagnostic protein snarls found in the brains of Alzheimer's patients that suggests a one-two punch of therapy may be needed to combat the neurodegenerative disease. Alzheimer's disease, which may affect as many as 5 million Americans and is among the most costly diseases to society in the United States and Europe, is characterized by two distinctive protein malformations: amyloid plaques and tau tangles. Amyloid plaques are sticky deposits made up of a short protein called amyloid beta, and tau tangles are made of short filaments of the tau protein.
So far no one has been able to explain how amyloid beta and the tau tangles wreak their damage on the nervous system. "We have known for a long time that amyloid beta was bad," said Scott Brady, professor and head of anatomy and cell biology at the UIC College of Medicine. "What we haven't understood is why it's bad." The findings, reported in a new study appearing in the Proceedings of the National Academy of Sciences Online Early Edition for March 16-20, suggest promising new targets for combination therapy. In previous work, published earlier this year, the researchers suggested how tau tangles work together with amyloid beta to create a perfect storm that destroys neural function and memory. "Cell death occurs at a very late stage of the disease," said Brady, principal investigator of the study. "Long before the cells die they lose function, and that function is critical for the symptoms that we see." Brady and his colleagues found that when short assemblies of amyloid -- rather than the long-chain plaques -- get inside neurons, they interfere with the cells' transport system. This limits their ability to send vital proteins and vesicles to where they are needed within the cell and interferes with the synaptic connections to other nerve cells.

Brain abnormality found in boys with attention deficit hyperactivity disorder

Researchers trying to uncover the mechanisms that cause attention deficit hyperactivity disorder and conduct disorder have found an abnormality in the brains of adolescent boys suffering from the conditions, but not where they expected to find it. Boys with either or both of these disorders exhibited a different pattern of brain activity than normally developing boys when they played a simple game that sometimes gave them a monetary reward for correct answers, according to a new study by a University of Washington research team. The research focused on two brain areas, the striatum and anterior cingulate cortex. The striatal region is a network of structures in the mid brain that motivates people to engage in pleasurable or rewarding behavior. The anterior cingulate is higher in the brain and normally activates when an expected reward stops. However, this process, called extinction, doesn't occur, at least as quickly, in boys with attention deficit hyperactivity or conduct disorders. Instead, the striatal region continues to be activated, said Theodore Beauchaine, a UW associate professor of psychology and senior author of the paper. "When children engage in impulsive behavior they are looking to stimulate themselves and have fun. Children with attention deficit hyperactivity disorder are always looking to have fun and that is what gets them in trouble," he said. "A behavior should stop when the reward stops. When you stop the reward for children with these disorders, they continue to focus on the reward long afterward and the anterior cingulate does not appear to become activated." Attention deficit hyperactivity disorder is one of the most common mental disorders among children, affecting between 3 and 5 percent of school-age youngsters, or an estimated 2 million. The researchers used functional magnetic resonance imaging to compare brain activity in 19 boys with either or both disorders and 11 normally developing boys. The adolescents ranged in age from 12 to 16. Their brains were scanned while they played the game. The boys looked at a screen and there was a button under each of their thumbs. When a light flashed on the left or right side of the screen they were instructed to press the button on that side. The screen lit up very fast, up to 100 times a minute. The boys received five cents for each correct response and could win up to $50. They were not penalized for wrong answers and their accumulated winnings showed up on the screen.

The Notch gene accelerates colon carcinogenesis

Professor Daniel Louvard (1) (CNRS Research Director and Director of the Curie Institute Research Centre) and his group, working in close partnership with Spyros Artavanis-Tsakonas (2), recently discovered how the Notch gene is involved in the pathogenic process leading to colon cancer. The Notch and Wnt signalling pathways play an important role in normal gut development and homeostasis. In mice, abnormal activation of these two signalling pathways increases the number of benign tumours-adenomas-in the intestine by a factor of over twenty compared with activation of the Wnt pathway alone. Moreover, these tumours grow extremely fast in the colon, mimicking the pathogenic process observed in humans. Cooperative action between these two pathways creates a favourable environment for malignant transformation. These findings (published online in PNAS) show that Notch acts as an "accelerator" in the development of colon cancer in humans, constituting an essential component of the pathogenic process. The question now is to find a "brake" that can counter this.
The gut, which represents a surface area equivalent to that of a tennis court, is in constant turnover completely renewing itself every five days. This turnover depends on the presence of stem cells and progenitor cells found in the crypts between intestinal villi. The stem cells give rise to progenitor cells which can in turn differentiate, over successive division cycles, to give the various different cell types that populate and form the gut. The key factor is to maintain a balance between differentiation and proliferation in the intestinal epithelium.

Cancer - Another step towards medication - Austrian Scientists identify a potential tumor suppressor

The gene Myc is an important factor for the growth of organisms by cell division. It causes the production of a protein which, as a transcription factor, controls the expression of up to 15 % of all human genes. When this gene mutates to an oncogene, the cell proliferates excessively and apoptosis is inhibited. Thereby the gene plays a decisive role in the development of many tumors. The problem is that pharmacological substances do not target Myc as it does not have enzymatic activity of its own. Thus, scientists worldwide are trying to find alternative ways to inhibit this oncogene. A team of scientists led by Klaus Bister and Markus Hartl of the Institute of Biochemistry and the Centre for Molecular Biosciences of the University of Innsbruck may have made an important step towards achieving this goal. For the first time, the scientists have shown that Myc suppresses the expression of the gene BASP1. This evidence prompted them to test the effect of BASP1 on the oncogene. In cell experiments they proved that BASP1 specifically inhibits the uncontrolled proliferation of Myc. „Until now the precise biochemical function of BASP1 is unknown“, Prof. Bister explains. „However, in our experiments we have found clear evidence that Myc-induced cell transformation can be specifically inhibited by BASP1, and consequently, the gene functions as a tumor suppressor.“ This finding may facilitate the development of new drugs which keep the development of tumors under control.