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News 16 march 2009

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Oil spill clean-up kills more fish than spills themselves, says Queen’s biologist

A new Queen's University study shows that detergents used to clean up spills of diesel oil actually increase its toxicity to fish, making it more harmful. "The detergents may be the best way to treat spills in the long term because the dispersed oil is diluted and degraded," says Biology professor Peter Hodson. "But in the short term, they increase the bioavailability and toxicity of the fuel to rainbow trout by 100-fold." The detergents are oil dispersants that decrease the surface tension between oil and water, allowing floating oil to mix with water as tiny droplets. Dr. Hodson and his team found that dispersion reduces the potential impacts of oil on surface-dwelling animals, While this should enhance biodegradation, it also creates a larger reservoir of oil in the water column. This increases the transfer of hydrocarbons from oil to water, Dr. Hodson explains. The hydrocarbons pass easily from water into tissues and are deadly to fish in the early stages of life. "This could seriously impair the health of fish populations, resulting in long-term reductions in economic returns to fisheries," he says.

Nanoscopic probes can track down and attack cancer cells

A researcher has developed probes that can help pinpoint the location of tumors and might one day be able to directly attack cancer cells. Joseph Irudayaraj, a Purdue University associate professor of agricultural and biological engineering, developed the nanoscale, multifunctional probes, which have antibodies on board, to search out and attach to cancer cells. A paper detailing the technology was released last week in the online version of Angewandte Chemie, an international chemistry journal. "If we have a tumor, these probes should have the ability to latch on to it," Irudayaraj said. "The probe could carry drugs to target, treat as well as reveal cancer cells." Scientists have developed probes that use gold nanorods or magnetic particles, but Irudayaraj's nanoprobes use both, making them easier to track with different imaging devices as they move toward cancer cells. The magnetic particles can be traced through the use of an MRI machine, while the gold nanorods are luminescent and can be traced through microscopy, a more sensitive and precise process. Irudayaraj said an MRI is less precise than optical luminescence in tracking the probes, but has the advantage of being able to track them deeper in tissue, expanding the probes' possible applications.

Alzheimer's Disease Neuroimaging Initiative announces completion of genome-wide analysis

Researchers announced today that a high-density genome wide analysis of participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI; www.adni-info.org) is more than 95% complete and that data will be shared with scientists around the world for further analysis. The ADNI data will be used by researchers to search for genes that contribute to the development of Alzheimer's disease, which currently affects up to 5 million people in the United States alone. ADNI, an ongoing $60 million project, is a public-private partnership supported primarily by the National Institutes of Health (NIH) with pharmaceutical and related industries and not-for-profit organizations providing support through the Foundation for the National Institutes of Health (FNIH). One of the largest scale neuroimaging projects ever undertaken, ADNI involves longitudinal magnetic resonance imaging (MRI) and positron emission tomography (PET) brain imaging and blood, urine and spinal fluid biomarker studies of more than 800 individuals, half of whom have mild cognitive impairment, a condition placing them at high risk for developing Alzheimer's disease or another dementia. The primary goal of ADNI is to determine whether brain imaging, other biological markers, and clinical and neuropsychological assessment can accurately measure the progression of mild cognitive impairment and early Alzheimer's disease. The identification of specific biomarkers of early Alzheimer's disease and disease progression will provide a useful tool for researchers and clinicians in both the diagnosis of early Alzheimer's disease and in the development, assessment and monitoring of new treatments. One major Alzheimer's disease risk gene, APOE, has been consistently shown to be associated with the form of the disease arising later in life that accounts for approximately 95 percent of all cases. It is widely suspected that variants in an ensemble of other genes play a role in susceptibility to the disease and may influence the age of onset, expression and rate of progression of neurodegenerative changes in the brain. "This new data set provides a unique opportunity to evaluate the associations between a highly comprehensive dataset based on brain imaging, clinical examinations and other biomarkers and the entire genome or selected candidate genes," said Andrew Saykin, Psy.D., director of the IU Center for Neuroimaging at the Indiana University School of Medicine, who leads the genetics research team.

Less of a stink in diabetes patients?

Hydrogen sulfide (H2S) is commonly associated with smell of rotten eggs, stink bombs and blocked drains but lower blood levels of the gas are possibly linked to cardiovascular complications in some male patients with type II diabetes, according to research recently presented by researchers at the Peninsula Medical School in the South West of England at the Annual Diabetes UK Professional Conference in Glasgow this week and published in Diabetic Medicine. H2S is produced naturally within our bodies, along with other chemical compounds such as nitric oxide, where it is believed to help regulate blood pressure. Research shows that a balance between these compounds relates to good health, whereas an imbalance could indicate disease. In the case of diabetes, common complications of the disease are high blood pressure and microvascular dysfunction, which leads to damage of the tiny blood vessels (microvessels) that deliver blood, oxygen and nutrients to the eyes, skin, nerves and kidney. Dr. Matt Whiteman of the Peninsula Medical School and colleagues from the Peninsula National Institute for Health Research (NIHR) Clinical Research Facility have compared the levels of H2S in blood samples taken from healthy people and male patients with type II diabetes and found markedly decreased levels of H2S in the diabetes patients. Lower H2S levels were associated with clinical markers of impaired microvessel function suggesting that a loss of this blood pressure lowering gas could be a contributing factor in the development of vascular complications in patients with diabetes.

Dendritic cells ensure immune tolerance

One of the most important tasks of the immune system is to identify what is foreign and what is self. If this distinction fails, then the body's own structures will be attacked, the result of which could be an autoimmune disease such as diabetes mellitus type 1 or multiple sclerosis. The only way to protect against these afflictions is to destroy all immune factors that turn against the body’s own tissue – in other words: immune tolerance. A team working with LMU researcher Dr. David Vöhringer has now investigated exactly what role dendritic cells play in this process. There has long been suspicion that these cells, which are important for the body’s defenses, are also essential for the establishment and maintenance of immune tolerance. “We investigated mice that lacked this cell type from birth,” reports Vöhringer. “It turned out that immune cells that attack the body’s own tissue survive in these animals, and thereby trigger an autoimmune response. It follows that dendritic cells play a major part in protecting against autoimmune disease.” T cells are a type of white blood cell that are key actors in the body's immune defenses. Each T cell has a receptor on its surface for recognizing just one single antigen. Antigens are molecular structures, mostly fragments of proteins. T cells do not dock onto free antigens, however: they rely on other cells which can present antigens to them. It is the dendritic cells that are primarily responsible for this job. They present the T cells with various antigens, and if an antigen matches a receptor, then that T cell will trigger an immune response from the body. This is how the body defends itself against pathogens and other intruders. But behind this tactic lies an element of danger to the organism: what happens if the antigen is not foreign, but originates from the body’s own tissue instead? A wrongly induced immune response can lead to a severe autoimmune disease that, if left untreated, could lead to destruction of organs or even death. So-called autoreactive T cells, which recognize the body’s own structures, must be eradicated or pacified to avoid that they can cause harm. A T cell screening process therefore takes place in the thymus, the bilobular organ in the upper thorax, to distinguish the good from the bad of these dangerous lone mavericks. Each individual T cell is tested, and the autoreactive ones destroyed.

Stress may cause the brain to become disconnected

The new paper by Hajszan and colleagues at Yale University suggests that in learned helplessness, an animal model for depression and PTSD, stress-related reductions in synapses in the hippocampus are directly related to the emergence of depression-like behavior. These data help to make the case that stress-related changes in the structure of nerve cells may have important behavioral consequences, explains Dr. Hajszan. "The importance of our findings is derived from the well-known fact that synapses have a great potential for rapid changes, which may underlie sudden mood swings. More importantly, it is feasible to restore hippocampal synapses in a very short period of time (hours or even minutes), which opens up exciting new avenues for developing rapid-acting antidepressants that may provide immediate relief from depressive symptoms."  It cannot yet be said that reductions in cortical volumes in patients with PTSD reflect reductions in the number of synapses. However, these findings underscore the potential importance of studying post-mortem human tissue to determine whether humans also show this pattern of neural changes. Dr. Krystal notes that "settling this issue could help us to better understand recent epidemiologic data suggesting that most of the adjustment problems of soldiers returning from Iraq and Afghanistan with mild traumatic brain injury (TBI) or post-concussive syndrome are attributable to PTSD." He adds, "We have tended to think of PTSD and mild TBI as unrelated at the neural level. However, with growing evidence from animal studies that PTSD may be associated with loss of neural connections, it may turn out that PTSD and mild TBI are two distinct, but interacting, ways that soldiers might be affected by their combat experience. " Research is ongoing in the authors' lab and in others as they continue to make progress in understanding how the brain is affected by depression and stress, and in developing targeted medications.

University of Pennsylvania Researchers Find that the Unexpected Is a Key to Human Learning

The human brain’s sensitivity to unexpected outcomes plays a fundamental role in the ability to adapt and learn new behaviors, according to a new study by a team of psychologists and neuroscientists from the University of Pennsylvania. Using a computer-based card game and microelectrodes to observe neuronal activity of the brain, the Penn study, published this week in the journal Science, suggests that neurons in the human substantia nigra, or SN, play a central role in reward-based learning, modulating learning based on the discrepancy between the expected and the realized outcome. “This is the first study to directly record neural activity underlying this learning process in humans, confirming the hypothesized role of the basal ganglia, which includes the SN, in models of reinforcement including learning, addiction and other disorders involving reward-seeking behavior,” said lead author Kareem Zaghloul, postdoctoral fellow in neurosurgery at Penn’s School off Medicine. “By responding to unexpected financial rewards, these cells encode information that seems to help participants maximize reward in the probabilistic learning task.” Learning, previously studied in animal models, seems to occur when dopaminergic neurons, which drive a larger basal ganglia circuit, are activated in response to unexpected rewards and depressed after the unexpected omission of reward. Put simply, a lucky win seems to be retained better than a probable loss.

Researchers develop DNA 'patch' for canine form of muscular dystrophy

Using a novel genetic technology that covers up genetic errors, researchers funded in part by the National Institutes of Health have developed a successful treatment for dogs with the canine version of Duchenne muscular dystrophy, a paralyzing, and ultimately fatal, muscle disease. The technology, known as "exon skipping" uses tailor-made snippets of DNA-like molecules as molecular "patches." These patches cover up mutant DNA sequences that code for making an important muscle protein. The mutant sequences occur in portions of the gene known as exons, which contain the information needed to make the muscle protein. By covering up the mutant regions, the DNA patches allowed the dogs to make an imperfect—but functional—version of the protein, and significantly improve their muscle functioning. Earlier studies showed that it was possible to inject the patches into the bloodstream of mice and deliver them throughout the animals' bodies. The current finding shows that the DNA patches could be delivered by injection throughout the entire body in a much larger animal than a mouse, raising the possibility that they might be successfully delivered throughout the body to human muscles as well. Moreover, the current study represents an advance over the earlier efforts in that it was able to use several different kinds of DNA patches. A combination of different patches, known as a cocktail, would be needed to treat most of the human cases of the disease, which can involve many different exons. The canine version of Duchenne muscular dystrophy occurs naturally in dogs, and affects the same gene that is affected in the human form of the disease. "This is a promising finding," said Duane Alexander, M.D., director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), one of the NIH institutes that provided partial funding for the study. "It's an important step toward realizing the goal of developing a treatment that could alleviate the symptoms of this disorder."

Music tuition can help children improve reading skills

Children exposed to a multi-year programme of music tuition involving training in increasingly complex rhythmic, tonal, and practical skills display superior cognitive performance in reading skills compared with their non-musically trained peers, according to a study published today in the journal Psychology of Music, published by SAGE. According to authors Joseph M Piro and Camilo Ortiz from Long Island University, USA, data from this study will help to clarify the role of music study on cognition and shed light on the question of the potential of music to enhance school performance in language and literacy. Studying children the two US elementary schools, one of which routinely trained children in music and one that did not, Piro and Ortiz aimed to investigate the hypothesis that children who have received keyboard instruction as part of a music curriculum increasing in difficulty over successive years would demonstrate significantly better performance on measures of vocabulary and verbal sequencing than students who did not receive keyboard instruction.
Several studies have reported positive associations between music education and increased abilities in non-musical (eg, linguistic, mathematical, and spatial) domains in children. The authors say there are similarities in the way that individuals interpret music and language and "because neural response to music is a widely distributed system within the brain…. it would not be unreasonable to expect that some processing networks for music and language behaviors, namely reading, located in both hemispheres of the brain would overlap." The aim of this study was to look at two specific reading subskills – vocabulary and verbal sequencing – which, according to the authors, are "are cornerstone components in the continuum of literacy development and a window into the subsequent successful acquisition of proficient reading and language skills such as decoding and reading comprehension."

Important new model shows how proteins find the right DNA sequences

Researchers at Uppsala University and Harvard University have collaboratively developed a new theoretical model to explain how proteins can rapidly find specific DNA sequences, even though there are many obstacles in the way on the chromosomes. The findings are being published today in the scientific journal Nature Physics. In living cells, DNA-binding proteins regulate the activity of various genes so that different cells carry out the right tasks at the right time. For this to work, the DNA-binding proteins need to find the right DNA site sufficiently quickly. The research team behind the new study has previously succeeded in determining that it takes only a few minutes for an individual protein molecule to look through the millions of nearly identical binding alternatives and find the right place to bind. This is nevertheless slower than what is predicted by the established theoretical model for how DNA-binding proteins find their way to the proper place by alternating between diffusing in the cell cytoplasm and along DNA strands. "By also taking into consideration the fact that there are many obstacles in the way when proteins are to diffuse along DNA strands, we can now calculate more exactly how long it takes them to find their way," says Johan Elf, associate professor of molecular biotechnology at the Center for Bioinformatics.

Gladstone scientists reveal key enzyme in fat absorption

Scientists at the Gladstone Institutes of Cardiovascular Disease (GICD) have found that a key enzyme involved in absorbing fat may also be a key to reducing it. The enzyme, acyl CoA: monoacylglycerol acyltransferase 2 or Mgat2 is found in the intestines and plays an important part in the uptake of dietary fat by catalyzing a critical step in making triglyceride, a kind of fat. Triglyceride accounts for nearly one-third of the fat eaten by people in developed countries. Researchers in the laboratory of Robert V. Farese, Jr. MD, found that mice that were genetically modified to lack Mgat2 remain normal on a low-fat diet. However, when fed a high-fat diet that is similar to that eaten by many Americans, the mice do not get fat and do not develop other symptoms of obesity, such as glucose intolerance, hypercholesterolemia, and fatty livers. The mice eat the same number of calories as other mice, and the calories are fully absorbed. Results of their study were published in the current issue of the journal Nature Medicine. "Because mice that lack this enzyme do not gain weight on a high-fat diet, it is an intriguing target for future interventions to prevent weight gain and the problems associated with that extra weight," said Dr. Farese. The mechanism of action, the researchers identified was that the lack of Mgat2 may reduce the uptake of fat in the small intestine and delay its entry into the blood. This process may dissociate fat from carbohydrate absorption and insulin secretion and ultimately lower the amount of fat stored and used. How this happens is not clear. One possibility is that the absorbed fat is partitioned more to tissues where it is burned up. "Differences in Mgat2 expression may contribute to the propensity of some people to gain weight from diets rich in fat," said Eric Yen, PhD, lead author of the study. "Our findings suggest that inhibiting this enzyme in the small intestine might be an effective way to treating metabolic diseases that result from excessive fat intake."

Blocking protein may help ease painful nerve condition

Scientists have identified the first gene that pulls the plug on ailing nerve cell branches from within the nerve cell, possibly helping to trigger the painful condition known as neuropathy. The condition is a side effect of some forms of chemotherapy and can also afflict patients with cancer, diabetes, kidney failure, viral infections, neurodegenerative disorders and other ailments. Researchers at Washington University School of Medicine in St. Louis showed that blocking the dual leucine zipper kinase (DLK) gene inhibits degeneration of ailing nerve cell branches, possibly preventing neuropathy. "Neuropathy can become so extraordinarily painful that some patients stop taking their chemotherapy, regardless of the consequences in their fight against cancer," says co-senior author Aaron DiAntonio, M.D., Ph.D., associate professor of developmental biology. "So we're very excited about the possibilities this gene may offer for reducing that pain." Scientists have known since 1850 that nerve cells have ways to prune branches (also known as axons) that are injured. Although axon pruning is also a normal part of early human development, inappropriate loss of axons in the adult nervous system causes painful sensations that have been compared to burning, freezing or electric shock and have come to be known as neuropathy. DiAntonio's lab previously revealed that the fruit fly's version of DLK helps establish synapses, junctures where two nerve cells communicate. But they found the gene doesn't do the same thing in mice. Curious about DLK's role in mammals, Bradley Miller, an M.D./Ph.D. student in DiAntonio's lab, consulted with co-senior author Jeffrey Milbrandt, M.D., Ph.D., the David Clayson Professor of Neurology. Milbrandt studies the role of various proteins in neurodegeneration. With support from the University's Hope Center for Neurological Disorders, they showed that the long axons of the sciatic nerve in mice with a mutated DLK gene resisted degeneration after it was surgically cut.

A sticky business -- how cancer cells become more 'gloopy' as they die

The viscosity, or 'gloopiness', of different parts of cancer cells increases dramatically when they are blasted with light-activated cancer drugs, according to new images that provide fundamental insights into how cancer cells die, published in Nature Chemistry today (15 March).The images reveal the physical changes that occur inside cancer cells whilst they are dying as a result of Photodynamic Therapy (PDT). This cancer treatment uses light to activate a drug that creates a short-lived toxic type of oxygen, called singlet oxygen, which kills cancerous cells.The research team behind the study says that revealing what happens to viscosity within a dying cancer cell is important because it helps give a better understanding of how cells function and which factors are important for controlling reactions inside cells. Ultimately this could help scientists design more efficient drugs for Photodynamic Therapy and other treatments.The research is also of wider significance because these are the first ever real-time maps showing viscosity changing over a period of time inside a cell during a biologically important process like cell death.Previous studies have shown that the viscosity of human cells and organs also changes in patients with diseases including diabetes and atherosclerosis, says lead author Dr Marina Kuimova from Imperial College London's Department of Chemistry.She explains - "We're still not quite sure exactly what the relationship is between increased stickiness inside cells and disease, but we expect that the two are related."

Iron is involved in prion disease-associated neuronal demise

Imbalance of iron homeostasis is a common feature of prion disease-affected human, mouse, and hamster brains, according to a new study by Dr. Neena Singh and colleagues at Case Western Reserve University School of Medicine, alongside collaborators from Creighton University. These findings, published March 13 in the open-access journal PLoS Pathogens, provide new insight into the mechanism of neurotoxicity in prion disorders, and novel avenues for the development of therapeutic strategies. Unlike other neurodegenerative conditions, prion disorders are sporadic, inherited, and infectious, and affect both humans and animals; common examples are mad cow disease in cattle, scrapie in sheep, and Creutzfeldt-Jakob disease in humans. The causative agent is a misfolded protein referred to as PrP-scrapie that replicates itself by changing the conformation of neighboring copies of the same protein, namely the prion protein. Aggregates of PrP-scrapie are toxic to brain cells and cause a spongy-like appearance in diseased brains. Research from the Singh laboratory suggests that accumulation of PrP-scrapie alters the metabolism of iron in diseased brains. The imbalance of brain iron homeostasis worsens with disease progression, and is not an outcome of end-stage disease. Since iron is highly toxic when mismanaged, this condition is likely to contribute significantly to prion-disease-associated neurotoxicity. The likely cause of this condition is loss of normal function of the prion protein in cellular iron metabolism demonstrated recently by Singh and colleagues, combined with gain of toxic function by the redox-active PrP-scrapie complex as shown in this report.