Posts tagged science

March 13, 2012

The next time you set a trap for that rat running around in your basement, here’s something to consider: you are going up against an opponent whose ability to assess the situation and make decisions is statistically just as good as yours.

A Cold Spring Harbor Laboratory (CSHL) study that compared the ability of humans and rodents to make perceptual decisions based on combining different modes of sensory stimuli—visual and auditory cues, for instance—has found that just like humans, rodents also combine multisensory information and exploit it in a “statistically optimal” way — or the most efficient and unbiased way possible.

"Statistically optimal combination of multiple sensory stimuli has been well documented in humans, but many have been skeptical about this behavior occurring in other species," explains Assistant Professor Anne Churchland, Ph.D., a neuroscientist who led the new study. "Our work is the first demonstration of its occurrence in rodents." The study appears in the March 14 issue of the Journal of Neuroscience.

This discovery is exciting, according to Churchland, because it suggests that the same evolutionarily conserved neural circuits underlie this behavior in both humans and rodents. “By observing this behavior in rodents, we have a chance to explore its neural basis – something that is not feasible to do in people,” Churchland says.

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ScienceDaily (Mar. 13, 2012) — A team of neuroscientists led by a Wayne State University School of Medicine professor has discovered stark developmental differences in brain network function in children of parents with schizophrenia when compared to those with no family history of mental illness.

The study, led by Vaibhav Diwadkar, Ph.D., assistant professor of psychiatry and behavioral neurosciences and co-director of the Division of Brain Research and Imaging Neuroscience, was published in the March 2012 issue of the American Medical Association journal Archives of General Psychiatry and is titled, “Disordered Corticolimbic Interactions During Affective Processing in Children and Adolescents at Risk for Schizophrenia Revealed by Functional Magnetic Resonance Imaging and Dynamic Causal Modeling.”

The results provide significant insight into plausible origins of schizophrenia in terms of dysfunctional brain networks in adolescence, demonstrate sophisticated analyses of functional magnetic resonance imaging (fMRI) data and clarify the understanding of developmental mechanisms in normal versus vulnerable brains. The resulting information can provide unique information to psychiatrists.

The study took place over three years, using MRI equipment at Harper University Hospital in Detroit. Using fMRI the researchers studied brain function in young individuals (8 to 20 years of age) as they observed pictures of human faces depicting positive, negative and neutral emotional expressions. Participants were recruited from the metropolitan Detroit area. Because children of patients are at highly increased risk for psychiatric illnesses such as schizophrenia, the team was interested in studying brain network function associated with emotional processing and the relevance of impaired network function as a potential predictor for schizophrenia.

To investigate brain networks, the researchers applied advanced analyses techniques to the fMRI data to investigate how brain regions dynamically communicate with each other. The study demonstrated that children at risk for the illness are characterized by reduced network communication and disordered network responses to emotional faces. This suggests that brain developmental processes are going awry in children whose parents have schizophrenia, suggesting this is a subgroup of interest to watch in future longitudinal studies.

"Brain network dysfunction associated with emotional processing is a potential predictor for the onset of emotional problems that may occur later in life and that are in turn associated with illnesses like schizophrenia," Diwadkar said. "If you clearly demonstrate there is something amiss in how the brain functions in children, there is something you can do about it. And that’s what we’re interested in."

The results don’t show whether schizophrenia will eventually develop in the subjects. “It doesn’t mean that they have it, or that they will have it,” he said.

"The kids we studied were perfectly normal if you looked at them," he said. "By using functional brain imaging we are trying to get underneath behavior."

"We are able to do this because we can investigate dynamic changes in brain network function by assessing changes in the fMRI signal. This allowed us to capture dramatic differences in how regions in the brain network are interacting with each other," he said.

According to the National Alliance on Mental Illness, schizophrenia affects men and women with equal frequency, but generally manifests in men in their late teens or early 20s, and in women in their late 20s or early 30s.

Source: Science Daily

ScienceDaily (Mar. 13, 2012) — A compound that previously progressed to Phase II clinical trials for cancer treatment slows neurological damage and improves brain function in an animal model of Alzheimer’s disease, according to a new study. The study published the week of March 13 in the Journal of Neuroscience shows that the compound epothilone D (EpoD) is effective in preventing further neurological damage and improving cognitive performance in a mouse model of Alzheimer’s disease (AD). The results establish how the drug might be used in early-stage AD patients.

This is an electron micrographic picture of a cross section of a nerve from an Alzheimer’s model mouse. Structural abnormalities in the nerve are indicated by the arrows. Alzheimer model mice that received the drug epothilone D had a significant reduction in the number of these abnormalities. (Credit: Zhang, et al. The Journal of Neuroscience 2012.)

Investigators from the Perelman School of Medicine at the University of Pennsylvania, led by first author Bin Zhang, MD, PhD, senior research investigator, and senior author Kurt R. Brunden, PhD, Director of Drug Discovery at the Center for Neurodegenerative Disease Research (CNDR), administered EpoD to aged mice that had memory deficits and inclusions within their brains that resemble the tangles formed by misfolded tau protein, a hallmark of AD. In nerve cells, tau normally stabilizes structures called microtubules, the molecular railroad tracks upon which cellular cargo is transported. Tangles may compromise microtubule stability, with resulting damage to nerve cells. A drug that could increase microtubule stability might improve nerve-cell function in AD and other diseases where tangles form in the brain.

EpoD acts by the same microtubule-stabilizing mechanism as the FDA-approved cancer drug paclitaxel (Taxol™). These drugs prevent cancer cell proliferation by over-stabilizing specialized microtubules involved in the separation of chromosomes during the process of cell division. However, the Penn researchers previously demonstrated that EpoD, unlike paclitaxel, readily enters the brain and so may be useful for treating AD and related disorders.

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March 13, 2012

Warm weather may hinder cognitive performance in people with multiple sclerosis (MS), according to results of a Kessler Foundation study e-published online ahead of print by Neurology. An accompanying editorial by Meier & Christodoulou, MS and heat: The smoke and the fire, details the study’s unique aspects, ie, longitudinal followup in a cohort with apparently quiescent disease.

Victoria M. Leavitt, Ph.D., research scientist at Kessler Foundation, is principal investigator for the study, which for the first time, shows a link between warm weather and cognition in people with MS. With more research, this information might help guide people with MS in making life decisions and assist their clinicians in choosing clinical treatment. Scientists may also want to consider the effect of warmer weather on cognition when designing and conducting clinical trials.

Kessler Foundation co-investigators are James F. Sumowski, Ph.D., Research Scientist, Nancy Chiaravalloti, Ph.D., Director of Neuropsychology & Neuroscience Research, and John DeLuca, Ph.D., Vice President for Research. All also have faculty appointments at UMDNJ-New Jersey Medical School.

Memory and processing speed were measured in 40 individuals with MS and 40 healthy people without MS. The study was conducted throughout the calendar year, and the daily temperature at the time of testing was recorded. The results showed that people with MS scored 70 percent higher on the tests on cooler days. There was no connection between daily temperature and cognitive performance for individuals without MS.

To confirm the effect of outdoor temperature, the group examined a separate sample of 45 persons with MS for whom cognitive tests were given at two sessions separated by a 6-month interval. For each person, cognitive performance was worse for testing during the warmer temperature. This finding is particularly important for researchers planning clinical trials with cognitive outcomes, especially since such trials frequently span a 6-month period. If baseline measurements of cognitive function are taken during warm months, the effect of the treatment may be inflated by the temperature effect. Cognitive performance may be a more sensitive indicator of subclinical disease activity than traditional assessments based on sensorimotor or EDSS (Expanded Disability Status score).

Provided by Kessler Foundation

Source: medicalxpress.com

Article Date: 13 Mar 2012 - 1:00 PDT

More than two-thirds of human genes have counterparts in the well-studied fruit fly, Drosophila melanogaster, so although it may seem that humans don’t have much in common with flies, the correspondence of our genetic instructions is astonishing. In fact, there are hundreds of inherited diseases in humans that have Drosophila counterparts.

At the Genetics Society of America’s 53rd Annual Drosophila Research Conference in Chicago, several scientific investigators shared their knowledge of some of these diseases, including ataxia-telangiectasia (A-T), a neurodegenerative disorder; Rett Syndrome, a neurodevelopmental disorder; and kidney stones, a common health ailment. All are the subject on ongoing research using the Drosophila model system.

Andrew Petersen, a graduate student in Dr. David Wassarman’s laboratory at the University of Wisconsin-Madison, discussed his experiments with a fly model of the rare childhood disease ataxia-telangiectasia. A-T causes cell death within the brain, poor coordination, characteristic spidery blood vessels that show through the skin, and susceptibility to leukemias and lymphomas. A-T generally results in a life expectancy of only 25 years.

A-T is normally lethal in flies, but Mr. Petersen induced a mutant that develops symptoms only when the environmental temperature rises above a certain level, allowing Mr. Petersen to control the lethality by varying the fly’s environment. The mutant flies lose their ability to climb up the sides of their vial habitats - a sign of neurodegeneration - and die prematurely. Their glial cells are primarily affected, rather than the neurons that the glia support. In addition, an innate immune response is activated in the compromised glia, a scenario reminiscent of Alzheimer’s and Parkinson’s diseases. “We are one step closer to knowing how these diseases occur and possibly how we can treat them,” Mr. Petersen concluded.

Sarah Certel, Ph.D., assistant professor of biological sciences at the University of Montana-Missoula, works with flies that have been altered to include the human gene MeCP2. This gene controls how neurons use many other genes, and the amount of the protein that it encodes must be within a specific range for the brain to develop normally. Too little of the protein and Rett syndrome results, a disorder on the X chromosome, which exclusively affects females in childhood. (Males with this mutation are generally miscarried or are stillborn.) It causes a constellation of symptoms including characteristic hand-wringing, autism, seizures, cognitive impairment, and loss of mobility. Yet too much of the protein causes similar problems.

In flies, altered levels of the MeCP2 protein affect sleep and aggression. For flies and most model organisms, sleep is inferred as the absence of activity during the day and night. To study sleep, Dr. Certel conducted “actograms” for individual flies. “The actogram records the activities of individually housed flies when they cross an infrared beam,” she explained. The flies’ sleep became fragmented, delayed, and shortened. “We’re studying the link between the cellular changes and behaviors,” she added.

Switching from the brain to the urinary system, it was noted that “Drosophila get kidney stones too” began Julian Dow, Ph.D., professor of molecular and integrative physiology at the University of Glasgow, United Kingdom. The fly version of a kidney is much simpler in design, a quartet of Malpighian tubules that are conveniently transparent.

Dr. Dow discussed a fly mutant called “rosy,” discovered a century ago, that corresponds to the rare human inborn error of metabolism called xanthinuria type 1, as well as a diet-induced blockage that corresponds to the more common human condition of calcium oxalate kidney stones. In time-lapse video, Dr. Dow showed stones appearing and growing in the Malpighian tubule.

“This was the first time in history that we saw kidney stones form - something that you cannot ethically do in humans,” he said. His research group, in collaboration with Dr. Michael Romero at the Mayo Institute, is now searching for chemical compounds that interfere with the formation of stones and their tendency to accrete into painful obstructions. They’ve already found a way to block a gene responsible for transporting the oxalate, slowing stone formation. With time, this work could help reduce the 250,000 emergency room admissions for kidney stones in the USA annually and the more than $2 billion in health care costs for treating them.

These were only three of several human diseases discussed at the Drosophila Conference. Others included oxidative stress, cancer linked to diabetes, amyloid build-up in Alzheimer’s disease, epilepsy, and muscular dystrophy. There are so many human diseases that have Drosophila counterparts that they are listed in a database called Homophila. Given the number that exist, we are certain to be learning more about our health from the fly in the years ahead.  

Source: Medical News Today

ScienceDaily (Mar. 13, 2012) — One of the trickiest parts of treating brain conditions is the blood brain barrier, a blockade of cells that prevent both harmful toxins and helpful pharmaceuticals from getting to the body’s control center. But, a technique published in JoVE, uses an MRI machine to guide the use of microbubbles and focused ultrasound to help drugs enter the brain, which may open new treatment avenues for devastating conditions like Alzheimer’s and brain cancers.

"It’s getting close to the point where this could be done safely in humans," said paper-author Meaghan O’Reilly, "there is a push towards applications."

The current method of disrupting the blood-brain barrier (BBB) is by using osmotic agents such as mannitol, which suck the water out of the cells that form the barrier, causing the gaps between them to get bigger. Unfortunately, this method opens large areas of the barrier, leaving the brain exposed to toxins.

The benefit of the microbubble technique is that it can be used on a very small area of the BBB. The microbubbles, made of lipids (fats) and gas, are injected into the blood stream. When focused ultrasound is applied, the bubbles expand and contract. It is thought that the force of the movement in the bubbles causes the cells that form the BBB to temporarily separate, which allows drugs to reach the brain.

"Microbubble technology has been around for years, though its applications have mostly been as contrast agents for diagnostic ultrasound," said JoVE Editorial Director, Dr. Beth Hovey. "This newer approach, using ultrasound to help the bubbles permeablize the blood brain barrier, will hopefully allow for better treatment of diseases within the brain."

In this method, O’Reilly and her colleagues use the MRI machine to ensure that the barrier opens, and they can also time how long it takes for it to close, which will be important for when the technique is used on patients.

"The ability of focused ultrasound combined with microbubbles to disrupt the blood brain barrier has been known for over a decade. However, because the actual technique can be challenging — there are critical steps involved — the video article fills a gap in the literature that is a major hindrance to people getting into the field," she said.

Source: Science Daily

ScienceDaily (Mar. 13, 2012) — People often wonder if computers make children smarter. Scientists at the University of California, Berkeley, are asking the reverse question: Can children make computers smarter? And the answer appears to be ‘yes.’

Research indicates that babies and toddlers do most of their learning as they “play.” (Credit: © matka_Wariatka / Fotolia)

UC Berkeley researchers are tapping the cognitive smarts of babies, toddlers and preschoolers to program computers to think more like humans.

If replicated in machines, the computational models based on baby brainpower could give a major boost to artificial intelligence, which historically has had difficulty handling nuances and uncertainty, researchers said

"Children are the greatest learning machines in the universe. Imagine if computers could learn as much and as quickly as they do," said Alison Gopnik a developmental psychologist at UC Berkeley and author of "The Scientist in the Crib" and "The Philosophical Baby."

In a wide range of experiments involving lollipops, flashing and spinning toys, and music makers, among other props, UC Berkeley researchers are finding that children — at younger and younger ages — are testing hypotheses, detecting statistical patterns and drawing conclusions while constantly adapting to changes.

"Young children are capable of solving problems that still pose a challenge for computers, such as learning languages and figuring out causal relationships," said Tom Griffiths, director of UC Berkeley’s Computational Cognitive Science Lab. "We are hoping to make computers smarter by making them a little more like children."

For example, researchers said, computers programmed with kids’ cognitive smarts could interact more intelligently and responsively with humans in applications such as computer tutoring programs and phone-answering robots.

And that’s not all.

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March 12th, 2012

Regular use of cholesterol-lowering statin drugs may be associated with a modest reduction in risk for developing Parkinson disease, particularly among younger patients, according to a study in the March issue of Archives of Neurology, one of the JAMA Archives journals.

Statins are one of the most prescribed classes of drugs in the United States and some researchers have hypothesized that the anti-inflammatory and immunomodulating effects of these medications may be neuroprotective. However, statins also may have unfavorable effects on lowering the level of plasma coenzyme Q10, which may be neuroprotective in patients with Parkinson disease (PD), the researchers write in their study background.

Xiang Gao, M.D., Ph.D., of Brigham and Women’s Hospital and Harvard School of Public Health, Boston, and colleagues conducted a prospective study that included 38,192 men and 90,874 women participating in the Health Professional Follow-up study and the Nurses’ Health study.

During 12 years of follow-up from 1994 to 2006, researchers documented 644 incident PD cases (338 in women and 306 in men).

“In summary, we observed an association between regular use of statins and lower risk of developing PD, particularly among younger patients,” the researchers comment. “However, our results should be interpreted with caution because only approximately 70 percent of users of cholesterol-lowering drugs at baseline were actual statin users. Further, the results were only marginally significant and could be due to chance.”

Researchers note that because they classified the use of any cholesterol-lowering drugs before 2000 as statin use, misclassification was inevitably introduced. They also did not collect information on the use of specific statins, which could have different effects on the central nervous system.

When researchers did observe a significant interaction between statin use and age in relation to PD risk it was among study participants younger than 60 years at the start of follow-up, not among those participants who were older.

The authors note that not only have epidemiologic studies produced mixed results on statin use and PD risk, but statins also may have unfavorable effects on the central nervous system.

“In contrast with use of ibuprofen, which has been consistently found to be inversely associated with PD risk in these cohorts as well as in other longitudinal studies, the overall epidemiological evidence relating stain use to PD risk remains unconvincing,” the authors conclude. “Given the potential adverse effects of statins, further prospective observational studies are needed to explore the potential effects of different subtypes of statin on risk of PD and other neurodegenerative diseases.”
(Arch Neurol. 2012;69[3]:380-384).

Source: Neuroscience News

March 12th, 2012

Scientists from the Monell Center report that seven of 12 related mammalian species have lost the sense of sweet taste. As each of the sweet-blind species eats only meat, the findings demonstrate that a liking for sweets is frequently lost during the evolution of diet specialization.

Previous research from the Monell team had revealed the remarkable finding that both domestic and wild cats are unable to taste sweet compounds due to defects in a gene that controls structure of the sweet taste receptor.

Cats are obligate carnivores, meaning that they subsist only on meat. In the current study, published online in Proceedings of the National Academy of Sciences USA, the Monell scientists next asked whether other strict carnivores have also lost the sweet taste receptor.

To do this, they examined sweet taste receptor genes from 12 related mammalian species with varying dietary habits. They once again found taste loss and to their surprise, it was widespread in the meat-eating species.

Senior author Gary Beauchamp, Ph.D., a behavioral biologist at Monell, comments, “Sweet taste was thought to be nearly a universal trait in animals. That evolution has independently led to its loss in so many different species was quite unexpected.”

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