April 27, 2009, 5:26 AM CT

Brain works best when cells keep right rhythms

It is said that each of us marches to the beat of a different drum, but new Stanford University research suggests that brain cells need to follow specific rhythms that must be kept for proper brain functioning. These rhythms don't appear to be working correctly in such diseases as schizophrenia and autism, and now two papers due to be published online this week by the journals Nature and Science demonstrate that precisely tuning the oscillation frequencies of certain neurons can affect how the brain processes information and implements feelings of reward.

"A unifying theme here is that of brain rhythms and 'arrhythmias'," said Karl Deisseroth, MD, PhD, associate professor of bioengineering and of psychiatry and behavioral sciences and senior author of both papers.

An arrhythmia is what heart specialists call a seriously irregular heartbeat. The new findings suggest that, like the cells that keep the beat of the heart (or the coxswain on a rowing team that calls out the rhythm of the strokes), certain brain cells can orchestrate oscillations that ultimately help govern behavior of other cells that are guided by those rhythms.

The brain's bit rate

In the Nature study, which will be published online April 26 along with a companion paper from MIT on which Deisseroth and graduate student Feng Zhang are also authors, Deisseroth's team focused on neurons in mice that produce a protein called parvalbumin. Some scientists have suspected that these neurons drive "gamma" brain waves that oscillate at a frequency of 40 times a second (or Hertz). These waves, as per the hypothesis, might affect the flow of information in the brain. To date this could never be proved because no one could selectively control the neurons and see the resulting effect on the information flow, or oscillations......... Posted by: Emily      Read more         Source

April 27, 2009, 5:19 AM CT

Details of bacterial 'injection' system

New details of the composition and structure of a needlelike protein complex on the surface of certain bacteria may help researchers develop new strategies to thwart infection. The research, conducted in part at the U.S. Department of Energy's Brookhaven National Laboratory, will be published April 26, 2009, in the advance online edition of Nature Structural & Molecular Biology

The researchers were studying a needlelike protein complex known as a "type III secretion system," or T3SS, on the surface of Shigella bacteria, a cause of dysentery. The secretion system is a complex protein structure that traverses the bacterial cell membrane and acts as a biological syringe to inject deadly proteins into intestinal cells. These proteins rupture the cell's innards, leading to bloody diarrhea and sometimes death. Similar secretion systems exist in a range of other infectious bacteria, including those that cause typhoid fever, some types of food poisoning, and plague.

"Understanding the 3D structure of these secretion proteins is important for the design of new broad-spectrum strategies to combat bacterial infections," said co-author of study Joseph Wall, a biophysicist at Brookhaven Lab.

Prior studies of the type III secretion system have revealed that it is composed of some 25 different kinds of proteins assembled into three major parts: a "bulb" that lies within the bacterial cell, a region spanning the inner and outer bacterial membranes, and a hollow, largely extracellular "needle." But to understand how the parts work together to secrete proteins, the researchers mandatory higher-resolution structural information, and knowledge of the chemical makeup and arrangement of the components......... Posted by: Emily      Read more         Source

April 27, 2009, 5:16 AM CT

Making waves in the brain

Researchers have studied high-frequency brain waves, known as gamma oscillations, for more than 50 years, believing them crucial to consciousness, attention, learning and memory. Now, for the first time, MIT scientists and his colleagues have found a way to induce these waves by shining laser light directly onto the brains of mice.

The work takes advantage of a newly developed technology known as optogenetics, which combines genetic engineering with light to manipulate the activity of individual nerve cells. The research helps explain how the brain produces gamma waves and provides new evidence of the role they play in regulating brain functions insights that could someday lead to new therapys for a range of brain-related disorders.

"Gamma waves are known to be [disrupted] in people with schizophrenia and other psychiatric and neurological diseases," says Li-Huei Tsai, Picower Professor of Neuroscience and a Howard Hughes Medical Institute investigator. "This new tool will give us a great chance to probe the function of these circuits".

Tsai co-authored a paper about the work that appears in the April 26 online issue of Nature.

Gamma oscillations reflect the synchronous activity of large interconnected networks of neurons, firing together at frequencies ranging from 20 to 80 cycles per second. "These oscillations are believed to be controlled by a specific class of inhibitory cells known as fast-spiking interneurons," says Jessica Cardin, co-main author on the study and a postdoctoral fellow at MIT's McGovern Institute for Brain Research. "But until now, a direct test of this idea was not possible"......... Posted by: Emily      Read more         Source

April 27, 2009, 5:09 AM CT

Building the lymphatic drainage system

Our bodies' tissues need continuous irrigation and drainage. Blood vessels feeding the tissues bring in the fluids, and drainage occurs via the lymphatic system. While much is known about how blood vessels are built, the same was not true for lymph vessels. Now though, Norrmn et al. have identified two of the lead engineers that direct drainage construction in the mouse embryo.

The engineers are the transcription factors, Foxc2 and NFATc1. Foxc2 had been implicated in lymph vessel development already, but Norrmn and his colleagues have now observed that the factor specifically regulates a late stage of lymph development when large, valve-containing vessels arise from more primitive capillaries. The study will be published online April 27 (www.jcb.org) and will appear in the May 4 print issue of the Journal of Cell Biology

Foxc2 built the lymph vessel valves with the help of NFATc1, which was a known heart valve engineer. Norrmn and his colleagues also showed that Foxc2 and NFATc1 physically interact and that a number of DNA binding sites for the two transcription factors are closely linked. This latter finding generated a long list of target genes that might be controlled by the two factors.

The team now plans to investigate these targets as well as to work out the upstream molecular pathways controlling Foxc2 and NFATc1. Whatever the mechanisms, if the team can show that Foxc2 and NFATc1 also prompt lymph vessel regeneration in adults, boosting these factors could help patients with lymph drainage problems including those that have suffered extensive tissue injuries, or have had lymph nodes removed as part of cancer therapy......... Posted by: Emily      Read more         Source

April 24, 2009, 5:16 AM CT

Chromosome breakpoints contribute to genetic variation

A newly released study reveals that contrary to decades of evolutionary thought chromosome regions that are prone to breakage when new species are formed are a rich source of genetic variation.

The functions of genes found in these "breakpoint regions" differ significantly from those occurring elsewhere in the chromosomes. This suggests that chromosomal organization plays an important evolutionary role, the scientists report.

The study, reported in the journal Genome Research, is the first to show that different parts of chromosomes can have very different evolutionary histories, said University of Illinois animal sciences professor Harris Lewin, who led the research. Lewin directs the Institute for Genomic Biology and is part of an international team that sequenced the cow genome

"Our results demonstrate that chromosome breakage in evolution is non-random and that the breakpoint regions and the more stable regions of chromosomes are evolving in distinctly different ways," he said.

When egg or sperm cells form in animals, maternal and paternal chromosomes first pair up and then recombine. The chromosomes literally break and reattach to one another. In most cases, the new chromosomes have the same arrangement of genes as the parent cells, but with new combinations of maternal and paternal genes......... Posted by: Emily      Read more         Source

April 24, 2009, 5:04 AM CT

Vitamin D levels linked to asthma severity

New research provides evidence for a link between vitamin D insufficiency and asthma severity.

Serum levels of vitamin D in more than 600 Costa Rican children were inversely associated with several indicators of allergy and asthma severity, including hospitalizations for asthma, use of inhaled steroids and total IgE levels, as per a research studythat will appear in the first issue for May of the American Journal of Respiratory and Critical Care Medicine

While prior in vitro studies have suggested that vitamin D may affect how airway cells respond to therapy with inhaled steroids, this is the first in vivo study of vitamin D and disease severity in children with asthma.

Juan Celedn, M.D., Dr. P.H. and Augusto Litonjua, M.D., M.P.H. of Harvard Medical School and his colleagues recruited 616 children with asthma living in the Central Valley of Costa Rica, a country known to have a high prevalence of asthma. Each child was assessed for allergic markers, including both allergen-specific and general sensitivity tests, and assessed for lung function and circulating vitamin D levels. Children whose forced expiratory volume in one second (FEV1) exceeded 65 percent of the predicted value were also tested for airway reactivity.

They observed that children with lower vitamin D levels were significantly more likely to have been hospitalized for asthma in the prior year, tended to have airways with increased hyperreactivity and were likely to have used more inhaled corticosteroids, all signifying higher asthma severity. These children were also significantly more likely to have several markers of allergy, including dust-mite sensitivity......... Posted by: Emily      Read more         Source

April 23, 2009, 5:02 AM CT

Gene switches on during development of epilepsy

A discovery made by scientists at Wake Forest University School of Medicine while studying mice may help explain how some people without a genetic predisposition to epilepsy can develop the disorder.

As per a research findings published this month in the Journal of Neuroscience, senior researcher Dwayne W. Godwin, Ph.D., a professor of neurobiology and anatomy, and his colleagues, report discovering that a gene, already known to predispose people who inherit an active form of it to certain forms of epilepsy, can actually be "switched on" in animals that do not appear to have inherited the active form, and therefore a genetic predisposition, to the condition. The gene codes a calcium channel in the brain that underlies seizures, so the finding may reveal a mechanism by which epilepsy develops in those with no apparent genetic predisposition to it.

"Epilepsy is a terrible disorder that affects millions of kids and adults all over the world," Godwin said. "There are a number of different forms of epilepsy with different symptoms. We don't know why some people acquire epilepsy the cause isn't always clear from the person's genetic makeup. We do know that in some forms of epilepsy, once someone has a seizure they tend to have more. Our findings from this study suggest that something about the brain changes that can lead to this increased tendency to have a seizure. Our study shows that an important change occurs in calcium channels that help to transmit this abnormal activity throughout the brain"......... Posted by: Emily      Read more         Source

April 21, 2009, 5:29 AM CT

Is it better for doctors or patient families to decide?

In the medical realm, people sometimes need to make very difficult choices, such as deciding to end life-support for a terminally ill patient. A newly released study in the Journal of Consumer Research delves into the question of whether it is preferable for patients' families or doctors to make those "tragic choices."

Authors Simona Botti (London Business School), Kristina Orfali, and Sheena S. Iyengar (both Columbia University) say that from the time of Hippocrates until the 1980s the "paternalistic model" dominated the field of bioethics. As per this model, doctors made decisions in their patients' best interest. A newer "autonomous model" assumes that patients should be informed of the pros and cons of various medical therapys and make decisions for themselves or family members. When it comes to tragic choices, how do these two models play out?

The scientists conducted in-depth analysis of nineteen interviews with American and French parents who had infants in Neonatal Intensive Care Units. "The experiences of these parents were similar because they were all confronted by the choice of whether to continue or interrupt their babies' life-support treatment, the decision to interrupt the therapy was made, and the baby died. Crucially, however, the decision model in neonatology varies across the two countries: In the U.S., the autonomous model is used, so the decision to interrupt life-support treatment was made by the parents themselves; on the contrary, in France, the paternalistic model still dominates, so the same decision was made by the physicians on behalf of the parents"......... Posted by: Emily      Read more         Source

April 8, 2009, 5:01 AM CT

Health of retinal blood vessels

Researchers at Schepens Eye Research Institute have observed that the growth factor known as TGF-β is essential to the health of blood vessels in the retina and that blocking it can cause retinal dysfunction. These findings, reported in the April 2 issue of PLoS ONE, may have an important impact on the prevention and therapy of diseases such as diabetic retinopathy and macular degeneration.

"These results are significant because they add to our understanding of the molecules that help to maintain blood vessels in a healthy state," says Patricia D'Amore, PhD, senior scientist at Schepens and principal investigator of the study, who adds that this information appears to be useful in understanding the changes that occur in the retinal microvasculature previous to the development of proliferative diabetic retinopathy.

"Insight into the role of this growth factor may also help clinicians monitor the use of systemic drugs targeting TGF-β, which is elevated in many conditions (such as cancer and fibrotic diseases) to limit any vision problems that might occur as a side effects." adds Tony Walshe, PhD, the first author of the study and a Postdoctoral Fellow in the D'Amore's laboratory team.

Capillaries are the smallest blood vessels in the body and the site at which oxygen and nutrients are transferred from the blood to the tissues. A capillary is composed of an endothelial cell, which forms the lining of the small tube, and a pericyte, which wraps around the outside of the tube. Researchers have long believed that communication between these two cell types is necessary to maintain blood vessel structure and function......... Posted by: Emily      Read more         Source

April 7, 2009, 5:19 AM CT

Evolution-proof insecticides may stall malaria forever

Killing just the older mosquitoes would be a more sustainable way of controlling malaria, as per entomologists who add that the approach may lead to evolution-proof insecticides that never become obsolete.

Each year malaria -- spread through mosquito bites -- kills about a million people, but a number of of the chemicals used to kill the insects become ineffective. Repeated exposure to an insecticide breeds a new generation of mosquitoes that are resistant to that particular insecticide.

"Insecticides sprayed on house walls or bed nets are some of the most successful ways of controlling malaria," said Andrew Read, professor of biology and entomology, Penn State. "But they work by killing the insects or denying them the human blood they turn into eggs. This imposes an enormous selection in favor of insecticide-resistant mosquitoes".

Read and colleagues Matthew Thomas, professor of entomology, Penn State, and Penelope Lynch, doctoral student, Open University, UK, argue that insecticides -- chemical or biological -- that kill only older mosquitoes are a more sustainable way to fight the deadly disease.

"If we killed only older mosquitoes we could control malaria and solve the problem of resistant mosquitoes," said Read. "This could be done by changing the way we use existing insecticides, even by simply diluting them," he added......... Posted by: Emily      Read more         Source