June 10, 2006, 4:56 PM CT

the Pulse of a Gene in Living Cells

Researchers at the Albert Einstein College of Medicine of Yeshiva University have observed for the first time that gene expression can occur in the form of discrete "pulses" of gene activity. The scientists used pioneering microscopy techniques, developed by Dr. Robert Singer and his colleagues at Einstein, that for the first time allow researchers to directly watch the behavior of a single gene in real time. Their findings appeared in the current issue of Current Biology.

When a gene is expressed or "turned on," genetic information is transferred from DNA into RNA. This process, known as transcription, is crucial for translating the gene's message into a functional protein. Diseases such as cancer can result when genes turn on at the improper time or in the wrong part of the body.

Scientists customarily use microarrays (also known as "gene chips") to assess gene expression in tumors and other tissues. But with millions of cells involved, microarrays reflect only "average" gene expression. Just how a gene is transcribed in a single cell-continuously, intermittently or some other way-has largely been a mystery.

Now, in observing a gene that plays a major role in how an organism develops, the Einstein scientists observed a phenomenon that until now has been indirectly observed and only in bacteria: pulses of transcription that turn on and off at irregular intervals. Dr. Singer and his co-workers used a fluorescent marker that sticks to the gene only when it is active. Under a microscope, this fluorescent marker appears when the gene turns on, then disappears (gene "off") and then appears again (gene "on").........

Posted by: Scott      Permalink         Source

June 8, 2006, 7:23 PM CT

Sugar Required For Healthy Brain Development

New approaches to preventing birth defects from a rare metabolic disorder could result from research completed at Washington University School of Medicine in St. Louis. The findings also may have implications for patients with neurodegenerative diseases such as Parkinson's.

To learn more about how glucose affects human development, Mary Carayannopoulos, Ph.D., instructor in pediatrics, developed the first vertebrate model of glucose homeostasis and embryonic development using the zebrafish. Their transparent embryos develop similarly to humans, except that they grow outside of the mother's body, where development can be more easily observed. The model provides the foundation for and insight into the roles of nutrition and genetics in human birth defects.

Carayannopoulos used the zebrafish model to study Glut1 deficiency. Glut1 is a protein that transports glucose in cerebrospinal fluid to the brain. Glut1 deficiency syndrome in humans is linked to microcephaly, epilepsy, developmental delays and other neurologic abnormalities.

Results of the study appear in the recent issue of the Journal of Biological Chemistry, but are available now online. Penny J. Jensen, Ph.D., staff scientist in the Department of Pediatrics, was lead author of the study.

Carayannopoulos lowered Glut1 levels in the zebrafish embryo. Over 72 hours of observing the developing fish, she found that Glut1 deficiency led to cell death in the brain, which uses glucose as its energy source. When injecting the zebrafish with another protein, Bad, which normally activates cell death, the Glut1 and Bad seemed to cancel each other out, correcting brain defects and promoting cell survival.........

Posted by: Daniel      Permalink         Source

June 8, 2006, 7:19 PM CT

Role Of Central Nervous System In MS-like Disease

It may sound like a case of blame the victim, but scientists at Washington University School of Medicine in St. Louis have shown that cells in the central nervous system can sometimes send out signals that invite hostile immune system attacks. In mice the scientists studied, this invitation resulted in damage to the protective covering of nerves, causing a disease resembling multiple sclerosis.

"It's been clear for quite a while that our own lymphocytes (white blood cells) have the ability to enter the central nervous system and react with the cells there," says John Russell, Ph.D., professor of molecular biology and pharmacology. "Under normal circumstances, the brain and the immune system cooperate to keep out those cells that might harm the brain. But in people with multiple sclerosis, they get in."

The scientists found that they could prevent destructive immune cells from entering nervous system tissue by eliminating a molecular switch that sends "come here" messages to immune cells. Ordinarily, flipping that switch would cause immune cells to rush to the vicinity of the cells that sent the signals and destroy whatever they consider a danger - including nerve cell coatings.

But in the mice in which the switch was removed, the scientists saw that immune cells previously primed by the researchers to attack the central nervous system (CNS) did not enter the CNS, and the mice stayed healthy.........

Posted by: Daniel      Permalink         Source

June 8, 2006, 7:15 PM CT

Erotic Images Elicit Strong Response From Brain

A new study suggests the brain is quickly turned on and "tuned in" when a person views erotic images.

Scientists at Washington University School of Medicine in St. Louis measured brainwave activity of 264 women as they viewed a series of 55 color slides that contained various scenes from water skiers to snarling dogs to partially-clad couples in sensual poses.

What they found may seem like a "no brainer." When study volunteers viewed erotic pictures, their brains produced electrical responses that were stronger than those elicited by other material that was viewed, no matter how pleasant or disturbing the other material may have been. This difference in brainwave response emerged very quickly, suggesting that different neural circuits may be involved in the processing of erotic images.

"That surprised us," says first author Andrey P. Anokhin, Ph.D., research assistant professor of psychiatry. "We believed both pleasant and disturbing images would evoke a rapid response, but erotic scenes always elicited the strongest response."

As subjects looked at the slides, electrodes on their scalps measured changes in the brain's electrical activity called event-related potentials (ERPs). The scientists learned that regardless of a picture's content, the brain acts very quickly to classify the visual image. The ERPs begin firing in the brain's cortex long before a person is conscious of whether they are seeing a picture that is pleasant, unpleasant or neutral.........

Posted by: Daniel      Permalink         Source

June 5, 2006, 11:17 PM CT

A New Way to Build Bone

Howard Hughes Medical Institute (HHMI) scientists at Stanford University have found that they can increase bone mass in mice by tweaking the shape of a regulatory protein.

HHMI investigator Gerald Crabtree and HHMI predoctoral fellow Monte Winslow report that slightly increasing the activity of a protein called NFATc1 causes massive bone accumulation, suggesting that NFATc1 or other proteins that regulate its activity will make good targets for drugs to treat osteoporosis. They report their findings as per a research findings reported in the June 6, 2006, issue of Developmental Cell.

In vertebrates, bone is constantly being formed and being broken down throughout life. Cells called osteoclasts continuously degrade bone, while cells called osteoblasts replenish it.

"Ideally, they are perfectly balanced," said Crabtree, the senior author of the study. "Over the course of a lifetime, if everything goes well, we'll maintain almost exactly identical bone mass." However, if the balance is upset, and more bone is destroyed than formed, osteoporosis results, increasing the risk of fractures.

The new study arose from the researchers' curiosity about reports that patients who were treated with the drug cyclosporine-often given to suppress the immune system before organ transplants-tend to lose bone mass. Those patients were also at increased risk of bone fractures, said first author Winslow, who led the study as an HHMI predoctoral fellow in Crabtree's lab. Winslow is now working as a postdoctoral fellow in the lab of HHMI investigator Tyler Jacks at the Massachusetts Institute of Technology.........

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June 4, 2006, 8:38 AM CT

Gene Therapy Protects Mice From Radiation

University of Pittsburgh School of Medicine scientists have successfully protected mice against the damaging effects that radiation can have on bone marrow using gene treatment. Based on these results, the scientists believe this approach may be able to protect first responders in the event of a radiological accident or the detonation of a crude radiological weapon, or "dirty bomb." The findings are being presented at the American Society of Gene Therapy annual meeting in Baltimore, May 31 to June 4.

Since the events of Sept.11, there has been growing concern that terrorists may use a dirty bomb--a conventional explosive wrapped in radiological material--or attack a nuclear power facility to disperse high-dose radiation across a populated area. Experts believe a significant number of the population would die within 30 days of exposure to a high dose of radiation from such an event, which has prompted the federal government to fund efforts to develop medical interventions against radiological and nuclear threats.

In this study, Pitt scientists used gene treatment to deliver the compound manganese superoxide dismutase-plasmid liposome (MnSOD-PL) to the cells of female mice. Twenty-four hours later, groups of mice that received the therapy and control mice that did not were exposed to varying doses of whole body radiation. Following irradiation, the mice were weighed daily and observed for signs of irradiation-induced damage to their bone marrow. Control mice irradiated at the higher doses lost weight and died fairly rapidly due to bone marrow damage. In contrast, mice treated with the MnSOD-PL gene treatment showed no changes in body weight, had little bone-marrow damage, and lived longer compared to the control irradiated mice.........

Posted by: Scott      Permalink         Source

June 1, 2006, 6:17 PM CT

How Brain Controls Movement

By training a group of human subjects to operate a robot-controlled joystick, Johns Hopkins scientists have shown that the slower the brain "learns" to control certain muscle movements, the more likely it is to remember the lesson over the long haul. The results, the researchers say, could alter rehabilitation approaches for people who have lost motor abilities to brain injuries like strokes.

In a report on the work in the May 23 issue of PLoS Biology, the scientists built on their observations that some parts of the brain learn - and forget - fast, while others learn more slowly and more lastingly. Both types of learning are critical.

"We believe our work is the first to show that motor learning involves different time scales and implies that the best strategy in rehabilitating a stroke patient should focus on slow learning because slow-learned motor skills will be maintained longer," says the report's senior author, Reza Shadmehr, Ph.D., a professor of biomedical engineering in the Institute of Basic Biomedical Sciences at Johns Hopkins.

Neuroresearchers long have thought that two things are mandatory for mastering such muscle control - time and error. Time refers to the need to "sleep on it," for the brain to somehow process and "remember" how to carefully control muscles. As for error, it's thought that mistakes help the brain and muscles fine-tune fine movements. The requirement for time and error explains why repetition of simple movements day after day is used routinely in rehabilitating partially paralyzed stroke patients and those with other brain injuries.........

Posted by: Daniel      Permalink         Source

May 30, 2006, 10:55 PM CT

Making Nerve Fibers Regenerae

Scientists at Children's Hospital Boston have discovered a naturally occurring growth factor that stimulates regeneration of injured nerve fibers (axons) in the central nervous system. Under normal conditions, most axons in the mature central nervous system (which consists of the brain, spinal cord and eye) cannot regrow after injury. The previously unrecognized growth factor, called oncomodulin, is described in the May 14 online edition of Nature Neuroscience.

Neuroresearchers Yuqin Yin, MD, PhD, and Larry Benowitz, PhD, who are also on the faculty of Harvard Medical School, did their studies in the optic nerve, which connects nerve cells in the eye's retina to the brain's visual centers, and is often used as a model in studying axon regeneration.

When oncomodulin was added to retinal nerve cells in a Petri dish, with known growth-promoting factors already present, axon growth nearly doubled. No other growth factor was as potent. In live rats with optic-nerve injury, oncomodulin released from tiny sustained-release capsules increased nerve regeneration 5- to 7-fold when given along with a drug that helps cells respond to oncomodulin. Yin, Benowitz and his colleagues also showed that oncomodulin switches on a variety of genes associated with axon growth.

Benowitz, the study's senior investigator, believes oncomodulin could someday prove useful in reversing optic-nerve damage caused by glaucoma, tumors or traumatic injury. In addition, the lab has shown that oncomodulin works on at least one other type of nerve cell, and now plans to test whether it also works on the types of brain cells that would be relevant to treating conditions like stroke and.........

Posted by: Daniel      Permalink         Source

May 30, 2006, 6:58 AM CT

Clever Bacteria Riding In The Stem-cell

Scientists have discovered a new clue to how bacterial parasites are able to produce a long-term infection that can spread through an insect population. They have found that a type of bacteria that infects insects actually hitchhikes in the eggs of fruit flies. This ensures that the bacteria are passed from mother to offspring.

The findings show that in the first stages of infection, Wolbachia bacteria home in on stem-cell niches in the fruit fly, where they can continually infect the cells that produce eggs. Stem-cell niches are specialized cellular environments that provide stem cells with the support needed for differentiation and self-renewal.

The new studies offer the first glimpses of how Wolbachia infection, which occurs in a wide range of insects, is passed from one generation to the next. As per the researchers, their experiments with the fruit fly Drosophila offer a valuable laboratory model for tracing the machinery bacteria use to infect insects. The basic studies could ultimately help researchers understand the mechanisms underlying insect-borne parasitic diseases that affect humans.

Howard Hughes Medical Institute (HHMI) investigator Eric Wieschaus, first author and HHMI research associate Horacio Frydman, Jennifer Li, and Drew Robson collaborated on the studies. The researchers, who are all at Princeton University, published their findings in the May 25, 2006, issue of the journal Nature.........

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May 29, 2006, 9:16 PM CT

Potential Treatments For Type 2 Diabetes

Scientists funded by the Canadian Institutes of Health Research (CIHR) and the Canadian Diabetes Association (CDA) have identified an unsuspected role of a protein named SHP-1 that could constitute a new therapeutic path against Type 2 Diabetes.

Under the direction of professor Andre Marette (Laval University), Nicole Beauchemin (McGill University), Martin Oliver (McGill University Health Centre) and Katherine Siminovitch (University of Toronto) were part of a Canadian and American team which published an article in the recent issue of Nature Medicine that explains the role of SHP-1 in the control of blood glucose.

The scientists already knew that SHP-1 played a role in regulating the immune system. However, no one had previously taken the time to verify if this protein was involved in the regulation of metabolism. This is precisely what this team of Canadian and American scientists did, thanks to a series of mutant or genetically modified mice producing little or no SHP-1.

"Our results indicate that these mice are extremely sensitive to insulin and, consequently, they are very effective in metabolising glucose at the level of the liver and the muscles," notes Andre Marette. In addition, the scientists highlighted that SHP-1 inhibits the decomposition of insulin by the liver. "This could explain the increase in the insulin concentrations of certain metabolic disorders associated with obesity," indicates the researcher.........

Posted by: JoAnn      Permalink         Source