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December 15, 2005, 7:46 PM CT

Neuron Sprouts Its Branches

Neuron Sprouts Its Branches Michael D. Ehlers, M.D., Ph.D.
Neurobiologists have gained new insights into how neurons control growth of the intricate tracery of branches called dendrites that enable them to connect with their neighbors. Dendritic connections are the basic receiving stations by which neurons form the signaling networks that constitute the brain's circuitry.

Such basic insights into neuronal growth will help scientists better understand brain development in children, as well as aid efforts to restore neuronal connections lost to injury, stroke or neurodegenerative disease, said the researchers.

In a paper published in the Dec. 8, 2005, issue of Neuron, Howard Hughes Medical Institute investigator Michael Ehlers and colleagues reported that structures called "Golgi outposts" play a central role as distribution points for proteins that form the building blocks of the growing dendrites.

Besides Ehlers, who is at Duke University Medical Center, other co-authors were April Horton in Ehlers' laboratory; Richard Weinberg of the University of North Carolina at Chapel Hill.; Bence Rácz in Weinberg's laboratory; and Eric Monson and Anna Lin of Duke's Department of Physics. The research was sponsored by The National Institutes of Health.

The Golgi apparatus is a cellular warehouse responsible for receiving, sorting and shipping cargoes of newly synthesized molecules needed for cell growth and function. Until the new findings, scientists believed that only a central Golgi apparatus played a role in such distribution, said Ehlers.

"In most mammalian cells, the Golgi has a very stereotyped structure, a stacked system that resides near the cell nucleus in the middle of the cell," he said. "But mammalian neurons in the brain are huge, with a surface area about ten thousand times that of the average cell. So, it was an entirely open question where all the membrane components came from to generate the complex surface of growing dendrites. And we thought these remote structures we had discovered in dendrites called Golgi outposts might play a role."........

Daniel      Permalink

December 14, 2005, 7:24 PM CT

Mathematics For Discerning Immune Response

Mathematics For Discerning Immune Response
The National Institutes of Health (NIH) has awarded the University of Pittsburgh School of Medicine a five-year, $9.1 million contract to develop sophisticated mathematical models for investigating how the immune system responds to the pathogens that cause flu, tuberculosis (TB) and tularemia, an particularly dangerous infection that some authorities believe could be used as a biological weapon. Such models should help expedite the development of vaccines and therapies against these and other infectious agents and help scientists and public health officials in their efforts to predict or prevent disease outbreaks as well as determine the best courses of therapy.

The contract establishes Pitt as an Immune Modeling Center, one of four supported by the NIH's National Institute of Allergy and Infectious Diseases (NIAID), and takes advantage of Pitt's existing collaborations with Carnegie Mellon University and the University of Michigan.

"This center's work will draw upon our expertise in mathematical modeling of the immune system as well as our knowledge about immunity to infectious diseases. Working as a team of immunologists, computational biologists, computer researchers and mathematicians, our goal is to capture the complexity of the immune system through mathematics," said Penelope A. Morel, M.D., associate professor of immunology and medicine at the University of Pittsburgh School of Medicine and principal investigator of the Pitt-based Immune Modeling Center. Shlomo Ta'asan, Ph.D., professor of mathematics in Carnegie Mellon's Mellon College of Science, is co-principal investigator of the center.

The Immune Modeling Center will focus on understanding the innate, or natural, and adaptive immune responses to influenza A virus, Mycobacterium tuberculosis, which causes TB, and Francisella tularensis, the bacterium responsible for tularemia. Since each of these organisms enters the body via the lung, the investigators will study the specific immune cells recruited to the lung and identify the particular genes expressed and the molecules produced in response to infection. A combination of mathematical and animal models will be employed to test different vaccine and therapeutic strategies, including a novel approach that aims to enhance immune response through certain proteins called cytokines.........

Mark      Permalink

December 14, 2005 7:11 PM CT

Comprehensive Effort to Explore Cancer Genomics

Comprehensive Effort to Explore Cancer Genomics
The National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both part of the National Institutes of Health (NIH), today launched a comprehensive effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, particularly large-scale genome sequencing. The overall effort, called The Cancer Genome Atlas (TCGA), will begin with a pilot project to determine the feasibility of a full-scale effort to systematically explore the universe of genomic changes involved in all types of human cancer.

"Now is the time to move forward with this pioneering initiative. Thanks to the tools and technologies developed by the Human Genome Project and recent advances in using genetic information to improve cancer diagnosis and therapy, it is now possible to envision a systematic effort to map the changes in the human genetic blueprint associated with all known forms of cancer," said NIH Director Elias A. Zerhouni, M.D. "This atlas of genomic changes will provide new insights into the biological basis of cancer, which in turn will lead to new tests to detect cancer in its early, most treatable stages; new therapies to target cancer at its most vulnerable points; and, ultimately, new strategies to prevent cancer."

NCI and NHGRI announced today at a news conference in Washington, D.C., that they have each committed $50 million over three years to the TCGA Pilot Project. The project will develop and test the complex science and technology framework needed to systematically identify and characterize the genetic mutations and other genomic changes associated with cancer. The pilot will involve a few types of cancer that will be chosen for their value in helping to determine the feasibility of a possible larger-scale project. The process for determining the types of cancers to be studied is currently underway.........

Daniel      Permalink

December 13, 2005

Intestinal Stem Cells of Fruit Fly

Intestinal Stem Cells of Fruit Fly
Howard Hughes Medical Institute scientists have identified stem cells in the gut of the fruit fly - a finding that may lead to new insights into digestive diseases, intestinal cancers, and the infection strategies used by insect-borne parasites. The new discovery puts to rest a scientific debate over whether invertebrates have gut stem cells.

From an evolutionary perspective, the discovery of immature cells that differentiate into multiple types of gut cells suggests that the digestive tract of the fruit fly is likely to be a more similar, albeit simpler, version of that found in humans.

As a result of the new findings, researchers now envision using the fruit fly - a genetically malleable model organism - to explore normal and pathogenic regeneration of the digestive tract in ways that were not available before.

The two HHMI research teams reported their independent findings on December 7, 2005, in two online research articles published in the journal Nature. The two groups were led by Craig Micchelli and HHMI investigator Norbert Perrimon, who are both at Harvard Medical School, and Benjamin Ohlstein and HHMI investigator Allan C. Spradling, who are both at the Carnegie Institution of Washington.

Eventhough Drosophila stem cells have proven invaluable in studying regenerating tissues such as the reproductive system, they had not been found in the digestive tract. In fact, a number of researchers believed that the fly intestinal tract was a relatively stable tissue, in contrast to those of humans and mice, which undergo constant turnover to replace cells damaged or lost to abrasion from ingested foods or exposure to toxins and pathogens.

To find out if the digestive tract of the fly harbored stem cells, both research groups began by using cell-tagging tracers. In this way, they determined that the Drosophila gut appeared to contain different types of cells - those that nestled against muscle tissue of the gut wall and those that extended into the interior space. Both groups used genetic techniques to label cell lineages in the Drosophila gut. Those approaches revealed that certain cells divided constantly, whereas others had differentiated into mature gut cells and ceased dividing.........

Scott      Permalink

December 13, 2005

Cells can live without molecules once considered essential

Cells can live without molecules once considered essential
Leave it to the bacteria that cause tooth decay to be able to live without something all cells were thought to require.

Researchers have long believed a certain biochemical pathway involved in the folding and delivery of proteins to cell membranes is essential for survival. Now University of Florida scientists have discovered that Streptococcus mutans, the decay-causing organism that thrives in a number of a mouth, can do just fine without it.

The findings, reported this month in the Proceedings of the National Academy of Sciences, have rocked the cellular biology scientific community, which has long considered the pathway to be crucial. The report may also explain why strains of the bacteria can survive in the harsh acidic environment they create in the mouth.

"We were met with skepticism ..... because the dogma was that this biochemical pathway is key for all living cells," said study investigator Jeannine Brady, an associate professor of oral biology at the UF College of Dentistry. "As far as we know, this is the first example of any bacteria that can cope without this pathway; all of the existing literature indicated it is vital.".

The signal recognition particle, or SRP, pathway is a primary mechanism by which proteins are chaperoned from cellular assembly lines, where they are made, to the protective outer surface of the cells, where they are inserted. Without a steady infusion of proteins, the membrane weakens and the cell - in this case, a bacterium - becomes unable to protect itself from harsh environmental conditions.

In the human mouth, its natural environment, it is typically S. mutans that goes on the attack. When sugary foods are eaten, the S. mutans population explodes, excreting lactic acid as it digests sugar. The acid makes life difficult for other helpful bacteria and demineralizes tooth enamel, causing decay.........

Scott      Permalink

December 12, 2005

Researchers Publish Dog Genome Sequence

Researchers Publish Dog Genome Sequence
An international team, led by scientists at the Broad Institute of MIT and Harvard, today announced the publication of the genome sequence of the dog. In the Dec. 8 issue of the journal Nature, the scientists present a detailed analysis of the dog genome and describe how the data offer the potential for improving the health of man and man's best friend.

"When compared with the genomes of human and other important organisms, the dog genome provides a powerful tool for identifying genetic factors that contribute to human health and disease," said Francis S. Collins, M.D., Ph.D., director of the National Human Genome Research Institute (NHGRI), which supported the research. "This milestone is particularly gratifying because it will also directly benefit veterinary researchers' efforts to better understand and treat diseases afflicting our loyal canine companions."

Efforts to create the genetic tools needed for mapping disease genes in dogs have gained momentum over the last 15 years, and already include a partial survey of the poodle genome. More than two years ago, Kerstin Lindblad-Toh, Ph.D., co-director of the genome sequencing and analysis program at the Broad Institute, and her colleagues embarked on a two-part project to assemble a complete map of the dog genome.

In the first phase, they acquired high-quality DNA sequence covering nearly 99 percent of the dog genome, from a female boxer named Tasha. The boxer was chosen as a representative of the average purebred dog to produce what has become a reference sequence for the dog genome community. Using the sequence information as a genetic "compass," they navigated the genomes of 10 different dog breeds and other related canine species, including the gray wolf and coyote. In this sampling, they pinpointed tiny spots of genetic variation, called single nucleotide polymorphisms (SNPs), which serve as recognizable signposts that can be used to locate the causes of genetic disease.........

Scott      Permalink

December 11, 2005

Willingness Of Minorities To Participate In Health Research

New findings by scientists at the National Institutes of Health show that minorities participate in health research studies at the same rate as non-Hispanic whites when they are made aware of the study and meet the medical requirements. The findings counter the widely held notion that minorities are less willing to participate and lead the scientists to suggest that minority involvement is more a matter of access than attitude.

The study was led by scientists in the Department of Clinical Bioethics at the National Institutes of Health Clinical Center, the hospital at NIH. The work is published online December 6, 2005 in the medical journal PLoS Medicine, published by the Public Library of Science.........
Janet      Permalink

MicroRNAs shape evolution (December 11, 2005)
RNA continues to shed its reputation as DNA's faithful sidekick. Now, scientists in the lab of Whitehead Institute Member David Bartel have found that a class of small RNAs called microRNAs influence the evolution of genes far more widely than prior research had indicated. "MicroRNAs are affecting the majority of protein-coding genes, either at a functional level or an evolutionary level," says Andrew Grimson, a post-doctoral fellow in Bartel's lab.

Flatworms yield insights (December 11, 2005)
If you take a planarian flatworm and chop it in half, something extraordinary happens: One section grows a new head, the other a new tail, and soon you have two new flatworms. Chop it into quarters, or eighths, and you'll notice the same thing. For centuries researchers have puzzled over this biological phenomenon, but only recently have they understood that these creatures are a goldmine for exploring how stem cells regenerate damaged tissue. Now, researchers at Whitehead Institute for Biomedical Research and University of Utah School of Medicine have begun to understand the biological processes of how the planarian flatworm achieves in itself what researchers hope to one day accomplish in the clinic: complete regeneration of damaged tissue.

  • Laser Light from Silicon (December 8, 2005)
  • Hair Follicle Stem Cells (December 8, 2005)

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