Growth Factor Stimulation Leads To Increase In New Neurons
Posted: Friday, August 24, 2001
Source: Howard Hughes Medical Institute (http://www.hhmi.org/)
August 24, 2001 – While teasing out the molecular signals that govern neural development in fruit flies, researchers have discovered how brain cells "remember" the order in which they are "born" from precursor stem cells. This type of molecular memory appears to determine the specific cell type the newly born cells will become and influences where in the developing brain those cells will reside permanently.
In an article published in the August 24, 2001, issue of the journal Cell, Howard Hughes Medical Institute investigator Chris Q. Doe and colleagues at the University of Oregon reported that Drosophila neural precursor cells, called neuroblasts, sequentially activate four different transcription factors. Transcription factors are proteins that activate or repress the expression of genes.
This sequence of transcription factor activation allows the neuroblasts to give rise to a series of different daughter cells, which ultimately become neurons and glial cells in the fruit fly brain. The scientists found that the daughter cells continue to produce the particular transcription factor that was active in the neuroblast at the time of their birth – a "memory" that allows neurons to maintain differences based on their time of birth. For example, first-born neurons always make the longest axon projections to distant targets, compared to later-born neurons from the same stem cell.
"Before we started this work, it was known that each neuroblast makes many different types of neurons and glia, and that occurs in a particular order," said Doe. "But the genes that control the fate of the cells in that sequence were not known. Also, it was not known whether there is one set of genes that works for all stem cells, or whether each of the many different types of stem cells in the fly has its own set of genes that work in some combination."
According to Doe, Drosophila is an ideal model for studying the order in which specific neural cells arise from stem cells because there are well known markers that can be used to determine the stage of development at which individual neurons are born. "So we can search for the molecular markers -- such as transcription factors, neurotransmitters and other gene products -- that reveal early, middle and late neurons," said Doe. "We can also create and study mutants in genes that affect this birth order."
In their experiments, the scientists sought to understand in what order the fly neuroblasts expressed four transcription factors that were good candidates for regulating the birth order of daughter cells. These transcription factor genes are called hunchback, Krüppel, pdm and castor.
"We first established when each neuron was born from a particular stem cell," said Doe. "And once we had that foundation, we looked for genes that correlated with the birth of the first-born cells, second-born, third-born, and so on. And then we manipulated those cells genetically to determine whether the transcription factors made any difference in the kinds of neuronal cells they would become."
The experiments revealed that the neuroblasts sequentially and transiently expressed hunchback, Krüppel, pdm and then castor in that order. "We found these windows of expression in which a neuroblast would express just one of the transcription factors," said Doe. "Then the daughter cells born during that window – say, the window during which hunchback was being expressed – would maintain hunchback expression permanently. And that's one way the daughter cells can have a molecular memory of their birth order."
This order of genes is critical for normal brain development, because when one of the first genes in the sequence (hunchback, for example) is artificially turned 'on' continuously in a stem cell, that cell will repeatedly make first-born neurons and never make the later-born neurons that it would normally, Doe explained. Thus, the sequential expression of all four genes is necessary to make different neurons from a single stem cell.
"The bottom line is that we have found four genes that work in a concerted way in every stem cell lineage," said Doe. "So, it's not that each stem cell has its own set of genes, but rather all of the Drosophila stem cells that we've been working on use that same set of four genes."
According to Doe, while fruit flies are evolutionarily distant from mammals, the lessons learned about neural development in the insect might well be important in understanding human neural development. "The Drosophila system is simple compared to mammals, but what I have found amazing is the apparent parallels between mammalian cortical development and neural stem cells in flies. Just as in flies, there are precursor cells in the mammalian central nervous system that sequentially produce the different types of neurons that go to the different cortical different layers."
Doe emphasized that researchers still do not know whether flies and mammals use the same kinds of transcription factors to control neural development. However, he and his colleagues are currently exploring possible parallels in neural development between flies and mammals.
According to Doe, if the transcription factors are similar, findings in flies could have important implications for the clinical use of human neural stem cells to regenerate brain tissue damaged by such disorders as Parkinson's disease.
"If stem cells undergo an irrevocable change as they go through this sequence of gene expression, they will not be very useful for therapeutic purposes, unless we can learn to reset them back to 'ground zero,'" said Doe. "Or, if we can learn to change them by re-expressing one or another of the transcription factors, we can essentially reset them so they can be used to replace particular kinds of neurons lost to disease," he said.
Note: This story has been adapted from a news release issued by Howard Hughes Medical Institute for journalists and other members of the public.
Send page by E-Mail Astronomers Go Behind The Milky Way To Solve X-Ray Mystery
Posted: Thursday, August 23, 2001
Source: NASA/Goddard Space Flight Center (http://www.gsfc.nasa.gov)
Through layers of gas and dust that stretch for more than 30,000 light-years, astronomers using NASA's Chandra X-ray Observatory have taken a long, hard look at the plane of the Milky Way galaxy and found that its X-ray glow comes from hot and diffuse gas. The findings, published in the August 10 issue of the journal Science, help to settle a long-standing mystery about the source of the X-ray emission from the galactic plane.
Scientists have debated whether the Milky Way plane's X-ray emission was diffuse light or from individual stars. Armed with Chandra, an international team led Dr. Ken Ebisawa of NASA's Goddard Space Flight Center, Greenbelt, MD, zoomed in on a tiny region of the galactic plane in the constellation Scutum.
"The point sources we saw in the galactic plane were actually active galaxies with bright cores millions of light-years behind our galaxy," said Ebisawa. "The number of these sources is consistent with the expected number of extragalactic sources in the background sky. We saw few additional point sources within our galaxy."
The observation marks the deepest X-ray look at the so-called "zone of avoidance" -- a region of space behind which no optical observation has ever been taken because thick dust and gas in the spiral arms of the Milky Way galaxy block out visible radiation. Infrared, radio and X-rays, however, can penetrate this dust and gas. Detection of diffuse X-rays emanating from the galactic plane, what we call the "Milky Way" in visible light, indicates the presence of plasma gas with temperatures of tens of millions of degrees Celsius.
Gas this hot would escape the gravitational confines of the Milky Way galaxy under normal ircumstances. The fact that it still lingers within the galactic plane is the next mystery to solve. One possibility, suggested by Ebisawa, is that hot plasma may be confined to the Milky Way by magnetic fields.
The Chandra observation, conducted in February 2000, lasted 28 hours. The team observed what was known to be a "blank" region of the galactic plane where the Japanese X-ray satellite ASCA had previously observed but found no individual X-ray sources.
The team also discovered 36 bright distant galaxies lurking in the background of this section of the galactic plane, while the foreground was devoid of stars or other individual objects emitting X-rays. Chandra, and now the European XMM-Newton satellite, are at long last beginning to collect light from behind our galaxy. X-ray radiation from the 36 newly discovered galaxies passes through the Milky Way on its journey toward Earth. This light, therefore, carries the imprint of all that it passes through and will allow astronomers to measure the distribution and physical condition of matter in our galaxy.
Participating in the Chandra observation and Science article are Yoshitomo Maeda of Pennsylvania State University, University Park; Hidehiro Kaneda of the Institute of Space and Astronautical Science in Japan; and Shigeo Yamauchi of Iwate University in Japan.
Chandra observed the galactic plane with its Advanced CCD Imaging Spectrometer (ACIS) instrument, which was developed for NASA by Pennsylvania State University, University Park, and Massachusetts Institute of Technology, Cambridge. NASA's Marshall Space Flight Center in Huntsville, AL, manages the Chandra program, and TRW, Inc., Redondo Beach, CA, is the prime contractor for the spacecraft. The Smithsonian's Chandra X-ray Center controls science and flight operations from Cambridge, MA.
Images associated with this release are available at: http://chandra.harvard.edu and http://chandra.nasa.gov
Editor's Note: The original news release can be found at
Send page by E-Mail Spacecraft Sees Solar System Under Construction
Posted: Wednesday, August 22, 2001
Source: NASA/Goddard Space Flight Center (http://www.gsfc.nasa.gov)
Far Ultraviolet Spectroscopic Explorer (FUSE) Spacecraft Sees Solar System Under Construction
A nearby young star recently gave birth to millions of comets, according to new observations using NASA's Far Ultraviolet Spectroscopic Explorer (FUSE) spacecraft. The result provides clues to how our own solar system formed and evolved.
The star, Beta Pictoris, is estimated to be about 20 million years old, relatively young for a star whose life will span billions of years. It is about 60 light years from Earth, in the direction of the southern constellation Pictor (Painter's Easel). (One light year is almost 6 trillion miles, or about 9.6 trillion kilometers.) A 200 billion-mile diameter disk of dust and gas surrounds Beta Pictoris, and previous observations have given hints that planets may be forming (or recently formed) deep within.
The new research by an international team of astronomers shows how the chemistry of the disk implies that comets have formed around Beta Pictoris as well, and gives additional evidence that these comets are evaporating by the millions. The journal Nature will publish this research August 16.
"We are very excited about these observations because they are a rare glimpse at the chaotic birth of a solar system," said Dr. George Sonneborn, FUSE Project Scientist at NASA's Goddard Space Flight Center in Greenbelt, Md. "Young planetary systems are surprisingly active; we are witnessing the birth and evaporation of millions and millions of comets."
A team of scientists from the Institut d'Astrophysique de Paris-CNRS (IAP, France) led by Dr. Alain Lecavelier des Etangs, together with colleagues from the Johns Hopkins University (Baltimore, Md.), and the Laboratoire d'Astrophysique de Marseille (France), has found no evidence of molecular hydrogen (H2), the most abundant molecule in the universe, in the Beta Pictoris disk. This was unexpected because the same team, using the Hubble Space Telescope, had previously found carbon monoxide (CO) in the Beta Pictoris disk. What is seen in the Beta Pictoris system is thus contrary to what is commonly seen in the gaseous clouds of our galaxy, where CO is only seen when H2 is present. When these clouds collapse, they form new stars and planetary systems; thus, they are the raw material for new solar systems like Beta Pictoris.
"In interstellar gas clouds, carbon monoxide gets broken apart by starlight in about 1,000 years, a relatively short time compared to the estimated 20 million-year age of Beta Pictoris. Since we still see carbon monoxide, we think the amount originally present in the cloud that formed Beta Pictoris is now locked up in some kind of reservoir where it is shielded from starlight as it is slowly released back into the Beta Pictoris disk," said Dr. Alfred Vidal-Madjar of IAP.
"Add this to the fact that the amount of molecular hydrogen is too low to be seen by FUSE. This is strange because normally there are about 100,000 molecular hydrogen molecules for every carbon monoxide molecule in interstellar gas clouds. So we think the molecular hydrogen has been locked away in some kind of reservoir also," said Lecavelier.
According to the researchers, comets, which consist largely of frozen gasses, are a likely reservoir. "In our own solar system, there is a swarm of thousands, perhaps millions, of comets beyond the orbit of Pluto, called the Kuiper belt. If a similar comet swarm surrounds Beta Pictoris, the comets would still be warm enough to slowly release carbon monoxide, but far too cold to release molecular hydrogen, which would remain locked up as water ice (H2O)," said Dr. Paul Feldman of the Johns Hopkins University.
FUSE uncovered new mysteries in the Beta Pictoris disk as well. "It gets really exciting when we compare our result to others," said Feldman. "Previous observations of infrared emission from Beta Pictoris with the Infrared Space Observatory actually contradict our lack of detection of ultraviolet absorption by molecular hydrogen along a narrow line-of-sight to the star. They claim to have detected a large amount of molecular hydrogen in the disk. If both results are correct, the only way for this conflict to be resolved is if the molecular hydrogen is not evenly distributed throughout the disk."
Molecular hydrogen absorbs certain kinds of ultraviolet light; when it does so, FUSE can detect its presence, but molecular hydrogen has to be more or less evenly distributed in a cloud to block ultraviolet light from stars behind the cloud, or it won't reveal itself to FUSE. However, molecular hydrogen can also emit infrared light; celestial objects containing molecular hydrogen will glow in infrared if they are warm enough, and can be seen directly by the Infrared Space Observatory, depending on how close they are and how brightly they glow.
"The molecular hydrogen clumps could be left over gas from the formation of the star, or perhaps from failed protoplanets. The initial carbon monoxide would no longer be in gaseous form but rather condensed into cometesimals or comets. All we can say for certain is that carbon monoxide must be continuously generated in the disk," said Feldman.
FUSE is a NASA Origins mission developed and operated by The Johns Hopkins University in collaboration with NASA's Goddard Space Flight Center, the Centre National d'Etudes Spatiales (France), the Canadian Space Agency, the University of Colorado, and the University of California, Berkeley. FUSE was launched on June 24, 1999, from Cape Canaveral on a three-year mission to obtain high resolution spectra in the far ultraviolet wavelength region (905-1185 Angstroms) of faint objects within and beyond our galaxy.
For more information about FUSE, refer to:
For images of the Beta Pictoris disk, refer to:
Planet-forming disks around other stars:
Editor's Note: The original news release can be found at
Send page by E-Mail For Aging Brains, Two Hemispheres Are Better Than One
Posted: Monday, August 20, 2001
Source: University Of Michigan (http://www.umich.edu)
ANN ARBOR --- Older adults actually use different regions of the brain than younger adults to perform the same memory and information processing tasks, according to University of Michigan research to be presented Aug. 24 at the annual meeting of the American Psychological Association in San Francisco.
The research, conducted by U-M cognitive neuroscientist Patricia Reuter-Lorenz and colleagues and funded by the National Institute on Aging, provides intriguing clues about how older adults compensate for some of the age-related declines in short-term memory and mental speed that plague so many older Americans.
"Older adults activate both hemispheres of the brain to remember what younger adults can remember using just one hemisphere," says Reuter-Lorenz, who has just received a new grant from the NIA to continue her research.
In the APA presentation, and in a series of recent publications in the Journal of Cognitive Neuroscience and the Proceedings of the National Academy of Science, Reuter-Lorenz and colleagues report on the findings of a series of studies that use functional positron emission tomography (PET) images to elucidate how the aging brain works. Not only have they found that as we age, two hemispheres are better than one, they have also discovered that in older adults, unexpected regions of the brain are activated for verbal and spatial memory tasks.
When younger adults hold information in short-term memory, like rehearsing a phone number, they activate a network of brain regions involved in speech and short-term verbal storage. Older adults activate these areas also, but show additional activation of a frontal cortex region that young adults use only when performing complex short-term memory tasks.
In one study, older and younger subjects were shown four letters, then asked to determine if a letter presented a few seconds later matched any of the initial four. As expected, Reuter-Lorenz found that seniors made more errors and were slower at the task than young subjects. And PET scans of the subjects' brains while they were being tested showed that older subjects activated more areas of the brain in both hemispheres than young subjects, who showed activity mainly in the left hemisphere.
In another study of spatial memory, subjects were shown a group of marked locations on a screen, then presented a few seconds later with a single mark and asked to determine whether its position matched any in the earlier group. Reuter-Lorenz again found different activation patterns for younger and older subjects. Younger subjects showed greater right hemisphere activation, while older subjects activated both left and right hemispheres.
"Recruiting additional regions of the brain seems to assist older adults in basic memory storage tasks," Reuter-Lorenz says. "But when it comes to more complex processing tasks, this strategy isn't as successful."
When seniors and young subjects were asked to determine the accuracy of a math calculation ((10x9) + 8 = 98), their performance was equivalent. But when subjects were presented with a word in addition to the math problem, and asked to remember it, the performance of seniors dropped dramatically.
Because regions at the front of the brain, in the area known as the dorsolateral prefrontal cortex (DLPFC), were "recruited" by the seniors for the simple short-term memory task, Reuter-Lorenz believes that these regions may have been preoccupied and less available for the more complex tasks.
Overall, though, Reuter-Lorenz believes that older adults benefit from bi-hemispheric processing. Using two hemispheres instead of one, and more of the brain overall, may allow seniors to compensate for some of the mental declines that come with age, she suggests. Moreover, by identifying precisely which areas of the brain seniors are using to remember and process information, she hopes that scientists and physicians will be able to develop more effective interventions to help seniors maintain and improve brain function well into old age.
Editor's Note: The original news release can be found at http://www.umich.edu/~newsinfo/Releases/2001/Aug01/r081501a.html
Send page by E-Mail Brain Activity Is Influenced By Chemical Signals
Posted: Monday, August 20, 2001
Source: University Of Chicago (http://www.uchicago.edu)
Brain Activity Is Influenced By Chemical Signals
Undetectable As Odors, University Of Chicago Researchers Find
Researchers at the University of Chicago have found for the first time that airborne "chemosignals," substances undetectable as odors, have a measurable impact on brain metabolism, according to a report released Wednesday, July 25.
A team of scientists led by the University’s Martha McClintock, one of the nation's leading experts on chemosignals and pheromones, and Suma Jacob, a University researcher, found marked differences in the brain activity among women exposed to the naturally produced male steroid androstadienone when compared to themselves when they had not been exposed to the substance.
A scan of the women's brains after exposure to the steroid showed increased activity in regions associated with smell as well as those areas associated with vision, attention and emotion, the researchers report in a paper, "Sustained Human Chemosignal Unconsciously Alters Brain Function," published in the current issue of the journal NeuroReport
Androstadienone is found in sweat, auxiliary hair, blood and semen. It is a common ingredient used in the manufacture of perfumes and colognes.
The results of the University of Chicago study suggest that chemosignals may be more influential than previously thought, said McClintock, the David Lee Shillinglaw Distinguished Service Professor in Psychology at the University.
"The widespread neural effects of this compound open the possibility that other olfactory signals may also have a significant impact on the whole human brain, even in the absence of conscious detection as an odor," she writes with four co-authors in the paper. The lead author is University researcher Suma Jacob. Other authors are Leann Kinnunen, a University researcher; John Metz, a Research Associate in Psychiatry at the University; and Malcomb Cooper, Associate Professor of Radiology at the University.
In earlier work, Jacob and McClintock established that androstadienone moderates a woman's mood. When women were exposed to a tiny amount of the steroid, they were able to maintain a positive attitude even after two hours of completing a tedious questionnaire.
In their current work, McClintock and Jacob sought to take the research to the next step to see how the steroid affects the brain. They used PET scan equipment to determine which areas of the brain were impacted by the androstadienone.
For the experiment, they told 10 women, aged 20 to 35, that they were conducting a study related to olfaction, but did not explain that they were studying the impact of the steroid.
Researchers placed a minute amount of androstadienone in propylene glycol. They used a small trace of clove oil in the solution to mask any possible odor. They tested each woman in separate sessions two days apart by swiping a sample of the clove-propylene glycol solution with the androstadienone under the women's noses in one test and a sample of the same solution without the steroid in another.
In order to avoid the women responding to external emotional experiences and to create a similar testing situation on the two days of the tests, they had the women sit at a computer and perform simple, nonstressful tasks as they received a glucose solution intravenously.
The women then lay with their heads in an open ring device that is part of the PET equipment, which measures the amount of the glucose just used by their brain. The equipment produced a chart of brain activity that highlighted which areas of the brain became more engaged and which became less active.
The scan showed that while areas of the brain associated with olfactory processing were more engaged when the steroid was present other areas changed as well, including regions associated with attention, emotion and vision processing.
"During PET neuroimaging, subjects' attention was focused on the visual discrimination task they had just performed on the computer. Our strong effects in this area support the hypothesis that androstadienone modulates ongoing behavior, or, more specifically, processing the task at hand," said McClintock.
McClintock added that an alternative explanation, just as exciting, is the possibility that the steroid plays a previously unknown role in processing visual information, as areas of the brain associated with vision were particularly active. Further study is needed to determine more precisely the role of androstadienone on brain function, she said.
Editor's Note: The original news release can be found at
Send page by E-Mail Women's moves to new communities has left mark
Posted: Monday, August 20, 2001
Women's moves to new communities has left mark on gene pool, study confirms
In most societies, women tend to move to their mate's communities rather than vice versa. A new study confirms this has left a mark in local gene pools.
Several studies have found different amounts of diversity in two categories of human DNA. One, the Y chromosome, is passed from father to son. The other, mitochondrial DNA, is passed from mother to daughter.
Studies have found that individual populations tend to have more variation in the female-inherited mitochondrial DNA than the male-inherited Y chromosome. And in comparisons across groups, scientists find lots of diversity in the Y chromosome DNA but lower levels in the mitchondrial DNA.
Scientists have suggested these patterns appear because women tend to move to their mate's home communities before having children. So they bring genetic diversity into the mitochondrial DNA of individual groups, while spreading it between populations, creating a more uniform blend in each. Men, in contrast, are more prone to stay home and not spread their Y chromosomes between groups, creating a genetic isolation that allows more discrepancy to develop from group to group. More
Send page by E-Mail Photosynthetic Link May Have Made Humankind Possible
Posted: Sunday, August 19, 2001
Scientists from Imperial College, London, have found an important evolutionary link between the two powerhouse protein complexes that drive photosynthesis.
This shared evolutionary adaptation may have been crucial for the establishment of environmental conditions required for the emergence of humankind.
For decades, scientists have debated whether there is a common evolutionary origin for the different photosynthetic organisms present today.
Reporting in today’s Nature, scientists from the Wolfson Laboratories, Department of Biological Sciences, Imperial College, now provide evidence for a link.
They have discovered a new protein supercomplex in the photosynthetic pathway that links two major proteins that were previously thought to work autonomously. More
Send page by E-Mail It's the chromosome Y and mighty
Posted: Saturday, August 18, 2001
It's the runt of the genome. A comma of a chromosome that might be called in evidence to show that the Creator has a feminist sense of humour. It has to be a joke. To design the one chromosome that appears only in male bodies, that sets the developing embryo off on the path of bigger muscles and more aggression, and then to make it such a weedy and insignificant thing.
Not only does it look like an afterthought, but even geneticists have traditionally had little positive to say about the Y chromosome. "There's nothing very interesting on it, is there? Just a few genes coding for sperm," says one researcher, crouched over her computer at the Department of Pathology in Cambridge, investigating the genes involved in breast cancer. "My colleagues thought I was really odd when I started studying it 15 years ago," adds Dr Nabeel Affara, the department's Y expert.
But the runty Y is enjoying the last laugh. Having sand kicked in its face by dismissive researchers will soon be a thing of the past. In recent years, it has been undergoing a Clark Kent-like transformation. A shrimp it may be, but it is turning out to be the wild frontier of the genome, where strange and important things happen. More
Send page by E-Mail Jupiter-Size Planet Found Orbiting Star In Big Dipper
Posted: Friday, August 17, 2001
Source: National Science Foundation (http://www.nsf.gov)
A team of astronomers has found a Jupiter-size planet in a circular orbit around a faint nearby star, raising intriguing prospects of finding a solar system with characteristics similar to our own.
The planet is the second found to orbit the star 47 Ursae Majoris in the Big Dipper, also known as Ursa Major or the Big Bear. The new planet is at least three-fourths the mass of Jupiter and orbits the star at a distance that, in our solar system, would place it beyond Mars but within the orbit of Jupiter.
"Astronomers have detected evidence of more than 70 extrasolar planets," said Morris Aizenman, a senior science advisor at the National Science Foundation (NSF). "Each discovery brings us closer to determining whether other planetary systems have features like those of our own."
"For the first time we have detected two planets in nearly circular orbits around the same star," said team member Debra Fischer of the University of California at Berkeley. "Most of the 70 planets people have found to date are in bizarre solar systems, with short periods and eccentric orbits close to the star. As our sensitivity improves we are finally seeing planets with longer orbital period, planetary systems that look more like our solar system."
The planet-search team, which is supported by NSF and NASA, has been instrumental in finding a majority of the extrasolar planets. Besides Fischer, the team includes Geoffrey Marcy, also of Berkeley; Paul Butler of the Carnegie Institution of Washington; Steve Vogt of the University of California at Santa Cruz; and Gregory Laughlin of NASA’s Ames Research Center. Their report on the new planet has been submitted to Astrophysical Journal.
A few years ago, Marcy and Butler discovered a planet more than twice the mass of Jupiter in a circular orbit around the same star. The star is one of 100 that the scientists have targeted since 1987 in their search for evidence of extrasolar planets. They use the 3-meter and 0.6-meter telescopes at the University of California’s Lick Observatory to measure Doppler-shifted light reaching the earth from stars. Regular changes in the Doppler shift, they believe, signal the presence of a planet periodically pulling the star toward or away from Earth.
Fischer was able to see the periodic wobble from the second planet, smaller and farther from the star than the first, because of improved instrumentation that can measure motions as small as three meters per second.
The star is a yellow star similar to the sun, probably about seven billion years old and located about 51 light years from Earth.
"Every new planetary system reveals some new quirk that we didn't expect. We've found planets in small orbits and wacky eccentric orbits," said Marcy. "With 47 Ursae Majoris, it's heartwarming to find a planetary system that finally reminds us of our solar system."
For a list of extrasolar planets, see: http://www.exoplanets.org
For illustrations, see: http://www.nsf.gov/od/lpa/news/press/01/newplanet.htm
Editor's Note: The original news release can be found at http://www.nsf.gov/od/lpa/news/press/01/pr0164.htm
Send page by E-Mail Genetic Mutation May Be Key To Onset Of Deadly Skin Cancer
Posted: Friday, August 17, 2001
Source: Johns Hopkins Medical Institutions (http://www.hopkinsmedicine.org/)
A Johns Hopkins scientist and a team of collaborators have discovered how precancerous moles may progress to melanomas, the most deadly type of skin cancer. The preliminary report, in the August 15 issue of Cancer Research, describes a link between two genes that trigger skin cancers and could serve as early diagnostic markers for the disease. The researchers say that, in melanomas, a cell growth regulatory gene known as Id1 deactivates an important tumor suppressor gene (p16/Ink4a), allowing cancer cells to grow uncontrollably.* High levels of Id1 proteins are found only in the first stages of melanoma, allowing it to be detected and treated while still in a curable stage. trigger skin cancers and could serve as early diagnostic markers for the disease.
“Telling the difference between precancerous moles and early-stage melanoma can be very difficult, and the treatments for these two lesions differ significantly,” explains Rhoda Alani, M.D., assistant professor of oncology, dermatology, molecular biology and genetics and director of the study. “If it’s melanoma, you want to catch it very early and treat it aggressively by removing as much tissue as possible to cure the disease.” Since Id1 is expressed in early-stage melanoma, it has the potential to serve as a definitive diagnostic marker although more studies are needed to confirm this use.trigger skin cancers and could serve as early diagnostic markers for the disease.
The scientists studied Id1 protein expression in 21 tissue samples from a variety of skin cancers, including normal non-cancerous moles (benign nevus), precancerous moles (dysplastic nevus), early-stage melanoma (in-situ melanoma), invasive melanoma and metastatic melanoma. “We found high levels of Id1 activity in the earliest phases of melanoma, when it’s limited to the top layer of the skin (or epidermis). Precancerous moles, invasive and metastatic melanomas do not express high levels of Id1,” reports Alani. Larger studies are planned.trigger skin cancers and could serve as early diagnostic markers for the disease.
The scientists speculate that while the Id1 gene shuts off p16/Ink4a in early melanomas and lifts the brake on uncontrolled cancer cell growth, various mutations or other DNA changes must also occur to the p16/Ink4a gene to damage it beyond repair. So, as the cancer progresses, Id1 becomes less important for shutting off the gene. “This may explain why we see lower expression of Id1 in more advanced melanomas,” says Alani.trigger skin cancers and could serve as early diagnostic markers for the disease.
Melanoma can progress very rapidly and spread to other parts of the body. When treated early, the chance for cure is very high. Only 12 percent of people with metastatic melanoma survive beyond five years.trigger skin cancers and could serve as early diagnostic markers for the disease.
Melanoma will strike 51,400 people in the United States this year, and 7,800 will die from the disease.trigger skin cancers and could serve as early diagnostic markers for the disease.
In addition to Alani, other participants in this research include David Polsky from NYU Medical Center; Alison Zuyung Young and Klaus J. Busam from Memorial Sloan-Kettering Cancer Center. This research was funded by The National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS).trigger skin cancers and could serve as early diagnostic markers for the disease.
Send page by E-Mail New View Of Primordial Helium Traces The Structure Of Early Universe
Posted: Monday, August 13, 2001
NASA's Far Ultraviolet Spectroscopic Explorer (FUSE) satellite has given astronomers their best glimpse yet at the ghostly cobweb of helium gas left over from the big bang, which underlies the universe's structure. The helium is not found in galaxies or stars but spread thinly through the vastness of space.
The observations help confirm theoretical models of how matter in the expanding universe condensed into a web-like structure pervading all of the space between galaxies. The helium traces the architecture of the universe back to very early times. This structure arose from small gravitational instabilities seeded in the chaos just after the big bang.
"Visible galaxies are only the peaks in the structure of the early universe. The FUSE observations of ionized helium show us the details of the hills and valleys between the mountain tops," says Gerard Kriss, leader of the FUSE observing team and astronomer at the Space Telescope Science Institute in Baltimore, MD.
The FUSE observations also bolster evidence that the early universe was re-energized by torrents of radiation from black holes in active galaxies, and a firestorm of star birth.
"The observed absorption by intergalactic helium agrees extremely well with theoretical predictions made at the University of Colorado of an intergalactic medium ionized by both quasars and starburst galaxies," says Michael Shull, member of the FUSE team and professor at Colorado.
The observation was accomplished by using the distant light from a quasar (a brilliant, active nucleus of a galaxy) to allow FUSE to peer across 10 billion light-years of seemingly empty space to make new and precise measurements of the universe's hidden structure.
The observations were made by collecting the light of a distant quasar for a total of twenty days, during two observing campaigns in August and October 2000. Along the trajectory to Earth intervening clouds containing hot helium gas modified the quasar's light. As light passes through intergalactic clouds, helium atoms in the gas absorb specific colors of the light in the far-ultraviolet range of the spectrum.
Complementary, simultaneous observations using NASA's Hubble Space Telescope showed the brightness of the quasar at longer ultraviolet wavelengths where the spectrum is unaffected by helium. The spectrum allows Kriss and co-investigators to trace how helium, which was opaque to radiation in the early universe, grew more transparent as the early universe expanded and was "re-ionized" by a flurry of quasar and galaxy formation, like an early-morning fog is burned off by the rising sun.
The helium nuclei were forged in the first few minutes of the big bang. As the universe expanded the nuclei captured electrons to form a cool gas of neutral atoms. This gas was then reheated and ionized by a "fireworks show in reverse" as torrents of radiation poured into space from the powerful black holes at the centers of some newly formed galaxies and from the firestorm of star birth in other galaxies.
Astronomers have pondered what exactly energized the early universe. By comparing the absorption caused by intergalactic hydrogen, which is visible in spectra from ground-based telescopes like the Keck Observatory, to the helium absorption seen with FUSE, astronomers are able to achieve a better understanding of the energy source.
Though more abundant, intergalactic hydrogen is less easily detected because it is so highly energized (ionized). Even when ionized, helium manages to retain an electron. This etches the light from the quasar with a "forest" of spectral absorption features.
Because the universe is expanding, these absorption features are found at many different wavelengths depending on the distances of the intergalactic clouds from Earth. The FUSE comparison of helium to hydrogen absorption favors an energy source that is a mix of quasars powered by supermassive black holes and the light from newly formed stars. Quasars, historically, have been the preferred power source to heat the early universe. The FUSE observations support other recent suggestions that star formation is also important.
"This is a very exciting discovery. The search for the spectral signatures of a forest of ionized helium gas in the early universe was one of the major objectives of the FUSE mission, and it has been fulfilled spectacularly," says Dr. George Sonneborn, FUSE Project Scientist at NASA's Goddard Space Flight Center in Greenbelt, MD.
Studying the intergalactic medium in ultraviolet light is one of the top tasks for FUSE. In the 1990s astronomers probed the distant universe using the ultraviolet capabilities of the Hubble Space Telescope and the Hopkins Ultraviolet Telescope (HUT) on the ASTRO-2 Space Shuttle mission.
The HUT observations, led by the late Arthur Davidsen of the Johns Hopkins University, gave the first inkling that the intergalactic medium was not a smooth distribution of gas between the galaxies. FUSE has the necessary combination of far-ultraviolet sensitivity and spectral resolution to make the definitive observation of structure in the intergalactic medium traced by ionized helium.
The Johns Hopkins University had the lead role in building FUSE under the direction of principal investigator Warren Moos, and they now operate the satellite for NASA. The FUSE results are being published in the August 10, 2001 issue of the journal Science.
The team next plans to use FUSE to look at other quasars to trace the universe's structure.
The FUSE is a NASA Origins mission developed and operated by The Johns Hopkins University in collaboration with NASA's Goddard Space Flight Center, the Centre National d'Etudes Spatiales (France), the Canadian Space Agency, the University of Colorado, and the University of California, Berkeley. FUSE was launched on June 24, 1999 on a three-year mission to obtain high-resolution spectra in the far ultraviolet wavelength region (905-1185 Angstroms) of faint galactic and extragalactic objects. For further information about FUSE, visit the mission web site at http://fuse.pha.jhu.edu.
NOTE TO EDITORS: An illustration is available on the Web at http://oposite.stsci.edu/pubinfo/pr/2001/27 and via links http://hubblesite.org/news_.and._views/ and http://oposite.stsci.edu/pubinfo/pictures.html.
The Space Telescope Science Institute (STScI) is operated by the Association of Universities for Research in Astronomy, Inc. (AURA), for NASA, under contract with the Goddard Space Flight Center, Greenbelt, MD. The Hubble Space Telescope is a project of international cooperation between NASA and the European Space Agency (ESA).
Editor's Note: The original news release can be found at http://oposite.stsci.edu/pubinfo/pr/2001/27/pr.html
Send page by E-Mail Receptor in the Human Eye to Control Body’s Biological Clock
Posted: Friday, August 10, 2001
Neuroscientists at Jefferson Medical College have clarified how the human eye uses light to regulate melatonin production, and in turn, the body’s biological clock.
They have discovered what appears to be a fifth human "photoreceptor," and which is the main one to regulate the biological – and non-visual – effects of light on the body. They have identified a novel photopigment in the human eye responsible for reacting to light and controlling the production of melatonin, which plays an important role in the body’s circadian rhythms. They also discovered that wavelengths of light in the blue region of the visible spectrum are the most effective in controlling melatonin production.
"This discovery will have an immediate impact on the therapeutic use of light for treating winter depression and circadian disorders," says George Brainard, Ph.D., professor of neurology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, who led the work. "Some makers of light therapy equipment are developing prototypes with enhanced blue light stimuli. More
Send page by E-Mail A Closer Look At The Genome's "Black Holes"
Posted: Friday, August 10, 2001
Source: Howard Hughes Medical Institute (http://www.hhmi.org/)
The centromeres of chromosomes -- considered by some to be the genomic equivalent of black holes -- may hold the answers to many scientific questions, according Howard Hughes Medical Institute investigator Steven Henikoff. For example, studies of the centromere may help in understanding the paradox that while centromeric DNA is evolving with extraordinary rapidity, it is still stable enough to perform its job during cell division.
In a review article published in the August 10, 2001, issue of the journal Science, Henikoff and colleagues Kami Ahmad and Harmit S. Malik at the Fred Hutchinson Cancer Research Center theorize that the rapid evolution of centromeric DNA may provide a mechanism by which newly evolving species rapidly become genetically incompatible with one another.
Each chromosome possesses a centromere, which is the site at which sister chromatids are held together. During mitosis and meiosis, the chromatid pair separates, and the centromere is the point of attachment of spindle fibers that pull each chromosome to opposite poles of the dividing cell. "While the centromere is a locus on the chromosome, it is different than a gene, because it is a locus that is acted upon by the apparatus of cell division," said Henikoff.
And unlike genes, which are amenable to mapping and sequencing, probing the genetic makeup of the centromere has proved to be a dead end because of the centromere’s unusual structure. "The centromere has remained enigmatic ever since it was discovered that centromeric DNA is highly repetitive," said Henikoff. "Current methodology really doesn’t allow the sequencing of centromeric DNA. Thus, nobody has sequenced the centromeres of the human genome, the fly genome, or that of any other complex organism. They remain big black holes often millions of bases in length in every chromosome."
The wide variability of centromeric DNA across different species has led some researchers to dismiss its importance. According to Henikoff, the centromere shouldn’t be dismissed so casually. “Some believe that centromeric DNA sequence is not all that important, because it is not conserved in evolution," said Henikoff. "That lack of conservation has led to the centromere paradox where stable inheritance occurs despite rapidly evolving DNA. Normally, the elements of the mitotic segregation machinery would be expected to be highly conserved, as are other essential cellular machines, such as ribosomes. But the central question with centromeric DNA is why it hasn't found some optimal sequence and just stayed there."
A key to stable centromere inheritance might be found in the proteins called histones, with which all DNA in the nucleus must associate in order for it to form beadlike structures called nucleosomes that bind DNA into compact packages. In the Science article, Henikoff and his colleagues suggest that the uniqueness of the centromeric histone H3 may teach researchers some interesting lessons about evolution.
"While histones are crucial, they are thought to be boring, because they are so highly conserved," said Henikoff. "Because the histones must interact reliably with the entire genome, there are few amino acid differences in these proteins between plants and animals." Centromeric histones, however, have evolved to be profoundly different among organisms.
"The idea that we explore in the Science review is that the centromeric histone and centromeric DNA are evolving rapidly, but in step, since the histone must interact with the centromeric DNA," said Henikoff.
Analysis of centromeric histones has revealed that they seem to be adapting constantly to the changing centromeric DNA. These evolutionary changes are occurring in parts of the histone that interact with DNA, Henikoff says, "so that tells us that it's the interaction with the DNA that's driving the evolution of the protein."
Henikoff and his colleagues theorize that this continuous evolution is being driven by a sort of competition among centromeric DNA that occurs during meiosis in the egg. Three of the four products of meiosis are discarded, and only one survives to become the oocyte nucleus. The "winning" centromeres are those whose chromosomes may show even a slight advantage in orienting themselves during meiosis, said Henikoff.
"What's important about this competitive process among centromeres is that it can result in fixation of winning centromeres. This process can be deleterious to the host genome, and so centromeric histones would evolve to restore parity between competing centromeres," Henikoff said. Bringing together incompatible centromeres and histones in hybrids would lead to their sterility or inviability.
"Understanding the basis of the sterility of cross-species breeding has been a huge problem in evolution ever since Darwin," he said. "The rapidly evolving centromeric DNA and histones and their incompatibility with their counterparts in another species might account for this phenomenon. We can test these ideas by analyzing the centromeric histones in emerging species."
Editor's Note: The original news release can be found at http://www.hhmi.org/news/henikoff.html
Send page by E-Mail Structure Shows Repair Protein Cradling Broken DNA
Posted: Thursday, August 9, 2001
Source: Howard Hughes Medical Institute (http://www.hhmi.org/)
Howard Hughes Medical Institute researchers have produced the first detailed images of a protein that performs the crucial task of detecting and repairing broken strands of DNA. The images show that the protein is constructed to cradle DNA while it is repaired and rejoined with great precision.
The images of the DNA-repair protein Ku were published in the August 9, 2001, issue of Nature by Howard Hughes Medical Institute investigator Jonathan Goldberg and colleagues John R. Walker and Richard A. Corpina at Memorial Sloan-Kettering Cancer Center. Breaks in double-stranded DNA can occur randomly as a result of exposure to ionizing radiation or as programmed events during the gene shuffling that is necessary to create infection-fighting lymphocytes. The Ku heterodimer, consisting of two subunits, Ku70 and Ku80, is a member of a family of DNA repair proteins that fixes damaged DNA in order to preserve the integrity of the genome. When Ku encounters damaged DNA, it initiates a repair process, called non-homologous end joining (NHEJ), which stitches double-stranded broken ends back together even though the ends of each DNA strand may not be complementary.
Ku’s role in maintaining the integrity of the genome was established by earlier studies in which HHMI investigator Frederick W. Alt and his colleagues knocked out Ku70 and other NHEJ components and found that DNA repair was compromised and that aberrant rearrangements of chromosomes occurred with high frequency. Although these studies reinforced the role of Ku in DNA repair, the details of how Ku senses and initiates repair were still sketchy. “The biochemistry is very clear,” Goldberg said. “Ku is sitting in the nucleus ready to sense DNA damage and to bind to DNA ends.”
What remained unclear, however, was how Ku was able to distinguish between broken ends and intact DNA with such precision. “Also, stitching DNA back together sounds dangerous because of the likelihood of losing genetic information,” he said. “But actually, the non-homologous end joining process is quite accurate, and we wanted to find out why Ku appears to be so necessary for that accuracy.”
Goldberg and his colleagues believed that seeing how Ku binds to DNA might provide answers to some of the questions about the Ku-DNA interaction. The researchers used a technique called x-ray crystallography to visualize the interplay between the Ku heterodimer and DNA. In x-ray crystallography, protein crystals are bombarded with intense x-ray beams. As the x-rays bounce off atoms in the crystal, they leave a diffraction pattern, which can then be analyzed to determine the three-dimensional structure of the protein.
Before they could get a full picture of the Ku-DNA complex, Goldberg and his colleagues decided to study the Ku heterodimer by itself. Their attempts to prepare crystals of the Ku protein yielded only a few usable crystals out of the hundreds they prepared. Fortunately, the scientists were able to use a technique pioneered by HHMI investigator Wayne Hendrickson to solve the complete structure of the Ku heterodimer from a single crystal. The technique, called multiple wavelength anomalous diffraction, was applied during crystallographic analyses performed at the National Synchrotron Light Source at Brookhaven National Laboratory.
After the Ku structure was determined, the scientists moved on to solving the structure of the Ku-DNA complex. In their studies, Goldberg and his colleagues had to mimic DNA breakage, ensuring that their test DNA fragment had only one accessible end -- in order to avoid Ku attaching at more than one site on the DNA. They accomplished this by blocking the other end of the DNA with a bulky DNA motif.
After solving the structure of Ku bound to DNA, Goldberg and his colleagues could see how the Ku heterodimer manages to “find” a broken DNA end regardless of its sequence. “The problem is that Ku is not like a transcription factor that binds to a specific DNA sequence,” said Goldberg. “Rather, it wants to recognize any broken DNA. And, the structure showed us that Ku is a ring-shaped molecule that can slide onto the end as soon as the break is formed.”
The structure of the Ku-DNA complex reveals that the Ku heterodimer forms a ring that encircles and “cradles” the end of the strand of DNA. “We believe that the Ku proteins have to hold the DNA ends together,” said Goldberg. “The question is how they hold the end of a piece of DNA without obscuring the end. We found that our protein has an extensive base that cradles the DNA, with a very narrow bridge that lies over the top -- holding one side of the DNA extensively, but leaving the other side almost completely exposed. We think this exposure might allow other repair factors to act on the broken ends to repair them.”
The scientists speculate that the Ku proteins on two broken ends link to one another to hold the two ends in position for joining the DNA back together. Goldberg and his colleagues also found that the Ku heterodimer makes no contact with the DNA bases, but rather grasps the sugar backbone of the DNA strand -- meaning that the protein does not “care” about the sequence of the DNA that it binds.
The scientists also have evidence that Ku holds the DNA in precise alignment to allow ready joining by repair enzymes. “It’s logical that if the protein precisely aligns the DNA ends, that gives an advantage to the repair proteins and the ligases that are going to ultimately join the DNA ends together,” said Goldberg.
Next, Goldberg and his colleagues plan to explore the structure of the Ku proteins attached to two broken strands of DNA in order to understand the mechanism by which they precisely align the ends. This precision is a key to the accuracy of the joining process in the absence of natural homology of the separated strands that could aid repair, Goldberg said.
Send page by E-Mail Emotional Impact Can Be Key to Memory
Posted: Tuesday, August 7, 2001
(ABC News) One of the keys to locking in a memory is how much emotion is attached to it.
"I think it's fascinating how some memories stick and others seem to disappear into thin air," says Stephan Hamann, an assistant psychology professor at Emory University who researches this very phenomenon.
Hamann uses functional magnetic resonance imaging, a technique that builds on standard MRI hardware, to chart activity in people's brains as they are shown different pictures and words.
Half of the stimuli are meant to evoke emotion, while the other half are neutral. Examining the data, Hamann is then able to "see what areas are more active at that particular time" when a picture or word is shown.
Results indicate that when items with high emotional content are shown, a specific area of the brain's temporal lobe called the amygdala lights up. The amygdala is the center of emotion in the brain and, it is becoming clear, a very strong tool for solidly hammering in a memory.
"When the amygdala detects emotion, it essentially boosts activity in areas of the brain that form memories," says Hamann. "And that's how it makes a stronger memory and a more vivid memory." More
Send page by E-Mail Discovery Will Change The Way Researchers Look At DNA Transcription
Posted: Thursday, August 2, 2001
CHAPEL HILL – Biological chemists at the University of North Carolina at Chapel Hill say a discovery they have made about how living organisms convert genetic instructions into action represents a fundamental advance in the understanding of the flow of genetic information.
The UNC scientists have found a previously unknown chemical site on a key enzyme that regulates production of the genetic messenger known as RNA. When the chemical site is occupied, it markedly speeds up the process by which the information contained in DNA, which serves as genetic blueprints, is converted into functions critical for maintaining life.
A report on the discovery appears in the July 27 issue of Cell, a scientific journal. Authors are Dr. Dorothy A. Erie, assistant professor of chemistry; Dr. J. Estelle Foster, a former student of Erie’s now at Eli Lilly and Company, the pharmaceutical manufacturer; and chemistry doctoral student Shannon F. Holmes. More
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