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Primates With Donor Eggs' Mitochondria: Breakthrough Could Help Prevent Some Maternally-based Diseases

ScienceDaily (Aug. 27, 2009) — Researchers at Oregon Health & Science University’s Oregon National Primate Research Center (ONPRC) believe they have developed one of the first forms of genetic therapy – a therapy aimed at preventing serious diseases in unborn children. Specifically, the therapy would combat inherited diseases passed on from mothers to their children through mutated DNA in cell mitochondria.
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The research is published in the Aug. 26 advance online edition of the journal Nature and will appear in a print edition of the journal at a later date.

“We believe this discovery in nonhuman primates can rapidly be translated into human therapies aimed at preventing inherited disorders passed from mothers to their children through the mitochondrial DNA, such as certain forms of cancer, diabetes, infertility, myopathies and neurodegenerative diseases,” explained Shoukhrat Mitalipov, Ph.D., an associate scientist in the Division of Reproductive Sciences at ONPRC, the Oregon Stem Cell Center and the departments of Obstetrics and Gynecology and Molecular & Medical Genetics of Oregon Health & Science University (OHSU). “Currently there are 150 known diseases caused by mutations of the mitochondrial DNA, and approximately 1 out of every 200 children is born with mitochondrial mutations.”

Mitochondria are structures that are found in all cells that provide energy for cell growth and metabolism, which is why they are often called the cell’s “power plant.” The structures produce energy to power each individual cell. Mitochondria also carry their own genetic material.

When an egg cell is fertilized by a sperm cell during reproduction, the embryo almost exclusively inherits the maternal mitochondria present in the egg. This means that any disease-causing genetic mutations that a mother carries in her mitochondrial DNA can be passed on to her offspring. The method developed by OHSU researchers transfers the mother’s chromosomes to a donated egg that has had its chromosomes removed, but which has healthy mitochondria, thereby preventing the disease from being passed on to one’s offspring.

Here is how the OHSU researchers’ method works: Scientists collected groups of unfertilized eggs from two female rhesus macaque monkeys (monkeys A and B). They then removed the chromosomes, which contain the genes found in the cell nucleus, from the eggs of monkey B, and then transplanted the nuclear genes from the eggs of monkey A into the eggs of monkey B. Then the eggs from monkey B, which now contained their own mitochondria but monkey A’s nuclear genes, were fertilized. The fertilized eggs developed into embryos that were implanted in surrogate monkeys.

The initial implantation of two embryos resulted in the birth of healthy twin monkeys, nicknamed “Mito” and “Tracker” (in reference to the procedure used for imaging of mitochondria). These monkeys are the world’s first animals derived by spindle transfer.

Follow-up testing showed that there was little to no trace of cross-animal mitochondrial transfer using this procedure. This demonstrates that the researchers were successful in isolating nuclear genetic material from mitochondrial genetic material during the transfer process.

“In theory, this research has demonstrated that it is possible to use this therapy in mothers carrying mitochondrial DNA diseases so that we can prevent those diseases from being passed on to their offspring,” added Mitalipov. “We believe that with the proper governmental approvals, our work can rapidly be translated into clinical trials for humans, and, eventually, approved therapies.”

“This breakthrough is an excellent example of how OHSU’s research findings can often be rapidly translated into health therapies that benefit residents of our state and the country as a whole,” said Dr. Joe Robertson, M.D., M.B.A., president of OHSU.

The research was funded by the Oregon National Primate Research Center, the Oregon Stem Cell Center; and the National Center for Research Resources and the National Institute of Child Health and Human Development, both components of the National Institutes of Health.
Adapted from materials provided by Oregon Health & Science University.
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Oregon Health & Science University (2009, August 27). Primates With Donor Eggs' Mitochondria: Breakthrough Could Help Prevent Some Maternally-based Diseases. ScienceDaily. Retrieved August 27, 2009, from http://www.sciencedaily.com­ /releases/2009/08/090826152555.htm
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A new scientific breakthrough could help break the chain of several maternally-based diseases passed from generation to generation. The technique has successfully resulted in the birth of twin monkeys named "Mito" and "Tracker," the world's first animals derived by a fertility method called spindle transfer. (Credit: Image courtesy of Oregon Health & Science University)
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Blast Waves May Cause Human Brain Injury Even Without Direct Head Impacts

ScienceDaily (Aug. 27, 2009) — New research on the effects of blast waves could lead to an enhanced understanding of head injuries and improved military helmet design.
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Using numerical hydrodynamic computer simulations, Lawrence Livermore scientists Willy Moss and Michael King, along with University of Rochester colleague Eric Blackman, have discovered that nonlethal blasts can induce enough skull flexure to generate potentially damaging loads in the brain, even without direct head impact.

Traumatic brain injury (TBI) results from mechanical loads in the brain, often without skull fracture, and causes complex, long-lasting symptoms.

TBI in civilians is usually caused by direct head impacts resulting from motor vehicle and sports accidents. TBI also has emerged among military combat personnel exposed to blast waves. As modern body armor has substantially reduced soldier fatalities from explosive attacks, the lower mortality rates have revealed the high prevalence of TBI.

There has been extensive research on how head impacts, for example from automobile accidents, cause traumatic brain injury. But TBIs resulting from blast waves without head impacts have not been well understood.

To tackle this puzzle, the team used three-dimensional hydrodynamic simulations to prove that direct action of the blast wave on the head causes skull flexure, producing mechanical loads in brain tissue comparable to those in an injury-inducing impact, even at nonlethal blast pressures as low as 1 bar above atmospheric pressure.

In particular, the team showed that blast waves affect the brain very differently from direct impacts.

The primary source of injury from direct impacts is the force resulting from the bulk acceleration of the head. In contrast, a blast wave squeezes the skull, creating pressures as large as an injury-inducing impact and pressure gradients in the brain that are much larger. This occurs even when the bulk head accelerations induced by a blast wave are much smaller than from a direct impact.

“The blast wave sweeps over the skull like a rolling pin going over dough,” said King, LLNL co-principal investigator.

Although the simulations show that the skull is deformed only about 50 microns (the width of a human hair), “this is large enough to generate potentially damaging loads in the brain,” according to Moss.

Because blast waves and direct impact affect the head in fundamentally different ways, armor systems that are designed to protect soldiers from impacts and projectiles may not be optimal for blast wave protection.

The team studied how helmets and their suspension systems influence the blast-induced mechanical loads in the brain.

They looked at two common systems: a nylon web system formerly used in the Personnel Armor Systems Ground Troops infantry helmet and viscoelastic foam pads like those in advanced combat helmets. Both helmets were modeled as hemi-ellipsoidal Kevlar shells.

In the first case, the 1.3 centimeter gap between the webbing and the shell allows the blast wave to “wash” under the helmet. In this case, the blast wave is focused by the shape of the helmet and the pressures under the helmet exceed those outside, so the helmet doesn't prevent the rippling deformation of the skull and pressure gradients in the brain.

In the second case, this “under wash” effect is mostly prevented by the presence of the foam pads, but under blast loading, the pads can become stiffer so that the blast wave-induced motion or deformation of the helmet is transferred to the skull. This can result in dangerous loads in the brain.

“The possibility that blasts may contribute to traumatic brain injury has implications for injury diagnosis and improved armor design,” Moss said.

Blackman added, “By comparing the effect of blasts on the head with the effect of head impacts we'd be able to make some sense of the distinct mechanisms of injury, the damage a solider might incur, and how a helmet might be designed to minimize both.”

The research appears online Aug. 26 in Physical Review Letters.
Adapted from materials provided by DOE/Lawrence Livermore National Laboratory.
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DOE/Lawrence Livermore National Laboratory (2009, August 27). Blast Waves May Cause Human Brain Injury Even Without Direct Head Impacts. ScienceDaily. Retrieved August 27, 2009, from http://www.sciencedaily.com­ /releases/2009/08/090826152713.htm

The Army's Advanced Combat Helmet replaced the older Personal Armor System for Ground Troops helmet. Its Kevlar shell provides ballistic and impact protection, and its reduced edge cut, although reducing area of coverage, improves soldiers' field of vision and hearing. (Credit: Photo courtesy U.S. Army)
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Heat Forms Potentially Harmful Substance In High-fructose Corn Syrup, Bee Study Finds

ScienceDaily (Aug. 27, 2009) — Researchers have established the conditions that foster formation of potentially dangerous levels of a toxic substance in the high-fructose corn syrup (HFCS) that is often fed to honey bees. Their study, which appears in the current issue of ACS' bi-weekly Journal of Agricultural and Food Chemistry, may also have implications for soft drinks and dozens of other human foods that contain HFCS. The substance, hydroxymethylfurfural (HMF), forms mainly from heating fructose.
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In the new study, Blaise LeBlanc and Gillian Eggleston and colleagues note HFCS's ubiquitous usage as a sweetener in beverages and processed foods. Some commercial beekeepers also feed it to bees to increase reproduction and honey production. When exposed to warm temperatures, HFCS can form HMF and kill honeybees. Some researchers believe that HMF may be a factor in Colony Collapse Disorder, a mysterious disease that has killed at least one-third of the honeybee population in the United States.

The scientists measured levels of HMF in HFCS products from different manufacturers over a period of 35 days at different temperatures. As temperatures rose, levels of HMF increased steadily. Levels jumped dramatically at about 120 degrees Fahrenheit.

"The data are important for commercial beekeepers, for manufacturers of HFCS, and for purposes of food storage. Because HFCS is incorporated as a sweetener in many processed foods, the data from this study are important for human health as well," the report states. It adds that studies have linked HMF to DNA damage in humans. In addition, HMF breaks down in the body to other substances potentially more harmful than HMF.

Journal reference:

1. LeBlanc et al. Formation of Hydroxymethylfurfural in Domestic High-Fructose Corn Syrup and Its Toxicity to the Honey Bee (Apis mellifera). Journal of Agricultural and Food Chemistry, 2009; 57 (16): 7369 DOI: 10.1021/jf9014526

Adapted from materials provided by American Chemical Society, via EurekAlert!, a service of AAAS.
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A new study shows that heat can produce a potentially toxic substance in high-fructose corn syrup that may kill honeybees. (Credit: Wikimedia Commons)
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Rats' Mental 'Instant Replay' Drives Next Moves

ScienceDaily (Aug. 27, 2009) — Researchers at MIT's Picower Institute for Learning and Memory have found that rats use a mental instant replay of their actions to help them decide what to do next, shedding new light on how animals and humans learn and remember.
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The work will appear in the Aug. 27 issue of the journal Neuron.

"By understanding how thoughts and memories are structured, we can gain insight into how they might be disrupted in diseases and disorders of memory and thought such as Alzheimer's and schizophrenia," said study author Matthew A. Wilson, the Sherman Fairchild Professor of Neuroscience at the Picower Institute. "This understanding may lead to new methods of diagnosis and treatment."

Wilson's laboratory explores how rats form and recall memories by recording — with an unprecedented level of accuracy — the activity of single neurons in the hippocampus while the animal is performing tasks, pausing between actions and sleeping. The hippocampus is the seahorse-shaped brain region researchers believe to be critical for learning and memory.

Wilson's previous work has shown that after the animals run a maze, their brains "replay" during sleep the sequence of events they experienced while awake. Researchers believe this process is key to sleep-reinforced memory consolidation in both animals and humans.

The latest study shows that these sequences also occur when the animals are awake and may help them decide what to do next.

Not-so-instant replay

When a rat moves through a maze, certain neurons called "place cells," which respond to the animal's physical environment, fire in patterns and sequences unique to different locations. By looking at the patterns of firing cells, researchers can tell which part of the maze the animal is running.

While the rat is awake but standing still in the maze, its neurons fire in the same pattern of activity that occurred while it was running. The mental replay of sequences of the animals' experience occurs in both forward and reverse time order.

"This may be the rat equivalent of 'thinking,'" Wilson said. "This thinking process looks very much like the reactivation of memory that we see during non-REM dream states, consisting of bursts of time-compressed memory sequences lasting a fraction of a second.

"So, thinking and dreaming may share the same memory reactivation mechanisms," he said.

Memory's building blocks

"This study brings together concepts related to thought, memory and dreams that all potentially arise from a unified mechanism rooted in the hippocampus," said co-author Fabian Kloosterman, senior postdoctoral associate.

The team's results show that long experiences, which in reality could have taken tens of seconds or minutes, are replayed in only a fraction of a second. To do this, the brain links together smaller pieces to construct the memory of the long experience.

The researchers speculated that this strategy could help different areas of the brain share information — and deal with multiple memories that may share content — in a flexible and efficient way. "These results suggest that extended replay is composed of chains of shorter subsequences, which may reflect a strategy for the storage and flexible expression of memories of prolonged experience," Wilson said.

Moreover, by comparing the content of the replay with the rat's physical location on the track and his actual behavior immediately before and after the replay event the researchers could tell the rat was not just thinking about his most recent experience but also about other options, such as: "What if I turned around and went back the way I came?" or "How would I get here if my starting point is at a distant location?"

This suggests that the same brain mechanisms come into play to remember the past and consider future actions, reinforcing recent work by neuroscientists outside of MIT who determined that in humans, cognitive processes related to episodic recall and evaluation of future events overlap to a high degree.

Memory formation and future planning are among the cognitive functions ravaged by diseases such as Alzheimer's disease, schizophrenia and psychosis.

"A better understanding of how we use memories, not only to learn from past experiences but also to explore our future options, can give us insights into how the system fails under these disease conditions," Kloosterman said.

The MIT researchers plan to further explore the link between awake replay and cognition in animals engaged in more cognitively demanding tasks such as those involving multiple choices, where the rat has to make a decision ("do I go left or right?") based on a prior learned rule.

In addition to Wilson, the study was led jointly by Kloosterman and MIT brain and cognitive sciences graduate student Thomas J. Davidson.

This research was supported by National Institutes of Health (NIH).
Adapted from materials provided by Massachusetts Institute of Technology.
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Massachusetts Institute of Technology (2009, August 27). Rats' Mental 'Instant Replay' Drives Next Moves. ScienceDaily. Retrieved August 27, 2009, from http://www.sciencedaily.com­ /releases/2009/08/090826152810.htm
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Researchers at MIT's Picower Institute for Learning and Memory have found that rats use a mental instant replay of their actions to help them decide what to do next, shedding new light on how animals and humans learn and remember. (Credit: iStockphoto/Oleg Kozlov)
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Trifid Nebula: A Massive Star Factory

ScienceDaily (Aug. 26, 2009) — A new image of the Trifid Nebula, shows just why it is a firm favorite of astronomers, amateur and professional alike. This massive star factory is so named for the dark dust bands that trisect its glowing heart, and is a rare combination of three nebula types, revealing the fury of freshly formed stars and presaging more star birth.
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Space & Time

* Nebulae
* Stars
* Astronomy
* Astrophysics
* Black Holes
* Extrasolar Planets

Reference

* Orion Nebula
* Star cluster
* Stellar evolution
* Planetary nebula

Smouldering several thousand light-years away in the constellation of Sagittarius (the Archer), the Trifid Nebula presents a compelling portrait of the early stages of a star’s life, from gestation to first light. The heat and “winds” of newly ignited, volatile stars stir the Trifid’s gas and dust-filled cauldron; in time, the dark tendrils of matter strewn throughout the area will themselves collapse and form new stars.

The French astronomer Charles Messier first observed the Trifid Nebula in June 1764, recording the hazy, glowing object as entry number 20 in his renowned catalogue. Observations made about 60 years later by John Herschel of the dust lanes that appear to divide the cosmic cloud into three lobes inspired the English astronomer to coin the name “Trifid”.

Made with the Wide-Field Imager camera attached to the MPG/ESO 2.2-metre telescope at ESO’s La Silla Observatory in northern Chile, this new image prominently displays the different regions of the Trifid Nebula as seen in visible light. In the bluish patch to the upper left, called a reflection nebula, gas scatters the light from nearby, Trifid-born stars. The largest of these stars shines most brightly in the hot, blue portion of the visible spectrum. This, along with the fact that dust grains and molecules scatter blue light more efficiently than red light — a property that explains why we have blue skies and red sunsets — imbues this portion of the Trifid Nebula with an azure hue.

Below, in the round, pink-reddish area typical of an emission nebula, the gas at the Trifid’s core is heated by hundreds of scorching young stars until it emits the red signature light of hydrogen, the major component of the gas, just as hot neon gas glows red-orange in illuminated signs all over the world.

The gases and dust that crisscross the Trifid Nebula make up the third kind of nebula in this cosmic cloud, known as dark nebulae, courtesy of their light-obscuring effects. Within these dark lanes, the remnants of previous star birth episodes continue to coalesce under gravity’s inexorable attraction. The rising density, pressure and temperature inside these gaseous blobs will eventually trigger nuclear fusion, and yet more stars will form.

In the lower part of this emission nebula, a finger of gas pokes out from the cloud, pointing directly at the central star powering the Trifid. This is an example of an evaporating gaseous globule, or "EGG", also seen in the Eagle Nebula, another star-forming region. At the tip of the finger, which was photographed by Hubble a knot of dense gas has resisted the onslaught of radiation from the massive star.
Adapted from materials provided by European Southern Observatory - ESO.
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European Southern Observatory - ESO (2009, August 26). Trifid Nebula: A Massive Star Factory. ScienceDaily. Retrieved August 27, 2009, from http://www.sciencedaily.com­ /releases/2009/08/090826073442.htm
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The massive star factory known as the Trifid Nebula was captured in all its glory with the Wide-Field Imager camera attached to the MPG/ESO 2.2-metre telescope at ESO's La Silla Observatory in northern Chile. So named for the dark dust bands that trisect its glowing heart, the Trifid Nebula is a rare combination of three nebulae types that reveal the fury of freshly formed stars and point to more star birth in the future. The field of view of the image is approximately 13 x 17 arcminutes. (Credit: ESO)
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