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The polypill has been hailed as the magic bullet to heart problems

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Pixilated brain: At the bottom, an MRI image shows a slice of the human brain. At the top is shown a magnified portion of this section, created using diffusion imaging. To create the image, scientists measured the direction of the water diffusion in brain tissue. The “flower petals” at each point show the directions of fastest diffusion. These are aligned along the neural pathways of the brain, because water diffuses directionally along the well-insulated neural wires that carry electrical signals. The different directions of diffusion are color-coded red, green, and blue. In this example, the bright red areas reveal the thick fiber tract, called the corpus callosum, which transfers information between the left and right sides of the brain.
Credit: David Shattuck, Arthur Toga, Paul Thompson/UCLA

The integrity of neural wiring is a big factor in determining intelligence. It’s also inheritable.

MIT Technology Review, March/April 2009, by Emily Singer — New research suggests that the layer of insulation coating neural wiring in the brain plays a critical role in determining intelligence. In addition, the quality of this insulation appears to be largely genetically determined, providing further support for the idea that IQ is partly inherited.

The findings, which result from a detailed study of twins’ brains, hint at how ever-improving brain-imaging technology could shed light on some of our most basic characteristics.

“The study answers some very fundamental questions about how the brain expresses intelligence,” says Philip Shaw, a child psychiatrist at the National Institute of Mental Health, in Bethesda, MD, who was not involved in the research.

The neural wires that transmit electrical messages from cell to cell in the brain are coated with a fatty layer called myelin. Much like the insulation on an electrical wire, myelin stops current from leaking out of the wire and boosts the speed with which messages travel through the brain–the higher quality the myelin, the faster the messages travel. These myelin-coated tracts make up the brain’s white matter, while the bodies of neural cells are called grey matter.

White matter is invisible on most brain scans, but a recently developed variation of magnetic resonance imaging, called diffusion-tensor imaging (DTI), allows scientists to map the complex neural wiring in our brains by measuring the diffusion of water molecules through tissue. Thanks to the fatty myelin coating, water diffuses along the length of neural wires, while in other types of brain tissue it moves in all different directions. Researchers can calculate the direction of fastest diffusion at each point in the brain and then construct a picture of the brain’s fiber tracts. A well-organized brain has well-functioning myelin, in which water can be seen clearly moving along specific paths. “Diffusion imaging gives a picture of how intact your brain connections are,” says Paul Thompson, a neuroscientist at the University of California, Los Angeles, who lead the study.

Thompson and his colleagues took DTI scans of 92 pairs of fraternal and identical twins. They found a strong correlation between the integrity of the white matter and performance on a standard IQ test. “Going forward, we are certainly going to think of white matter structure as an important contributor of intelligence,” says Van Wedeen, a neuroscientist at Massachusetts General Hospital in Boston, who was also not involved in the research. “It also changes how you think about what IQ is measuring,” says Wedeen. The research was published last month in the Journal of Neuroscience.

If white matter is linked to both processing speed and IQ, this raises the question: is intelligence merely a function of how fast your brain works? Previous research has linked processing speed to IQ, but the tests used in the study are measures of general intelligence, including verbal skills, math, and logic. “Processing speed plays a big part in how intelligent you are, but it’s not the only factor,” says Shaw.

The new study is among the first to link a specific neural architecture to IQ in healthy individuals. “Most people have focused on grey matter,” says Shaw. “This is good evidence we should be looking at white matter as well.” Previous studies using DTI have linked white matter damage to Alzheimer’s disease, chronic alcoholism, and traumatic brain injury.

The UCLA researchers took the study a step further by comparing the white matter architecture of identical twins, who share almost all their DNA, and fraternal twins, who share only half. Results showed that the quality of the white matter is highly genetically determined, although the influence of genetics varies by brain area. According to the findings, about 85 percent of the variation in white matter in the parietal lobe, which is involved in mathematics, logic, and visual-spatial skills, can be attributed to genetics. But only about 45 percent of the variation in the temporal lobe, which plays a central role in learning and memory, appears to be inherited.

Thompson and his collaborators also analyzed the twins’ DNA, and they are now looking for specific genetic variations that are linked to the quality of the brain’s white matter. The researchers have already found a candidate–the gene for a protein called BDNF, which promotes cell growth. “People with one variation have more intact fibers,” says Thompson.

The search for the genetic and neuroanatomical basis of intelligence has been controversial, largely because opponents fear it will spawn a deterministic view of abilities and education. “People worry that if something is genetic, they have no power to influence it,” says Thompson. “But that’s not true at all.” For example, both an average runner and a genetically gifted one can benefit from training.

But the debate may be moot since, as Wedeen points out, it is unlikely that an individual brain scan could predict a person’s IQ. “The report described aggregate data over number of individuals,” he says. “That’s not the same as saying we can do a scan and determine a person’s intelligence. That may be in the offing, but we don’t know that yet.”

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This fireworks display is actually a microscope image of a zebrafish retina immunolabeled for ultraviolet cones (magenta) and rods (green). The image shows the regular pattern of the cones and the scattered pattern of the rods typical of a normal fish. The labeling was performed by Karen Alverez-Delfin, doctoral candidate at Florida State University. (Credit: Florida State Associate Professor James Fadool and Alverez-Delfin)

Florida State University, April 9, 2009 — Among zebrafish, the eyes have it. Inside them is a mosaic of light-sensitive cells whose structure and functions are nearly identical to those of humans. There, biologists at The Florida State University discovered a gene mutation that determines if the cells develop as rods (the photoreceptors responsible for dim-light vision) or as cones (the photoreceptors needed for color vision).

Described in a paper published in the Proceedings of the National Academy of Sciences (PNAS), the landmark study of retinal development in zebrafish larvae and the genetic switch it has identified should shed new light on the molecular mechanisms underlying that development and, consequently, provide needed insight on inherited retinal diseases in humans.

From FSU’s Department of Biological Science and Program in Neuroscience, doctoral candidate Karen Alvarez-Delfin (first author of the PNAS paper), postdoctoral fellow Ann Morris (second author), and Associate Professor James M. Fadool are the first scientists to identify the crucial function of a previously known gene called “tbx2b.” The researchers have named the newfound allele (a different form of a gene) “lor” — for “lots-of-rods” — because the mutation results in too many rods and fewer ultraviolet cones than in the normal eye.

“Our goal is to generate animal models of inherited diseases of the eye and retina to understand the progression of disease and find more effective treatments for blindness,” said Fadool, faculty advisor to Alvarez-Delfin and principal investigator for Morris’s ongoing research. “We are excited about the mutation that Karen has identified because it is one of the few mutations in this clinically critical pathway that is responsible for cells developing into one photoreceptor subtype rather than another.”

“What is striking in this case is that the photoreceptor cell changes we observed in the retinas of zebrafish are opposite to the changes identified in Enhanced S-cone syndrome (ESCS), an inherited human retinal dystrophy in which the rods express genes usually only found in cones, eventually leading to blindness,” Alvarez-Delfin said. “Equally surprising is that this study and others from our lab show that while alterations in photoreceptor development in the human and mouse eyes lead to retinal degeneration and blindness, they don’t in zebrafish. Therefore, the work from our Florida State lab and with our collaborators at the University of Pennsylvania, Vanderbilt University and the University of Louisville should provide a model for better understanding the differences in outcomes between mammals and fish, and why the human mutation leads to degenerative disease.”

Morris calls the zebrafish an ideal genetic model for studies of development and disease. The common aquarium species are vertebrates, like humans. Their retinal organization and cell types are similar to those in humans. Zebrafish mature rapidly, and lay many eggs. The embryos are transparent, and they develop externally, unlike mammals, which develop in utero.

“This lets us study developmental processes such as the formation of tissues and organs in living animals,” she said.

“From a developmental biology perspective, our research will help us unravel the competing signals necessary for generating the different photoreceptor cell types in their appropriate numbers and arrangement,” Morris said. “The highly specialized nature of rods and cones may make them particularly vulnerable to inherited diseases and environmental damage in humans. Understanding the genetic processes of photoreceptor development could lead to clinical treatments for the millions of people affected by photoreceptor cell dystrophies such as retinitis pigmentosa and macular degeneration.”

The mosaic arrangement of photoreceptors in fish was first described more than 100 years ago, but the J. Fadool laboratory at Florida State was the first to successfully take advantage of the pattern to identify mutations affecting photoreceptor development and degeneration.

“Imagine a tile mosaic,” Fadool said. “That is the kind of geometric pattern formed by the rod and cone photoreceptors in the zebrafish retina. This mosaic is similar to the pattern of a checkerboard but with four colors rather than two alternating in a square pattern. The red-, green-, blue-, and ultraviolet-sensitive cones are always arranged in a precise repeating pattern. Human retinas have a photoreceptor mosaic, too, but here the term is used loosely, because while the arrangement of the different photoreceptors is nonrandom, they don’t form the geometric pattern observed in zebrafish.

“So how do we ask a fish if it has photoreceptor defects?” he asked.

Fadool explained that because the mosaic pattern of zebrafish photoreceptors is so precise, mutations causing subtle alterations are easier to uncover than in retinas with a “messier” arrangement.

“Just as we can easily recognize a checkerboard mistakenly manufactured with some of the squares changed from black to red or with all-black squares, by using fluorescent labeling and fluorescence microscopes we can see similar changes in the pattern of the zebrafish photoreceptor mosaic,” he said. “Karen showed that within the mosaic of the lots-of-rod fish, the position on the checkerboard normally occupied by a UV cone is replaced with a rod. The identity of the mutated gene is then discovered using a combination of classical genetics and genomic resources.”

Funding for the Fadool laboratory’s zebrafish research comes in large part from a five-year grant totaling more than $1.7 million from the National Institutes of Health.

Journal reference:

1. Alvarez-Delfin et al. Tbx2b is required for ultraviolet photoreceptor cell specification during zebrafish retinal development. Proceedings of the National Academy of Sciences, 2009; 106 (6): 2023 DOI: 10.1073/pnas.0809439106

Adapted from materials provided by Florida State University.

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Diabetes Discovery

Computer Scientists Make Laser Eye Operation Simpler

A new technique called Patterned Scanning Laser uses a computer instead of a human to apply laser pulses to burn away abnormal blood vessels. Instead of manually operating the laser, the pattern of one or two thousand laser pulses is automatically applied. Diabetes affects over 20 million Americans. It can cause many serious health problems, including blindness. Treatment for eye problems is possible, but can be extremely painful. Now, thanks to chemical physics, there is a new laser technology, called PASCAL, can treat patients in just five minutes, and virtually pain-free.

Chris Ladas has type 2 diabetes and suffers from blurred vision, or diabetic retinopathy, because of it. Diabetic retinopathy blocks blood vessels in the retina and causes blurry vision.

The old method of treatment consisted of retinal surgeons using a laser to treat the disease. Some patients describe it as being poked in the eye with a sharp object for 45 minutes. Ladas describes the experience, “It was very stressful, very difficult, and in some cases it was quite painful.”

Currently used by more than 150 doctors across the country, PASCAL delivers rapid laser pulses in patterns, shooting 50 laser pulses all at once. The laser burns away weakened blood vessels on the retina on the back of the eye before they burst, saving vision for millions. David Mordaunt, Ph.D., a chemical physicist and CEO of OptiMedica in Santa Clara, California, explains the benefits of PASCAL technology, “Fifty laser spots can be delivered in the time it would take traditionally one laser spot to be delivered.” Ladas has started using PASCAL technology to help treat his blurred vision. He may need treatments for life in order to save his sight, but the technology makes living with the disease easier. Ladas told DBIS, “It was probably about 90 percent less painful than the previous treatments.”

The American Association of Physicists in Medicine and the Optical Society of America contributed to the information contained in the TV portion of this report.

BACKGROUND: Conventional laser approaches to treating diabetic retinopathy — a leading cause of blindness in adults — can feel like getting poked in the eye. But a new technique called Patterned Scanning Laser (PASCAL) aims to make treatment of this common condition less painful and much faster. The technique can also be used to treat other retinal diseases, such as age-related macular degeneration.

ABOUT THE DISEASE: Diabetic retinopathy blocks blood vessels in the retina, the light-sensitive tissue in the back of the eye. As the retina struggles to maintain its blood supply, it begins to grow new but very fragile blood vessels. These thin vessel walls can tear, leaking blood and fluids. This clouds the vision, and can create “floaters” or large blood spots. Left untreated, the disease will cause blindness.

LASING A PATH: Conventional laser eye surgery uses a pulsed, tightly focused beam of light to burn away the abnormal blood vessels before they have a chance to burst, killing part of the retina cells in order that the rest may live. By controlling the size, position and number of laser pulses, the surgeon can control how much tissue is removed. The surgeon uses a joystick to aim the laser and a foot pedal to shoot the pulses, generating rectangular or circular patterns of 20 to 60 laser burns at the edge of the retina. It can take up to four 15-minute sessions to apply the 1000 to 2000 laser burns needed to complete the treatment. With PASCAL, the surgeon can complete the entire procedure in less than five minutes because a computer program automates the laser burn patterns so that doctors can apply the entire pattern with a single shot. It is also less painful because the laser bursts don”t last as long, thanks to PASCAL’s improved controls. The heat from the laser has less time to build up in the tissue and diffuse into the layer of nerve cells

HOW LASERS WORK: “Laser” is an acronym for Light Amplification by Stimulated Emission of Radiation. It describes any device that creates and amplifies a narrow, focused beam of light whose photons are all traveling in the same direction, rather than emitting every which way at once. Lasers can be configured to emit many different colors in the spectrum, but each laser can emit only that one color. There are many different types of laser, but all of them have an empty cavity containing a lasing medium: either a crystal like ruby or garnet, or a gas or liquid. There are two mirrors on either end of the cavity, one of which is half-silvered, meaning that it will reflect some light and let some light through. In a laser, the atoms or molecules of the lasing medium are “pumped” by applying intense flashes of light or electricity. The end result is a sudden burst of so-called “coherent” light as all the atoms discharge in a rapid chain reaction.

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Mouse esophagus stem cells have the capacity to contribute to the repair of esophageal epithelium after induction of injury. (Credit: Image courtesy of University of Pennsylvania School of Medicine)

ScienceDaily.com — Researchers at the University of Pennsylvania School of Medicine have discovered stem cells in the esophagus of mice that were able to grow into tissue-like structures and when placed into immune-deficient mice were able to form parts of an esophagus lining.

“The immediate implication is that we’ll have a better understanding of the role of these stem cells in normal biology, as well as in regenerative and cancer biology,” says senior author Anil K. Rustgi, MD, the T. Grier Miller Professor of Medicine and Genetics and Chief of Gastroenterology. “Down the road, we will develop a panel of markers that will define these stem cells and use them in replacement therapy for diseases like gastroesophogeal reflux disease [GERD] and also to understand Barrett’s esophagus, a precursor to esophageal adenocarcinoma and how to reverse that before it becomes cancer.”

Diseases of the esophagus are very common in the United States and worldwide. “Benign forms include GERD and millions are affected,” notes Rustgi.

GERD can sometimes lead to inflammation of the esophagus, called esophagitis. “In some of these cases esophagitis can lead to a swapping of the normal lining of the esophagus with a lining that looks more like the intestinal lining and that’s called Barrett’s esophagus,” explains Rustgi. “This can lead to cancer of the esophagus, which is the fastest rising cancer in the US, increasing by 7 to 8 percent a year.”

The researchers set out to identify and characterize potential stem cells–those with the ability to self renew–in the esophagus to understand normal biology and how injured cells may one day be repaired.

First, they grew mouse esophageal cells they suspected were adult stem cells. Those cells formed colonies that self renewed. These cells then grew into esophageal lining tissue in a three-dimensional culture apparatus. “These tissue culture cells formed a mature epithelium sitting on top of the matrix,” says Rustgi. “The whole construct is a form of tissue engineering.”

The investigators then tested their pieces of esophageal lining in whole animals. When the tissue-engineered patches were transplanted under the skin of immunodeficient mice, the cells formed epithelial structures. Additionally, in a mouse model of injury of the esophagus in a normal mouse, which mimics what happens during acid reflux, green-stained stem cells migrated to the injured lining cells and co-labeled with the repaired cells, indicating involvement of the stem cells in tissue repair and regeneration.

Eventually the researchers will develop genetically engineered mouse models to be able to track molecular markers of esophageal stem cells found in a micorarray study. The group has already developed a library of human esophageal cell lines and is looking for human versions of markers already identified in mice.

“The ultimate goal is to identify esophageal stem cells in a patient, grow the patient’s own stem cells, and inject them locally to replace diseased tissue with normal lining,” says Rustgi.

The investigators report their findings online in December 2008 in the Journal of Clinical Investigation. Penn co-authors are Jiri Kalabis, Kenji Oyama, Takaomi Okawa, Hiroshi Nakagawa, Carmen Z. Michaylira, Douglas B. Stairs, and J. Alan Diehl (Department of Cancer Biology), as well as Jose-Luiz Figueiredo and Umar Mahmood from Massachusetts General Hospital, Molecular Center for Imaging Research, Boston, and Meenhard Herlyn, from The Wistar Institute, Philadelphia.

This work was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute.

Adapted from materials provided by University of Pennsylvania School of Medicine.

HHS HealthBeat (April 08, 2009)

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From the U.S. Department of Health and Human Services – HHS HealthBeat.

Can alcohol give people courage? A researcher thinks alcohol instead can reduce the brain’s ability to detect fear.

Jodi Gilman of the National Institutes of Health examined that. She and her colleagues gave people doses of alcohol or a fake substitute intravenously, and then watched their brain images as they were shown pictures of faces expressing fear.

Normally, fear-response centers react when people see other people being afraid. But Gilman says that’s not what happened after the volunteers got the alcohol:

[Jodi Gilman speaks] “None of this increased brain activity to the fearful faces was detected. So this indicates that, during intoxication, threat detecting brain circuits couldn’t tell the difference between a threatening and a non-threatening stimulus.”

Gilman says this may explain the impaired judgment that can come from drinking.

The study was in The Journal of Neuroscience.

Learn more at hhs.gov.

HHS HealthBeat is a production of the U.S. Department of Health and Human Services

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Mean sea ice thickness in meters for March (left) and September (right) based on six models. Top panels: September ice extent reached the current level by these models. Bottom panels: Arctic reached nearly “ice-free summer” conditions.
(Credit: University of Washington / NOAA)

NOAA, April 9, 2009 — Summers in the Arctic may be ice-free in as few as 30 years, not at the end of the century as previously expected. The updated forecast is the result of a new analysis of computer models coupled with the most recent summer ice measurements.

“The Arctic is changing faster than anticipated,” said James Overland, an oceanographer at NOAA’s Pacific Marine Environmental Laboratory and co-author of the study, which will appear April 3 in Geophysical Research Letters. “It’s a combination of natural variability, along with warmer air and sea conditions caused by increased greenhouse gases.”

Overland and his co-author, Muyin Wang, a University of Washington research scientist with the Joint Institute for the Study of the Atmosphere and Ocean in Seattle, analyzed projections from six computer models, including three with sophisticated sea ice physics capabilities. That data was then combined with observations of summer sea ice loss in 2007 and 2008.

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Data visualization: Arctic sea ice.
(Credit: NOAA)

The area covered by summer sea ice is expected to decline from its current 4.6 million square kilometers (about 1.8 million square miles) to about 1 million square kilometers (about 390,000 square miles) – a loss approximately two-fifths the size of the continental U.S. Much of the sea ice would remain in the area north of Canada and Greenland and decrease between Alaska and Russia in the Pacific Arctic.

“The Arctic is often called the ‘Earth’s refrigerator’ because the sea ice helps cool the planet by reflecting the sun’s radiation back into space,” said Wang. “With less ice, the sun’s warmth is instead absorbed by the open water, contributing to warmer temperatures in the water and the air.”

NOAA understands and predicts changes in the Earth’s environment, from the depths of the ocean to the