Science Life

Cancer Causing Gene Protein Found

noreply@blogger.com (Kakariku) — Thu, 18 Sep 2008 21:39:00 +0000

Dr. Tak Mak and scientists at The Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital have discovered the role of two "cousins" in the genetic family tree of cancer development.

The findings, published online today in the journal Genes and Development, plant the seed for a critical new branch of scientific inquiry, says Dr. Mak, principal investigator. Dr. Mak, Director of The Campbell Family Institute is also a Professor, University of Toronto, in the Departments of Medical Biophysics and Immunology.

The cousins are proteins related to the gene p53 family – the patriarch known for two decades to be the master gatekeeper that controls all cancer development. When gene p53 is defective, it loses its ability to regulate healthy cells and suppress cancer.

"Until now, we thought these cousins (TAp73 protein isoforms) were not involved in cancer. Our results prove that they are. This is fundamental to understanding every human cancer and furthering the science."

In the lab, Dr. Mak and his team challenged traditional thinking about the role of these proteins. "Before, scientists studied only whether these proteins were present or absent. We decided to study how they interact with each other and discovered that they actually have a split personality. When we turn one 'on' or 'off', the other changes behavior and becomes part of the cancer-causing process. The key is understanding the ratio of the interaction."

"The next step is to understand how the ratio affects cell division that leads to human cancer," says Dr. Mak, whose work was supported by the Canadian Institutes for Health Research.

A Unique Way to Measure Dark Energy with Galaxies and Quasars

noreply@blogger.com (Kakariku) — Thu, 18 Sep 2008 21:39:00 +0000

The Sloan Digital Sky Survey (SDSS) uses a 2.5-meter telescope with a wider field of view than any other large telescope, located on a mountaintop in New Mexico called Apache Point and devoted solely to mapping the universe. We now know that some three-quarters of the universe consists of dark energy, whose very existence was unsuspected when telescope construction began in 1994 and still controversial when the first Sloan survey started in 2000.

Investigating dark energy has since emerged as one of the most crucial tasks of the SDSS. SDSS-III, the third major mapping program, started in midsummer 2008, with the biggest of its four component surveys being a dark-energy probe called BOSS, the Baryon Oscillation Spectroscopic Survey.

Astrophysicist David Schlegel, since 2004 a member of the Physics Division at the U.S. Department of Energy's Lawrence Berkeley National Laboratory, is the principal investigator of BOSS; formerly of Princeton University, Schlegel has been part of the SDSS team since its beginning.

"To tell the truth, the first time I heard about dark energy I was skeptical," Schlegel says.

The evidence came from studies, pioneered by the Supernova Cosmology Project based at Berkeley Lab, comparing the brightness and redshift of distant Type Ia supernovae. The results showed that the expansion of the universe was accelerating, driven by something which, being unknown, was soon tagged with the label dark energy.

Schlegel was soon won over, however, and immediately realized that the Sloan telescope, "which has an enormous field of view," could be used for quite a different kind of dark energy measurement, one completely independent of supernova studies. Baryon acoustic oscillation is a fancy name for the way galaxies are distributed; their density varies regularly, bunching up roughly every 500 million light years and providing a natural measuring stick or "ruler" for measuring how much the universe has expanded since early in its history.

To use a 500-million-light-year ruler, however, one has to have at least a few billion light years to use it in. The Sloan telescope was custom-designed to take in such an enormous volume of space.
Anisotropies in the cosmic microwave background, originating when the universe was less than 400,000 years old, are directly related to variations in the density of galaxies as observed today.
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The distribution of visible mass in the universe

"Baryon" (meaning protons and neutrons and other relatively massive particles) is shorthand for ordinary matter. For almost the first 400,000 years, the universe was so dense that particles of matter were thoroughly entangled with particles of light (photons), the whole a vast, quivering, liquid-like blob where density variations caused sound waves (pressure waves) to move spherically outward at over half the speed of light.

Suddenly the expanding universe cooled enough for light and matter to "decouple." Photons shot through transparent space unimpeded; the speed of sound plummeted. What had been variations in the density of the liquid universe left two marks in the now-transparent sky.

Variations in the temperature of the radiation that filled the early universe have descended to us as anisotropies in the cosmic microwave background (CMB). Variations in the density of matter persist in the clustering of galaxies, as baryon acoustic oscillations (BAO). The two scales, the roughly one-degree anisotropy of the CMB and the 500-million-light-year clustering of BAO, are closely related; the standard ruler of the universe measured from BAO can be calculated from the CMB for any epoch since decoupling.

Schlegel and his colleague Nikhil Padmanabhan, who came to Berkeley Lab from Princeton in late 2006, first used the SDSS telescope to complete the largest three-dimensional map of the universe ever made until then: 8,000 square degrees of sky out to a distance of 5.6 billion light years, determining the clustering of 60,000 luminous red galaxies. This program, part of SDSS-II, measured galactic distances to a redshift of z = 0.35 and detected the 500-million-light-year scale of BAO.

"We were mostly excited that we could make a measurement," Schlegel says. "We proved we had a ruler we could use."

"With BOSS, we're going from a measurement to a much more precise measurement that we can use to constrain dark energy," says Padmanabhan.

BOSS will double the volume of space in which red luminous galaxies will be studied, observing 10,000 square degrees of sky out to redshifts of z = 0.7; the galaxy sample will increase from 60,000 to 1.5 million. BOSS will also include a new kind of object, measuring up to 200,000 quasars at even more extreme redshifts of z = 2 or more.
David Schlegel, principal investigator of BOSS, shows one of the numerous "plug plates " used to map and select hundreds of galaxies for each exposure. Light from each galaxy enters a...
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"The epoch of the most common quasars was at redshifts between 2 and 3," Schlegel says, "just enough that we can still see them at optical wavelengths in the blue and ultraviolet; in this respect, nature was kind to us. BOSS will be the first look at dark energy at these redshifts. Only a few Type Ia supernovae have been found beyond redshift 1."

Galaxies and quasars provide different ways to measure the expansion of the universe using baryon acoustic oscillation. The angle of separation among galaxies across the sky and the distance of their separation along the line of sight (at different redshifts) shows how much the BAO cosmic ruler has changed since baryons and photons decoupled.

"At the moment of decoupling, baryon oscillations were frozen," says Padmanabhan. "A really simple geometry test tells us how much the scale has expanded – and accelerated – since the oscillations were frozen in."

Quasars allow a look at a different kind of baryonic oscillation from the distribution of galaxies, that of the varying density of the gas in the universe, which can be probed at hundreds of points along the line of sight to each quasar.

The measured spectrum of an individual quasar is conditioned by the absorption of its light by clouds of hydrogen gas between the quasar and the viewer. "If the universe were empty, the spectra would be featureless," Schlegel says. "We are using the quasars as a backlight to measure hydrogen absorption."

Because the CMB precisely locks in the value of BAO at the moment on decoupling – equivalent to a redshift z = 1,089 – it greatly leverages the accuracy of baryon acoustic oscillations at much more recent epochs and lower redshifts. Padmanabham says that "BOSS will be within a factor of 2 of the best possible map of BAO in the universe."

Schlegel adds, "No one will repeat this experiment."

What it will take

Good as the Sloan telescope is, BOSS will require some major improvements in instrumentation, to be carried out under the direction of Berkeley Lab physicist Natalie Roe. The first task is to increase the number of objects that can be measured with each exposure.

Objects to be included in the survey (galaxies or quasars) are first chosen and located from previous photos. A hole is drilled in a metal "plug plate," a mask to reduce ambient light. An optical fiber is plugged into each hole to carry the light from the object directly to the CCDs. The diameter, separation, and other characteristics of the fibers put a limit on how many can be used at once. At present the limit is 640; BOSS will increase that number to 1,000 fibers with improved optics, allowing more objects and less sky contamination in each exposure.

Higher redshifts call for CCDs with better sensitivity to the red and near-infrared end of the spectrum. The Berkeley Lab high-resistance CCD, descended from silicon detectors used in high-energy physics, is particularly suited to this purpose and is integral to the Lab's proposed SuperNova/Acceleration Probe (SNAP) satellite, the inspiration and leading contender for the NASA/DOE Joint Dark Energy Mission (JDEM). SNAP will study both supernovae and "weak lensing" (a third approach to measuring dark energy). BOSS will use the same rugged, highly red-sensitive CCDs to study luminous red galaxies.

BAO and supernovae are two highly complementary ways of approaching the wide-open questions of dark energy – for example, whether dark energy has been constant or variable over time, or even whether it may be illusory, with its most obvious effect, the accelerating expansion of the universe, resulting instead from some unperceived flaw in Einstein's General Theory of Relativity. Although BAO and supernova studies are both purely geometric, they are independent.

To study expansion using distant Type Ia supernova, scientists must determine their brightness as measured against "nearby" Type Ias. Baryon oscillation studies do almost the reverse, measuring the expansion of the universe by calibrating the dimensions of the BAO cosmic ruler, seen in relatively nearby objects, against the scale that was frozen in when the universe was less than 400,000 years old. BOSS will be able to determine BAO with an accuracy approaching one percent, one of the most precise possible measurements of the expansion of the universe.

Source

3-D virtual reality environment by UCLA

noreply@blogger.com (Kakariku) — Thu, 18 Sep 2008 12:31:00 +0000

Its name sounds like something out of science fiction, but the StarCAVE at the University of California, San Diego is now a science fact. The virtual-reality environment allows groups of scientists to venture into worlds as small as nanoparticles and as big as the cosmos – permitting new insights that could fuel discoveries in many fields. Early users of the StarCAVE include UC San Diego researchers in biomedicine, neuroscience, structural engineering, archaeology, earth science, genomics, art history and other disciplines.
Photo of Calit2 researchers explore proteins in 3D
Calit2 researchers explore proteins in 3-D from the Protein Data Bank, displayed inside the StarCAVE.

The StarCAVE is a five-sided virtual reality (VR) room where scientific models and animations are projected in stereo on 360-degree screens surrounding the viewer, and onto the floor as well. It was constructed by the UC San Diego division of the California Institute for Telecommunications and Information Technology (Calit2). At less than $1 million, the StarCAVE immersive environment cost approximately the same as earlier VR systems, while offering much higher resolution and contrast.

“When you’re inside the StarCAVE the quality of the image is stunning,” said Thomas A. DeFanti, director of visualization at Calit2 and one of the pioneers of VR systems. “The StarCAVE supports 20/40 vision and the images are very high contrast, thanks to the room’s unique shape and special screens that allow viewers to use 3-D polarizing glasses. You can fly over a strand of DNA and look in front, behind and below you, or navigate through the superstructure of a building to detect where damage from an earthquake may have occurred.”

A research paper about the design and construction of the StarCAVE appears in the current issue of the Elsevier journal, Future Generation Computer Systems (FGCS), and is available online at ScienceDirect.* DeFanti’s co-authors on “The StarCAVE, a Third-Generation CAVE and Virtual Reality OptIPortal,” include Calit2’s Gregory Dawe, Jurgen P. Schulze, Peter Otto, Javier Girado, Falko Kuester, Larry Smarr and Ramesh Rao (all at UC San Diego), as well as Daniel J. Sandin of the University of Illinois at Chicago’s Electronic Visualization Lab (EVL), and Javier Girado (now at Qualcomm Inc.).

The StarCAVE represents the third generation of surround-VR rooms. DeFanti’s team built and named the original Cave Automated Virtual Environment (CAVE) at the University of Illinois at Chicago in 1991. A second-generation model built ten years later at EVL is now the standard surround-VR technology and is widely used around the world and marketed by Mechdyne Corp. The first- and second-generation CAVEs require viewers to wear battery-powered ‘shutter’ glasses; the StarCAVE provides an improved 3-D experience and allows viewers to wear only lightweight, polarized ‘sun’ glasses.
Photo of Calit2 Director of Visualization Tom DeFanti inside the StarCAVE virtual reality system
Calit2 Director of Visualization Tom DeFanti inside the StarCAVE virtual reality system.

The room operates at a combined resolution of over 68 million pixels – 34 million per eye – distributed over 15 rear-projected walls and two floor screens. Each side of the pentagon-shaped room has three stacked screens, with the bottom and top screens titled inward by 15 degrees to increase the feeling of immersion (while also reducing the ghosting, or ‘seeing double’, that bedevils VR systems).

Because the StarCAVE is designed to help scientists, DeFanti and his team made sure to incorporate the latest in computer graphics processing – using 34 of the newest nVIDIA chips that can generate highly complex images. Thirty-four high-definition projectors (two per screen) create very bright left and right eye visuals, i.e. stereo or 3-D, per screen. Each pair of projectors is powered by a high-end, quad-core PC running on Linux, with dual graphics processing units and dual network cards to achieve gigabit Ethernet or 10GigE networking.

“With its advanced networking, the StarCAVE is the best virtual-reality portal within the OptIPuter network,” said Calit2’s DeFanti, co-principal investigator on the National Science Foundation-funded OptIPuter project. “That network now connects more than 20 so-called OptIPortals which are up and running around the world. They are ultra-high-resolution, tiled display walls, but for some researchers, flat display walls just aren’t enough: they want the realism that comes from the fully immersive 3-D experience that only a 360-degree VR room such as the StarCAVE can offer.”

Adding to the virtual reality in the StarCAVE is the surround sound system, which harnesses recent advances in wave field synthesis – a way to maximize the perception of many channels of sound emanating from different sides of the room. Calit2 also worked closely with Meyer Sound, Inc., to customize the installation of three arrays of five conventional high-quality speakers to provide 5.1 surround sound or up to 15 channels of discreet audio diffusion (with a subwoofer channel built into the floor structure).

Users of the StarCAVE can interact with the visuals on the 360-degree display – by pointing a “wand” that makes it easy to fly through the 3-D images and zoom in or out. The exact position of the wand and the user is determined by a multi-camera wireless tracking system.

Among the VR room’s other features, it is wheelchair accessible, and it was designed to withstand earthquakes. One of the StarCAVE’s five walls (along with its six projectors, three screens and three computers) rolls back on steel rails to provide access for users into the space, and the wall rolls back into place to provide the full 360-degree, immersive VR experience.

While the StarCAVE was in development, computer scientists were working on new applications to adapt computer programs for display in the VR environment. The room connects to the Protein Data Bank, so users can pull up one or multiple proteins and fly around them to find similarities and differences between the proteins. A virtual replica of Calit2’s headquarters building at UC San Diego, Atkinson Hall, has been used by neuroscientists who want to know if the human brain operates differently in virtual reality versus reality in ‘wayfinding’ situations.

“We also created an application which displays computer-aided design models of parts of the new San Francisco Oakland Bay Bridge,” said DeFanti. “The application allows users to walk/fly through these parts at their real size, to find material clashes, construction errors, and generally to draw conclusions about whether the structure could be built as designed.”

Superhard, Super Slippery Diamonds

noreply@blogger.com (Kakariku) — Wed, 16 Jul 2008 07:41:00 +0000

They call diamonds “ice,” and not just because they sparkle. Engineers and physicists have long studied diamond because even though the material is as hard as an ice ball to the head, diamond slips and slides with remarkably low friction, making it an ideal material or coating for seals, high performance tools and high-tech moving parts.

Robert Carpick, associate professor in the Department of Mechanical Engineering and Applied Mechanics at the University of Pennsylvania, and his group led a collaboration with researchers from Argonne National Laboratories, the University of Wisconsin-Madison and the University of Florida to determine what makes diamond films such slippery customers, settling a debate on the scientific origin of its properties and providing new knowledge that will help create the next generation of super low friction materials.

The Penn experiments, the first study of diamond friction convincingly supported by spectroscopy, looked at two of the main hypotheses posited for years as to why diamonds demonstrate such low friction and wear properties. Using a highly specialized technique know as photoelectron emission microscopy, or PEEM, the study reveals that this slippery behavior comes from passivation of atomic bonds at the diamond surface that were broken during sliding and not from the diamond turning into its more stable form, graphite. The bonds are passivated by dissociative adsorption of water molecules from the surrounding environment. The researchers also found that friction increases dramatically if there is not enough water vapor in the environment.

Some previous explanations for the source of diamond’s super low friction and wear assumed that the friction between sliding diamond surfaces imparted energy to the material, converting diamond into graphite, itself a lubricating material. However, until this study no detailed spectroscopic tests had ever been performed to determine the legitimacy of this hypothesis. The PEEM instrument, part of the Advanced Light Source at Lawrence Berkeley National Laboratory, allowed the group to image and identify the chemical changes on the diamond surface that occurred during the sliding experiment.

The team tested a thin film form of diamond known as ultrananocrystalline diamond and found super low friction (a friction coefficient ~0.01, which is more slippery than typical ice) and low wear, even in extremely dry conditions, (relative humidity ~1.0%). Using a microtribometer, a precise friction tester, and X—ray photoelectron emission microscopy, a spatially resolved X-ray spectroscopy technique, they examined wear tracks produced by sliding ultrananocrystalline diamond surfaces together at different relative humidities and loads. They found no detectable formation of graphite and just a small amount of carbon re-bonded from diamond to amorphous carbon. However, oxygen was present on the worn part of the surface, indicating that bonds broken during sliding were eventually passivated by the water molecules in the environment.

Neuroscientists spot nature/nurture gene link

noreply@blogger.com (Kakariku) — Wed, 16 Jul 2008 07:37:00 +0000

Neuroscientists at MIT's Picower Institute for Learning and Memory found that a previously unsuspected set of genes links nature and nurture during a crucial period of brain development

Nature--in the form of genes--and nurture--in the form of environmental influences--are fundamentally intertwined during this period.

"Our work points to how a disorder can be genetic and yet be dependent on the environment," said co-author Mriganka Sur, Sherman Fairchild Professor of Neuroscience at the Picower Institute and chair of MIT's brain and cognitive sciences department. "Many genes require activity to be expressed and make their assigned proteins. They alter their expression when activity is altered. Thus, we reveal an important mechanism of brain development that should open up a window into the mechanisms and treatment of brain disorders such as autism."

In the brain, some genes are only expressed, or turned on, in response to stimulus from the outside world. Like a panel of switches that turn lights on and off, genes that don't receive electricity don't "turn on" and express their particular proteins.

Sur and colleagues found a set of novel genes--including a calcium sensor called cardiac Troponin C, or cTropC--particularly sensitive to a critical period of development. The lack of proteins from these genes during a key phase of development could be one of the culprits in developing autism.

Researchers have long investigated the molecular mechanisms involved in monocular deprivation--when one eye is deprived of sight during a critical period of brain development, that eye becomes permanently blind, even after it is uncovered. This phenomenon is considered an important model for brain development because synapses for the covered eye--deprived of environmental stimulus, or what Sur calls "nurture"--shrivel up or get reassigned to other uses.

Sur and his colleagues looked at which genes are expressed, and which are not, when this phenomenon occurs. They hoped to pin down the correlation between nature--meaning the genes--and the external environment, or nurture. By identifying which genes are particularly apt to switch their expression patterns in response to "nurture," the researchers potentially narrowed down the ones that may be implicated in developmental disorders.

Researchers believe autism spectrum disorders are tied to brain changes that occur during critical periods of development. Different but overlapping critical periods are thought to exist for various cognitive functions affected in autism, such as language and social behaviors.

"Autism is a strongly genetic disorder: genes set up risk factors but by themselves simply make proteins," Sur said. "Genes work together with other influences. In the case of autism, these influences are unknown but could be molecules made by other genes or chemicals from the environment."

If scientists understood how genes changed in response to environmental influences during this crucial developmental period, they might be able to one day prevent or reverse the changes.

New method devised for protecting private data

noreply@blogger.com (Kakariku) — Sun, 20 Apr 2008 10:35:00 +0000

Companies and organizations that keep sensitive personal information on millions of Americans have become attractive targets for hackers in recent years, resulting in billions of dollars in losses for U.S. businesses and misery for countless consumers.

But now Amit Sahai, an associate professor of computer science at the UCLA Henry Samueli School of Engineering and Applied Science, and his colleagues have devised a new data-protection method they hope will put Internet criminals out of business.

"We want to change the rules of the game on hackers and even out the playing field," Sahai said.

Along with co-authors Brent Waters, a UCLA computer science alumnus, and Jonathan Katz of the University of Maryland, Sahai has come up with a mathematical system -- known as functional encryption -- that will not only help to simplify the encryption of data in servers but will also allow access to the data in an intuitive way, making it much harder for hackers to gain access to sensitive information but much easier for programmers to secure it.

While the method is not yet available for public use, it has received close attention from the data-encryption community. The authors' study, chosen as one of the top four papers at Eurocrypt 2008 -- one of two flagship international conferences in cryptography -- was presented this week at the conference in Istanbul.

In it, Sahai and his colleagues suggest that the biggest problem in data security today is that the world relies on "trusted servers" to store and secure data.

"This 'trusted server' model is a simple model," Sahai said. "It's easy to implement. It's easy to put into practice. Information is placed in the server at face value and the server itself is simply given the task of deciding who to give the data to. Because of the simplicity in programming, these servers have become ubiquitous and are prime targets -- everyone wants to attack them."

An additional problem with trusted servers, the authors say, is the current trend toward replicating data on a wide scale.

"To create robustness and availability, data is stored on several trusted servers as backups," said Waters, currently with the nonprofit research institute SRI. "If one server goes down, another can be accessed. There is a trade-off between data availability and security. The more replicated servers there are, the more targets there are for hackers."

The results of this lack of security speak for themselves. According to a 2007 FBI analysis, Internet crime costs U.S. businesses some $67 billion annually, including the indirect expense of repairing hacked systems. TJX, the parent company of discount clothing chains T.J. Maxx and Marshalls, revealed that during a recent 18-month period, hackers had stolen 45.6 million credit card numbers and other sensitive customer information. For every two Americans, one private record has been stolen through computer data breaches alone.

Cryptography, the practice and study of hiding information, is considered to be a branch of both mathematics and computer science and is closely tied to information theory, computer security and engineering. And while the technology of encryption has been around a long time, encrypting data and then deciding how to allow access to hundreds or even thousands of people has been a dilemma, Sahai said.

"Imagine current encryption technology as a lock and key -- the data is locked, and to allow different people access, many copies of the key need to be made," he said. "One record might need to be accessed by 10,000 people, so you make 10,000 copies of that key. With millions of documents and thousands of keys per document, you can imagine how very, very complicated it gets. It becomes much too complicated to manage. So even though we've had very strong encryption technology now for decades, it's just not used, or it is used incorrectly."

The study authors' new functional encryption method allows a programmer to simply plug in his criteria for the information. The mathematical system will then produce an encrypted record that only people matching the criteria can decrypt. The complex system of managing many keys is now simplified, and servers hold encrypted data that the servers themselves can't read. The information looks like gibberish to hackers.

In addition, the new mathematical system allows for keys to be personalized -- only one key is needed to unlock all the information that is available to that person.

"This is the key innovation in our system," Sahai said. "We have this mathematical method for randomization of personalizing keys so that your key doesn't just depend on what attributes you have, like what your name is. Further, there is some mathematical hardening that is personalized to you, so that you can't combine it with anyone else's keys to do anything meaningful."

The system severely restricts what a hacker can do. If he is an insider, he is limited by what access he legitimately has, and since keys are personalized, it becomes much easier to trace who accessed and released the information in the first place.

Sahai and Waters are considered the founders of the area of functional encryption. Sahai recently won a prestigious 2007 Okawa Research Grant Award from Japan's Okawa Foundation for his work in this area.

"Some of this work is already being implemented and is actually being incorporated into some research systems," Sahai said. "It's making its way closer to practice. Brent and I were able to apply for a patent on the very initial work we did, which was bought by a company called Voltage Security. There certainly is interest from the U.S. military and the U.S. Department of Homeland Security as well."

"Our goal is to rethink what encryption is," Waters said. "Over the years, people have taken on a somewhat rigid view of what encryption is. What we're hoping to do is show that we can build simpler and more powerful systems by changing the way we think. Eventually, we hope to get rid of complex infrastructures and do things in a simpler manner that is also more secure and cost-effective."

VIA

Gene variant increases risk of asthma

noreply@blogger.com (Kakariku) — Sun, 20 Apr 2008 10:33:00 +0000

A tiny variation in a gene known as CHI3L1 increases susceptibility to asthma, bronchial hyperresponsiveness and decline in lung function, researchers report early online in the New England Journal of Medicine. (The printed version will appear in the April 17 issue). The gene variant causes increased blood levels of YKL-40, a biomarker for asthma. A slightly different version of the genetic variation lowers YKL-40 levels and protects against asthma.

Although the original discovery came from a study of a genetically isolated population, the Hutterites of South Dakota, the researchers were able to confirm the same connections between the CHI3L1 variations, YKL-40 levels and asthma susceptibility in three genetically diverse Caucasian populations from Chicago; Madison, Wisconsin; and Freiberg, Germany.

This gene, "may have important implications in the early identification of, susceptibility to, and prevention and treatment of asthma,” said Elizabeth G. Nabel, M.D., director, the National Heart, Lung, and Blood Institute.

"This is exciting because it connects asthma susceptibility to a whole new pathway at the protein and the genetic levels," said study author Carole Ober, professor of human genetics at the University of Chicago Medical Center. "There is a good deal more we need to find out about this connection, but now we know where to look."

"This is also the most significant genetic discovery based on our years of gathering data on asthma in the Hutterites," Ober added. "This is a group with enormous potential to advance our understanding of the genetic underpinnings of disease. We now have a remarkable collection of data, which we expect will lead us to many more insights."

Ober and colleagues at the University of Chicago had long been searching for genetic factors that could influence the risk of common diseases, such as asthma. To simplify this quest, they have focused since 1994 on the Hutterites, a genetically isolated U.S. religious community descended from about 90 people. The Hutterites came to the United States in 1874 and settled in small communal farming colonies in what is now South Dakota. Today Hutterite communities are present in the Dakotas, Minnesota, Montana, Washington and Canada.

They provide an ideal community for genetic studies because they are all members of a large pedigree that is known back to the 1700's and they live communally, sharing resources and maintaining a traditional lifestyle. "They eat the same food, live off the same allowance and have the same education," said Ober, who has been working with them since 1979. They have similar, but not identical genomes. "So the genes that make a difference are easier to detect."

In 1996 and 1997, Ober's team gathered clinical data about asthma from more than 700 members of the Hutterite communities, and stored blood samples that were recently used to measure YKL-40 levels. About 11 percent of Hutterites had asthma and another 12 percent had bronchial hyperresponsiveness.

The genetic studies took on a sharper focus in 2007, when a team led by Geoffrey Chupp of Yale University showed that, on average, patients with asthma had higher levels of the protein YKL-40 in their blood than people without asthma, and that those with more severe asthma had even higher levels.

YKL-40, a natural suspect as a cause of asthma, belongs to a family of enzymes called chitinases. These enzymes are part of the innate immune system's response to chitin, a common biologic polymer found especially in insects – including dust mites and cockroaches, which have been associated with asthma – as well as in certain disease-causing organisms, including fungi and parasitic worms. The chitinases help break down chitin. They also trigger inflammation, which is a central component of asthma.

Working with Chupp's laboratory, Ober found that mean YKL-40 levels were also increased among Hutterites with asthma or hyperresponsive airways. Ober's group also showed that these elevated YKL-40 levels were handed down from generation to generation, indicating that differences between individuals were due nearly entirely to genetic differences.

So they began looking for variations in the CHI3L1 gene on chromosome 1 that codes for YKL-40. They found one very slight genetic difference between those with asthma and those without. Hutterites with asthma were more likely to have a small but consistent variation in one part of the gene, called a promoter, which regulates when the gene is expressed.

That variation changes one DNA base pair, out of the 3 billion in the human genome, at a location in the CHI3L1gene known as -131C/G. Those with asthma were more likely to have a cytosine (C), rather than guanine (G) at this location.

Those inheriting two copies of a C at -131 had higher YKL-40 levels and an asthma prevalence of 0.20. Those with CG had intermediate YKL-40 levels and an asthma prevalence of 0.12. Those with GG had the lowest YKL-40 levels and a prevalence of only 0.08, less than half that of the CC allele.

To see if these results could be generalized from the genetically isolated Hutterite population to a more diverse group, the researchers tested the same variations in the CHI3L1 gene in 178 Caucasian children enrolled in prospective birth cohort, known as COAST, a collaboration led by Robert Lemanske of the University of Wisconsin at Madison.

They also looked for correlations between asthma and SNP -131C/G in two clinical samples, one from the Children's University Hospital in Freiberg, Germany (344 children with asthma and 294 without), and one from the asthma clinics at the University of Chicago Medical Center (99 children and adults with asthma and 197 without).

In the two clinical samples, those with the CC configuration at position 131 were more likely to have asthma, with CG intermediate and GG the lowest risk of the disease. In the COAST cohort, many subject were still too young to have developed asthma, but the genetic patterns was closely associated with YKL-40 levels, and this association was already present at birth.

The authors suspect that the change from C to G at this site reduces expression of the gene, resulting in lower levels of YKL-40 and protection from asthma.

Although variation in CHI3L1 appears to be one of the most significant genetic triggers yet discovered for susceptibility to asthma, it is far from the sole cause of the disease, the researcher caution. In the Hutterites, it explains 9.4 percent of the variance in YKL-40 levels, suggesting that additional genetic variants also influence these levels. Finding those variations "could identify additional genes," they add, "with significant impact on asthma risk and lung function."

"This evolutionarily ancient pathway involving the innate immune system plays a surprisingly important role in asthma pathogenesis," said Ober, "and a single genetic variant in the CHI3L1 gene may account for most of this risk."

This could have a significant impact on drug development, she added. "For some people, if you block YKL-40 you might dramatically reduce the severity of the disease. Knowing the genotype at SNP -131C might identify those who most likely to benefit from such a treatment."

Scientists show first 3-D image of antibody gene

noreply@blogger.com (Kakariku) — Sun, 20 Apr 2008 10:31:00 +0000

Using a multidisciplinary mix of geometry, biological research and techniques developed to solve problems on supercomputers, scientists at the University of California, San Diego have shown for the first time how a genome is organized in three-dimensional space.

The 3-D structure of the immunoglobulin locus in B cells is shown, with the relative positions of the different portions of the immunoglobulin genes. Grey objects indicate constant regions. Blue objects indicate proximal variable regions. Green objects indicate distal variable regions. Red line indicates the linker connecting the proximal variable and joining regions.

Researchers led by Cornelis Murre, a professor of biology at UC San Diego, and Steve Cutchin, senior scientist for visualization services at the San Diego Supercomputer Center (SDSC), used the gene encoding the immunoglobulin heavy chain locus — responsible for generating diverse kinds of antibodies — to demonstrate the structure of the genome.

The observations, the researchers say, permit an insight into the structure of the human genome, which until now has remained elusive.

Their results, “The 3-D Structure of the Immunoglobulin Heavy Chain Locus: Implications for Long-Range Genomic Interactions,” are published in the April 18 issue of the journal Cell.

Because the genome is the most essential part of the cell for storing and accessing genetic information, the complete DNA sequence of a wide variety of genomes has been revealed in studies performed in a large number of laboratories — “a tremendous success that has provided insight into mechanisms that underpin the development of a wide variety of diseases,” the authors say.

However, Murre said, “it has remained unclear as to how the genome is organized in three-dimensional space. This is an important issue since the regulation of gene expression is controlled by interactions of genomic elements that are separated by large genomic distances. Thus, our team wanted to determine how the genome is structured within the nucleus.”

The experiments described in the Cell paper, he said, provide a first glimpse into this question. “As a model system, we used the gene encoding for the immunoglobulin heavy chain locus, because it is responsible for generating the wide diversity of antibodies.”

Having measured the distances that separate the various parts of the gene, Murre said, the researchers, in collaboration with Cutchin at the SDSC, then used geometry to resolve the first structure of a genetic locus.

His work, said Cutchin, involved computational geometry, scientific visualization, computational methods and numerical methods.

“The resulting structure shows that the antibody gene is organized into ‘flower-like’ structures that are connected by linkers,” said Murre. “These flowers contain the various parts that ultimately generate the wide variety of antibodies. This is the first time that geometry has been used to determine the structure of a genetic locus. Ultimately, the same approach should be used to elucidate the structure of the entire human genome.”

Release of Darwin’s papers includes first draft of Theory of Evolution

noreply@blogger.com (Kakariku) — Sun, 20 Apr 2008 10:30:00 +0000

The first draft of Charles Darwin’s Theory of Evolution is among thousands of his private papers made accessible online for the very first time.

For decades these were only available to scholars at Cambridge University Library.

But they can now be seen free of charge by anyone around the globe at Darwin Online (http://darwin-online.org.uk/).

The publication of Darwin’s private papers is the largest in history, totalling about 20,000 items in nearly 90,000 images.

As well as the first draft of his theory of evolution, the vast collection of Darwin-related items includes thousands of notes and drafts of his scientific writings, notes from the voyage of the Beagle - with his musings on Galapagos birds - and his first recorded doubts about the permanence of species. It also contains photographs of Darwin and his family, newspaper clippings, reviews of his books and much more.

On a less scientific note, there is material revealing Victorian family life such as Emma Darwin’s recipe book. Contained within are delicacies such as 'Ilkley pudding'; and a rudimentary recipe for boiling rice, scrawled in Darwin’s own handwriting.

Dr John van Wyhe, Director of The Complete Work of Charles Darwin Online at Cambridge University, said: “Charles Darwin is one of the most influential scientists in history. The collection of his papers now online is extremely important and therefore very exciting.

“This release makes his private papers, mountains of notes, experiments, and research behind his world-changing publications available to the world for free.

“His publications have always been available in the public sphere - but these papers have until now only been accessible to scholars.”

The immensity of the collection means even if you viewed one image per minute, it would still take more than two months to see all of the material made available today.

Covering Darwin’s life from childhood, the papers also feature his boyhood notes on birds, proofs of his Origin of Species, as well as caricatures and obituaries and much more.

Dr van Wyhe added: “Darwin changed our understanding of nature forever. His papers reveal how immensely detailed his researches were. The release of his papers online marks a revolution in the public's access to - and hopefully appreciation of - one of the most important collections of primary materials in the history of science.”

Genome analysis reveals new protein associated with breast cancer progression

noreply@blogger.com (Kakariku) — Sun, 20 Apr 2008 10:24:00 +0000

A novel systems-based approach that combines comprehensive gene expression profiling with genome-wide transcription factor analysis and protein-protein interaction has led researchers to an important genetic marker that can help physicians know which breast cancer patients are at highest risk and will require more aggressive treatment, a research team based at the University of Chicago Medical Center reports in the April 15, 2008, issue of the journal Molecular Systems Biology.

The researchers found that high expression of a protein known as H2A.Z, which is associated with the expression of genes within the nucleus, can help physicians predict which patients are most at risk for disease spread and death. It could also serve as a new target for therapy.

“Elevated H2A.Z expression is significantly associated with metastasis and shorter survival, and it could quickly help doctors make better predictions and treatment choices for their patients,” said study director Kevin White, PhD, professor of human genetics and director of the Institute for Genomics and Systems Biology at the University of Chicago and Argonne National Laboratory. “It could also provide clues to new therapies.”

“But, perhaps more important,” he added, “we think we have developed an integrated approach to genomic analysis that can be applied to a wide range of cancers.”

Instead of a standard whole-genome analysis, looking for genetic variations that correlate with disease risk, White and colleagues integrated multiple genetic technologies to measure the effects of estrogens, which play a crucial role in many breast cancers, on multiple cellular pathways, what they refer to as a “transcriptional regulatory cascade.”

The female hormone estrogen acts by binding to the estrogen receptor, which carries the hormone’s signal to a cell’s nucleus, where it activates many other genes. One of those genes is a known cancer-related gene called c-MYC, which in turn regulates its own cascade of gene targets.

White’s team set out to map out the many sequential genetic events that occur in breast cancer cells after estrogen binding, using a series of innovative technologies. They ultimately found that estrogen-stimulated c-MYC enhanced production of H2A.Z, which altered the positioning and activation of various genes in ways that increased the odds that a cancer would spread to the lymph nodes and ultimately to distant sites, often resulting in the patient’s death.

This is not a simple process. In tumor cells from patients with estrogen-dependent breast cancers, the researchers found estrogen affected 1,615 genetic regions. One of those was the promoter for the gene for c-MYC, which, when activated, could bind another set of overlapping 311 genetic regions.

Both estrogen and c-MYC interact with the gene for H2A.Z, leading to increased production of this protein in breast cancer cells. When the researchers looked at tumor tissue samples collected from 500 patients, they found that elevated levels of H2A.Z were highly correlated with the spread of the cancer to lymph nodes and decreased patient survival. Adding H2A.Z expression to other known risk factors provided “significant prognostic information,” the authors note, “beyond what these factors alone provide.”

“Although it has been implicated in genomic stability and gene transcription, H2A.Z has never been reported to be associated with cancer,” said White. “We would not have found this clinically important factor without taking such a large-scale integrated approach.”

“We suspect this integrated systems approach will lead us to a number of previously unsuspected genes that play a role in disease initiation and progression,” he said. “Many of these could become targets for new treatments.”

Less sleep, more TV leads to fat toddlers

noreply@blogger.com (Kakariku) — Sun, 13 Apr 2008 09:10:00 +0000

Infants and toddlers who sleep less than 12 hours a day are twice as likely to become overweight by age 3 than children who sleep longer. In addition, high levels of television viewing combined with less sleep elevate the risk, so that children who sleep less than 12 hours and who view two or more hours of television per day have a 16 percent chance of becoming overweight by age 3.

“Mounting research suggests that decreased sleep time may be more hazardous to our health than we imagined,” says Elsie Taveras, assistant professor in Harvard Medical School’s Department of Ambulatory Care and Prevention and lead author on the study. “We are now learning that those hazardous effects are true even for young infants.”

Results are published in the April 2008 issue of Archives of Pediatric & Adolescent Medicine.

The study team identified 915 mother-infant pairs from Project Viva, a long-term study of the effects of diet and other lifestyle factors on maternal and child health over time. Infant weight and measurements were taken at several in-person visits up to 3 years of age. Mothers reported how many hours their child slept per day on average at 6 months, 1 year, and 2 years postpartum.

Parents were also asked to report the average number of hours their children watched television on weekdays and weekends.

The combination of low levels of sleep and high levels of television viewing appeared to be synergistic and was associated with markedly higher body mass index (BMI) scores and increased odds of becoming overweight.

“Although previous studies have shown a similar link between sleep restriction and overweight in older children, adolescents, and adults, this is the first study to examine the connection in very young children,” says Matthew Gillman, Harvard Medical School associate professor and director of the Obesity Prevention Program in the Department of Ambulatory Care and Prevention. Gillman is also the study’s senior author.

Television viewing is also a known risk factor for children becoming overweight.

These study results support efforts to reduce television viewing and to promote adequate sleep to help reduce unhealthy childhood weight gain. Children who are overweight are often at higher risk for obesity and related conditions, such as hyperlipidemia, hypertension, asthma, and type 2 diabetes.

“Getting enough sleep is becoming more and more difficult with TV, Internet, and video games in the rooms where children sleep,” says Taveras. “Our findings suggest that parents may wish to employ proven sleep hygiene techniques, such as removing TV from children’s bedrooms, to improve sleep quality and perhaps sleep duration.”

Engineering Prof Builds Brains for Robotic Cars

noreply@blogger.com (Kakariku) — Sun, 13 Apr 2008 09:06:00 +0000

Jonathan Sprinkle wants to build robotic vehicles that pass the Turing Test.

The test, proposed by Alan Turing in a 1950 paper, “Computing Machinery and Intelligence,” requires a robot’s behavior to be so lifelike that an observer can't tell if he’s dealing with a robot or a person.

Sprinkle, an assistant professor at The University of Arizona, and professor J. Mikael Eklund, of the University of Ontario Institute of Technology, have already passed the Turing Test with a control system they designed for a T-33 jet trainer. A veteran F-15 pilot who flew against the T-33 in a test at Edwards Air Force Base said it looked like a recent flight school graduate was at the controls.

Following his success with flight-based systems, Sprinkle has placed his robotic control expertise firmly on the ground, where he’s applying it to smart cars that drive themselves.

This research effort began with a DARPA Urban Challenge project Sprinkle worked on at the University of California, Berkeley. The Urban Challenge race took place in November, with smart vehicles driving themselves through 60 miles of simulated city traffic.

While the Urban Challenge got engineers involved in designing autonomous vehicles it didn’t foster robust designs, Sprinkle noted. As engineers faced tight deadlines, they hacked systems just to make them work instead of creating optimized, integrated designs. “The downside of that is that you don't get a holistic approach to the system,” said Sprinkle, who is with the UA’s electrical and computer engineering department.

Searching for Repeatable Results

“Some of the better teams out there had 30 to 40 people working on a single car,” he added. “And if they wanted to do this project again, they would have to have the same car. They would probably have to have exactly the same people. If they gave another team the code and the car, they probably couldn't make it run because there is so much knowledge involved in the order in which things start up.”

Obviously, these are not robust control systems that can be mass produced and bolted into thousands of vehicles.

Sprinkle would like to see the engineering community take a collective deep breath following the Urban Challenge, step back and design a system that isn't specific to one group of researchers or a single prototype vehicle.

The best way to do this is to work on each component of the system in detail, he said.

“In my research at UA, I want to give a small component of the system to each student, such as a path planner, and have them design a really solid one,” Sprinkle said. “I want to isolate the student to work on just one piece of the software to make it as robust as possible. I think that's where it needs to go. Each person understands a small piece of the problem in depth, and when you plug all those pieces together in the end, it should work.”

Simulations Save Time, Money

A lot of this new research is being done with computer simulations in Sprinkle's lab. Although field testing is an important part of vehicle development, Sprinkle believes much faster progress can be made initially with simulations because they don't require an expensive car and thousands of hours of tinkering with hardware.

Much of Sprinkle’s research is based on Model Predictive Control techniques, which involve combining models of various behaviors (such as obstacle avoidance) with data from the real world to calculate future moves (braking, turning or acceleration, for instance).

“You want to spend less time designing control algorithms, and more time telling the machine that certain things are good and certain things are bad and then having the control algorithm sort that out,” he said.

“If you see a traffic cone ahead when you're driving, for instance, you know that you can turn the steering wheel and don't need to change the accelerator,” he said. “You can just swerve out of the way. Sometimes you have to brake and use the accelerator in rapid succession, but, in your mind, you have a timeline for doing those various actions. Model Predictive Control follows the same logic. It's pretty magical, amazing stuff.”

The result is a control system that anticipates what will happen ahead and plans for future scenarios, rather than driving reactively in the present moment.

One way to further enhance Model Predictive Control would be to record the actions of a human driver and overlay the human’s driving style on the robotic system. “That would make it feel like a human is driving,” Sprinkle said. And the robotic car would move a step closer to passing the Turing Test.

Testing Multi-Core Sensors

In related research, Sprinkle is studying multicore computer processors. They offer a huge increase in computational speed and power, both of which are valuable for robotic cars. But there's a danger that they may make the system less stable.

Procedures that were previously handled by a single processor in linear fashion are now split up into shared tasks being done simultaneously by two or more processors. The processors are trading information, but there’s no guarantee that they're doing so at exactly the right time.

“We're doing some experiments to look at the possibilities of failure in these systems and to identify indicators that show when the system is failing,” Sprinkle said.

Cutting Sensor Costs

While autonomous vehicles now use lasers to learn about their environment, Sprinkle says large numbers of lasers aren’t practical for production cars. “If you want to build an autonomous car now, you basically have to start by buying $40,000 in lasers,” he said. “But if you can put something like a video camera in the car to help gather data, reducing the number of lasers, you'll have a more affordable, lower-cost sensor system.”

Although autonomous cars are experimental these days, Sprinkle believes that in 10 or 20 years we may see cars that can pull out of the parking garage and drive over to pick us up at the office.

But before that happens, there's plenty of research to be done by thousands of people.

“These procedures are couched in a really serious amount of nonlinear systems equations, and nonlinear differential equations,” Sprinkle said. “The problem is how you change that math into something that executes on a computer. That's where software engineering needs to go.

“That's what I really want to teach my students. Otherwise, we're just teaching them to compile things – and that's no fun – and how to do data structures. Data structures have already been done. It's not new.

“I don't want just any data structure,” he said. “I want a data structure that will drive my car.”

Cambridge academics shed new light on the Sun

noreply@blogger.com (Kakariku) — Sun, 13 Apr 2008 09:04:00 +0000

New insights into solar activity have been revealed thanks to research from a group of Cambridge academics.

The work comes from the Atomic Astrophysics Group (AAG) at the University’s Department of Applied Mathematics and Theoretical Physics, who have been collaborating on an international solar mission, the Hinode project, with a number of space agencies.

Their research involves detailed analyses of regions of intense activity in the Sun’s atmosphere, the corona. Through examination of the ultraviolet radiation given off by these areas, known as active regions, they have found a variety of dynamic activities, including jets and flows of gas with speeds of up to 150 kilometres per second.

Temperatures within the corona are extremely high (in excess of one million degrees), whereas the solar surface is much cooler at about 6000 degrees. AAG has been seeking to understand why the corona is so hot and what the linkages are between the solar surface and atmosphere.

For the first time, the team have been able to measure physical characteristics, such as the density and temperature of features of the solar atmosphere in great detail. They found strong connections between changes in the magnetic field of the solar surface and events in the overlying active regions.

These new insights have been made possible through the Hinode spacecraft, which has provided unprecedented views of the Sun. The AAG team work mainly with the EUV Imaging Spectrometer (EIS), led by the UK.

Cristina Chifor, a graduate student with AAG, said: “Since its launch, Hinode has been returning exciting new results. Last year, I had the opportunity to go out to Japan, visit the institute where Hinode is operated, and carry out the daily planning of Hinode/EIS observations.

“It was great fun to be able to 'drive' an instrument so far away in space and to see the data coming down from the spacecraft shortly after. It was a fantastic experience, and Japan is a wonderful place to visit.”

Their results will further our understanding of solar phenomena which can affect the Earth’s environment. Active regions on the Sun can produce huge explosions of gas, which can damage satellites and cause aurora (as seen, for example, in the Northern Lights). They will also increase our knowledge of stars in general.

Dr Helen Mason, group leader for AAG, said: “The Hinode satellite is providing us with some stunning new observations. We can see the Sun in far more detail than we were previously able to. The more detail we see, the more challenging it is to explain! I am so pleased that a younger generation of solar researchers have the opportunity to experience the excitement of working on new solar space observations.”

AAG has 'swept the board' with their results, having four papers published in a special issue of Astronomy and Astrophysics (Vol 481) and one of their images (from C. Chifor et al.) on the front cover.

The Hinode spacecraft was launched in September 2006, as a joint UK, European, US and Japanese mission. The mission is operated by Institute of Space and Astronautical Science and Japan Aerospace Exploration Agency in collaboration with NASA, European Space Agency, Science and Technology Facilities Council and Norwegian Space Centre.

Arizona Cancer Center Studying Benefits of Green Tea Extract

noreply@blogger.com (Kakariku) — Thu, 10 Apr 2008 20:04:00 +0000

The Arizona Cancer Center at The University of Arizona is studying the effects of Polyphenon E, a green tea extract, on prostate cancer prevention. This study will determine whether Polyphenon E affects cancer-related biomarkers in blood and/or prostate tissue in men with prostate cancer.

Tea is one of the world’s most consumed beverages. Polyphenon E is a chemically defined, decaffeinated, catechin-enriched green tea extract. Catechins are plant chemicals that are considered powerful antioxidants and have multiple beneficial biological effects that could lead to cancer prevention.

Prostate cancer is the most common type of cancer found in American men, other than skin cancer. The American Cancer Society estimates that there will be about 186,320 new cases of prostate cancer in the United States in 2008.

Past and ongoing research in numerous experimental studies and in one clinical trial provide evidence that green tea or green tea extracts such as Polyphenon E may have the potential to lower the risk of prostate cancer in the human population. However, rigorous clinical investigations are needed to determine whether green tea extracts such as Polyphenon E are effective at preventing prostate cancer.

The three-year study at the Arizona Cancer Center will recruit men with a recent diagnosis of organ-confined prostate cancer and scheduled to have the prostate removed within three to six weeks from the start of the study.

Eligible participants will take either four Polyphenon E capsules or a matched placebo each morning with food up to the day of their surgery. They will provide blood samples prior to capsule intake and again right before surgery. In addition, they will complete a diary and calendar of the capsules and other medications taken, illnesses and hospitalizations. All qualified participants will be compensated for their role in this study.

Following their surgery, tissue from their prostates will be analyzed to determine whether any of the tea components can be detected.

Heart Dieases predetermined by oxygen levels in the Womb

noreply@blogger.com (Kakariku) — Thu, 10 Apr 2008 19:39:00 +0000

The amount of oxygen available to a baby in the womb can affect their susceptibility to developing cardiovascular disease later in life.

Research from scientists at the University of Cambridge indicates that your risk of developing cardiovascular disease can be predetermined before birth, not only by your genes, but also by their interaction with the quality of the environment you experience in the womb. Their research was presented this week at the annual Society for Endocrinology, British Endocrine Society meeting.

The Cambridge researchers, led by Dr Dino Giussani, examined the role that oxygen availability in the womb plays in programming your susceptibility to different diseases. His group found that babies that don’t receive enough oxygen in the womb, e.g. due to pre-eclampsia (high-blood pressure during pregnancy) or placental insufficiency, are more likely to suffer from cardiovascular disease when they are adult.

A reduction of oxygen levels in the womb can lead to reduced growth rates in the baby and to changes in the way that their cardiovascular, metabolic and endocrine systems develop. Combined, these alterations to the development of key systems in the body can leave the baby more prone to developing cardiovascular disease later in life.

Dr Giussani’s research also indicates methods by which we can potentially combat this problem. The detrimental effects of low oxygen levels on the development of the fetus’ cardiovascular system appear to be due to the generation of oxidative stress. Treatment with antioxidants in animal pregnancies complicated by low oxygenation can reverse these effects on the developing cardiovascular system and this could form the basis for new therapeutic techniques to prevent the early origin of heart disease in complicated human pregnancy.

Cardiovascular disease is the most common cause of death in the UK, accounting for 4 in every 10 deaths. Almost 2.6 million people are affected by heart and circulatory conditions in the UK, with someone having a heart attack every 2 seconds.

Dr Giussani said: “We have known for a while that changes in maternal nutrition can affect fetal development and influence disease susceptibility later in life, but relatively little work has investigated how low oxygen levels in the womb may affect infant development. Our research shows that changes to the amount of oxygen available in the womb can have a profound influence on the development of the fetus in both the short and long term, and trigger an early origin of heart disease.

“Interestingly, the adverse effects on the developing heart and circulation of poor fetal oxygenation are due to oxidative stress. This gives us the opportunity to combat prenatal origins of heart disease by fetal exposure to antioxidant therapy. This may halt the development of heart disease at its very origin, bringing preventative medicine back into the womb.”

A Giant of Astronomy and a Quantum of Solace

noreply@blogger.com (Kakariku) — Tue, 08 Apr 2008 18:28:00 +0000

Cerro Paranal, the 2600m high mountain in the Chilean Atacama Desert that hosts ESO's Very Large Telescope, will be the stage for scenes in the next James Bond movie, "Quantum of Solace".
Looking akin to Mars, with its red sand and lack of vegetation, the Atacama Desert is thought to be the driest place on Earth. Cerro Paranal is home to ESO's Very Large Telescope (VLT), which, with its array of four giant 8.2-m individual telescopes, is the world's most advanced optical observatory. The high-altitude site and extreme dryness make excellent conditions for astronomical observations.

"We needed a unique site for a unique set of telescopes, and we found it at Paranal," said Andreas Kaufer, ESO's Paranal Director. "We are very excited that the Bond production team have also chosen this location."

The excellent astronomical conditions at Paranal come at a price, however. In this forbidding desert environment, virtually nothing can grow outside. The humidity drops below 10%, there are intense ultraviolet rays from the sun, and the high altitude leaves people short of breath. Living in this extremely isolated place feels like visiting another planet.

To make it possible for people to live and work here, a hotel or "Residencia" was built in the base camp, allowing them to escape from the arid outside environment. Here, returning from long shifts at the VLT and other installations on the mountain, they can breathe moist air and relax, sheltered from the harsh conditions outside. The Residencia's award-winning design, including an enclosed tropical garden and pool under a futuristic domed roof, gives its interior a feeling of open space within the protective walls - this is a true "haven in the desert".

It is this unique building that serves as the backdrop for the James Bond filming.

QUANTUM OF SOLACE producer, Michael G. Wilson said: "The Residencia of Paranal Observatory caught the attention of our director, Marc Forster and production designer, Dennis Gassner, both for its exceptional design and its remote location in the Atacama desert. It is a true oasis and the perfect hide-out for Dominic Greene, our villain, whom 007 is tracking in our new James Bond film."

In addition to the shooting at the Residencia, further action will take place at the Paranal airstrip.

The film crew present on Paranal includes Englishman Daniel Craig, taking again the role of James Bond, French actor Mathieu Amalric, leading lady Olga Kurylenko, from the Ukraine, as well as acclaimed Mexican actors, Joaquin Cosio and Jesus Ochoa. This cast from across Europe and Latin America mirrors the international staff that works for ESO at Paranal.

After leaving Paranal at the end of the week, the film crew will shoot in other locations close to Antofagasta. Other sequences have been filmed in Panama and, following the Chilean locations, the unit will be travelling to Italy and Austria before returning to Pinewood Studios near London in May.

Phytoplankton species deviates from norm: No CO2 absorbed in photosynthesis

noreply@blogger.com (Kakariku) — Sun, 06 Apr 2008 19:35:00 +0000

A widespread species of ocean-dwelling microorganisms has been found to employ a never-before-seen alternative method of photosynthesis.

The discovery has implications not only for scientists' basic understanding of photosynthesis—arguably the most important biological process on Earth—but also for the amount of carbon dioxide that phytoplankton pull from the atmosphere.

Until now, it was thought that all the photosynthetic algae and bacteria living in the ocean drew carbon dioxide out of the air and used it to build sugars and other carbon-rich molecules to use as fuel. But two new studies by researchers at Stanford and the Carnegie Institution show that Synechococcus, a type of cyanobacteria (formerly called blue-green algae) that dominates much of the world's oceans, has evolved a mechanism that short-circuits photosynthetic carbon-dioxide fixation while still producing energy. The alternate approach is found in regions of the ocean where some of the ingredients necessary for traditional photosynthesis are in short supply.

"The amount of carbon dioxide being drawn down by the phytoplankton in nutrient-poor oceans might turn out to be significantly lower than we thought," said Shaun Bailey, a postdoctoral researcher working in the Carnegie Institution's Department of Plant Biology with Arthur Grossman, a staff scientist at the institution and a professor, by courtesy, in Stanford's Biology Department.

Bailey is the lead author of the paper describing part of the work in Biochimica et Biophysica Acta 1777 (2008). Kate Mackey, a graduate student in civil and environmental engineering at Stanford, is lead author of a second paper describing the work, currently in press at Limnology and Oceanography.

Until now, researchers have estimated marine photosynthetic activity by analyzing satellite images of the world's oceans to determine how much chlorophyll was in the water. Since chlorophyll is needed for photosynthesis, it was thought that measuring its concentration would be a straightforward way of estimating the amount of photosynthesis that would occur and therefore how much carbon dioxide would be consumed, or "fixed," by the phytoplankton. But the new work suggests that the relationship between the amount of chlorophyll in the water and the amount of carbon dioxide fixation by phytoplankton is not consistent throughout the world's oceans.

"There is a new twist on photosynthesis here, and that has to be accounted for when it comes to CO2 modeling," Bailey said, adding that, in some cases, the models may overestimate the amount of carbon fixation that occurs in nutrient-poor waters.

It is not yet clear what the finding might mean to studies of long-term global warming, he said, but it will have to be incorporated into any models that include carbon fixing by phytoplankton as a factor.

Synechococcus caught the interest of Grossman and his team because it thrives in vast areas of the ocean that are relatively deficient in iron, an element that is critical for certain reactions in the normal process of photosynthesis. How Synechococcus could maintain its abundance in the face of that deficiency was a puzzle.

"It seems that Synechococcus in the oligotrophic [nutrient-poor] oceans has solved the iron problem, at least in part by short-circuiting the standard photosynthetic process," Grossman said. "Much of the time this organism bypasses stages in photosynthesis that require the most iron. As it turns out, these are also the stages in which CO2 is taken from the atmosphere."

"We realized very quickly that there was something different about the Synechococcus that we were studying," said Bailey, the lead postdoctoral fellow working on the project. "The uptake of CO2 and the photosynthetic activities didn't match, so we knew that something other than CO2 was being consumed by photosynthesis, and it turned out to be oxygen." The researchers have tentatively identified the enzyme involved in this process to be plastoquinol terminal oxidase, or PTOX.

Bailey worked with Synechococcus in the laboratory, but recently this newly discovered phenomenon was shown to occur in nature by Mackey, who made direct measurements of photosynthesis in field samples from the Atlantic and Pacific oceans.

"The low-nutrient, low-iron environments account for about half of the area of the world's oceans, so they represent a large portion of the Earth's surface available for photosynthesis," Mackey said. "Our findings show that this novel cycle occurs in two major ocean basins and suggest that a substantial amount of energy from sunlight gets re-routed away from carbon fixation during photosynthesis. This may mean that less CO2 is being removed from the atmosphere by the open ocean photosynthetic organisms than was previously believed."

"This discovery represents a paradigm shift in our view of photosynthesis by organisms in the vast, nutrient-starved areas of the open ocean," said Joe Berry of the Carnegie Institution's Department of Global Ecology. "We had assumed that like higher plants, the goal was to make carbohydrates from CO2 and store them for later use as a source of energy for any number of cellular functions or growth. We now know that some organisms short-circuit this complicated process, using light in a minimalist way to power cellular processes directly with a far simpler and cheaper—in terms of scarce nutrients such as iron—photosynthetic apparatus. We don't know the full significance of this finding yet, but it is certain to change the way we interpret optical measurements of photosynthetic pigments in the ocean and the way we model ocean productivity."

Wolf Frommer, director of the Carnegie Institution's Department of Plant Biology, agreed on the discovery's ground-breaking importance. "If we thought we have understood photosynthesis, this study proves that there is much to be learned about these basic physiological processes," he said.

Eating meat led to smaller stomachs, bigger brains

noreply@blogger.com (Kakariku) — Sun, 06 Apr 2008 19:34:00 +0000

Behind glass cases, Harvard’s Peabody Museum of Archaeology displays ancient tools, weapons, clothing, and art — enough to jar you back into the past.

But the venerable museum offered a jarring moment of another sort in its Geological Lecture Hall last month (March 20). Paleoanthropologist Leslie Aiello delivered a late-afternoon talk on diet, energy, and evolution. It was jolting to see her, slight and matronly, stand before a story-high screen filled with images of rugged early hominids on a savannah, gathered around fallen game.

Then again, Aiello — as one of her admirers put it — is the “alpha female” among anthropologists who make a study of human origins. She co-wrote the widely used text “An Introduction to Human Evolutionary Anatomy” (Academic Press, 1990), based on the idea that the fossil record offers clues to how early hominids looked, moved, and even ate.

Aiello — a professor for three decades at University College, London, and now president of the Manhattan-based Wenner-Gren Foundation for Anthropological Research — was in Cambridge to deliver the 2008 George Peabody Founder’s Lecture.

Introducing Aiello was Daniel E. Lieberman, a professor of biological anthropology at Harvard and a proponent of the idea that upright walking and long-distance endurance running set early humans on their novel evolutionary path.

He held up a well-thumbed copy of Aiello’s book and said, “Her CV is so long, it’s hard to know where to start.” But two seminal ideas stand out, said Lieberman. One is that in evolutionary terms, big human brains — with enormous energy requirements — are inversely proportional to gut size.

This idea — called the Expensive Tissue Hypothesis (ETH) in Aiello’s co-authored 1992 paper — argues that around 1.5 million years ago early humans began to eat more meat, a compact, high-energy source of calories that does not require a large intestinal system.

A second seminal idea posited by Aiello and another colleague is that increased brain size meant higher reproductive costs for females — who, over time, compensated in part by increasing in size at a greater rate than males of the genus Homo. (Homo erectus females had a 64 percent larger body mass than earlier hominids; males of the species — though still larger than females — were larger than their earlier male counterparts by only 45 percent.)

In her lecture, Aiello revisited ETH to see how scientifically robust an idea it was after more than 15 years of academic scrutiny.

The idea is still viable, she said, but in an era of better testing technology and accelerating scholarship on human origins, ETH has theoretical competitors explaining the evolution of bigger brain size.

For one, some scientists say that walking upright — “bipedalism” — is the most important way to support larger brain size. (Upright hunters and gatherers were more efficient than their quadripedal counterparts.) Others say that the key to supporting big brains is the smaller muscle mass of hominids compared to apes.

And still other scientists have pointed out that ETH doesn’t hold true for all animals, including birds and bats.

Said the modest Aiello, “we’re much further along in understanding energy tradeoffs and evolution than 15 years ago.”

But for whatever reason, she said, “encephalization” — the tendency of some species to evolve larger brains — is the third stage that led humans to civilization. (One earlier stage is bipedalism. The oldest is “terrestriality,” the movement of early hominids from canopied forests — rich in lower-calorie foods — to savannahs, where small game, carrion, and insects supplemented a plant-based diet.)

Around 1.5 million years ago there was “a lot going on” in evolutionary terms, said Aiello. Hominid habitat changed, along with the size of early human craniums (larger) and jaws (smaller).

But growing brain size presented a metabolic problem. A gram of brain tissue takes 20 times more energy to grow and maintain than a gram of tissue from the kidney, heart, or liver, she said. Gut tissue is metabolically expensive too — so as brains grew gut sizes shrank.

It’s likely that meat eating “made it possible for humans to evolve a larger brain size,” said Aiello. Early human ancestors probably consumed more animal foods — termites and small mammals – than the 2 percent of carnivorous caloric intake associated with chimpanzees.

The social implications of increased meat eating were interesting, said Aiellio. In most primates, there’s no food sharing between females and offspring, she said. But the difficulty of getting meat led to cooperative food sharing among early humans, strengthening the bond between a female and her offspring.

Increased meat eating also likely led to an increased division of labor between the sexes, said Aiello. The males would hunt and provide; the females — faced with more intensive motherhoods — would raise the hominid young, who were dependent longer than ape infants.

But is there evidence in the fossil record for a transition to what Aiello called “a high-quality animal-based diet”?

Briefly, yes. For one, animal bones from 2.5 million years ago showed cut marks thought to be from the earliest stone tools. And earlier species of early hominids had strong jaws and molar-like teeth; later species were more like modern humans, with weaker jaws, smaller faces, and smaller teeth.

There are other of bits of evidence pointing to meat eating by early humans, said Aiello. “My favorite are the tapeworms.”

Parasite historians — yes, there are some — say that hyenas and early humans were infected by the same type of tapeworms, which suggests they shared booty from scavenged carrion. (Such analysis is possible because of “isotopic ecology,” the study of microscopic traces of food-related isotopes in both fossils and living creatures.)

Our human ancestors were not wholly carnivores — “that would be silly,” said Aiello, who does not argue that meat-eating caused bigger brains — just that it made bigger brains possible.

About 1.5 million years ago, she said, “there was a definite dietary change to foods of high nutritional value [that were] easy to digest.”

Better food sources and the social changes they engendered accelerated our human ancestors toward civilization. “Whatever was happening here,” said Aiello of the highest branch in the primate tree, “Homo erectus got it right.”

Study shows that stimuli unrelated to decision can still influence men’s choices

noreply@blogger.com (Kakariku) — Sun, 06 Apr 2008 19:30:00 +0000

Attractive women plus cool cars equal brisk sales for auto dealers as men snap up those cars, prompted—or so advertising theory goes—by the association. But is the human male really so easily swayed? Can the irrelevant image of an alluring female posing by the merchandise actually encourage a heterosexual man to purchase it?

Possibly, according to a new study by Stanford researchers.

The study showed that when heterosexual men are exposed to positive emotional stimuli—in this case, erotic photos of a man and woman—an area of the brain associated with anticipation of reward is stimulated. In the immediate aftermath of that stimulation, men are consistently more likely to take bigger financial risks than they otherwise would, said Brian Knutson, assistant professor of psychology.

"This is the first study to demonstrate that emotional stimuli can influence financial risk-taking," said Knutson, lead author of a paper describing the research in the current issue of NeuroReport. The hard evidence was gathered by functional magnetic resonance imaging (fMRI) of participants' brains as they viewed photographs of positive, negative or neutral subjects and then had to quickly make a decision to choose one of two levels of financial risk in a required gamble.

Knutson and collaborator Camelia Kuhnen (who received her PhD from the Stanford Graduate School of Business in 2006 and is now assistant professor of finance at Northwestern University) had already shown in a 2005 study using fMRI that brain activity could be used to predict whether people were about to take a financial risk. When they were, an area of the brain called the nucleus accumbens showed increased activation. When they were about to choose to avoid the risk, a different area called the insula showed increased activation.

"We knew that we should be looking at [the nucleus accumbens] from the previous study. But what we didn't know is whether we could somehow control the activation in that area by presenting some completely irrelevant stimulus," Knutson said. "And whether that would change activation in that area and actually change behavior."

Knutson and his colleagues studied heterosexual male undergraduate college students. The images the men viewed were intended to stimulate an emotional response. Erotic images were used to elicit a positive response, snakes and spiders to prompt a negative response, and office supplies to trigger a neutral response.

In case any of the subjects found office supplies more repellent than snakes and spiders, the researchers had the men rate each image after the scans. They then derived personalized ratings from each of the participants, which were used to make sure that whatever brain activation they observed was properly correlated with the actual emotional response of the viewer.

After viewing each image, the participants immediately had to decide whether to take the high-risk option of gambling a dollar or the low-risk option of gambling a dime. Regardless of their choice, they had a 50-50 chance of winning or losing. Knutson and his colleagues gave each man $10 to gamble with prior to entering the MRI scanner. "We wanted them to care," Knutson said. Depending on the men's gambles and the random outcomes, they won or lost. "We took that money back if they lost it," he said.

"What we saw is that when they viewed the erotic pictures, the activation in their nucleus accumbens increased compared to the other stimuli, and also that they had increased activation in that region before choosing the high-risk gamble," Knutson said.

The researchers then applied a statistical analysis to determine whether the activation in the nucleus accumbens accounted for some of the behavioral effect. "The answer was yes, at least in the case of the positive stimuli," Knutson said. "After people had seen those erotic pictures, they tended to pick the high-risk gamble more often, especially if they had been picking the low-risk gamble before.

"The interesting finding from an economic standpoint is that these completely irrelevant stimuli, these pictures that have nothing to do with the gambles or the history of outcomes that people have experienced with these gambles, still influence behavior," he said. "They seem to do so at least partially by influencing activation of these brain regions."

The findings have implications for what might make emotional appeals effective or ineffective in applications ranging from advertising to finance to politics and, perhaps not surprisingly, gambling.

"If you go to the casinos, people are wearing skimpy costumes, they're giving you free alcohol, there are bells and lights and things like that, which don't necessarily seem related to the odds of the gambling," Knutson said. "But these are cues that might activate brain regions that encourage risk-taking and therefore get people to gamble more."

So does draping a seductive woman over the hood of a car in an advertisement really help sell that car?

"Well, yes and no," Knutson said. "It may work sometimes under some conditions."

"Our trials are happening relatively fast, changing on a second-to-second basis," he noted. "We're forcing people to immediately make a decision, and the emotional stimuli appear in close temporal proximity to the decision itself.

"If you have these kinds of appeals, you'd better make it easy for people to make an immediate decision. You should put them under time pressure," he said.

Knutson emphasized that there is still ample work to be done in deciphering the effects of emotional stimuli on behavior. He plans to study women's responses in the future, as well as to examine other types of emotional stimuli. He also intends to examine the influence of time, to see how transient or lasting the influences of various emotional stimuli might prove to be.

"This is just a first step," he said. "It's an existence proof that some irrelevant emotional stimuli can influence some immediate financial decisions and that we can track down one brain basis for this influence."

Discovery of the First Sex Chromosome Gene Tied to Male Infertility

noreply@blogger.com (Kakariku) — Sun, 06 Apr 2008 19:29:00 +0000

A team of scientists led by University of Pennsylvania veterinary researchers have identified a gene, TEX11, located on the X chromosome, which when disrupted in mice renders the males sterile and reduces female fecundity. This is the first study of the genetic causes of infertility that links a particular sex chromosome meiosis-specific gene to sterility.

As with mice, the TEX11 gene is also located on the human X chromosome. Given that disruption of TEX11 causes azoospermia, or non-measurable sperm levels in mice, mutations in the human TEX11 gene may be a genetic cause of infertility in men. Because men have only one X chromosome that they inherit from their mother and thus only one copy of the TEX11 gene, any mutation could theoretically lead to sterility. Like other X-linked disorders such as color blindness and muscular dystrophy, genetic mutation causing a son’s infertility could be passed from his mother.

Researchers hypothesize that a screening of the TEX11 gene may provide a pre-birth diagnosis for infertility in men.

The study, published in the March issue of Genes & Development, also reports the first meiosis-specific factor ever found on the X chromosome. Meiosis is the process of cell division that produces gametes in both sexes. During meiosis, homologous chromosomes undergo pairing, synapsis, recombination and faithful segregation. Meiosis allows the exchange of genetic material between paternal and maternal genomes to produce genetically diverse gametes (sperm or eggs). Therefore, defects in meiosis are a leading cause of both infertility and birth defects.

An estimated 15 percent of couples are affected by infertility worldwide, yet the genetic causes of male infertility remain largely unknown. For decades, conventional wisdom stated that the X chromosome had little to do with meiosis or infertility because the X chromosome is silenced during male meiosis. This thinking led to fertility studies that focused on the Y chromosome and autosomes.

In fact, Jeremy Wang, assistant professor in the Department of Animal Biology at the University of Pennsylvania’s School of Veterinary Medicine, and his team revealed in an earlier study of mouse male germ cells that nearly one third of the germ cell-specific genes they identified are located on the X-chromosome.

Wang and his team found that sex chromosomes did play a role in meiosis. Although these X-linked, germ cell-specific genes undergo inactivation during later stages of male meiosis, they play a role in the early stages. Specifically, researchers found that TEX11 forms discrete foci on meiotic chromosomes and appears to be a novel constituent of the meiotic recombination machinery. The team genetically engineered male mice such that they lacked TEX11 function and found that this caused chromosomal asynapsis during the process of gamete formation.

This means that homologous chromosomes failed to pair together during meiosis and chromosomes formed fewer crossovers, i.e. sites where they recombine, during the initial stages of meiosis. These failures led to elimination of spermatocytes at later stages in the genetic recombination process and, ultimately, male infertility.

Researchers hypothesize that because TEX11 interacts with SYCP2, an integral component of the protein complex that mediates synapsis during meiosis, TEX11 promotes both synapsis and genetic recombination and may provide a physical link between these two meiotic processes.

The study was performed by Wang and Fang Yang in the Department of Animal Biology in Penn’s School of Veterinary Medicine; Katarina Gell and Christer Höög of the Department of Cell and Molecular Biology at the Karolinska Institutet; Godfried W. van der Heijden and David C. Page of the Howard Hughes Medical Institute, Whitehead Institute and Department of Biology of the Massachusetts Institute of Technology; Sigrid Eckardt, N. Adrian Leu and K. John McLaughlin of the Center for Animal Transgenesis and Germ Cell Research at Penn Vet’s New Bolton Center; Ricardo Benavente of the Department of Cell and Developmental Biology at the University of Würzburg; and Chengtao Her of the School of Molecular Biosciences and Center for Reproductive Biology at Washington State University.

Common aquatic animals show resistance to radiation

noreply@blogger.com (Kakariku) — Sun, 06 Apr 2008 19:26:00 +0000

Scientists at Harvard University have found that a common class of freshwater invertebrate animals called bdelloid rotifers are extraordinarily resistant to ionizing radiation, surviving and continuing to reproduce after doses of gamma radiation much greater than that tolerated by any other animal species studied to date.

Because free radicals such as those generated by radiation have been implicated in inflammation, cancer, and aging in higher organisms, the findings — published this week in the Proceedings of the National Academy of Sciences by Harvard’s Matthew Meselson and graduate student Eugene Gladyshev — could stimulate new lines of research into these medically important problems.

“Bdelloid rotifers are far more resistant to ionizing radiation than any of the hundreds of other animal species for which radiation resistance has been examined,” says Meselson, Thomas Dudley Cabot Professor of the Natural Sciences in Harvard’s Faculty of Arts and Sciences. “They are able to recover and resume normal reproduction after receiving a dose of radiation that shatters their genomes, causing hundreds of DNA double-strand breaks which they are nevertheless able to repair.”

Meselson and Gladyshev found that the bdelloid rotifers Adineta vaga and Philodina roseola remained reproductively viable after doses of radiation roughly five times greater than other classes of rotifers and other animals could endure.

Such radiation resistance appears not to be the result of any special protection of DNA itself against breakage, the researchers say, but instead reflects bdelloid rotifers’ extraordinary ability to protect their DNA-repairing machinery from radiation damage.

Roughly a half-millimeter in size and commonly observed under microscopes in high school biology classes, bdelloid rotifers are highly unusual in several regards: They appear to be exclusively asexual, have relatively few transposable genes, and can survive and reproduce after complete desiccation at any stage of their life cycle. Meselson and Gladyshev hypothesize that it’s this last property that explains bdelloids’ apparently unique resistance to radiation.

Bdelloid rotifers have been widely studied since at least 1702, when the renowned Dutch scientist and microscopy pioneer Anton van Leeuwenhoek added water to dust retrieved from a rain gutter on his house and observed the organisms in the resulting fluid. He subsequently described the creatures in a letter to Britain’s Royal Society, which still counts an envelope of van Leeuwenhoek’s rain-gutter dust among its holdings.

Promising New Nanotechnology for Spinal Cord Injury

noreply@blogger.com (Kakariku) — Wed, 02 Apr 2008 20:13:00 +0000

A spinal cord injury often leads to permanent paralysis and loss of sensation below the site of the injury because the damaged nerve fibers can't regenerate. The nerve fibers or axons have the capacity to grow again, but don’t because they're blocked by scar tissue that develops around the injury.

Northwestern University researchers have shown that a nano-engineered gel inhibits the formation of scar tissue at the injury site and enables the severed spinal cord fibers to regenerate and grow. The gel is injected as a liquid into the spinal cord and self -assembles into a scaffold that supports the new nerve fibers as they grow up and down the spinal cord, penetrating the site of the injury.

When the gel was injected into mice with a spinal cord injury, after six weeks the animals had a greatly enhanced ability to use their hind legs and walk.

The research is published today in the April 2 issue of the Journal of Neuroscience.

"We are very excited about this," said lead author John Kessler, M.D., Davee Professor of Stem Cell Biology at Northwestern University's Feinberg School of Medicine. "We can inject this without damaging the tissue. It has great potential for treating human beings."

Kessler stressed caution, however, in interpreting the results. "It's important to understand that something that works in mice will not necessarily work in human beings. At this point in time we have no information about whether this would work in human beings."

"There is no magic bullet or one single thing that solves the spinal cord injury, but this gives us a brand new technology to be able to think about treating this disorder," said Kessler, also the chair of the Davee Department of Neurology at the Feinberg School. "It could be used in combination with other technologies including stem cells, drugs or other kinds of interventions."

“We designed our self-assembling nanostructures -- the building blocks of the gel -- to promote neuron growth,” said co-author Samuel I. Stupp, Board of Trustees Professor of Materials Science and Engineering, Chemistry, and Medicine and director of Northwestern’s Institute for BioNanotechnology in Medicine. “To actually see the regeneration of axons in the spinal cord after injury is a fascinating outcome.”

The nano-engineered gel works in several ways to support the regeneration of spinal cord nerve fibers. In addition to reducing the formation of scar tissue, it also instructs the stem cells --which would normally form scar tissue -- to instead to produce a helpful new cell that makes myelin. Myelin is a substance that sheaths the axons of the spinal cord to permit the rapid transmission of nerve impulses.

The gel's scaffolding also supports the growth of the axons in two critical directions -- up the spinal cord to the brain (the sensory axons) and down to the legs (the motor axons.) "Not everybody realizes you have to grow the fibers up the spinal cord so you can feel where the floor is. If you can't feel where the floor is with your feet, you can't walk," Kessler said.

Now Northwestern researchers are working on developing the nano-engineered gel to be acceptable as a pharmaceutical for the Food and Drug Administration.

If the gel is approved for humans, a clinical trial could begin in several years.

"It's a long way from helping a rodent to walk again and helping a human being walk again," Kessler stressed again. "People should never lose sight of that. But this is still exciting because it gives us a new technology for treating spinal cord injury."

Can Robots Cure Cancer

noreply@blogger.com (Kakariku) — Wed, 02 Apr 2008 20:11:00 +0000

New research released at the Society of Interventional Radiology's (SIR) Annual Scientific Meeting in Washington, D.C. holds promise of a new interventional imaging capability using advanced robotics provided by Siemens Healthcare, to improve the value of chemoembolization in treating cancer.

The research, presented by Dr. John Angle, Associate Professor of Radiology, Chief, Division of Angiography, University of Virginia Health System in Charlottesville, at the "Advanced Imaging Symposium," reveals clinical results from his case study using the Siemens Artis zeego, a multi-axis C-arm that employs robotic technology to enable large-volume syngo DynaCT acquisition for liver chemoembolization.

The Artis zeego is part of the new Artis zee family of interventional imaging systems introduced by Siemens. According to Angle, the combination of the Artis zeego and large-volume syngo(R) DynaCT enables the physician to see the whole abdomen or the entire liver for chemoembolization and biopsies, and provides reliable post-TACE assessment of lipidol uptake.

"The Artis zeego's support for expanded syngo DynaCT anatomical coverage enables the entire liver to be imaged without moving the patient," said Angle. "We have found the system to be reliable, stable and very easy to use. We plan on expanding the scope of cases for which we use the Artis zeego."

The Artis zeego, which recently received FDA 510(k) clearance, offers breakthrough versatility, enhanced image quality and streamlined workflow across an array of clinical environments, from body and neurointerventional radiology suites to operating rooms and hybrid rooms. Additionally, Frost & Sullivan recently selected the Artis zeego as winner of the 2008 Frost & Sullivan Technology Innovation Award at their Excellence in Medical Technologies Awards banquet.

The versatility of the Artis zee family is exemplified by the revolutionary new Artis zeego to extend imaging capabilities through virtually unrestricted C-arm positioning. The ability to support two non-concentric rotations supports advanced cross-sectional imaging, which is not achievable with traditional C-arm systems. The Artis zeego makes it possible for the position of the isocenter to be adjusted according to the procedural needs or the height of the physician, which is particularly beneficial to a physician during lengthy procedures while wearing a heavy lead-shielded apron. The adjustable isocenter also enables off-center rotational angiography for all areas of the body and supports advanced 3D imaging techniques, including cross-sectional imaging through Siemens' first-to-market syngo DynaCT.

Gene's 'selective signature' helps scientists identify instances of natural selection in microbial evolution

noreply@blogger.com (Kakariku) — Wed, 02 Apr 2008 20:06:00 +0000

Microbes, the oldest and most numerous creatures on Earth, have a rich genomic history that offers clues to changes in the environment that have occurred over hundreds of millions of years.

While scientists are becoming increasingly aware of the many important environmental roles played by microbes living today--they process the food in our intestines, they keep carbon moving through the ocean food web, they can be harnessed to process sewage and build specific proteins--they still know little about these tiny critters, particularly marine microbes, which generally are classified into species based on their ecological niche. For instance, two species of marine microbe might look very similar physically, but one may have adapted to life in a particularly dark part of the ocean, while its sister species may have adapted to feeding off a nutrient that is rare in most parts of the ocean, but exists in abundance in one small area.

Scientists at MIT who are trying to understand existing microbes by studying their genetic history recently created a new approach to the study of microbial genomes that may hasten our collective understanding of microbial evolution.

The researchers have reversed the usual order of inquiry, which is to study an organism, then try to identify which proteins and genes are involved in a particular function. Instead, they have come up with a simple mathematical formula that makes it possible to analyze a gene family (a single type of gene or protein that exists in many creatures) simultaneously in a group of ecologically distinct species.

This means that we can begin to identify occurrences of natural selection in an organism's evolution simply by looking at its genome and comparing it with many others at once. This would allow them to take advantage of the nearly 2,500 microbes whose genomes have already been sequenced.

The new method determines the "selective signature" of a gene, that is, the pattern of fast or slow evolution of that gene across a group of species, and uses that signature to infer gene function or to map changes to shifts in an organism's environment.

"By comparing across species, we looked for changes in genes that reflect natural selection and then asked, 'How does this gene relate to the ecology of the species it occurs in?'" said Eric Alm, the Doherty Assistant Professor of Ocean Utilization in the Departments of Civil and Environmental Engineering and Biological Engineering. Natural selection occurs when a random genetic mutation helps an organism survive and becomes fixed in the population. "The selective signature method also allows us to focus on a single species and better understand the selective pressures on it," said Alm.

"Our hope is that other researchers will take this tool and apply it to sets of related species with fully sequenced genomes to understand the genetic basis of that ecological divergence," said graduate student B. Jesse Shapiro, who coauthored with Alm a paper published in the February issue of PLoS Genetics.

Their work also suggests that evolution occurs on functional modules--genes that may not sit together on the genome, but that encode proteins that perform similar functions.

"When we see similar results across all the genes in a pathway, it suggests the genomic landscape may be organized into functional modules even at the level of natural selection," said Alm. "If that's true, it may be easier than expected to understand the complex evolutionary pressures on a cell."

For example, in Idiomarina loihiensis, a marine bacterium that has adapted to life near sulfurous hydrothermal vents in the ocean floor, the genes involved in metabolizing sugar and the amino acid phenylalanine underwent significant changes (over hundreds of millions of years) that may help the bacterium obtain carbon from amino acids rather than from sugars, a necessity for life in that ecological niche. In one of I. loihiensis' sister species, Colwellia psychrerythraea, some of those same genes have been lost altogether, an indication that sugar metabolism is no longer important for Colwellia.

Shapiro and Alm focused on 744 protein families among 30 species of gamma-proteobacteria that shared a common ancestor roughly one to two billion years ago. These bacteria include the laboratory model organism E. coli, as well as intracellular parasites of aphids, pathogens like the bacteria that cause cholera, and soil and plant bacteria. They mapped the evolutionary distance of each species from the ancestor and incorporated information about the gene family (for instance, important proteins evolve more slowly than less-vital ones) and the normal rate of evolution in a particular species' genome in order to determine a gene's selective signature.

"These are experiments we could never perform in a lab," said Alm. "But Mother Nature has put genes into an environment and run an evolutionary experiment over billions of years. What we're doing is mining that data to see if genes that perform a similar function, say motility, evolve at the same rate in different species. To the extent that they differ, it helps us to understand how change in core genes drives functional divergence between species across the tree of life."

New research provides insight into menopause

noreply@blogger.com (Kakariku) — Tue, 01 Apr 2008 08:32:00 +0000

nsight into why females of some species undergo menopause while others do not has proven elusive despite an understanding of the biological mechanisms behind the change.

However, new research by scientists at the Universities of Cambridge and Exeter suggests that menopause is an adaptation to minimize reproductive competition between generations of females in the same family unit.

Even in 'natural fertility' human societies (i.e., those without access to modern medicine or technology) women typically survive for many years after they have ceased to reproduce. Menopause represents an evolutionary puzzle because theory suggests that there should be no selection for genes which promote survival past the end of reproduction. The current explanation was proposed 50 years ago and is known as the 'grandmother hypothesis': Natural selection can favour post-reproductive survival if older non-breeding women can help their children survive and reproduce.

The problem is that data from natural fertility societies suggests that grandmothering benefits are too small to favour switching off reproduction by age fifty in order to help. So while the grandmother hypothesis can explain why women continue to survive after they have stopped breeding, it can't explain why they stop breeding in the first place.

In this paper, published today in the journal PNAS, the researchers propose that the timing of reproductive cessation in humans is best understood as an evolutionary adaptation to reduce reproductive competition between generations of females in the same family unit.

Reproductive competition is ubiquitous in other cooperative vertebrates, but up to now its potential role in human life history evolution has been overlooked. The research demonstrates that humans are unique among primates because there is almost no overlap of reproductive generations. In natural fertility populations, women on average have their first baby at 19 years and their last baby at 38 years; in other words, women stop breeding when the next generation starts to breed.

Moreover, the scientists go on to demonstrate that this pattern is expected given the female-dispersal system thought to characterize ancestral humans. Female dispersal means that reproductive competition in ancestral human families would have involved 'mothers-in-law' competing with 'daughters-in-law'. In these circumstances younger females have a decisive advantage in competition because a mother-in-law is related to her daughter-in-law's offspring (and therefore share's an interest in her reproductive success), but not vice versa.

The researchers developed a simple mathematical model of this competition which predicts that older women should cease breeding when younger women in the same social unit start to breed. This hypothesis and model can thus explain the observed timing of reproductive cessation in humans, and so contributes to a much better understanding of how menopause evolved.

Despite vast differences in wealth, resources, and access to medicine, women in all societies experience menopause. This suggests that the human fertility schedule is hard-wired into our genetic makeup as a consequence of our evolutionary history, prior to more recent cultural and technological advances.

Dr Michael Cant at the University of Exeter explains, “Women everywhere experience a rapid decline in fertility after the age of forty, culminating in menopause around ten years later. Our study helps to explain why this phase of rapid 'senescence' of the reproductive system starts when it does, and why women, on average, stop having children a full ten years before the onset of menopause.”

It also helps to explain why in some societies (particularly in Africa and Asia), women are required by social law to stop having children when their first grandchild is born. A better understanding of the selective forces that have shaped the genetically programmed human fertility schedule may in future provide medical insights into the genetic causes of premature ovarian failure and other diseases of low fertility.

“The grandmother hypothesis was proposed 50 years ago by the American evolutionary biologist George Williams,”says Dr Cant. “However, data on grandmother effects indicate that something key is missing from Williams’ argument. Our study suggests the missing part of the puzzle, and generates a raft of new testable predictions.”

Dr Rufus Johnstone at the University of Cambridge adds, “It should open up new avenues for research on menopause and fertility in humans, and provide new insights into the evolution of menopause in the two other species in which it occurs under natural conditions - killer whales and pilot whales."