Scientists Challenged to Create Better Tools for Image Analysis

Thursday, April 9, 2009

The Allen Institute for Brain Science, the Howard Hughes Medical Institute (HHMI), and the Krasnow Institute for Advanced Study at George Mason University are launching an international scientific challenge to speed development of new computational tools that accurately and automatically reconstruct the “shape” of brain cells from available light microscopy data.

The organizers hope the DIADEM Challenge—short for Digital Reconstruction of Axonal and Dendritic Morphology—will lead to innovative solutions to a frustrating problem that has slowed efforts to create a functional atlas of the brain. Neuroscientists agree that a systematic characterization of neurons with their dendrites and axons is essential, since these tree-like structures are highly correlated with the electric activity of, and precise connections between, neurons and are thus linked to the functions of specific brain circuits. But scientists currently spend weeks—and, in some cases, months—tracing the intricate neuronal processes by hand, using data supplied by imaging studies.

“Manual tracing of neurons has created an intolerable bottleneck and is currently limiting the pace of discovery in neural circuit analysis.”
Giorgio A. Ascoli

“Manual tracing of neurons has created an intolerable bottleneck and is currently limiting the pace of discovery in neural circuit analysis,” said Giorgio A. Ascoli of the Krasnow Institute for Advanced Study. “Automating this process will open the exciting path to the comprehensive characterization of neuronal structure and connectivity.”

The DIADEM Challenge is open to individuals and teams from the private sector and academic laboratories. The organizers will award a $75,000 cash prize to the winning individual or team whose algorithm is judged to perform the best in tests using real data. Funding for the prize is provided by HHMI and the Allen Institute.

“Solving this computational bottleneck will be key for larger scale studies of brain wiring and to generate an atlas of connections in the brain,” said Allan Jones of the Allen Institute. “Sponsoring the DIADEM Challenge fits in well with the Allen Institute’s mission of providing broad enabling tools and data to the scientific community.”

Competitors will have a year to implement an algorithm for digital reconstruction of neuronal morphology and to test it against manual reconstruction, which is the current “gold standard.” Up to five finalists will compete in a final round at HHMI’s Janelia Farm Research Campus in Ashburn, Virginia, in August 2010.

The National Institutes of Health is providing partial support to a scientific conference that is independent of—but held in conjunction with—the final round of the DIADEM Challenge. Yuan Liu, program director for Computational Neuroscience and Neuroinformatics at the National Institute of Neurological Disorders and Stroke, is co-organizing the scientific conference with Ascoli and Karel Svoboda of Janelia Farm.

The idea for the DIADEM Challenge was originally discussed in 2007 at a scientific workshop at Janelia Farm. Scientists at the meeting noted that progress in understanding neural circuits was being slowed by the tedious task of tracing the structure of individual nerve cells by hand.

Even with the advent of computer technology that enables mapping in three dimensions, the full reconstruction of single neurons may take months. The vast majority of axons (the long neuronal projections that transmit information to neighboring cells) and dendrites (the branches on nerve cells that receive information from neighboring cells) must be traced manually. Researchers trace axons and dendrites that have been labeled with markers, such as green fluorescent protein, and imaged using a variety of microscopy techniques.

Participants in the DIADEM Challenge will have the opportunity to test their algorithms on the latest data supplied by neuroscientists. Thus, they will have a chance to assess their solutions in a real-world environment.

Ascoli, Liu, and Svoboda believe the DIADEM Challenge and associated conference could lead to significant scientific and technical advancements.

“It will certainly result in a critical assessment of the remaining obstacles to a complete solution,” said Svoboda. “This will be an exciting opportunity to bring computational and experimental scientists together to see if they can solve this problem.”

Full details about the DIADEM Challenge—including detailed rules and information for competitors—can be found at www.diademchallenge.org.

Source: HHMI

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Time Stamp: 4/9/2009 at 3:21:15 PM UTC

Rice-led project aims to boost performance on every chip

Wednesday, April 8, 2009

DARPA awards $16 million to Rice University to improve compilers

The Defense Advanced Research Projects Agency (DARPA), as part of its Architecture Aware Compiler Environment Program, has awarded Rice University $16 million to develop a new set of tools that can improve the performance of virtually any application running on any microprocessor.

The PACE project -- short for "platform-aware compilation environment" -- centers on ubiquitous computer programs called compilers. All microprocessors -- not just those in PCs but also the ones powering cell phones, game systems, cars and even electronic toys -- have their own compilers to translate human-written computer applications into the binary 1s and 0s that a processor can execute.

"To use a new computer system effectively, an applications programmer needs a high-quality compiler, one that can translate the application in a way that achieves a reasonable fraction of the available performance," said Keith Cooper, Rice’s John and Ann Doerr Professor in Computational Engineering and a principal investigator on the PACE project. "Unfortunately, it typically takes about five years to develop a high-quality compiler for a new computer system, and because that's longer than the effective life cycle of most microprocessors, we rarely see a case where applications make good use of a processor's resources."

The plethora of microprocessors only adds to the problem. Most electronic gadgets -- everything from iPhones to digital hearing aids and GPS systems to antilock brakes -- have a specialized "embedded" microprocessor. New personal computers and laptops typically contain two or more general-purpose processors on a "multicore" chip from Intel or AMD, as well as a high-performance graphics processor, a sound card processor and other specialized processors. Sony's PlayStation 3 game system has an IBM Cell Broadband Engine that contains one general-purpose microprocessor and eight specialized processors.

Cooper said the military's interest in funding PACE stems from its heavy reliance on computing, ranging from supercomputers for global weather forecasts to portable devices used by infantry.

"When a compiler translates human-written code into executable code, it makes myriad choices that have a direct impact on how fast the application runs, how much power it uses and how much memory it uses," Cooper said.

The tools PACE project researchers hope to build will cut the time needed to create high-quality compilers. In addition, the PACE team will learn as it goes, measuring and weighing the goals, capabilities and performance of each processor, to create compilers that are optimized for particular situations.

Krishna Palem, Rice's Ken and Audrey Kennedy Professor of Computer Science, said, "It is a rare treat to be working with this 'dream team' and continue Rice's rich tradition in compiler research. PACE involves many innovations using radical ideas intended to allow compilers to learn and adapt, much as humans do during infancy."

The PACE "dream team" includes researchers from Rice, Texas Instruments, ET International, Ohio State University and Stanford University. Rice's team consists of five pre-eminent compiler researchers: Keith Cooper, John Mellor-Crummey, Krishna Palem, Vivek Sarkar and Linda Torczon. Each will lead part of the research and development activity. Researchers outside Rice include Reid Tatge of Texas Instruments; Rishi Khan, director of research and development at ET International; P. Sadayappan, professor of computer science and engineering at Ohio State; and Sanjiva Lele, professor of aeronautics and astronautics and of mechanical engineering at Stanford.

Vivek Sarkar, Rice's E.D. Butcher Chair in Engineering and professor of computer science, likened PACE's challenge to the famous test computer scientist Alan Turing posed in 1950: A computer could only be said to be truly intelligent if its actions were indistinguishable from a human's.

"This is akin to a Turing Test for compilers," Sarkar said. "Our goal is to enable PACE tools to be used as a substitute for the time-consuming human expertise that is currently needed to improve the quality of compilers for any given platform.

"The challenge is daunting," he said. "It's not just hard, it is DARPA-hard."

Because the PACE project will focus on portable performance, Cooper said, the researchers will rely on vendor-supplied compilers -- for languages such as C and Fortran -- to perform the final steps of code generation for the target systems. The output of the PACE tools will be a distinct version of an application's code for each kind of processor in the system. Each of those codes will be specifically optimized for the processor, the surrounding system and the vendor compiler.

Sarkar said, "In this way, the PACE system will manage the application performance that can be achieved using less-ambitious compilers for the component processors."

Source: Rice University / Jade Boyd

Permalink: http://www.sflorg.com/comm_center/unv_funding/p899_33.html

Time Stamp: 4/8/2009 at 2:06:12 PM UTC

Research reveals new information about antibiotic resistance in bacteria

Tuesday, April 7, 2009

Scientists at the University of Cambridge have uncovered the final piece in the jigsaw revealing the structure of ‘efflux pumps’ which allow Salmonella and other disease-causing bacteria to develop resistance to antibiotics and other drugs. The research, supported by the Wellcome Trust, allows greater understanding of how bacteria escape treatment and may help scientists develop new strategies to prevent antibiotic resistance.

Efflux pumps have evolved as survival mechanisms for the bacteria, reducing the concentration of noxious chemicals within the cells to levels that do not inhibit bacterial functions. These substances include naturally-occurring molecules toxic to the bacteria, such as bile salts in our gut. However, bacteria now also use the pumps to expel many antibiotics and other drugs that we use in the therapy of infections. The efflux pumps can deal with a great many drugs so they are important in the increasing incidence of bacterial multi-drug resistance, which is a growing threat to clinical treatment of infections.

Professors Vassilis Koronakis and Colin Hughes from the University of Cambridge have spent two decades studying the structure and function of these pumps. Now, together with Dr Martyn Simmons, a Cambridge Oppenheimer Research Fellow, the researchers have elucidated the structure of the final component of the pumps, enabling them to see more clearly how the bacteria evade antibiotics and develop resistance.

Salmonella and other so-called 'Gram-negative' bacteria, such as E. coli and Pseudomonas, are bound by two membranes, so the efflux pumps must therefore traverse both membranes in order to pump substances out. Other types of cells, such as human cancer cells and malaria parasites, also have efflux pumps, but these cells only contain a single membrane that the pumps have to cross, making their structure much more simple.

"The challenge for the bacteria is to rid itself of potentially damaging molecules across the unique envelope," says Professor Hughes. "They do this using beautifully simple, yet complex, biological nanomachines."

The bacterial pumps pick up drugs via a transporter in the inner membrane, which delivers them to a "trash chute" known as a TolC exit duct in the outer membrane. A third component - the "adapter" - connects these two components, opening the TolC exit duct to eject drugs out of the cell. The researchers have now managed to elucidate this whole tripartite structure, which is published in the Proceedings of the National Academy of Sciences.

Professor Hughes suggests that knowing the structure of the bacterial tripartite pumps allows further research to better understand how they work, and presents new possibilities for developing crucial new antibiotics. "This new research shows how the bits come together. Knowing the key components and their assembly can open up new therapeutic targets - in particular by preventing the pumps assembling in the first place."

Source: University of Cambridge

Permalink: http://www.sflorg.com/comm_center/unv_science/p898_235.html

Time Stamp: 4/7/2009 at 2:25:58 PM UTC

How the Retina Works

Tuesday, April 7, 2009

Like a Multi-layered Jigsaw Puzzle of Receptive Fields

About 1.25 million neurons in the retina -- each of which views the world only through a small jagged window called a receptive field -- collectively form the seamless picture we rely on to navigate our environment. Receptive fields fit together like pieces of a puzzle, preventing “blind spots” and excessive overlap that could blur our perception of the world, according to researchers at the Salk Institute for Biological Studies.

In the April 7 issue of the journal Public Library of Science, Biology, the scientists say their findings suggest that the nervous system operates with higher precision than previously appreciated and that apparent irregularities in individual cells may actually be coordinated and finely tuned to make the most of the world around us.

Previously, the observed irregularities of individual receptive fields suggested that the collective visual coverage might be uneven and irregular, potentially posing a problem for high-resolution vision. “The striking coordination we found when we examined a whole population indicated that neuronal circuits in the retina may sample the visual scene with high precision, perhaps in a manner that approaches the optimum for high-resolution vision,” says senior author E.J. Chichilnisky, Ph.D., an associate professor in the Systems Neurobiology Laboratories.

All visual information reaching the brain is transmitted by retinal ganglion cells. Each of the 20 or so distinct ganglion cell types is thought to transmit a complete visual image to the brain, because the receptive fields of each type form a regular lattice covering visual space. However, within each regular lattice, the individual cells’ receptive fields have irregular and inconsistent shapes, which could potentially result in patchy coverage of the visual field.

To understand how the visual system overcomes this problem, postdoctoral researcher and first author Jeffrey L. Gauthier, Ph.D., used a microscopic electrode array to record the activity of ganglion cells in isolated patches of retina, the tissue lining the back of the eye.

After monitoring hundreds of ganglion cells over several hours, he distinguished between different cell types based on their light response properties. “Often people record from many cells simultaneously but they don’t know which cell belongs to which type,” says Gauthier. Without this information, he says, he wouldn’t have been able to observe that the receptive fields of neighboring cells of a specific type interlock, complementing each others’ irregular shapes.

“The receptive fields of all four cell types we examined were precisely coordinated,” he says, “but we saw no coordination between cells of different types, emphasizing the importance of clearly distinguishing one cell type from another when studying sensory encoding by a population of neurons.”

Researchers who also contributed to the work include postdoctoral fellows Greg D. Field, Ph.D., Martin Greschner, Ph.D., and Jonathon Shlens, Ph.D., all in the Chichilnisky Laboratory, as well as postdoctoral researcher Alexander Sher, Ph.D., and professor Alan M. Litke, Ph.D., both at the Santa Cruz Institute for Particle Physics, University of California, Santa Cruz.

This work was supported by the National Institutes of Health, the National Science Foundation, the Chapman Foundation, the Helen Hay Whitney Foundation, the Burroughs Wellcome Fund, the Deutscher Akademischer Austauschdienst and the McKnight Foundation.

The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.

Image Caption: Each neuron in the retina views the world through a small, irregularly shaped window. These regions fit together like pieces of a puzzle, preventing "blind spot" and excessive overlap that could blur our perception of the world.

Image Credit: Dr. Jeffrey Gauthier / Salk Institute for Biological Studies

Source: Salk Institute

Permalink: http://www.sflorg.com/comm_center/science/p897_24.html

Time Stamp: 4/7/2009 at 4:08:16 AM UTC

Earthshine reflects Earth’s oceans and continents from the dark side of the Moon

Tuesday, April 7, 2009

Researchers from the University of Melbourne and Princeton University have shown for the first time that the difference in reflection of light from the Earth’s land masses and oceans can be seen on the dark side of the moon, a phenomenon known as earthshine.

Sally Langford from the University of Melbourne’s School of Physics who conducted the study as part of her PhD, says that the brightness of the reflected earthshine varied as the Earth rotated, revealing the difference between the intense mirror-like reflections of the ocean compared to the dimmer land.

“In the future, astronomers hope to find planets like the Earth around other stars. However these planets will be too small to allow an image to be made of their surface,” she said.

“We can use earthshine, together with our knowledge of the Earth's surface to help interpret the physical make up of new planets.”

This is the first study in the world to use the reflection of the Earth to measure the effect of continents and oceans on the apparent brightness of a planet. Other studies have used a color spectrum and infrared sensors to identify vegetation, or for climate monitoring.

The three year study involved taking images of the Moon to measure the earth’s brightness as it rotated, allowing Ms Langford to detect the difference in signal from land and water.

Observations of the Moon were made from Mount Macedon in Victoria, for around three days each month when the Moon was rising or setting. The study was conducted so that in the evening, when the Moon was a waxing crescent, the reflected earthshine originated from Indian Ocean and Africa’s east coast. In the morning, when the Moon was a waning crescent – it originated only from the Pacific Ocean.

“When we observe earthshine from the Moon in the early evening we see the bright reflection from the Indian Ocean, then as the Earth rotates the continent of Africa blocks this reflection, and the Moon becomes darker,” Ms Langford said.

“If we find Earth sized planets and watch their brightness as they rotate, we will be able to assess properties like the existence of land and oceans.”

The paper is published in this week’s edition of the international journal Astrobiology.

Source: University of Melbourne

Permalink: http://www.sflorg.com/comm_center/unv_space/p896_37.html

Time Stamp: 4/7/2009 at 3:21:05 AM UTC

Researchers Regenerate Axons Necessary for Voluntary Movement

Tuesday, April 7, 2009

For the first time, researchers have clearly shown regeneration of a critical type of nerve fiber that travels between the brain and the spinal cord and which is required for voluntary movement. The regeneration was accomplished in a brain injury site in rats by scientists at the University of California, San Diego School of Medicine and is described in a study to be published in the April 6th early on-line edition of the Proceedings of the National Academy of Sciences (PNAS).

“This finding establishes a method for regenerating a system of nerve fibers called corticospinal motor axons. Restoring these axons is an essential step in one day enabling patients to regain voluntary movement after spinal cord injury,” said Mark Tuszynski, MD, PhD, professor of neurosciences, director of the Center for Neural Repair at UC San Diego and neurologist at the Veterans Affairs San Diego Health System.

The corticospinal tract is a massive collection of nerve fibers called axons – long, slender projections of neurons that travel between the cerebral cortex of the brain and the spinal cord, carrying signals for movement from the brain to the body. Voluntary movement occurs through the activation of the upper motor neuron that resides in the frontal lobe of the brain and extends its axon down the spinal cord to the lower motor neuron. The lower motor neuron, in turn, sends its axon out to the muscle cells. In spinal cord injuries, the axons that run along the corticospinal tract are severed so that the lower motor neurons, below the site of injury, are disconnected from the brain.

“Previous spinal cord injury studies have shown regeneration of other nerve fiber systems that contribute to movement, but have not convincingly shown regeneration of the corticospinal system,” said Tuszynski, theorizing this was due to a limited intrinsic ability of corticospinal neurons to turn on genes that allow regeneration after injury. He added that, without regeneration of corticospinal axons, it is questionable whether functional recovery would be attainable in humans.

The UC San Diego team achieved corticospinal regeneration by genetically engineering the injured neurons to over-express receptors for a type of nervous system growth factor called brain-derived neurotrophic factor (BDNF). The growth factor was delivered to a brain lesion site in injured rats. There, the axons – because they now expressed trkB, the receptor for BDNF– were able to respond to the growth factor and regenerate into the injury site. In the absence of overexpression of trkB, no regeneration occurred.

Although functional recovery in the animals was not assessed, the new study shows for the first time that regeneration of the corticospinal system – which normally does not respond to treatment – can be achieved in a brain lesion site.

“The next step will be to try this in a spinal cord injury site, once we get the injured
neurons to send the growth factor receptor all the way down the axon and into the spinal cord,” said Tuszynski, adding that the UC San Diego research team is now working on this. “We will then assess whether regeneration of corticospinal nerve fibers will lead to functional recovery and restored movement in animal models.”

This work builds on another study from Tuszynski’s laboratory, published in the February 8, 2009 issue of Nature Medicine, which reported that BDNF also exhibits potential as a therapy for reducing brain cell loss in Alzheimer’s disease.

The lead author of the study was Edmund R. Hollis II, PhD. Additional contributors to the article included Pouya Jamshidi, Karin Low and Armin Blesch of the UC San Diego Department of Neurosciences. Their work was supported by grants from the National Institutes of Health, the Veterans Administration, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and the Bernard and Anne Spitzer Charitable Trust.

Source: University of California, San Diego

Permalink: http://www.sflorg.com/comm_center/unv_medical/p895_214.html

Time Stamp: 4/7/2009 at 2:39:38 AM UTC

First Successful Powered Flight of the Longbow Fire Control Radar Electronics Unit Configuration

Monday, April 6, 2009

On An Apache Block III Prototype Helicopter Achieved

The Longbow Limited Liability Company, a joint venture of Northrop Grumman Corporation (NYSE:NOC) and Lockheed Martin (NYSE:LMT), recently marked the first successful powered flight of the Radar Electronics Unit (REU) configuration of the Longbow Fire Control Radar (FCR) onboard an AH-64D Apache Block III prototype attack helicopter.

The Longbow Fire Control Radar system enables the Apache Longbow to rapidly search, detect, locate, classify, prioritize and engage both moving and stationary targets. The advanced REU improves power ratios and provides built-in processor expansion growth for new operating modes that will expand the Apache's role and missions. The REU is a key capability that will be integrated on all Apache Block III aircraft. One of its design features is that it may be installed to operate on Apache Block I or Block II aircraft with appropriate modifications, in addition to the Block III aircraft.

"The Longbow REU configuration is a significant capability advancement for the Longbow Apache AH-64D, the most versatile attack helicopter in the world," said Steve Considine, Longbow LLC vice-president and director of Longbow Aviation Programs at Northrop Grumman's Land Forces Division. "The REU's design preserves the two-level maintenance concept, lowers operations and supportability costs and improves reliability three fold, all while reducing the size and weight of the radar electronics on the Apache by half."

The Longbow system, as currently configured by the U.S. Army, consists of: the Longbow fire control radar; the AGM-114L fire-and-forget radar frequency Longbow Hellfire millimeter wave-guided missile, the all-digital M299 launcher and the AN/APR-48A Radio Frequency Interferometer for the AH-64 Apache helicopter. The Longbow REU configuration will be fielded on the Apache Block III aircraft beginning in 2011.

Headquartered in Bethesda, Md., Lockheed Martin is a global security company that employs about 146,000 people worldwide and is principally engaged in the research, design, development, manufacture, integration and sustainment of advanced technology systems, products and services. The corporation reported 2008 sales of $42.7 billion.

Northrop Grumman Corporation is a leading global security company whose 120,000 employees provide innovative systems, products, and solutions in aerospace, electronics, information systems, shipbuilding and technical services to government and commercial customers worldwide.

Source: Northrop Grumman

Permalink: http://www.sflorg.com/comm_center/northrop_grumman/p894_10.html

Time Stamp: 4/6/2009 at 4:39:12 PM UTC

Under Embargo Till: 16:00 UTC April 06, 2009
Posted: 16:00 UTC 04/06/2009

Gene Helps Protect Tumor Suppressor in Breast Cancer

Monday, April 6, 2009

Scientists at The University of Texas M. D. Anderson Cancer Center have discovered a gene that protects PTEN, a major tumor-suppressor that is reduced but rarely mutated in about half of all breast cancers.

The gene Rak helps protect and regulate PTEN, which also is important in several other types of cancer, the team reports in the April edition of Cancer Cell. Causes for diminished PTEN protein levels in breast cancer absent a mutation of the PTEN gene have eluded researchers, who knew for several years that a piece of the puzzle was missing.

"We've clearly discovered the missing link that explains how Rak can stabilize PTEN protein to prevent breast cancer development," said lead author Shiaw-Yih Lin, Ph.D., an assistant professor in the Department of Systems Biology at M. D. Anderson. "Our research explains why PTEN is defective in breast cancer and provides important clues for the development of effective therapy in Rak- or PTEN-defective breast cancers."

In addition to breast cancer, PTEN frequently is mutated or inactivated in glioblastoma, melanoma, and cancers of the prostate and endometrium. The severity of PTEN irregularities strongly correlates with the tumor stage and grade. For example, complete loss of PTEN expression is found more frequently in metastatic cancer than in primary tumors.

In the laboratory, researchers found Rak can stabilize PTEN protein and function as a tumor suppressor gene to prevent breast cancer development.

To examine the correlation between Rak and PTEN protein expression, researchers analyzed cells from 42 breast cancers. Rak expression showed a strong positive correlation with PTEN.

They also investigated the effect of Rak expression by injecting mice with cells that over-expressed Rak. All the mice injected with Rak-overexpressing cells remained tumor free, whereas all the control mice developed tumors.

"To further assess whether Rak is a bona fide breast tumor suppressor gene, we sought to determine if loss of Rak expression would transform normal mammary epithelial cells," Lin said. "We injected control cells or cells in which Rak was compromised into the mammary glands of healthy mice and monitored tumor growth. Notably, all the mice injected with Rak-knockdown cells, but none of the mice injected with control cells, developed tumors."

Recent studies have shown that the PTEN protein is destroyed when it is bound by the enzyme NEDD4-1, which attaches targeting molecules called ubiquitins that mark PTEN for destruction by the ubiquitin proteasome complex.

Lin and colleagues showed that Rak saves PTEN from degradation by attaching a phosphate group to the protein, blocking NEDD4-1 from binding to PTEN.

Although this study demonstrates a PTEN-dependent function of Rak, Lin says much research remains ahead on yet-unidentified PTEN-independent functions of Rak in tumor suppression.

"Recently, we found that Rak can prevent spontaneous DNA damage and has a critical role in suppressing cancer stem cells," he said. "So, we will expand our research efforts toward determining how Rak helps to maintain genomic integrity."

PTEN
This work was supported in part by a grant from the National Cancer Institute.

Source: University of Texas M. D. Anderson Cancer Center

Permalink: http://www.sflorg.com/comm_center/unv_medical/p893_213.html

Time Stamp: 4/6/2009 at 16:00:00 UTC

Gutsy Germs Succumb to Baby Broccoli

Monday, April 6, 2009

A small, pilot study in 50 people in Japan suggests that eating two and a half ounces of broccoli sprouts daily for two months may confer some protection against a rampant stomach bug that causes gastritis, ulcers and even stomach cancer.

Citing their new “demonstration of principle” study, a Johns Hopkins researcher and an international team of scientists caution that eating sprouts containing sulforaphane did not cure infection by the bacterium Helicobacter pylori (H. pylori). They do not suggest that eating this or any amount of broccoli sprouts will protect anyone from stomach cancer or cure GI diseases.

However, the study does show that eating a daily dose of broccoli sprouts reduced by more than 40 percent the level of HpSA, a highly specific measure of the presence of components of H. pylori shed into the stool of infected people. There was no HpSA level change in control subjects who ate alfalfa sprouts. The HpSA levels returned to pretreatment levels eight weeks after people stopped eating the broccoli sprouts, suggesting that although they reduce H. pylori colonization, they do not eradicate it.

“The highlight of the study is that we identified a food that, if eaten regularly, might potentially have an effect on the cause of a lot of gastric problems and perhaps even ultimately help prevent stomach cancer,” says Jed W. Fahey, M.S., Sc.D., an author of the paper who is a nutritional biochemist in the Lewis B. and Dorothy Cullman Cancer Chemoprotection Center at the Johns Hopkins University School of Medicine.

The discovery that sulforaphane is a potent antibiotic against H. pylori was reported in 2002 by Fahey and colleagues at Johns Hopkins. “Broccoli sprouts have a much higher concentration of sulforaphane than mature heads,” Fahey explains, adding that further investigation is needed to affirm the results of this clinical trial and move the research forward. The study, published April 6 in Cancer Prevention Research, builds on earlier test-tube and mouse studies at Johns Hopkins and elsewhere about the potential value of sulforaphane, a naturally occurring biochemical found in relative abundance in fresh broccoli sprouts.

Sulforaphane appears to trigger cells in the body, including in the gastrointestinal tract, to produce enzymes that protect against oxygen radicals, DNA-damaging chemicals, and inflammation.

In the new report, the team also shows that when H. pylori-infected mice sipped broccoli-sprout smoothies for eight weeks, there was up to a fourfold increase in the activity of two of these key enzymes that protect cells against oxidative damage. In addition, the number of Helicobacter bacteria in the mice’s stomachs decreased by almost a hundredfold it did not change in infected control animals that drank plain water. The researchers also noted a greater than 50 percent reduction in inflammation of the primary target of this bacterium – the body of the stomach – in treated mice but not in controls.

In a related experiment, the team fed the same dose of broccoli sprouts for the same amount of time to H. pylori-infected mice that had been genetically engineered to lack the Nrf2 gene that activates protective enzymes. “These knock-out mice didn’t respond,” Fahey says, which confirms previous findings for a role of Nrf2 in protection against H. pylori-induced inflammation and gastritis.

Classified a carcinogen by the World Health Organization, H. pylori is a gastrointestinal tract germ that manages to thrive in the lining of the stomach despite the strength of natural acids there that rival that of car batteries. Afflicting several billion people – roughly half of the world’s population – this corkscrew-shaped bacterium has long been associated with stomach ulcers, which now are frequently cured by antibiotics. Research strongly suggests that the bacteria also are linked to high rates of stomach cancer in some countries, that strains resistant to standard antibiotics are prevalent, and that multiple courses of standard antibiotics do not always eliminate the infection.

Working in Japan where there is high incidence of chronic H. pylori-infection, the research team gave 25 H. pylori-infected subjects two and a half ounces (70 grams) per day of broccoli sprouts for two months. Another 25 infected people consumed an equivalent amount of alfalfa sprouts which, although rich in phytochemicals, don’t contain sulforaphane.

The researchers assessed the severity of Helicobacter infection at the start of the study, after four and eight weeks of treatment, and again eight weeks after intervention was stopped. They used breath tests to assess colonization by H. pylori bacteria and blood tests to judge the severity of inflammation in the stomach lining; in addition, they looked for antigens in stool samples to help determine the extent of the infections.

“We know that a dose of a couple ounces a day of broccoli sprouts is enough to elevate the body’s protective enzymes,” Fahey says. “That is the mechanism by which we think a lot of the chemoprotective effects are occurring.

“What we don’t know is whether it’s going to prevent people from getting stomach cancer. But the fact that the levels of infection and inflammation were reduced suggests the likelihood of getting gastritis and ulcers and cancer is probably reduced.”

In disclosure of a potential conflict of interest, Fahey is a cofounder of, but holds no equity in, a company that is licensed by The Johns Hopkins University to produce broccoli sprouts. A portion of the proceeds is used to help support cancer research, but no such funds were provided to support this study.

“It’s exciting that a chronic bacterial infection that poses great hazards to hundreds of millions of people globally can be ameliorated by a specific dietary strategy,” says Paul Talalay, M.D., John Jacob Abel Distinguished Service Professor of Pharmacology and Experimental Therapeutics and director of the Lewis B. and Dorothy Cullman Cancer Chemoprotection Center at Johns Hopkins’ Institute for Basic Biomedical Sciences.

Talalay directs the lab where, in 1992, his team discovered the health-promoting properties of sulforaphane. A longtime proponent of cancer prevention and chemoprotection, Talalay eats fresh broccoli sprouts regularly, as does Fahey.

“I like them,” Fahey says. “I eat them all the time, but not every day. Variety is the spice of life: I eat blueberries on the other days.”

In addition to Fahey, the authors of the paper are Akinori Yanaka, Atsushi Fukumoto, Mari Nakayama and Souta Inoue, Tokyo University of Science, Japan; Masayuki Yamamoto, Songhua Zhang, Masafumi Tauchi, Hideo Suzuki and Ichinosuke Hyodo, University of Tsukuba, Japan.

Image Caption: It’s baby broccoli sprouts – not these mature heads which Jed Fahey holds – that researchers found effective in fighting a bacteria that causes gastritis, ulcers, and stomach cancer.

Image Credit: Johns Hopkins Medicine

Source: Johns Hopkins Medicine

Permalink: http://www.sflorg.com/comm_center/unv_medical/p892_212.html

Time Stamp: 4/6/2009 at 2:01:25 PM UTC

Cambridge research puts new test for sickle cell disease on horizon

Monday, April 6, 2009

A new method for diagnosing sickle cell disease has been found by researchers from Cambridge and Oxford Universities. This new test would be cheaper and easier to use than existing methods and provide a simpler alternative for use in developing nations.

Sickle cell disease is an inherited disorder that affects red blood cells. Each year 200,000 infants are born with sickle cell disease in Africa while the condition affects 15,000 people in the UK.

Normal red blood cells contain hemoglobin A, a protein that helps red blood cells carry oxygen around the body, but sickle cell sufferers carry an alternative form of the protein, hemoglobin S. This change causes the red blood cell to adopt a new, inflexible, shape, similar to a sickle, meaning that they can no longer fit through the body's small blood vessels.

These sickle cells can then stick to the blood vessels, blocking the flow of blood to organs and leading to extreme periods of pain for the sufferer. These sickle cells are also destroyed more quickly in the blood compared to normal blood cells, resulting in anemia.

The research team have discovered that deoxygenated sickle cells, unlike normal red blood cells, allow sugars into the cell when placed in certain solutions. This causes the cells to break open and release hemoglobin, which could be used to indicate the presence of sickle cells and ultimately the development of a simpler diagnostic test.

Dr John Gibson, from the Department of Veterinary Medicine and one of the lead researchers, said: "This research could have a significant impact on people with sickle cell in two ways: Our findings could result in a simple test to diagnose sickle cell based on whether red blood cells absorb sugars. This would be particularly important in pregnancy as mothers with sickle cell tend to be anemic and have more sickling crises, which could be life-threatening to the baby. As the test is simple and likely to be inexpensive, it could be used to diagnose the condition in developing countries that don't have the resources for expensive tests. Early detection in babies could help families be better prepared to manage the condition."

It is thought that the abnormalities in the S hemoglobin lead to changes in the permeability of the red blood cell membrane causing the cells to shrink. This research has lead to a greater understanding of the mechanisms and pathways by which sickle cells lose salts and water and become dehydrated. This research could also lead to the development of drugs to block this pathway and hopefully reduce both the number of sickle cells in the blood and crises.

Source: University of Cambridge

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Time Stamp: 4/6/2009 at 1:27:55 PM UTC