Date:March 14, 2014Source:Institute of Food TechnologistsSummary:A new study found that the production of a mixed raspberry jelly with black and yellow raspberries could be a good alternative to just one-colored jelly.determined that a jelly with both red, yellow and black raspberries had a high sensory acceptability, even greater than traditional jelly prepared only with the red raspberry.Raspberries are among the most popular berries in the world and are high in antioxidants that offer significant health benefits to consumers. The red raspberry is most commonly used in processed products like juices, jams, jellies and preserves because of its short shelf life. A new study in the Journal of Food Science, published by the Institute of Food Technologists (IFT), found that the production of a mixed raspberry jelly with black and yellow raspberries could be a good alternative to just one-colored jelly.Black raspberries, which produce clusters of small fruit with a dark purple color, stand out among the yellow and red variety as an excellent choice for cultivation because of their excellent adaptability, high productivity and fruit quality. Researchers at the University of Lavras in Brazil determined that a jelly with both red, yellow and black raspberries had a high sensory acceptability, even greater than traditional jelly prepared only with the red raspberry.More research is needed to study the feasibility of using yellow and black raspberries on other products.Story Source:The above story is based on materials provided by Institute of Food Technologists. Note: Materials may be edited for content and length.Journal Reference:Vanessa Rios de Souza, Patrcia Aparecida Pimenta Pereira, Ana Carla Marques Pinheiro, Cleiton Antnio Nunes, Rafael Pio, Fabiana Queiroz. Evaluation of the Jelly Processing Potential of Raspberries Adapted in Brazil. Journal of Food Science, 2014; 79 (3): S407 DOI: 10.1111/1750-3841.12354 Cite This Page:MLA APA Chicago Institute of Food Technologists. “People accept three-colored raspberry jelly, study finds.” ScienceDaily. ScienceDaily, 14 March 2014. .Institute of Food Technologists. …Read more
After searching hundreds of millions of objects across our sky, NASA’s Wide-Field Infrared Survey Explorer (WISE) has turned up no evidence of the hypothesized celestial body in our solar system commonly dubbed “Planet X.”Researchers previously had theorized about the existence of this large, but unseen celestial body, suspected to lie somewhere beyond the orbit of Pluto. In addition to “Planet X,” the body had garnered other nicknames, including “Nemesis” and “Tyche.”This recent study, which involved an examination of WISE data covering the entire sky in infrared light, found no object the size of Saturn or larger exists out to a distance of 10,000 astronomical units (au), and no object larger than Jupiter exists out to 26,000 au. One astronomical unit equals 93 million miles. Earth is 1 au, and Pluto about 40 au, from the sun.”The outer solar system probably does not contain a large gas giant planet, or a small, companion star,” said Kevin Luhman of the Center for Exoplanets and Habitable Worlds at Penn State University, University Park, Pa., author of a paper in the Astrophysical Journal describing the results.But searches of the WISE catalog are not coming up empty. A second study reveals several thousand new residents in our sun’s “backyard,” consisting of stars and cool bodies called brown dwarfs.”Neighboring star systems that have been hiding in plain sight just jump out in the WISE data,” said Ned Wright of the University of California, Los Angeles, the principal investigator of the mission.The second WISE study, which concentrated on objects beyond our solar system, found 3,525 stars and brown dwarfs within 500 light-years of our sun.”We’re finding objects that were totally overlooked before,” said Davy Kirkpatrick of NASA’s Infrared and Processing Analysis Center at the California Institute of Technology, Pasadena, Calif. Kirkpatrick is lead author of the second paper, also in the Astrophysical Journal. Some of these 3,525 objects also were found in the Luhman study, which catalogued 762 objects.The WISE mission operated from 2010 through early 2011, during which time it performed two full scans of the sky — with essentially a six-month gap between scans. The survey captured images of nearly 750 million asteroids, stars and galaxies. In November 2013, NASA released data from the AllWISE program, which now enables astronomers to compare the two full-sky surveys to look for moving objects.In general, the more an object in the WISE images appears to move over time, the closer it is. This visual clue is the same effect at work when one observes a plane flying low to the ground versus the same plane flying at higher altitude. …Read more
Roguish runaway stars can have a big impact on their surroundings as they plunge through the Milky Way galaxy. Their high-speed encounters shock the galaxy, creating arcs, as seen in a newly released image from NASA’s Spitzer Space Telescope.In this case, the speedster star is known as Kappa Cassiopeiae, or HD 2905 to astronomers. It is a massive, hot supergiant moving at around 2.5 million mph relative to its neighbors (1,100 kilometers per second). But what really makes the star stand out in this image is the surrounding, streaky red glow of material in its path. Such structures are called bow shocks, and they can often be seen in front of the fastest, most massive stars in the galaxy.Bow shocks form where the magnetic fields and wind of particles flowing off a star collide with the diffuse, and usually invisible, gas and dust that fill the space between stars. How these shocks light up tells astronomers about the conditions around the star and in space. Slow-moving stars like our sun have bow shocks that are nearly invisible at all wavelengths of light, but fast stars like Kappa Cassiopeiae create shocks that can be seen by Spitzer’s infrared detectors.Incredibly, this shock is created about 4 light-years ahead of Kappa Cassiopeiae, showing what a sizable impact this star has on its surroundings. (This is about the same distance that we are from Proxima Centauri, the nearest star beyond the sun.)The Kappa Cassiopeiae bow shock shows up as a vividly red color. The faint green features in this image result from carbon molecules, called polycyclic aromatic hydrocarbons, in dust clouds along the line of sight that are illuminated by starlight.Delicate red filaments run through this infrared nebula, crossing the bow shock. Some astronomers have suggested these filaments may be tracing out features of the magnetic field that runs throughout our galaxy. …Read more
Declines in the underlying brain skills needed to think, remember and learn are normal in aging. In fact, this cognitive decline is a fact of life for most older Americans.Therapies to improve the cognitive health of older adults are critically important for lessening declines in mental performance as people age. While physical activity and cognitive training are among the efforts aimed at preventing or delaying cognitive decline, dietary modifications and supplements have recently generated considerable interest.Now a University of South Florida (USF) study reports that a formula of nutrients high in antioxidants and other natural components helped boost the speed at which the brains of older adults processed information.The USF-developed nutritional supplement, containing extracts from blueberries and green tea combined with vitamin D3 and amino acids, including carnosine, was tested by the USF researchers in a clinical trial enrolling 105 healthy adults, ages 65 to 85.The two-month study evaluated the effects of the formula, called NT-020, on the cognitive performance of these older adults, who had no diagnosed memory disorders.Those randomized to the group of 52 volunteers receiving NT-020 demonstrated improvements in cognitive processing speed, while the 53 volunteers randomized to receive a placebo did not. Reduced cognitive processing speed, which can slow thinking and learning, has been associated with advancing age, the researchers said.The study, conducted at the USF Health Byrd Alzheimer’s Institute, appears in the current issue of Rejuvenation Research (Vol. 17 No. 1, 2014). Participants from both groups took a battery of memory tests before and after the interventions.”After two months, test results showed modest improvements in two measures of cognitive processing speed for those taking NT-020 compared to those taking placebo,” said Brent Small, PhD, a professor in USF’s School of Aging Studies. “Processing speed is most often affected early on in the course of cognitive aging. Successful performance in processing tasks often underlies more complex cognitive outcomes, such as memory and verbal ability.”Blueberries, a major ingredient in the NT-020 formula, are rich in polyphenols, a type of antioxidant containing a polyphenolic, or natural phenol substructure.”The basis for the use of polyphenol-rich nutritional supplements as a moderator of age-related cognitive decline is the age-related increase in oxidative stress and inflammation,” said study co-principal investigator Paula C. Bickford, PhD, a professor in the Department of Neurosurgery and Brain Repair, USF Health Morsani College of Medicine, and senior research career scientist at the James A. …Read more
Aug. 15, 2013 — By means of the quantum-mechanical entanglement of spatially separated light fields, researchers in Tokyo and Mainz have managed to teleport photonic qubits with extreme reliability. This means that a decisive breakthrough has been achieved some 15 years after the first experiments in the field of optical teleportation. The success of the experiment conducted in Tokyo is attributable to the use of a hybrid technique in which two conceptually different and previously incompatible approaches were combined.”Discrete digital optical quantum information can now be transmitted continuously — at the touch of a button, if you will,” explained Professor Peter van Loock of Johannes Gutenberg University Mainz (JGU). As a theoretical physicist, van Loock advised the experimental physicists in the research team headed by Professor Akira Furusawa of the University of Tokyo on how they could most efficiently perform the teleportation experiment to ultimately verify the success of quantum teleportation. Their findings have now been published in the journal Nature.Quantum teleportation involves the transfer of arbitrary quantum states from a sender, dubbed Alice, to a spatially distant receiver, named Bob. This requires that Alice and Bob initially share an entangled quantum state across the space in question, e.g., in the form of entangled photons. Quantum teleportation is of fundamental importance to the processing of quantum information (quantum computing) and quantum communication. Photons are especially valued as ideal information carriers for quantum communication since they can be used to transmit signals at the speed of light. A photon can represent a quantum bit or qubit analogous to a binary digit (bit) in standard classical information processing. …Read more
July 11, 2013 — In a pair of recent papers, researchers at MIT’s Computer Science and Artificial Intelligence Laboratory have demonstrated that, for a few specific tasks, it’s possible to write computer programs using ordinary language rather than special-purpose programming languages.The work may be of some help to programmers, and it could let nonprogrammers manipulate common types of files — like word-processing documents and spreadsheets — in ways that previously required familiarity with programming languages. But the researchers’ methods could also prove applicable to other programming tasks, expanding the range of contexts in which programmers can specify functions using ordinary language.”I don’t think that we will be able to do this for everything in programming, but there are areas where there are a lot of examples of how humans have done translation,” says Regina Barzilay, an associate professor of computer science and electrical engineering and a co-author on both papers. “If the information is available, you may be able to learn how to translate this language to code.”In other cases, Barzilay says, programmers may already be in the practice of writing specifications that describe computational tasks in precise and formal language. “Even though they’re written in natural language, and they do exhibit some variability, they’re not exactly Shakespeare,” Barzilay says. “So again, you can translate them.”The researchers’ recent papers demonstrate both approaches. In work presented in June at the annual Conference of the North American Chapter of the Association for Computational Linguistics, Barzilay and graduate student Nate Kushman used examples harvested from the Web to train a computer system to convert natural-language descriptions into so-called “regular expressions”: combinations of symbols that enable file searches that are far more flexible than the standard search functions available in desktop software.In a paper being presented at the Association for Computational Linguistics’ annual conference in August, Barzilay and another of her graduate students, Tao Lei, team up with professor of electrical engineering and computer science Martin Rinard and his graduate student Fan Long to describe a system that automatically learned how to handle data stored in different file formats, based on specifications prepared for a popular programming competition.Regular irregularitiesAs Kushman explains, computer science researchers have had some success with systems that translate questions written in natural language into special-purpose formal languages — languages used to specify database searches, for instance. “Usually, the way those techniques work is that they’re finding some fairly direct mapping between the natural language and this formal representation,” Kushman says. “In general, the logical forms are handwritten so that they have this nice mapping.”Unfortunately, Kushman says, that approach doesn’t work with regular expressions, strings of symbols that can describe the data contained in a file with great specificity. A regular expression could indicate, say, just those numerical entries in a spreadsheet that are three columns over from a cell containing a word of any length whose final three letters are “BOS.”But regular expressions, as ordinarily written, don’t map well onto natural language. For example, Kushman explains, the regular expression used to search for a three-letter word starting with “a” would contain a symbol indicating the start of a word, another indicating the letter “a,” a set of symbols indicating the identification of a letter, and a set of symbols indicating that the previous operation should be repeated twice. …Read more
July 9, 2013 — Sensory processing disorders (SPD) are more prevalent in children than autism and as common as attention deficit hyperactivity disorder, yet it receives far less attention partly because it’s never been recognized as a distinct disease.In a groundbreaking new study from UC San Francisco, researchers have found that children affected with SPD have quantifiable differences in brain structure, for the first time showing a biological basis for the disease that sets it apart from other neurodevelopmental disorders.One of the reasons SPD has been overlooked until now is that it often occurs in children who also have ADHD or autism, and the disorders have not been listed in the Diagnostic and Statistical Manual used by psychiatrists and psychologists.”Until now, SPD hasn’t had a known biological underpinning,” said senior author Pratik Mukherjee, MD, PhD, a professor of radiology and biomedical imaging and bioengineering at UCSF. “Our findings point the way to establishing a biological basis for the disease that can be easily measured and used as a diagnostic tool,” Mukherjee said.The work is published in the open access online journal NeuroImage:Clinical.’Out of Sync’ KidsSensory processing disorders affect 5 to 16 percent of school-aged children.Children with SPD struggle with how to process stimulation, which can cause a wide range of symptoms including hypersensitivity to sound, sight and touch, poor fine motor skills and easy distractibility. Some SPD children cannot tolerate the sound of a vacuum, while others can’t hold a pencil or struggle with social interaction. Furthermore, a sound that one day is an irritant can the next day be sought out. The disease can be baffling for parents and has been a source of much controversy for clinicians, according to the researchers.”Most people don’t know how to support these kids because they don’t fall into a traditional clinical group,” said Elysa Marco, MD, who led the study along with postdoctoral fellow Julia Owen, PhD. Marco is a cognitive and behavioral child neurologist at UCSF Benioff Children’s Hospital, ranked among the nation’s best and one of California’s top-ranked centers for neurology and other specialties, according to the 2013-2014 U.S. News & World Report Best Children’s Hospitals survey.”Sometimes they are called the ‘out of sync’ kids. Their language is good, but they seem to have trouble with just about everything else, especially emotional regulation and distraction. In the real world, they’re just less able to process information efficiently, and they get left out and bullied,” said Marco, who treats affected children in her cognitive and behavioral neurology clinic.”If we can better understand these kids who are falling through the cracks, we will not only help a whole lot of families, but we will better understand sensory processing in general. This work is laying the foundation for expanding our research and clinical evaluation of children with a wide range of neurodevelopmental challenges – stretching beyond autism and ADHD,” she said.Imaging the Brain’s White MatterIn the study, researchers used an advanced form of MRI called diffusion tensor imaging (DTI), which measures the microscopic movement of water molecules within the brain in order to give information about the brain’s white matter tracts. …Read more
July 2, 2013 — How is it possible for a human eye to figure out letters that are twisted and looped in crazy directions, like those in the little security test internet users are often given on websites?It seems easy to us — the human brain just does it. But the apparent simplicity of this task is an illusion. The task is actually so complex, no one has been able to write computer code that translates these distorted letters the same way that neural networks can. That’s why this test, called a CAPTCHA, is used to distinguish a human response from computer bots that try to steal sensitive information.Now, a team of neuroscientists at the Salk Institute for Biological Studies has taken on the challenge of exploring how the brain accomplishes this remarkable task. Two studies published within days of each other demonstrate how complex a visual task decoding a CAPTCHA, or any image made of simple and intricate elements, actually is to the brain.The findings of the two studies, published June 19 in Neuron and June 24 in the Proceedings of the National Academy of Sciences (PNAS), take two important steps forward in understanding vision, and rewrite what was believed to be established science. The results show that what neuroscientists thought they knew about one piece of the puzzle was too simple to be true.Their deep and detailed research — -involving recordings from hundreds of neurons — -may also have future clinical and practical implications, says the study’s senior co-authors, Salk neuroscientists Tatyana Sharpee and John Reynolds.”Understanding how the brain creates a visual image can help humans whose brains are malfunctioning in various different ways — -such as people who have lost the ability to see,” says Sharpee, an associate professor in the Computational Neurobiology Laboratory. “One way of solving that problem is to figure out how the brain — -not the eye, but the cortex — — processes information about the world. If you have that code then you can directly stimulate neurons in the cortex and allow people to see.”Reynolds, a professor in the Systems Neurobiology Laboratory, says an indirect benefit of understanding the way the brain works is the possibility of building computer systems that can act like humans.”The reason that machines are limited in their capacity to recognize things in the world around us is that we don’t really understand how the brain does it as well as it does,” he says.The scientists emphasize that these are long-term goals that they are striving to reach, a step at a time.Integrating parts into wholesIn these studies, Salk neurobiologists sought to figure out how a part of the visual cortex known as area V4 is able to distinguish between different visual stimuli even as the stimuli move around in space. V4 is responsible for an intermediate step in neural processing of images.”Neurons in the visual system are sensitive to regions of space — — they are like little windows into the world,” says Reynolds. “In the earliest stages of processing, these windows — -known as receptive fields — -are small. …Read more
June 25, 2013 — Hungry people are often difficult to deal with. A good meal can affect more than our mood, it can also influence our willingness to take risks. This phenomenon is also apparent across a very diverse range of species in the animal kingdom. Experiments conducted on the fruit fly, Drosophila, by scientists at the Max Planck Institute of Neurobiology in Martinsried have shown that hunger not only modifies behaviour, but also changes pathways in the brain.Animal behaviour is radically affected by the availability and amount of food. Studies prove that the willingness of many animals to take risks increases or declines depending on whether the animal is hungry or full. For example, a predator only hunts more dangerous prey when it is close to starvation. This behaviour has also been documented in humans in recent years: one study showed that hungry subjects took significantly more financial risks than their sated colleagues.Also the fruit fly, Drosophila, changes its behaviour depending on its nutritional state. The animals usually perceive even low quantities of carbon dioxide to be a sign of danger and opt to take flight. However, rotting fruit and plants — the flies’ main sources of food — also release carbon dioxide. Neurobiologists in Martinsried have now discovered how the brain deals with this constant conflict in deciding between a hazardous substance and a potential food source taking advantage of the fly as a great genetic model organism for circuit neuroscience.In various experiments, the scientists presented the flies with environments containing carbon dioxide or a mix of carbon dioxide and the smell of food. …Read more
May 31, 2013 — Researchers at the University of Georgia, Athens, have identified a strong link between the prevalence and load of certain food-borne pathogens on poultry farms, and later downstream at the processing plant. They report their findings in a manuscript published ahead of print in the journal Applied and Environmental Microbiology.”This study suggests that reducing foodborne pathogen loads on broiler chicken farms would help to reduce pathogen loads at processing, and may ultimately help to reduce the risk of foodborne illness,” says Roy Berghaus, an author on the study. “This is important because most of our efforts towards reducing foodborne pathogens are currently focused on what happens during processing. Processing interventions are effective but they can only do so much.”Salmonella and Campylobacter bacteria cause an estimated 1.9 million food-borne illnesses in the US annually, and poultry is a major source of both. Earlier studies have linked pathogen prevalence on the farm and at processing, but none has measured the strength of the associations between pathogen loads, according to the report. In the current study, Salmonella and Campylobacter detected at the processing plant were found in farm samples 96 and 71 percent of the time, respectively.The prevalence of both pathogens dropped during processing, Salmonella from 45.9 percent to 2.4 percent, and Campylobacterfrom 68.7 to 43.6 percent, according to the report.The two pathogens are major contributors to human misery in the US. Among 104 different pathogen-food combinations, Campylobacter and Salmonella infections from poultry were recently ranked first and fourth, respectively in terms of “combined impact on the total cost of illness and loss of quality-adjusted life years,” according to the report.The team suggests that fewer pathogens on the farm would reduce contamination levels at the processing plant, and notes that “vaccination of breeder hens, competitive exclusion products and the use of acidified water during feed withdrawal” have all reduced Salmonella in commercial broiler flocks. However “reliable approaches to reduce Campylobactercolonization are currently unavailable,” although post-processing freezing has reduced Campylobacterloads on carcasses.Read more
May 30, 2013 — The prospects of a robotic manufacturing base operating off Earth is not as far-fetched as it used to be according to a study published by a team of NASA researchers led by a Kennedy Space Center physicist.
Because asteroids are loaded with minerals that are rare on Earth, near-Earth asteroids and the asteroid belt could become the mining centers for remotely operated excavators and processing machinery. In 20 years, an industry barely imagined now could be sending refined materials, rare metals and even free, clean energy to Earth from asteroids and other bodies.
In their paper called “Affordable, Rapid Bootstrapping of the Space Industry and Solar System Civilization,” published in the Journal of Aerospace Engineering, Phil Metzger, Anthony Muscatello, Robert Mueller and James Mantovani detail an intriguing path toward developing a self-sustaining, space-based industry that would use resources from asteroids and other heavenly bodies to meet the needs of humanity.
The result would provide the most profound societal changes since the Industrial Revolution introduced large-scale machinery and manufacturing techniques in the late 18th and early 19th centuries, said Metzger the Kennedy-based physicist who led the evaluation.
“We’re predicting that we are on the verge of the next revolution in human civilization,” Metzger said.
Two fundamental developments make this prospect possible: robotics and the discovery of fundamental elements to make plastic and rubber and metals existing throughout space.
“Now that we know we can get carbon in space, the basic elements that we need for industry are all within reach,” Metzger said. “That was game-changing for us. The asteroid belt has a billion times more platinum than is found on Earth. There is literally a billion times the metal that is on the Earth, and all the water you could ever need.”
Another critical technology also is coming in at just the right time: additive manufacturing in the form of 3D printers that can turn out individual pieces that can be assembled into ever-more-complex machinery and increasingly capable robots.
“The idea is you start with resources out of Earth’s gravity well in the vicinity of the Earth,” Metzger said. “But what we argued is that you can establish industry in space for a surprisingly low cost, much less than anybody previously thought.”
The finished minerals could be returned to Earth or used in space to build new machinery or as supplies for astronauts as they explore the solar system.
So where to start?
The closer to Earth, the better — at least at first.
NASA is searching for an asteroid of about 500 tons that can be moved into a path within the moon’s orbit so astronauts can visit it as early as 2021 to take samples of the space rock.
“When we wrote this paper we were focused on the moon as a source of near-Earth resources, but near Earth asteroids work equally well and offer several additional advantages,” Metzger said. “It takes less fuel to bring resources away from the lower gravity of an asteroid, and since the ultimate goal is to move the industry to the asteroid main belt starting with asteroids first will help develop the correct technologies.”
But all asteroids are not created equal, and each one is likely to offer a unique fingerprint of substances created when the solar system formed billions of years ago.
“There are some types of asteroids that would be fantastic for space resources,” Metzger said. “It’s primordial solar system material. You can make plastics and you can make rubber by combining the carbon and the hydrogen.”
A near-Earth asteroid or other nearby body presumably will contain enough material to allow a robotic system to mine the materials and refine them into usable metal or other substances. Those materials would be formed into pieces and assembled into another robot system that would itself build similar models and advance the design.
“The first generation only makes the simplest materials, it can include metal and therefore you can make structure out of metal and then you can send robots that will attach electronics and wiring onto the metal,” Metzger said. “So by making the easiest thing, you’ve reduced the largest amount of mass that you have to launch.”
The first generation of machinery would be akin to the simple mechanical devices of the 1700s, with each new generation advancing quickly to the modern vanguard of abilities. They would start with gas production and the creation of solar cells, vital for providing a power source.
Each new robot could add improvements to each successive model and quickly advance the mining and manufacturing capabilities. It would not take long for the miners to produce more material than they need for themselves and they could start shipping precious metals back to Earth, riding on heat shields made of the leftover soil that doesn’t contain any precious material.
Kennedy researchers already have tested heat shield samples made from soil.
Bodies near Earth also were recently revealed to contain water ice, which gives planners the chemicals needed to produce fuel and air. With those resources available, the robotic miners would be able to propel themselves farther out into the solar system, mainly to the resource-rich asteroid belt between Mars and Jupiter. There they could set up more manufacturing and refining facilities.
Perhaps the most unusual aspect of the whole endeavor is that it would not take many launches from Earth to achieve. Launch costs, which now run at best $1,000 per pound, would be saved because robots building themselves in space from material gathered there wouldn’t need anything produced by people. Very quickly, only the computer chips, electronics boards and wiring would need to come from Earth.
“We took it through six generations of robotic development and you can achieve full closure and make everything in space,” Metzger said. “We showed you can get it down to launching 12 tons of hardware, which is incredibly small.”
For comparison, that would be less than half the weight of the Apollo command and service modules flown on a moon mission.
This enterprise would take years to establish, but not as long as one might think. And the payoff for Earth would be felt when the first shipments of materials began arriving from space. A sudden influx of rare metals, for instance, would drive down the price of those materials on Earth and allow a similar drastic reduction in manufacturing costs for products made with the materials.
There are numerous examples of such revolutions taking place over and over again on Earth, including the discovery after the Civil War of a process for refining bauxite into aluminum that made the metal go from being as valuable as gold to something soda cans are made of. Does that mean soda cans would be made from platinum? Maybe not, but the changes could be just as dramatic.
“You could grow an industry that is a million times bigger than the United States’ in the main asteroid belt,” Metzger said. “Then you really are capable of terraforming planets and doing all the other great things because it wouldn’t cost you anything” in terms of labor, resources or materials.Read more
May 30, 2013 — Researchers at the Stanford University School of Medicine have found that a naturally occurring protein secreted only in discrete areas of the mammalian brain may act as a Valium-like brake on certain types of epileptic seizures.
The protein is known as diazepam binding inhibitor, or DBI. It calms the rhythms of a key brain circuit and so could prove valuable in developing novel, less side-effect-prone therapies not only for epilepsy but possibly for anxiety and sleep disorders, too. The researchers’ discoveries will be published May 30 in Neuron.
“This is one of the most exciting findings we have had in many years,” said John Huguenard, PhD, professor of neurology and neurological sciences and the study’s senior author. “Our results show for the first time that a nucleus deep in the middle of the brain generates a small protein product, or peptide, that acts just like benzodiazepines.” This drug class includes not only the anti-anxiety compound Valium (generic name diazepam), first marketed in 1965, but its predecessor Librium, discovered in 1955, and the more recently developed sleep aid Halcyon.
Valium, which is notoriously addictive, prone to abuse and dangerous at high doses, was an early drug treatment for epilepsy, but it has fallen out of use for this purpose because its efficacy quickly wears off and because newer, better anti-epileptic drugs have come along.
For decades, DBI has also been known to researchers under a different name: ACBP. In fact, it is found in every cell of the body, where it is an intracellular transporter of a metabolite called acyl-CoA. “But in a very specific and very important brain circuit that we’ve been studying for many years, DBI not only leaves the cells that made it but is — or undergoes further processing to become — a natural anti-epileptic compound,” Huguenard said. “In this circuit, DBI or one of its peptide fragments acts just like Valium biochemically and produces the same neurological effect.”
Other endogenous (internally produced) substances have been shown to cause effects similar to psychoactive drugs. In 1974, endogenous proteins called endorphins, with biochemical activity and painkilling properties similar to that of opiates, were isolated. A more recently identified set of substances, the endocannabinoids, mimic the memory-, appetite- and analgesia-regulating actions of the psychoactive components of cannabis, or marijuana.
DBI binds to receptors that sit on nerve-cell surfaces and are responsive to a tiny but important chemical messenger, or neurotransmitter, called GABA. The roughly one-fifth of all nerve cells in the brain that are inhibitory mainly do their job by secreting GABA, which binds to receptors on nearby nerve cells, rendering those cells temporarily unable to fire any electrical signals of their own.
Benzodiazepine drugs enhance GABA-induced inhibition by binding to a different site on GABA receptors from the one GABA binds to. That changes the receptor’s shape, making it hyper-responsive to GABA. These receptors come in many different types and subtypes, not all of which are responsive to benzodiazepines. DBI binds to the same spot to which benzodiazepines bind on benzodiazepine-responsive GABA receptors. But until now, exactly what this means has remained unclear.
Huguenard, along with postdoctoral scholar and lead author Catherine Christian, PhD, and several Stanford colleagues zeroed in on DBI’s function in the thalamus, a deep-brain structure that serves as a relay station for sensory information, and which previous studies in the Huguenard lab have implicated on the initiation of seizures. The researchers used single-nerve-cell-recording techniques to show that within a GABA-secreting nerve-cell cluster called the thalamic reticular nucleus, DBI has the same inhibition-boosting effect on benzodiazepine-responsive GABA receptors as do benzodiazepines. Using bioengineered mice in which those receptors’ benzodiazepine-binding site was defective, they showed that DBI lost its effect, which Huguenard and Christian suggested makes these mice seizure-prone.
In another seizure-prone mouse strain in which that site is intact but the gene for DBI is missing, the scientists saw diminished inhibitory activity on the part of benzodiazepine-responsive GABA receptors. Re-introducing the DBI gene to the brains of these mice via a sophisticated laboratory technique restored the strength of the GABA-induced inhibition. In normal mice, a compound known to block the benzodiazepine-binding site weakened these same receptors’ inhibitory activity in the thalamic reticular nucleus, even in the absence of any administered benzodiazepines. This suggested that some naturally occurring benzodiazepine-like substance was being displaced from the benzodiazepine-binding site by the drug. In DBI-gene-lacking mice, the blocking agent had no effect at all.
Huguenard’s team also showed that DBI has the same inhibition-enhancing effect on nerve cells in an adjacent thalamic region — but also that, importantly, no DBI is naturally generated in or near this region; in the corticothalamic circuit, at least, DBI appears to be released only in the thalamic reticular nucleus. So, the actions of DBI on GABA receptors appear to be tightly controlled to occur only in specific brain areas.
Huguenard doesn’t know yet whether it is DBI per se, or one of its peptide fragments (and if so which one), that is exerting the active inhibitory role. But, he said, by finding out exactly which cells are releasing DBI under what biochemical circumstances, it may someday be possible to develop agents that could jump-start and boost its activity in epileptic patients at the very onset of seizures, effectively nipping them in the bud.Read more