Robot Arm Improves Performance of Brain-Controlled Device

Robot Arm Improves Performance of Brain-Controlled Device

  10:34:00 AM    Science Lover

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The performance of a brain-machine interface designed to help paralyzed subjects move objects with their thoughts is improved with the addition of a robotic arm providing sensory feedback, a new study from the University of Chicago finds.

During the experiment, monkeys used their brain signals to move a computer cursor (red circle) to randomly placed targets (squares). When visual and proprioceptive feedback were included, the monkey's hand was moved by a robotic exoskeleton. The additional sensory information resulted in the cursor hitting the target faster and more directly. (Credit: Courtesy, with permission: Hatsopoulos, et al. The Journal of Neuroscience 2010.)

Devices that translate brain activity into the movement of a computer cursor or an external robotic arm have already proven successful in humans. But in these early systems, vision was the only tool a subject could use to help control the motion.

Adding a robot arm that provided kinesthetic information about movement and position in space improved the performance of monkeys using a brain-machine interface in a study published December 14 in The Journal of Neuroscience. Incorporating this sense may improve the design of "wearable robots" to help patients with spinal cord injuries, researchers said.

"A lot of patients that are motor-disabled might have partial sensory feedback," said Nicholas Hatsopoulos, PhD, Associate Professor and Chair of Computational Neuroscience at the University of Chicago. "That got us thinking that maybe we could use this natural form of feedback with wearable robots to provide that kind of feedback."

In the experiments, monkeys controlled a cursor without actively moving their arm via a device that translated activity in the primary motor cortex of their brain into cursor motion. While wearing a sleeve-like robotic exoskeleton that moved their arm in tandem with the cursor, the monkey's control of the cursor improved, hitting targets faster and via straighter paths than without the exoskeleton.

"We saw a 40 percent improvement in cursor control when the robotic exoskeleton passively moved the monkeys' arm," Hatsopoulos said. "This could be quite significant for daily activities being performed by a paralyzed patient that was equipped with such a system."

When a person moves their arm or hand, they use sensory feedback called proprioception to control that motion. For example, if one reaches out to grab a coffee mug, sensory neurons in the arm and hand send information back to the brain about where one's limbs are positioned and moving. Proprioception tells a person where their arm is positioned, even if their eyes are closed.

But in patients with conditions where sensory neurons die out, executing basic motor tasks such as buttoning a shirt or even walking becomes exceptionally difficult. Paraplegic subjects in the early clinical trials of brain-machine interfaces faced similar difficulty in attempting to move a computer cursor or robot arm using only visual cues. Those troubles helped researchers realize the importance of proprioception feedback, Hatsopoulos said.

"In the early days when we were doing this, we didn't even consider sensory feedback as an important component of the system," Hatsopoulos said. "We really thought it was just one-way: signals were coming from the brain, and then out to control the limb. It's only more recently that the community has really realized that there is this loop with feedback coming back."

Reflecting this loop, the researchers on the new study also observed changes in the brain activity recorded from the monkeys when sensory feedback was added to the set-up. With proprioception feedback, the information in the cell firing patterns of the primary motor cortex contained more information than in trials with only visual feedback, Hatsopoulos said, reflecting an improved signal-to-noise ratio.

The improvement seen from adding proprioception feedback may inform the next generation of brain-machine interface devices, Hatsopoulos said. Already, scientists are developing different types of "wearable robots" to augment a person's natural abilities. Combining a decoder of cortical activity with a robotic exoskeleton for the arm or hand can serve a dual purpose: allowing a paralyzed subject to move the limb, while also providing sensory feedback.

To benefit from this solution, a paralyzed patient must have retained some residual sensory information from the limbs despite the loss of motor function -- a common occurrence, Hatsopoulos said, particularly in patients with ALS, locked-in syndrome, or incomplete spinal cord injury. For patients without both motor and sensory function, direct stimulation of sensory cortex may be able to simulate the sensation of limb movement. Further research in that direction is currently underway, Hatsopoulos said.

"I think all the components are there; there's nothing here that's holding us back conceptually," Hatsopoulos said. "I think using these wearable robots and controlling them with the brain is, in my opinion, probably the most promising approach to take in helping paralyzed individuals regain the ability to move."

Funding for the research was provided by the National Institute of Neurological Disorders and Stroke and the Paralyzed Veterans of America Research Foundation.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect to us.

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Bioengineers Discover How Particles Self-Assemble in Flowing Fluids

Bioengineers Discover How Particles Self-Assemble in Flowing Fluids

  10:10:00 AM    Science Lover

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From atomic crystals to spiral galaxies, self-assembly is ubiquitous in nature. In biological processes, self-assembly at the molecular level is particularly prevalent.

A simple microfluidic "filter" structure converts 
microparticle streams with smaller interparticle 
spacings to trains of larger spacing. The channel 
width is about half the diameter of a human hair 
at the expansion. (Credit: Image courtesy 
of University of California - Los Angeles)

Phospholipids, for example, will self-assemble into a bilayer to form a cell membrane, and actin, a protein that supports and shapes a cell's structure, continuously self-assembles and disassembles during cell movement.

Bioengineers at the UCLA Henry Samueli School of Engineering and Applied Science have been exploring a unique phenomenon whereby randomly dispersed microparticles self-assemble into a highly organized structure as they flow through microscale channels.

This self-assembly behavior was unexpected, the researchers said, for such a simple system containing only particles, fluid and a conduit through which these elements flow. The particles formed lattice-like structures due to a unique combination of hydrodynamic interactions.

The research, published online December 13 in the journal Proceedings of the National Academy of Sciences, was led by UCLA postdoctoral scholar Wonhee Lee and UCLA assistant professor of bioengineering Dino Di Carlo.

The research team discovered the mechanism that leads to this self-assembly behavior through a series of careful experiments and numerical simulations. They found that continuous disturbance of the fluid induced by each flowing and rotating particle drives neighboring particles away, while migration of particles to localized streams due to the momentum of the fluid acts to stabilize the spacing between particles at a finite distance. In essence, the combination of repulsion and localization leads to an organized structure.

Once they understood the mechanism, the team developed microchannels that allowed for "tuning" of the spatial frequency of particles within an organized particle train. They found that by simply adding short regions of expanded channel width, the particles could be induced to self-assemble into different structures in a controllable and potentially programmable way.

"Programmable control of flowing microscale particles may be important in opening up new capabilities in biomedicine, materials synthesis and computation, similar to how improved control of flowing electrons has enabled a revolution in computing and communication," Di Carlo said.

For example, controlling the positions of microscale bioparticles, such as cells in flowing channels, is important for the operation of blood analysis and counting diagnostic systems. In addition, improving the uniformity of cell concentrations entering the microscale volume of a print head can enable burgeoning fields such as "tissue printing," in which single cells in a polymer ink are sequentially positioned to form a functional tissue architecture, such as the cylindrical lumen of a blood vessel.

More complete control of lattices of particles may also allow tunable manufacturing of optical or acoustic metamaterials that interact uniquely with light and sound waves based on the arrangement of the embedded particles, the researchers said.

Disclaimer: Views expressed in this article do not necessarily reflect us.

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Neutron Stars and String Theory in a Lab: Chilled Atoms Give Clues to Deep Space and Particle Physics

Neutron Stars and String Theory in a Lab: Chilled Atoms Give Clues to Deep Space and Particle Physics

  8:22:00 PM    Science Lover

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Using lasers to contain some ultra-chilled atoms, a team of scientists has measured the viscosity or stickiness of a gas often considered to be the sixth state of matter. The measurements verify that this gas can be used as a "scale model" of exotic matter, such as super-high temperature superconductors, the nuclear matter of neutron stars, and even the state of matter created microseconds after the Big Bang.

Artist's rendering of a neutron star. (Credit: NASA/Dana Berry)

The results may also allow experimental tests of string theory in the future.

Duke physicist John Thomas made the viscosity measurements using an ultra-cold Fermi gas of lithium-6 atoms trapped in a millimeter-sized bowl made of laser light. When cooled and placed inside a magnetic field of the correct size, the atoms interact as strongly as the laws of quantum mechanics allow. This strongly interacting gas exhibits "remarkable properties," such as nearly frictionless fluid flow, Thomas said.

The team's report appears in the Dec. 10 issue of Science.

Under the ultra-cold conditions, the properties of the gas are determined by a universal ruler, or natural length scale, much like the scale on an architect's drawing. The ruler for the atomic gas is the average spacing between the atoms. According to quantum physics, this spacing determines all other natural scales, such as the scale for energy, temperature and viscosity, making the ultra-cold gas a scale model for other exotic matter. Thomas said that he and others have verified the gas as a universal scale model for properties such as temperature, but this is the first time they've tested the scaling of viscosity, which happens to be of particular interest to scientists right now.

Thomas first measured the viscosity of the gas at a few billionths of a degree Kelvin, or -459 degrees Fahrenheit. Turning off the trap that confines the gas, and then recapturing it caused the radius of the Fermi gas to vibrate. The oscillation, called a breathing mode, resembles the jiggling of a piece of jelly. The longer the vibrations lasted, the lower the viscosity. At slightly higher temperatures, millionths of a degree Kelvin, the researchers instead observed how fast the gas changed from a cigar shape to a pancake after being released from the trap. A slower change in shape had a higher viscosity.

These results are "extremely important to the field of condensed matter physics and to high temperature superconductivity in particular," said Kathy Levin, a theorist at the University of Chicago, who was not involved in the research. She said that the viscosity of the Fermi gas is similar to the conductivity of a superfluid, which flows with no resistance. This "perfect fluidity" is also observed in the condensed matter world, especially in materials used to make high temperature superconductors. The new data, especially at lower temperatures, "seem quite consistent" with predictions of how superconductors should flow, Levin said.

The Fermi gas as a scale model is also important for studying elements of the cosmos that scientists can't probe in a lab, said Duke physicist Berndt Mueller. Even a very small chunk of a neutron star, a dead star that hasn't become a black hole, would weigh billions of tons on Earth and be much too dense to study. The data showing the universal properties of the Fermi gas, however, let physicists calculate the scale from lithium-6 atomic spacing to the spacing between neutrons in these stars. The measurements made on the Fermi gas can then be used to determine the natural energy and other properties for these stars, which can be compared to theorists' predictions. Similar calculations can be made for the quark-gluon plasma, the state of matter created just microseconds after the Big Bang and being studied in particle accelerators such as the Large Hadron Collider in Geneva.

Thomas said the new results also give experimental insight into predictions made using string theory, the mathematical construct uniting the classical world of gravity with quantum physics. String theorists have provided a lower bound for the ratio of the viscosity or fluid flow to the entropy, or disorder, in a strongly-interacting system. The new experiments measured both properties in the Fermi gas and showed that the gas minimum is between four and five times the string theorists' lower bound.

"The measurements do not test string theory directly," Thomas said, noting a few caveats-- the lower bound is derived for high-energy systems, where Einstein's theory of relativity is essential, while the Fermi gas experiments study low-energy gases. If string theorists create new calculations specifically for a Fermi gas, scientists would be able to make precise experimental tests of the theory with equipment no larger than a desktop.

Disclaimer: Views expressed in this article do not necessarily reflect to us.

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Alzheimer's: 'Cleansing' Brain of Plaques

Alzheimer's: 'Cleansing' Brain of Plaques

  8:08:00 PM    Science Lover

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New molecular tools developed at the University of Michigan show promise for "cleansing" the brain of amyloid plaques, implicated in Alzheimer's disease.

Small Molecules for Metal-Amyloid Species in the Brain. 
(Credit: Mi Hee Lim and Joseph J. Braymer)

A hallmark of Alzheimer's disease -- a neurodegenerative disease with no cure -- is the aggregation of protein-like bits known as amyloid-beta peptides into clumps in the brain called plaques. These plaques and their intermediate messes can cause cell death, leading to the disease's devastating symptoms of memory loss and other mental difficulties.

The mechanisms responsible for the formation of these misfolded proteins and their associations with Alzheimer's disease are not entirely understood, but it's thought that copper and zinc ions are somehow involved.

The research, led by assistant professor Mi Hee Lim, was published online Dec. 3 in the Proceedings of the National Academy of Science.
 
In earlier work, Lim and her team developed dual-purpose molecular tools that both grab metal ions and interact with amyloid-beta. The researchers went on to show that in solutions with or without living cells, the molecules were able to regulate copper-induced amyloid-beta aggregation, not only disrupting the formation of clumps, but also breaking up clumps that already had formed.

Building upon that first generation of compounds, Lim and lab members Jung-Suk Choi and Joseph Braymer now report a second generation of compounds that are more stable in biological environments. The researchers tested one of those compounds, described in the PNAS paper, in homogenized brain tissue samples from Alzheimer's disease patients.

"We found that our compound is capable of disassembling the misfolded amyloid clumps to form smaller amyloid pieces, which might be 'cleansed' from the brain more easily, demonstrating a therapeutic application of our compound," said Lim, who has joint appointments in the Life Sciences Institute and the Department of Chemistry. In addition, preliminary tests show that the bi-functional small molecules have a strong potential to cross the blood-brain barrier, the barricade of cells that separates brain tissue from circulating blood, protecting the brain from harmful substances in the bloodstream.

"Crossing this barrier is essential for any treatment like this to be successful," Lim said.

Next steps include more intensive testing of the new compounds for diagnostic and therapeutic properties.

Lim and her team collaborated with Ayyalusamy Ramamoorthy, professor of chemistry and biophysics on this work, with funding from the U-M Horace H. Rackham School of Graduate Studies, the Alzheimer's Art Quilt Initiative, and the National Institutes of Health.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment.

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Brains Wired So We Can Better Hear Ourselves

Brains Wired So We Can Better Hear Ourselves

  8:02:00 PM    Science Lover

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Like the mute button on the TV remote control, our brains filter out unwanted noise so we can focus on what we're listening to. But when it comes to following our own speech, a new brain study from the University of California, Berkeley, shows that instead of one homogenous mute button, we have a network of volume settings that can selectively silence and amplify the sounds we make and hear.

Activity in the auditory cortex when we speak and listen 
is amplified in some regions of the brain and muted in 
others. In this image, the black line represents muting 
activity when we speak. (Credit: Courtesy 
of Adeen Flinker)

Neuroscientists from UC Berkeley, UCSF and Johns Hopkins University tracked the electrical signals emitted from the brains of hospitalized epilepsy patients. They discovered that neurons in one part of the patients' hearing mechanism were dimmed when they talked, while neurons in other parts lit up.

Their findings, published Dec. 8, 2010 in the Journal of Neuroscience, offer new clues about how we hear ourselves above the noise of our surroundings and monitor what we say. Previous studies have shown a selective auditory system in monkeys that can amplify their self-produced mating, food and danger alert calls, but until this latest study, it was not clear how the human auditory system is wired.

"We used to think that the human auditory system is mostly suppressed during speech, but we found closely knit patches of cortex with very different sensitivities to our own speech that paint a more complicated picture," said Adeen Flinker, a doctoral student in neuroscience at UC Berkeley and lead author of the study.

"We found evidence of millions of neurons firing together every time you hear a sound right next to millions of neurons ignoring external sounds but firing together every time you speak," Flinker added. "Such a mosaic of responses could play an important role in how we are able to distinguish our own speech from that of others."

While the study doesn't specifically address why humans need to track their own speech so closely, Flinker theorizes that, among other things, tracking our own speech is important for language development, monitoring what we say and adjusting to various noise environments.

"Whether it's learning a new language or talking to friends in a noisy bar, we need to hear what we say and change our speech dynamically according to our needs and environment," Flinker said.

He noted that people with schizophrenia have trouble distinguishing their own internal voices from the voices of others, suggesting that they may lack this selective auditory mechanism. The findings may be helpful in better understanding some aspects of auditory hallucinations, he said.

Moreover, with the finding of sub-regions of brain cells each tasked with a different volume control job -- and located just a few millimeters apart -- the results pave the way for a more detailed mapping of the auditory cortex to guide brain surgery.

In addition to Flinker, the study's authors are Robert Knight, director of the Helen Wills Neuroscience Institute at UC Berkeley; neurosurgeons Edward Chang, Nicholas Barbaro and neurologist Heidi Kirsch of the University of California, San Francisco; and Nathan Crone, a neurologist at Johns Hopkins University in Maryland.

The auditory cortex is a region of the brain's temporal lobe that deals with sound. In hearing, the human ear converts vibrations into electrical signals that are sent to relay stations in the brain's auditory cortex where they are refined and processed. Language is mostly processed in the left hemisphere of the brain.

In the study, researchers examined the electrical activity in the healthy brain tissue of patients who were being treated for seizures. The patients had volunteered to help out in the experiment during lulls in their treatment, as electrodes had already been implanted over their auditory cortices to track the focal points of their seizures.

Researchers instructed the patients to perform such tasks as repeating words and vowels they heard, and recorded the activity. In comparing the activity of electrical signals discharged during speaking and hearing, they found that some regions of the auditory cortex showed less activity during speech, while others showed the same or higher levels.

"This shows that our brain has a complex sensitivity to our own speech that helps us distinguish between our vocalizations and those of others, and makes sure that what we say is actually what we meant to say," Flinker said.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Science Updates or its staff.

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No Wrong Side To This Bad

No Wrong Side To This Bad

  10:28:00 AM    Science Lover

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US researchers have created a smart hospital bed that is aware of its surrounding. The intelligent bed will make important decisions regarding the patients' healthcare which will involve both improving and saving precious lives.

A prototype of the smart bed that is being tested at the University of New Hampshire could revolutionise health care In the future

John LaCourse, professor at the University of New Hampshire, is currently negotiating with hospital bed manufacturers

to adopt his prograq~.med algorithm, which could become the basis for computerised hospital beds.

These smart hospital beds would communicate with and respond to medical devices that monitor a patient's condition.

"Perhaps a sleeping patient moves, causing a drop in blood pressure. The blood pressure monitor would communicate

this change to the bed and the bed, in turn, would move up or down until the patients' blood pressure is stabilised," he says.

IMPROVED POST-SURGERY CARE

Post-surgical needs may also be met with this bed. "Procedures such as retinal surgery require exact blood pressure levels," says LaCourse. "A smart hospital bed would adjust itself to maintain these levels for patients."

Even quality-of-life conditions such as bed sores could be addressed. "Instead of requiring hospital staff to move the patient, monitors could send signals to the bed to roll the patient to his left or right to avoid bed sores," says LaCourse.

"Microprocessors installed into the bed can also sense respiration patterns to determine when breathing has ceased, the bed moves in such a way that the breathing resumes," said Jonathan Waters, who is working on modifying the bed for sleep apnoea.

PLUG AND PLAY

The ultimate success of LaCourse's project rests with the plug-and-play component. Plug-and-play means that medical devices – everything from blood pressure monitors to breathing machines- "can talk to each other and share patient information which greatly reduces care errors," explains LaCourse.

To realise plug-and-play capability, however, LaCourse's technology must become the industry standard for hospital bed manufacturers. 1n this way, medical devices could seamlessly connect to and exchange patient data.

LaCourse is hopeful that, within two to three years, his technology may be accepted by most if not all hospital bed companies.

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Dark Matter Could Transfer Energy in the Sun

Dark Matter Could Transfer Energy in the Sun

  10:05:00 AM    Science Lover

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Researchers from the Institute for Corpuscular Physics (IFIC) and other European groups have studied the effects of the presence of dark matter in the Sun. According to their calculations, low mass dark matter particles could be transferring energy from the core to the external parts of the Sun, which would affect the quantity of neutrinos that reach Earth.

Scientists believe that the majority of the dark matter 
particles gather together in the centre of the Sun, 
but in their elliptic orbits they also travel to the outer
part, interacting and exchanging with the solar atoms. 
In this way, the WIMPs transport the energy from the 
burning central core to the cooler peripheral
parts. (Credit: Hinode JAXA/NASA/PPARC)

"We assume that the dark matter particles interact weakly with the Sun's atoms, and what we have done is calculate at what level these interactions can occur, in order to better describe the structure and evolution of the Sun," Marco Taoso, researcher at the IFIC, a combined centre of the Spanish National Research Council and the University of Valencia, explains.

The astrophysical observations suggest that our galaxy is situated in a halo of dark matter particles. According to the models, some of these particles, the WIMPs (Weakly Interacting Massive Particles) interact weakly with other normal ones, such as atoms, and could be building up on the inside of stars. The study, recently published in the journal Physical Review D, carries out an in-depth study of the case of the Sun in particular.

"When the WIMPs pass through the Sun they can break up the atoms of our star and lose energy. This prevents them from escaping the gravitational force of the Sun which captures them, and they become trapped, orbiting inside it, with no way of escaping," the researcher points out.

The dark matter cools down the Sun's core

Scientists believe that the majority of the dark matter particles gather together in the centre of the Sun, but in their elliptic orbits they also travel to the outer part, interacting and exchanging with the solar atoms. In this way, the WIMPs transport the energy from the burning central core to the cooler peripheral parts.

"This effect produces a cooling down of the core, the region from where the neutrinos originate due to the nuclear reactions of the Sun," Taoso points out. "And this corresponds to a reduction in the flux of solar neutrinos, since these depend greatly on the temperature of the core."

The neutrinos that reach Earth can be measured by means of different techniques. These data can be used to detect the modifications of the solar temperature caused by the WIMPs. The transport of energy by these particles depends on the likelihood of them interacting with the atoms, and the "size" of these interactions is related to the reduction in the neutrino flux.

"As a result, current data about solar neutrinos can be used to put limits on the extent of the interactions between dark matter and atoms, and using numerical codes we have proved that certain values correspond to a reduction in the flux of solar neutrinos and clash with the measurements," the scientist reveals.

The team has applied their calculations to better understand the effects of low mass dark matter particles (between 4 and 10 gigaelectronvolts). At this level we find models that attempt to explain the results of experiments such as DAMA (beneath an Italian mountain) or CoGent (in a mine in the USA), which look for dark material using "scintillators" or WIMP detectors.

Debate about WIMP and solar composition

This year another study by scientists from Oxford University (United Kingdom) also appeared. It states that WIMPs not only reduce the fluxes of solar neutrinos, but also, furthermore, modify the structure of the Sun and can explain its composition.

"Our calculations, however, show that the modifications of the star's structure are too small to support this claim and that the WIMPs cannot explain the problem of the composition of the sun," Taoso concludes.

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The Future of Metabolic Engineering: Designer Molecules, Cells and Microorganisms

The Future of Metabolic Engineering: Designer Molecules, Cells and Microorganisms

  5:22:00 PM    Science Lover

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Will we one day design and create molecules, cells and microorganisms that produce specific chemical products from simple, readily-available, inexpensive starting materials? Will the synthetic organic chemistry now used to produce pharmaceutical drugs, plastics and a host of other products eventually be surpassed by metabolic engineering as the mainstay of our chemical industries? Yes, according to Jay Keasling, chemical engineer and one of the world's foremost practitioners of metabolic engineering.

Metabolic engineering - the practice of 
altering genes and metabolic pathways 
within a cell or microorganism -- could 
one day be used to mass-produce biofuels, 
pharmaceuticals and other chemical 
products from inexpensive and renewable 
starting materials. (Credit: Flavio Robles, 
Berkeley Lab Public Affairs)

In a paper published in the journal Science Keasling discusses the potential of metabolic engineering -- one of the principal techniques of modern biotechnology -- for the microbial production of many of the chemicals that are currently derived from non-renewable resources or limited natural resources. Examples include, among a great many other possibilities, the replacement of gasoline and other transportation fuels with clean, green and renewable biofuels.

"Continued development of the tools of metabolic engineering will be necessary to expand the range of products that can be produced using biological systems, Keasling says. "However, when more of these tools are available, metabolic engineering should be just as powerful as synthetic organic chemistry, and together the two disciplines can greatly expand the number of chemical products available from renewable resources."

Keasling is the chief executive officer for the Joint BioEnergy Institute, a U.S. Department of Energy (DOE) bioenergy research center. He also holds joint appointments with the Lawrence Berkeley National Laboratory (Berkeley Lab), where he oversees that institute's biosciences research programs, and the University of California (UC), Berkeley, where he serves as director of the Synthetic Biology Engineering Research Center, and is the Hubbard Howe Jr. Distinguished Professor of Biochemical Engineering.

Metabolic engineering is the practice of altering genes and metabolic pathways within a cell or microorganism to increase its production of a specific substance. Keasling led one of the most successful efforts to date in the application of metabolic engineering, when he combined it with synthetic organic chemistry techniques to develop a microbial-based means of producing artemisinin, the most potent of all anti-malaria drugs. He and his research group at JBEI are now applying that same combination to the synthesis of liquid transportation fuels from lignocellulosic biomass. In all cases, the goal is to engineer microbes to perform as much of the chemistry required to produce a desired final product as possible.

"To date, microbial production of natural chemical products has been achieved by transferring product-specific enzymes or entire metabolic pathways from rare or genetically intractable organisms to those that can be readily engineered," Keasling says. "Production of non-natural specialty chemicals, bulk chemicals, and fuels has been enabled by combining enzymes or pathways from different hosts into a single microorganism, and by engineering enzymes to have new function."

These efforts have utilized well-known, industrial microorganisms, but future efforts, he says, may include designer molecules and cells that are tailor-made for the desired chemical and production process.

"In any future, metabolic engineering will soon rival and potentially eclipse synthetic organic chemistry," Keasling says.

Keasling cites the production of active pharmaceutical ingredients as one area where metabolic engineering enjoys a distinct advantage over synthetic organic chemistry. This includes three specific classes of chemicals -- alkaloids, which are primarily derived from plants; polyketides and non-ribosomal peptides, which are produced by various bacteria and fungi; and isoprenoids, which also are typically produced by microbes.

"Many of these natural products are too complex to be chemically synthesized and yet have a value that justifies the cost of developing a genetically engineered microorganism," Keasling says. "The cost of starting materials is generally a small fraction of the complete cost of these products, and relatively little starting material is necessary so availability is not an issue."

Keasling also says that metabolic engineering could provide a valuable alternative means of producing variations of terpenes, the hydrocarbon compounds common to the resins of conifers, in a form that could yield pharmaceuticals that are more effective for the treatment of human disease than the forms that nature has provided.

Perhaps the ripest targets of opportunity for future metabolic engineering efforts are petroleum-based bulk chemical products, including gasoline and other fuels, polymers and solvents. Because such products can be inexpensively catalyzed from petroleum, microbial production has until now been rare, but with fluctuating oil prices, dwindling resources and other considerations, the situation, Keasling says, has changed.

"It is now possible to consider production of these inexpensive bulk chemicals from low-cost starting materials, such as starch, sucrose, or cellulosic biomass with a microbial catalyst," he says. "The key to producing these bulk chemicals in metabolically-engineered cells will be our ability to make the exact molecule needed for existing products rather than something 'similar but green' that will require extensive product testing before it can be used."

In his Science paper, Keasling discusses the formidable roadblocks that stand in the way of a future in which microorganisms and molecules can be tailor-made through metabolic engineering, including the need for "debugging routines" that can find and fix errors in engineered cells. However, he is convinced these roadblocks can and will be overcome.

"One can even envision a day when cell manufacturing is done by different companies, each specializing in certain aspects of the synthesis, with one company constructing the chromosome, one company building the membrane and cell wall bag, and one company filling this bag with the basic molecules needed to boot up the cell."

The Joint BioEnergy Institute (JBEI) is one of three Bioenergy Research Centers funded by the U.S. Department of Energy to advance the development of the next generation of biofuels. It is a scientific partnership led by Berkeley Lab and including the Sandia National Laboratories, the University of California campuses of Berkeley and Davis, the Carnegie Institution for Science, and the Lawrence Livermore National Laboratory.

The Synthetic Biology Engineering Research Center (SynBERC) is a multi-institution partnership, funded by the National Science Foundation, that is aimed at "making biology easier to engineer." The SynBERC partnership is led by UC Berkeley and includes UC San Francisco, Harvard, MIT, Stanford, and Prairie View A&M University.

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Antibacterial Soaps: Being Too Clean Can Make People Sick, Study Suggests

Antibacterial Soaps: Being Too Clean Can Make People Sick, Study Suggests

  9:57:00 AM    Science Lover

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Young people who are overexposed to antibacterial soaps containing triclosan may suffer more allergies, and exposure to higher levels of Bisphenol A among adults may negatively influence the immune system, a new University of Michigan School of Public Health study suggests.

Young people who are overexposed to antibacterial 
soaps containing triclosan may suffer more allergies, and 
exposure to higher levels of Bisphenol A among adults 
may negatively influence the immune system, a new 
University of Michigan School of Public Health study 
suggests. (Credit: iStockphoto/Jorge Salcedo)

Triclosan is a chemical compound widely used in products such as antibacterial soaps, toothpaste, pens, diaper bags and medical devices. Bisphenol A (BPA) is found in many plastics and, for example, as a protective lining in food cans. Both of these chemicals are in a class of environmental toxicants called endocrine-disrupting compounds (EDCs), which are believed to negatively impact human health by mimicking or affecting hormones.

Using data from the 2003-2006 National Health and Nutrition Examination Survey, U-M researchers compared urinary BPA and triclosan with cytomegalovirus (CMV) antibody levels and diagnosis of allergies or hay fever in a sample of U.S. adults and children over age 6. Allergy and hay fever diagnosis and CMV antibodies were used as two separate markers of immune alterations.

"We found that people over age 18 with higher levels of BPA exposure had higher CMV antibody levels, which suggests their cell-mediated immune system may not be functioning properly," said Erin Rees Clayton, research investigator at the U-M School of Public Health and first author on the paper.

Researchers also found that people age 18 and under with higher levels of triclosan were more likely to report diagnosis of allergies and hay fever.

There is growing concern among the scientific community and consumer groups that these EDCs are dangerous to humans at lower levels than previously thought.

"The triclosan findings in the younger age groups may support the 'hygiene hypothesis,' which maintains living in very clean and hygienic environments may impact our exposure to micro-organisms that are beneficial for development of the immune system," said Allison Aiello, associate professor at the U-M School of Public Health and principal investigator on the study.

As an antimicrobial agent found in many household products, triclosan may play a role in changing the micro-organisms to which we are exposed in such a way that our immune system development in childhood is affected.

"It is possible that a person can be too clean for their own good," said Aiello, who is also a visiting associate professor of epidemiology at Harvard.

Previous animal studies indicate that BPA and triclosan may affect the immune system, but this is the first known study to look at exposure to BPA and triclosan as it relates to human immune function, Aiello said.

One surprise finding is that with BPA exposure, age seems to matter, said Rees Clayton. In people 18 or older, higher amounts of BPA were associated with higher CMV levels, but in people younger than 18 the reverse was true.

"This suggests the timing of the exposure to BPA and perhaps the quantity and length of time we are exposed to BPA may be affecting the immune system response," Rees Clayton said.

This is just the first step, she said, but a very important one. Going forward, researchers would like to study the long-term effects of BPA and triclosan in people to see if they can establish a causal relationship.

One limitation of the study is that it measured disease and exposure simultaneously and thus shows only part of the picture, Aiello said.

"It is possible, for example, that individuals who have an allergy are more hygienic because of their condition, and that the relationship we observed is, therefore, not causal or is an example of reverse causation," Aiello said.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment.

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