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Saturday, July 7, 2012

Houdini-Like Vanishing Act in Space


Astronomers report a baffling discovery never seen before: An extraordinary amount of dust around a nearby star has mysteriously disappeared.

Dust today, gone tomorrow. An artist's conceptualization of the dusty TYC 8241 2652 system as it may have appeared several years ago, when it was emitting large amounts of excess infrared radiation.
Dust today, gone tomorrow. An artist's conceptualization 
of the dusty TYC 8241 2652 system as it may have appeared 
several years ago, when it was emitting large amounts of 
excess infrared radiation. (Credit: Gemini Observatory/
AURA artwork by Lynette Cook))
"It's like the classic magician's trick -- now you see it, now you don't," said Carl Melis, a postdoctoral scholar at UC San Diego and lead author of the research. "Only in this case, we're talking about enough dust to fill an inner solar system, and it really is gone!"

"It's as if the rings around Saturn had disappeared," said co-author Benjamin Zuckerman, a UCLA professor of physics and astronomy. "This is even more shocking because the dusty disc of rocky debris was bigger and much more massive than Saturn's rings. The disc around this star, if it were in our solar system, would have extended from the sun halfway out to Earth, near the orbit of Mercury."

The research on this cosmic vanishing act, which occurred around a star some 450 light years from Earth, in the direction of the constellation Centaurus, appears July 5 in the journal Nature.

"A perplexing thing about this discovery is that we don't have a satisfactory explanation to address what happened around this star," said Melis, a former UCLA astronomy graduate student. "The disappearing act appears to be independent of the star itself, as there is no evidence to suggest that the star zapped the dust with some sort of mega-flare or any other violent event."

Melis describes the star, designated TYC 8241 2652, as a "young analog of our sun" that only a few years ago displayed all of the characteristics of "hosting a solar system in the making," before transforming completely. Now, very little of the warm, dusty material thought to originate from collisions of rocky planets is apparent.

"Nothing like this has ever been seen in the many hundreds of stars that astronomers have studied for dust rings," Zuckerman said. "This disappearance is remarkably fast, even on a human time scale, much less an astronomical scale. The dust disappearance at TYC 8241 2652 was so bizarre and so quick, initially I figured that our observations must simply be wrong in some strange way."

Norm Murray, director of the Canadian Institute for Theoretical Astrophysics, who was not part of the research group, said, "The history of astronomy has shown that events that are not predicted and hard to explain can be game-changers."

The dust had been present around the star since at least 1983 (no one had observed the star in the infrared before then), and it continued to glow brightly in the infrared for 25 years. In 2009, it started to dim. By 2010, the dust emission was gone; the astronomers observed the star twice that year from the Gemini Observatory in Chile, six months apart. An infrared image obtained by the Gemini telescope as recently as May 1 of this year confirmed that the warm dust has now been gone for two-and-a-half years.

Like Earth, warm dust absorbs the energy of sunlight and re-radiates that heat energy as infrared radiation.

Because so much dust had been orbiting around the star, planets very likely are forming there, said Zuckerman, whose research is funded by NASA.

The lack of an existing model for what is going on around this star is forcing astronomers to rethink what happens within young solar systems in the making. The dust likely resulted from a violent collision -- but that would not explain where it went. Was it somehow swallowed by the star?

"Although we've identified a couple of mechanisms that are potentially viable, none are really compelling," Melis said. "In one case, gas produced in the impact that released the dust helps to quickly drag the dust particles into the star and thus to their doom. In another possibility, collisions of large rocks left over from an original major impact provide a fresh infusion of dust particles into the disc, which then instigate a runaway process where small grains chip into oblivion both themselves and also larger grains."

Major dusty regions are known to exist in our own solar system and include the asteroid belt between the orbits of Mars and Jupiter and another located beyond the orbit of Neptune. Nearly 30 years ago, NASA's Infrared Astronomical Satellite (IRAS) first discovered many similar regions orbiting other stars -- but no disappearing act like the one at TYC 8241 2652 has ever been seen during these three decades.

The research is based on multiple sets of observations of TYC 8241 2652 obtained with the Thermal-Region Camera Spectrograph on the Gemini South telescope in Chile, the IRAS, NASA's Wide-field Infrared Survey Explorer (WISE) satellite, NASA's Infrared Telescope on Mauna Kea in Hawaii, the Herschel Space Telescope of the European Space Agency (ESA), and AKARI (a Japanese/ESA infrared satellite).

"We were lucky to catch this disappearing act," Zuckerman said. "Such events could be relatively common, without our knowing it."

Co-authors of the Nature paper are Joseph Rhee, a former UCLA postdoctoral scholar in astronomy, who is now an astronomer at California State Polytechnic University in Pomona; Inseok Song, an assistant professor of physics and astronomy at the University of Georgia who also was a postdoctoral researcher at UCLA; and astronomers Simon Murphy and Michael Bessell at the Australian National University.

Thursday, June 14, 2012

Self-Assembling Nanocubes for Lenses


Researchers at the University of California, San Diego Jacobs School of Engineering have developed a technique that enables metallic nanocrystals to self-assemble into larger, complex materials for next-generation antennas and lenses. The metal nanocrystals are cube-shaped and, like bricks or Tetris blocks, spontaneously organize themselves into larger-scale structures with precise orientations relative to one another.

UC San Diego nanoengineers have developed a technique that enables silver nanocubes to self-assemble into larger-scale structures for use in new optical chemical and biological sensors, and optical circuitry. (Credit: Image courtesy of University of California - San Diego)
UC San Diego nanoengineers have developed a 
technique that enables silver nanocubes to 
self-assemble into larger-scale structures for use in 
new optical chemical and biological sensors, and 
optical circuitry. (Credit: Image courtesy of 
University of California - San Diego)

Their findings were published online June 10 in the journal Nature Nanotechnology.

This research is in the new field of nanoplasmonics, where researchers are developing materials that can manipulate light using structures that are smaller than the wavelength of light itself. The nanocubes used in this study were less than 0.1 microns; by comparison, the breadth of a human hair is 100 microns. Precise orientation is necessary so that the cubes can confine light (for a nanoscale antenna) or focus light (for a nanoscale lens) at different wavelengths.

"Our findings could have important implications in developing new optical chemical and biological sensors, where light interacts with molecules, and in optical circuitry, where light can be used to deliver information," said Andrea Tao, a professor in the Department of NanoEngineering at the Jacobs School. Tao collaborated with nanoengineering professor Gaurav Arya and post-doctoral researcher Bo Gao.

To construct objects like antennas and lenses, Tao's team is using chemically synthesized metal nanocrystals. The nanocrystals can be synthesized into different shapes to build these structures; in this study, Tao's team created tiny cubes composed of crystalline silver that can confine light when organized into multi-particle groupings. Confining light into ultra-small volumes could allow optical sensors that are extremely sensitive and that could allow researchers to monitor how a single molecule moves, reacts, and changes with time.

To control how the cubes organize, Tao and her colleagues developed a method to graft polymer chains to the silver cube surfaces that modify how the cubes interact with each other. Normally when objects like cubes stack, they pack side-by-side like Tetris blocks. Using simulations, Tao's team predicted that placing short polymer chains on the cube surface would cause them to stack normally, while placing long polymer chains would cause the cubes to stack edge-to-edge. The approach is simple, robust, and versatile.

In demonstrating their technique, the researchers created macroscopic films of nanocubes with these two different orientations and showed that the films reflected and transmitted different wavelengths of light.

The research was supported by the National Science Foundation, the Hellman Foundation, and Jacobs School of Engineering at UC San Diego.

New Energy Source for Future Medical Implants: Sugar


MIT engineers have developed a fuel cell that runs on the same sugar that powers human cells: glucose. This glucose fuel cell could be used to drive highly efficient brain implants of the future, which could help paralyzed patients move their arms and legs again.

This silicon wafer consists of glucose fuel cells of varying sizes; the largest is 64 by 64 mm. Image: (Credit: Sarpeshkar Lab)
This silicon wafer consists of glucose fuel cells of varying sizes; 
the largest is 64 by 64 mm. Image: (Credit: Sarpeshkar Lab)

The fuel cell, described in the June 12 edition of the journal PLoS ONE, strips electrons from glucose molecules to create a small electric current. The researchers, led by Rahul Sarpeshkar, an associate professor of electrical engineering and computer science at MIT, fabricated the fuel cell on a silicon chip, allowing it to be integrated with other circuits that would be needed for a brain implant.

The idea of a glucose fuel cell is not new: In the 1970s, scientists showed they could power a pacemaker with a glucose fuel cell, but the idea was abandoned in favor of lithium-ion batteries, which could provide significantly more power per unit area than glucose fuel cells. These glucose fuel cells also utilized enzymes that proved to be impractical for long-term implantation in the body, since they eventually ceased to function efficiently.

The new twist to the MIT fuel cell described in PLoS ONE is that it is fabricated from silicon, using the same technology used to make semiconductor electronic chips. The fuel cell has no biological components: It consists of a platinum catalyst that strips electrons from glucose, mimicking the activity of cellular enzymes that break down glucose to generate ATP, the cell's energy currency. (Platinum has a proven record of long-term biocompatibility within the body.) So far, the fuel cell can generate up to hundreds of microwatts -- enough to power an ultra-low-power and clinically useful neural implant.

"It will be a few more years into the future before you see people with spinal-cord injuries receive such implantable systems in the context of standard medical care, but those are the sorts of devices you could envision powering from a glucose-based fuel cell," says Benjamin Rapoport, a former graduate student in the Sarpeshkar lab and the first author on the new MIT study.

Rapoport calculated that in theory, the glucose fuel cell could get all the sugar it needs from the cerebrospinal fluid (CSF) that bathes the brain and protects it from banging into the skull. There are very few cells in the CSF, so it's highly unlikely that an implant located there would provoke an immune response. There is also significant glucose in the CSF, which does not generally get used by the body. Since only a small fraction of the available power is utilized by the glucose fuel cell, the impact on the brain's function would likely be small.

Karim Oweiss, an associate professor of electrical engineering, computer science and neuroscience at Michigan State University, says the work is a good step toward developing implantable medical devices that don't require external power sources.

"It's a proof of concept that they can generate enough power to meet the requirements," says Oweiss, adding that the next step will be to demonstrate that it can work in a living animal.

A team of researchers at Brown University, Massachusetts General Hospital and other institutions recently demonstrated that paralyzed patients could use a brain-machine interface to move a robotic arm; those implants have to be plugged into a wall outlet.

Mimicking biology with microelectronics

Sarpeshkar's group is a leader in the field of ultra-low-power electronics, having pioneered such designs for cochlear implants and brain implants. "The glucose fuel cell, when combined with such ultra-low-power electronics, can enable brain implants or other implants to be completely self-powered," says Sarpeshkar, author of the book "Ultra Low Power Bioelectronics." This book discusses how the combination of ultra-low-power and energy-harvesting design can enable self-powered devices for medical, bio-inspired and portable applications.

Sarpeshkar's group has worked on all aspects of implantable brain-machine interfaces and neural prosthetics, including recording from nerves, stimulating nerves, decoding nerve signals and communicating wirelessly with implants. One such neural prosthetic is designed to record electrical activity from hundreds of neurons in the brain's motor cortex, which is responsible for controlling movement. That data is amplified and converted into a digital signal so that computers -- or in the Sarpeshkar team's work, brain-implanted microchips -- can analyze it and determine which patterns of brain activity produce movement.

The fabrication of the glucose fuel cell was done in collaboration with Jakub Kedzierski at MIT's Lincoln Laboratory. "This collaboration with Lincoln Lab helped make a long-term goal of mine -- to create glucose-powered bioelectronics -- a reality," Sarpeshkar says. Although he has just begun working on bringing ultra-low-power and medical technology to market, he cautions that glucose-powered implantable medical devices are still many years away.

Monday, June 11, 2012

Researchers Watch Tiny Living Machines Self-Assemble


Enabling bioengineers to design new molecular machines for nanotechnology applications is one of the possible outcomes of a study by University of Montreal researchers that was published in Nature Structural and Molecular Biology June 10. The scientists have developed a new approach to visualize how proteins assemble, which may also significantly aid our understanding of diseases such as Alzheimer's and Parkinson's, which are caused by errors in assembly.

Vallée-Bélisle and Michnick have developed a new approach to visualize how proteins assemble, which may also significantly aid our understanding of diseases such as Alzheimer’s and Parkinson’s, which are caused by errors in assembly. Here shown are two different assembly stages (purple and red) of the protein ubiquitin and the fluorescent probe used to visualize these stage (tryptophan: see yellow).
Vallée-Bélisle and Michnick have developed a new 
approach to visualize how proteins assemble, which may 
also significantly aid our understanding of diseases such 
as Alzheimer’s and Parkinson’s, which are caused by errors 
in assembly. Here shown are two different assembly stages 
(purple and red) of the protein ubiquitin and the fluorescent 
probe used to visualize these stage (tryptophan: see yellow).

"In order to survive, all creatures, from bacteria to humans, monitor and transform their environments using small protein nanomachines made of thousands of atoms," explained the senior author of the study, Prof. Stephen Michnick of the university's department of biochemistry. "For example, in our sinuses, there are complex receptor proteins that are activated in the presence of different odor molecules. Some of those scents warn us of danger; others tell us that food is nearby." Proteins are made of long linear chains of amino acids, which have evolved over millions of years to self-assemble extremely rapidly -- often within thousandths of a split second -- into a working nanomachine. "One of the main challenges for biochemists is to understand how these linear chains assemble into their correct structure given an astronomically large number of other possible forms," Michnick said.

"To understand how a protein goes from a linear chain to a unique assembled structure, we need to capture snapshots of its shape at each stage of assembly said Dr. Alexis Vallée-Bélisle, first author of the study. "The problem is that each step exists for a fleetingly short time and no available technique enables us to obtain precise structural information on these states within such a small time frame. We developed a strategy to monitor protein assembly by integrating fluorescent probes throughout the linear protein chain so that we could detect the structure of each stage of protein assembly, step by step to its final structure."

The protein assembly process is not the end of its journey, as a protein can change, through chemical modifications or with age, to take on different forms and functions. "Understanding how a protein goes from being one thing to becoming another is the first step towards understanding and designing protein nanomachines for biotechnologies such as medical and environmental diagnostic sensors, drug synthesis of delivery," Vallée-Bélisle said.

This research was supported by the Natural Sciences and Engineering Research Council of Canada and Le fond de recherché du Québec, Nature et Technologie. The article, "Visualizing transient protein folding intermediates by tryptophan scanning mutagenesis," published in Nature Structural & Molecular Biology, was coauthored by Alexis Vallée-Bélisle and Stephen W. Michnick of the Département de Biochimie de l'Université de Montréal. The University of Montreal is known officially as Université de Montréal.

Saturday, June 9, 2012

Engineered Robot Interacts With Live FishEngineered Robot Interacts With Live Fish


A bioinspired robot has provided the first experimental evidence that live zebrafish can be influenced by engineered robots.

A robotic zebrafish.
A robotic zebrafish. 
(Credit: Image courtesy of Institute of Physics)

Results published 8 June in IOP Publishing's journal Bioinspiration and Biomimetics, provide a stepping stone on the path to using autonomous robots in an open environment to monitor and control fish behaviour.

In the future, water-based robots could potentially contribute to the protection of endangered animals and the control of pest species.

The robot, created by researchers from Polytechnic Institute of New York University and Instituto Superiore di Sanitá, Italy, was 15 centimetres long and spray-painted with the characteristic blue stripes of the zebrafish. The tail of the robot was mechanically controlled by the researchers to mimic the action of the zebrafish itself.

When placed in a 65 litre fish tank, the movements of the robot's tail attracted both individual and shoals of zebrafish; the researchers believe that such capability was influenced by its bioinspired features which were optimised to increase attraction.

For example, the robot was given a rounder shape to mimic a fertile female, which is preferred by both male and female zebrafish, and its colour pattern -- a magnified stripe width and saturated yellow pigment -- emphasized distinctive biologically relevant features.

The robot was in a fixed position in the tank so that the tail movements could be controlled, recorded and, most importantly, associated with the behaviour of the zebrafish.

The fish tank where the experiments took place was divided into one large middle section and two smaller sections at either end, separated by transparent Plexiglas. A total of 16 experiments were performed in which individual, and then shoals of, zebrafish were placed in the middle compartment of the tank and two stimuli were placed at either end behind the Plexiglass.

The combinations of stimuli were: one fish versus an empty space; ten fish versus an empty space; ten fish versus one fish; the robot versus an empty space, and the robot versus one fish.

A camera was placed above the tank to monitor the movements of the zebrafish, and statistical tests were performed to calculate whether the robot acted as an attractive, neutral or aversive stimulus and whether this relationship depends on the fish being isolated or in a shoal.

Although the live zebrafish tended to prefer each other to the robot, when given the choice to spend time next to the robotic fish or an empty space, both the individual fish and shoal of fish preferred the robot. While the noise of the robot's motor was shown to decrease its attraction, the actual beating of the tail emphasized its attractiveness.

The corresponding author, Dr Maurizio Porfiri, said: "These findings provide practical evidence that a species' preference for conspecifics may be used to inspire the design of robots which can actively engage their source of inspiration.

"New studies are currently underway in our lab investigating the interactions between fish and robotic fish when they are free to swim together under controlled and ecologically complex conditions."

Quantum Computers Move Closer to Reality, Thanks to Highly Enriched and Highly Purified Silicon


The quantum computer is a futuristic machine that could operate at speeds even more mind-boggling than the world's fastest super-computers.

SFU physicist Mike Thewalt and grad student Kamyar Saeedi with a sample of highly isotopically enriched silicon - its unique properties could advance quantum computing. (Credit: Image courtesy of Simon Fraser University)
SFU physicist Mike Thewalt and grad student Kamyar 
Saeedi with a sample of highly isotopically enriched silicon - 
its unique properties could advance quantum computing. 
(Credit: Image courtesy of Simon Fraser University)

Research involving physicist Mike Thewalt of Simon Fraser University offers a new step towards making quantum computing a reality, through the unique properties of highly enriched and highly purified silicon.

Quantum computers right now exist pretty much in physicists' concepts, and theoretical research. There are some basic quantum computers in existence, but nobody yet can build a truly practical one -- or really knows how.

Such computers will harness the powers of atoms and sub-atomic particles (ions, photons, electrons) to perform memory and processing tasks, thanks to strange sub-atomic properties.

What Thewalt and colleagues at Oxford University and in Germany have found is that their special silicon allows processes to take place and be observed in a solid state that scientists used to think required a near-perfect vacuum.

And, using this 28Si they have extended to three minutes -- from a matter of seconds -- the time in which scientists can manipulate, observe and measure the processes.

"It's by far a record in solid-state systems," Thewalt says. "If you'd asked people a few years ago if this was possible, they'd have said no. It opens new ways of using solid-state semi-conductors such as silicon as a base for quantum computing.

"You can start to do things that people thought you could only do in a vacuum. What we have found, and what wasn't anticipated, are the sharp spectral lines (optical qualities) in the 28Silicon we have been testing. It's so pure, and so perfect. There's no other material like it."

But the world is still a long way from practical quantum computers, he notes.

Quantum computing is a concept that challenges everything we know or understand about today's computers.

Your desktop or laptop computer processes "bits" of information. The bit is a fundamental unit of information, seen by your computer has having a value of either "1" or "0."

That last paragraph, when written in Word, contains 181 characters including spaces. In your home computer, that simple paragraph is processed as a string of some 1,448 "1"s and "0"s.

But in the quantum computer, the "quantum bit" (also known as a "qubit") can be both a "1" and a "0" -- and all values between 0 and 1 -- at the same time.

Says Thewalt: "A classical 1/0 bit can be thought of as a person being either at the North or South Pole, whereas a qubit can be anywhere on the surface of the globe -- its actual state is described by two parameters similar to latitude and longitude."

Make a practical quantum computer with enough qubits available and it could complete in minutes calculations that would take today's super-computers years, and your laptop perhaps millions of years.

The work by Thewalt and his fellow researchers opens up yet another avenue of research and application that may, in time, lead to practical breakthroughs in quantum computing.

Friday, June 1, 2012

Building Molecular 'Cages' to Fight Disease



UCLA biochemists have designed specialized proteins that assemble themselves to form tiny molecular cages hundreds of times smaller than a single cell. The creation of these miniature structures may be the first step toward developing new methods of drug delivery or even designing artificial vaccines.

This is a molecular cage created by designing specialized protein puzzle pieces. Every color represents a separate protein, where cylindrical segments indicate rigid parts and ribbon-like segments indicate flexible parts of each protein chain. The grey sphere in the protein cage was placed there to indicate the empty space in the middle of the container and is not part of the molecular structure. (Credit: Todd Yeates, Yen-Ting Lai/UCLA Chemistry and Biochemistry)
This is a molecular cage created by designing 
specialized protein puzzle pieces. Every color 
represents a separate protein, where cylindrical 
segments indicate rigid parts and ribbon-like 
segments indicate flexible parts of each protein 
chain. The grey sphere in the protein cage was 
placed there to indicate the empty space in the 
middle of the container and is not part of the 
molecular structure. (Credit: Todd Yeates, Yen-
Ting Lai/UCLA Chemistry and Biochemistry)
"This is the first decisive demonstration of an approach that can be used to combine protein molecules together to create a whole array of nanoscale materials," said Todd Yeates, a UCLA professor of chemistry and biochemistry and a member of the UCLA-DOE Institute of Genomics and Proteomics and the California NanoSystems Institute at UCLA.

Published June 1 in the journal Science, the research could be utilized to create cages from any number of different proteins, with potential applications across the fields of medicine and molecular biology.

UCLA graduate student Yen-Ting Lai, lead author of the study, used computer models to identify two proteins that could be combined to form perfectly shaped three-dimensional puzzle pieces. Twelve of these specialized pieces fit together to create a molecular cage a mere fraction of the size of a virus.

"If you just connect two random proteins together, you expect to get an irregular network," said Yeates, senior author of the study. "In order to control the geometry, the idea was to make a rigid link holding the two proteins in place as if they were parts of a toy puzzle."

The specifically designed proteins intermesh to form a hollow lattice that could act as a vessel for drug delivery, he said.

"In principle, it would be possible to attach a recognition sequence for cancer cells on the outside of the cage, with a toxin or some other 'magic bullet' contained inside," said Yeates. "That way, the drug could be delivered directly to certain targets like tumor cells."

At this stage, the assembled protein cages are porous enough that a drug placed inside would likely leak out during the delivery process, Lai said. His next project will involve constructing a new molecular cage with an interior that will be better sealed.

Another use for the versatile protein structures might be as artificial vaccines. Some traditional vaccines use an inactive surface protein from a virus to trick the body's immune system into thinking it is under attack. This method isn't always effective, because sometimes the protein in question doesn't look enough like the virus to trigger a strong response from the body's defenders.

However, by decorating the surface of a molecular cage with segments of virus-derived proteins, the tiny structures might better mimic a virus, stimulating an immune response even stronger than a traditional vaccine and better protecting the human recipient from illness.

Before these protein structures can be used in medical applications, the molecular containers themselves must be constructed from human-like proteins, rather than the currently employed bacterial proteins that the human body might immediately clear from circulation, Yeates said.

"Our first challenge will be repeating these kinds of designs with molecules that are less likely to generate a host immune response," he said. "Generally, we want to use proteins that look like human proteins so the body does not recognize them as foreign."

The idea of building complex, self-assembled protein structures has been Yeates' ambition since he published a paper outlining preliminary work on this method in 2001. Yet the concept remained on the back burner for 10 years until Yen-Ting Lai joined Yeates' research group. With three master's degrees -- in structural biology, bioinformatics and biomedical engineering -- Lai had the right combination of skills to bring the research to fruition, Yeates said.

This project is federally funded by the National Science Foundation. Other co-authors include UCLA senior staff scientist Duilio Cascio.

A second breakthrough


A second paper co-authored by Yeates creates similarly designed molecular cages using multiple copies of the same protein as building blocks. The scientists control the shape of the cage by computing the sequence of amino acids necessary to link the proteins together at the correct angles. The research, also published May 31 in Science, resulted from a collaboration between the UCLA team and professor David Baker at the University of Washington.

This alternative method represents a more versatile approach because it requires only one type of protein to form a structure, Yeates said. However, devising different kinds of links between the identical proteins remains a major challenge. Lead author Neil King, a postdoctoral scholar at the University of Washington and a former student of Yeates, took the numerous computer-generated possibilities and tested each version experimentally until he found one which produced the right behavior.

This research is federally funded by the National Institutes of Health and the U.S. Department of Energy. Other UCLA co-authors include senior staff researcher Michael Sawaya.

Friday, April 27, 2012

Metabolic Switch for Storing or Burning Fat


From Feast to Famine: A Metabolic Switch That May Help Diabetes Treatment



Humans are built to hunger for fat, packing it on during times of feast
and burning it during periods of famine. But when deluged by foods rich
in fat and sugar, the modern waistline often far exceeds the need to
store energy for lean times, and the result has been an epidemic of
diabetes, heart disease and other obesity-related problems.

The Salk researchers discovered that mice lacking a protein known as fibroblast growth factor 1 (FGF1) were unable to store and use fat normally. When these mice were switched from a high-fat diet to a normal diet, they developed uneven lumps of fat (seen in white in the above image) in their body tissues, suggesting that their fat metabolism mechanisms had gone awry. (Credit: Courtesy of Jae Myoung Suh, research associate, Gene Expression Laboratory)
The Salk researchers discovered that mice lacking a
protein known as fibroblast growth factor 1 (FGF1)
were unable to store and use fat normally. When these
mice were switched from a high-fat diet to a normal diet,
they developed uneven lumps of fat (seen in white in the
above image) in their body tissues, suggesting that their
fat metabolism mechanisms had gone awry. (Credit:
Courtesy of Jae Myoung Suh, research associate, Gene
Expression Laboratory)
Now, scientists at the Salk Institute for Biological Studies have identified the linchpin of fat metabolism, a protein known as fibroblast growth factor 1 (FGF1), which may open new avenues in the treatment of diabetes.

In a paper published April 22 in Nature, the Evans lab reports that FGF1 activity is triggered by a high-fat diet and that mice lacking the protein swiftly develop diabetes. This suggests that FGF1 is crucial to maintaining the body's sensitivity to insulin and normal levels of sugar in the blood.

"Because humans are good at storing fat during times of plenty, we are also excellent at surviving times of famine," says Ronald M. Evans, a professor in Salk's Gene Expression Laboratory and lead author of the paper. "The fat tissues of our body are like batteries, providing us with a steady source of energy when food is scarce. FGF1 governs the expansion and contraction of fat and thus controls the ebb and flow of energy throughout our body."

Obesity rates have soared in the United States in recent decades, with more than one third of U.S. adults and 17 percent of children and adolescents now considered obese, according to the Centers for Disease Control and Prevention.

As the number of overweight people has grown, so too has the incidence of metabolic disease, with nearly 26 million Americans estimated to have obesity-related type 2 diabetes. With annual costs exceeding well over $200 billion, obesity is a chronic disease that is consuming a huge portion of our health care dollars.

Although exercise and calorie restriction are known to be effective at preventing and treating diabetes, the obesity epidemic continues to grow and new drugs to treat the problem are desperately needed. Against this backdrop, the Evans' lab discovery is an important breakthrough -- -- and a surprise.

"The discovery of FGF1 was unexpected -- -- and intriguing -- -- because it was believed to do nothing," says Jae Myoung Suh, a postdoctoral researcher in Evans' laboratory and co-first author on the paper. "If you deplete FGF1 from the body, nothing happens when the mice are fed a steady low fat diet. But when given a high-fat, "Western-style" diet the mice develop an aggressive form of diabetes and experience a system-wide breakdown of their metabolic health."

"These abnormalities cause abdominal or stomach fat to become inflamed," says Michael Downes, a senior staff scientist in Salk's Gene Expression Laboratory and co-lead author on the paper. "This is important because inflamed visceral fat has been linked to heightened risk for diabetes and other obesity-related diseases, such as heart disease and stroke."

The scientists also found that FGF1 is regulated by the antidiabetic drug Actos, which is used to increase the body's sensitivity to insulin. But Actos and related drugs, though helpful, have side effects that limit their use.

Thus, Evans and his colleagues plan to explore whether FGF1 might point to a new way to control diabetes by avoiding the drawbacks of Actos and providing a more natural means of increasing insulin sensitivity.

The research was supported by the National Institutes of Health, the Leona M. and Harry B. Helmsley Charitable Trust and the Howard Hughes Medical Institute.

Friday, April 6, 2012

Scientists Redraw the Blueprint of the Body's Biological Clock



The discovery of a major gear in the biological clock that tells the body when to sleep and metabolize food may lead to new drugs to treat sleep problems and metabolic disorders, including diabetes.

Scientists Redraw the Blueprint of the Body's Biological Clock
The discovery of a major gear in the
biological clock that tells the body when
to sleep and metabolize food may lead
to new drugs to treat sleep problems and
metabolic disorders, including diabetes.
(Credit: © nicobatista / Fotolia)
Scientists at the Salk Institute for Biological Studies, led by Ronald M. Evans, a professor in Salk's Gene Expression Laboratory, showed that two cellular switches found on the nucleus of mouse cells, known as REV-ERBα and REV-ERBβ, are essential for maintaining normal sleeping and eating cycles and for metabolism of nutrients from food.

The findings, reported March 29 in Nature, describe a powerful link between circadian rhythms and metabolism and suggest a new avenue for treating disorders of both systems, including jet lag, sleep disorders, obesity and diabetes.

"This fundamentally changes our knowledge about the workings of the circadian clock and how it orchestrates our sleep-wake cycles, when we eat and even the times our bodies metabolize nutrients," says Evans. "Nuclear receptors can be targeted with drugs, which suggests we might be able to target REV-ERBα and β to treat disorders of sleep and metabolism."

Nurses, emergency personnel and others who work shifts that alter the normal 24-hour cycle of waking and sleeping are at much higher risk for a number of diseases, including metabolic disorders such as diabetes. To address this, scientists are trying to understand precisely how the biological clock works and uncover possible targets for drugs that could adjust the circadian rhythm in people with sleep disorders and circadian-associated metabolic disorders.

In mammals, the circadian timing system is orchestrated by a central clock in the brain and subsidiary clocks in most other organs. The master clock in the brain is set by light and determines the overall diurnal or nocturnal preference of an animal, including sleep-wake cycles and feeding behavior.

Scientists knew that two genes, BMAL1 and CLOCK, worked together at the core of the clock's molecular machinery to activate the network of circadian genes. In this way, BMAL1 acts like the accelerator on a car, activating genes to rev up our physiology each morning so that we are alert, hungry and physically active.

Prior to this work REV-ERBα and β were thought to play only a minor role in these cycles, possibly working together to slow CLOCK-BMAL1 activity to make minor adjustments to keep the clock running on time.

However, genetic studies of two genes with similar functions can be very difficult and thus the real importance of REV-ERBα and β remained mysterious.

The Salk scientists got around this hurdle by developing mice in which both genes could be turned off in the liver at any point by giving them an estrogen derivative called tamoxifen. Now mice could develop normally to adulthood, at which point the scientists could turn off REV-ERBα and REV-ERBβ in their livers -- -- an organ crucial to maintaining the correct balance of sugar and fat in blood -- -- to see what effects it had on circadian rhythms and metabolism.

"When we turned off both receptors, the animal's biological clocks went haywire," says Han Cho, first author on the paper and a postdoctoral researcher in Evan's laboratory. "The mice started running on their exercise wheels when they should have been resting. This suggested REV-ERBα and REV-ERBβ aren't an auxiliary system that makes minor adjustments, but an integral part of the clock's core mechanism. Without them, the clock can't function properly."

Digging more deeply into the clockworks, the Salk scientists mapped out the genes that the REV-ERBs control to keep the body operating on the right schedule, finding that they overlap with hundreds of the same genes controlled by CLOCK and BMAL1. This and other findings suggested that the REV-ERBs, act as a break on the genes BMAL1 activates.

"We thought that the core of the clock was an accelerator, and that all REV-ERBα and REV-ERBβ did was to pull the foot off that pedal," says Evans. "What we've shown is that these receptors act directly as a break to slow clock activity. Now we've got a accelerator and a break, each equally important in creating the daily rhythm of the clock."

The scientists also found that the REV-ERBs control the activity of hundreds of genes involved metabolism, including those responsible for controlling levels of fats and bile. The mice in which REV-ERBα and REV-ERBβ were turned off had high levels of fat and sugar in their blood -- -- common problems in people with metabolic disorders.

"This explains how our cellular metabolism is tied to daylight cycles determined by the movements of the sun and the earth," says Satchidananda Panda, an associate professor in Salk's Regulatory Biology Laboratory and co-author on the paper. "Now we want to find ways of leveraging this mechanism to fix a person's metabolic rhythms when they are disrupted by travel, shift work or sleep disorders."

Other researchers on the study were Xuan Zhao, Megumi Hatori, Ruth T. Yu, Grant D. Barish, Michael T. Lam, Ling-Wa Chong, Luciano DiTacchio, Annette R. Atkins and Michael Downes, from the Salk Institute; Christopher K. Glass, of University of California San Diego; Christopher Liddle, of University of Sydney, Australia; and Johan Auwerx, of Ecole Polytechnique Fédérale, Switzerland.

The research was supported by the National Institutes of Health, the National Health and Medical Research Council of Australia, the Leona M. and Harry B. Helmsley Charitable Trust, the Glenn Foundation for Medical Research and the Howard Hughes Medical Institute.

Wednesday, April 4, 2012

Electricity and Carbon Dioxide Used to Generate Alternative Fuel



Imagine being able to use electricity to power your car -- even if it's not an electric vehicle. Researchers at the UCLA Henry Samueli School of Engineering and Applied Science have for the first time demonstrated a method for converting carbon dioxide into liquid fuel isobutanol using electricity.

Producing fuel from CO2 and sunlight.
Producing fuel from CO2 and sunlight. (Credit: Image
courtesy of University of California - Los Angeles)

Today, electrical energy generated by various methods is still difficult to store efficiently. Chemical batteries, hydraulic pumping and water splitting suffer from low energy-density storage or incompatibility with current transportation infrastructure.

In a study published March 30 in the journal Science, James Liao, UCLA's Ralph M. Parsons Foundation Chair in Chemical Engineering, and his team report a method for storing electrical energy as chemical energy in higher alcohols, which can be used as liquid transportation fuels.

"The current way to store electricity is with lithium ion batteries, in which the density is low, but when you store it in liquid fuel, the density could actually be very high," Liao said. "In addition, we have the potential to use electricity as transportation fuel without needing to change current infrastructure."

Liao and his team genetically engineered a lithoautotrophic microorganism known as Ralstonia eutropha H16 to produce isobutanol and 3-methyl-1-butanol in an electro-bioreactor using carbon dioxide as the sole carbon source and electricity as the sole energy input.

Photosynthesis is the process of converting light energy to chemical energy and storing it in the bonds of sugar. There are two parts to photosynthesis -- a light reaction and a dark reaction. The light reaction converts light energy to chemical energy and must take place in the light. The dark reaction, which converts CO2 to sugar, doesn't directly need light to occur.

"We've been able to separate the light reaction from the dark reaction and instead of using biological photosynthesis, we are using solar panels to convert the sunlight to electrical energy, then to a chemical intermediate, and using that to power carbon dioxide fixation to produce the fuel," Liao said. "This method could be more efficient than the biological system."

Liao explained that with biological systems, the plants used require large areas of agricultural land. However, because Liao's method does not require the light and dark reactions to take place together, solar panels, for example, can be built in the desert or on rooftops.

Theoretically, the hydrogen generated by solar electricity can drive CO2 conversion in lithoautotrophic microorganisms engineered to synthesize high-energy density liquid fuels. But the low solubility, low mass-transfer rate and the safety issues surrounding hydrogen limit the efficiency and scalability of such processes. Instead Liao's team found formic acid to be a favorable substitute and efficient energy carrier.

"Instead of using hydrogen, we use formic acid as the intermediary," Liao said. "We use electricity to generate formic acid and then use the formic acid to power the CO2 fixation in bacteria in the dark to produce isobutanol and higher alcohols."

The electrochemical formate production and the biological CO2 fixation and higher alcohol synthesis now open up the possibility of electricity-driven bioconversion of CO2 to a variety of chemicals. In addition, the transformation of formate into liquid fuel will also play an important role in the biomass refinery process, according to Liao.

"We've demonstrated the principle, and now we think we can scale up," he said. "That's our next step."

The study was funded by a grant from the U.S. Department of Energy's Advanced Research Projects Agency-Energy (ARPA-E).