Scientists Create Cell Assembly Line: New Technology Synthesizes Cellular Structures from Simple Starting Materials

Scientists Create Cell Assembly Line: New Technology Synthesizes Cellular Structures from Simple Starting Materials

  12:29:00 AM    Science Lover

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Borrowing a page from modern manufacturing, scientists from the Florida campus of The Scripps Research Institute have built a microscopic assembly line that mass produces synthetic cell-like compartments.

Artist's rendering of cell structure. 
(Credit: iStockphoto/Sebastian Kaulitzki)

 

The new computer-controlled system represents a technological leap forward in the race to create the complex membrane structures of biological cells from simple chemical starting materials.

"Biology is full of synthetic targets that have inspired chemists for more than a century," said Brian Paegel, Scripps Research assistant professor and lead author of a new study published in the Journal of the American Chemical Society. "The lipid membrane assemblies of cells and their organelles pose a daunting challenge to the chemist who wants to synthesize these structures with the same rational approaches used in the preparation of small molecules."

While most cellular components such as genes or proteins are easily prepared in the laboratory, little has been done to develop a method of synthesizing cell membranes in a uniform, automated way. Current approaches are capricious in nature, yielding complex mixtures of products and inefficient cargo loading into the resultant cell-like structures.

The new technology transforms the previously difficult synthesis of cell membranes into a controlled process, customizable over a range of cell sizes, and highly efficient in terms of cargo encapsulation.

The membrane that surrounds all cells, organelles and vesicles -- small subcellular compartments -- consists of a phospholipid bilayer that serves as a barrier, separating an internal space from the external medium.

The new process creates a laboratory version of this bilayer that is formed into small, cell-sized compartments.

How It Works

"The assembly-line process is simple and, from a chemistry standpoint, mechanistically clear," said Sandro Matosevic, research associate and co-author of the study.

A microfluidic circuit generates water droplets in lipid-containing oil. The lipid-coated droplets travel down one branch of a Y-shaped circuit and merge with a second water stream at the Y-junction. The combined flows of droplets in oil and water travel in parallel streams toward a triangular guidepost.

Then, the triangular guide diverts the lipid-coated droplets into the parallel water stream as a wing dam might divert a line of small boats into another part of a river. As the droplets cross the oil-water interface, a second layer of lipids deposits on the droplet, forming a bilayer.

The end result is a continuous stream of uniformly shaped cell-like compartments.

The newly created vesicles range from 20 to 70 micrometers in diameter -- from about the size of a skin cell to that of a human hair. The entire circuit fits on a glass chip roughly the size of a poker chip.

The researchers also tested the synthetic bilayers for their ability to house a prototypical membrane protein. The proteins correctly inserted into the synthetic membrane, proving that they resemble membranes found in biological cells.

"Membranes and compartmentalization are ubiquitous themes in biology," noted Paegel. "We are constructing these synthetic systems to understand why compartmentalized chemistry is a hallmark of life, and how it might be leveraged in therapeutic delivery."

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New Kinds of Superconductivity? Physicists Demonstrate Coveted 'Spin-Orbit Coupling' in Atomic Gases

New Kinds of Superconductivity? Physicists Demonstrate Coveted 'Spin-Orbit Coupling' in Atomic Gases

  1:14:00 PM    Science Lover

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Physicists at the Joint Quantum Institute (JQI), a collaboration of the National Institute of Standards and Technology (NIST) and the University of Maryland-College Park, have for the first time caused a gas of atoms to exhibit an important quantum phenomenon known as spin-orbit coupling. Their technique opens new possibilities for studying and better understanding fundamental physics and has potential applications to quantum computing, next-generation "spintronics" devices and even "atomtronic" devices built from ultracold atoms.

In an ultracold gas of nearly 200,000 rubidium-87 atoms (shown as the large humps) the atoms can occupy one of two energy levels (represented as red and blue); lasers then link together these levels as a function of the atoms' motion. At first atoms in the red and blue energy states occupy the same region (Phase Mixed), then at higher laser strengths, they separate into different regions (Phase Separated). (Credit: Ian Spielman, JQI/NIST)

 

In the researchers' demonstration of spin-orbit coupling, two lasers allow an atom's motion to flip it between a pair of energy states. The new work, published in Nature, demonstrates this effect for the first time in bosons, which make up one of the two major classes of particles. The same technique could be applied to fermions, the other major class of particles, according to the researchers. The special properties of fermions would make them ideal for studying new kinds of interactions between two particles -- for example those leading to novel "p-wave" superconductivity, which may enable a long-sought form of quantum computing known as topological quantum computation.

In an unexpected development, the team also discovered that the lasers modified how the atoms interacted with each other and caused atoms in one energy state to separate in space from atoms in the other energy state.

One of the most important phenomena in quantum physics, spin-orbit coupling describes the interplay that can occur between a particle's internal properties and its external properties. In atoms, it usually describes interactions that only occur within an atom: how an electron's orbit around an atom's core (nucleus) affects the orientation of the electron's internal bar-magnet-like "spin." In semiconductor materials such as gallium arsenide, spin-orbit coupling is an interaction between an electron's spin and its linear motion in a material.

"Spin-orbit coupling is often a bad thing," said JQI's Ian Spielman, senior author of the paper. "Researchers make 'spintronic' devices out of gallium arsenide, and if you've prepared a spin in some desired orientation, the last thing you'd want it to do is to flip to some other spin when it's moving."

"But from the point of view of fundamental physics, spin-orbit coupling is really interesting," he said. "It's what drives these new kinds of materials called 'topological insulators.'"

One of the hottest topics in physics right now, topological insulators are special materials in which location is everything: the ability of electrons to flow depends on where they are located within the material. Most regions of such a material are insulating, and electric current does not flow freely. But in a flat, two-dimensional topological insulator, current can flow freely along the edge in one direction for one type of spin, and the opposite direction for the opposite kind of spin. In 3-D topological insulators, electrons would flow freely on the surface but be inhibited inside the material. While researchers have been making higher and higher quality versions of this special class of material in solids, spin-orbit coupling in trapped ultracold gases of atoms could help realize topological insulators in their purest, most pristine form, as gases are free of impurity atoms and the other complexities of solid materials.

Usually, atoms do not exhibit the same kind of spin-orbit coupling as electrons exhibit in gallium-arsenide crystals. While each individual atom has its own spin-orbit coupling going on between its internal components (electrons and nucleus), the atom's overall motion generally is not affected by its internal energy state.

But the researchers were able to change that. In their experiment, researchers trapped and cooled a gas of about 200,000 rubidium-87 atoms down to 100 nanokelvins, 3 billion times colder than room temperature. The researchers selected a pair of energy states, analogous to the "spin-up" and "spin-down" states in an electron, from the available atomic energy levels. An atom could occupy either of these "pseudospin" states. Then researchers shined a pair of lasers on the atoms so as to change the relationship between the atom's energy and its momentum (its mass times velocity), and therefore its motion. This created spin-orbit coupling in the atom: the moving atom flipped between its two "spin" states at a rate that depended upon its velocity.

"This demonstrates that the idea of using laser light to create spin-orbit coupling in atoms works. This is all we expected to see," Spielman said. "But something else really neat happened."

They turned up the intensity of their lasers, and atoms of one spin state began to repel the atoms in the other spin state, causing them to separate.

"We changed fundamentally how these atoms interacted with one another," Spielman said. "We hadn't anticipated that and got lucky."

The rubidium atoms in the researchers' experiment were bosons, sociable particles that can all crowd into the same space even if they possess identical values in their properties including spin. But Spielman's calculations show that they could also create this same effect in ultracold gases of fermions. Fermions, the more antisocial type of atoms, cannot occupy the same space when they are in an identical state. And compared to other methods for creating new interactions between fermions, the spin states would be easier to control and longer lived.

A spin-orbit-coupled Fermi gas could interact with itself because the lasers effectively split each atom into two distinct components, each with its own spin state, and two such atoms with different velocities could then interact and pair up with one other. This kind of pairing opens up possibilities, Spielman said, for studying novel forms of superconductivity, particularly "p-wave" superconductivity, in which two paired atoms have a quantum-mechanical phase that depends on their relative orientation. Such p-wave superconductors may enable a form of quantum computing known as topological quantum computation.

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Liver, Not Brain, May Be Origin of Alzheimer’s Plaques

Liver, Not Brain, May Be Origin of Alzheimer’s Plaques

  10:02:00 AM    Science Lover

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Unexpected results from a Scripps Research Institute and ModGene, LLC study could completely alter scientists' ideas about Alzheimer's disease -- pointing to the liver instead of the brain as the source of the "amyloid" that deposits as brain plaques associated with this devastating condition. The findings could offer a relatively simple approach for Alzheimer's prevention and treatment.

New research suggests that the liver instead of the brain 
may be the source of the "amyloid" that deposits as brain 
plaques associated with Alzheimer's disease. 
(Credit: iStockphoto/David Marchal)

 

The study was published online March 3 in The Journal of Neuroscience Research.

In the study, the scientists used a mouse model for Alzheimer's disease to identify genes that influence the amount of amyloid that accumulates in the brain. They found three genes that protected mice from brain amyloid accumulation and deposition. For each gene, lower expression in the liver protected the mouse brain. One of the genes encodes presenilin -- a cell membrane protein believed to contribute to the development of human Alzheimer's.

"This unexpected finding holds promise for the development of new therapies to fight Alzheimer's," said Scripps Research Professor Greg Sutcliffe, who led the study. "This could greatly simplify the challenge of developing therapies and prevention."

An estimated 5.1 million Americans have Alzheimer's disease, including nearly half of people age 85 and older. By 2050, the number of people age 65 and over with this disease will range from 11 million to 16 million unless science finds a way to prevent or effectively treat it. In addition to the human misery caused by the disease, there is the unfathomable cost. A new report from the Alzheimer's Association shows that in the absence of disease-modifying treatments, the cumulative costs of care for people with Alzheimer's from 2010 to 2050 will exceed $20 trillion.

A Genetic Search-and-Find Mission

In trying to help solve the Alzheimer's puzzle, in the past few years Sutcliffe and his collaborators have focused their research on naturally occurring, inherited differences in neurological disease susceptibility among different mouse strains, creating extensive databases cataloging gene activity in different tissues, as measured by mRNA accumulation. These data offer up maps of trait expression that can be superimposed on maps of disease modifier genes.

As is the case with nearly all scientific discovery, Sutcliffe's research builds on previous findings. Several years ago, researchers at Case Western Reserve mapped three genes that modify the accumulation of pathological beta amyloid in the brains of a transgenic mouse model of Alzheimer's disease to large chromosomal regions, each containing hundreds of genes. The Case Western scientists used crosses between the B6 and D2 strains of mice, studying more than 500 progeny.

Using the results from this study, Sutcliffe turned his databases of gene expression to the mouse model of Alzheimer's, looking for differences in gene expression that correlated with differences in disease susceptibility between the B6 and D2 strains. This intensive work involved writing computer programs that identified each genetic difference that distinguished the B6 and D2 genomes, then running mathematical correlation analysis (known as regression analysis) of each difference. Correlations were made between the genotype differences (B6 or D2) and the amount of mRNA product made from each of the more than 25,000 genes in a particular tissue in the 40 recombinant inbred mouse strains. These correlations were repeated 10 times to cover 10 tissues, the liver being one of them.

"A key aspect of this work was learning how to ask questions of massive data sets to glean information about the identities of heritable modifier genes," Sutcliffe said. "This was novel and, in a sense, groundbreaking work: we were inventing a new way to identify modifier genes, putting all of these steps together and automating the process. We realized we could learn about how a transgene's pathogenic effect was being modified without studying the transgenic mice ourselves."

Looking for a Few Good Candidates

Sutcliffe's gene hunt offered up good matches, candidates, for each of the three disease modifier genes discovered by the Case Western scientists, and one of these candidates -- the mouse gene corresponding to a gene known to predispose humans carrying particular variations of it to develop early-onset Alzheimer's disease -- was of special interest to his team.

"The product of that gene, called Presenilin2, is part of an enzyme complex involved in the generation of pathogenic beta amyloid," Sutcliffe explained. "Unexpectedly, heritable expression of Presenilin2 was found in the liver but not in the brain. Higher expression of Presenilin2 in the liver correlated with greater accumulation of beta amyloid in the brain and development of Alzheimer's-like pathology."

This finding suggested that significant concentrations of beta amyloid might originate in the liver, circulate in the blood, and enter the brain. If true, blocking production of beta amyloid in the liver should protect the brain.

To test this hypothesis, Sutcliffe's team set up an in vivo experiment using wild-type mice since they would most closely replicate the natural beta amyloid-producing environment. "We reasoned that if brain amyloid was being born in the liver and transported to the brain by the blood, then that should be the case in all mice," Sutcliffe said, "and one would predict in humans, too."

The mice were administered imatinib (trade name Gleevec, an FDA-approved cancer drug), a relatively new drug currently approved for treatment of chronic myelogenous leukemia and gastrointestinal tumors. The drug potently reduces the production of beta amyloid in neuroblastoma cells transfected by amyloid precursor protein (APP) and also in cell-free extracts prepared from the transfected cells. Importantly, Gleevec has poor penetration of the blood-brain barrier in both mice and humans.

"This characteristic of the drug is precisely why we chose to use it," Sutcliffe explained. "Because it doesn't penetrate the blood-brain barrier, we were able to focus on the production of amyloid outside of the brain and how that production might contribute to amyloid that accumulates in the brain, where it is associated with disease."

The mice were injected with Gleevec twice a day for seven days; then plasma and brain tissue were collected, and the amount of beta amyloid in the blood and brain was measured. The findings: the drug dramatically reduced beta amyloid not only in the blood, but also in the brain where the drug cannot penetrate. Thus, an appreciable portion of brain amyloid must originate outside of the brain, and imatinib represents a candidate for preventing and treating Alzheimer's.

As for the future of this research, Sutcliffe says he hopes to find a partner and investors to move the work into clinical trials and new drug development.

In addition to Sutcliffe, the authors of the study, titled "Peripheral reduction of β-amyloid is sufficient to reduce brain Aβ: implications for Alzheimer's disease," include Peter Hedlund and Elizabeth Thomas of Scripps Research, and Floyd Bloom and Brian Hilbush of ModGene, LLC, which funded the project.

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Parts of Brain Can Switch Functions: In People Born Blind, Brain Regions That Usually Process Vision Can Tackle Language

Parts of Brain Can Switch Functions: In People Born Blind, Brain Regions That Usually Process Vision Can Tackle Language

  9:52:00 AM    Science Lover

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When your brain encounters sensory stimuli, such as the scent of your morning coffee or the sound of a honking car, that input gets shuttled to the appropriate brain region for analysis. The coffee aroma goes to the olfactory cortex, while sounds are processed in the auditory cortex.

MRI scan of brain. (Credit: iStockphoto)

 

That division of labor suggests that the brain's structure follows a predetermined, genetic blueprint. However, evidence is mounting that brain regions can take over functions they were not genetically destined to perform. In a landmark 1996 study of people blinded early in life, neuroscientists showed that the visual cortex could participate in a nonvisual function -- reading Braille.

Now, a study from MIT neuroscientists shows that in individuals born blind, parts of the visual cortex are recruited for language processing. The finding suggests that the visual cortex can dramatically change its function -- from visual processing to language -- and it also appears to overturn the idea that language processing can only occur in highly specialized brain regions that are genetically programmed for language tasks.

"Your brain is not a prepackaged kind of thing. It doesn't develop along a fixed trajectory, rather, it's a self-building toolkit. The building process is profoundly influenced by the experiences you have during your development," says Marina Bedny, an MIT postdoctoral associate in the Department of Brain and Cognitive Sciences and lead author of the study, which appears in the Proceedings of the National Academy of Sciences the week of Feb. 28.

Flexible connections

For more than a century, neuroscientists have known that two specialized brain regions -- called Broca's area and Wernicke's area -- are necessary to produce and understand language, respectively. Those areas are thought to have intrinsic properties, such as specific internal arrangement of cells and connectivity with other brain regions, which make them uniquely suited to process language.

Other functions -- including vision and hearing -- also have distinct processing centers in the sensory cortices. However, there appears to be some flexibility in assigning brain functions. Previous studies in animals (in the laboratory of Mriganka Sur, MIT professor of brain and cognitive sciences) have shown that sensory brain regions can process information from a different sense if input is rewired to them surgically early in life. For example, connecting the eyes to the auditory cortex can provoke that brain region to process images instead of sounds.

Until now, no such evidence existed for flexibility in language processing. Previous studies of congenitally blind people had shown some activity in the left visual cortex of blind subjects during some verbal tasks, such as reading Braille, but no one had shown that this might indicate full-fledged language processing.

Bedny and her colleagues, including senior author Rebecca Saxe, assistant professor of brain and cognitive sciences, and Alvaro Pascual-Leone, professor of neurology at Harvard Medical School, set out to investigate whether visual brain regions in blind people might be involved in more complex language tasks, such as processing sentence structure and analyzing word meanings.

To do that, the researchers scanned blind subjects (using functional magnetic resonance imaging) as they performed a sentence comprehension task. The researchers hypothesized that if the visual cortex was involved in language processing, those brain areas should show the same sensitivity to linguistic information as classic language areas such as Broca's and Wernicke's areas.

They found that was indeed the case -- visual brain regions were sensitive to sentence structure and word meanings in the same way as classic language regions, Bedny says. "The idea that these brain regions could go from vision to language is just crazy," she says. "It suggests that the intrinsic function of a brain area is constrained only loosely, and that experience can have really a big impact on the function of a piece of brain tissue."

Bedny notes that the research does not refute the idea that the human brain needs Broca's and Wernicke's areas for language. "We haven't shown that every possible part of language can be supported by this part of the brain [the visual cortex]. It just suggests that a part of the brain can participate in language processing without having evolved to do so," she says.

Redistribution

One unanswered question is why the visual cortex would be recruited for language processing, when the language processing areas of blind people already function normally. According to Bedny, it may be the result of a natural redistribution of tasks during brain development.

"As these brain functions are getting parceled out, the visual cortex isn't getting its typical function, which is to do vision. And so it enters this competitive game of who's going to do what. The whole developmental dynamic has changed," she says.

This study, combined with other studies of blind people, suggest that different parts of the visual cortex get divvied up for different functions during development, Bedny says. A subset of (left-brain) visual areas appears to be involved in language, including the left primary visual cortex.

It's possible that this redistribution gives blind people an advantage in language processing. The researchers are planning follow-up work in which they will study whether blind people perform better than sighted people in complex language tasks such as parsing complicated sentences or performing language tests while being distracted.

The researchers are also working to pinpoint more precisely the visual cortex's role in language processing, and they are studying blind children to figure out when during development the visual cortex starts processing language.
 

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Atomic Antennas Transmit Quantum Information Across a Microchip

Atomic Antennas Transmit Quantum Information Across a Microchip

  12:48:00 AM    Science Lover

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The Austrian research group led by physicist Rainer Blatt suggests a fundamentally novel architecture for quantum computation. They have experimentally demonstrated quantum antennas, which enable the exchange of quantum information between two separate memory cells located on a computer chip. This offers new opportunities to build practical quantum computers.

Quantum antennae enable the exchange of quantum 
information between two separate memory cells located 
on a computer chip. (Credit: Harald Ritsch)

 

The researchers have published their work in the scientific journal Nature.

Six years ago scientists at the University of Innsbruck realized the first quantum byte -- a quantum computer with eight entangled quantum particles; a record that still stands. "Nevertheless, to make practical use of a quantum computer that performs calculations, we need a lot more quantum bits," says Prof. Rainer Blatt, who, with his research team at the Institute for Experimental Physics, created the first quantum byte in an electromagnetic ion trap. "In these traps we cannot string together large numbers of ions and control them simultaneously."

To solve this problem, the scientists have started to design a quantum computer based on a system of many small registers, which have to be linked. To achieve this, Innsbruck quantum physicists have now developed a revolutionary approach based on a concept formulated by theoretical physicists Ignacio Cirac and Peter Zoller. In their experiment, the physicists electromagnetically coupled two groups of ions over a distance of about 50 micrometers. Here, the motion of the particles serves as an antenna. "The particles oscillate like electrons in the poles of a TV antenna and thereby generate an electromagnetic field," explains Blatt. "If one antenna is tuned to the other one, the receiving end picks up the signal of the sender, which results in coupling." The energy exchange taking place in this process could be the basis for fundamental computing operations of a quantum computer.

Antennas amplify transmission

"We implemented this new concept in a very simple way," explains Rainer Blatt. In a miniaturized ion trap a double-well potential was created, trapping the calcium ions. The two wells were separated by 54 micrometers. "By applying a voltage to the electrodes of the ion trap, we were able to match the oscillation frequencies of the ions," says Blatt.

"This resulted in a coupling process and an energy exchange, which can be used to transmit quantum information." A direct coupling of two mechanical oscillations at the quantum level has never been demonstrated before. In addition, the scientists show that the coupling is amplified by using more ions in each well. "These additional ions function as antennas and increase the distance and speed of the transmission," says Rainer Blatt, who is excited about the new concept. This work constitutes a promising approach for building a fully functioning quantum computer.

"The new technology offers the possibility to distribute entanglement. At the same time, we are able to target each memory cell individually," explains Rainer Blatt. The new quantum computer could be based on a chip with many micro traps, where ions communicate with each other through electromagnetic coupling. This new approach represents an important step towards practical quantum technologies for information processing.

The quantum researchers are supported by the Austrian Science Fund FWF, the European Union, the European Research Council and the Federation of Austrian Industries Tyrol.

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Scientists Steer Car With the Power of Thought

Scientists Steer Car With the Power of Thought

  8:04:00 AM    Science Lover

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You need to keep your thoughts from wandering, if you drive using the new technology from the AutoNOMOS innovation labs of Freie Universität Berlin. The computer scientists have developed a system making it possible to steer a car with your thoughts. Using new commercially available sensors to measure brain waves -- sensors for recording electroencephalograms (EEG) -- the scientists were able to distinguish the bioelectrical wave patterns for control commands such as "left," "right," "accelerate" or "brake" in a test subject.

Computer scientists have developed a system making it 
possible to steer a car with your thoughts. (Credit: Image 
courtesy of Freie Universitaet Berlin)

They then succeeded in developing an interface to connect the sensors to their otherwise purely computer-controlled vehicle, so that it can now be "controlled" via thoughts. Driving by thought control was tested on the site of the former Tempelhof Airport.

The scientists from Freie Universität first used the sensors for measuring brain waves in such a way that a person can move a virtual cube in different directions with the power of his or her thoughts. The test subject thinks of four situations that are associated with driving, for example, "turn left" or "accelerate." In this way the person trained the computer to interpret bioelectrical wave patterns emitted from his or her brain and to link them to a command that could later be used to control the car. The computer scientists connected the measuring device with the steering, accelerator, and brakes of a computer-controlled vehicle, which made it possible for the subject to influence the movement of the car just using his or her thoughts.

"In our test runs, a driver equipped with EEG sensors was able to control the car with no problem -- there was only a slight delay between the envisaged commands and the response of the car," said Prof. Raúl Rojas, who heads the AutoNOMOS project at Freie Universität Berlin. In a second test version, the car drove largely automatically, but via the EEG sensors the driver was able to determine the direction at intersections.

The AutoNOMOS Project at Freie Universität Berlin is studying the technology for the autonomous vehicles of the future. With the EEG experiments they investigate hybrid control approaches, i.e., those in which people work with machines.

The computer scientists have made a short film about their research, which is available at: http://tinyurl.com/BrainDriver

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Male Fertility Is in the Bones: First Evidence That Skeleton Plays a Role in Reproduction

Male Fertility Is in the Bones: First Evidence That Skeleton Plays a Role in Reproduction

  11:19:00 AM    Science Lover

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Researchers at Columbia University Medical Center have discovered that the skeleton acts as a regulator of fertility in male mice through a hormone released by bone, known as osteocalcin.

Researchers have found an altogether unexpected 
connection between a hormone produced in bone and male 
fertility. The study shows that the skeletal hormone known as 
osteocalcin boosts testosterone production to support the 
survival of the germ cells that go on to become mature sperm. 
(Credit: iStockphoto/Max Delson Martins Santos)

 

The research, led by Gerard Karsenty, M.D., Ph.D., chair of the Department of Genetics and Development at Columbia University Medical Center, is slated to appear online on February 17 in Cell, ahead of the journal's print edition, scheduled for March 4.

Until now, interactions between bone and the reproductive system have focused only on the influence of gonads on the build-up of bone mass.

"Since communication between two organs in the body is rarely one-way, the fact that the gonads regulate bone really begs the question: Does bone regulate the gonads?" said Dr. Karsenty.

Dr. Karsenty and his team found their first clue to an answer in the reproductive success of their lab mice. Previously, the researchers had observed that males whose skeletons did not secrete a hormone called osteocalcin were poor breeders.

The investigators then did several experiments that show that osteocalcin enhances the production of testosterone, a sex steroid hormone controlling male fertility. As they added osteocalcin to cells that, when in our body produce testosterone, its synthesis increased. Similarly, when they injected osteocalcin into male mice, circulating levels of testosterone also went up.

Conversely, when osteocalcin is not present, testosterone levels drop, which causes a decline in sperm count, the researchers found. When osteocalcin-deficient male mice were bred with normal female mice, the pairs only produced half the number of litters as did pairs with normal males, along with a decrease in the number of pups per litter.

Though the findings have not yet been confirmed in humans, Dr. Karsenty expects to find similar characteristics in humans, based on other similarities between mouse and human hormones.

If osteocalcin also promotes testosterone production in men, low osteocalcin levels may be the reason why some infertile men have unexplained low levels of testosterone.

Skeleton Regulates Male Fertility, But Not Female

Remarkably, although the new findings stemmed from an observation about estrogen and bone mass, the researchers could not find any evidence that the skeleton influences female reproduction.

Estrogen is considered one of the most powerful hormones that control bone; when ovaries stop producing estrogen in women after menopause, bone mass rapidly declines and can lead to osteoporosis.

Sex hormones, namely estrogen in women and testosterone in men, have been known to affect skeletal growth, but until now, studies of the interaction between bone and the reproductive system have focused only on how sex hormones affect the skeleton.

"We do not know why the skeleton regulates male fertility, and not female. However, if you want to propagate the species, it's probably easier to do this by facilitating the reproductive ability of males," said Dr. Karsenty. "This is the only rationale I can think of to explain why osteocalcin regulates reproduction in male and not in female mice."

Other Novel Functions of Osteocalcin Reported Earlier

The unexpected connection between the skeleton and male fertility is one of a string of surprising findings in the past few years regarding the skeleton. In previous papers, Dr. Karsenty has found that osteocalcin helps control insulin secretion, glucose metabolism and body weight.

"What this work shows is that we know so little physiology, that by asking apparently naïve questions, we can make important discoveries," Dr. Karsenty says. "It also shows that bone exerts an important array of functions all affected during the aging process. As such, these findings suggest that bone is not just a victim of the aging process, but that it may be an active determinant of aging as well."

Next Steps and Potential Drug Development

Next, the researchers plan to determine the signaling pathways used by osteocalcin to enhance testosterone production.

And as for potential drug development, since the researchers have also identified a receptor of osteocalcin, more flexibility in designing a drug that mimics the effect of osteocalcin is expected.

Whether it's for glucose metabolism or fertility, says Dr. Karsenty, knowing the receptor will make it easier for chemists to develop a compound that will bind to it.

"This study expands the physiological repertoire of osteocalcin, and provides the first evidence that the skeleton is a regulator of reproduction," said Dr. Karsenty.

Authors of the Cell study are: Franck Oury, Ph.D. (CUMC); Grzegorz Sumara, Ph.D. (CUMC); Olga Sumara, Ph.D. (CUMC); Mathieu Ferron, Ph.D. (CUMC); Haixin Chang, Ph.D. (Cornell University); Charles E. Smith, Ph.D. (McGill University); Louis Hermo, Ph.D. (McGill University); Susan Suarez, Ph.D. (Cornell University); Bryan L Roth, Ph.D.(UNC-Chapel Hill); Patricia Ducy, Ph.D. (CUMC); and Gerard Karsenty, M.D., Ph.D. (CUMC).

This study was supported in part by the National Institute of Child Health Research (NICHR) and the National Institutes of Health (NIH).

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Wireless Heart Implant Reduces HospitalizationsA pressure-sensing implant helps heart-failure patients stay healthy.

Wireless Heart Implant Reduces HospitalizationsA pressure-sensing implant helps heart-failure patients stay healthy.

  10:29:00 AM    Science Lover

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A wireless sensor developed by Atlanta-based CardioMEMS reduced the number of hospitalizations in patients with heart failure by 39 percent. The tiny implant monitors fluid pressure in the pulmonary artery and transmits the data wirelessly to physicians, who can adjust patients' medications accordingly.

Researchers say the sensor may significantly lower health-care costs and improve quality of life for people with congestive heart failure. The device is one of several prototypes being developed by CardioMEMS and other medical implant companies to provide continuous, personalized wireless monitors for such patients.

Pressure patrol: A new wireless sensor the size of a paper
clip measures fluid pressure in the pulmonary artery. The
metalloops on either end anchor the sensor to the artery
walls, while the self-contained transducer in the middle
takes pressure readings. The sensor is activated by radio
frequency, transmitting data wirelessly to physicians
via modem.Credit: OSU Medical Center/CardioMEMS

"I think the study shows this kind of device is incredibly useful in improving outcomes in patients and directing therapy," says Marc Jay Semigran, medical director of the Mass General Heart Failure and Cardiac Transplant Program, who was not involved in the study.

Hospitals admit 1.1 million adults each year for congestive heart failure, a condition in which pressure builds up in the circulatory system and the heart fails to pump blood adequately to the rest of the body. The American Heart Association estimates that the chronic condition costs the health-care system $29 billion per year. CardioMEMS aims to reduce that figure by providing an accurate way to continuously monitor patients after they've left the hospital.

The device is implanted in the pulmonary artery, an area that carries a low risk of clotting. It is smaller than other implants under development because it does not require a battery or a wire to take pressure readings. Two metal loops hold it to the sides of the artery, and a pressure transducer records the flow of fluids through the blood vessel. The sensor is powered externally by a receiver built into a pillow. When a patient lies on the pillow, the sensor is activated to take measurements and send them wirelessly to a computer, where physicians can review the data. In a large six-month clinical trial published this month in the Lancet, 550 patients from 64 centers across the United States were equipped with the device and instructed to take readings once a day. Patients were divided into two groups. The first took medication instructions from physicians who monitored the sensor data. The second took instructions from physicians who relied on traditional indicators like weight and blood pressure. Over the six months, patients in the first group experienced 39 percent fewer hospitalizations than those in the second.

Today, physicians often assess pulmonary pressure when initially evaluating a patient, but they do so far less frequently in follow-up evaluation. That's because the measurement requires doctors to snake a catheter into a patient's heart and inflate a balloon. However, fluid pressure changes by the day, and monitoring those fluctuations continuously is essential to treating heart failure effectively.

"Over the years, we found that pressures go up long before patients develop symptoms and call a doctor to say they're sick," says Philip Adamson, director of the Heart Failure Institute at Oklahoma Heart Hospital, the principal investigator in the CardioMEMS clinical trial. "By utilizing the pressure sensor information, we're given the ability to make changes in medications long before patients bring themselves to the doctor, and that's how we reduced hospitalizations."

Over the past few years, several companies have jockeyed to be first on the market with a continuous pressure-sensing cardiac implant. In 2007, Medtronic failed to get FDA approval for its sensor, a stopwatch-size, battery-powered implant wired to the heart. The device reduced hospitalizations by 22 percent, but FDA regulators did not consider that worth the risks associated with implanting it. Researchers also found that the wire connecting the sensor to the heart degraded over time.

CardioMEMS is currently seeking approval for its sensor from the U.S. Food and Drug Administration and has submitted results from the clinical study for FDA review. In the next two or three years, the company plans to integrate the sensor's receiver into a patient's cell phone, which will be able to instantly read pressure data and upload it for both physicians and patients to review.

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Next-Generation Electronic Devices: Conduction, Surface States in Topological Insulator Nanoribbons Controlled

Next-Generation Electronic Devices: Conduction, Surface States in Topological Insulator Nanoribbons Controlled

  10:25:00 AM    Science Lover

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In recent years, topological insulators have become one of the hottest topics in physics. These new materials act as both insulators and conductors, with their interior preventing the flow of electrical currents while their edges or surfaces allow the movement of a charge.

Bismuth telluride nanoribbon crystalline structure. 
(Credit: Image courtesy of University 
of California - Los Angeles)

Perhaps most importantly, the surfaces of topological insulators enable the transport of spin-polarized electrons while preventing the "scattering" typically associated with power consumption, in which electrons deviate from their trajectory, resulting in dissipation.

Because of such characteristics, these materials hold great potential for use in future transistors, memory devices and magnetic sensors that are highly energy efficient and require less power.

In a study published Feb. 13 in Nature Nanotechnology, researchers from UCLA's Henry Samueli School of Engineering and Applied Science and from the materials division of Australia's University of Queensland show the promise of surface-conduction channels in topological insulator nanoribbons made of bismuth telluride and demonstrate that surface states in these nanoribbons are "tunable" -- able to be turned on and off depending on the position of the Fermi level.

"Our finding enables a variety of opportunities in building potential new-generation, low-dissipation nanoelectronic and spintronic devices, from magnetic sensing to storage," said Kang L. Wang, the Raytheon Professor of Electrical Engineering at UCLA Engineering, whose team carried out the research.

Bismuth telluride is well known as a thermoelectric material and has also been predicted to be a three-dimensional topological insulator with robust and unique surface states. Recent experiments with bismuth telluride bulk materials have also suggested two-dimensional conduction channels originating from the surface states. But it has been a great challenge to modify surface conduction, because of dominant bulk contribution due to impurities and thermal excitations in such small-band-gap semiconductors.

The development of topological insulator nanoribbons has helped. With their large surface-to-volume ratios, these nanoribbons significantly enhance surface conditions and enable surface manipulation by external means.

Wang and his team used thin bismuth telluride nanoribbons as conducting channels in field-effect transistor structures. These rely on an electric field to control the Fermi level and hence the conductivity of a channel. The researchers were able to demonstrate for the first time the possibility of controlling surface states in topological insulator nanostructures.

"We have demonstrated a clear surface conduction by partially removing the bulk conduction using an external electric field," said Faxian Xiu, a UCLA staff research associate and lead author of the study. "By properly tuning the gate voltage, very high surface conduction was achieved, up to 51 percent, which represents the highest values in topological insulators."

"This research is very exciting because of the possibility to build nanodevices with a novel operating principle," said Wang, who is also associate director of the California NanoSystems Institute (CNSI) at UCLA. "Very similar to the development of graphene, the topological insulators could be made into high-speed transistors and ultra-high-sensitivity sensors."

The new findings shed light on the controllability of the surface spin states in topological insulator nanoribbons and demonstrate significant progress toward high surface electric conditions for practical device applications. The next step for Wang's team is to produce high-speed devices based on their discovery.

"The ideal scenario is to achieve 100 percent surface conduction with a complete insulating state in the bulk," Xiu said. "Based on the current work, we are targeting high-performance transistors with power consumption that is much less than the conventional complementary metal-oxide semiconductors (CMOS) technology used typically in today's electronics."

Study collaborators Jin Zou, a professor of materials engineering at the University of Queensland; Yong Wang, a Queensland International Fellow; and Zou's team at the division of materials at the University of Queensland contributed significantly to this work. A portion of the research was also done in Alexandros Shailos' lab at UCLA.

The study was funded by the Focus Center Research Program -- Center on Functional Engineered Nano Architectonics (FENA) at UCLA Engineering; the U.S. Defense Advanced Research Projects Agency (DARPA); and the Australian Research Council. The research on topological insulators was pioneered by FENA's Shoucheng Zhang, a professor of physics at Stanford University.

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Watch 3D films on cellphone!

Watch 3D films on cellphone!

  1:55:00 AM    Science Lover

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Watching 3D films on your cellphone would now be possible thanks to researchers who have combined the new mobile radio standard LTE-advanced with a video coding technique.

Researchers at the Fraunhofer Institute for Telecommunications, Heinrich-Hertz-Institut, HHI in Berlin, Germany, have come up with a special compression technique for films in especially good high-resolution HD quality.

Watching 3-D films on your cell 
phone would now be possible.

 

It computes the films down to low data rates while maintaining quality: H.264/AVC. What the H.246/AVC video format is to high-definition films, the Multiview Video Coding (MVC) is to 3D films.

Thomas Schierl explained that "MVC is used to pack together the two images needed for the stereoscopic 3D effect to measurably reduce the film's bit rate," and this technique can be used to reduce the size of 3D films as much as 40 per cent.

That means that you can quickly receive excellent quality 3-D films in connection with the new 3G-LTE mobile radio standard. Key is the radio resource management integrated into the LTE system that allows flexible data transmission while including various quality of service classes.

Thomas Wirth, another scientist at the HHI, added, "The 2D and 3D bit streams divided up by MVC can be prioritized for each user at the air interface to support different services, thus opening up a completely new field for business models."

The new technology would be shown at the Mobile World Congress in Barcelona

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