Doctors Grow Parkinsonian Human Brain Cells In Vitro, Shedding Light on the Genetics of the Disease

By Rebecca Boyle

Parkinson's Disease in the Brain The brownish area is a Lewy body, an abnormal protein chunk that develops inside brain cells in Parkinson's disease. Wikipedia

For the first time, Parkinson’s researchers have made human brain cells derived from the skin cells of patients who carry a mutated gene related to Parkinson’s disease. This means researchers can now track exactly how this mutation, in a gene called parkin, causes the disease in about 10 percent of Parkinson’s patients.

This is a major breakthrough because it will allow researchers to study brain cells affected by Parkinson’s in real time. Animals that do not have this gene cannot readily develop Parkinson’s-like symptoms, so researchers must use human neurons, but it’s generally difficult if not impossible to get live human brain cells to study.

Instead, Jian Feng and colleagues at the State University of New York-Buffalo took skin cells from four patients, including two healthy patients and two patients carrying the Parkin mutation. They induced the skin cells to become pluripotent stem cells, and then differentiated them into neurons — specifically, mid-brain neurons that create dopamine, called dopaminergic neurons. The loss of these neurons, which are the brain’s primary source of dopamine, causes Parkinson’s symptoms like loss of motor control.

The parkin gene indirectly harms those neurons. Here’s how it works: parkin regulates the production of an enzyme, monamine oxidase, which in turn keeps dopamine at bay. Parkin mutations do not control this MAO, and the MAO essentially runs amok, causing harm to the dopamine-producing neurons.

The Parkin gene mutation was present in the donors’ DNA, so the lab-created brain cells had the same traits that the patients’ real brain cells would have. This allowed the researchers to watch the gene mutation at work.

The neurons showed all the signs of MAO-related stress and a drop in dopamine uptake. But here’s the interesting part — when the researchers injected the normal version of Parkin, they could reverse the defects.

So this research is useful for two reasons — the cells themselves could be used to better study Parkinson’s disease itself, and they could also help screen new drugs or gene therapies that could be used to treat Parkinson’s disease, the researchers say.

The paper was published Tuesday in Nature Communications.

Attacks on Android Devices Intensify

COMMUNICATIONS

Rising security incidents and poorly defended phones suggest 2012 could be a risky year for smart-phone users.

• BY DAVID TALBOT

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A recent rise in Android malware—combined with increased efforts to combat the threat—highlight the fact that, just like tech companies, app makers, and users, hackers are fast turning their attention to mobile devices. What's more, experts say, such devices are often configured in ways that make it easier for malware to thrive.

Several new types of Android malware have been spotted "in the wild" in recent weeks, and they demonstrate growing sophistication. One specimen, dubbed Opfake, is a bogus Web browser that automatically makes calls to premium phone lines. Opfake exhibits a powerful trick previously seen only in desktop malware, whereby the code repeatedly mutates to make anti-virus detection more difficult.

To counter the rising tide of threats, Google last week announced it had launched an app prescreening tool called Bouncer that runs a server-based simulation to check apps for malicious behavior—such as attempts to access or send personal data, or simply send out pricey text messages. Google blocks them before they get into the official Android Market. 

Bouncer has been used quietly for several months; in the second half of 2011, the Android market saw a 40 percent decrease in malware apps identified as potentially malicious, compared to the first half of the year, wrote Hiroshi Lockheimer, Google's Android engineering vice president, in a blog post.

In a similar move, the mobile security firmLookout says it is testing new methods for Android users that quarantine and scan downloaded apps. Whereas many existing tools screen the phone for already installed malware, a new tool would allow users to delay installation of a downloaded app until a check was complete. "For many users who install apps outside of Android Market, there is a need for pre-installation detection," says Derek Halliday, senior security manager at Lookout.

Lookout found, at the end of 2011, that 4 percent of Android users were likely to encounter malware over the course of the year—up from 1 percent of users a year ago, though part of the increase may be a function of improved detection, Halliday says.

Android is the most popular smart-phone operating system in the world, with 52.5 percent of the global market at the end of 2011, according to Gartner.

Don’t click it: The app button at bottom left—which arrived with a free game from a Chinese Android marketplace— steals data if clicked. Roughly translated, the Chinese characters mean “system setting shortcut.”
Xuxian Jiang

Google and Lookout's moves are a reaction to the relatively recent trend of malware writers intensively focusing on the official Android Market, and not just third-party app-dealing sites. "Since the vast majority of users rely on the official Android Market, it's understandable that there's increased focus there. At the same time, there are all kinds of other places where users can potentially acquire malware," says Halliday.

Meanwhile, new research is finding that Android phones themselves are often vulnerable out of the box. At the Network and Distributed System Security Symposium in San Diego this week, one research paper painted a bleak picture, reporting that many major brands come with factory settings that amount to a preweakened immune system, with various settings fixed to allow apps to access personal data, such as GPS position or stored contacts.

Xuxian Jiang, a computer scientist at North Carolina State University, said that his group studied eight mass-market phones—the HTC Legend, Evo 4G and Wildfire S, the Motorola Droid and Droid X, the Samsung Epic 4G, and the Google Nexus One and Nexus 4S.  All but the two Google phones came out of the box with permissions pregranted for apps to access data that isn't needed for those apps to function, undercutting a pillar of Android's permission-based security model. The researchers say they have notified the phone makers about the findings.     

 "There is a trend where malware is going to grow, and is going to evolve," Jiang says. "Google's Bouncer will be helpful to move in the right direction, but more work needs to be done to contain the malware growth." And part of that should include making phones more conservative in what they allow apps to do by default, he adds. The effort also requires more and better screening tools; his group is working on one tool called Droid Ranger.

Permissive factory settings on phones are no accident, says Radu Sion, a computer scientist and security researcher at Stony Brook University. The hotly competitive commercial landscape rewards makers of devices that are easiest for average consumers to use. "The usability of devices becomes more and more important. Most vendors will err on the side of usability—then they will sell more."

But creating an easy plug-and-play experience means not making the user individually authorize various data releases—which makes the devices more vulnerable to malware.  

So far, the malware problem has been an annoyance rather than a major threat, but the pieces are in place for the situation to grow worse quickly, Sion says: "Android is not going to be safe anytime soon until we have some high-profile attacks. Right now, the malware is not a huge problem. Guys in Ukraine have not zoomed in on Android yet, but it's very easy to come in there. It's going to become a big problem."

Charge Your Phone (and Your Car) from Afar

Over the air: Witricity’s CEO Eric Giler holds a light that is powered remotely by the pad behind it.
Witricity

Charging systems that send power farther through the air will soon be on sale.

• BY KEVIN BULLIS

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Eric Giler points a remote control at a small black pad leaned up against a wall, and three lamps instantly light up and a tablet computer starts charging. The funny thing is, the devices all sit several feet away from the black pad, which provides power, and aren't plugged in.

Giler is the CEO of Witricity, a startup that hopes to revolutionize electronics by replacing wireless charging systems with ones that send power safely through the air. The nearly five-year-old company uses technology developed at MIT that extends the range of inductive wireless charging.

Witricity says its first products—for charging portable electronics—could be on the market later this year. Within a year or two, similar technology could allow electric-vehicle owners to charge their cars without plugging them in. This could be followed by wireless power for heart pumps and other medical implants.

The idea of wireless power transfer is hardly new. Nikola Tesla demonstrated a version of it a hundred years ago, and inductive chargers for electric toothbrushes and video game controllers are now widespread. But the inductive chargers available today work over only very short distances and require physical contact between the charger and electronic device, which isn't much more convenient than plugging a device in.

Inductive charging systems work by passing a current through a coil to generate a magnetic field, which creates another electric current in a similarly sized and oriented coil in the other device. Move these coils apart, and the efficiency of energy transfer drops off quickly. To increase the distance at which the power is transferred efficiently, Witricity tunes the sending and receiving coils to resonate with each other at a specific frequency with very little energy loss within each resonator.

The distance that power can be transferred in this way depends on the size of the coils. If both the sending and receiving coils are small, as may be the case with a system for mobile phones, the charger and the phone need to be placed within several centimeters to charge efficiently. But Witricity has also shown prototypes with larger coils that can send power at distances of about a meter. (Power can also be beamed with lasers and microwaves, but this requires a direct line of sight and can raise safety concerns.)

Park and charge: These pads transmit power wirelessly from the floor of a garage to the bottom of a car.
Witricity

It's also possible to boost the signal with coils called repeaters. In the demonstration Giler gave, coils installed under carpet squares allow power to leapfrog from a wall outlet to anywhere in the room.

Witricity is one of a handful of companies working to extend the range of electric chargers.  The company has developed a prototype table that charges devices placed anywhere on its surface—even if they remain inside a backpack or purse—and a wireless keyboard and mouse that can be powered from a computer monitor, eliminating the need for batteries. (Apple has patented a similar idea.) The company has also developed a charger for electric cars. It's a half-meter-wide pad that sits on the floor of a garage—just drive over it, and the car starts to charge.

Witricity is partnering with several companies to bring the technology to market. It has a multimillion-dollar contract with Toyota to develop charging for battery-powered vehicles (soon it might not make sense to call them plug-in electric vehicles), and has also announced a partnership with Taiwanese electronics manufacturer Mediatek to develop products for charging portable electronics.

Katie Hall, Witricity's chief technology officer, says the company is working on components that will add the necessary electronics to a portable device. It's also working to make charging sleeves for mobile phones that are no larger than the covers people typically use to protect their phones. The company isn't certain how much these will cost, but Hall says the system for charging cars wouldn't cost much more to make than the chargers that electric-vehicle owners often install in their garages anyway.

Several other companies are developing inductive chargers that can send power efficiently through the air. Siemens and BMW are developing chargers for electric cars, and Qualcomm recently bought a startup that had developed its own wireless electric-car chargers. A company called Fulton Technologies has technology that sends wireless power through a few centimeters of marble, as well as from the floor of a garage to an electric vehicle.

A handful of researchers are even working to extend the concept to allow charging of electric vehicles while they are out on the road. Researchers at Oak Ridge and Stanford recently developed detailed concepts for such a system. In a $2.7 million federally funded project, researchers at Utah State University are installing a system to charge buses as they stop along a route in Salt Lake City.

In the Oak Ridge model, 200 coils would be embedded in a section of the roadway and controlled by a single roadside device; successive coils would be energized as electric vehicles pass over them, providing enough power for the vehicle to reach the next series of coils a mile down the road.

John Miller, a research scientist at Oak Ridge, estimates that each series of coils plus the controller would cost less than a million dollars. "Wireless chargers for electric vehicles are so convenient. You don't have to mess with plug cables. You don't care what the weather is. You don't even have to think about it. I think it's going to catch on superfast," Miller says.

How the Zebra Got Its Stripes

Zebra. If there was a 'Just So' story for how the zebra got its stripes, I'm sure that Rudyard Kipling would have come up with an amusing and entertaining camouflage explanation. But would he have come up with the explanation that Gábor Horváth and colleagues from Hungary and Sweden have: that zebra's stripes stave off blood-sucking insects? (Credit: © davy liger / Fotolia)

Science Daily  — If there was a 'Just So' story for how the zebra got its stripes, I'm sure that Rudyard Kipling would have come up with an amusing and entertaining camouflage explanation. But would he have come up with the explanation that Gábor Horváth and colleagues from Hungary and Sweden have: that zebra's stripes stave off blood-sucking insects?

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The team publishes their discovery that zebra stripes is the least attractive hide pattern for voracious horsefiles in the Journal of Experimental Biology athttp://jeb.biologists.org/.

Horseflies (tabanids) deliver nasty bites, carry disease and distract grazing animals from feeding. According to Horváth, these insects are attracted to horizontally polarized light because reflections from water are horizontally polarized and aquatic insects use this phenomenon to identify stretches of water where they can mate and lay eggs. However, blood-sucking female tabanids are also guided to victims by linearly polarized light reflected from their hides. Explaining that horseflies are more attracted to dark horses than to white horses, the team also points out that developing zebra embryos start out with a dark skin, but go on to develop white stripes before birth. The team wondered whether the zebra's stripy hide might have evolved to disrupt their attractive dark skins and make them less appealing to voracious bloodsuckers, such as tabanids.

Travelling to a horsefly-infested horse farm near Budapest, the team tested how attractive these blood-sucking insects found black and white striped patterns by varying the width, density and angle of the stripes and the direction of polarization of the light that they reflected. Trapping attracted insects with oil and glue, the team found that the patterns attracted fewer flies as the stripes became narrower, with the narrowest stripes attracting the fewest tabanids.

The team then tested the attractiveness of white, dark and striped horse models. Suspecting that the striped horse would attract an intermediate number of flies between the white and dark models, the team was surprised to find that the striped model was the least attractive of all.

Finally, when the team measured the stripe widths and polarization patterns of light reflected from real zebra hides, they found that the zebra's pattern correlated well with the patterns that were least attractive to horseflies.

"We conclude that zebras have evolved a coat pattern in which the stripes are narrow enough to ensure minimum attractiveness to tabanid flies," says the team and they add, "The selection pressure for striped coat patterns as a response to blood-sucking dipteran parasites is probably high in this region [Africa]."

New avenue for treating colon cancer

 by Biomechanism 

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An international research team led by cell biologists at the University of California, Riverside has uncovered a new insight into colon cancer, the third leading cause of cancer-related deaths in the United States. The research provides potential new avenues for diagnosing and treating the disease.

Led by Frances Sladek at UC Riverside and Graham Robertson at the University of Sydney, Australia, the team analyzed about 450 human colon cancer specimens and found that in nearly 80 percent of them the variants of a gene, HNF4A, are out of balance.

Human beings express several variants of the HNF4A gene, classified as P1 and P2 variants. Some tissues, like liver, have just one type of variant but the colon has both P1 and P2 variants. The P1 variant is found in the nuclei of cells in the normal colon but in the human colon cancer samples this variant is frequently either absent or located outside of the nucleus and, presumably, no longer functional.

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Using human colon cancer cell lines and in vitro assays, the researchers found that the imbalance observed in the human tumor tissues seemed to be the result of a complex, multi-step process by an enzyme, Src kinase. Src kinase has been known to be activated in colon cancer but, until now, it was not known to act on the HNF4a protein (HNF4A is the gene, a stretch of DNA; HNF4a is the protein encoded by HNF4A). The UCR group found that activated Src modifies the P1 but not the P2 variant. The net result is loss of the P1 variant in the nuclei of cells in the colon.

Study results appeared online last week in the Proceedings of the National Academy of Sciences.

“Loss of nuclear P1 HNF4a protein in the colon may be an early sign of colon cancer,” explained Sladek, a professor of cell biology and toxicologist. “A healthy colon has a good but delicate balance of the two HNF4a variants. If you could prevent the loss of the P1 variant via drugs, you might be able to maintain a normal colon and prevent colon cancer.”

The researchers found another factor that increases a person’s susceptibility to the disease: certain “single nucleotide polymorphisms” or SNPs located in the HNF4A gene. An SNP is a DNA sequence variation — a minor change in the genomic sequence that accounts for the variations we see between individuals. SNPs are the most common type of genetic variation among people.

Karthikeyani Chellappa (left) is a postdoctoral researcher in the lab of Frances Sladek, a professor of cell biology and toxicologist at UC Riverside. Photo credit: UCR Strategic Communications.

“Individuals with certain SNPs may be more susceptible to colon cancer,” said Karthikeyani Chellappa, a postdoctoral researcher in Sladek’s lab and the first author of the research paper. “That’s because these SNPs result in a greater amount of modification and a faster degradation of HNF4a by Src, at least in cell-based assays. It still needs to be investigated, though, whether individuals carrying these SNPs are indeed more susceptible to colon cancer.”

Sladek noted that drugs are already available for inhibiting the activity of Src kinase.

“Some of these drugs are in clinical trials for colon cancer,” she said. “It would be exciting to determine whether these drugs can maintain the P1 HNF4a protein levels, as well as inhibit the Src kinase activity.”

A multifactorial disease influenced by genetics and the environment, colon cancer starts as a small polyp in the large intestine (colon) or the rectum (end of the colon). While most of the polyps are benign, some do turn cancerous. With proper screening, the disease can be detected early, when it is most curable.

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The research was supported in part by a National Institutes of Health grant to Sladek.

Courtesy University of California, Riverside (http://www.ucr.edu) 

Climate speeds up microbial change

THE UNIVERSITY OF WAIKATO

Climate change in Antarctica’s Dry Valleys may affect the area more rapidly than previously expected. Image: sandwich_girl, Flickr CC-licensed An international team of Antarctic researchers think climate change in Antarctica’s Dry Valleys may affect the area more rapidly than previously expected. The scientists, led by Professor Craig Cary at the University of Waikato, have been studying ecosystems in the region for many years and have found that microbial communities in the soil undergo rapid and lasting changes in response to contemporary environmental conditions. The results of their investigation have been published this week in Nature Communications, an international online science journal. Biological Changes “We used to think that changes in microbial change took place slowly over centuries,” says Professor Cary, “but the research we’ve been doing indicates that the bacteria living in the soil are inherently sensitive to climate variability - minor temperature variations could lead to cascading changes in hydrology and biogeochemical cycling and could dramatically affect ecosystem function.” Professor Cary says a recent climate change report for Antarctica predicts the continent may experience more changes as the ozone hole begins to close over the next 50 years. “It’s important we keep documenting the current biodiversity in Antarctica so we can better predict the effects of climate change.” The research was supported through grants from the New Zealand Foundation for Research Science and Technology, Antarctica New Zealand and the National Science Foundation. The scientists measured the rate at which observed biological changes occurred beneath a seal carcass and at a nearby control site. They found that under the carcass the soil environment changed by stabilising temperatures, elevating relative humidity and reducing ultraviolet exposure. They then had to find out how quickly these changes occurred. Using Seal Carcasses To do this they transferred a 250-year-old carcass to an untouched site and used community DNA fingerprinting and new sequencing techniques to track the changes in microbial composition and structure. It took only two years for major changes to occur during the five year study. Professor Cary says Polar systems are particularly susceptible to climate change and this study will provide a foundation for future observations on the fate of life in these extreme environments. Editor's Note: Original news release can be found here.

New power source found

RMIT UNIVERSITY

The researchers learned that a nanotube is an excellent conductor of heat from burning fuel. Image: 3dts/iStockphoto Researchers at the Massachusetts Institute of Technology (MIT) and RMIT University have made a breakthrough in energy storage and power generation. The power generated relative to the energy source size is three to four times greater than what is currently possible with the best lithium-ion batteries. While on sabbatical from RMIT in 2009 and 2010, Associate Professor Dr Kourosh Kalantar-zadeh, from the School of Electrical and Computer Engineering, joined MIT Associate Professor Michael Strano's nanotechnology research group. The team was working on measuring the acceleration of a chemical reaction along a nanotube when they discovered that the reaction generated power. Now the two researchers are using their combined expertise in chemistry and nanomaterials to explore this phenomenon. Their work titled Nanodynamite: Fuel-coated nanotubes could provide bursts of power to the smallest systems is in the December IEEE Spectrum Magazine, the publication of the IEEE, the world's largest professional technology association. Associate Professor Kalantar-zadeh said that his experimental system, based on one of the materials that have come from nanotechnology — carbon nanotubes — generates power, something researchers had not seen before. “By coating a nanotube in nitrocellulose fuel and igniting one end, we set off a combustion wave along it and learned that a nanotube is an excellent conductor of heat from burning fuel. Even better, the combustion wave creates a strong electric current,” he said. “Our discovery that a thermopower wave works best across these tubes because of their dual conductivity turns conventional thermoelectricity on its head. “It's the first viable nanoscale approach to power generation that exploits the thermoelectric effect by overcoming the feasibility issues associated with minimising dimensions. “But there are multiple angles to explore when it comes to taming these exotic waves and, ultimately, finding out if they're the wave of the future.” Editor's Note: Original news release can be found here.