Tuesday, October 5, 2010

AIDS VIRUS LINEAGE MUCH OLDER THAN PREVIOUSLY THOUGHT

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The study results have implications for HIV. The simian immunodeficiency virus, unlike HIV, does not cause AIDS in most of its primate hosts. If it took thousands of years for SIV to evolve into a primarily non-lethal state, it would likely take a very long time for HIV to naturally follow the same trajectory.

An ancestor of HIV that infects monkeys is thousands of years older than previously thought, suggesting that HIV, which causes AIDS, is not likely to stop killing humans anytime soon, finds a study by University of Arizona and Tulane University researchers.

The simian immunodeficiency virus, or SIV, is at least 32,000 to 75,000 years old, and likely much older, according to a genetic analysis of unique SIV strains found in monkeys on Bioko Island, a former peninsula that separated from mainland Africa after the Ice Age more than 10,000 years ago. The research, which appears in the Sept. 17 issue of the journal Science, calls into question previous DNA sequencing data that estimated the virus' age at only a few hundred years.

The study results have implications for HIV. SIV, unlike HIV, does not cause AIDS in most of its primate hosts. If it took thousands of years for SIV to evolve into a primarily non-lethal state, it would likely take a very long time for HIV to naturally follow the same trajectory.

"HIV is the odd man out because, by and large, all the other species of immunodeficiency viruses impose a much lower mortality on their host species," said Michael Worobey, a professor in the UA's department of ecology and evolutionary biology, who led the study in conjunction with virologist Preston Marx of Tulane University.

"So, if SIV entered the picture relatively recently as was previously thought, we would think it achieved a much lower virulence over a short timescale," Worobey said. "But our findings suggest the opposite. If HIV is going to evolve to lower virulence, it is unlikely to happen anytime soon."

The study also raises a question about the origin of HIV, which scientists believe evolved from SIV. If humans have been exposed to SIV-infected monkeys for thousands of years, why did the HIV epidemic only begin in the 20th century?

"Something happened in the 20th century to change this relatively benign monkey virus into something that was much more potent and could start the epidemic. We don't know what that flashpoint was, but there had to be one," Marx said.

Finding these virus strains trapped on Bioko Island settles a long-standing debate, Worobey said.

"It's like finding a fossilized piece of virus evolution," he said. "We now have this little island that is revealing clues about SIV, and it says, ‘It's old.' Now we know that humans were almost certainly exposed to SIV for a long time, probably hundreds of thousands of years."

"Reconstructing the evolutionary past by comparing the genes of these viruses is like looking out onto the ocean," Worobey said. "You can see a long way, but you don't know what lies beyond the horizon. At some point in the past, you don't know what happened. There is a whole lot of ocean out there that you can't get at with the methods that we have been using in trying to tease apart the relationships among these pathogens."

According to Worobey, SIV was distributed across the African continent before Bioko Island separated from the continent about 10,000 years ago.

"When that happened, whatever viruses were circulating at the time became isolated from the virus populations on mainland Africa," he said.

Marx, a virologist at the Tulane National Primate Research Center, tested his theory that SIV had ancient origins by seeking out DNA samples from monkey populations that had been isolated for thousands of years.

His research team collected bush meat samples from Bioko Drills (Mandrillus leucophaeus). The scientists found four different strains of SIV that were highly genetically divergent from those found on the mainland. Worobey then compared DNA sequences of the viruses with the assumption that the island strains evolved in isolation for more than 10,000 years.

The computer modeling showed the rate of mutation to be much slower than previously thought, indicating that the virus is between 32,000 and 75,000 years old. These dates set a new minimum age for SIV, although it is likely to be even older, Marx said.

Worobey said the study has implications for a lot of rapidly evolving pathogens.

"Our methods are great to describe and predict the short-term changes of viruses like the flu or HIV, but we need to be skeptical of inferences in deep time. We found there is a big disconnect between the rapid evolution for which those pathogens are famous and the incredible degree of conservation we've found."

"Being able to study these viruses in an isolated setting is a unique opportunity," he added.

"As far as we know, there is no other place like Bioko Island," Worobey said. "Nowhere else could we do this kind of deep time calibration. Some of the primate species on Bioko only have a few hundred individuals left and might go extinct in the not-too-distant future. We might not have been able to do this research 10 or 20 years from now."

"Looking into the eyes of these animals and knowing they carry the progenitor of HIV in their bodies sends a shiver down my spine."

(Photo: Preston Marx, Tulane University)

University of Arizona

STRESS BEFORE CANCER THERAPY COULD HELP DEADLY CELLS SURVIVE TREATMENT, LEAD TO DISEASE RECURRENCE

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Patients who experience physical or psychological stress – including rigorous exercise – one or two days before a cancer treatment might be unknowingly sabotaging their therapy, new research suggests.

Stress in the body – even physical stress caused by intense exercise – activates a stress-sensitive protein that can spark a series of events that allow cancer cells to survive such treatments as chemotherapy and radiation, according to the research.

Though the study involved a series of experiments in breast cancer cell cultures, the researchers say the findings are a clear indication that cancer cells have found a way to adapt and resist treatment with the help of this stress-inducible protein.

This cancer cell survival can be traced to the presence of heat shock factor-1, which previous research has linked to stress. Ohio State University researchers first noticed that this common protein can help heart tissue survive in a toxic environment, leading the scientists to suspect that in cancer, this phenomenon could have serious consequences.

A series of experiments using breast cancer cells showed that a protein activated by the presence of heat shock factor-1 could block the process that kills cancer cells even after the cells’ DNA was damaged by radiation. The same was true when the cells were subjected to a common chemotherapy drug.

The researchers hope to develop a drug that could suppress heat shock factor-1 as a supplement to cancer therapy, but in the meantime, they recommend that patients avoid both psychological and physical stress in the days leading up to a cancer treatment.

“One of the known inducers of this factor is exercise. I am not against exercise, but the timing is critical. It looks like any intense or prolonged physical activity a couple of days before the start of cancer therapy is highly risky, and has potential to reduce the benefits of the treatment,” said Govindasamy Ilangovan, lead author of the study and associate professor of internal medicine at Ohio State.

The study appears online in the journal Molecular Cancer Research.

Ilangovan, an investigator in Ohio State’s Davis Heart and Lung Research Institute, specializes in cardiovascular medicine. But when he observed in previous research that this stress-inducible protein could salvage heart cells that otherwise were doomed to die, he collaborated with radiology specialists to test the protein’s effects in cancer.

While he used breast cancer cells for this study, he suspects that the widespread presence of heat shock factor-1 in the body means the protein could have this same effect on any kind of adenocarcinoma, a class of cancer cells that originate in a gland.

Heat shock factor-1 activates a specific protein, known as Hsp27, that ends up helping the cancer cells survive, Ilangovan said.

The researchers conducted numerous experiments to observe how Hsp27 behaves in cancer cells after they undergo ultraviolet-C radiation. The radiation is used as a model for treatments designed to kill cancer cells by damaging their DNA. In this study, the stress of the UV radiation itself also induced the heat shock factor and, subsequently, Hsp27, which reduced the cell death.

In every experiment, a heightened presence of the Hsp27 protein was associated with lower levels of other proteins that participate in the process of cell death. When the researchers introduced siRNA, a molecule that interferes with Hsp27’s function, the cell death mechanism was restored.

When the breast cancer cells were treated with doxorubicin, a common chemotherapy drug, the experiment produced similar results. When the Hsp27 protein was silenced, more of the cancer cells died.

“We clearly showed that a reduction in the level of the Hsp27 protein made the cancer cells more susceptible to both treatments,” Ilangovan said.

This finding suggested to the scientists that a drug with the same effects as the interference molecule could stop Hsp27 from preventing cancer cell death. No such drug currently exists, and the siRNA molecule isn’t suitable for use in patients, Ilangovan said.

But the interfering molecule had a significant effect, in one experiment leading to the death of at least 60 percent of the cancer cells that had undergone UV radiation.

Among the key reactions the researchers observed was Hsp27’s relationship to a protein called p21, which allows cells to pause, repair themselves and continue dividing, leading to their survival. Damage to the DNA in cancer cells should disable this step in cell division, but the research showed that the Hsp27 caused p21 to change positions in a way that allowed for cell survival.

“It looks like a compensatory act. We are doing something to kill the cell, but cells have their own compensatory action to oppose that,” Ilangovan said.

After irradiation, the levels of Hsp27 reached their height within 48 hours, suggesting that the protein is highly active in the two days following any stressful event that activates heat shock factor-1.

“The process that sets these activities in motion takes a couple of days,” Ilangovan said. “It is not proven in a clinical setting, but our hypothesis leads us to strongly caution cancer patients about avoiding stress because that stress might trigger recurrence of cancer cell growth.”

(Photo: OSU)

Ohio State University

NANO ANTENNA CONCENTRATES LIGHT

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Everybody who's ever used a TV, radio or cell phone knows what an antenna does: It captures the aerial signals that make those devices practical. A lab at Rice University has built an antenna that captures light in the same way, at a small scale that has big potential.

Condensed matter physicist Doug Natelson and graduate student Dan Ward have found a way to make an optical antenna from two gold tips separated by a nanoscale gap that gathers light from a laser. The tips "grab the light and concentrate it down into a tiny space," Natelson said, leading to a thousand-fold increase in light intensity in the gap.

Getting an accurate measurement of the effect is a first, said Natelson, who reported the results in today's online edition of the journal Nature Nanotechnology. He expects the discovery will be useful in the development of tools for optics and for chemical and biological sensing, even at the single-molecule scale, with implications for industrial safety, defense and homeland security.

The paper by Natelson, Ward and their colleagues in Germany and Spain details the team's technique, which involves shining laser light into the gap between a pair of gold tips less than a nanometer apart – about a hundred-thousandth the width of a human hair.

"You can ignore the fact that your car antenna is built out of atoms; it just works," said Natelson, a Rice professor of physics and astronomy, and also electrical and computer engineering. "But when you have tiny pieces of metal very close to each other, you have to worry about all the details. The fields are going to be big, the situation's going to be complicated and you're really constrained. We've been able to use some physics that only come into play when things are very close together to help figure out what's going on."

The key to measuring light amplification turned out to be measuring something else, specifically the electrical current flowing between the gold tips.

Putting the nanotips so close together allows charge to flow via quantum tunneling as the electrons are pushed from one side to the other. The researchers could get electrons moving by pushing them at low frequencies with a voltage, in a highly controllable, measurable way. They could also get them flowing by shining the laser, which pushes the charge at the very high frequency of the light. Being able to compare the two processes set a standard by which the light amplification could be determined, Natelson said. Their German and Spanish coauthors helped supply the necessary theoretical justification for the analysis.

The amplification is a plasmonic effect, Natelson said. Plasmons, which may be excited by light, are oscillating electrons in metallic structures that act like ripples in a pool. "You've got a metal structure, you shine light on it, the light makes the electrons in this metal structure slosh around," he said. "You can think of the electrons in the metal as an incompressible fluid, like water in a bathtub. And when you get them sloshing back and forth, you get electric fields.

"At the surfaces of the metal, these fields can be very big – much bigger than those from the original radiation," he said. "What was hard to measure was just how big. We didn't know how much the two sides were sloshing up and down – and that's exactly the thing we care about."

By simultaneously measuring the low-frequency electrically driven and the high-frequency optically driven currents between the tips, "we can figure out the voltage zinging back and forth at the really high frequencies that are characteristic of light," he said.

Natelson said his lab's homebuilt apparatus, which combines nanoscale electronics and optics, is fairly unusual. "There are a lot of people who do optics. There are a lot who do nanoscale electrical measurements," he said. "There are still not too many people who combine the two."

The custom rig gave the Rice researchers a measure of control over thermal and electrical properties that have stymied other investigators. The tips are cooled to 80 Kelvin, about -315 degrees Fahrenheit, and are electrically insulated from their silicon bases, keeping at bay stray voltages that could skew the results.

"The reason we're studying these enhanced fields is not just because they're there," Natelson said. "If you can enhance the local field by a factor of 1,000, there are lots of things you can do in terms of sensors and non-linear optics. Anything that gives you a handle on what's happening at these tiny scales is very useful.

"This is one of those rare, happy cases where you are able to actually get information – very local information – about exactly something you care about."

Rice University

ROBOTS COULD IMPROVE EVERYDAY LIFE AT HOME OR WORK

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They're mundane, yet daunting tasks: Tidying a messy room. Assembling a bookshelf from a kit of parts. Fetching a hairbrush for someone who can't do it herself. What if a robot could do it for you?

Assistant professor of computer science Ashutosh Saxena is working to bring such robots into homes and offices. He leads Cornell's Personal Robotics Lab, which develops software for complex, high-level robotics. Among the lab's goals are programming robots that can clean up a disheveled room, assemble an Ikea bookshelf and load and unload a dishwasher -- all without human intervention.

Saxena, who joined the Cornell faculty in 2009, believes robots can make people's lives better and more productive.

"Just like people buy a car, I envision that in five to 10 years, people will buy an assistive robot that will be cheaper or about the same cost as a car," Saxena said.

One of the biggest technical challenges is endowing robots with the ability to learn in uncertain environments. It's one thing to make a robot do simple tasks: Pick up this pen. Move to the left. Do a 360. It's quite another to make a robot understand how to pick up an object it's never encountered or navigate a room it's never seen.

Saxena, who led the manipulation group in the STAIR project (Stanford Artificial Intelligence Robot) at Stanford University, has researched how to make robots perceive information in cluttered and unknown environments. His work has also enabled robots to estimate depth from a single image.

"For example, if you look at a new object, how would you pick it up? If you are in a new environment, how do you figure out how far away things are?" he said.

On a typical afternoon in Upson Hall's Personal Robotics Lab, Saxena and his students can be found huddled around a computer perfecting the coding to make their robots come alive.

One of their research platforms is a robotic arm with a gripper. Using a camera, the robot evaluates an object -- say, a cup or plate -- and figures out how best to grab it. This technology will eventually integrate into the full-fledged dishwasher-loading robot.

Graduate student Yun Jiang has worked on a fast, efficient algorithm to make the robotic arm identify what she calls "grasping points," or the parts of an object that would be best to grab onto. Her main contribution has been to simultaneously find both the location and orientation of the arm when it is picking up an object.

Writing such programs involves finding the balance between the specific features of an object -- from the stem of a wine glass to the handle of a brush -- and the general geometric patterns that can serve as guidelines for the robot to identify.

"Although the objects may differ in appearance, they should share some common grasping patterns, and those patterns have some features that we are looking for," Jiang said. Writing an algorithm that can identify generalized features and apply them to a wide variety of objects is a difficult challenge, Saxena added.

Another set of students works on a roving robot with a camera. Its job is to find an object, such as a shoe, by systematically scanning the room.

"In a cluttered room, it is notoriously difficult for today's object detection algorithms to reliably find an object as simple as a shoe," Saxena said.

The key is to not look at this task in isolation, he explained. If the three-dimensional structure of the room is known, it becomes easier to find the objects. The lab is building learning algorithms to enable roboticists to quickly combine several perception algorithms into a more reliable one.

Graduate students Congcong Li and Adarsh Kowdle presented these projects at the European Conference on Computer Vision, held in Greece Sept. 5-11. They will present again at the Neural Information Processing Systems conference in Vancouver this December.

Saxena sees the robots one day making a critical difference in people's lives -- for example, among the elderly or people with disabilities, who need help for everyday things. But robotics could also make people's lives easier in general.

"There are so many people who just want to get household chores done," he said.

(Photo: Yale U.)

Cornell University

UT SOUTHWESTERN PLASTIC SURGEONS OFFER LATEST FAT-BUSTING LASER TARGETING STUBBORN INCHES

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Stephanie Martinez had one of the most universal desires – to shed a few stubborn inches from her waist, hips and thighs – without harsh diets, needles or other surgical interventions that require staying at home and taking time off from work.

So she agreed to help UT Southwestern Medical Center plastic surgeons evaluate Zerona, a new type of body-contouring laser that moves effortlessly across the outer skin, disrupting fat cells so they flush out of the body naturally.

After lying on her back for 20 minutes, then on her stomach for another 20 minutes while an array of light waved over her waist, hips and thighs, Ms. Martinez, 36, was able to walk out of the room and immediately return to work. Compared to traditional liposuction, Zerona requires no incisions, and there are no burning aftereffects, as with other types of lasers.

“There was really no downside. You can do it during your lunch hour,” she said. “It didn‘t hurt or anything. That’s what I loved about it. There’s no invasive surgery or poking or injecting. You just lie there and relax.”

The laser, just approved by the Food and Drug Administration to be both safe and effective for noninvasive body slimming, can be used on the waist, hips and thighs and may also work for other applications, such as male breast reduction or neck and arm flab. The procedure requires six, 40-minute sessions over a two-week period.

“Zerona is really for helping you fit into your clothes,” said Dr. Jeffrey Kenkel, vice chairman of plastic surgery and director of the Clinical Center for Cosmetic Laser Treatment at UT Southwestern.

Zerona does not supplant traditional liposuction for those needing a more significant contour change, so good candidates need to be close to their ideal body weight and have good skin quality to see good results, he said.

“I lost inches on both thighs and on my hips – about 2½ inches on my hips. My stomach area is my real problem area, and I lost nearly 3 inches,” Ms Martinez said.

The low-level lasers cause fat cells to lose the fat, Dr. Kenkel explained. The body then disposes of it naturally through absorption or excretion.

“We’re a clearinghouse for technology, and we’ve been excited by the data from Zerona,” said Dr. Kenkel, whose research focuses on laser treatments.

The lasers have been used for many years for managing joint pain. Already-released data from a previous study on Zerona reported that patients lost an average of 3.64 inches from their waist, hips and thighs combined. By comparison, the control group lost an average of 1/2 inch.

“To ensure you’re spending your money wisely to get the results you want, every patient should be evaluated by a physician first, and you should consult a board-certified plastic surgeon rather than just heading down to the closest spa,” said Dr. Kenkel, who is also chief of plastic surgery at the Dallas Veterans Affairs Medical Center.

“Just having the latest technology won’t guarantee you see the transformation you envisioned. As plastic surgeons on the cutting edge of technology, we can really give an objective assessment about what all the options are.”

(Photo: UT Southwestern)

The University of Texas Southwestern

PARTING THE WATERS: COMPUTER MODELING APPLIES PHYSICS TO RED SEA ESCAPE ROUTE

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The biblical account of the parting of the Red Sea has inspired and mystified people for millennia. A new computer modeling study by researchers at the National Center for Atmospheric Research (NCAR) and the University of Colorado at Boulder (CU) shows how the movement of wind as described in the book of Exodus could have parted the waters.

The computer simulations show that a strong east wind, blowing overnight, could have pushed water back at a bend where an ancient river is believed to have merged with a coastal lagoon along the Mediterranean Sea. With the water pushed back into both waterways, a land bridge would have opened at the bend, enabling people to walk across exposed mud flats to safety. As soon as the wind died down, the waters would have rushed back in.

The study is intended to present a possible scenario of events that are said to have taken place more than 3,000 years ago, although experts are uncertain whether they actually occurred. The research was based on a reconstruction of the likely locations and depths of Nile delta waterways, which have shifted considerably over time.

“The simulations match fairly closely with the account in Exodus,” says Carl Drews of NCAR, the lead author. “The parting of the waters can be understood through fluid dynamics. The wind moves the water in a way that’s in accordance with physical laws, creating a safe passage with water on two sides and then abruptly allowing the water to rush back in.”

The study is part of a larger research project by Drews into the impacts of winds on water depths, including the extent to which Pacific Ocean typhoons can drive storm surges. By pinpointing a possible site south of the Mediterranean Sea for the crossing, the study also could be of benefit to experts seeking to research whether such an event ever took place. Archeologists and Egyptologists have found little direct evidence to substantiate many of the events described in Exodus.

The work, published in the online journal, PLoS ONE, arose out of Drews’ master’s thesis in atmospheric and oceanic sciences at CU. The computing time and other resources were supported by the National Science Foundation.

The Exodus account describes Moses and the fleeing Israelites trapped between the Pharaoh's advancing chariots and a body of water that has been variously translated as the Red Sea or the Sea of Reeds. In a divine miracle, the account continues, a mighty east wind blows all night, splitting the waters and leaving a passage of dry land with walls of water on both sides. The Israelites are able to flee to the other shore. But when the Pharaoh's army attempts to pursue them in the morning, the waters rush back and drown the soldiers.

Scientists from time to time have tried to study whether the parting of the waters, one of the famous miracles in the Bible, can also be understood through natural processes. Some have speculated about a tsunami, which would have caused waters to retreat and advance rapidly. But such an event would not have caused the gradual overnight divide of the waters as described in the Bible, nor would it necessarily have been associated with winds.

Other researchers have focused on a phenomenon known as “wind setdown,” in which a particularly strong and persistent wind can lower water levels in one area while piling up water downwind. Wind setdowns, which are the opposite of storm surges, have been widely documented, including an event in the Nile delta in the 19th century when a powerful wind pushed away about five feet of water and exposed dry land.

A previous computer modeling study into the Red Sea crossing by a pair of Russian researchers, Naum Voltzinger and Alexei Androsov, found that winds blowing from the northwest at minimal hurricane force (74 miles per hour) could, in theory, have exposed an underwater reef near the modern-day Suez Canal. This would have enabled people to walk across. The Russian study built on earlier work by oceanographers Doron Nof of Florida State University and Nathan Paldor of Hebrew University of Jerusalem that looked at the possible role of wind setdown.

The new study, by Drews and CU oceanographer Weiqing Han, found that a reef would have had to be entirely flat for the water to drain off in 12 hours. A more realistic reef with lower and deeper sections would have retained channels that would have been difficult to wade through. In addition, Drews and Han were skeptical that refugees could have crossed during nearly hurricane-force winds.

Studying maps of the ancient topography of the Nile delta, the researchers found an alternative site for the crossing about 75 miles north of the Suez reef and just south of the Mediterranean Sea. Although there are uncertainties about the waterways of the time, some oceanographers believe that an ancient branch of the Nile River flowed into a coastal lagoon then known as the Lake of Tanis. The two waterways would have come together to form a U-shaped curve.

An extensive analysis of archeological records, satellite measurements, and current-day maps enabled the research team to estimate the water flow and depth that may have existed 3,000 years ago. Drews and Han then used a specialized ocean computer model to simulate the impact of an overnight wind at that site.

They found that a wind of 63 miles an hour, lasting for 12 hours, would have pushed back waters estimated to be six feet deep. This would have exposed mud flats for four hours, creating a dry passage about 2 to 2.5 miles long and 3 miles wide. The water would be pushed back into both the lake and the channel of the river, creating barriers of water on both sides of newly exposed mud flats.

As soon as the winds stopped, the waters would come rushing back, much like a tidal bore. Anyone still on the mud flats would be at risk of drowning.

The set of 14 computer model simulations also showed that dry land could have been exposed in two nearby sites during a windstorm from the east. However, those sites contained only a single body of water and the wind would have pushed the water to one side rather than creating a dry passage through two areas of water.

“People have always been fascinated by this Exodus story, wondering if it comes from historical facts,” Drews says. “What this study shows is that the description of the waters parting indeed has a basis in physical laws."

(Photo: Nicolle Rager Fuller)

National Center for Atmospheric Research (NCAR)

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