Male Semen Makes HIV More Potent

Male Semen Makes HIV More Potent

Component peptide ferries virus into mucosal cells, ratcheting up infectivity as much as 100,000 times 

 
HIV FERRY: Scientists have discovered that a protein fragment found in human semen increases the infectiousness of the HIV virus.

More than 80 percent of human immunodeficiency virus (HIV) infections are transmitted via sexual intercourse. And researchers may have discovered at least one reason why. According to a new study published in Cell, a component of human semen may facilitate the spread of the virus by targeting immune system cells, in some cases making the pathogen up to 100,000 times more virulent.

The team of German scientists had initially set out to determine if semen contained factors that inhibit the HIV infection. "We were not expecting to find an enhancer, and we were even more surprised about the strength," says report co-author Frank Kirchhoff, a virologist at the University of Ulm Clinic in Germany. "Most enhancers have maybe a two- or three-fold effect, but here the effect was amazing—more than 50-fold and, under certain conditions, more than 100,000-fold."

HIV, the virus that leads to AIDS, has infected 60 million people worldwide (causing 25 million deaths) since it was discovered in humans in 1981. The transmission rate from intravaginal sexual intercourse is estimated at one in every 200 to 2,000 acts. In Africa, 60 percent of new infections are in women who have had sex with HIV-positive men.

Kirchhoff and his team screened through many of the 900 proteins found in seminal fluid in their hunt for potential inhibitors and enhancers of HIV transmission. Among the enhancing factors uncovered were fragments of a protein called prostatic acid phosphatase that is secreted by the prostate gland. An analysis of the peptide's structure in semen indicated that it hooked up with similar fragments to create amyloid fibers (clusters of protein fragments that have also been implicated in diseases such as Alzheimer's). The scientists refer to the amyloid fibers as "semen-derived enhancer of virus infection" (SEVI). If they do not link to become fibers, the researchers report, the peptide segments remain inactive and do not enhance viral transmission.

When assembled, however, these fibers then act like ferries, trapping and shuttling HIV virus particles to target cells. The researchers found that HIV spiked into semen was more successful than the virus alone at infecting T cells and macrophages (immune system cells that are believed to be the infection's initial targets in the body). They also tested the threshold of virus needed to infect human tonsil cells, noting that in the presence of semen, far fewer HIV particles were needed for transmission.

Researchers injected both the naked virus and SEVI-treated HIV into the tails of rats that had been given human immune system cells. The HIV with the semen component was five times more effective at transmitting the virus. In situations where low levels of virus are transferred—as during intercourse—Kirchhoff says, SEVI can make HIV up to 100,000 times more likely to spread when compared with the virus alone.

In an editorial accompanying the article, postdoctoral fellow Nadia Roan, along with Warner Greene, a senior investigator at the University of California, San Francisco's Gladstone Institute of Virology and Immunology, wrote: "If SEVI truly increases the real world heterosexual spread of HIV by several orders of magnitude, then negating the activity of this factor could conceivably diminish these frequencies to levels that might virtually eliminate semen-driven HIV transmission."

But, others say more work is needed to fully comprehend the role of prostatic acid phosphatase in viral transmission. "I don't think you can really make any interpretation of that experiment other than it makes the virus more infectious if it reaches target cells … which is very difficult across mucosal surfaces," says Robin Shattock, a professor of cellular and molecular infection at St George's, University of London. The sentiment is echoed by Myron Cohen, an epidemiologist at the Center for Infectious Diseases at the University of North Carolina School of Medicine in Chapel Hill: "We need to understand every detail about the biology of HIV transmission…; the [next] logical experiments are to demonstrate in rhesus macaque models that this is playing a role in transmission."

Selection Spurred Recent Evolution, Researchers Say

Selection Spurred Recent Evolution, Researchers Say

Researchers analyzing variation in the human genome have concluded that human evolution accelerated enormously in the last 40,000 years under the force of natural selection.

A Speedier Timeline

The finding contradicts a widely held assumption that human evolution came to a halt 10,000 years ago or even 50,000 years ago. Some evolutionary psychologists, for example, assume that the mind has not evolved since the Ice Age ended 10,000 years ago.

But other experts expressed reservations about the new report, saying it is interesting but more work needs to be done.

The new survey — led by Robert K. Moyzis of the University of California, Irvine, and Henry C. Harpending of the University of Utah — developed a method of spotting human genes that have become more common through being favored by natural selection. They say that some 7 percent of human genes bear the signature of natural selection.

By dating the time that each of the genes came under selection, they have found that the rate of human evolution was fairly steady until about 50,000 years ago and then accelerated up until 10,000 years ago, they report in the current issue of The Proceedings of the National Academy of Sciences. The high rate of selection has probably continued to the present day, Dr. Moyzis said, but current data are not adequate to pick up recent selection.

The brisk rate of human selection occurred for two reasons, Dr. Moyzis’ team says. One was that the population started to grow, first in Africa and then in the rest of the world after the first modern humans left Africa. The larger size of the population meant that there were more mutations for natural selection to work on. The second reason for the accelerated evolution was that the expanding human populations in Africa and Eurasia were encountering climates and diseases to which they had to adapt genetically. The extra mutations in their growing populations allowed them to do so.

Dr. Moyzis said it was widely assumed that once people developed culture, they protected themselves from the environment and from the forces of natural selection. But people also had to adapt to the environments that their culture created, and the new analysis shows that evolution continued even faster than before.

The researchers took their data from the HapMap project, a survey designed by the National Institutes of Health to look at sites of common variation in the human genome and to help identify the genes responsible for common diseases. The HapMap data, generated by analyzing the genomes of people from Africa, East Asia and Europe, has also been a trove for people studying human evolutionary history.

David Reich, a population geneticist at the Harvard Medical School, said the new report was “a very interesting and exciting hypothesis” but that the authors had not ruled out other explanations of the data. The power of their test for selected genes falls off in looking both at more ancient and more recent events, he said, so the overall picture might not be correct.

Similar reservations were expressed by Jonathan Pritchard, a population geneticist at the University of Chicago.

“My feeling is that they haven’t been cautious enough,” he said. “This paper will probably stimulate others to study this question.”

Trashed Tech: Where Do Old Cell Phones, TVs and PCs Go to Die?

Trashed Tech: Where Do Old Cell Phones, TVs and PCs Go to Die?

Electronic waste is reaching critical mass, releasing toxic chemicals into the environment. The solution? Recycling and toxin-free electrical components

With the holiday season officially upon us, the hunt is on for the hottest cell phones, flat-screen plasma TVs and video game systems. This seasonal new tech surge will no doubt please gadget lovers, but it will also result in a heap of old electronic devices being dumped into a waste stream already awash in refuse laden with cadmium, lead, mercury and other toxins.

A projected increase in toxic trash—such as analog television sets expected to become obsolete by the end of 2009—has government agencies and environmental watchdogs pushing for recycling options and the use of environment-friendly components in new devices. Still, it's a message that consumers and device manufacturers have yet to take to heart even as more products flood the market.

The electronics industry generates about $2 billion in U.S. sales annually, according to a report ("Management of Electronic Waste in the United States") released by the Environmental Protection Agency (EPA) in April. The Consumer Electronics Association, an Arlington, Va.–based trade group says that Americans owned some three billion electronic devices in 2005, the latest year for which data is available, despite tossing or recycling about 304 million electronic devices that same year. About two thirds of the discarded devices were still functioning, upping the danger that they would crack during transport or when crushed by garbage trucks, tossed into landfills or incinerated (more of an issue in developing countries), thereby releasing toxic chemicals into the environment.

Two years ago, the U.S. generated an astonishing 2.6 million tons of electronic waste, which is 1.4 percent of the country's total waste stream. Only 12.6 percent of this so-called "e-waste" was recycled. Worse, e-waste is growing faster than any other type of trash the EPA regulates, including medical and industrial waste. Unwanted cell phones, televisions, PCs (including desktops, laptops, portables and computer monitors), computer peripherals (including printers, scanners and fax machines), computer mouses and keyboards amounted to more than 1.9 million tons of solid municipal waste in the U.S.; of that, more than 1.5 million tons were dumped primarily into landfills, whereas the rest was recycled, the EPA says.

A projected increase in sales will add to the growing e-junk pile. The EPA estimates that roughly 283 million PCs will be sold in 2008, up from 255 million this year. And these new computers are pushing the old models out the door at a rapid pace: U.S. residential and business users scrap about 133,000 PCs daily. Cell phones are also quickly becoming part of the waste stream. More than one billion mobile phones shipped worldwide in 2006, according to Framingham, Mass.–based technology research firm IDC—22.5 percent more than the 832.8 million units shipped a year earlier. By 2008, the United Nations Environment Programme (the U.N.'s environmental arm) projects that the number of cell phone users around the world will climb to two billion. Meanwhile, 130 million of these devices are thrown out annually.

Televisions and monitors are another major cause of concern, primarily because the Federal Communications Commission (FCC) plans to auction off the analog part of the television spectrum in 2009. "This means people will have to get analog-to-digital converter boxes for their TVs, or they'll be putting their old TVs out by the curb," says Lloyd Hicks, waste prevention program advisor at INFORM, Inc., an environmental research organization in New York City. "We need to have recycling plans in place before then."

Just to give you an idea of Americans' love affair with TV: they purchased 2.5 million new TV sets just to watch the 2007 Super Bowl, up from 1.7 million the previous January, says the National Retail Federation, based in Washington, D.C. The flurry of new flat-screen LCD and plasma televisions has raised concern about toxins used in their production as well as what will happen to the televisions being replaced. "We've really struggled with understanding what TV makers are doing about take-back," says Alexandra McPherson, project director for Clean Production Action (CPA), a Spring Brook, N.Y., nonprofit that promotes the use of products free of poisonous materials.

The EPA acknowledges that toxins in electronics are a problem, but says there's no need to panic–at least, not yet. "We all feel that it is not an environmental crisis," says Clare Lindsay, project director for the EPA Office of Solid Waste's extended product responsibility program. "The presence of some toxic materials does not create a crisis. We believe that landfills can safely manage most of these waste products. Is it the best idea? No, the better way is recycling. But we haven't seen any contamination of ground water associated with electronics discarded in landfills."

She says there has been "enormous progress'' over the past five years in raising consumer awareness about the benefits of recycling over simply junking unwanted electronics. Manufacturers are also beginning to understand that if they avoid using toxic materials, their products will be much easier to recycle or trash.

"Arguably, the responsibility for recycling is more at the front end of the manufacturing process than at the back-end disposal," Lindsay says. "Everyone recognizes that reusing, refurbishing and upgrading older electronics is better for the environment. Recycling is better than simply throwing something out, but reselling and refurbishing is even better."

One of the biggest problems with used computers, though, is that it is often cheaper to buy a new one with the latest software and technology than to refurbish an aging machine.

Less than 20 percent of electronic devices discarded between 2003 and 2005 were sent to recycling facilities; the rest were dumped and mostly ended up in landfills. In 2005 about 61 percent (107,500 tons) of cathode-ray tube (CRT) monitors and televisions collected for recycling were exported outside the U.S. for remanufacture or refurbishment, the EPA says. That same year, about 24,000 tons of CRT glass—which is filled with lead to protect viewers from the x-rays produced by the monitor—was sold to markets abroad to replace damaged CRTs in various countries, and North American waste and recycling companies recovered about 10,000 tons of lead (meaning it was not placed into landfills or incinerated).

An added benefit of recycling electronic materials—be they copper, lead or silicon—is that we will not have to mine as much from the earth, says Bob Dellinger, the EPA Office of Solid Waste's director of hazardous waste identification. "In essence, recycling stretches the raw materials we have available," he says. A lot of energy is wasted in the mining and refining of raw materials. For example, only 4 percent of copper ore is usable, the rest is waste.

The EPA is trying to promote the purchase of green products through a number of initiatives, including its epeat.net Web site, which lists manufacturers that have agreed to reduce the amount of toxic materials used in their products. This has had some influence, Lindsay says, because whether domestic or foreign, manufacturers want to have a good reputation in this country. Another program is Plug-In, which encourages manufacturers and retailers to take back used electronics so that customers do not simply throw them in the weekly trash.

PC makers including Apple, Dell, Hewlett-Packard and Sony now take back their products at no charge—an aggressive approach to a clean environment, CPA's McPherson says. But she notes that with the exception of Sony, the same cannot be said of most TV manufacturers.

Since September, Sony has allowed its consumer electronics customers to drop off their old products at one of Waste Management, Inc.'s 75 Recycle America eCycling drop-off sites throughout the U.S. Sony expects the number of these centers to double by the end of next year and plans to offer customers the option of shipping their used Sony products to the sites. This is part of a broader Sony goal of recycling one pound of old consumer electronics equipment for every pound of new products sold.

One Sony competitor has taken steps to produce a greener product. Panasonic Corporation of North America, the principal U.S. subsidiary of Matsushita Electric Industrial Co., Ltd., claimed in November 2006 that its plasma TVs featured lead oxide–free plasma display panels. The company estimated that last year it cut the use of about 300 metric tons of lead (roughly the weight of two 747 commercial airplanes) from its production environment.

PCs, however, are generally replaced more frequently than televisions. For that reason, computer manufacturers must make a concerted effort to take back old equipment from their customers, McPherson says. "We believe the research [shows that] if a company takes back its waste," she says, "it's more likely to design out harmful materials in the first place."

BROKEN: Discarded electronics can crack during transport or when crushed by garbage trucks, tossed into landfills or incinerated (more of an issue in developing countries), thereby releasing toxic chemicals into the environment

MOUNTING PROBLEM: The EPA estimates that roughly 283 million PCs will be sold in 2008, up from 255 million this year. And these new computers are pushing the old models out the door at a rapid pace: U.S. residential and business users scrap about 133,000 PCs daily.

TRASHED: Two years ago, the U.S. generated an astonishing 2.6 million tons of electronic waste, which is 1.4 percent of the country's total waste stream. Only 12.6 percent of this so-called "e-waste" was recycled.

NASA reveals crystal clear map of Antarctica

NASA reveals crystal clear map of Antarctica

The US space agency on Tuesday unveiled a new map of Antarctica with satellite images of unprecedented clarity that scientists say will transform research into the frozen continent.

The map was produced from about 1,100 pictures taken by NASA's satellite Landsat 7, showing precise details of landscape features half the size of a basketball court.

The result is the most precise map of Antarctica ever made with accurate colors and high-resolution views, the National Aeronautics and Space Administration said in a release. It was made to coincide with the International Polar Year, 2007-2008.

"This mosaic of images opens up a new window to the Antarctic that we just haven't had before," said Robert Bindschadler, chief scientist of the Hydrospheric and Biospheric Sciences Laboratory at NASA in Greenbelt, Maryland.

"It will open new windows of opportunity for scientific research as well as enable the public to become much more familiar with Antarctica and how scientists use imagery in their research," Bindschadler said.

He compared the new map to "watching high-definition TV in living color versus watching the picture on a grainy black-and-white television."

He said the map will allow scientists to better survey and follow changes on the southernmost continent, where the effects of global warming have become increasingly apparent.

NASA also said the detailed map could help guide scientific expeditions to the polar region and assist researchers studying changes in elevation in more remote areas.

The map was the work of a team of researchers at NASA, the US Geological Survey and the British Antarctic Survey using 1,100 images taken by Landsat 7 between 1999 and 2001.

The first satellite pictures of Antarctica were taken in 1972 after the launch of the first Landsat satellite. Before that, scientists trying to map Antarctica relied on airplanes and survey ships.


The US space agency on Tuesday unveiled a new map of Antarctica with satellite images of unprecedented clarity that scientists say will transform research into the frozen continent.

Nanoparticles Enable Surgical Strikes against Cancer

Nanoparticles Enable Surgical Strikes against Cancer

Microscopic instruments that target only cancerous cells could replace less precise methods that also kill healthy tissue

BONDING: Researchers at the Harvard-MIT Division of Health Sciences and Technology are studying ways to use nanoparticles held together by a variety of different DNA sequences (seen here) to locate and treat potentially cancerous tumors.
Courtesy of iStockphoto; Mark Evans

In a bid to progress beyond the shotgun approach to fighting cancer—blasting malignant cells with toxic chemicals or radiation, which kills surrounding healthy cells in the process—researchers at the Harvard-MIT Division of Health Sciences and Technology (HST) are using nanotechnology to develop seek-and-destroy models to zero in on and dismantle tumors without damaging nearby normal tissue.

HST takes an interdisciplinary approach to biomedicine. It consists of physicians, scientists and students from the Massachusetts Institute of Technology, Harvard Medical School, Harvard University, Boston-area teaching hospitals and other research centers. A team of researchers, led by Sangeeta Bhatia, an associate professor at HST and in M.I.T.'s department of electrical engineering and computer science, report in Advanced Materials that they have developed and tested injectable multifunctional nanoparticles—particles billionths of a meter in size—that they expect to become a new, potent weapon against cancer. (To provide some perspective, the width of a human hair is about 80,000 nanometers, or 0.003 inches.)

Nanoparticles could help treat cancer in a number of ways. They could be introduced into the bloodstream to locate and map tumors so that physicians would know what they were up against. Nanoparticles could also be designed to carry a payload of drugs that could be released near or even inside tumors to shrink or eliminate them.

HST researchers have experimented with polymer-coated iron oxide nanoparticles held together by DNA tethers to help them create a visual image of a tumor through magnetic resonance imaging. To test the particles, the researchers implanted mice with a tumorlike gel saturated with nanoparticles and placed those mice into the wells of cup-shaped electrical coils, which activated the nanoparticles via magnetic pulses.

The researchers subjected the metallic iron oxide particles to radiation until the DNA bonds holding them together broke, releasing fluorescent materials. "We just wanted to focus on characterizing the kinetics and temperature sensitivity using a payload we could detect," says Geoff von Maltzahn, an HST graduate student who has been working on the project since its inception in 2004.

The researchers are studying DNA sequences to gauge the point at which heat activates the nanoparticles after they have reached tumors in the body. One advantage of a DNA tether, the HST team members say, is that its melting point is tunable—scientists would be able to control when the bonds between the nanoparticles break by creating links of varying lengths with different DNA sequences.

Exposing the nanoparticles to a low-frequency electromagnetic field causes them to radiate heat that, in turn, erases the tethers and releases the drugs. The waves in the magnetic field used by the HST researchers have the same frequency range as radio waves (between 350 and 400 kilohertz). These waves pass harmlessly through the body and heat only the nanoparticles. In comparison, microwaves, which would cook tissue, are about a million times more powerful with frequencies measured in the gigahertz range.

Von Maltzahn and six other researchers, including Bhatia, wrapped up their initial study about a year ago and are now planning to replace the original fluorescent payload with a more therapeutic one, such as an enzyme that could be injected directly into the tumor to attack it from the inside out. Their goal is to eventually be able to release nanoparticles intravenously into the bloodstream and activate those particles by heat or magnetism as needed.

One open question is: What will happen to the nanoparticles after they are used? Since the particles are biodegradable, von Maltzahn says, the polymers would most likely make their way to the liver and be eliminated; the iron would probably be absorbed by the blood. Despite the potential of nanosize treatments for cancer, the researchers are unable to predict when such treatments might be available.