Stressed proteins can cause blood clots for hours

Mar. 5, 2013 ? New research from Rice University, Baylor College of Medicine (BCM) and the Puget Sound Blood Center (PSBC) has revealed how stresses of flow in the small blood vessels of the heart and brain could cause a common protein to change shape and form dangerous blood clots. The scientists were surprised to find that the proteins could remain in the dangerous, clot-initiating shape for up to five hours before returning to their normal, healthy shape.

The study -- the first of its kind -- focused on a protein called von Willebrand factor, or VWF, a key player in clot formation. A team led by Rice physicist Ching-Hwa Kiang found that "shear" forces, like those found in small arteries of patients with atherosclerosis, cause snippets of nonclotting VWF to change into a clot-forming shape for hours at a time. The finding appears online this week in Physical Review Letters.

"When I first heard what Dr. Kiang's team had found, I was shocked," said blood platelet expert Dr. Joel Moake, a study co-author who holds joint appointments at Rice and BCM. Moake, whose research group was the first to describe how high shear stress could cause platelets to stick to VWF, said, "I had thought that the condition might last for such a short time that it would be unmeasurable. No one expected to find that this condition would persist for hours. This has profound clinical implications."

Kiang, associate professor of physics and astronomy and of bioengineering, studies the forces involved in protein folding. Proteins are the workhorses of biology. Tens of thousands are produced each second in every living cell, and each of these folds into a characteristic shape within moments of its creation. Despite its ubiquity, protein folding is an immensely complex process that is shrouded in mystery.

Kiang is a pioneer in the use of atomic force microscopes (AFM) to shed light on the fundamental physical processes involved in protein folding. The AFM has a tiny needle with a tip measuring just a few atoms across. The needle is suspended from a tiny arm that bobs up and down over a surface. Kiang's team uses the bobbing needle to grab and pull apart individual protein molecules. By stretching these like rubber bands, her team has shown it can measure the precise physical forces that hold them in their folded shape.

"In this study, we did more than just measure the forces; we used those measurements to see what state the molecule was in," Kiang said. "In this way, we were able to study the dynamics of the molecule, to see how it changed over a period of time."

Moake, a senior research scientist in bioengineering at Rice and professor of medicine at BCM, said the work is vitally important because it helps explain the workings of VWF.

"VWF is synthesized in the cells that line the walls of blood vessels, and it's stored there until the cells get signals that the vessels are in danger of injury," Moake said. "In response to those stimuli, the cell secretes VWF. It's a long protein, and one end remains anchored to the cell while the rest unfurls from the wall like a streamer."

The act of unfurling makes VWF sticky for platelets, and that begins the process of hemostasis, which prevents people from bleeding to death when blood vessels are damaged by cuts and wounds.

"The body recognizes when clotting must stop -- when there are too many strings, too much sticking, too many platelet clumps -- and it uses an enzyme to clip the long VWF strings," Moake explained. "First, it makes large, soluble versions of the strings that remain somewhat sticky, and then these large soluble portions of VWF are reduced into smaller subunits of VWF that circulate in the plasma."

Under normal conditions, these circulating subunits, which are called PVWF, fold into compact shapes and cease to be sticky to platelets. However, previous research had shown that a type of physical stress called "shear" -- which can arise in partially occluded arterial blood vessels with high flow rates -- could cause PVWF to become sticky to platelets.

"That's all we knew," Moake said. "We didn't know how the conformation of the PVWF protein changed. That is why Dr. Kiang's research is so important and makes it more likely that therapeutic interventions can be more rationally designed."

To study the problem, Kiang's lab worked closely with Moake's team at Rice's BioScience Research Collaborative and with researchers from the laboratory of co-author Jing-fei Dong, formerly of BCM and now at PSBC in Seattle. Moake's and Dong's groups prepared samples of PVWF, subjecting some to the shear stresses known to induce clot formation. Kiang's team used AFMs to test the samples. Through a combination of experiments and deductive reasoning, her team determined exactly which portion of PVWF changed its conformation during shear stress. They also determined how long the protein remained partially unfurled before relaxing into its natural shape.

"The next step will be to design new experiments that allow us to monitor the proteins as they bind to platelets and initiate clot formation," Kiang said. "That will tell us even more about the physical properties of the proteins and provide more clues about potential therapies."

The research was supported by the National Institutes of Health, the National Science Foundation, the Alliance for NanoHealth, the Welch Foundation, the Mary R. Gibson Foundation and the Everett Hinkson Fund. Study co-authors include Rice graduate students Sithara Wijeratne and Eric Frey, former Rice graduate student Eric Botello, BCM researchers Hui-Chun Yeh and Angela Bergeron, Rice undergraduate Jay Patel, PSBC's Zhou Zhou and Rice senior research technicians Leticia Nolasco and Nancy Turner.

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The above story is reprinted from materials provided by Rice University. The original article was written by Jade Boyd.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. Sithara S. Wijeratne, Eric Botello, Hui-Chun Yeh, Zhou Zhou, Angela L. Bergeron, Eric W. Frey, Jay M. Patel, Leticia Nolasco, Nancy A. Turner, Joel L. Moake, Jing-Fei Dong, and Ching-Hwa Kiang. Mechanical Activation of a Multimeric Adhesive Protein Through Domain Conformational Change. Physical Review Letters, 2013 DOI: 10.1103/PhysRevLett.110.108102

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/matter_energy/biochemistry/~3/wWpqEdbBShI/130305145815.htm

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Scientists say baby born with HIV apparently cured

WASHINGTON (AP) ? A baby born with the virus that causes AIDS appears to have been cured, scientists announced Sunday, describing the case of a child from Mississippi who's now 2? and has been off medication for about a year with no signs of infection.

There's no guarantee the child will remain healthy, although sophisticated testing uncovered just traces of the virus' genetic material still lingering. If so, it would mark only the world's second reported cure.

Specialists say Sunday's announcement, at a major AIDS meeting in Atlanta, offers promising clues for efforts to eliminate HIV infection in children, especially in AIDS-plagued African countries where too many babies are born with the virus.

"You could call this about as close to a cure, if not a cure, that we've seen," Dr. Anthony Fauci of the National Institutes of Health, who is familiar with the findings, told The Associated Press.

A doctor gave this baby faster and stronger treatment than is usual, starting a three-drug infusion within 30 hours of birth. That was before tests confirmed the infant was infected and not just at risk from a mother whose HIV wasn't diagnosed until she was in labor.

"I just felt like this baby was at higher-than-normal risk, and deserved our best shot," Dr. Hannah Gay, a pediatric HIV specialist at the University of Mississippi, said in an interview.

That fast action apparently knocked out HIV in the baby's blood before it could form hideouts in the body. Those so-called reservoirs of dormant cells usually rapidly reinfect anyone who stops medication, said Dr. Deborah Persaud of Johns Hopkins Children's Center. She led the investigation that deemed the child "functionally cured," meaning in long-term remission even if all traces of the virus haven't been completely eradicated.

Next, Persaud's team is planning a study to try to prove that, with more aggressive treatment of other high-risk babies. "Maybe we'll be able to block this reservoir seeding," Persaud said.

No one should stop anti-AIDS drugs as a result of this case, Fauci cautioned.

But "it opens up a lot of doors" to research if other children can be helped, he said. "It makes perfect sense what happened."

Better than treatment is to prevent babies from being born with HIV in the first place.

About 300,000 children were born with HIV in 2011, mostly in poor countries where only about 60 percent of infected pregnant women get treatment that can keep them from passing the virus to their babies. In the U.S., such births are very rare because HIV testing and treatment long have been part of prenatal care.

"We can't promise to cure babies who are infected. We can promise to prevent the vast majority of transmissions if the moms are tested during every pregnancy," Gay stressed.

The only other person considered cured of the AIDS virus underwent a very different and risky kind of treatment ? a bone marrow transplant from a special donor, one of the rare people who is naturally resistant to HIV. Timothy Ray Brown of San Francisco has not needed HIV medications in the five years since that transplant.

The Mississippi case shows "there may be different cures for different populations of HIV-infected people," said Dr. Rowena Johnston of amFAR, the Foundation for AIDS Research. That group funded Persaud's team to explore possible cases of pediatric cures.

It also suggests that scientists should look back at other children who've been treated since shortly after birth, including some reports of possible cures in the late 1990s that were dismissed at the time, said Dr. Steven Deeks of the University of California, San Francisco, who also has seen the findings.

"This will likely inspire the field, make people more optimistic that this is possible," he said.

In the Mississippi case, the mother had had no prenatal care when she came to a rural emergency room in advanced labor. A rapid test detected HIV. In such cases, doctors typically give the newborn low-dose medication in hopes of preventing HIV from taking root. But the small hospital didn't have the proper liquid kind, and sent the infant to Gay's medical center. She gave the baby higher treatment-level doses.

The child responded well through age 18 months, when the family temporarily quit returning and stopped treatment, researchers said. When they returned several months later, remarkably, Gay's standard tests detected no virus in the child's blood.

Ten months after treatment stopped, a battery of super-sensitive tests at half a dozen laboratories found no sign of the virus' return. There were only some remnants of genetic material that don't appear able to replicate, Persaud said.

In Mississippi, Gay gives the child a check-up every few months: "I just check for the virus and keep praying that it stays gone."

The mother's HIV is being controlled with medication and she is "quite excited for her child," Gay added.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/89ae8247abe8493fae24405546e9a1aa/Article_2013-03-04-HIV-Baby%20Cure?/id-b1a51c3687384ccf8bee0aef799a3590

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NHL drafts the wrong players due to birthday bias

Feb. 27, 2013 ? A hockey player's birthday strongly biases how professional teams assess his talent, according to a new study by Grand Valley State University researchers. The findings were published in the online journal PLOS ONE.

The research, led by Robert Deaner, associate professor of psychology at Grand Valley, shows that, on average, National Hockey League (NHL) draftees born between July and December are much more likely than those born in the first three months of the year to have successful careers. In particular, 34 percent of draftees were born in the last six months of the year, but these individuals played 42 percent of the games and scored 44 percent of the points accumulated by those in the study. By contrast, those born in the first three months of the year constituted 36 percent of draftees but only played 28 percent of the games and only scored 25 percent of the points.

The study focused on Canadian players because in Canadian youth ice hockey there is a January 1 cut-off date. This means players born later in the year would have been consistently younger than their age group peers.

"There's no doubt that drafting professional athletes is an inexact science," said Deaner. "Plenty of sure-fire first-round picks fizzle while some late-round picks unexpectedly become stars. But our results show that, at least since 1980, NHL teams have been consistently fooled by players' birthdays or something associated with them. They greatly underestimate the promise of players born in the second half of the year, the ones who have always been relatively younger than their peers. For any given draft slot, relatively younger players are about twice as likely to be successful. So if teams really wanted to win, they should have drafted more of the relatively younger players."

Background and Significance

Previous studies have demonstrated relative age effects (RAEs), which occur when those who are relatively older for their age group are more likely to succeed. For example, in elite Canadian youth ice hockey, roughly 40 percent of players are born in the first three months of the year while only 15 percent are born in the last three months. Although RAEs are well established in many sports and educational settings, their underlying causes remain unclear. The new study provides the most direct evidence yet that selection bias is a crucial cause of RAEs. Selection bias means that evaluators, such as teachers and coaches, grant fewer opportunities to relatively younger individuals than is warranted by their talent.

"There are many possible causes of RAEs," said Deaner. "For instance, a youth coach may mainly select relatively older players because those players' greater size means they are actually more likely to help the team. Researchers believe, however, that selection bias is also a big cause of RAEs, but there has never been a direct test of selection bias. We could make this test because we had a good measure of perceived talent, the order or slot in which each player was drafted. And we had good measures of realized talent, how long they were able to stay in the NHL and how many points they scored there. Because relatively younger players consistently performed better than would be expected based on their draft slots, we've shown selection bias."

The researchers admit that they don't fully understand the selection bias they discovered. "We don't know yet why the evaluations of NHL teams are biased, but there are several ways it could work. Because being many months older than one's peers can be a big advantage as a child or early teen, the relatively older players might be more likely to be on the most elite junior teams when they are 17 or 18, and scouts might be swayed by that," said Deaner. "Another possibility, suggested by educational studies, is an 'underdog' effect. This would involve relatively younger individuals developing better work habits so that they improve more in adulthood."

The authors believe their pro hockey results have implications for education. Deaner noted: "We have to be careful about assuming too much because a teacher deciding which children should be tracked into advanced classes is a much different situation than hockey teams assessing which adults are likely to develop into NHL stars. But, for many reasons, one would think that NHL teams should be less biased than educators. First, NHL teams are evaluating adults not children, meaning that relative age differences are proportionally smaller. Second, NHL teams are aware of RAEs, but educators may not be. Third, NHL teams have vast resources to evaluate individuals while educators do not. Fourth, NHL teams pay a steep price for poor evaluation whereas educators may not. So overall, in many situations, evaluations of ability may be greatly colored by an individual's relative age. This may even happen when the teachers and coaches know about RAEs."

Co-authors of the study were Aaron Lowen of Grand Valley State University and Steven Cobley of the University of Sydney.

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The above story is reprinted from materials provided by Grand Valley State University.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. Robert O. Deaner, Aaron Lowen, Stephen Cobley. Born at the Wrong Time: Selection Bias in the NHL Draft. PLoS ONE, 2013; 8 (2): e57753 DOI: 10.1371/journal.pone.0057753

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/most_popular/~3/aiKTLbZhmbM/130227183506.htm

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Month end loans: Take Care of Your Issues In A Hassle Free Manner

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Football's next big hit? Steady 'ball's eye view' of game now possible

John Roach , NBC News ? ? ? 11 hrs.

For anyone who?s ever imagined what it?s like to be a football caught in the end zone and spiked on the turf in celebration, your dream is alive. Robotics researchers have embedded a camera into a football and developed an algorithm to give fans a new view ? from the pigskin?s perspective.

When the football is thrown in a spiral, the embedded camera records a succession of frames as the ball rotates. The challenge is that, since footballs can spin at a stomach-churning 600 revolutions per minute, the raw video is unwatchable. The software algorithm converts the blurry, spinning footage into a stable, wide-angle view by discarding sky-facing frames and stitching together the remaining frames for a panorama.

The result is a field-facing view from the ball's perspective as it?s tossed down the field. Check it out in the video below.

The researchers at Carnegie Mellon University and the University of Electro-Communications in Tokyo realize the NFL may block the idea before camera-embedded footballs are fielded for regular play, but the technology is promising for game analysis during the pre-and post-game shows, for example.

The researchers suggest an artsy project that could capture the expressions of the faces of players during a game of catch. Perhaps this could be used to provide a baseball?s view of a homerun hit or a soccer ball soaring into the goal. How about a golf ball? In any case, as cameras get smaller ? and more shock-resistant ? more possibilities arise.

Progress on the BallCam will be presented March 8 at the Augmented Human International Conference in Stuttgart, Germany. Further fine tuning is needed to make the images flawless, such as a faster camera sensor and other techniques to reduce all the blurring.

John Roach is a contributing writer for NBC News. To learn more about him, check out his website. For more of our Future of Technology series, watch the featured video below.

Source: http://www.nbcnews.com/technology/futureoftech/footballs-next-big-hit-steady-balls-eye-view-game-now-1C8589666

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