High Blood Pressure a Neglected Disease, Report Declares

Public health officials and health care providers need to step up their efforts to reduce Americans' increasing rates of high blood pressure and better treat those with the condition, which triggers more than one-third of heart attacks and almost half of heart failures in the United States each year, says a new report from the Institute of Medicine.

Policies that create environments which support healthier eating, lowered sodium consumption, and increased physical activity offer greater promise of reducing the high hypertension rate than merely educating individuals about the dangers of high blood pressure, said the committee that wrote the report.Roughly three-quarters of Americans recognize the importance of having their blood pressure checked, but this awareness has not translated into sustained reductions in the condition.Nearly one-third of U.S. adults have high blood pressure, and it accounts for about one in six adult deaths annually, a 25 percent increase from 1995 to 2005.

Given that many individuals with high blood pressure have not been diagnosed and the majority of patients with hypertension do not have it under control, the report also calls on public health and medical officials to explore ways to improve health care providers' adherence to treatment guidelines.Multiple studies show that physicians are unlikely to start or intensify treatment for mild to moderate hypertension and that they are less aggressive about treating older patients, who are the most likely to have the condition and benefit from therapy.In addition, public health officials should work with health insurance plans to reduce or eliminate deductibles and co-payments for anti-hypertensive drugs to improve patients' compliance with treatment regimens.

"Although hypertension is relatively easy to prevent, simple to diagnose, and relatively inexpensive to treat, it remains the second leading cause of death among Americans, and as such should rightly be called a neglected disease," said committee chair David Fleming, director and health officer, Public Health -- Seattle/King County, Seattle. "Undiagnosed and uncontrolled cases are occurring at alarming rates, even though many people with hypertension see their doctors regularly.We think health care providers can do better at helping patients control their blood pressure, but what will make the biggest difference is creating environments that help people avoid the condition in the first place through healthy eating and active living."

The committee's review of the science points to heavy weight, inactivity, and unhealthy diets containing too much salt and too little potassium as the major risk factors for high blood pressure.Fortunately, all can be prevented through behavioral changes, but the typical American community and lifestyle make a poor diet and inactivity easier patterns to fall into than healthy eating and active living.

The report calls for the U.S. Centers for Disease Control and Prevention to work with partners in the public and private sectors to promote policies that make it easier for people to engage in regular physical activity, cut calories, and reduce their intake of foods containing high levels of sodium while increasing their exposure and access to produce and other foods containing potassium.

Based on available data, the committee estimated that hypertension prevalence might be reduced by as much as 22 percent if Americans consumed less salt in their diet and ate more vegetables, fruit, and lean protein.A recent study calculated that reducing salt intake from 3,400 milligrams to the currently advised maximum intake level of 2,300 milligrams per day could bring down the number of individuals with high blood pressure by about 11.1 million and result in approximately $17.8 billion in health care cost savings annually. The committee also estimated that an initiative to help overweight and obese Americans each lose 10 pounds could reduce the prevalence of high blood pressure in the overall population by 7 percent to 8 percent. An exercise program that gets physically inactive people more active could decrease prevalence by 4 percent to 6 percent.

Efforts to get health care providers to follow current guidelines for treatment and prevention are also needed, the report says.The committee noted that lack of physician adherence to treatment guidelines for hypertension is a significant reason why many patients are unaware of their condition and do not have it under control.Data show that 86 percent of individuals with uncontrolled hypertension have insurance and visit their doctors.Since it is not clear why providers frequently do not follow the guidelines, CDC officials should research this issue as well as work with accreditation programs to improve providers' adherence to recommended treatment regimens.

Out-of-pocket costs are a significant reason why some hypertensive patients reduce or discontinue their medications, the report notes.CDC should encourage the Medicare and Medicaid programs and private insurers to find ways to eliminate or reduce deductibles and co-payments for anti-hypertensive medications and to work with the pharmaceutical industry to standardize and simplify applications for patient assistance programs that provide reduced-cost or free hypertension medications.

The report was sponsored by the U.S. Centers for Disease Control and Prevention's Division for Heart Disease and Stroke Prevention.Established in 1970 under the charter of the National Academy of Sciences, the Institute of Medicine provides independent, objective, evidence-based advice to policymakers, health professionals, the private sector, and the public.The National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and National Research Council make up the National Academies.A committee roster follows.

Copies of A Population-Based Policy and Systems Change Approach to Prevent and Control Hypertension are available from the National Academies Press, on the Internet at http://www.nap.edu. Information on the study can also be found at http://www.iom.edu/reducehypertension.

Courtesy: ScienceDaily

Target Cancer A Roller Coaster Chase for a Cure

PHILADELPHIA — His patient, a spunky Italian-American woman in her 60s, was waiting in an exam room down the hall for the answer: Was the experimental drug stopping her deadly skin cancer?

But as Dr. Keith Flaherty read out the measurements of her tumors from the latest CT scan, he could not keep the distress from his voice.

“She’s worse,” he said to the clinical trial nurse at the University of Pennsylvania’s melanoma clinic.

Like the 17 other patients on the drug trial — the corporate lawyer, the receptionist with young children, the Philadelphia philanthropist — the woman known in the trial as Patient 18 was going to die, most likely within months.

In the exam room, her gratitude for his failed efforts to save her tore at his heart.

He had been so optimistic. A radical departure from standard chemotherapy, the drug was designed to reverse the effect of a genetic mutation particular to the patient’s tumors. The approach represented what some oncologists see as the best bet for attacking all types of cancer.

And as he returned to his office that autumn afternoon two years ago, Dr. Flaherty was already calculating the next step: he wanted to test the drug at a more potent dose before giving it to more patients in a larger trial. It would require retooling the drug in a costly and complicated task that might not work, and he would have to make his case to two companies that had already poured hundreds of millions of dollars into the drug and were eager to move it forward.

“This,” he insisted to colleagues, “is the best drug we’re going to get.”

Dozens of such “targeted” drugs are emerging from the laboratory, rooted in decades of research and backed by unprecedented investment by pharmaceutical companies, which stand to profit from drugs that prolong life even by weeks.

But putting them to their truest test falls to a small band of doctors committed to running experimental drug trials for patients they have no other way to heal.

At a time when cancer still kills one in four Americans, it is a job that requires as much hubris as heart. To chronicle the trial of the drug known as PLX4032 is to ride a roller coaster of breakthroughs and setbacks at what many oncologists see as a watershed moment in understanding the genetic changes that cause cancer.

Over three tumultuous years, Dr. Flaherty saw patients who drove hundreds of miles for their monthly dose, and one who arrived barely able to walk. Some took 32 pills a day. When it became clear they were not absorbing the drug, he asked them to take the pills with high-fat foods like hamburgers and eggs, which might help dissolve them.

At academic conferences, he clashed with other oncologists who warned that targeted therapy had almost never had long-lasting results. At Penn, he badgered laboratory researchers whose animal tests might provide early clues for how a drug would behave in his patients.

And always, he ended up on his BlackBerry, e-mailing, calling, cajoling the drug makers to commit even more resources to the new category of drugs he so deeply believed in.

A five-and-a-half-foot streak of outsize energy, Dr. Flaherty, 39, seemed buoyed by an innate optimism and a faith in the scientific logic underlying the approach.

But at his clinic, where he gave vials of pills to patients whose tumors were often erupting, black and bumpy across their arms and legs, he told them only what he believed to be true.

“This,” he said, “is our best shot.”

The Driver Gene

In many ways, Keith Flaherty had been training to run the trial of this drug since his residency in the late 1990s at Brigham and Women’s Hospital in Boston.

There he grew to despise chemotherapy, which rarely cured cancer in its advanced stages, even as he learned to dispense it. The mainstay of cancer treatment for half a century, the chemotherapy drugs attacked all fast-growing cells, poisoning those that grow fast normally as well as the cancerous ones.

Drawn to oncology for the reason other residents often rejected it, Dr. Flaherty found strength in the intensity of treating patients who knew that they, and he, were fighting for their lives.

But he also chose the field because advances in understanding cancer’s molecular biology convinced him it might finally be possible to cure the disease — and he wanted to have a hand in it.

Healthy cells turned cancerous, biologists knew, when certain genes that control their growth were mutated, either by random accidents or exposure to toxins like tobacco smoke and ultraviolet light. Once altered, like an accelerator stuck to the floor, they constantly signaled cells to grow.

What mattered in terms of treatment was therefore not only where a tumor originated, like the lungs or the colon, but also which set of these “driver” genes was fueling its growth. Drugs that blocked the proteins that carried the genes’ signals, some believed, could defuse a cancer without serious side effects.

Dr. Flaherty arrived at Penn for a fellowship in the fall of 2000 just as one of the first such drugs, Gleevec, was inducing complete remission in patients with a rare leukemia. Yet many oncologists remained skeptical that its success could be replicated in common cancers that were more aggressive and genetically complex.

And there was no guarantee that the pharmaceutical industry, which already viewed cancer as too fragmented a market, would invest in developing drugs tailored to what were probably dozens of driver genes that had yet to be identified.

Dr. Flaherty, however, was convinced that what he called the “targeted therapy revolution” was around the corner. It was the only real hope, he told friends, colleagues, medical students and whoever would listen, “because it is based on what makes cancer tick.”

A career that combined treating patients with testing drugs would be far less lucrative than private practice. Such doctors are not allowed to have a financial stake in a drug, for obvious reasons. But Dr. Flaherty, the son of two medical researchers, had always wanted to pursue research.

He accumulated an encyclopedic knowledge of the targeted drugs in development and gravitated to melanoma, where the absence of reliable treatments made patients eager to try experimental ones.

The cancer, which struck 70,000 Americans last year, is easily treatable in its earliest stages, but almost always fatal within a year once it spreads beyond the skin.

In early 2002, when Dr. Flaherty started seeing patients on his own, the available trials still centered on chemotherapy drugs, and he sought to soften recitation of their toxic side effects — nausea, anemia, infection, hair loss — by mocking his own lack of hair.

“I’ve got bigger problems than hair loss,” many patients said.

“Tell me about it,” the doctor replied, invariably eliciting laughter.

He wore bow ties under his lab coat, and told patients to leave their health to him. Yet when grateful families gave him money for research, or sent him bow ties to add to his collection, he felt like a fraud. “What I do is palliative care,” he told his wife, a primary-care physician, in a form of self-indictment.

So when an article in the journal Nature brought news of what was almost surely one of the driver genes in melanoma in the spring of 2002, Dr. Flaherty could hardly contain himself. British scientists analyzing hundreds of tumor samples, he read, had found the same gene mutated in more than half of melanomas, and smaller numbers of other cancers as well. It was called B-RAF.

Dr. Flaherty, who has a near-photographic memory, was not accustomed to rereading. But in his campus office that morning, he scrolled through the article on his computer again to be sure he had understood. The presence of the same B-RAF mutation in so many cancers, he thought, meant it was one of the biggest genetic smoking guns yet identified in cancer. A drug that blocked the protein made by the defective gene might have enormous consequences for patients — and he knew of one that just might work.

Dr. Flaherty raced to the melanoma clinic. “We have to jump on this,” he urged his mentor, Dr. Lynn Schuchter.

For a junior faculty member, he was more confident than he had a right to be, Dr. Schuchter thought. Yet his optimism was infectious.

She would make trials of drugs that homed in on B-RAF a top priority, she told him.

That first effort, however, was destined to fail.

Dashed Hopes

Possessed of an energy that even friends called manic, Dr. Flaherty was used to finding diffuse outlets for it. In medical school at Johns Hopkins, he had read the entire works of Proust and cultivated bonsai. In Philadelphia, he collected a library of first edition books; copied the entire works of Mozart, Bach and Beethoven onto CD; and restored by hand the 150-year-old home he had bought with his wife, Dr. Mira Kautzky.

Raised in an affluent part of Baltimore, an A- student who had avoided exerting himself for the extra grade at boarding school at Phillips Andover and as an undergraduate at Yale, he now told his wife, “I feel like I’m applying myself for the first time.”

And if she wished that his version of taking care of their two young daughters did not so often involve settling them in front of golf tournaments on TV while he pored over patient charts and wrote trial protocols — the girls became avid fans of the sport — she also understood what drove him.

Over the next four years, with the backing of his superiors at Penn, Dr. Flaherty enrolled several hundred patients in trials of the drug, developed by an academic pioneer in targeted therapy and now owned by Bayer.

He asked the trial nurses to work weekends processing blood and tissue samples. And he evangelized the targeted approach at scientific conferences, where he invariably found himself outnumbered by melanoma researchers devoted to a class of drugs that sought to harness the immune system to attack cancer.

While a single targeted drug was likely to hold off cancer for only a limited time, immunotherapy can be curative. But after decades of effort, the only such treatment approved for use in melanoma helped just a tiny fraction of patients.

“You’re swinging for the fences on every pitch,” Dr. Flaherty told the immune therapists. And, he thought to himself, they were mediocre batters at best.

But for all his self-confidence, Dr. Flaherty found himself sobbing uncontrollably one evening in late 2004 over a letter from the wife of a patient who had died, the latest of several patients on the targeted drug whom he had lost in recent weeks. The reminders of the hope and trust that people put in him, he told his wife that night, “can be overwhelming.”

To many of Dr. Flaherty’s colleagues, the failure of the Bayer drug indicated that melanoma would prove impervious to targeted therapy. And to many other oncologists, it was a blow to the notion that targeted therapy would work in any cancer as its proponents envisioned.

Dr. Flaherty brushed them off.

“We just had the wrong drug,” he insisted whenever he could. “The principle holds.”

But more often than not, when he gave his targeted therapy pep talks, he found himself talking to half-empty rooms, waiting, in awkward silence, for questions no one cared enough to ask.

PLX4032

While some concluded that Dr. Flaherty was toiling in vain, a small biotechnology company in Berkeley, Calif., called Plexxikon was keeping close track of his work.

Ever since the B-RAF mutation had been identified as so prevalent in melanoma tumors, the company’s scientists had been working on a drug aimed at it, and when they invited him for a visit in early 2006, Dr. Flaherty could not fend off a wave of excitement.

One reason the Bayer drug had failed, he believed, was because it blocked proteins in healthy cells as well as cancerous ones, inducing nasty side effects that limited how much of the drug patients could tolerate.

The drug Plexxikon called PLX4032 was different, designed to bind to the B-RAF protein only in cancer cells. Human tumors with the mutation, grafted into mice, Plexxikon’s chief scientist told Dr. Flaherty, had stopped growing when exposed to the drug. And no amount seemed to induce side effects in dogs or monkeys.

An investment in the drug by Roche, the Swiss pharmaceutical giant, shortly after Dr. Flaherty signed on to lead its first human trial alleviated his concern that Plexxikon might not have the wherewithal to pull it off.

But the partnership also raised the financial stakes. Roche was to dole out, a chunk at a time, nearly $700 million to Plexxikon as it passed certain milestones on the way to the hoped-for approval by the Food and Drug Administration. The first hurdle was the completion of the trial Dr. Flaherty was to run, known as Phase 1, in which the goal was to determine the highest dose humans could safely tolerate.

For both companies, Dr. Flaherty knew, time was money. By now, Gleevec, the drug that had proved so effective in a rare leukemia, was generating a billion dollars a year for the company that owned it, and other companies had taken note. Competing drugs that aimed to block the B-RAF protein, and others that might play a role in fueling melanoma, were under development.

Still, as the trial opened in December 2006, Dr. Flaherty insisted on an approach that slowed them down. The companies had stipulated that any cancer patient could participate, a standard practice to speed the process of settling on a safe dose before moving on to a larger, Phase 2 trial.

But in the case of a targeted drug like PLX4032, Dr. Flaherty believed, it made far more sense to give it only to the patients for whom it was made.

Whenever possible, Dr. Flaherty and his co-investigator, Dr. Paul Chapman of Memorial Sloan-Kettering Cancer Center, agreed, they would screen tumors first for the B-RAF mutation, and offer a spot on the trial for those who had it.

It might take longer to find the right patients. But it was the best way to see if the drug worked — or did not.

Falling Short

In patients whose cancer bubbled in black lesions on their skin, Dr. Flaherty and Dr. Chapman sliced off tumor samples themselves. For those whose tumors had mushroomed internally, they requested a sample from whichever hospital had removed them.

Always, they warned prospective participants to consider the health risks of taking a drug that had never been given to humans. Perhaps worst of all, Dr. Flaherty emphasized, they could be devoting precious last days to blood work and X-rays.

But more often than in any other trial he had led, patients waved aside the concerns.

“It’s like a rope you’ve been thrown when you’re drowning, that’s made just for you,” one patient said.

“Is my head going to fall off?” asked a Philadelphia patient in her 50s. “Then bring it on.”

Dr. Flaherty had nominated Dr. Chapman, 54, as his chief collaborator on the trial, despite his longtime allegiance to immunotherapy and outspoken skepticism that blocking B-RAF could keep melanoma at bay.

Dr. Chapman, a senior clinical researcher in melanoma, was an especially rigorous clinical researcher, Dr. Flaherty knew, and he believed Dr. Chapman would give PLX4032 its fairest chance.

But the Sloan-Kettering doctor’s lack of enthusiasm in the investigators’ first conference call with Dr. Keith Nolop, Plexxikon’s medical director, made Dr. Flaherty slightly uneasy. “I’m really looking forward to this study,” Dr. Flaherty said in what is considered a customary statement of enthusiasm at the beginning of a trial, waiting for Dr. Chapman to add a few words of support.

On the other end of the line, there was only silence.

“I’m assuming it’s not going to work,” he told Dr. Flaherty flatly. “I hope I’m wrong.”

Typically, Phase 1 trials are limited to a few dozen patients and end when the dose reaches the point where side effects like rashes and diarrhea make patients too uncomfortable.

Dr. Flaherty and Dr. Chapman started the first three patients on 200 milligrams per day. After two months with no side effects — and no response — they doubled it.

Two more months passed, still nothing. They gave three more patients 800 milligrams, the equivalent of the dose that made tumors stop growing in mice. Even shrinking tumors, the doctors knew, would not mean the cancer had been cured but might at least offer a reprieve.

Dr. Flaherty pounced on the scans when they arrived. In some patients, tumors had remained the same size. “Maybe we’re starting to see something,” he could not help thinking. But at the next set of scans, the disease had progressed. On conference calls, Dr. Nolop sometimes referred to those patients as “responders.”

“They’re not responders,” Dr. Flaherty gently corrected him: under the accepted definition, tumors had to shrink to qualify patients as responders.

By the time they had doubled the dose four times, Dr. Flaherty could not help wondering if the targeted therapy skeptics were right. Dr. Chapman, crisp and businesslike on the weekly calls, supplied no comfort. He pointed out new research that B-RAF was mutated even in benign moles, and therefore could not be the key driver in melanoma.

The woman known in the trial as Patient 18 was one of the three who took 1,600 milligrams — 32 pills a day, she complained mildly, was a lot of pills.

This drug “doesn’t look so hot,” Maryann Redlinger, the trial nurse, told the doctor, urging him to keep an emotional distance.

Already, the two doctors had seen some patients on the trial die.

“I am deeply sorry and disappointed that I fell short of what you and I wanted,” Dr. Flaherty told their relatives, in an endless series of condolence calls that never became routine.

The higher doses, Dr. Flaherty and Dr. Chapman realized, were not getting from the digestive tract into their patients’ bloodstreams. The Phase 1 trial had accomplished its official goal: it had established that the drug was safe at the maximum dose the body could absorb. Yet everyone involved in the trial had hoped to see the tumors shrink.

“We need to get more in,” Dr. Flaherty pressed on their next conference call. At the suggestion of a Roche scientist, the doctors instructed patients to take the drug with high-fat foods in hopes that would help it dissolve more readily, but to no avail. The only recourse was to try to reformulate the drug so that patients could absorb a higher dose, an unusual undertaking at this stage in testing.

The companies were already trying to make the drug more potent, but Roche scientists said the reformulation would require a feat of chemistry that might not succeed. And it would mean several months of delay.

“This looks like our dose,” Dr. Nolop ventured on a conference call in the fall of 2007, as Dr. Flaherty and Dr. Chapman recalled. “This is about as high as it can go.”

Dr. Flaherty saw no way to fight it.

By rights, it was time to move to a larger Phase 2 trial. Roche and Plexxikon, he knew, could make good money on a drug that provided as little as an extra month or two of life to melanoma patients, as it still stood a chance of showing it could do in a larger trial. Doctors, too, would welcome the ability to provide even that for their patients.

Then, over the phone line, came support from an unexpected quarter.

“This is not your dose,” Dr. Chapman said. “For all we know we’re 10 times, 100 times too low!”

They had seen, Dr. Chapman said, not a single side effect. And tumors were still growing in the very patients for whom the drug was intended. If they moved to Phase 2 now, he continued, they would never know if a higher dose of the drug could have shrunk those tumors. If the idea had been to test the hypothesis that blocking the B-RAF protein could stop the melanoma, he said, they had not done that yet.

Dr. Flaherty, on the phone in his office at Penn, all but pumped his fist.

In December 2007, the companies halted the trial. They would wait while Roche chemists tried to reformulate the drug.

The First Responder

Elmer Bucksbaum came to see Dr. Flaherty at the melanoma clinic in the spring of 2008. He was accompanied by his son-in-law, Marc Lovitz, whose own father had died of melanoma just one month after the diagnosis. Now Mr. Lovitz was trying to prepare his wife and mother-in-law for the likelihood that there would be nothing the doctor could do for Mr. Bucksbaum.

“We know he doesn’t have long,” he told Dr. Flaherty.

Dr. Flaherty examined the patient, an 89-year-old retired film editor who had moved from Florida to live with his daughter. While he waited for a tumor sample from Mr. Bucksbaum’s neck for B-RAF screening, Dr. Flaherty secured him a spot on an immune therapy trial.

By the time Mr. Bucksbaum returned, a few months later, Dr. Flaherty had received the new PLX4032 from Roche. It was, the company promised, 10 times as potent as the previous one, packaged in a way the body could more easily absorb.

Mr. Bucksbaum’s tumor had tested positive for the B-RAF mutation. But the other trial had given him colitis. He had been bedridden for weeks. He had lesions around his eyes and on his neck, on his liver and in his lungs. The doctor was not sure if his patient had the will to try another experimental therapy.

Instead, Dr. Flaherty described hospice, as he often did with patients who had reached this point, without using the loaded word.

“Look,” he said, “we could focus on the things we can do to make you feel as good as you can feel.”

“Isn’t there anything else?” Mr. Bucksbaum asked.

He took his first PLX pills on Sept. 30, 2008.

To speed the trial as it resumed, Dr. Flaherty worked with collaborators at four other cancer centers to bring in patients. Mark Bunting, 43, an airline pilot in Sandy, Utah, flew to the University of California, Los Angeles, on Oct. 8 to get his pills.

Randy Williams, a contractor in Jonesboro, Ark., drove nine hours to Houston to enroll that month. Rita Quigley, a triage nurse, received her pills in Nashville. At Sloan-Kettering, Dr. Chapman added a patient with a large tumor in his abdomen.

When Mr. Bucksbaum returned to Dr. Flaherty’s clinic at the end of October, his skin lesions were gone.

“That’s good news,” the doctor told him cautiously.

But external tumors came and went with melanoma treatments. The internal tumors were what mattered. The doctor would not know about those until he looked at the scans Mr. Bucksbaum brought in on a disk four weeks later.

The clinic was backed up that day, and it was close to 5 p.m. when Dr. Flaherty called in the trial nurse to read her the tumor measurements. For a moment, he thought he had opened the wrong file. He strained to see any tumor at all.

It would be at least a week before he knew if Mr. Bucksbaum was an aberration.

Courtesy: The NewYork Times

Diversity of Corals, Algae in Warm Indian Ocean Suggests Resilience to Future Global Warming

Penn State researchers and their international collaborators have discovered a diversity of corals harboring unusual species of symbiotic algae in the warm waters of the Andaman Sea in the northeastern Indian Ocean.

"The existence of so many novel coral symbioses thriving in a place that is too warm for most corals gives us hope that coral reefs and the ecosystems they support may persist -- at least in some places -- in the face of global warming," said the team's leader, Penn State Assistant Professor of Biology Todd LaJeunesse. According to LaJeunesse, the comprehensiveness of the team's survey, which also included analysis of the corals and symbiotic algae living in the cooler western Indian Ocean and Great Barrier Reef area of Australia, is unparalleled by any other study.

The team's findings will be published during the week ending 20 February 2010 in an early online issue of the Journal of Biogeography.

Corals are colonies of tiny animals that derive nutrients and energy from golden-brown, photosynthetic algae that live inside the corals' cells. "This symbiotic relationship is sensitive to changes in the environment," said LaJeunesse. "For example, because the algae are photosynthetic, they are very sensitive to changes in light. They are also sensitive to temperature," he said. "An increase in sea-surface temperature of just a few degrees Fahrenheit for a period of several months can cause many of the coral-algal symbioses to break down and the algae to be expelled. This process is known as bleaching because it leaves behind the clear animal tissue and the white skeleton underneath. When bleaching is severe, due to either high temperatures or low light availability, corals soon die without their symbiotic partners."

LaJeunesse said that continued global warming eventually may cause the demise of coral-reef ecosystems, which would have major impacts on the tourism and food-fisheries industries. According to team member Ove Hoegh-Guldberg, a professor at the University of Queensland in Australia, coral-dominated reefs may become scarce within the next 30 to 50 years, given the increase in the number of bleaching events that recently have taken place.

"The fact that the Andaman Sea and other regions around Southeast Asia are home to such a high diversity of corals is surprising because the water there is so warm and sometimes murky," said LaJeunesse. "The inshore locations we surveyed are not the sort of places where you would expect to see thriving coral communities. Not only is the water warm and murky, but the tidal flux is so great that many of the corals can spend hours out of water, exposed to the harsh sun and dry air."

The team identified the species of algae that associate with corals, as well as giant clams, sea anemones, zoanthids, and other reef-dwelling animals that form close symbiotic relationships with the single-celled algae that are referred to as zooxanthellae. In the Andaman Sea, the scientists found a variety of seemingly thermally tolerant algae species, with one species being particularly abundant. Called Symbiodinium trenchi, the species is a generalist organism -- one that is able to associate with a variety of hosts. Corals harboring this symbiont appear to be tolerant of high heat. LaJeunesse found the same species in the Caribbean Ocean during a bleaching event that took place in 2005. "Symbiodinium trenchi, which normally occurs in very low numbers in the Caribbean, was able to take advantage of the warming event and become more prolific because of its apparent tolerance of high temperatures," he said. "The species appears to have saved certain colonies of coral from the damaging effects of unusually warm water."

In contrast, the scientists found very few thermally tolerant algae species in the cooler western Indian Ocean and Great Barrier Reef area. According to LaJeunesse, the Andaman Sea is on average three or four degrees Fahrenheit warmer than the western Indian Ocean and the Great Barrier Reef area. "Symbiodinium trenchi and other related symbiont species can tolerate this warm water, but if global warming causes the water to warm further, even these species might not be able to deal with it," he said. "However, if the water warms by three or four degrees Fahrenheit in the cooler western Indian Ocean or Great Barrier Reef area, Symbiodinium trenchi easily could persist. The problem is that Symbiodinium trenchi occurs in very low numbers in these cooler areas and, so far, has not proliferated during bleaching events as it has in the Caribbean."

LaJeunesse said that some scientists have suggested that reefs suffering from high water temperatures might be "seeded" with the thermally tolerant Symbiodinium trenchi; however, he is not sure the approach will work. "Symbiodinium trenchi forms symbiotic associations only with corals and other animals that acquire their symbionts from the environment," he said. "Other species of coral are born with algae already in their cells. If Symbiodinium trenchi were introduced into a new environment, it may be able to 'rescue' some species that acquire their symbionts from the environment, but it would not be able to 'rescue' species that are born with algae already in their cells because these species have evolved special relationships with their algae."

Not only is LaJeunesse concerned that "seeding" reefs with algae, like Symbiodinium trenchi, will fail to "rescue" animals that are born with algae already in their cells, but he also is concerned about possible negative repercussions. "You never know what the effects might be of introducing an organism into an ecosystem in which it is not well established," he said.

LaJeunesse explained that the diversity of species the team found in the Andaman Sea likely is the result of the dramatic changes in the ocean environment that the region has experienced since the beginning of the Pleistocene Epoch. Typically, during times of environmental change, generalist species of algae that are able to associate with a variety of animal hosts are more successful than specialist species of algae that can associate only with particular hosts because the generalists can spread to many hosts, thus forming new combinations that might be better suited to the new environment. Once the environmental change has stabilized, some of the generalist species form special associations with new hosts and, as a result, become new specialist species.

LaJeunesse said that one of the team's most important findings is that coral-algal symbioses are much more ecologically and evolutionarily responsive to environmental changes than previously was believed. "The responsiveness of these symbioses to historical climate change gives us hope that some species may survive in some places in the face of future warming," he said. "Yet, even though these symbiotic relationships have persisted through historical climate changes, they never have experienced the rapid rate of warming that we are seeing today. So, while we shouldn't underestimate life and its ability to respond to change, we also should do everything in our power not to test its resilience."

This research was funded by the World Bank, Penn State University, Florida International University, and the U.S. National Science Foundation.

Courtesy: ScienceDaily

Evidence Builds on Color of Dinosaurs

Until last week, paleontologists could offer no clear-cut evidence for the color of dinosaurs. Then researchers provided evidence that a dinosaur called Sinosauropteryx had a white-and-ginger striped tail. And now a team of paleontologists has published a full-body portrait of another dinosaur, in striking plumage that would have delighted that great painter of birds John James Audubon.

“This is actual science, not ‘Avatar,’ ” said Richard O. Prum, an evolutionary biologist at Yale and co-author of the new study, published in Science.

Dr. Prum and his colleagues took advantage of the fact that feathers contain pigment-loaded sacs called melanosomes. In 2009, they demonstrated that melanosomes survived for millions of years in fossil bird feathers. The shape and arrangement of melanosomes help produce the color of feathers, so the scientists were able to get clues about the color of fossil feathers from their melanosomes alone.

That discovery prompted British and Chinese scientists to examine fossils of dinosaurs that are covered with featherlike structures. The 125-million-year-old species Sinosauropteryx, for example, has bristles on its skin, and scientists found melanosomes in the tail bristles. They concluded that the dinosaur had reddish-and-white rings along its tail.

The discovery, which the researchers reported last week in Nature, supports research showing that birds are dinosaurs, having descended from a group of bipedal dinosaurs called theropods.

Dr. Prum and his colleagues, meanwhile, had set out on a similar quest. “We had a dream: to put colors on a dinosaur,” said Jakob Vinther, a graduate student at Yale.

Working with paleontologists at the Beijing Museum of Natural History and Peking University, the researchers began to study a 150-million-year-old species called Anchiornis huxleyi. The chicken-sized theropod was festooned with long feathers on its arms and legs.

The researchers removed 29 chips, each the size of a poppy seed, from across the dinosaur’s body. Mr. Vinther put the chips under a microscope and discovered melanosomes.

To figure out the colors of Anchiornis feathers, Mr. Vinther and his colleagues turned to Matthew Shawkey, a University of Akron biologist who has made detailed studies of melanosome patterns in living birds. Dr. Shawkey can accurately predict the color of feathers from melanosomes alone. The scientists used the same method to decipher Anchiornis’s color pattern.

Anchiornis had a crown of reddish feathers surrounding dark gray ones, and its face was mottled with reddish and black spots. Its body was dark gray, but its limb feathers were white with black tips.

Given the full detail of the findings, Dr. Prum said, “it was like writing the first entry in a Jurassic field guide to feathered dinosaurs.”

Luis M. Chiappe, a paleontologist at the Natural History Museum of Los Angeles County who was not involved in the research, praised the rigor and detail of the new study. “For a dinosaur scientist, this is like the birth of color TV,” Dr. Chiappe said.

The color pattern of Anchiornis is reminiscent of living birds. A breed of chickens called Silver Spangled Hamburgs, for example, has white, black-tipped wing feathers. Dr. Prum speculated that studying these chickens might allow scientists to determine the specific mutations that gave rise to Anchiornis’s plumage.

The color pattern on Anchiornis was so extravagant that the scientists are confident it served some visual function. “It was definitely for showing off,” Mr. Vinther said.

Some features, like the crest, might have allowed the dinosaur to attract mates. But white and black limb feathers might have helped Anchiornis escape predators. A number of living animals like zebras use similar color patterns to dazzle predators, so that they can run away.

The researchers expect many more surprises as scientists look at other dinosaur fossils.

“There is a big chapter of dinosaur biology that we can open up now,” Mr. Vinther said.

Courtesy: Newyork Times

Master Gene SRC-3 Enables Breast Cancer Growth, Invasion

The master gene called SRC-3 (steroid receptor coactivator 3) not only enhances estrogen-dependent growth of cancer cells by activating and encouraging the transcription of a genetic message into a protein, it also sends a signal to the cell membrane to promote cell motility or movement -- a key element of cancer spread or metastasis, said Baylor College of Medicine researchers and collaborators in a report that appears in the current issue of the journal Molecular Cell.

The finding not only uncovers a new activity for SRC-3 at the cell's periphery, it also clears up a mystery about how the message that tells a cell to invade gets from the epidermal growth factor receptor (EGFR) to the activating enzyme called FAK (focal adhesion kinase) found on the cell's membrane, said Dr. Bert O'Malley, chair of molecular and cellular biology at BCM and the report's senior author.

"Two-thirds of breast cancers over express the gene SRC-3," said O'Malley, who is the 2008 National Medal of Science recipient. "The work represented in this paper shows that a coactivator gene (SRC-3) can produce an alternative form of its coactivator protein -- a shorter form that is missing the part of the protein that keeps it in the nucleus. With that portion (called an exon) gone, it leaves the nucleus and goes into the cytoplasm (or general area of the cell) and travels to the membrane," he said.

"At the membrane, the enzyme PAK1 (p21-activted kinase 1) phosphorylates (attaches a phosphate molecule that activates the coactivator) SRC-3, allowing it to function at the membrane," said O'Malley, responsible for identifying the first receptor coactivator and advancing the field in general.

The finding explains how the epidermal growth factor receptor at the membrane gets a signal to the enzyme that tells the cell to move -- and ultimately grow, allowing the cancer to invade surrounding tissue, said O'Malley.

"Now we have a final picture as to why epidermal growth factor receptor and the estrogen receptor are the most dangerous combination of molecules overproduced in breast cancer," said O'Malley. "When they are both over functioning, people die quickly and are resistant to therapy."

Others who took part in the research include: Weiwen Long, Ping Yi, Larbi Amazit, Heather L. LaMarca, Felicity Ashcroft, Michael A. Mancini, Sophia Y. Tsai and Ming-Jer Tsai, all of BCM and Rakesh Kumar of the George Washington University Medical Center in Washington, DC. Amazit is now at INSERM in France.

Funding for this report came from the National Institutes of Health and the Welch Foundation.

Courtesy: ScienceDaily

Hospital-Clean Hands, Without All the Scrubbing

HOSPITAL workers often have to wash their hands dozens of times a day — and may need a minute or more to do the process right, by scrubbing with soap and water. But new devices could reduce the task to just four seconds, cleaning even hard-to-reach areas under fingernails.

Instead of scrubbing, the workers would put their hands into a small box that bathes them with plasma — the same sort of luminous gas found in neon signs, fluorescent tubes and TV displays. This plasma, though, is at room temperature and pressure, and is engineered to zap germs, including the drug-resistant supergerm MRSA.

The technology is being developed in several laboratories. Gregor Morfill, who created several prototypes using the technology at the Max Planck Institute for Extraterrestrial Physics in Garching, Germany, says the plasma quickly inactivates not only bacteria but also viruses and fungi.

Dr. Morfill and his colleagues have tested their devices on hands and feet. “It works on athlete’s foot,” he said. “And the nice thing is, you don’t have to take your socks off. They are disinfected, too.” (The cleaning takes a bit longer when socks are added to the job, he said — about 25 seconds. “And it doesn’t yet work through shoes,” he added.)

Plasmas engineered to zap microorganisms aren’t new. During the last decade, they have come into use to sterilize some medical instruments. But using them on human tissue is another matter, said Mark Kushner, director of the Michigan Institute for Plasma Science and Engineering and a professor at the University of Michigan in Ann Arbor. “Many thousands of volts drive the generation of plasma,” he said, “and normally one doesn’t want to touch thousands of volts.” But the design of the new hand sanitizers, he said, protects people from doing so. Reassured by that design, about five years ago he put his naked thumb into a jet of microbe-destroying plasma at the lab of another plasma researcher.

“It was just one of those leaps of faith,” he said. (His thumb survived just fine.)

Research in the field of plasma medicine has grown quickly in the last decade, with at least 50 groups worldwide working on medical uses, Professor Kushner estimated.

He said that there were many documented cases of plasmas being applied for sanitizing skin or other body parts, and “for speeding the rate of blood clotting in wound healing.”

“Plasmas turn out to have beneficial effects,” he said.

Dr. Morfill, who has a plasma research laboratory inside the international space station, took an unusual route to studying medical uses of plasmas. He was researching the natural plasmas of space, including the charged dust in Saturn’s rings, and decided to develop plasmas for health on earth.

He has developed several prototypes of hand-cleaning devices that can be mounted on walls, as well as a portable, battery-operated model the size of a large electric toothbrush. Companies are interested in manufacturing the devices, he said, which may one day be particularly useful in developing countries where medical services can be scarce.

The devices can probably be built for $100 or less, as no expensive parts are used, he said.

The plasma cleaners make their antibacterial cocktails by running electrical current through air, said David B. Graves, a professor of chemical engineering at the University of California, Berkeley, who has worked on low-temperature plasma applications for 25 years.

Professor Graves is doing computer simulations of the chemical reactions that occur in the Morfill plasmas. The electric current ionizes the oxygen, nitrogen and water vapor in the air, he said, eventually creating the nitric oxide, hydrogen peroxide and particles that are so effective against bacteria, viruses and fungi.

Many other cleaning applications of plasma are being researched. In addition to hand sanitizers, Michael G. Kong, a professor of bioelectrics engineering at Loughborough University in Leicestershire, England, has developed a prototype for plasma jets that can be built into air-conditioning systems. As air is transmitted through the system from one hospital room to another, for example, the jets inactivate microorganisms, fungi and viruses in the air.

IN the Netherlands, Gerrit M. W. Kroesen, a professor of plasma physics at the Eindhoven University of Technology, is focusing on the treatment of burn wounds. “We have seen that plasmas help with disinfection,” he said. “They also stimulate regeneration of tissue.”

The first products to reach hospitals, after surface cleaners and instrument disinfectants, will probably be hand sanitizers, said Alexander Fridman, a professor and director of the Drexel Plasma Institute at Drexel University in Philadelphia.

“Hand sanitizers are the low-hanging fruit here,” he said, as their safety can be demonstrated relatively easily.

But other potential applications, including treatment of burns or cancers, are further away. “We are able to do miracles with this technology,” he said, “but we have to make sure the treatments are not toxic.”

E-mail: novelties@nytimes.com.

Luminous 3-D Jungle Is a Biologist’s Dream

When watching a Hollywood movie that has robed itself in the themes and paraphernalia of science, a scientist expects to feel anything from annoyance to infuriation at facts misconstrued or processes misrepresented. What a scientist does not expect is to enter into a state of ecstatic wonderment, to have the urge to leap up and shout: “Yes! That’s exactly what it’s like!”

So it is time for all the biologists who have not yet done so to shut their laptops and run from their laboratories directly to the movie theaters, put on 3-D glasses and watch the film “Avatar.” In fact, anyone who loves a biologist or may want to be one, or better yet, anyone who hates a biologist — and certainly everyone who has ever sneered at a tree-hugger — should do the same. Because the director James Cameron’s otherworldly tale of romance and battle, aliens and armadas, has somehow managed to do what no other film has done. It has recreated what is the heart of biology: the naked, heart-stopping wonder of really seeing the living world.

The real beauty of it, though, is that you do not have to be a scientist to enjoy the experience. “Avatar” is well within reach of becoming the highest-grossing film of all time. And while the movie’s dazzling animation and use of 3-D has received so much attention, it cannot be anything but the intense wonder so powerfully elicited, rather than merely the technical wizardry itself, that has people lining up to see it.

There have, of course, been many films that have depicted the excitement of scientists during discovery (think of Laura Dern in “Jurassic Park,” gleefully sticking her hand into a pile of dinosaur dung), and, from “Lord of the Rings” to “Star Trek,” there has been no shortage of on-screen fantastical floras and faunas.

But rather than having us giggling at a tribble or worrying over the safety of the children when a T. rex attacks, Mr. Cameron somehow has the audience seeing organisms in the tropical-forest-gone-mad of the planet Pandora just the way a biologist sees them. With each glance, we are reminded of organisms we already know, while marveling over the new and trying quickly to put this novelty into some kind of sensible place in the mind. It is a mental tickle, and wonderful confusion sparks the thought, “Oh, that looks like a horse, but wait, it has six legs and it’s blue, and whoa, that looks like a jellyfish but it’s floating in the air and glowing.”

The clues that we are “not in Kansas anymore,” as we are told early on, can be seen in every aspect of the life of Pandora. If there is one color that is most decidedly not a classic Earth tone, one that is least associated with living things, it might just be neon blue. And so many things on Pandora, like the Pterodactyl-like ikran and the deerlike yerik, are a staring, screaming blue. Another thing we do not expect from most living things is light. Yet on Pandora, life glows everywhere in the night, including the long, pulsating white Spanish-moss-like strands elegantly dangling off tree branches and the brightly glowing green and purple ferns.

And touching closest to home, Mr. Cameron has put a version of ourselves on Pandora, the Na’vi people, with whom he uses every trick. For they are blue, they have bioluminescing spots on their faces and they display the other of Pandora organisms’ stunning quirks: they are huge, at 10 feet tall.

To so strongly experience these kinds of wonderfully shocking similarities and dissimilarities among living things is the kind of experience that has largely been the prerogative of biologists — especially those known as taxonomists, who spend their days ordering and naming the living things on Earth. But now, thanks to Mr. Cameron, the entire world is not only experiencing this but also reveling in it.

What is sort of funny for me is that I spent much of the last six years working on a book about exactly this, about how inside of all humans there is a deep desire and ability to really see life, to see order among living things, and about the joy that comes with it. So at the end of “Naming Nature” (W. W. Norton, 2009), I make a plea to readers to go out into the world and see the life and find the order in the living world around them. I may have to amend the paperback to suggest, or you may want to begin by, heading into a darkened room to see “Avatar” and have your mind blown.

Please excuse me if I seem a bit breathless, but the experience I had when I first saw the film (in 2-D, no less) shocked me. I felt as if someone had filmed my favorite dreams from those best nights of sleep where I wander and play through a landscape of familiar yet strange creatures, taking a swim and noticing dinosaurs paddling by, going out for a walk and spying several entirely new species of penguins, going sledding with giant tortoises. Less than the details of the movie, it was, I realized, the same feeling of elation, of wonder at life.

Perhaps that kind of potent joy is now the only way to fire up a vision of order in life. Many biologists of my generation (I will be 47 this month) were inspired to careers in science by the now quaint Time-Life series of illustrated books on animals or by the television program “Wild Kingdom,” rugged on-screen stuff for its time (“Now my assistant Jim will attempt to sedate the cheetah”). But maybe that isn’t enough anymore.

Maybe it takes a dreamlike ecstasy to break through to a world so jaded, to reach people who have seen David Attenborough here, there and everywhere, who have clicked — bored — past the Animal Planet channel hundreds of times without ever really seeing the animals. Maybe it takes a lizard that can glow like fire and hover like a helicopter and a staring troop of iridescent blue lemurs to wake us up. Maybe “Avatar” is what we need to bring our inner taxonomist back to life, to get us to really see.

And waking up and seeing is what “Avatar” is about, as its characters tell us repeatedly, as when the marine hero, Jake Sully, played by Sam Worthington, struggles to make sense of his love interest’s passion for life on Pandora.

“Try to see the forest through her eyes,” urges Dr. Grace Augustine, played by Sigourney Weaver, head of the Avatar project.

And here we have yet another reason for scientists to love this movie. Who has not tired of seeing scientists portrayed as either grant-greedy maniacs or naïve dangers to humanity, shouting “I’m sure the creatures are friendly!” just before being devoured? In films, scientists are often assumed to be inhuman to some degree, and if they become more human as a film proceeds, it is by becoming less of a scientist.

Instead, in “Avatar,” Dr. Augustine begins as usual, abrasive and obsessed with her own project. But the audience begins to like her more and more, not because she becomes less involved with the life on Pandora, but because we become more involved with it.

“Get it?” she asks, after explaining the beauty and importance of the life on Pandora to her corporate nemesis. And though he does not, by that point, we do.

And — spoiler alert! — that is why when she, dying, arrives at the most sacred and most biologically important site on Pandora, it is with a sympathy and respect that we laugh when her first thought is that she really needs to take some samples. There is no line between her wonder, her love of the living world and her science. We get it.

Courtesy: New york Times

Chromosomal Test By Molecular Biologists Determines Cancer Spread

A new biopsy test, created by molecular biologists, can tell ocular melanoma patients if theirs is the kind that will spread. Using very thin needles, surgeons collect cells from tumors and analyze them. If tumors are missing a copy of chromosome three, patients are at high risk of having their cancer spread. While there's no cure for ocular melanoma, patients who are at higher risk can be followed more closely and put on experimental treatments.

Ocular melanoma, or eye cancer, is a serious disease that affects about 2,000 Americans each year. Roughly half of patients will die from the cancer because their tumor spreads to other areas of the body. Now, a new test can tell patients if they're looking at life ... or death.

Just like everyone, Susan Izanstark-Rosenthal relies on her eyes every second of every day. "I'm an attorney, and I read and write all day long," she says.

But about a year ago, she didn't know if she'd be able to see out of her left eye ever again. Rosenthal was diagnosed with ocular melanoma. Surgery followed.

"It was very scary, and I didn't know when I woke up if I'd be able to see in the other eye," she says. Even scarier -- she found out she could die if her cancer spread. Ocular oncologist Tara Young, says a new biopsy test can tell patients if their tumor is the kind that will spread.

"It represents the first step that we've been able to make in a long time with this cancer," Young, of the Jules Stein Eye Institute at UCLA, tells DBIS.

Using very thin needles, surgeons collect cells from tumors and analyze them. If tumors are missing a copy of chromosome three, patients are at high risk of having their cancer spread. If tumors are normal, they have a very low risk.

"If someone could tell you that you were gonna go and die of your cancer, I think that most people want that information and that knowledge, so that they can just take a little bit more control over their lives," Young says.

Only a handful of medical centers across the country are performing the eye biopsy technique. While there's no cure for ocular melanoma, patients who are at higher risk can be followed more closely and put on experimental treatments. She says so far, all of her patients have wanted to know the results of their biopsy.

Rosenthal wasn't missing a copy. It's a great relief for her -- and her daughter. "It's given me, once again, a reminder that you need to appreciate every day and be very grateful for what you have," Rosenthal says.

BACKGROUND: The Jules Stein Eye Institute at the University of California, Los Angeles, is the first center in the country to practice analyzing rare eye cancers at a level as small as a molecule. The new biopsy technique looks for a certain chromosome within the tumor that can predict which tumors have a high risk of spreading. Physicians can determine this earlier, and thereby recommend much more aggressive treatment, resulting in longer survival rates for their patients. Since 2005, JSEI has performed more than 70 procedures.

ABOUT THE DISEASE: Ocular melanoma -- eye cancer -- is a particularly rare and aggressive form of cancer that attacks the pigment cells in the retina. There are essentially two types of intraocular melanoma: low-grade tumors, which grow slowly and rarely metastasize, and high-grade tumors, which grow more quickly and metastasize at a very early stage. Once a tumor metastasizes, the cancer spreads quickly to the liver and other organs, and a patient has only 6 to 12 months to live in most cases, although some can survive for as long as 5 years. The National Eye Institute reports some 2000 newly diagnosed cases of ocular melanoma per year in the US and Canada's roughly seven in one million people. It affects people of all ages and races, and is not hereditary. Ocular melanoma kills nearly half of those who develop it

IT'S ALL IN THE GENES: Doctors understand very little about the molecular changes that result in this aggressive behavior, but they now know that patients who are missing one copy of chromosome 3 in their tumor tissue are more likely to have highly aggressive cancers. For the first time, UCLA surgeons have demonstrated that it is feasible and safe to perform a biopsy on a living eye. They use an ultra-fine needle to collect cells from the cancer before surgery and send the sample to the lab for culture. After growing the tumor cells, a geneticist analyzes them to determine which are missing a copy of chromosome 3. This genetic marker tells them which patients require more aggressive treatment for their cancer.

WHAT ARE CHROMOSOMES? A chromosome is a single large macromolecule of DNA, and constitutes a physically organized form of DNA in a cell. It is a very long, continuous piece of DNA (a single DNA molecule), which contains many genes, regulatory elements and other intervening nucleotide sequences. A broader definition of "chromosome" also includes the DNA-bound proteins which serve to package and manage the DNA. The word chromosome comes from the Greek chroma ('color') and soma ('body') due to its capacity to be stained very strongly with dyes.

Courtesy: ScienceDaily

Physicists Kill Cancer With 'Nanobubbles'

Using lasers and nanoparticles, scientists at Rice University have discovered a new technique for singling out individual diseased cells and destroying them with tiny explosions. The scientists used lasers to make "nanobubbles" by zapping gold nanoparticles inside cells. In tests on cancer cells, they found they could tune the lasers to create either small, bright bubbles that were visible but harmless or large bubbles that burst the cells.

"Single-cell targeting is one of the most touted advantages of nanomedicine, and our approach delivers on that promise with a localized effect inside an individual cell," said Rice physicist Dmitri Lapotko, the lead researcher on the project. "The idea is to spot and treat unhealthy cells early, before a disease progresses to the point of making people extremely ill."

The research is available online in the journal Nanotechnology.

Nanobubbles are created when gold nanoparticles are struck by short laser pulses. The short-lived bubbles are very bright and can be made smaller or larger by varying the power of the laser. Because they are visible under a microscope, nanobubbles can be used to either diagnose sick cells or to track the explosions that are destroying them.

In laboratory studies published last year, Lapotko and colleagues at the Laboratory for Laser Cytotechnologies at the A.V. Lykov Heat and Mass Transfer Institute in Minsk, Belarus, applied nanobubbles to arterial plaque. They found that they could blast right through the deposits that block arteries.

"The bubbles work like a jackhammer," Lapotko said.

In the current study, Lapotko and Rice colleague Jason Hafner, associate professor of physics and astronomy and of chemistry, tested the approach on leukemia cells and cells from head and neck cancers. They attached antibodies to the nanoparticles so they would target only the cancer cells, and they found the technique was effective at locating and killing the cancer cells.

Lapotko said the nanobubble technology could be used for "theranostics," a single process that combines diagnosis and therapy. In addition, because the cell-bursting nanobubbles also show up on microscopes in real time, Lapotko said the technique can be use for post-therapeutic assessment, or what physicians often refer to as "guidance."

Hafner said, "The mechanical and optical properties of the bubbles offer unique advantages in localizing the biomedical applications to the individual cell level, or perhaps even to work within cells."

The research resulted from collaboration between Rice and the Lykov Institute of the Academy of Science of Belarus, which recently established the US-Belarus Research Lab of Fundamental and Biomedical Nanophotonics.

Co-authors of the Nanotechnology paper include Ehab Hanna of the University of Texas M.D. Anderson Cancer Center and Ekaterina Lukianova-Hleb of the Lykov Institute.

Courtesy: ScienceDaily

'Artificial Pancreas' a Step Nearer for Children With Type 1 Diabetes

Scientists in Cambridge have made a significant step towards developing a so-called "artificial pancreas" system for managing type 1 diabetes in children. The team has developed and successfully tested a new algorithm, providing a stepping stone to home testing for the artificial pancreas.

The new study -- funded by Juvenile Diabetes Research Foundation (JDRF) and published in The Lancet -- shows that using an artificial pancreas system overnight can significantly reduce the risk of hypoglycemia, when blood glucose levels drop dangerously low, while sleeping. These so-called "hypos" are a major concern for children and adults with type 1 diabetes.

An artificial pancreas system combines a continuous glucose monitor and an insulin pump, both already on the market, and uses a sophisticated algorithm to calculate the appropriate amount of insulin to deliver based on the real-time glucose readings.

As well as obviating the need for multiple daily finger prick tests and insulin injections, the artificial pancreas should offer better control of blood glucose levels overnight.

In the new study, 17 children and teenagers aged between 5 and 18 with type 1 diabetes were studied during 54 nights in hospital. The team measured how well the artificial pancreas system controlled glucose levels compared with the children's regular continuous subcutaneous insulin infusion (CSII) pump, which delivers insulin at preselected rates.

The study included nights when the children went to bed after eating a large evening meal or having done early evening exercise. Both are challenging to manage, a large evening meal because it can lead to so-called "insulin stacking" and, as a result, a potentially dangerous drop in blood glucose levels later in the night, and late afternoon or early evening exercise because it increases the body's need for glucose in the early morning and can therefore increase the risk of night time hypoglycaemia.

The pooled results showed the artificial pancreas kept blood glucose levels in the normal range for 60% of the time, compared with 40% for the CSII. The artificial pancreas halved the time that blood glucose levels fell below 3.9mmol/l -- the level considered as mild hypoglycaemia. It also prevented blood glucose falling below 3.0mmol/l, which is defined as significant hypoglycaemia, compared with nine hypoglycaemia events in the control studies.

According to lead author Dr Roman Hovorka of the Institute of Metabolic Science at the University of Cambridge: "Our results show that commercially-available devices, when coupled with the algorithm we developed, can improve glucose control in children and significantly reduce the risk of hypos overnight."

"This is the first randomised study showing the potential benefit of the artificial pancreas system overnight using commercially-available sensors and pumps. Our study provides a stepping stone for testing the system at home."

Type 1 diabetes is a chronic, life threatening condition which is on the increase in the UK, particularly in the under fives. Children and adults require multiple daily insulin injections or pump infusions and many finger prick blood tests each day. However, treatment with insulin brings with it the risk of hypoglycaemia, one of the most feared short-term complications of type 1 diabetes for children and their parents.

Recent technological developments in blood glucose monitors and devices for continuous administration of insulin -- such as those used in this study -- can improve blood glucose control, but more needs to be done.

Commenting on the results Karen Addington, Chief Executive of JDRF said: "This study is proof of principle that type 1 diabetes in children can be safely managed overnight with an artificial pancreas system. We need to redouble our efforts to move the artificial pancreas from a concept in the clinic to a reality in the home of children and adults with type 1 diabetes."

Courtesy: ScienceDaily

Prions and the persistence of memory

Prions are a special class of proteins best known as the source for mad cow and other neurodegenerative diseases.

Despite this negative reputation, according to a new report in the today’s issue of Cell, a prion may also have important and very positive roles in brain function. The researchers suggest that a prion-like protein may participate in memory in higher eukaryotes, from sea slugs on up.

“The persistence of memory is a fundamental problem,” said Kausik Si of Stowers Institute for Medical Research. “Experiences are temporal; they happen once, but somehow must lead to changes [in the brain] that are somewhat permanent.”

Those changes must be mediated by molecules, including proteins. “The question is: how can you maintain a stable state with unstable biological molecules,” Si said.

And now, research conducted by Si in collaboration with Nobel laureate Eric Kandel, suggests that prions may be one solution to that problem. Prions are distinguished by their ability to assume at least two distinct conformational states, one of which is dominant and self-perpetuating. That means that once a protein switches to its ‘prion state’ it has the ability to convert other ‘non-prion’ proteins to that state as well. Therefore, once engaged, the ‘prion state’ is self-renewing and stable.

The findings suggest that memory traces may depend on a fairly unique mechanism involving a prion-like protein known as CPEB, Si said, adding to a growing body of evidence that proteins with the characteristics ascribed to disease-causing prions may have a broader role in biology.

Scientists have known for some time that plenty of prion-like proteins are found in relatively simple organisms such as yeast, some of which have known functions. A report by another group in Cell last year suggested that prions in yeast may serve as an important source of variation in nature.

Si’s team made its discovery in studies of the sea slug Aplysia, which has served as an elemental model for learning and memory for decades. When you touch the animals’ gills, they withdraw. When the slugs are trained by touching their gill and delivering a shock, that withdrawal reaction becomes stronger for up to a month.

Scientists long ago traced that simple learned behaviour to a specific set of sensory and motor neurons, which are stimulated by the nerve messenger serotonin. But Si wanted to better understand the underlying molecular details. In a survey of proteins made at the synapse when serotonin is applied, he turned up CPEB. Upon closer examination of the protein’s sequence, Si had what he calls his “aha moment.” He realized CPEB looked a lot like the prions others had found in yeast.

He earlier reported evidence that the slug protein does display prion-like properties when inserted into yeast. They now provide evidence that those characteristics hold when the protein is expressed in its usual spot — Aplysia sensory neurons. The proteins switch to their prion state and clump together (as prions typically do) in the presence of serotonin. An antibody that targets the clumped prion protein blocks the persistence of neural connections that are the cellular basis for learning and memory.

“These results are consistent with the idea that ApCPEB can act as a self-sustaining prion-like protein in the nervous system and thereby might allow the activity-dependent change in synaptic efficacy to persist for long periods of time,” the researchers conclude. Si cautions, however, that they haven’t yet proven that blocking CPEB’s ability to self-perpetuate also blocks memory. For that, he says they would need to see whether a slug with a mutant version of the protein would learn but then quickly forget.

“Persistence of memory is a difficult problem,” Si said. The new evidence offers “at least an idea” for how this may happen and he suspects the prion-like protein’s apparent role in memory may turn out to be a more general phenomenon. His group is following up on their findings by investigating the role of the fly version of CPEB, and Si notes that humans do have a similar protein.

Courtesy: Biochemistry.org