OREGON STATE UNIVERSITY

scientific research and advances

Lipoic acid helps restore, synchronize the “biological clock”

CORVALLIS, Ore. – Researchers have discovered a possible explanation for the surprisingly large range of biological effects that are linked to a micronutrient called lipoic acid: It appears to reset and synchronize circadian rhythms, or the “biological clock” found in most life forms.

The ability of lipoic acid to help restore a more normal circadian rhythm to aging animals could explain its apparent value in so many important biological functions, ranging from stress resistance to cardiac function, hormonal balance, muscle performance, glucose metabolism and the aging process.

The findings were made by biochemists from the Linus Pauling Institute at Oregon State University, and published in Biochemical and Biophysical Research Communications, a professional journal. The research was supported by the National Institutes of Health, through the National Center for Complementary and Alternative Medicine.

Lipoic acid has been the focus in recent years of increasing research by scientists around the world, who continue to find previously unknown effects of this micronutrient. As an antioxidant and compound essential for aerobic metabolism, it’s found at higher levels in organ meats and leafy vegetables such as spinach and broccoli.

“This could be a breakthrough in our understanding of why lipoic acid is so important and how it functions,” said Tory Hagen, the Helen P. Rumbel Professor for Healthy Aging Research in the Linus Pauling Institute, and a professor of biochemistry and biophysics in the OSU College of Science.

“Circadian rhythms are day-night cycles that affect the daily ebb and flow of critical biological processes,” Hagen said. “The more we improve our understanding of them, the more we find them involved in so many aspects of life.”

Almost one-third of all genes are influenced by circadian rhythms, and when out of balance they can play roles in cancer, heart disease, inflammation, hormonal imbalance and many other areas, the OSU researchers said.

Of particular importance is the dysfunction of circadian rhythms with age.

“In old animals, including elderly humans, it’s well-known that circadian rhythms break down and certain enzymes don’t function as efficiently, or as well as they should,” said Dove Keith, a research associate in the Linus Pauling Institute and lead author on this study.

“This is very important, and probably deserves a great deal more study than it is getting,” Keith said. “If lipoic acid offers a way to help synchronize and restore circadian rhythms, it could be quite significant.”

In this case the scientists studied the “circadian clock” of the liver. Lipid metabolism by the liver is relevant to normal energy use, metabolism, and when dysfunctional can help contribute to the “metabolic syndrome” that puts millions of people at higher risk of heart disease, diabetes and cancer.

Researchers fed laboratory animals higher levels of lipoic acid than might be attained in a normal diet, while monitoring proteins known to be affected by disruption of the circadian clock in older animals.

They found that lipoic acid helped remediate some of the liver dysfunction that’s often common in old age, and significantly improved the function of their circadian rhythms.

In previous research, scientists found that the amount of lipoic acid that could aid liver and normal lipid function was the equivalent of about 600 milligrams daily for a 150-pound human, more than could normally be obtained through the diet.

A primary goal of research in the Linus Pauling Institute and the OSU Center for Healthy Aging Research is to promote what scientists call “healthspan” – not just the ability to live a long life, but to have comparatively good health and normal activities during almost all of one’s life. Research on lipoic acid, at OSU and elsewhere, suggests it has value toward that goal.

Continued research will explore this process and its role in circadian function, whether it can be sustained, and optimal intake levels that might be needed to improve health.

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Tory Hagen, 541-737-5083

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Shifting rhythms

Rhythms decline with age

New assay to spot fake malaria drugs could save thousands of lives

CORVALLIS, Ore. – Chemists and students in science and engineering at Oregon State University have created a new type of chemical test, or assay, that’s inexpensive, simple, and can tell whether or not one of the primary drugs being used to treat malaria is genuine – an enormous and deadly problem in the developing world.

The World Health Organization has estimated that about 200,000 lives a year may be lost due to the use of counterfeit anti-malarial drugs. When commercialized, the new OSU technology may be able to help address that problem by testing drugs for efficacy at a cost of a few cents.

When broadly implemented, this might save thousands of lives every year around the world, and similar technology could also be developed for other types of medications and diseases, experts say.

Findings on the new technology were just published in Talanta, a professional journal.

“There are laboratory methods to analyze medications such as this, but they often are not available or widely used in the developing world where malaria kills thousands of people every year,” said Vincent Remcho, a professor of chemistry and Patricia Valian Reser Faculty Scholar in the OSU College of Science, a position which helped support this work.

“What we need are inexpensive, accurate assays that can detect adulterated pharmaceuticals in the field, simple enough that anyone can use them,” Remcho said. “Our technology should provide that.”

The system created at OSU looks about as simple, and is almost as cheap, as a sheet of paper. But it’s actually a highly sophisticated “colorimetric” assay that consumers could use to tell whether or not they are getting the medication they paid for – artesunate - which is by far the most important drug used to treat serious cases of malaria. The assay also verifies that an adequate level of the drug is present.

In some places in the developing world, more than 80 percent of outlets are selling counterfeit pharmaceuticals, researchers have found. One survey found that 38-53 percent of outlets in Cambodia, Laos, Myanmar, Thailand and Vietnam had no active drug in the product that was being sold. Artesunate, which can cost $1 to $2 per adult treatment, is considered an expensive drug by the standards of the developing world, making counterfeit drugs profitable since the disease is so prevalent.

Besides allowing thousands of needless deaths, the spread of counterfeit drugs with sub-therapeutic levels of artesunate can promote the development of new strains of multi-drug resistant malaria, with global impacts. Government officials could also use the new system as a rapid screening tool to help combat the larger problem of drug counterfeiting.

The new technology is an application of microfluidics, in this instance paper microfluidics, in which a film is impressed onto paper that can then detect the presence and level of the artesunate drug. A single pill can be crushed, dissolved in water, and when a drop of the solution is placed on the paper, it turns yellow if the drug is present. The intensity of the color indicates the level of the drug, which can be compared to a simple color chart.

OSU undergraduate and graduate students in chemistry and computer science working on this project in the Remcho lab took the system a step further, and created an app for an iPhone that could be used to measure the color, and tell with an even higher degree of accuracy both the presence and level of the drug.

The technology is similar to what can be accomplished with computers and expensive laboratory equipment, but is much simpler and less expensive. As a result, use of this approach may significantly expand in medicine, scientists said.

“This is conceptually similar to what we do with integrated circuit chips in computers, but we’re pushing fluids around instead of electrons, to reveal chemical information that’s useful to us,” Remcho said.  “Chemical communication is how Mother Nature does it, and the long term applications of this approach really are mind-blowing.”

Colorimetric assays have already been developed for measurement of many biomarker targets of interest, Remcho said, and could be expanded for a wide range of other medical conditions, pharmaceutical and diagnostic tests, pathogen detection, environmental analysis and other uses.

With a proof of concept of the new technology complete, the researchers may work with the OSU Advantage to commercialize the technology, ultimately with global application. As an incubator for startup and early stage organizations, OSU Advantage connects business with faculty expertise and student talent to bring technology such as this to market.

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Vincent Remcho, 541-737-8181

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Paper assay

Drug assay

Antibiotic use prevalent in hospice patients despite limited evidence of its value

CORVALLIS, Ore. – New research suggests that use of antibiotics is still prevalent among terminal patients who have chosen hospice care as an end-of-life option, despite little evidence that the medications improve symptoms or quality of life, and sometimes may cause unwanted side effects.

The use of antibiotics is so engrained in contemporary medicine that 21 percent of patients being discharged from hospitals directly to a hospice program leave with a prescription for antibiotics, even though more than one fourth of them don’t have a documented infection during their hospital admission.

About 27 percent of hospice patients are still taking antibiotics in the final week of their life.

This raises serious questions about whether such broad and continued antibiotic use is appropriate in so many hospice cases, experts say, where the underlying concept is to control pain and protect the remaining quality of life without aggressively continuing medical treatment.

Additional concerns with antibiotic use, the study concluded, include medication side effects and adverse events, increased risk of subsequent opportunistic infections, prolonging the dying process and increasing the risk of developing antibiotic resistant microorganisms.

The findings were just published in Antimicrobial Agents and Chemotherapy by researchers from Oregon State University and the Oregon Health & Science University. It was supported by the National Institutes of Health.

“Hospice care is very patient centered and in terminal patients it focuses on palliative care and symptom relief, not curative therapy,” said Jon Furuno, an associate professor in the Oregon State University/Oregon Health & Science University College of Pharmacy.

“It’s not for everyone, and it’s a serious decision people usually make in consultation with their family, nurses and doctors. These are tough conversations to have.

“Having decided to use hospice, however, the frequency and prevalence of antibiotic use in this patient population is a concern,” Furuno said. “Antibiotics themselves can have serious side effects that sometimes cause new problems, a factor that often isn’t adequately considered. And in terminally-ill people they may or may not work anyway.”

Issues such as this, Furuno said, continue to crop up in the evolving issue of hospice care, which is still growing in popularity as many people choose to naturally allow their life to end with limited medical treatment and often in their own homes. Hospice is covered by Medicare for people with a life expectancy of less than six months, helps to control medical costs and reduce hospital stays, and its services are now used by more than one third of dying Americans.

Unnecessary and inappropriate antibiotic use is already a concern across all segments of society, researchers said in the report, and more efforts are clearly needed to address the issue in hospice patients. The design of the study probably leads to it underestimating the significance of the problem, the researchers wrote in their conclusion.

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Jon Furuno, 503-418-9361

Review: Lead ammunition can be deadly, though mitigation may help

CORVALLIS, Ore. – The ingestion of lead ammunition and lead fishing tackle accounts for illness and mortality in more than 120 different species of birds in North America, according to a newly published review of scientific studies on the issue.

What impact that has at the population level for species is less clear, the researchers say, as is how to deal with the growing controversy over the use of lead for hunting and fishing. The lead issue is complex and steps to mitigate the impacts will be challenging – from cost and performance factors to manufacturing output – but they are possible, the authors point out.

“Although lead shot has been banned for waterfowl hunting in the United States since 1991, and in Canada since 1999, exposure to lead remains a problem for many bird species,” said Susan Haig, supervisory wildlife ecologist with the U.S. Geological Survey and lead author on the study. “However, we did find several examples of ways wildlife managers have helped reduce exposure of birds to lead.”

The review of scientific studies, conducted by biologists from several different institutions and agencies, was published in the July edition of the journal The Condor: Ornithological Applications. A companion perspective article, written by Clinton Epps, an associate professor in the Department of Fisheries and Wildlife at Oregon State University, examines the challenges of transitioning to non-lead ammunition.

In their papers, the researchers do not call for any policy changes, but they outline some of the challenges of reducing the use of lead and explore tactics that have been used to reduce lead exposure.

“Shifting to non-lead alternatives is a lot more complicated than some people think,” said Epps, who has hunted for more than 30 years. “Any efforts to shift hunters and fishermen from using lead needs to be well-informed and collaborative. Everyone concerned with this issue must be prepared to invest time, money, and expertise to work not only with hunters and fishermen, but with ammunition and tackle manufacturers.”

Epps has looked at copper bullets as one less-toxic alternative to lead and notes that they generally work well in modern firearms commonly used for big game hunting. However, effective non-lead alternatives have not yet been developed for all types of hunting firearms, he added.

In the review article, the researchers outline the availability of non-lead ammunition in October 2013 in 35 different calibers and 51 rifle-cartridge configurations at three major online retailers. Of the non-lead options sold by those retailers, only a small proportion was actually in stock: Cabela’s had non-lead ammunition in 18 percent of available sizes; Cheaper Than Dirt, 27 percent; and Bass Pro Shops, 10 percent.

“Non-lead bullets can be difficult to find in all calibers needed, but availability is improving,” Epps said. “Premium quality hunting ammunition costs about the same for lead-based and non-lead options, but I see a lot of people using the cheaper options, which invariably contain lead, so cost may be an issue – particularly for high-volume users.”

The physical properties of lead – including high density, low melting point, malleability and resistance to corrosion – have made it popular in the manufacturing of ammunition and fishing sinkers. However, many birds are sensitive to lead exposure, affecting the structure and function of kidneys, bones, the central nervous system and the blood system. Impacts range from lethargy and anorexia, to reproductive issues and death.

In their review, the researchers noted that lead has widely varying impacts.

  • One study of common loon carcasses found across six New England states found that about 23 percent (118 of 522) of the deaths were caused by ingestion of lead fishing tackle and ammunition;
  • California condors are extremely susceptible to lead poisoning and suffer significant mortality, yet a related species known as turkey vultures can survive with greater and longer exposure to lead;
  • Few studies have been done on population-level impacts of lead with the most complete studies conducted on waterfowl, where deaths from lead poisoning are estimated to be 2-3 percent overall, and 4 percent in mallard ducks.

A survey by the U.S. Geological Survey in 2013 found that 69,000 metric tons (a metric ton is about 2,204 pounds) of lead were used in the production of ammunition in the United States in one year. Annual estimates of lead fishing weights sold in the U.S. equal 3,977 metric tons.

Birds and other animals ingest lead in different ways, according to Haig. Loons, for example, were found to have swallowed lead sinkers and jigs, perhaps mistaking them for prey. Scavengers including condors and eagles often feed on carcasses of animals killed by hunters and cannot avoid incidental lead ingestion.

“Some birds use lead pellets or fragments as grit to aid in digestion after consuming it at hunting areas or shooting ranges,” said Haig, who is a courtesy professor of wildlife ecology at OSU. “Another potentially important lead source is recreational shooting of ground squirrels, which leaves lead-laced carcasses available to be eaten by golden eagles, Swainson’s hawks and other birds of prey.

“We found one estimate that more than 1.1 million ground squirrels were shot in one state during a one-year period,” she added. “It would be helpful to better understand what kinds of risk this poses to raptor scavengers.”

The review outlines some steps to reduce lead exposure to birds, including redistributing shot in the surface soil by cultivating sediments; raising water levels in wetlands to reduce access by feeding birds; and providing alternative uncontaminated food sources.

“Managers have found a number of ways to reduce the risk of lead exposure to birds while preserving the important role hunting plays in wildlife conservation,” Haig said.

One example cited involved Arizona Game and Fish working with other groups in that state on a voluntary approach to the issue.

“They formed a coalition to educate hunters about the negative effects of lead,” Haig pointed out. “The result was more than 80 percent compliance with voluntary non-lead ammunition use among hunters on the Kaibab Plateau and no birds were found with lead poisoning the following year.”

Other authors on the review include Jesse D’Elia, U.S. Fish and Wildlife Service and OSU Department of Fisheries and Wildlife; Collin Eagles-Smith, U.S. Geological Survey and OSU Fisheries and Wildlife; Garth Herring, U.S. Geological Survey; Jeanne M. Fair, Los Alamos National Laboratory; Jennifer Gervais, Oregon Wildlife Institute and OSU Fisheries and Wildlife; James W. Rivers, OSU Department of Forest Ecosystems and Society; and John H. Schulz, University of Missouri.

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Susan Haig, 541-750-0981, susan_haig@usgs.gov; Clint Epps, 541-737-2478, Clinton.epps@oregonstate.edu

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Figure 2 Magpie on carcass
magpie feedng on a carcass

SAR11, oceans’ most abundant organism, has ability to create methane

CORVALLIS, Ore. – The oxygen-rich surface waters of the world’s major oceans are supersaturated with methane – a powerful greenhouse gas that is roughly 20 times more potent than carbon dioxide – yet little is known about the source of this methane.

Now a new study by researchers at Oregon State University demonstrates the ability of some strains of the oceans’ most abundant organism – SAR11 – to generate methane as a byproduct of breaking down a compound for its phosphorus.

Results of the study are being published this week in Nature Communications. It was funded by the National Science Foundation and the Gordon and Betty Moore Foundation.

“Anaerobic methane biogenesis was the only process known to produce methane in the oceans and that requires environments with very low levels of oxygen,” said Angelicque “Angel” White, a researcher in OSU’s College of Earth, Ocean, and Atmospheric Sciences and co-author on the study. “In the vast central gyres of the Pacific and Atlantic oceans, the surface waters have lots of oxygen from mixing with the atmosphere – and yet they also have lots of methane, hence the term ‘marine methane paradox.’

“We’ve now learned that certain strains of SAR11, when starved for phosphorus, turn to a compound known as methylphosphonic acid,” White added. “The organisms produce enzymes that can break this compound apart, freeing up phosphorus that can be used for growth – and leaving methane behind.”

The discovery is an important piece of the puzzle in understanding the Earth’s methane cycle, scientists say. It builds on a series of studies conducted by researchers from several institutions around the world over the past several years.

Previous research has shown that adding methylphosphonic acid, or MPn, to seawater produces methane, though no one knew exactly how. Then a laboratory study led by David Karl of the University of Hawaii and OSU’s White found that an organism called Trichodesmium could break down MPn and thus it could be a potential source of phosphorus, which is a critical mineral essential to every living organism.

However, Trichodesmium are rare in the marine environment and unlikely to be the only source for vast methane deposits in the surface waters.

So White turned to Steve Giovannoni, a distinguished professor of microbiology at OSU, who not only maintains the world’s largest bank of SAR11 strains, but who also discovered and identified SAR11 in 1990. In a series of experiments, White, Giovannoni, and graduate students Paul Carini and Emily Campbell tested the capacity of different SAR11 strains to consume MPn and cleave off methane.

“We found that some did produce a methane byproduct, and some didn’t,” White said. “Just as some humans have a different capacity for breaking down compounds for nutrition than others, so do these organisms. The bottom line is that this shows phosphate-starved bacterioplankton have the capability of producing methane and doing so in oxygen-rich waters.”

SAR11 is the smallest free-living cell known and also has the smallest genome, or genetic structure, of any independent cell. Yet it dominates life in the oceans, thrives where most other cells would die, and plays a huge role in the cycling of carbon on Earth.

These bacteria are so dominant that their combined weight exceeds that of all the fish in the world's oceans, scientists say. In a marine environment that's low in nutrients and other resources, they are able to survive and replicate in extraordinary numbers – a milliliter of seawater, for instance, might contain 500,000 of these cells.

"The ocean is a competitive environment and these bacteria apparently won the race," said Giovannoni, a professor in OSU’s College of Science. "Our analysis of the SAR11 genome indicates that they became the dominant life form in the oceans largely by being the simplest.”

“Their ability to cleave off methane is an interesting finding because it provides a partial explanation for why methane is so abundant in the high-oxygen waters of the mid-ocean regions,” Giovannoni added. “Just how much they contribute to the methane budget still needs to be determined.”

Since the discovery of SAR11, scientists have been interested in their role in the Earth’s carbon budget. Now their possible implication in methane creation gives the study of these bacteria new importance.

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Angel White, 541-737-6397; awhite@coas.oregonstate.edu; Steve Giovannoni, 541-737-1835, steve.giovannoni@oregonstate.edu

Video games could provide venue for exploring sustainability concepts

CORVALLIS, Ore. – Could playing video games help people understand and address global sustainability issues such as pollution, drought or climate change? At least two researchers believe so, outlining their argument in a concept paper published in the journal “First Monday.”

Video games have the potential to educate the public and encourage development of creative solutions to social, economic and environmental problems, said Oregon State University’s Shawna Kelly, one of the two authors of the article.

“Video games encourage creative and strategic thinking, which could help people make sense of complex problems,” said Kelly, who teaches new media communications in the School of Arts and Communication at Oregon State’s College of Liberal Arts.

“Entertainment has always been a space for exposing people to new ideas. Using video games, it’s possible to introduce sustainability concepts to the mass public in a way that’s not pedantic, that’s not educational,” Kelly said. “Instead, it could be fun and it could be challenging.”

Kelly wrote the paper with Bonnie Nardi, an anthropologist with University of California, Irvine's Department of Informatics, who studies sustainability, collapse-preparedness and information technology. 

Kelly and Nardi identified four key areas in which video games could support sustainable practices. The areas are:

  • Shift away from growth as the end goal of a game. Uncontrollable growth is unsustainable and asks little of players’ imaginations.
  • Emphasize scavenging instead of combat to collect resources. Encourage players to interact with their environment in creative ways instead of simply looking for targets.
  • Offer complex avenues for social interaction. Move beyond “us versus them” and focus on other types of social collaborations.
  • Encourage strategizing with resources such as scenarios that incorporate long-term consequences and interdependencies of resource use.

Some video games already are using some of the elements Kelly and Nardi recommend. Economics-based games such as “EVE Online” challenge players to strategize between their short-term personal resource demands and the long-term needs of a larger group of players, their corporation. “DayZ” is a combat simulation game that requires players to scavenge for resources and work with other players, deciding on their own which players are friends and which are enemies.

Those are the kinds of game mechanics that make video games fun and challenging, but those mechanics also could be used to encourage players to think about real problems related to sustainability, Kelly said.

The culture of video gaming rewards people for solving problems and coming up with unique solutions. There is a common interest and connection among players, and knowledge is easily shared via game-specific wikis, message boards, instant messaging and more, Kelly pointed out.

“There’s a huge set of people out there who love to problem-solve,” she said. “Why not harness that power that is already there?”

That doesn’t mean someone should go out and develop “The Sustainability Game,” Kelly said. While video games have proven to be a good educational tool, there is a sense that those who play video games for entertainment don’t want forced educational components, she said.

“The attitude is ‘don’t make me learn something,’ ” Kelly said. “Instead, make the problems accessible to the gaming community and see what emerges.”

Kelly plans to continue exploring the relationship between video games and sustainability through additional research supported by OSU’s New Media Communications department. She’s planning to conduct a systematic survey of the use of sustainability concepts in current video games during the 2014-15 school year using undergraduate student research assistants and resources from New Media Communications.

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“Molecular movie” technology may enable big gains in bioimaging, health research

CORVALLIS, Ore. – Researchers today announced the creation of an imaging technology more powerful than anything that has existed before, and is fast enough to observe life processes as they actually happen at the molecular level.

Chemical and biological actions can now be measured as they are occurring or, in old-fashioned movie parlance, one frame at a time. This will allow creation of improved biosensors to study everything from nerve impulses to cancer metastasis as it occurs.

The measurements, created by the use of short pulse lasers and bioluminescent proteins, are made in femtoseconds, which is one-millionth of one-billionth of a second. A femtosecond, compared to one second, is about the same as one second compared to 32 million years.

That’s a pretty fast shutter speed, and it should change the way biological research and physical chemistry are being done, scientists say.

Findings on the new technology were published today in Proceedings of the National Academy of Sciences, by researchers from Oregon State University and the University of Alberta.

“With this technology we’re going to be able to slow down the observation of living processes and understand the exact sequences of biochemical reactions,” said Chong Fang, an assistant professor of chemistry in the OSU College of Science, and lead author on the research.

“We believe this is the first time ever that you can really see chemistry in action inside a biosensor,” he said. “This is a much more powerful tool to study, understand and tune biological processes.”

The system uses advanced pulse laser technology that is fairly new and builds upon the use of “green fluorescent proteins” that are popular in bioimaging and biomedicine. These remarkable proteins glow when light is shined upon them. Their discovery in 1962, and the applications that followed, were the basis for a Nobel Prize in 2008.

Existing biosensor systems, however, are created largely by random chance or trial and error. By comparison, the speed of the new approach will allow scientists to “see” what is happening at the molecular level and create whatever kind of sensor they want by rational design. This will improve the study of everything from cell metabolism to nerve impulses, how a flu virus infects a person, or how a malignant tumor spreads.

“For decades, to create the sensors we have now, people have been largely shooting in the dark,” Fang said. “This is a fundamental breakthrough in how to create biosensors for medical research from the bottom up. It’s like daylight has finally come.”

The technology, for instance, can follow the proton transfer associated with the movement of calcium ions – one of the most basic aspects of almost all living systems, and also one of the fastest. This movement of protons is integral to everything from respiration to cell metabolism and even plant photosynthesis.  Scientists will now be able to identify what is going on, one step at a time, and then use that knowledge to create customized biosensors for improved imaging of life processes.

“If you think of this in photographic terms,” Fang said, “we now have a camera fast enough to capture the molecular dance of life. We’re making molecular movies. And with this, we’re going to be able to create sensors that answer some important, new questions in biophysics, biochemistry, materials science and biomedical problems.”

The research was supported by OSU, the University of Alberta, the Natural Sciences and Engineering Research Council of Canada, and the Canadian Institutes of Health Research.

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Chong Fang, 541-737-6704

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Molecular movies

Molecular movies

NSF awards $200,000 to develop technology to treat sepsis, a global killer

CORVALLIS, Ore. – The National Science Foundation has just awarded $200,000 to engineers at Oregon State University who have developed a new technology that they believe could revolutionize the treatment and prevention of sepsis.

Sepsis is a “hidden killer” that in the United States actually kills more people every year than AIDS, prostate cancer and breast cancer combined.

More commonly called “blood poisoning,” sepsis can quickly turn a modest infection into a whole-body inflammation, based on a dysfunctional immune response to endotoxins that are released from the cell walls of bacteria. When severe, this can lead to multiple organ failure and death.

When treatment is begun early enough, sepsis can sometimes be successfully treated with antibiotics. But they are not always effective and the mortality rate for the condition is still 28-50 percent. About one in every four people in a hospital emergency room is there because of sepsis, and millions of people die from it around the world every year, according to reports in the New England Journal of Medicine and other studies.

In pioneering research, OSU experts have used microchannel technology and special coatings to create a small device through which blood could be processed, removing the problematic endotoxins and preventing sepsis. Several recent professional publications have reported on their progress.

“More work remains to be done, and the support from the National Science Foundation will be instrumental in that,” said Adam Higgins, principal investigator on the grant and an assistant professor in the OSU School of Chemical, Biological and Environmental Engineering. “When complete, we believe this technology will treat sepsis effectively at low cost, or even prevent it when used as a prophylactic treatment.”

This technology may finally offer a way to tackle sepsis other than antibiotics, the researchers said.

“This doesn’t just kill bacteria and leave floating fragments behind, it sticks to and removes the circulating bacteria and endotoxin particles that might help trigger a sepsis reaction,” said Karl Schilke, the OSU Callahan Faculty Scholar in Chemical Engineering.

“We hope to emboss the device out of low-cost polymers, so it should be inexpensive enough that it can be used once and then discarded,” Schilke said. “The low cost would also allow treatment even before sepsis is apparent. Anytime there’s a concern about sepsis developing – due to an injury, a wound, an operation, or an infection – you could get ahead of the problem.”

“A big part of the problem with sepsis is that it moves so rapidly,” said Joe McGuire, professor and head of the OSU Department of Chemical, Biological and Environmental Engineering. “By the time it’s apparent what the problem is, it’s often too late to treat it.

“If given early enough, antibiotics and other treatments can sometimes, but not always, stop this process,” McGuire said. “Once these bacterial fragments are in the blood stream the antibiotics won’t always work. You can have successfully eradicated the living bacteria even as you’re dying.”

The approach being developed at the OSU College of Engineering is to move blood through a very small processor, about the size of a coffee mug, and literally grab the endotoxins and remove them.

Microchannels make this possible. They can provide accelerated heat and mass transfer as fluids move through tiny tubes the width of a human hair. Applications are already being studied in everything from heat exchangers to solar energy. They can be produced in mass quantity at low cost, stamped onto a range of metals or plastics, and used to process a large volume of liquid in a comparatively short time.

In the system developed at Oregon State, blood can be pumped through thousands of microchannels that are coated with what researchers call “pendant polymer brushes,” with repeating chains of carbon and oxygen atoms anchored on the surface. This helps prevent blood proteins and cells from sticking or coagulating. On the end of each pendant chain is a peptide – or bioactive agent – that binds tightly to the endotoxin and removes it from the blood, which then goes directly back to the patient.

Sepsis is fairly common. It can develop after an injury from an automobile accident, a dirty wound, an extended operation in a hospital that carries a risk of infection, or infectious illnesses in people with weak or compromised immune systems.

In the U.S., more than $20 billion was spent on this problem in 2011. It’s the single most expensive cause of health problems that require hospitalization.

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Adam Higgins, 541-737-6245

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Sepsis device

Sepsis device

Study links Greenland ice sheet collapse, sea level rise 400,000 years ago

CORVALLIS, Ore. – A new study suggests that a warming period more than 400,000 years ago pushed the Greenland ice sheet past its stability threshold, resulting in a nearly complete deglaciation of southern Greenland and raising global sea levels some 4-6 meters.

The study is one of the first to zero in on how the vast Greenland ice sheet responded to warmer temperatures during that period, which were caused by changes in the Earth’s orbit around the sun.

Results of the study, which was funded by the National Science Foundation, are being published this week in the journal Nature.

“The climate 400,000 years ago was not that much different than what we see today, or at least what is predicted for the end of the century,” said Anders Carlson, an associate professor at Oregon State University and co-author on the study. “The forcing was different, but what is important is that the region crossed the threshold allowing the southern portion of the ice sheet to all but disappear.

“This may give us a better sense of what may happen in the future as temperatures continue rising,” Carlson added.

Few reliable models and little proxy data exist to document the extent of the Greenland ice sheet loss during a period known as the Marine Isotope Stage 11. This was an exceptionally long warm period between ice ages that resulted in a global sea level rise of about 6-13 meters above present. However, scientists have been unsure of how much sea level rise could be attributed to Greenland, and how much may have resulted from the melting of Antarctic ice sheets or other causes.

To find the answer, the researchers examined sediment cores collected off the coast of Greenland from what is called the Eirik Drift. During several years of research, they sampled the chemistry of the glacial stream sediment on the island and discovered that different parts of Greenland have unique chemical features. During the presence of ice sheets, the sediments are scraped off and carried into the water where they are deposited in the Eirik Drift.

“Each terrain has a distinct fingerprint,” Carlson noted. “They also have different tectonic histories and so changes between the terrains allow us to predict how old the sediments are, as well as where they came from. The sediments are only deposited when there is significant ice to erode the terrain. The absence of terrestrial deposits in the sediment suggests the absence of ice.

“Not only can we estimate how much ice there was,” he added, “but the isotopic signature can tell us where ice was present, or from where it was missing.”

This first “ice sheet tracer” utilizes strontium, lead and neodymium isotopes to track the terrestrial chemistry.

The researchers’ analysis of the scope of the ice loss suggests that deglaciation in southern Greenland 400,000 years ago would have accounted for at least four meters – and possibly up to six meters – of global sea level rise. Other studies have shown, however, that sea levels during that period were at least six meters above present, and may have been as much as 13 meters higher.

Carlson said the ice sheet loss likely went beyond the southern edges of Greenland, though not all the way to the center, which has not been ice-free for at least one million years.

In their Nature article, the researchers contrasted the events of Marine Isotope Stage 11 with another warming period that occurred about 125,000 years ago and resulted in a sea level rise of 5-10 meters. Their analysis of the sediment record suggests that not as much of the Greenland ice sheet was lost – in fact, only enough to contribute to a sea level rise of less than 2.5 meters.

“However, other studies have shown that Antarctica may have been unstable at the time and melting there may have made up the difference,” Carlson pointed out.

The researchers say the discovery of an ice sheet tracer that can be documented through sediment core analysis is a major step to understanding the history of ice sheets in Greenland – and their impact on global climate and sea level changes. They acknowledge the need for more widespread coring data and temperature reconstructions.

“This is the first step toward more complete knowledge of the ice history,” Carlson said, “but it is an important one.”

Lead author on the Nature study is Alberto Reyes, who worked as a postdoctoral researcher for Carlson when both were at the University of Wisconsin-Madison. Carlson is now on the faculty in Oregon State’s College of Earth, Ocean, and Atmospheric Sciences.

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Anders Carlson, 541-737-3625; acarlson@coas.oregonstate.edu

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Discovery of a bud-break gene could lead to trees adapted for a changing climate

CORVALLIS, Ore. — Scientists have confirmed the function of a gene that controls the awakening of trees from winter dormancy, a critical factor in their ability to adjust to environmental changes associated with climate change.

While other researchers have identified genes involved in producing the first green leaves of spring, the discovery of a master regulator in poplar trees (Populus species) could eventually lead to breeding plants that are better adapted for warmer climates.

The results of the study that began more than a decade ago at Oregon State University were published today in the Proceedings of the National Academy of Sciences, by scientists from Michigan Technological University and Oregon State.

“No one has ever isolated a controlling gene for this timing in a wild plant, outside of Arabidopsis, a small flowering plant related to mustard and cabbage,” said Steve Strauss, co-author and distinguished professor of forest biotechnology at OSU. “This is the first time a gene that controls the timing of bud break in trees has been identified.”

The timings of annual cycles — when trees open their leaves, when they produce flowers, when they go dormant — help trees adapt to changes in environmental signals like those associated with climate, but the genetics have to keep up, Strauss said.

While trees possess the genetic diversity to adjust to current conditions, climate models suggest that temperature and precipitation patterns in many parts of the world may expose trees to more stressful conditions in the future. Experts have suggested that some tree species may not be able to cope with these changes fast enough, whether by adaptation or migration. As a result, forest health may decline, trees may disappear from places they are currently found, and some species may even go extinct. 

“For example, are there going to be healthy and widespread populations of Douglas fir in Oregon in a hundred years?” said Strauss. “That depends on the natural diversity that we have and how much the environment changes. Will there be sufficient genetic diversity around to evolve populations that can cope with a much warmer and likely drier climate? We just don’t know.”

Strauss called the confirmation of the bud-break gene — which scientists named EBB1 for short — a “first step” in developing the ability to engineer adaptability into trees in the future.

“Having this knowledge enables you to engineer changes when they might become urgent,” he said.

Yordan Yordanov and Victor Busov at Michigan Tech worked with Cathleen Ma and Strauss at Oregon State to trace the function of EBB1 in buds and other plant tissues responsible for setting forth the first green shoots of spring. They developed modified trees that overproduced EBB1 genes and emerged from dormancy earlier in the year. They also showed that trees with less EBB1 activity emerged from dormancy later.

“The absence of EBB1 during dormancy allows the tree to progress through the physiological, developmental and adaptive changes leading to dormancy,” said Busov, “while the expression of EBB1 in specific cell layers prior to bud-break enables reactivation of growth in the cells that develop into shoots and leaves, and re-entry into the active growth phase of the tree.”

The study began when Strauss noticed poplar trees emerging earlier than others in an experimental field trial at Oregon State. One April morning, he found that four seedling trees in a 2.5-acre test plot were putting forth leaves at least a week before all the other trees. Strauss and Busov, a former post-doctoral researcher at Oregon State, led efforts to identify the genes responsible.

They found that EBB1 codes for a protein that helps to restart cell division in a part of the tree known as meristem, which is analogous to stem cells in animals. EBB1 also plays a role in suppressing genes that prepare trees for dormancy in the fall and in other processes such as nutrient cycling and root growth that are critical for survival. Altogether, they found nearly 1,000 other poplar genes whose activity is affected by EBB1.

It’s unlikely that plant breeders will use the finding any time soon, Strauss said. Breeders tend to rely on large clusters of genes that are associated with specific traits such as hardiness, tree shape or flowering. However, as more genes of this kind are identified, the opportunity to breed or engineer trees adapted to extreme conditions will grow.

Funding for the research was provided by the U.S. Department of Agriculture, the U.S. Department of Energy and the Tree Biosafety and Genomics Research Cooperative at Oregon State.

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Steve Strauss, 541-737-6578

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