OREGON STATE UNIVERSITY

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“Selfish” DNA in animal mitochondria offers possible tool to study aging

The study this story is based on is available online: http://bit.ly/OLw6YY

CORVALLIS, Ore. – Researchers at Oregon State University have discovered, for the first time in any animal species, a type of “selfish” mitochondrial DNA that is actually hurting the organism and lessening its chance to survive – and bears a strong similarity to some damage done to human cells as they age.

The findings, just published in the journal PLoS One, are a biological oddity previously unknown in animals. But they may also provide an important new tool to study human aging, scientists said.

Such selfish mitochondrial DNA has been found before in plants, but not animals. In this case, the discovery was made almost by accident during some genetic research being done on a nematode, Caenorhabditis briggsaea type of small roundworm.

“We weren’t even looking for this when we found it, at first we thought it must be a laboratory error,” said Dee Denver, an OSU associate professor of zoology. “Selfish DNA is not supposed to be found in animals. But it could turn out to be fairly important as a new genetic model to study the type of mitochondrial decay that is associated with human aging.”

DNA is the material that holds the basic genetic code for living organisms, and through complex biological processes guides beneficial cellular functions. Some of it is also found in the mitochondria, or energy-producing “powerhouse” of cells, which at one point in evolution was separate from the other DNA.

The mitochondria generally act for the benefit of the cell, even though it is somewhat separate. But the “selfish” DNA found in some plant mitochondria – and now in animals – has major differences. It tends to copy itself faster than other DNA, has no function useful to the cell, and in some cases actually harms the cell. In plants, for instance, it can affect flowering and sometimes cause sterility.

“We had seen this DNA before in this nematode and knew it was harmful, but didn’t realize it was selfish,” said Katie Clark, an OSU postdoctoral fellow. “Worms with it had less offspring than those without, they had less muscle activity. It might suggest that natural selection doesn’t work very well in this species.”

That’s part of the general quandary of selfish DNA in general, the scientists said. If it doesn’t help the organism survive and reproduce, why hasn’t it disappeared as a result of evolutionary pressure? Its persistence, they say, is an example of how natural selection doesn’t always work, either at the organism or cellular level. Biological progress is not perfect.

In this case, the population sizes of the nematode may be too small to eliminate the selfish DNA, researchers said.

What’s also interesting, they say, is that the defects this selfish DNA cause in this roundworm are surprisingly similar to the decayed mitochondrial DNA that accumulates as one aspect of human aging. More of the selfish DNA is also found in the worms as they age.

Further study of these biological differences may help shed light on what can cause the mitochondrial dysfunction, Denver said, and give researchers a new tool with which to study the aging process.

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Dee Denver, 541-737-3698

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Roundworm with "selfish" DNA

Roundworm

Mechanism discovered for regulation of cell division

CORVALLIS, Ore. — Oregon State University scientists have revealed a new mechanism in the process of cell division. Their findings, reported today in the Journal of Biological Chemistry, add vital new details to one of the critical events in the life of a cell and could lead to novel treatments for human diseases from Alzheimer’s to cancer.

The study focused on three proteins that affect one of the central features of cell division, the mitotic spindle. One of the proteins, dynein, is a molecular motor that transports molecules during the development of the mitotic spindle and other structures in the cell. Two other proteins regulate dynein: dynactin, which is essential for linking dynein to other molecules; and NudE, whose depletion in experiments performed on mice produces a small brain and mental retardation.

“Protein molecules require a unique specific shape to recognize other proteins and do their biological function,” said Elisar Barbar, professor of biophysics at Oregon State and leader of the team that performed the research. “What is intriguing about the interplay of these three proteins is that the dynein segment that recognizes both dynactin and NudE does not have a specific shape. It belongs to a special class of proteins referred to as intrinsically disordered proteins. These proteins have multiple shapes and fluctuate quickly among them depending on alterations in environmental or cellular conditions.”

In work supported by the National Science Foundation and National Institutes of Health, the Barbar lab used a powerful tool ideally suited to reveal protein shapes, nuclear magnetic resonance spectroscopy, which can show multiple protein forms. The researchers used it to show that a segment of dynein changes shape depending on cellular conditions.

The shift in protein shapes has implications for the regulation of dynein and the formation of the mitotic spindle. The Barbar group found that the two dynein regulators bind to the same segment of dynein. However, dynactin binds to an additional disordered segment. By manipulating the length and chemical modification of this segment, one protein regulator can be selected over the other even when both are present in the same cellular compartment.

These results “offer a novel role for protein disorder in controlling cellular processes,” said Barbar.

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Elisar Barbar, 33 6 12 31 53 60 (in France until July 24), 49-6221-547102 (in Germany July 24 to August 4), 541-737-4143 (in Corvallis after August 4)

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dynein_model.full

Environmental concerns increasing infectious disease in amphibians

CORVALLIS, Ore. – Climate change, habitat destruction, pollution and invasive species are all involved in the global crisis of amphibian declines and extinctions, researchers suggest in a new analysis, but increasingly these forces are causing actual mortality in the form of infectious disease.

Amphibians are now, and always have been hosts for a wide range of infectious organisms, including viruses, bacteria and fungi, scientists said in a review published in Philosophical Transactions of the Royal Society B.

But in recent decades, disease seems to have taken a more prominent role in causing mortality. Because of multiple stresses, many induced by humans, amphibians now succumb to diseases they may historically have been better able to resist or tolerate.

“There’s more and more evidence of the role of disease in the biodiversity crisis, in both amphibians and other types of animals,” said Andrew Blaustein, a distinguished professor of zoology at Oregon State University and author of the recent analysis.

“It’s normal for animals to deal with infectious organisms, often many of them simultaneously,” he said. “But in the face of pollution, a reduced immune response, climate change, evolving pathogens and many other stresses in such a short period of time, many species now simply can’t survive.”

The current extinction rates of amphibians - which existed even before dinosaurs roamed the Earth - may be more than 200 times the background rate of extinction, the scientists note in this report. From an evolutionary perspective, amphibians that survived for hundreds of millions of years may be undergoing a major extinction event.

Because they have both terrestrial and aquatic life stages amphibians are exposed to various environmental forces more than some other animals, scientists say, and a higher percentage of them are threatened with extinction than are birds or mammals. However, similar concerns may become apparent in many animal species, including humans, as environmental changes and stresses grow, they said.

Among the observations in this report:

  • Infectious disease around the world is increasing at an unprecedented rate.
  • Natural stresses such as competition and predation have been joined by human-induced stresses, ranging from pollution to global warming.
  • These forces can reduce immune competence in amphibians, even as climate change, invasive species and other factors increase pathogen spread, persistence, growth and mortality.
  • Some amphibians deal with stress by hormonal changes such as increased production of glucocorticoids, but on a sustained basis, that approach can further suppress their immune system.
  • Warmer winters and night-time temperatures may reduce the cycle of pathogen die-offs that would naturally occur in colder regions.

These forces are complex, the researchers noted. The effects of climate change on amphibian disease, for instance, my cause some pathogens to increase in prevalence and severity, while others decline.

Understanding the driving forces behind these changes, the scientists said, will be important not only to address amphibian declines but also to deal with emerging infections in many other plants and animals, including humans. Such impacts can affect wildlife conservation, economic growth and human health.

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Deformed leopard frog

Deformed frog

Increase in RDA for vitamin C could help reduce heart disease, stroke, cancer

CORVALLIS, Ore. – The recommended dietary allowance, or RDA, of vitamin C is less than half what it should be, scientists argue in a recent report, because medical experts insist on evaluating this natural, but critical nutrient in the same way they do pharmaceutical drugs and reach faulty conclusions as a result.

The researchers, in Critical Reviews in Food Science and Nutrition, say there’s compelling evidence that the RDA of vitamin C should be raised to 200 milligrams per day for adults, up from its current levels in the United States of 75 milligrams for women and 90 for men.

Rather than just prevent the vitamin C deficiency disease of scurvy, they say, it’s appropriate to seek optimum levels that will saturate cells and tissues, pose no risk, and may have significant effects on public health at almost no expense – about a penny a day if taken as a dietary supplement.

“It’s time to bring some common sense to this issue, look at the totality of the scientific evidence, and go beyond some clinical trials that are inherently flawed,” said Balz Frei, professor and director of the Linus Pauling Institute at Oregon State University, and one of the world’s leading experts on the role of vitamin C in optimum health.

“Significant numbers of people in the U.S. and around the world are deficient in vitamin C, and there’s growing evidence that more of this vitamin could help prevent chronic disease,” Frei said. “The way clinical researchers study micronutrients right now, with the same type of so-called ‘phase three randomized placebo-controlled trials’ used to test pharmaceutical drugs, almost ensures they will find no beneficial effect. We need to get past that.”

Unlike testing the safety or function of a prescription drug, the researchers said, such trials are ill suited to demonstrate the disease prevention capabilities of substances that are already present in the human body and required for normal metabolism. Some benefits of micronutrients in lowering chronic disease risk also show up only after many years or even decades of optimal consumption of vitamin C – a factor often not captured in shorter-term clinical studies.

A wider body of metabolic, pharmacokinetic, laboratory and demographic studies suggests just the opposite, that higher levels of vitamin C could help reduce the chronic diseases that today kill most people in the developed world – heart disease, stroke, cancer, and the underlying issues that lead to them, such as high blood pressure, chronic inflammation, poor immune response and atherosclerosis.

“We believe solid research shows the RDA should be increased,” Frei said. “And the benefit-to-risk ratio is very high. A 200 milligram intake of vitamin C on a daily basis poses absolutely no risk, but there is strong evidence it would provide multiple, substantial health benefits.”

An excellent diet with the recommended five to nine daily servings of fruits and raw or steam-cooked vegetables, together with a six-ounce glass of orange juice, could provide 200 milligrams of vitamin C a day. But most Americans and people around the world do not have an excellent diet.

Even at the current low RDAs, various studies in the U.S. and Canada have found that about a quarter to a third of people are marginally deficient in vitamin C, and up to 20 percent in some populations are severely deficient – including college students, who often have less-than-perfect diets. Smokers and older adults are also at significant risk.

Even marginal deficiency can lead to malaise, fatigue, and lethargy, researchers note. Healthier levels of vitamin C can enhance immune function, reduce inflammatory conditions such as atherosclerosis, and significantly lower blood pressure.

  • A recent analysis of 29 human studies concluded that daily supplements of 500 milligrams of vitamin C significantly reduced blood pressure, both systolic and diastolic. High blood pressure is a major risk factor for heart disease and stroke, and directly attributes to an estimated 400,000 deaths annually in the U.S.
  • A study in Europe of almost 20,000 men and women found that mortality from cardiovascular disease was 60 percent lower when comparing the blood plasma concentration of vitamin C in the highest 20 percent of people to the lowest 20 percent.
  • Another research effort found that men with the lowest serum vitamin C levels had a 62 percent higher risk of cancer-related death after a 12-16 year period, compared to those with the highest vitamin C levels.

Laboratory studies with animals – which may be more accurate than human studies because they can be done in controlled conditions and with animals of identical genetic makeup - can document reasons that could explain all of these findings, Frei said.

Critics have suggested that some of these differences are simply due to better overall diet, not vitamin C levels, but the scientists noted in this report that some health benefits correlate even more strongly to vitamin C plasma levels than fruit and vegetable consumption.

Scientists in France and Denmark collaborated on this report. Research at OSU on these issues has been supported by the National Center for Complementary and Alternative Medicine, a division of the National Institutes of Health.

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Fresh fruit

Fresh fruit

Viruses linked to algae that control coral health

CORVALLIS, Ore. – Scientists have discovered two viruses that appear to infect the single-celled microalgae that reside in corals and are important for coral growth and health, and they say the viruses could play a role in the serious decline of coral ecosystems around the world.

These viruses, including an RNA virus never before isolated from a coral, have been shown for the first time to clearly be associated with these microalgae called Symbiodinium. If it’s proven that they are infecting those algae and causing disease, it will be another step toward understanding the multiple threats that coral reefs are facing.

The research was published today in the ISME Journal, in work supported by the National Science Foundation.

“We’re way behind in our knowledge of how viral disease may affect coral health,” said Adrienne Correa, a researcher with the Department of Microbiology at Oregon State University. “If viral infection is causing some bleaching, it could be important in the death of corals and contribute to reef decline. This potential threat from viruses is just starting to be recognized.”

Corals co-exist with these algae in a symbiotic relationship, scientists say, in which the algae provide energy to the coral, and contribute to the construction of reefs. The coral in turn offers a place for the algae to live and provides nutrients for it.

Corals and viruses have evolved along with their resident algae for millions of years. They have persisted through previous climate oscillations, and the presence of viruses within corals or their algae doesn’t necessarily indicate they are affecting coral colony health. If viruses are causing disease or bleaching of colonies, it’s also unknown whether this is happening now more than in the past.

“Corals are known to face various environmental threats, such a warming temperatures, competition and pollution,” Correa said. “Some of the environmental changes of the past were likely more gradual and allowed the coral and its associates more time to adapt.

“The stresses challenging coral reefs now are more intense and frequent,” she said. “This may mean viruses cause more problems for corals and their algae now than they did historically.”

In continued research at OSU, scientists will inoculate Symbiodinium with the viruses and try to prove they are causing actual disease. If the viruses are killing the algae, scientists said, it could have significant implications for coral reef health and survival. There are almost two dozen known diseases that are affecting coral, and scientists still do not know the cause of most of them.

Coral abundance has declined about 80 percent in the Caribbean Sea in the past 30-40 years, and about one-third of all corals around the world are threatened with extinction.

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Bleached coral

Bleached coral

New compound could become “cool blue” for energy efficiency in buildings

CORVALLIS, Ore. – A new type of durable, environmentally-benign blue pigment discovered at Oregon State University has also been found to have unusual characteristics in reflecting heat – it’s a “cool blue” compound that could become important in new approaches to saving energy in buildings.

The compound, which has now received patent approval, was discovered about three years ago almost by chance, as OSU scientists were studying some materials for their electrical properties.

Its potential use to help reduce heat absorption on the roofs and walls of buildings – which is an evolving field of considerable interest in warm regions where cooling is a major expense – adds another role for the material, which is now being considered for various commercial applications.

“This pigment has infrared heat reflectivity of about 40 percent, which is significantly higher than most blue pigments now being used,” said Mas Subramanian, an OSU professor of chemistry who discovered the compound.

“The more we discover about the pigment, the more interesting it gets,” Subramanian said. “We already knew it had advantages of being more durable, safe and fairly easy to produce. Now it also appears to be a new candidate for energy efficiency.”

“Cool roofing,” in which paints are used to reflect significant portions of the sun’s heat and thereby reduce cooling costs, is an important new trend in “green” construction and energy efficiency, experts say. Such reflective coatings also are more aesthetically pleasing, have less thermal degradation, reduce the “heat island” effect in cities, lower peak energy demand, and reduce air pollution due to lower energy use and power plant emissions.

“We’re seeking licensing partners for this invention right now,” said Mary Phillips, associate director of the Office for Commercialization and Corporate Development at OSU. “We believe it can contribute to new energy efficiency solutions around the world.”

In general, any darker color of the type often used for roofs, houses, automobiles or other applications will tend to absorb more heat. But some compounds, like the one discovered at OSU, have dark tones but also the ability to reflect heat in the infrared spectrum, which is responsible for most of the heat energy absorbed from sunlight.

The material created at OSU, researchers say, is probably the best blue pigment humans have produced since ancient times – going back to efforts by the Egyptians, the Han dynasty in China and Mayan cultures. Blue pigments have been sought through history but often had serious drawbacks, such as decaying quickly, being toxic, costly or carcinogenic.

In research funded by the National Science Foundation, OSU scientists discovered this material by coincidence while they were looking for something else.

Some manganese compounds came out of a 2,000 degree Fahrenheit oven transformed into a beautiful blue, which researchers later determined was due to an unusual “trigonal bipyramidal coordination” of their molecules that changed when exposed to extreme heat.

Research will continue at OSU on the heat reflectance capabilities of the new compound and the underlying molecular structure responsible for it, scientists said.

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Mas Subramanian, 541-737-8235

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Pigment discovery

Crystalline structure

Jurassic pain: Giant “flea-like” insects plagued dinosaurs

CORVALLIS, Ore. – It takes a gutsy insect to sneak up on a dinosaur while it sleeps, crawl onto its soft underbelly and give it a bite that would feel like a needle going in – but giant “flea-like” animals, possibly the oldest of their type ever discovered, did just that.

And a few actually lived through the experience, based on the discovery of remarkable fossils of these creatures, just announced in Current Biology, a professional journal.

These flea-like animals, similar but not identical to modern fleas, were probably 10 times the size of a flea you might find crawling on the family dog – with an extra-painful bite to match.  

“These were insects much larger than modern fleas and from the size of their proboscis we can tell they would have been mean,” said George Poinar, Jr., a professor emeritus of zoology at Oregon State University.

“You wouldn’t talk much about the good old days if you got bit by this insect,” Poinar said. “It would have felt about like a hypodermic needle going in – a flea shot, if not a flu shot. We can be thankful our modern fleas are not nearly this big.”

Poinar, an international expert in ancient and extinct insect life forms, said it’s possible that the soft-bodied, flea-like insects found in these fossils from Inner Mongolia are the evolutionary ancestors of modern fleas, but most likely they belong to a separate and now extinct lineage.

Called Pseudopulex jurassicus and Pseudopulex magnus, they had bodies that were more flat, like a bedbug or tick, and long claws that could reach over scales on the skin of dinosaurs so they could hold onto them tightly while sucking blood. Modern fleas are more laterally compressed and have shorter antennae, and are able to move quickly through the fur or feathers of their victims.

“These are really well-preserved fossils that give us another glimpse of life into the really distant past, the Cretaceous and Jurassic,” said Poinar, who has also studied “younger” fleas from 40-50 million years ago preserved in amber.

All true fleas are adapted to feeding on warm-blooded vertebrates, Poinar said, and today 94 percent of the 2,300 known species attack mammals, while the remainder feed on birds. But the unusual characteristics and abilities of the flea-like animals found in these fossils lead scientists to believe their prey were some of the biggest kids on the block – dinosaurs in which they could have fed on the softer skin between scales.

Modern fleas, the report noted, have done plenty of damage. Hardly a dog or cat alive has escaped their attack, and they brought mankind such diseases as bubonic plague, which has killed 75 million people.

But their bite itself, at least, didn’t feel like a needle going in, by an insect that wasn’t even afraid of a dinosaur.

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George Poinar, Jr., 541-737-5366

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Ancient insect

Flea-like insect

Nanotube technology leading to fast, lower-cost medical diagnostics

CORVALLIS, Ore. – Researchers at Oregon State University have tapped into the extraordinary power of carbon “nanotubes” to increase the speed of biological sensors, a technology that might one day allow a doctor to routinely perform lab tests in minutes, speeding diagnosis and treatment while reducing costs.

The new findings have almost tripled the speed of prototype nano-biosensors, and should find applications not only in medicine but in toxicology, environmental monitoring, new drug development and other fields.

The research was just reported in Lab on a Chip, a professional journal. More refinements are necessary before the systems are ready for commercial production, scientists say, but they hold great potential.

“With these types of sensors, it should be possible to do many medical lab tests in minutes, allowing the doctor to make a diagnosis during a single office visit,” said Ethan Minot, an OSU assistant professor of physics. “Many existing tests take days, cost quite a bit and require trained laboratory technicians.

“This approach should accomplish the same thing with a hand-held sensor, and might cut the cost of an existing $50 lab test to about $1,” he said.

The key to the new technology, the researchers say, is the unusual capability of carbon nanotubes. An outgrowth of nanotechnology, which deals with extraordinarily small particles near the molecular level, these nanotubes are long, hollow structures that have unique mechanical, optical and electronic properties, and are finding many applications.

In this case, carbon nanotubes can be used to detect a protein on the surface of a sensor. The nanotubes change their electrical resistance when a protein lands on them, and the extent of this change can be measured to determine the presence of a particular protein – such as serum and ductal protein biomarkers that may be indicators of breast cancer.

The newest advance was the creation of a way to keep proteins from sticking to other surfaces, like fluid sticking to the wall of a pipe. By finding a way to essentially “grease the pipe,” OSU researchers were able to speed the sensing process by 2.5 times.

Further work is needed to improve the selective binding of proteins, the scientists said, before it is ready to develop into commercial biosensors.

“Electronic detection of blood-borne biomarker proteins offers the exciting possibility of point-of-care medical diagnostics,” the researchers wrote in their study. “Ideally such electronic biosensor devices would be low-cost and would quantify multiple biomarkers within a few minutes.”

This work was a collaboration of researchers in the OSU Department of Physics, Department of Chemistry, and the University of California at Santa Barbara. A co-author was Vincent Remcho, professor and interim dean of the OSU College of Science, and a national expert in new biosensing technology.

The research was supported by the U.S. Army Research Laboratory through the Oregon Nanoscience and Microtechnologies Institute.

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Ethan Minot, 541-737-9671

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Nanotube sensor

Nanotube sensor

Corvallis Science Pub to focus on biofuels

CORVALLIS, Ore. – In the search for new local energy sources, a young Corvallis company is betting on two of the Willamette Valley’s most abundant crops – wheat and ryegrass.

At the March 12 Corvallis Science Pub, Chris Beatty, president of Trillium FiberFuels, and Vince Remcho, an Oregon State University chemist, will discuss Trillium’s collaboration with OSU to develop ethanol and other products from agricultural waste products.

The program will begin at 6 p.m. on Monday, March 12, at the Old World Deli, 341 Second St. in Corvallis. It is free and open to the public.

According to the Renewable Fuels Association, the nation produced more than 13 billion gallons of ethanol in 2010, mostly from corn. The 2007 federal energy act set a national target of 36 billion gallons by 2022. Much of the gap is expected to be filled by ethanol from cellulose.

Yeast is typically used to ferment biomass sugars into ethanol. One challenge is that xylose, the second most common sugar, does not ferment. Trillium’s technology uses an enzyme to convert xylose to a form that yeast can ferment.

In their presentation, Beatty and Remcho will discuss the potential for this technology to expand the nation's biofuel industry. In addition, they will outline “some interesting opportunities in the biomass sugar world that have emerged during Trillium's journey,” Beatty said.

Sponsors of Science Pub include Terra magazine at OSU, the Downtown Corvallis Association and the Oregon Museum of Science and Industry.

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Vince Remcho, 541-737-8181

OSU graduate student receives outreach teaching award

CORVALLIS, Ore. – Sarah Eddy, a graduate student at Oregon State University, is one of only eight students in the nation to receive the K. Patricia Cross Award.

The award, presented by the American Association of Colleges and Universities, is given to people who display leadership in teaching, civic engagement, and improving the campus culture around teaching.

Although majoring in zoology, Eddy also researched effective teaching practices for the science classroom. She designed and taught three graduate level seminars on science pedagogy and developing outreach activities. She co-founded Broader Impacts and Outreach by Graduate Students, or BIO-GradS, a group that provides workshops to help high school students learn about biology.

“This work is important and really rewarding,” Eddy said. “We don’t always convey the exciting parts of biology that can make students more driven to learn. You have to show what you can actually do with learning.”

In continuing work, Eddy hopes to identify, through large scale classroom experiments, science teaching methods and curriculum that increase retention and learning of at-risk students.

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Sarah Eddy

Sarah Eddy