OREGON STATE UNIVERSITY

scientific research and advances

Vitamin E deficiency linked to embryo damage, death

CORVALLIS, Ore. – Researchers for the first time have explained how deficient levels of vitamin E can cause neurologic damage to an embryo, failure to normally develop and ultimately death – a process that in women can be one cause of miscarriage.

The research was published by scientists from Oregon State University in Free Radical Biology and Medicine. It answers some questions about the biologic activities of vitamin E that have been debated since 1922, when this essential micronutrient was first discovered, in part for its role in preventing embryonic mortality.

The research also made clear the importance of vitamin E status for any woman who is planning to, or might become pregnant, scientists said.

The study, done with zebrafish embryos, showed that severe vitamin E deficiency causes the depletion of essential fatty acids, especially the omega-3 fatty acid DHA, which has been shown to be of critical importance to health in multiple studies in recent years.

When this happens, cells use glucose to prevent or reduce damage. Lacking glucose for energy, many physical and neurologic features, especially the brain, simply don’t get built, and death can be the result. Restoration of glucose can repair some of the damage, but some physical deformities remain.

In the growing embryo of a zebrafish – which goes from a cell to a swimming fish in about five days – a severe vitamin E deficiency causes 70-80 percent mortality, the study showed.

“Vitamin E has many biologic roles, only one of which is to serve as an antioxidant,” said Maret Traber, a professor in the OSU College of Public Health and Human Sciences, and Ava Helen Pauling Professor in the Linus Pauling Institute.

“In the growing embryo, vitamin E plays a major role in protecting essential fats such as DHA. Loss and oxidation of these fats can begin a chain reaction that involves glucose, depletes the cell of other antioxidants such as vitamin C, robs the cell of energy, and ultimately has a lethal outcome.”

When vitamin E is deficient, the embryonic brain is literally starved of necessary energy and nutrients, particularly DHA and choline, the researchers concluded in their study.

The neurological development of zebrafish is very similar to that of humans, Traber said, which make them a good model for this research.

“The importance of vitamin E in embryonic development, the very earliest days of vertebrate life, is part of what actually led to its discovery,” Traber said. “Since then we’ve learned much more about the need for this micronutrient in women. One study done in Bangladesh, for instance, showed that pregnant women with lower levels of vitamin E had double the risk of miscarriages as another group with adequate nutrition.”

Nutrition surveys suggest that about 96 percent of women in the U.S. have inadequate intakes of vitamin E in their diet, Traber said. The problem may be of even greater concern in young adult women who avoid high-fat foods and may not have a diet rich in oils, nuts and seeds, some of the foods with the highest levels of this micronutrient. The human body can create DHA from some foods, but not vitamin E.

In a human fetus, some of the most critical periods for neurologic and brain development are in the first few weeks of pregnancy. Given the difficulty of obtaining vitamin E in the diet, this would suggest that any woman who is planning to or may become pregnant should take a multivitamin with the recommended daily allowance of vitamin E and some other micronutrients, Traber said.

Collaborators on this research were from the Catholic University of Korea and the University of Southern California. The study was supported by the National Institutes of Health, the National Science Foundation and the Helen P. Rumbel endowment to the Linus Pauling Institute.

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Maret Traber, 541-737-7977

maret.traber@oregonstate.edu

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Third Oregon climate assessment report shows state still warming, despite frigid winter

CORVALLIS, Ore. – Don’t let this winter fool you. Oregon’s climate continues to warm; there are impacts on the state’s physical, biological and human-managed systems; and more studies are pointing to greenhouse gas emissions as the reason for these climate trends and events.

That is the conclusion of the third Oregon Climate Assessment Report, a synthesis of peer-reviewed scientific studies over the past three years. The legislatively mandated report was produced by the Oregon Climate Change Research Institute at Oregon State University and is being presented this month to key Oregon political leaders.

“Oregonians shouldn’t be swayed by this winter, which is colder than any of the ones we’ve had since 1990,” noted Philip Mote, director of the OSU center and a co-author on the report. “Overall, temperatures are still getting warmer – in Oregon, throughout the United States, and globally – and the impacts are very real.

“For Oregonians, it means warmer temperatures, lower snowpack and less water during the summer. And more and more studies are confirming greenhouse gas emissions as the cause.”

Kathie Dello, associate director of the Oregon Climate Change Research Institute, points out that although December of 2016 was the 11th coldest December on record in Oregon in 122 years of monitoring, the year was still among the top 10 warmest years on record for the state.

The climate assessment report, led by Meghan Dalton, a research assistant with the institute in the College of Earth, Ocean, and Atmospheric Sciences at OSU, looked at more than 300 studies published from 2013-16 by researchers at universities, state and federal agencies, and elsewhere. Dalton led a team of researchers who synthesized the literature and developed the report.

“The year 2015 has been described as foreshadowing what we can expect as normal conditions by the mid-21st century,” Dalton said. “There were warmer temperatures that led to drought, low snowpack, and greater wildfire risk, with less water in the summer. That appears to be our future.”

Snowpack in the past three years has varied greatly, according to Dello.

“In 2015, we basically had no snow to speak of,” Dello said. “In 2016, we had a lot of snow, but most of it got wiped out by warm temperatures in late winter and early spring. So far this year, we have had a lot of snow, but warmer temperatures are moving in, and we still have a lot of winter left. We’re cautiously optimistic. Large year-to-year changes like that are still expected, even in a warming climate.”

The report notes that a warming climate and earlier spring may have a few beneficial results. Farmers, for example, may benefit from a longer growing season, though water could be an issue for some crops.

The report analyzes potential impacts of climate change for Oregon’s many regions. Among the findings:

  • The Oregon Coast: Sea level rise will increase the risk of erosion and flooding and higher estuary temperatures will challenge migrating salmon and steelhead. One study estimated that warming of Yaquina Bay by 1.3 to 2.9 degrees (F) would result in 40 additional days of temperatures not meeting the criteria for protecting salmonids.
  • The Willamette Valley: Heat waves are expected to become longer, more common and more intense; operating rules for reservoirs may have to change to balance flood risk and summer water supply; air quality will decline, and wildfire risk will increase. A study of fire activity concluded that there will be a three-fold to nine-fold increase in the amount of area burned in the basin by the year 2100.
  • The Cascade Mountains: More precipitation will fall as rain instead of snow, with elevations between 3,000 feet and 6,000 feet being the most sensitive. In addition to potential impacts on ski resorts, there likely will be a change in when water is available. Cascades forests will probably be subject to more wildfire, drought, insect damage and disease, and some studies suggest that woodlands will shift from predominantly conifer to mixed conifer forests. The risk of increased incidence of respiratory illness from wildfire smoke is a top public health risk in Jackson County.
  • Eastern Oregon: Water will be a huge issue in the east with snowpack decline, and the same forest issues face the Blue Mountains as the Cascades. Increased wildfire risk may create more days of heavy smoke affecting public health, and fires will threaten the forests. Salmon in the John Day basin and other river systems will be challenged with warmer temperatures, and rangeland and sagebrush habitat is threatened by non-native weeds and grasses.

“A lot of the studies we cited focus on the physical aspects of warming, from snowpack to wildfire, but there are a lot of people who will be affected,” Dello said. “We can’t forget that Oregonians, their families, their jobs and their resources are at risk. There is still time to do something, but time is running short.”

A copy of the report is available at http://occri.net/

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Kathie Dello, 541-737-8927, kdello@coas.oregonstate.edu; Phil Mote, 541-913-2274, pmote@coas.oregonstate.edu

Globe-trotting pollutants raise some cancer risks four times higher than predicted

CORVALLIS, Ore. -- A new way of looking at how pollutants ride through the atmosphere has quadrupled the estimate of global lung cancer risk from a pollutant caused by combustion, to a level that is now double the allowable limit recommended by the World Health Organization.

The findings, published this week in the Proceedings of the National Academy of Sciences Early Edition online, showed that tiny floating particles can grow semi-solid around pollutants, allowing them to last longer and travel much farther than what previous global climate models predicted.

Scientists said the new estimates more closely match actual measurements of the pollutants from more than 300 urban and rural settings.

The study was done by scientists at Oregon State University, the Department of Energy’s Pacific Northwest National Laboratory, or PNNL, and Peking University. The research was primarily supported by PNNL.

"We developed and implemented new modeling approaches based on laboratory measurements to include shielding of toxics by organic aerosols, in a global climate model that resulted in large improvements of model predictions," said PNNL scientist and lead author Manish Shrivastava.

"This work brings together theory, lab experiments and field observations to show how viscous organic aerosols can largely elevate global human exposure to toxic particles, by shielding them from chemical degradation in the atmosphere."

Pollutants from fossil fuel burning, forest fires and biofuel consumption include air-polluting chemicals known as polycyclic aromatic hydrocarbons, or PAHs. In the United States, the Environmental Protection Agency has identified several PAHs as cancer-causing agents.

But PAHs have been difficult to represent in past climate models. Simulations of their degradation process fail to match the amount of PAH that is actually measured in the environment.

To look more closely at how far PAHs can travel while riding shielded on a viscous aerosol, the researchers compared the new model's numbers to PAH concentrations actually measured by Oregon State University scientists at the top of Mount Bachelor in the central Oregon Cascade Range.

“Our team found that the predictions with the new shielded models of PAHs came in at concentrations similar to what we measured on the mountain,” said Staci Simonich, a toxicologist and chemist in the College of Agricultural Sciences and College of Science at OSU, and international expert on the transport of PAHs.

“The level of PAHs we measured on Mount Bachelor was four times higher than previous models had predicted, and there’s evidence the aerosols came all the way from the other side of the Pacific Ocean.”

These tiny airborne particles form clouds, cause precipitation and reduce air quality, yet they are the most poorly understood aspect of the climate system.

A smidge of soot at their core, aerosols are tiny balls of gases, pollutants, and other molecules that coalesce around the core. Many of the molecules that coat the core are what's known as "organics." They arise from living matter such as vegetation -- leaves and branches, for example, or even the molecule responsible for the pine smell that wafts from forests.

Other molecules such as pollutant PAHs also stick to the aerosol. Researchers long thought that PAHs could move freely within the organic coating of an aerosol. This ease of movement allowed the PAH to travel to the surface where ozone -- a common chemical in the atmosphere -- can break it down.

But scientists' understanding of aerosols has changed in the last five years or so.

Recent experiments led by PNNL coauthor Alla Zelenyuk show that, depending on the conditions, the aerosol coatings can actually be quite viscous. If the atmosphere is cool and dry, the coating can become as viscous as tar, trapping PAHs and other chemicals. By preventing their movement, the viscous coating shields the PAHs from degradation.

Researchers developed a new way of representing PAHs in a global climate model, and ran it to simulate PAH concentrations from 2008 to 2010. They examined one of the most carcinogenic PAHs in particular, called BaP. Simulations were compared to data from 69 rural sites and 294 urban sites worldwide, and showed that predictions from shielded PAHs were far more accurate than previous, unshielded ones.

Scientists also analyzed how far the protected PAHs could travel, using both old and new models. In all cases, the shielded PAHs traveled across oceans and continents, whereas in the previous version they barely moved from their country of origin.

To look at the impact globe-trotting PAHs might have on human health, Shrivastava combined a global climate model, running either the shielded PAH scenario or the previous unshielded one, with a lifetime cancer risk assessment model developed by coauthors Huizhong Shen and Shu Tao, both then at Peking University.

Globally, the previous model predicted half a cancer death out of every 100,000 people, which is half the limit outlined by the World Health Organization (WHO) for PAH exposure. But using the new model, which showed that shielded PAHs actually travel great distances, the global risk was four times that, or two cancer deaths per 100,000 people, which exceeds WHO standards.

The WHO standards were not exceeded everywhere. It was higher in China and India and lower in the United States and Western Europe. The extent of shielding was also much lower over the tropics compared to the mid- and high-latitudes. As the aerosols traversed the warm and humid tropics, ozone could get access to the PAHs and oxidize them.

"We don't know what implications more PAH oxidation products over the tropics have for future human or environmental health risk assessments,” said Shrivastava. “We need to better understand how the shielding of PAHs varies with the complexity of aerosol composition, atmospheric chemical aging of aerosols, temperature and relative humidity. I was initially surprised to see so much oxidation over the tropics."

Other supporters of this research included the National Institute of Environmental Health Sciences, the National Science Foundation, the Ministry of Education, Youth and Sports of the Czech Republic, and the Department of Energy Office of Science.

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Staci Simonich, 541-737-9194

staci.simonich@oregonstate.edu

Mary Beckman, 509-375-3688

mary.beckman@pnnl.gov

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New technique could lead to safer, more efficient uranium extraction, aid environmental cleanup

CORVALLIS, Ore. – The separation of uranium, a key part of the nuclear fuel cycle, could potentially be done more safely and efficiently through a new technique developed by chemistry researchers at Oregon State University.

The technique uses soap-like chemicals known as surfactants to extract uranium from an aqueous solution into a kerosene solution in the form of hollow clusters. Aside from fuel preparation, it may also find value in legacy waste treatment and for the cleanup of environmental contamination.

The research at OSU involves a unique form of uranium discovered in 2005, uranyl peroxide capsules, and how those negatively charged clusters form in alkaline conditions. Results were recently published in the European Journal of Inorganic Chemistry.

“This is a very different direction,” said study lead author Harrison Neal, a graduate student in Oregon State’s College of Science. “A lot of the work done now is in acid, and we’re at the other end of the pH scale in base. It’s a very different approach, overall using less harmful, less toxic chemicals.”

Throughout the nuclear fuel cycle, many separations are required – in mining, enrichment and fuel fabrication, and then after fuel use, for the recovery of usable spent isotopes and the encapsulation and storage of unusable radioactive components.

“When you use nuclear fuel, the radioactive decay products poison the fuel and make it less effective,” said May Nyman, professor of chemistry at Oregon State and corresponding author on the research. “You have to take it, dissolve it, get the good stuff out and make new fuel.”

Nyman notes the work represents significant fundamental research in the field of cluster chemistry because it allows for the study of uranyl clusters in the organic phase and can pave the way to improved understanding of ion association.

“With extracting these clusters into the organic phase, the clusters themselves are hollow, so when we get them into the organic solution, they’re still containing other atoms, molecules, other ions,” Neal added. “We can study how these ions interact with these cages that they’re in. The fundamental research is understanding how the ions get inside and what they do once they’re inside because they’re stuck there.”

When the clusters form, each contains 20 to 60 uranium atoms, “so we can extract them in whole bunches instead of one at a time,” Nyman said. “It’s an atom-efficient approach.”

Existing separation techniques require two extraction molecules for every uranium ion, whereas the OSU technique requires less than one extraction molecule per ion.

Scientists from the University of Notre Dame collaborated on the research, which was supported by the U.S. Department of Energy.

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Steve Lundeberg, 541-737-4039

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Uranyl peroxide capsules

Ancient, scary and alien-looking specimen forms a rarity in the insect world – a new order

CORVALLIS, Ore. – Researchers at Oregon State University have discovered a 100-million-year-old insect preserved in amber with a triangular head, almost-alien and “E.T.-like” appearance and features so unusual that it has been placed in its own scientific “order” – an incredibly rare event.

There are about 1 million described species of insects, and millions more still to be discovered, but every species of insect on Earth has been placed in only 31 existing orders. Now there’s one more.

The findings have been published in the journal Cretaceous Research and describe this small, wingless female insect that probably lived in fissures in the bark of trees, looking for mites, worms or fungi to feed on while dinosaurs lumbered nearby. It was tiny, but scary looking.

“This insect has a number of features that just don’t match those of any other insect species that I know,” said George Poinar, Jr., an emeritus professor of entomology in the OSU College of Science and one of the world’s leading experts on plant and animal life forms found preserved in the semi-precious stone amber.

“I had never really seen anything like it. It appears to be unique in the insect world, and after considerable discussion we decided it had to take its place in a new order.”

Perhaps most unusual, Poinar said, was a triangular head with bulging eyes, with the vertex of the right triangle located at the base of the neck. This is different from any other known insect, and would have given this species the ability to see almost 180 degrees by turning its head sideways.

The insect, probably an omnivore, also had a long, narrow, flat body, and long slender legs. It could have moved quickly, and literally seen behind itself. It also had glands on the neck that secreted a deposit that scientists believe most likely was a chemical to repel predators.

The insect has been assigned to the newly created order Aethiocarenodea, and the species has been named Aethiocarenus burmanicus, in reference to the Hukawng Valley mines of Myanmar – previously known as Burma – where it was found. Only one other specimen of this insect has been located, also preserved in Burmese amber, Poinar said.

Those two specimens, which clearly belong to the same species, now comprise the totality of the order Aethiocarenodea. The largest order of insects, by comparison, is Coleoptera, the beetles, with hundreds of thousands of known species.

Needless to say, this species from such ancient amber is long extinct. It obviously had special features that allowed it to survive in the forests of what is now Burma, 100 million years ago, but for some unknown reason it disappeared. Loss of its preferred habitat is a likely possibility.

“The strangest thing about this insect is that the head looked so much like the way aliens are often portrayed,” Poinar said. “With its long neck, big eyes and strange oblong head, I thought it resembled E.T. I even made a Halloween mask that resembled the head of this insect. But when I wore the mask when trick-or-treaters came by, it scared the little kids so much I took it off.”

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George Poinar, Jr.

poinarg@science.oregonstate.edu

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‘Navigators’ help indigenous cancer patients overcome barriers to diagnosis, treatment

CORVALLIS, Ore. – New research shows that patient “navigators” are a valuable resource for American Indians and Alaskan Natives with cancer as they try to overcome barriers to diagnosis and care, and may offer a path to improved treatment outcomes.

The findings, recently published in the Journal of Primary Prevention, are important because American Indians and Alaskan Natives are stricken with cancer at the same rate as non-Hispanic white people but have lower five-year survivorship rates, and are more likely to die of cancer in general.

Indigenous patients in the Pacific Northwest working with a navigator were almost four times more likely to have a definitive diagnosis within a year of an abnormal screening result than patients without a navigator, the research indicated.

In addition, patients in the study praised their navigators’ ability to provide emotional and logistical support throughout the complicated and often-confusing treatment process. A navigator coordinated patients’ care between multiple providers and agencies and helped connect patients to support groups and other resources.

Megan Cahn, a postdoctoral research associate in Oregon State University’s College of Public Health and Human Sciences, was a co-author of the study along with scientists from the Northwest Tribal Epidemiology Center. The center, one of 12 in the nation, collaborates with the region’s tribes on health-related research, surveillance, training and technical assistance.

The patients in the study all received care through tribal community health clinics, which receive funding from the Indian Health Service. The project was part of a larger program by the National Cancer Institute examining the effectiveness of the patient navigator model in populations with sub-optimal cancer outcomes.

“One of the big concerns for tribal populations is that they have lower screening rates,” Cahn said. “If you don’t screen, then you don’t detect cancer until someone is showing symptoms. A big part of the program was to see if there was a way to get individuals with an abnormal screening result to get a definitive diagnosis, to shorten that window and get treatment in a timely fashion.

“We found that patients enrolled in a navigator program were 3.6 times more likely to have a definitive diagnosis within a year.”

The researchers also learned that not only was the navigator program measurably effective, the patients liked it – an important indicator of the program’s long-term success potential.

“If the patients don’t find it acceptable, the program won’t continue to work,” Cahn said.

A patient navigator was hired by the tribe at each of three tribal clinics in Idaho and Oregon, and researchers interviewed 40 patients for their perceptions of the program. The average age of the participants was 54.4, and 65 percent were female. Thirty-four of the 40 rated the navigator program as “good” or “excellent,” and one added she felt the navigator had saved her life.

In addition to the screening and diagnosis issue, the research found that the main barriers to cancer treatment cited by tribal members were physical and emotional obstacles - symptoms of the cancer itself or side effects from treatment, and “also the emotional response to the diagnosis.”

“There’s a lot of fear and anxiety and shock, and those fears often lead patients to be reluctant to continue with treatment,” Cahn said. “Some of them felt like they had received mistreatment or had been misdiagnosed, plus there were financial barriers: the cost of care and a lack of coordination regarding payment for the services.

“Other barriers were concerns around transportation – some people would have to travel several hours to get treatment, and the availability and cost of public transportation were problems. Navigators could help come up with strategies that were effective for addressing these logistical barriers.”

Sometimes a navigator would accompany a patient to an appointment and help the patient understand what the doctor was saying. Navigators also provided direct emotional support as well as referring patients to support groups.

“Patients said they valued that navigators were part of their communities and respected their culture,” Cahn said. “It made them feel like the navigators were invested in the community and the patients and their families.”

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Steve Lundeberg, 541-737-4039

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Scientists zero in on global ocean temperatures during last interglaciation period

CORVALLIS, Ore. – During the last major interglaciation period, when ice sheets in Greenland and Antarctica were smaller than today resulting in a global sea level that was 20 to 30 feet higher, scientists believe ocean temperatures were warmer than at most times in the Earth’s recent history.

However, those estimates of ocean temperatures show a high level of uncertainty, making it difficult to accurately project warming into the future and its impacts on sea level rise.

Now a team of scientists has assembled data from around the world in a comprehensive analysis of global ocean temperatures during the interglaciation period from 129,000 to 116,000 years ago. The team found that global average ocean temperatures were roughly half a degree (Celsius) warmer during that period than during pre-industrial times and nearly identical to the average temperature over the last 20 years.

Results of the study, which was supported by the National Science Foundation, appear this week in the journal Science.

“Half a degree may not sound like very much, but in terms of average global ocean temperature, it actually is quite substantial,” said lead author Jeremy Hoffman, who led the work as a doctoral student at Oregon State University, and is now a staff scientist with the Science Museum of Virginia. “The problem is that computer models have not been able to simulate this amount of warming for the last interglaciation. Because these are the same models used to project future temperatures, this suggests that they may be missing important processes that would result in even warmer temperatures than now considered.”

The last interglaciation period was one of the warmest periods on Earth in the last 800,000 years. A previous study by Oregon State researchers and published in Science documented the higher sea levels and scientists have hypothesized that warmer ocean temperatures may have been part of the process.

Peter Clark, an Oregon State climate scientist and co-author on the study, said one reason for warmer temperatures during the last interglaciation, and the decline of the Greenland ice sheet, was a shift in Earth’s orbit around the sun.

“Although carbon dioxide levels then were comparable to the pre-industrial era, solar insolation in the northern hemisphere during the summer was much higher,” said Clark, who has the title of distinguished professor in OSU’s College of Earth, Ocean, and Atmospheric Sciences. “This more intense solar insolation contributed to the warmer temperatures.”

The researchers believe the melting of the Greenland ice sheet weakened the Atlantic Meridional Overturning Circulation, or AMOC, a system of currents that usually brings warmer water from the tropics to the south. As it weakened, sea surface temperatures rose in the southern hemisphere, also contributing to warmer global temperatures.

“It was a double whammy,” Clark said. “Solar insolation warmed the northern hemisphere, a weakened AMOC warmed the south.”

Earth’s orbit around the sun is different today, resulting in less solar insolation. The planet has warmed by about one degree (Celsius) since 1750, however, because of human influence.

Other authors on the study included Andrew Parnell of University College Dublin in Ireland, and Feng He from the University of Wisconsin.

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Peter Clark, 541-737-1247

clarkp@geo.oregonstate.edu

Molecule shows ability to thwart pathogens’ genetic resistance to antibiotic

CORVALLIS, Ore. – Oregon State University researchers have developed a new weapon in the battle against antibiotic-resistant germs - a molecule that neutralizes the bugs’ ability to destroy the antibiotic.

Scientists at OSU were part of an international collaboration that demonstrated the molecule’s ability to inhibit expression of an enzyme that makes bacteria resistant to a wide range of penicillins.

The molecule is a PPMO, short for peptide-conjugated phosphorodiamidate morpholino oligomer. The enzyme it combats is known as New Delhi metallo-beta-lactamase, or NDM-1, and it’s accompanied by additional genes that encode resistance to most if not all antibiotics.

“We’re targeting a resistance mechanism that’s shared by a whole bunch of pathogens,” said Bruce Geller, professor of microbiology in OSU’s College of Science and College of Agricultural Sciences, who’s been researching molecular medicine for more than a decade. “It’s the same gene in different types of bacteria, so you only have to have one PPMO that’s effective for all of them, which is different than other PPMOs that are genus specific.”

The Oregon State study showed that in vitro the new PPMO restored the ability of an antibiotic -- in this case meropenem, an ultra-broad-spectrum drug of the carbapenem class -- to fight three different genera of bacteria that express NDM-1. The research also demonstrated that a combination of the PPMO and meropenem was effective in treating mice infected with a pathogenic strain of E. coli that is NDM-1 positive.

Results of the study, supported by a grant from the National Institutes of Health, were recently published in the Journal of Antimicrobial Chemotherapy.

Geller says the PPMO will likely be ready for testing in humans in about three years.

“We’ve lost the ability to use many of our mainstream antibiotics,” Geller said. “Everything’s resistant to them now. That’s left us to try to develop new drugs to stay one step ahead of the bacteria, but the more we look the more we don’t find anything new. So that’s left us with making modifications to existing antibiotics, but as soon as you make a chemical change, the bugs mutate and now they’re resistant to the new, chemically modified antibiotic.”

That progression, Geller explains, made the carbapenems, the most advanced penicillin-type antibiotic, the last line of defense against bacterial infection.

“The significance of NDM-1 is that it is destroys carbapenems, so doctors have had to pull out an antibiotic, colistin, that hadn’t been used in decades because it’s toxic to the kidneys,” Geller said. “That is literally the last antibiotic that can be used on an NDM-1-expressing organism, and we now have bacteria that are completely resistant to all known antibiotics. But a PPMO can restore susceptibility to antibiotics that have already been approved, so we can get a PPMO approved and then go back and use these antibiotics that had become useless.”

In addition to Geller, the research team included Oregon State postdoctoral scholars Erin Sully and Lixin Li and OSU undergraduate student Christina Moody, as well as scientists from Sarepta Therapeutics, Harvard Medical School, the University of Fribourg, and the University of Texas Southwestern.

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Steve Lundeberg, 541-737-4039

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Millions of people with metabolic syndrome may need more vitamin E

CORVALLIS, Ore. – New research has shown that people with metabolic syndrome need significantly more vitamin E – which could be a serious public health concern, in light of the millions of people who have this condition that’s often related to obesity.

A study just published in the American Journal of Clinical Nutrition also made it clear that conventional tests to measure vitamin E levels in the blood may have limited accuracy compared to tests made in research laboratories, to the point that conventional tests can actually mask an underlying problem.

Vitamin E – one of the more difficult micronutrients to obtain by dietary means – is an antioxidant important for cell protection. It also affects gene expression, immune function, aids in repair of wounds and the damage of atherosclerosis, is important for vision and neurologic function, and largely prevents fat from going rancid.

Nutrition surveys have estimated that 92 percent of men and 96 percent of women in the United States fail to get an adequate daily intake of vitamin E in their diet. It is found at high levels in almonds, wheat germ, various seeds and oils, and at much lower levels in some vegetables and salad greens, such as spinach and kale.

This study was done by researchers in the Linus Pauling Institute at Oregon State University and the Human Nutrition Program at The Ohio State University, as a double-blind, crossover clinical trial focusing on vitamin E levels in people with metabolic syndrome. It was supported by the National Institutes of Health, the National Dairy Council and DSM Nutrition.

“The research showed that people with metabolic syndrome need about 30-50 percent more vitamin E than those who are generally healthy,” said Maret Traber, a professor in the OSU College of Public Health and Human Sciences, and Ava Helen Pauling Professor in the Linus Pauling Institute.

“In previous work we showed that people with metabolic syndrome had lower bioavailability of vitamin E. Our current work uses a novel approach to measure how much vitamin E the body needs. This study clearly demonstrates that people with metabolic syndrome need a higher intake of this vitamin.”

More than 30 percent of the American public are obese, and more than 25 percent of the adults in the United States meet the criteria for metabolic syndrome, putting them at significantly increased risk for cardiovascular disease and type-2 diabetes – primary causes of death in the developed world.

That syndrome is defined by diagnosis of three or more of several conditions, including abdominal obesity, elevated lipids, high blood pressure, pro-inflammatory state, a pro-thrombotic state and insulin resistance or impaired glucose tolerance.

This research, for the first time, also clearly outlined a flaw with conventional approaches to measuring vitamin E.

By “labeling” vitamin E with deuterium, a stable isotope of hydrogen, scientists were able to measure the amount of the micronutrient that was eliminated by the body, compared to the intake. The advanced research laboratory tests, which are not available to the general public, showed that people with metabolic syndrome retained 30-50 percent more vitamin E than healthy people – showing that they needed it. When the body doesn’t need vitamin E, the excess is excreted.

But in the group with metabolic syndrome, even as their tissues were taking up and retaining the needed vitamin E, their blood levels by conventional measurement appeared about the same as those of a normal, healthy person.

“We’ve discovered that vitamin E levels often look normal in the blood, because this micronutrient is attracted to high cholesterol and fat,” Traber said. “So vitamin E can stay at higher levels in the circulatory system and give the illusion of adequate levels, even as tissues are deficient.

“This basically means that conventional vitamin E blood tests as they are now being done are useless.”

The findings support the conclusion that people with metabolic syndrome have higher levels of oxidative and inflammatory stress, scientists said in their conclusion, and require more antioxidants such as vitamins E as a result.

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Maret Traber, 541-737-7977

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Air pollution and lack of physical activity pose competing threats to children in China

CORVALLIS, Ore. – Children and adolescents in mainland China are facing two serious and conflicting public health threats: ongoing exposure to air pollution and an increasingly sedentary lifestyle with little regular physical activity outside school.

Health workers and policymakers need to find ways to address both of these issues so that

children can be more physically active without suffering the health risks caused by exposure to air pollution, an Oregon State University researcher suggests in a new commentary published this month in The Journal of Pediatrics

“The question is how do we balance the virtues of physical activity with the hazards of air pollution?” said Brad Cardinal, a kinesiology professor in the College of Public Health and Human Sciences at Oregon State University and a national expert on the benefits of physical activity. “Ultimately, we have to find ways for people to stay active despite the air pollution.”

Many cities and countries around the world grapple with air pollution issues, but there is particular concern for children growing up in China in part because they tend to commute more on foot or bike and their playgrounds and sports fields are often found near busy streets or highways, Cardinal said. The impacts of air pollution contributed to 1.2 million deaths in 2010. 

At the same time, very few Chinese children today are participating in moderate or vigorous physical activity outside of school, and the number of overweight and obese children in China has more than doubled in the last 25 years.

Children are particularly susceptible to adverse health impacts from both short- and long-term exposure to air pollution, in part because they have higher rates of respiration and tend to take shallower breaths. Air pollution has been associated with increases in asthma, chronic cough and other respiratory problems in children that are likely to be exacerbated by heavy breathing from vigorous exercise, Cardinal said. 

So how do public health officials approach these competing challenges? Cardinal and his co-author, Qi Si of Zhejiang University in China and a former visiting scholar at OSU, suggest the two problems should be addressed together.

They recommend four urgent steps for health officials and policymakers who are grappling with these issues: 

  • Increase awareness among parents, children, health workers, educators, and policymakers on the causes and impacts of air pollution on children and adolescents, as well as the potential harm when coupled with outdoor physical activity
  • Add air quality systems at school sites, so pollution can be measured when and where children are engaging in physical activity
  • Adjust the intensity of outdoor physical activity during the school day on the basis of air pollution monitoring results
  • Educate children about exercising in polluted environments, including instruction to stop activity when they notice problems such as coughing, chest tightness or wheezing

Since schools are the base for much of the physical activity of today’s children, they are a critical piece in addressing both issues, Cardinal said. Monitoring the micro-climate at a school would provide better, more localized information for school officials making decisions about whether children should be outside exercising or at what level of intensity. 

“Doing some kind of physical activity, even if it is not as vigorous, is still better than having no physical activity for the children,” he said.

Clothing accessories or fitness equipment could also be designed to help protect children from pollution during outdoor play activities on days when air quality levels were low, he said.

“The goal is to get people thinking about these complex problems and real-world solutions,” Cardinal said. “The hope is that someone will innovate appropriate solutions for addressing both of these problems.” 

The National Health and Fitness Technology Research Key Laboratory of Zhejiang Province provided support for this project.

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Brad Cardinal, 541-737-2506, brad.cardinal@oregonstate.edu

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