OREGON STATE UNIVERSITY

college of science

An ancient killer: ancestral malarial organisms traced to age of dinosaurs

CORVALLIS, Ore. – A new analysis of the prehistoric origin of malaria suggests that it evolved in insects at least 100 million years ago, and the first vertebrate hosts of this disease were probably reptiles, which at that time would have included the dinosaurs.

Malaria, a scourge on human society that still kills more than 400,000 people a year, is often thought to be of more modern origin - ranging from 15,000 to 8 million years old, caused primarily by one genus of protozoa, Plasmodium, and spread by anopheline mosquitoes.

But the ancestral forms of this disease used different insect vectors and different malarial strains, and may literally have helped shape animal survival and evolution on Earth, according to George Poinar, Jr., a researcher in the College of Science at Oregon State University.

Poinar suggested in the journal American Entomologist that the origins of this deadly disease, which today can infect animals ranging from humans and other mammals to birds and reptiles, may have begun in an insect such as the biting midge more than 100 million years ago. And in previous work, Poinar and his wife, Roberta, implicated malaria and the evolution of blood-sucking insects as disease vectors that could have played a significant role in the extinction of the dinosaurs.

“Scientists have argued and disagreed for a long time about how malaria evolved and how old it is,” Poinar said. “I think the fossil evidence shows that modern malaria vectored by mosquitoes is at least 20 million years old, and earlier forms of the disease, carried by biting midges, are at least 100 million years old and probably much older.”

Since the sexual reproduction stage of malaria only occurs in insects, Poinar said in the new study that they must be considered the primary hosts of the disease, not the vertebrate animals that they infect with disease-causing protozoa. And he believes the evidence points toward the Gregarinida as a protozoan parasite group that could have been the progenitors of malaria, since they readily infect the insects that vector malaria today.

Understanding the ancient history of malaria evolution, Poinar said, might offer clues to how its modern-day life cycle works, how it evolved, and what might make possible targets to interrupt its transmission through its most common vector, the Anopheles mosquito.

Understanding the evolution of malaria also takes one on a worldwide journey, according to evidence found in insects preserved in amber. Poinar is an international expert in using plant and animal life forms preserved in this semi-precious stone to help learn more about the biology and ecology of the distant past.

Poinar was the first to discover a type of malaria in a 15-20 million-year-old fossil from the New World, in what is now the Dominican Republic. It was the first fossil record of Plasmodium malaria, one type of which is now the strain that infects and kills humans.

Even further back, malaria may have been one of the diseases that arose, along with the evolution of insects, and had a huge impact on animal evolution. In a 2007 book, “What Bugged the Dinosaurs? Insects, Disease and Death in the Cretaceous,” George and Roberta Poinar argued that insects carried diseases that contributed to the widespread extinction of the dinosaurs around the “K-T boundary” about 65 million years ago.

“There were catastrophic events known to have happened around that time, such as asteroid impacts and lava flows,” Poinar said. “But it’s still clear that dinosaurs declined and slowly became extinct over thousands of years, which suggests other issues must also have been at work. Insects, microbial pathogens and vertebrate diseases were just emerging around that same time, including malaria.”

Avian malaria has been implicated in the extinction of many bird species in Hawaii just in recent decades, especially in species with no natural resistance to the disease. Different forms of malaria, which is now known to be an ancient disease, may have been at work many millions of years ago and probably had other implications affecting the outcome of vertebrate survival, Poinar said.

The first human recording of malaria was in China in 2,700 B.C., and some researchers say it may have helped lead to the fall of the Roman Empire. In 2015 there were 214 million cases worldwide, according to the World Health Organization. Immunity does not occur naturally and the search for a vaccine has not yet been achieved.

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Biting midge


Biting midge
with ancestral malaria


Oldest fossil showing Plasmodium malaria
Oldest fossil with
Plasmodium malaria

DNA evidence shows that salmon hatcheries cause substantial, rapid genetic changes

CORVALLIS, Ore. – A new study on steelhead trout in Oregon offers genetic evidence that wild and hatchery fish are different at the DNA level, and that they can become different with surprising speed.

The research, published today in Nature Communications, found that after one generation of hatchery culture, the offspring of wild fish and first-generation hatchery fish differed in the activity of more than 700 genes.

A single generation of adaptation to the hatchery resulted in observable changes at the DNA level that were passed on to offspring, scientists reported.

This research was conducted at Oregon State University in collaboration with the Oregon Department of Fisheries and Wildlife. Scientists say the findings essentially close the case on whether or not wild and hatchery fish can be genetically different.

Differences in survival and reproductive success between hatchery and wild fish have long offered evidence of rapid adaptation to the hatchery environment. This new DNA evidence directly measured the activity of all genes in the offspring of hatchery and wild fish. It conclusively demonstrates that the genetic differences between hatchery and wild fish are large in scale and fully heritable.

“A fish hatchery is a very artificial environment that causes strong natural selection pressures,” said Michael Blouin, a professor of integrative biology in the OSU College of Science. “A concrete box with 50,000 other fish all crowded together and fed pellet food is clearly a lot different than an open stream.”

It’s not clear exactly what traits are being selected for, but the study was able to identify some genetic changes that may explain how the fish are responding to the novel environment in the hatchery.

“We observed that a large number of genes were involved in pathways related to wound healing, immunity, and metabolism, and this is consistent with the idea that the earliest stages of domestication may involve adapting to highly crowded conditions,” said Mark Christie, lead author of the study.

Aside from crowding, which is common in the hatchery, injuries also happen more often and disease can be more prevalent.

The genetic changes are substantial and rapid, the study found. It’s literally a process of evolution at work, but in this case it does not take multiple generations or long periods of time.

“We expected hatcheries to have a genetic impact,” Blouin said. “However, the large amount of change we observed at the DNA level was really amazing. This was a surprising result.”

With the question put to rest of whether hatchery fish are different, Blouin said, it may now be possible to determine exactly how they are different, and work to address that problem. When the genetic changes that occur in a hatchery environment are better understood, it could be possible to change the way fish are raised in order to produce hatchery fish that are more like wild fish. This research is a first step in that direction.

This work was performed using steelhead trout from the Hood River in Oregon. It was supported by the Bonneville Power Administration and the Oregon Department of Fish and Wildlife.

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Michael Blouin, 541-737-2362

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Steelhead


Steelhead trout


Juvenile steelhead trout
Juvenile steelhead

Ancient flowering plant was beautiful - but probably poisonous

CORVALLIS, Ore. – Researchers today announced in the journal Nature Plants the discovery of the first-ever fossil specimens of an “asterid” – a group of flowering plants that gave us everything from the potato to tomatoes, tobacco, petunias and our morning cup of coffee.

But these two 20-30 million-year-old fossil flowers, found perfectly preserved in a piece of amber, came from the dark side of the asterid group – they belong to the genus Strychnos, which ultimately gave rise to some of the world’s most famous poisons, including strychnine and curare.

Poisons that would later find their way into blow-gun weapons, rat control, Sherlock Holmes stories and the movie “Psycho” appear to have had some of their ancestral and biological roots in the prehistoric jungles of what’s now the Dominican Republic, researchers say.

“The specimens are beautiful, perfectly preserved fossil flowers, which at one point in time were borne by plants that lived in a steamy tropical forest with both large and small trees, climbing vines, palms, grasses and other vegetation,” said George Poinar, Jr., a courtesy professor in the College of Science at Oregon State University, and one of the world’s experts on plant and animal life forms preserved in amber.

“Specimens such as this are what give us insights into the ecology of ecosystems in the distant past,” Poinar said.  “It shows that the asterids, which later gave humans all types of foods and other products, were already evolving many millions of years ago.”

Asterids, the researchers noted in this study, are among Earth’s most important and diverse plants, with 10 orders, 98 families, and about 80,000 species. They represent about one-third of all the Earth’s diversity of angiosperms, or flowering plants.

And one ancient genus, which has now been shown to be inherently toxic, existed for millions of years before humans appeared on the planet.

“Species of the genus Strychnos are almost all toxic in some way,” Poinar said. “Each plant has its own alkaloids with varying effects. Some are more toxic than others, and it may be that they were successful because their poisons offered some defense against herbivores.

“Today some of these toxins have been shown to possess useful and even medicinal properties.”

As natural poisons that humans came to understand and use, two extracts from plants in the Strychnos genus ultimately became famous – strychnine and curare.

Strychnine had practical uses for decades as a pesticide, and was often the deadly component of rat poison. But it also captured the imagination of writers, and was used by Norman Bates in the movie “Psycho” to kill his mother and her male companion. In small doses, it can increase mental and muscular activity.

Curare has an even stranger history. Sir Walter Raleigh may have first encountered it in 1596 when he observed poison arrows in South America, where natives also developed the poison in blow-gun darts to paralyze hunted prey. Curare was featured as the murder weapon in one Sherlock Holmes novel, and in lower doses it has been used as a muscle relaxant in surgery.

There are now about 200 species of Strychnos plants around the world, in forms ranging from shrubs to trees and woody climbing vines, mostly in the tropics. They are still being studied for medicinal properties, such as for the treatment of parasitic worm infections and even as drugs to treat malaria.

The discovery of these two fossil flowers, researchers said, suggests that many other related plant families could have evolved in the Late Cretaceous in tropical forests. Their fossil remains, however, still await discovery.

The co-author of this study, Lena Struwe, is an expert on plants in the strychnine family, Loganiaceae, and is a plant biologist at Rutgers University.

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Ancient asterid


Asterid fossil


Asterid flower
Top of flower

Herpes outbreak, other marine viruses linked to coral bleaching event

CORVALLIS, Ore. – A study at Oregon State University has concluded that significant outbreaks of viruses may be associated with coral bleaching events, especially as a result of multiple environmental stresses.

One such event was documented even as it happened in a three-day period. It showed how an explosion of three viral groups, including a herpes-like virus, occurred just as corals were bleaching in one part of the Great Barrier Reef off the east coast of Australia.

The findings, reported in Frontiers in Microbiology, take on special significance as the world is now experiencing just the third incidence ever recorded of coral bleaching on a global scale, according to the National Oceanic and Atmospheric Administration, or NOAA.

Coral bleaching can occur when corals are exposed to stressful environmental conditions, such as warmer water, overfishing or pollution. This can cause them to expel symbiotic algae that live in their tissues and lose their color. The coral loses its major source of food and is more susceptible to disease. In severe or prolonged cases the bleaching can be lethal to the corals.

“People all over the world are concerned about long-term coral survival,” said Rebecca Vega-Thurber, an assistant professor of microbiology in the OSU College of Science and corresponding author on the study. “This research suggests that viral infection could be an important part of the problem that until now has been undocumented, and has received very little attention.”

In a natural experiment, an area of corals on the Great Barrier Reef was exposed to high levels of ultraviolet light at low tides during a period of heavy rain and high temperatures, all of which are sources of stress for the corals. At that time, viral loads in those corals exploded to levels 2-4 times higher than ever recorded in corals, and there was a significant bleaching event over just three days.

The viruses included retroviruses and megaviruses, and a type of herpes virus was particularly abundant. Herpes viruses are ancient and are found in a wide range of mammals, marine invertebrates, oysters, corals and other animals.

The findings, Vega-Thurber said, suggest that a range of stresses may have made the corals susceptible to viral attack, particularly high water temperatures such as those that can be caused by an El Nino event and global warming.

“This is bad news,” Vega-Thurber said. “This bleaching event occurred in a very short period on a pristine reef. It may recover, but incidents like this are now happening more widely all around the world.”

Last year, NOAA declared that the world was now experiencing its third global coral bleaching event, the last two being in 1998 and again in 2010. The current event began in the northern Pacific Ocean in 2014, moved south during 2015, and may continue into this year, NOAA officials said.

NOAA estimated that by the end of last year, almost 95 percent of U.S. coral reefs were exposed to ocean conditions that can cause corals to bleach.  If corals die, there will be less shoreline protection from storms, and fewer habitats for fish and other marine life.

Viruses are abundant, normal and diverse residents of stony coral colonies, the researchers noted in their study. Viruses may become a serious threat only when their numbers reach extremely high levels, which in this case was associated with other stressful environmental conditions, scientists said.

This work was supported by the National Science Foundation.

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Rebecca Vega-Thurber, 541-737-1851

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Bleached coral
Coral bleaching

New therapy halts progression of Lou Gehrig’s disease in mice

CORVALLIS, Ore. – Researchers at Oregon State University announced today that they have essentially stopped the progression of amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, for nearly two years in one type of mouse model used to study the disease – allowing the mice to approach their normal lifespan.

The findings, scientists indicate, are some of the most compelling ever produced in the search for a therapy for ALS, a debilitating and fatal disease, and were just published in Neurobiology of Disease.

“We are shocked at how well this treatment can stop the progression of ALS,” said Joseph Beckman, lead author on this study, a distinguished professor of biochemistry and biophysics in the College of Science at Oregon State University, and principal investigator and holder of the Burgess and Elizabeth Jamieson Chair in OSU’s Linus Pauling Institute.

In decades of work, no treatment has been discovered for ALS that can do anything but prolong human survival less than a month. The mouse model used in this study is one that scientists believe may more closely resemble the human reaction to this treatment, which consists of a compound called copper-ATSM.

It’s not yet known if humans will have the same response, but researchers are moving as quickly as possible toward human clinical trials, testing first for safety and then efficacy of the new approach.

ALS was identified as a progressive and fatal neurodegenerative disease in the late 1800s, and gained international recognition in 1939 when it was diagnosed in American baseball legend Lou Gehrig. It’s known to be caused by the death and deterioration of motor neurons in the spinal cord, which in turn has been linked to mutations in copper, zinc superoxide dismutase.

Copper-ATSM is a known compound that helps deliver copper specifically to cells with damaged mitochondria, and reaches the spinal cord where it’s needed to treat ALS. This compound has low toxicity, easily penetrates the blood-brain barrier, is already used in human medicine at much lower doses for some purposes, and is well tolerated in laboratory animals at far higher levels. Any copper not needed after use of copper-ATSM is quickly flushed out of the body.

Experts caution, however, that this approach is not as simple as taking a nutritional supplement of copper, which can be toxic at even moderate doses. Such supplements would be of no value to people with ALS, they said.

The new findings were reported by scientists from OSU; the University of Melbourne in Australia; University of Texas Southwestern; University of Central Florida; and the Pasteur Institute of Montevideo in Uruguay. The study is available as open access in Neurobiology of Disease.

Using the new treatment, researchers were able to stop the progression of ALS in one type of transgenic mouse model, which ordinarily would die within two weeks without treatment. Some of these mice have survived for more than 650 days, 500 days longer than any previous research has been able to achieve.

In some experiments, the treatment was begun, and then withheld. In this circumstance the mice began to show ALS symptoms within two months after treatment was stopped, and would die within another month. But if treatment was resumed, the mice gained weight, progression of the disease once again was stopped, and the mice lived another 6-12 months.

In 2012, Beckman was recognized as the leading medical researcher in Oregon, with the Discovery Award from the Medical Research Foundation of Oregon. He is also director of OSU’s Environmental Health Sciences Center, funded by the National Institutes of Health to support research on the role of the environment in causing disease.

“We have a solid understanding of why the treatment works in the mice, and we predict it should work in both familial and possibly sporadic human patients,” Beckman said. “But we won’t know until we try.”

Familial ALS patients are those with more of a family history of the disease, while sporadic patients reflect the larger general population.

“We want people to understand that we are moving to human trials as quickly as we can,” Beckman said. “In humans who develop ALS, the average time from onset to death is only three to four years.”

The advances are based on substantial scientific progress in understanding the disease processes of ALS and basic research in biochemistry. The transgenic mice used in these studies have been engineered to carry the human gene for “copper chaperone for superoxide dismutase,” or CCS gene. CCS inserts copper into superoxide dismustase, or SOD, and transgenic mice carrying these human genes die rapidly without treatment.

After years of research, scientists have developed an approach to treating ALS that’s based on bringing copper into specific cells in the spinal cord and mitochondria weakened by copper deficiency. Copper is a metal that helps to stabilize SOD, an antioxidant protein whose proper function is essential to life. But when it lacks its metal co-factors, SOD can “unfold” and become toxic, leading to the death of motor neurons.

There’s some evidence that this approach, which works in part by improving mitochondrial function, may also have value in Parkinson’s disease and other conditions, researchers said. Research is progressing on those topics as well. 

The treatment is unlikely to allow significant recovery from neuronal loss already caused by ALS, the scientists said, but could slow further disease progression when started after diagnosis. It could also potentially treat carriers of SOD mutant genes that cause ALS.

This work has been supported by the Department of Defense Congressionally Directed Medical Research Program, the U.S. National Institutes of Health, the Amyotrophic Lateral Sclerosis Association, the Australian National Health and Medical Research Association, and gifts by Michael Camillo and Burgess and Elizabeth Jamieson to the Linus Pauling Institute.

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Joseph Beckman, 541-737-8867

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Copper, zinc superoxide dismutase
Copper, zinc superoxide dismutase

Research identifies key genetic link in the biology of aging

CORVALLIS, Ore. – New research at Oregon State University suggests it may be possible to slow age-related disease with new types of treatments.

Scientists have tracked the syndromes associated with aging to their biochemical roots, and identified a breakdown in genetic communication as part of the problem. The findings imply that aging happens for a reason, and that while aspects of it may be inevitable, there could be ways to slow down disease development.

The newest study relate to a protein, Nrf2, that helps regulate gene expression and the body’s reaction to various types of stressors. The research was published in Free Radical Biology and Medicine, in work supported by the National Institutes of Health and the Medical Research Foundation of Oregon.

“We’re very excited about the potential of this area of research,” said Tory Hagen, corresponding author on this study, and the Helen P. Rumbel Professor for Health Aging Research in the Linus Pauling Institute and the OSU Department of Biochemistry and Biophysics in the College of Science.

“At least one important part of what we call aging appears to be a breakdown in genetic communication, in which a regulator of stress resistance declines with age,” Hagen said. “As people age and their metabolic problems increase, the levels of this regulator, Nrf2, should be increasing, but in fact they are declining.”

Nrf2 is both a monitor and a messenger, OSU researchers say. It’s constantly on the lookout for problems with cells that may be caused by the many metabolic insults of life – oxidative stress, toxins, pollutants, and other metabolic dysfunction.

When it finds a problem, Nrf2 essentially goes back to the cellular nucleus and rings the alarm bell, where it can “turn on” up to 200 genes that are responsible for cell repair, detoxification of carcinogens, protein and lipid metabolism, antioxidant protection and other actions. In their report, the scientists called it a “longevity-assurance” factor.

Nrf2 is so important that it’s found in many life forms, not just humans, and it’s constantly manufactured by cells throughout the body. About half of it is used up every 20 minutes as it performs its life-protective functions. Metabolic insults routinely increase with age, and if things were working properly, the amount of Nrf2 that goes back into the nucleus should also increase to help deal with those insults.

Instead, the level of nuclear Nrf2 declines, and the OSU scientists say they have discovered why.

“The levels of Nrf2, and the functions associated with it, are routinely about 30-40 percent lower in older laboratory animals,” said Kate Shay, director of the Healthy Aging Core Laboratory at OSU and co-author on this study. “We’ve been able to show for the first time what we believe is the cause.”

The reason for this decline, the scientists said, is increasing levels of a micro-RNA called miRNA-146a.

Micro-RNAs have been one of the most profound scientific discoveries of the past 20 years. They were once thought to be “junk DNA” because researchers could see them but they had no apparent biological role. They are now understood to be anything but junk – they help play a major role in genetic signaling, controlling what genes are “expressed,” or turned on and off to perform their function.

In humans, miRNA-146a plays a significant role. It can turn on the inflammation processes that, in something like a wound, help prevent infection and begin the healing process. But with aging, this study now shows that miRNA-146a expression doesn’t shut down properly, and it can significantly reduce the levels of Nrf2.

This can cause part of the chronic, low-grade inflammation that is associated with the degenerative diseases that now kill most people in the developed world, including heart disease, cancer, diabetes and neurological disease.

“The action of miRNA-146a in older people appears to turn from a good to a bad influence,” Shay said. “It may be causing our detoxification processes to decline just when we need them the most.”

Some of the things found to be healthy for individuals, in diet or lifestyle, may be so because they help to conserve the proper balance between the actions of miRNA-146a and Nrf2, the OSU researchers said. Alternatively, it may be possible to reduce excessive levels of miRNA-146a with compounds that interfere with its function. There may also be other micro-RNAs associated with this process, they said, that need further research.

“Overall, these results provide novel insights for the age-related decline in Nrf2 and identify new targets to maintain Nrf2-dependent detoxification with age,” the researchers wrote in their conclusion.

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Tory Hagen, 541-737-5083

Harbor seal deaths show presence of bacterial infection

CORVALLIS, Ore. – A study by microbiologists at Oregon State University has concluded that an unsuspected bacterial infection, rather than a viral disease, was associated with the stranding and death of seven harbor seals on the California coast in 2009.

The research, made with a powerful investigative method called “meta-transcriptomics,” found a high incidence of infection in the seals with the bacterial pathogen Burkholderia, and provides the first report in the Americas of this bacteria in a wild harbor seal.

The bacteria probably did not directly cause the death of the seals, researchers say, but this provides  further evidence of the increase in emerging marine pathogens, and the need for improved monitoring and study of zoonotic diseases that could affect both human and wildlife populations.

In light of these findings, OSU researchers also remind the public that they should not touch stranded or dead marine mammals.

The research was recently published in PLOS ONE, in work supported by the Oregon Sea Grant program and the National Science Foundation.

“We now have improved tools to better identify new diseases as they emerge from natural reservoirs, and can record and track these events,” said Rebecca Vega-Thurber, an assistant professor of microbiology in the OSU College of Science. “It’s becoming clear there are more pathogens than we knew of in the past, and that some of them can move into human populations.

“This is why it’s increasingly important that we accurately pinpoint the cause of these diseases, and understand the full range of causes that may factor into these deaths.”

Cases such as this, the researchers said, point out that it’s not always a single pathogen that causes death, but a combination of pathogens, changing environmental influences, weakened hosts and other forces. In this seal-stranding event, the scientists also found evidence of Coxiella burnettii, another bacterial pathogen, at high levels in one animal.

Advances in this type of monitoring are being made with the comparatively new field of meta-transcriptomics, which has been referred to as a way to eavesdrop on the viral and microbial world, to catalogue and compare sequences from suspected pathogens. It’s just now being applied to marine systems, which are often reservoirs for pathogens that can emerge into terrestrial populations.

This phenomenon seems to be picking up speed, the researchers noted in their study.

About 61 percent of emerging human diseases arise from zoonotic pathogens, and about 70 percent of these originate from wildlife. The recent Ebola outbreak in Africa was one example; the bacterial pathogen that causes tuberculosis was introduced to the Americas from pinnipeds; and influenza has been shown to be transmitted from seals to humans.  In recent years, viral disease has been implicated in the deaths of tens of thousands of harbor seals.

Almost half of marine mammals die from unknown causes, the researchers said, but the use of new high-speed, analytic tools could offer ways to change that. The techniques don’t require prior information about the viruses and bacterial infections that may be affecting wildlife.

In the case of the stranded harbor seals in this study, it was initially suspected that viruses were the cause. This study largely ruled that out, but identified bacterial infection in the animals’ brains. The final cause of death is still unknown and research on that issue is continuing.

“These analytic tools should be increasingly useful in the future, and show us just what genes the pathogens may be using during an infection,” said Stephanie Rosales, a doctoral student in the OSU College of Science, and lead author on this study.  “A lot of new environmental changes and stresses are taking place that may lead to new emerging diseases, and we should be tracking them as they evolve.”

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Rebecca Vega-Thurber, 541-737-1851

Vitamin D, xanthohumol may offer new approach to obesity epidemic

CORVALLIS, Ore. – A growing body of evidence suggests that two natural compounds, vitamin D and xanthohumol, have the ability to address imbalances in gut microbiota that may set the stage for obesity and metabolic syndrome - problems that affect about one out of every three adults in the United States.

To explore and identify the specific mechanisms by which these compounds have beneficial effects, researchers in the Linus Pauling Institute at Oregon State University have received a new five-year, $2.64 million grant from the National Institutes of Health.

The possible payoff of this research, they say, may be an entirely new way to reduce or prevent some of the major diseases that are killing millions of people every year, such as heart disease and type-2 diabetes.

The new approach would attempt, using high dose supplementation, to prevent disease from developing, instead of treating it after the fact.

“The benefits of xanthohumol and vitamin D have been clearly shown in laboratory studies to reduce weight gain and improve gut barrier defenses,” said Adrian Gombart, an associate professor of biochemistry and biophysics in the OSU College of Science, and a principal investigator with the Linus Pauling Institute. “These compounds appear to activate nuclear receptors and pathways that may affect microbe composition, and in the process reduce the damage from metabolic syndrome.”

One study published by OSU researchers two years ago in the Journal of Biological Chemistry found that rats given xanthohumol supplements, which are made from hops, had a 14 percent reduction in weight gain, a 25 percent reduction in plasma fasting glucose, and improved lipid metabolism, compared to a control group of rats that ate the same amount of food. They had a higher rate of fatty acid oxidation and energy metabolism. In simple terms, they burned more fat.

In other studies, higher levels of vitamin D status in humans have been associated with reduced risk of obesity, metabolic syndrome, cancer, infectious diseases, autoimmune diseases, and other health problems.

Other lead investigators on this research include Claudia Maier, an OSU professor of chemistry; Fred Stevens, a professor in the OSU College of Pharmacy and also a principal investigator with the Linus Pauling Institute; and Balz Frei, a distinguished professor of biochemistry and biophysics, and director of the Linus Pauling Institute.

The OSU researchers believe some of the benefits of vitamin D and/or xanthohumol may be a strong increase in the expression of the cathelicidin antimicrobial peptide, or CAMP gene. The hypothesis to be tested in this research, using animal models, is that higher CAMP levels improve gut epithelial barrier function, reduce inflammation, modify gut microbiota and in the process reduce problems with obesity and metabolic syndrome.

“Some of the benefits we’re seeing are fairly clear and dramatic, and we need to better understand the mechanisms that cause them,” Stevens said.

The compounds may also affect liver function, shutting down metabolic pathways that produce fat and glucose, he said.

Vitamin D can be obtained through either the diet or produced by the skin, with adequate exposure to sunshine. Millions of people who live in temperate zones around the world, however, have been found to have inadequate levels of this vitamin, but this can be corrected by taking a supplement.

Xanthohumol, a flavonoid, is also a natural compound and is found in the hops used to make beer. Researchers point out, however, that the levels of xanthohumol being used in this research greatly exceed any amount that could be obtained by drinking beer.

Direct health care costs arising from obesity and related disorders accounts for almost 10 percent of U.S. health care expenditures each year, the researchers said. The health care costs of diabetes alone were estimated in the U.S. at $176 billion in 2012, and it’s one of the leading causes of death in the nation.

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Adrian Gombart, 541-737-8018

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Hops


Xanthohumol in hops


Vitamin D
Vitamin D in milk

Discovery about protein structure opens window on basic life process

CORVALLIS, Ore. – Biochemists at Oregon State University have made a fundamental discovery about protein structure that sheds new light on how proteins fold, which is one of the most basic processes of life.

The findings, announced today in Science Advances, will help scientists better understand some important changes that proteins undergo. It had previously been thought to be impossible to characterize these changes, in part because the transitions are so incredibly small and fleeting.

The changes relate to how proteins convert from one observable shape to another – and they happen in less than one trillionth of a second, in molecules that are less than one millionth of an inch in size. It had been known that these changes must happen and they have been simulated by computers, but prior to this no one had ever observed how they happen.

Now they have, in part by recognizing the value of certain data collected by many researchers over the last two decades.

“Actual evidence of these transitions was hiding in plain sight all this time,” said Andrew Brereton, an OSU doctoral student and lead author on this study. “We just didn’t know what to look for, and didn’t understand how significant it was.”

All proteins start as linear chains of building blocks and then quickly fold to their proper shape, going through many high-energy transitions along the way. Proper folding is essential to the biological function of proteins, and when it doesn’t happen correctly, protein folding diseases can be one result – such as Alzheimer’s disease, Lou Gehrig’s disease, amyloidosis and others.

Proteins themselves are a critical component of life, the workhorses of biology. They are comparatively large, specialty molecules that can do everything from perceiving light to changing shape and making muscles function. Even the process of thinking involves proteins at the end of one neuron passing a message to different proteins on the next neuron.

A powerful tool called X-ray crystallography has been able to capture images of proteins in their more stable shapes, but what was unknown is exactly how they got from one stable form to another. The changes in shape that are needed for those transitions are fleeting and involve distortions in the molecules that are extreme and difficult to predict.

What the OSU researchers discovered, however, is that the stable shapes adopted by a few proteins actually contained some parts that were trapped in the act of changing shape, conceptually similar to finding mosquitos trapped in amber.

“We discovered that some proteins were holding single building blocks in shapes that were supposed to be impossible to find in a stable form,” said Andrew Karplus, the corresponding author on the study and a distinguished professor of biochemistry and biophysics in the OSU College of Science.

“Apparently about one building block out of every 6,000 gets trapped in a highly unlikely shape that is like a single frame in a movie,” Karplus said. “The set of these trapped residues taken together have basically allowed us to make a movie that shows how these special protein shape changes occur. And what this movie shows has real differences from what the computer simulations had predicted.”

As with most fundamental discoveries, the researchers said, the full value of the findings may take years or decades to play out.

What is clear is that proteins are key to some of the most fundamental processes of life, and this new information has revealed the first direct views of specific details of one aspect of protein folding in a way that had not been considered possible.

“In the 1870s an English photographer named Eadweard Muybridge made some famous photographs that settled a debate which had been going on for decades, about whether horses as they run actually lift all four feet off the ground at the same time,” Karplus said.

“His novel series of stop-action photos proved that they did, and opened up a whole new understanding of animal locomotion,” he said. “In a similar way, our results change the way researchers can now look at one of the ways proteins change shape, and that’s a pretty fundamental part of life.”

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Andrew Karplus, 541-737-3200

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Protein structural changes

Protein folding


Instants in time
Stop-action of running horse

Ocean protection gaining momentum, but still lags progress made on land

CORVALLIS, Ore. – Extraordinary progress in the past decade has brought 1.6 percent of the world’s ocean to a category of “strongly protected,” researchers say in a new analysis, but the accomplishments are still far behind those that have been achieved on land – and those that are urgently needed.

In a report published today in the journal Science, researchers from Oregon State University point out that numerous international policy agreements call for protecting 10 percent of coastal and marine areas by 2020, while some conservation organizations and most scientists say 20-50 percent of ocean protection is needed.

The science of marine protected areas is now mature and extensive, the researchers say, and the multiple threats facing the Earth’s ocean from overfishing, climate change, loss of biodiversity, acidification and many other issues warrant more accelerated, science-driven action.

“The world is well on its way to meeting targets set for protection on land, but far from its goals for ocean protection,” said Jane Lubchenco, who is the OSU University Distinguished Professor and Adviser in Marine Studies, former NOAA administrator, U.S. Science Envoy for the Ocean and a marine biologist in the OSU College of Science.

“We’ve seen an acceleration of progress in recent years, and that’s good,” Lubchenco said. “But the politics of ocean protection are too often disconnected from the science and knowledge that supports it, and there are many things we can do to help bridge that gap.”

There have been significant and recent success stories, the scientists pointed out.

Earlier this month three new, large and fully protected areas were announced at the United Nations and at the Our Ocean conference, which encompass waters around Chile and New Zealand. Last year, the U.S. expanded by six times the Pacific Remote Island Marine National Monument; and the United Kingdom created what will be the world’s largest fully protected marine area, the Pitcairn Islands Marine Reserve.

“Even if we lump together all protection categories, however, only 3.5 percent of the ocean has any form of protection,” said Kirsten Grorud-Colvert, an OSU assistant professor of research and director of the Science of Marine Reserves Project.

“In contrast, the target to protect 17 percent of the terrestrial part of the planet is expected to be met by 2020, and it already stands at 15 percent,” Grorud-Colverts said. “There is so much more that needs to be done to protect the ocean, and we have the scientific knowledge to inform the decision-making.”

Marine protection can range from “lightly protected,” which allows some protection but significant extractive activity, to the “full” protection usually identified as marine reserves. Such areas, covering an almost undectable total area of the ocean a decade ago, are rapidly gaining attention as their social, economic, and environmental benefits become more clear.

To further speed that progress, the OSU researchers highlighted seven key findings. They include:

  • Full protection works. Fully protected and effectively enforced areas generally result in significant increases in biomass, size of individuals and diversity inside a reserve. Those benefits in turn often spill over to adjacent areas outside the reserve.
  • Habitats are connected. Many species move among habitats during their life cycles, so a range of protected areas will aid in protecting biodiversity and enhancing benefits inside and outside the reserve.
  • Networks allow fishing. A network, or set of reserves that are connected by the movement of juveniles and adults, can provide many of the benefits of a single large area, while still allowing fishing between the reserves.
  • Engaging users usually improves outcomes. Fishers, managers, conservation advocates, and scientists can work together to address both conservation and fishery goals.
  • Reserves can enhance resilience. Large and strategically placed reserves can assist in adapting to environmental and climatic changes.
  • Planning saves money. Smart planning can reduce costs of creating reserves and increase their economic benefits, in some cases making them more valuable than before the reserve was created.
  • Ecosystems matter. Complementary efforts to ensure sustainable uses outside a reserve are needed, and should be integrated to ensure viable levels of activities such as fishing, aquaculture, energy generation, recreation and marine protection. The goal is to use the ocean without using it up.

The scientists said that policy improvements can be aided by embracing more options, bringing more users into the discussion, and changing incentives so that economic and social impacts can be minimized. New enforcement technologies can also help, along with integrating reserves with other management measures.

“An accelerated pace of protection will be needed for the ocean to provide the full range of benefits people want and need,” the scientists wrote in their conclusion.

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Jane Lubchenco, 541-737-5337

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Coral reefs

Coral reef

 

Multiple species

Easter Island

 

Butterfly fish

Butterfly fish