OREGON STATE UNIVERSITY

college of science

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

Discovery about new battery overturns decades of false assumptions

CORVALLIS, Ore. – New findings at Oregon State University have overturned a scientific dogma that stood for decades, by showing that potassium can work with graphite in a potassium-ion battery – a discovery that could pose a challenge and sustainable alternative to the widely-used lithium-ion battery.

Lithium-ion batteries are ubiquitous in devices all over the world, ranging from cell phones to laptop computers and electric cars. But there may soon be a new type of battery based on materials that are far more abundant and less costly.

A potassium-ion battery has been shown to be possible. And the last time this possibility was explored was when Herbert Hoover was president, the Great Depression was in full swing and the Charles Lindbergh baby kidnapping was the big news story of the year – 1932.

“For decades, people have assumed that potassium couldn’t work with graphite or other bulk carbon anodes in a battery,” said Xiulei (David) Ji, the lead author of the study and an assistant professor of chemistry in the College of Science at Oregon State University.

“That assumption is incorrect,” Ji said. “It’s really shocking that no one ever reported on this issue for 83 years.”

The Journal of the American Chemical Society published the findings from this discovery, which was supported by the U.S. Department of Energy and done in collaboration with OSU researchers Zelang Jian and Wei Luo. A patent is also pending on the new technology.

The findings are of considerable importance, researchers say, because they open some new alternatives to batteries that can work with well-established and inexpensive graphite as the anode, or high-energy reservoir of electrons. Lithium can do that, as the charge carrier whose ions migrate into the graphite and create an electrical current.

Aside from its ability to work well with a carbon anode, however, lithium is quite rare, found in only 0.0017 percent, by weight, of the Earth’s crust. Because of that it’s comparatively expensive, and it’s difficult to recycle. Researchers have yet to duplicate its performance with less costly and more readily available materials, such as sodium, magnesium, or potassium.

“The cost-related problems with lithium are sufficient that you won’t really gain much with economies of scale,” Ji said. “With most products, as you make more of them, the cost goes down. With lithium the reverse may be true in the near future. So we have to find alternatives.”

That alternative, he said, may be potassium, which is 880 times more abundant in the Earth’s crust than lithium. The new findings show that it can work effectively with graphite or soft carbon in the anode of an electrochemical battery. Right now, batteries based on this approach don’t have performance that equals those of lithium-ion batteries, but improvements in technology should narrow the gap, he said.

“It’s safe to say that the energy density of a potassium-ion battery may never exceed that of lithium-ion batteries,” he said. “But they may provide a long cycling life, a high power density, a lot lower cost, and be ready to take the advantage of the existing manufacturing processes of carbon anode materials.”

Electrical energy storage in batteries is essential not only for consumer products such as cell phones and computers, but also in transportation, industry power backup, micro-grid storage, and for the wider use of renewable energy.

OSU officials say they are seeking support for further research and to help commercialize the new technology, through the OSU Office of Commercialization and Corporate Development.

 

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Xiulei (David) Ji, 541-737-6798

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Potassium-ion battery

Battery characteristics

Bacteria in ancient flea may be ancestor of the Black Death

CORVALLIS, Ore. – About 20 million years ago a single flea became entombed in amber with tiny bacteria attached to it, providing what researchers believe may be the oldest evidence on Earth of a dreaded and historic killer – an ancient strain of the bubonic plague.

If indeed the fossil bacteria are related to plague bacteria, Yersinia pestis, the discovery would show that this scourge, which killed more than half the population of Europe in the 14th century, actually had been around for millions of years before that, traveled around much of the world, and predates the human race.

Findings on this extraordinary amber fossil have been published in the Journal of Medical Entomology by George Poinar, Jr., an entomology researcher in the College of Science at Oregon State University, and a leading expert on plant and animal life forms found preserved in this semi-precious stone.

It can’t be determined with certainty that these bacteria, which were attached to the flea’s proboscis in a dried droplet and compacted in its rectum, are related to Yersinia pestis, scientists say. But their size, shape and characteristics are consistent with modern forms of those bacteria. They are a coccobacillus bacteria; they are seen in both rod and nearly spherical shapes; and are similar to those of Yersinia pestis. Of the pathogenic bacteria transmitted by fleas today, only Yersinia has such shapes.

“Aside from physical characteristics of the fossil bacteria that are similar to plague bacteria, their location in the rectum of the flea is known to occur in modern plague bacteria,” Poinar said. “And in this fossil, the presence of similar bacteria in a dried droplet on the proboscis of the flea is consistent with the method of transmission of plague bacteria by modern fleas.”

These findings are in conflict with modern genomic studies indicating that the flea-plague-vertebrate cycle evolved only in the past 20,000 years, rather than 20 million. However, today there are several strains of Yersinia pestis, and there is evidence that past outbreaks of this disease were caused by still different strains, some of which are extinct today.

While human strains of Yersinia could well have evolved some 10,000 to 20,000 years ago, Poinar said, ancient Yersinia strains that evolved as rodent parasites could have appeared long before humans existed. These ancient strains would certainly be extinct by now, he said.  

The complex mode of transmission of plague is also reflected in the flea seen in this fossil.

When a flea feeds on a plague-infected animal, the Yersinia pestis bacteria taken up with the blood often form a viscous mass in the flea’s proventriculus, located between the stomach and esophagus. When this happens, the fleas can’t obtain enough blood, and as they attempt to feed again, bacteria are often forced back out through the proboscis and into the wound.

This blockage is in part what makes them effective vectors of the plague, and the dried droplets on the proboscis of the fossil flea could represent a sample of the sticky bacterial mass that was regurgitated.

“If this is an ancient strain of Yersinia, it would be extraordinary,” Poinar said. “It would show that plague is actually an ancient disease that no doubt was infecting and possibly causing some extinction of animals long before any humans existed. Plague may have played a larger role in the past than we imagined.”

The fossil flea originated from amber mines in what is now the Dominican Republic, between Puerto Plata and Santiago. Millions of years ago the area was a tropical moist forest.

Very few fleas of any type have been found preserved in amber, Poinar said, and none have been reported with associated microorganisms, as in this case. This specimen had some other unique morphological features that indicate it’s a species that long ago went extinct.

But it was the associated bacteria that fascinated the researchers.

“Since the dried droplet with bacteria is still attached to the tip of the proboscis, the flea may have become entrapped in resin shortly after it had fed on an infected animal,” Poinar said. “This might have been one of the rodents that occurred in the Dominican amber forest. Rodent hair has been recovered from that amber source.”

Flea-like creatures found in conventional stone fossils date back to the time of the dinosaurs, Poinar said, and the role of insects in general, and as carriers of disease, may have played a role in the demise of the ancient reptiles.

In 2008, Poinar and his wife, Roberta Poinar, wrote a book “What Bugged the Dinosaurs? Insects, Disease and Death in the Cretaceous.” It explored the evolutionary rise of insects around the same time that dinosaurs went extinct. The thesis developed in the book added insect-borne diseases as a likely component, that, along with other biotic and abiotic factors such as climate change, asteroid impacts and volcanic eruptions, led to  the extinction of the dinosaurs. Some modern diseases such as leishmaniasis and malaria clearly date to those times.

Bubonic plague in modern times can infect and kill a wide range of animals, in addition to humans. It is still endemic in many countries, including the United States where it’s been found in prairie dogs and some other animals. Even though today it is treatable with antibiotics, in the U.S. four people have died from plague so far this year.

During the Middle Ages, however, three phases of the disease – bubonic, septicemic and pneumonic plague - earned a feared reputation. Periodic waves of what was called the Black Death, for the gruesome condition in which it left its victims, swept through Europe and Asia, altogether killing an estimated 75 to 200 million people.

Scholars say that religious, social and economic changes caused by the plague altered the course of world history.

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Earth science offers key to many United Nations “Sustainable Development Goals”

CORVALLIS, Ore. – A group of ecologists at Oregon State University argue that scientific “business as usual” will fall far short of what is needed to achieve the 17 Sustainable Development Goals that are expected to be adopted by the United Nations General Assembly this month.

In a commentary published today in Nature Geoscience, the researchers suggest that these goals, which are designed to guide national and international actions for the next 15 years, can only be met if the Earth science community becomes more engaged and begins to “deliver on its social contract with society.”

“The world’s current approach to dealing with its multiple demands and needs is not adequately based in science, and it’s unsustainable,” said Jane Lubchenco, lead author, and the OSU University Distinguished Professor and Adviser in Marine Studies, former NOAA administrator and U.S. Science Envoy for the Ocean.

“Our international leaders are now committing themselves to alleviating poverty, enabling smart development, and ensuring opportunity for all,” said Lubchenco, an environmental scientist in the OSU College of Science, “while at the same time, tackling climate change, protecting biodiversity, achieving food and water security and stopping pollution.

“These are enormous, difficult, but not impossible challenges,” said Lubchenco, who also serves on the United Nations Sustainable Development Solutions Network Leadership Council. “Earth scientists are needed if the goals are to be met.

The OSU researchers said that the goals being considered by the United Nations contain a solid balance of environmental, social and economic issues, and in this paper they made a number of recommendations to help best achieve them.

“The golden opportunity for scientists is to focus research efforts on real-world problems,” she said, “to create new knowledge that is useable and responsive to society’s needs, to share knowledge widely, and demonstrate how sustainability based on science will ultimately benefit everyone.

“With this approach, seemingly intractable problems may actually be solvable,” she said. “Scientists are good at problem-solving, so we hope they will become more engaged.” 

The recommendations in the analysis include:

·         Consideration of the environment must not be delayed while more socially urgent goals demand attention.

·         Earth scientists could produce more useful and relevant science, and also share it more broadly with non-scientists.

·         Science that addresses issues ranging from water management to resource extraction and disaster mitigation needs to be made more accessible and understandable to potential users – policy makers, resource managers and the general public.

·         Scientists should not assume they know what users want and need, but rather must listen and work closely with civil society, industry, business and political leaders to create relationships built on trust, and devise solutions to big challenges.

·         The academic structure, which now often acts as an impediment to scientists engaging with society, must create systems that recognize, enable and reward such engagement.

The best place to start with many of these efforts, the researchers said, is with cutting-edge research that can help address needs relevant to the development goals, and identify practical solutions.

In their commentary, the scientists cited examples where such successes have occurred in the field of marine sciences.

One success focused on reforming small-scale fisheries in developing countries. These fisheries are a key to achieving multiple sustainable development goals such as food security and poverty alleviation. Yet they are notoriously difficult to reform, the researchers said, threatening the livelihood, health and well-being of millions of small-scale fishers and their communities.

Recently, researchers from ecology, economics, sociology and anthropology collaborated with each other and with local communities to devise solutions that ended overfishing, rebuilt depleted stocks and protected key habitats and biodiversity. Community and local fishers are now continuing to use the approaches that brought these social, economic and environmental benefits.

Engagement of scientists was key, but so too was their engagement with local communities to co-define problems and solutions, the researchers said. More cooperative solutions like these that are grounded in science, but owned by communities and that can be replicated elsewhere are urgently needed.

The development goals being considered by the United Nations, if properly executed, could help meet needs of people around the world and enable development while safeguarding Earth’s life support systems on which humanity depends, the researchers said, and good science is critical to this mission.

“The challenge is how to use the planet’s resources fairly without using them up,” they wrote in the commentary.

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Ban on microbeads offers best chance to protect oceans, aquatic species

CORVALLIS, Ore. – An outright ban on the common use of plastic “microbeads” from products that enter wastewater is the best way to protect water quality, wildlife, and resources used by people, a group of conservation scientists suggest in a new analysis.

These microbeads are one part of the microplastic problem in oceans, freshwater lakes and rivers, but are a special concern because in many products they are literally designed to be flushed down the drain. And even at conservative estimates, the collective total of microbeads being produced today is enormous.

In an article just published in the journal Environmental Science and Technology, scientists from seven institutions say that nontoxic and biodegradable alternatives exist for microbeads, which are used in hundreds of products as abrasive scrubbers, ranging from face washes to toothpaste. Around the size of a grain of sand, they can provide a gritty texture to products where that is needed.

“We’re facing a plastic crisis and don’t even know it,” said Stephanie Green, the David H. Smith Conservation Research Fellow in the College of Science at Oregon State University, and co-author of this report.

“Part of this problem can now start with brushing your teeth in the morning,” she said. “Contaminants like these microbeads are not something our wastewater treatment plants were built to handle, and the overall amount of contamination is huge. The microbeads are very durable.”

In this analysis, and using conservative methodology, the researchers estimated that 8 billion microbeads per day are being emitted into aquatic habitats in the United States – about 2.9 trillion beads per year, enough to wrap around the Earth more than seven times if lined up end to end.

The other 99 percent of the microbeads – another 800 billion – end up in sludge from sewage plants, which is often spread over areas of land. Many of those microbeads can then make their way into streams and oceans through runoff.

“Microbeads are just one of many types of microplastic found in aquatic habitats and in the gut content of wildlife,” said Chelsea Rochman, the David H. Smith Conservation Research Postdoctoral Fellow at the University of California/Davis, and lead author on the analysis.

“We’ve demonstrated in previous studies that microplastic of the same type, size and shape as many microbeads can transfer contaminants to animals and cause toxic effects,” Rochman said. “We argue that the scientific evidence regarding microplastic supports legislation calling for a removal of plastic microbeads from personal care products.”

Even though microbeads are just one part of the larger concern about plastic debris that end up in oceans and other aquatic habitat, they are also one of the most controllable. With growing awareness of this problem, a number of companies have committed to stop using microbeads in their “rinse off” personal care products, and several states have already regulated or banned the products.

The researchers point out in their analysis, however, that some bans have included loopholes using strategic wording. Many microbeads are used in personal care products that are not “rinse off,” such as deodorants and cleaners. And some regulations use the term “biodegradable” to specify what products are allowed – but some microbeads can biodegrade just slightly, which may allow their continued use.

If legislation is sought, “new wording should ensure that a material that is persistent, bioaccumulative, or toxic is not added to products designed to go down the drain,” the researchers wrote in their report.

“The probability of risk from microbead pollution is high, while the solution to this problem is simple,” they concluded.

All the authors on this study were funded by the David H. Smith Postdoctoral Research Fellowship Program, which works to develop science-based policy options for conservation and environmental issues. Other collaborators were from the University of Wyoming, University of California/Berkeley, Wildlife Conservation Society, College of William and Mary, and Georgia State University.

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(Editor's Note: A data error was printed in the sixth paragraph of an earlier version of this story that was publicly released. That error has been fixed and this version of the story is now accurate. OSU News and Research Communications regrets the error.)

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