OREGON STATE UNIVERSITY

scientific research and advances

New colors, a new world of pigments continue to evolve from accidental blue discovery

CORVALLIS, Ore. – A bright blue compound that was first discovered by accident seven years ago in an Oregon State University laboratory – and has since garnered global attention – has now led to the more rational and methodical development of other colors that may ultimately change the world of pigments.

Findings on the newest pigments, in shades of violet and purple, were just published in Inorganic Chemistry, a journal of the American Chemical Society.

More important, researchers say, is that progress made since the first accidental discovery of this family of inorganic compounds has allowed intensive science to take the place of luck. What’s emerging is a fundamental understanding of the chemistry involved in these “trigonal bipyramidal” compounds.

As the basis for pigments, they are quite remarkable.

Compared to the flaws that exist in many of the compounds they replace, they are all thermally stable, chemically inert, non-toxic and non-carcinogenic. For commercial use, they also have the extraordinary characteristic of reflecting heat, which is highly unusual for dark colors and potentially of great value for saving energy.

All of the compounds have been patented, and are being developed commercially by a private company. Yellow, green and orange colors have already been created, along with the original blue. The research has been supported by the National Science Foundation.

These developments began in 2009 when OSU researchers were studying some manganese oxide compounds for their potential electronic properties, and when one compound came out of an extraordinarily hot oven – about 2,000 degree Fahrenheit – it had turned a vivid blue, now known as “YInMn” blue.

The scientists noticed and took advantage of this unexpected result. They used the compound to create a pigment that was environmentally benign, resisted heat and acid, and was easily made from readily available raw materials.

“No one knew then that these compounds existed,” said Mas Subramanian, the Milton Harris Professor of Materials Science in the OSU College of Science, and corresponding author on the new publication.

“Now we’ve been able to move beyond the accident and really understand the chemistry, including its structure and synthesis. We can produce different colors by using the same basic chemical structure but tweaking things a little, by replacing manganese atoms by iron, copper, zinc and/or titanium. And we’re slowly moving toward what we really want, what everyone keeps asking for, the Holy Grail of pigments - a bright, new, durable, nontoxic red.”

Along with blue, Subramanian said, a stable, nonorganic red pigment would have huge commercial demand.

In this process, the OSU researchers are opening the door to new, inexpensive types of pigments that leave behind some of the toxic compounds historically used to create colors – lead, cadmium, mercury, even arsenic and cyanide. And the bonus of solar heat reflection has huge value for many applications, such as building construction or vehicles, where this characteristic can reduce cooling expenses and something other than white is desired.

Based on the novelty of the discovery and the growing value of these pigments, this research has captured international media attention and broad public fascination – a single online video received 14 million views.

The newest colors of violet and purple, the researchers noted in their study, have long been associated with royalty, aristocracy, piety and faith. The first pigments of these colors date back to cave paintings in France in 25,000 B.C., they said. And Chinese Han purple, the first synthetic purple pigment, was found in some murals in tombs more than 2,000 years old.

Pigments still being used to produce these colors are in some cases chemically and thermally unstable, and subject to increasing environmental regulations.

Applications of the new pigments, the researchers said in their report, may be found in high-performance plastics and coatings, building exteriors, cool roofing, vinyl siding, automobiles, and even art production or restoration.

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Mas Subramanian, 541-737-8235

mas.subramanian@oregonstate.edu

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New pigments
Pigment colors

Is there a right way to quit your job? Research finds some ways are better than others

CORVALLIS, Ore. – Most everybody has been there: you’ve decided to quit your job and now you have to inform your employer that you’re leaving. So what is the best way to resign?

Turns out, there are generally seven ways in which people quit their jobs, and there are two key factors that determine whether a person resigns in a positive way or in a way that could have damaging consequences for the business, new research from Oregon State University shows.

Those predictors are whether an employee feels they are being treated fairly at work, and whether they feel they are respected by their boss, said Anthony Klotz, an assistant professor in the College of Business at OSU and lead author of the paper. Those who feel they are respected and treated fairly are more likely to resign in a positive manner.

“As an employee, you are pretty powerless for much of your work life, until you decide to quit,” he said. “That is the one time you feel empowered and have a chance to even the score if you feel like you’ve been treated badly.”

Employee resignations are part of doing business; in the U.S. and western Europe, resignation rates run about 10 percent per year, while in parts of Asia, they can be much higher. But there is little known about how employees go about quitting their jobs, and what the implications of their resignations may have for the company, good or bad.

“There is a lot of research about why people quit their jobs. But very little is known about how people quit,” Klotz said. “Employers as well as employees want to know what the right way is.”

Klotz and his co-author, Mark Bolino of the University of Oklahoma, set out to learn more about how employees quit their jobs and the consequences of their choices when doing so. Their findings were published recently in the Journal of Applied Psychology. The study was supported by the Society for Human Resource Management Foundation.

Through a series of studies, including interviews with employees and employers, the researchers found that generally, employees quit in one of seven ways:

  • By the book: These resignations involve a face-to-face meeting with one’s manager to announce the resignation, a standard notice period, and an explanation of the reason for quitting.
  • Perfunctory: These resignations are similar to “by the book” resignations, except the meeting tends to be shorter and the reason for quitting is not provided.
  • Grateful goodbye: Employees express gratitude toward their employer and often offer to help with the transition period.
  • In the loop: In these resignations, employees typically confide in their manager that they are contemplating quitting, or are looking for another job, before formally resigning.
  • Avoidant: This occurs when employees let other employees such as peers, mentors, or human resources representatives know that they plan to leave rather than giving notice to their immediate boss.
  • Bridge burning: In this resignation style, employees seek to harm the organization or its members on their way out the door, often through verbal assaults.
  • Impulsive quitting: Some employees simply walk off the job, never to return or communicate with their employer again. This can leave the organization in quite a lurch, given it is the only style in which no notice is provided.

The by the book and perfunctory resignations are the most common, but roughly one in 10 employees quits in bridge-burning style. Avoidant, bridge burning and impulsive quitting are seen as potentially harmful resignation styles for employers. 

In addition, the researchers found that managers were particularly frustrated by employees who resigned using bridge burning, avoidant or perfunctory styles, so employees who want to leave on good terms should avoid those styles, Klotz said.

The study findings also indicated that managers responded the least negatively to resignations when employees kept them “in the loop” and when employees followed organizational policies regarding resignation. Quitting in these more positive styles is a good idea for employees who want a positive recommendation from a former supervisor or may consider returning to that company one day.

The managers’ attitudes toward the perfunctory resignation was a bit surprising, he said, and seemed to be rooted in the fact that employees using that style did not provide reasons for their decisions to resign.

Each resignation situation is unique to that employee and their relationship to the company, Klotz noted, so the best way to resign at one company may not be the best way to resign at another. But companies would be well-served to review their employee handbooks and update their formal resignation policies to reflect best practices for current company needs, he said.

Understanding why employees quit in the ways they do is particularly important for companies that could suffer if an employee uses his or her departure as an opportunity to damage the company’s reputation or create other problems, Klotz said.

“Turnover is common, it’s expensive, it’s disruptive and it can be contagious,” he said. “But this damage is mitigated when employees resign in a positive manner. So to the extent you can, as an employer, you want to have employees resign in a positive manner.”

Companies also should consider monitoring how employees quit for potential signs of management issues. If a number of employees quit in a negative way, that could be a sign of a poor supervisor or other problems with company treatment of employees, he said.

Klotz said he would also like to further study the “lame duck period,” between the time an employee gives notice to their last day on the job, to better understand what happens during that period.

“Is it better to just say ‘see ya’ and pay the employee’s salary for two weeks, or is it better to have the person stay for a transition period such as training their replacement?” Klotz said. “It’s often a very weird time for the employer and the employee.”

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Anthony Klotz, 541-737-6044

anthony.klotz@oregonstate.edu

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Anthony Klotz

Anthony Klotz


Exit sign
Exit sign

Salmon trucking success could open miles of historical spawning habitat

NEWPORT, Ore. – For the past several years, technicians have been trucking spring Chinook salmon above Foster Dam in Sweet Home to see if they would spawn, and if their offspring could survive the passage over the dam and subsequent ocean migration to eventually return as adults some 3-5 years later.

A new study examining the genetic origin of adult spring Chinook returning to Foster Dam offers definitive proof that the offspring survived, potentially opening up miles of spawning habitat on the upper South Santiam and other river systems.

Results of the study have been published in the Canadian Journal of Fisheries and Aquatic Sciences.

“With a little human assistance, it is now clear that we can restore natural production to areas above some dams and there is prime habitat on some river systems, such as the North Santiam above Detroit Dam,” said Kathleen O’Malley, an Oregon State University geneticist and principal investigator on the project. “This could really contribute to the long-term population viability in some river systems.”

Some past studies have explored whether salmon that spawned above dams could survive as juveniles going back through the dams, but this new study is one of the first to assess whether those fish successfully would return years later as adults.

Beginning in 2007, technicians from Oregon Department of Fish and Wildlife and the U.S. Army Corps of Engineers took genetic samples of adult salmon trucked above the dam. During the first two years, most of those adult salmon were reared in hatcheries and released as juveniles, but in 2009 they began using only wild-born fish, hoping to give a boost to that population. Since then, researchers have taken genetic samples from returning adult salmon to see if their parents were among those released above the dam.

The key is the “cohort replacement rate,” O’Malley said. If you release 100 female salmon above the dam, will you get at least 100 females from that population returning as adults to the dam for a rate of 1.0?  The researchers have to sample for several years to determine the success rate of one cohort, since spring Chinook can return as 3-, 4- or 5-year olds.

In 2007, ODFW released 385 hatchery-origin adult salmon and 18 wild-born salmon above Foster Dam, and the cohort replacement rate was .96. In 2008, 527 hatchery-origin fish and 163 wild-born fish were released, and the replacement rate was 1.16.

In 2009, the shift was made to all wild-born fish and ODFW released 434 spring Chinook above Foster Dam. When the researchers completed their genetic analysis for that year they found a cohort replacement rate of 1.56.

“It could be a one-year anomaly, or it may be an indication that wild-born fish are fitter and better able to survive and reproduce above the dams,” O’Malley said. “It is promising, though.”

Dams can limit downstream damage from potential floods, the researchers say, but there is little protection for spawning salmon above the dams. One flood occurred in 2010, and the researchers are just finishing their analysis of that year. Many of the spawning beds were wiped out, thus the cohort replacement rate likely will be lower. Although re-establishment of spawning activity above the dams has the potential to enhance productivity, those efforts are vulnerable to environmental processes.

“One limiting factor is that we don’t know for sure what an appropriate replacement rate is,” O’Malley pointed out. “We know that 1.0 is the bare minimum – one fish dies and another takes its place. But it won’t be clear what a good number will be to sustain and expand the population until we have several years of research.”

Researchers and fisheries managers note that ocean conditions play an important role in determining the number of adult salmon that survive to return and spawn, and can account for a significant amount of inter-annual variability in salmon abundance. It is important to have a population that is sufficiently productive across years in order to survive poor environmental conditions – in the ocean, or in fresh water – in any single given year.

ODFW also has released fish above dams on the North Santiam River and Fall Creek and OSU researchers are using genetics to monitor some of the first returning adults in these systems.

“One reason we think that the South Santiam reintroduction is going so well is that the reservoir is smaller and the dam is lower than in others systems in the Willamette basin,” O’Malley said. “The salmon’s downstream survival rate is likely higher than it may be on other river systems.”

The project is funded by the Army Corps of Engineers.

O’Malley is an associate professor in the Department of Fisheries and Wildlife at OSU, who is affiliated with the Coastal Oregon Marine Experiment Station at the university’s Hatfield Marine Science Center in Newport.

Other authors on the study include Melissa Evans and Dave Jacobson of Oregon State; Jinliang Wang of the Zoological Society of London; and Michael Hogansen and Marc Johnson of the Oregon Department of Fish and Wildlife. Evans, the lead author, now works for the Fish and Wildlife Department of the Shoshone-Bannock Tribes in Idaho.

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Kathleen O’Malley, 541-961-3311, kathleen.omalley@oregonstate.edu

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Aerial video of South Santiam: https://www.youtube.com/watch?v=zEb5l8lGtb8&

 

 

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Spring Chinook bypassing Foster Dam

 

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Foster Dam trapping operation

Simple test may help address $150 billion problem of post-operative delirium

PORTLAND, Ore. – Researchers at VA Portland Health Care System (VAPORHCS), in collaboration with Oregon State University and Oregon Health & Science University, have identified a simple test that takes about 2-3 minutes and can predict which surgical candidates are most at risk of delirium, a common complication following surgery in older patients.

Delirium, or acute confusion and disorientation, has become a $150 billion national problem.

After surgery, delirium can lead to slower recovery, a long-term worsening of memory and thinking, and even death - while significantly increasing health care costs. Identification of those most at risk could help guide decisions about whether or not to have surgery, and allow prompt, low-cost interventions after surgery to help prevent this problem.

The findings were just published in the Journal of the American Geriatric Society by doctors from the Veterans Affairs Research Department in Portland, who led and funded the study, and worked with partnering investigators from OSU and OHSU.

“Before this study, identifying people at risk for delirium following surgery required complicated or time-consuming evaluations,” said Dr. Sarah Goodlin, the lead VAPORHCS investigator for the study.

“We try to avoid delirium whenever possible, but our tools have been limited. Now we believe we can identify people at high risk and help physicians make informed decisions with their patients about the hazards and benefits of pursuing elective surgery.”

Further research will be needed to confirm the findings and broaden them to other groups, Goodlin said. This research, for instance, was done with 76 veterans age 65 or older who were almost exclusively male.

Several tests have been available for some time to test memory and mental function. One test, a brief screening tool called the “Mini-Cog,” was developed by Dr. Soo Borson at the University of Washington to detect dementia.

The current research found that one way of using and scoring the Mini-Cog offered high predictive accuracy of delirium following elective surgery with major anesthesia. Other tests and patient factors did not really improve the predictive risk of delirium.

“We wanted to identify a tool that was simple and accurate, and the Mini-Cog does that,” said Amber An DO, who designed the study with Goodlin during her geriatric medicine fellowship.

The Mini-Cog may help to prevent this problem, said David Lee, an assistant professor in the OSU/OHSU College of Pharmacy, and co-author on the study.

“This is such a serious issue,” Lee said. “Delirium can cause serious health and cognitive problems, begin a process of decline that can lead to dementia, and can almost double the cost of a hospital stay.”

However, the researchers pointed out in their study that medical care is more effective at preventing delirium, especially in people at moderate risk, than in treating it once it develops. That makes a predictive tool all the more helpful. More research is needed to understand steps that can be taken during or following surgery to decrease post-operative delirium rates.

The Mini-Cog test itself is quick and simple, can be done in any language and has no ethnic, educational or cultural barriers. A person is told three ordinary words and asked to repeat them, such as “apple,” “watch” and “penny.” They are then asked to draw a simple clock face, including the numbers and hands set to a specific time. Finally, they are asked to repeat the three words they were told. That’s all there is to the test.

The authors of the current study scored the Mini-Cog from 0-5. A person gets 2 points for correctly drawing a clock and time; and 1 point each for recalling the three words.

According to this research, a person with a score of 0-1 had a 50 percent or greater probability of post-operative delirium. Those with a score of 3 had a 20 percent probability; a score of 4 a 13 percent probability; and a score of 5 less than 5 percent probability of delirium after surgery.

The incidence of delirium ranges from 7-10 percent in older adults after simple elective surgery, rising to at least half of older adults undergoing emergency, cardiac or orthopedic surgery. Individuals who develop delirium are more likely to be debilitated, require skilled nursing care, and die in the year after surgery.

Factors that have been significantly associated with delirium risk include existing dementia, depression, use of multiple medications, sensory impairment, and the use of alcohol or psychoactive drugs.

 

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Daniel Herrigstad, 503-402-2975

daniel.herrigstad@va.gov

Hatfield Marine Science Center to host ocean research film fest

NEWPORT, Ore. – A mini-film festival outlining some of the latest in coastal research and marine initiatives will be held on Thursday, Sept. 22, at Oregon State University’s Hatfield Marine Science Center in Newport.

The series of short films will run from 5 to 6:30 p.m. and again from 7 to 8:30 p.m. in the Hennings Auditorium of the Visitor Center. The HMSC Film Festival is free and open to the public.

Among the topics in the films are:

  • Oregon State University’s Marine Studies Initiative;
  • Ocean sound in the bottom of the Mariana Trench, with NOAA’s Bob Dziak;
  • Blue whales nursing, with Leigh Torres of OSU’s Marine Mammal Institute;
  • Ocean acidification, by OSU’s Justin Smith, with Caren Braby and Steven Rumrill of ODFW;
  • At sea larvae and plankton sampling with faculty and students from the Cowen/Sponaugle Lab at HMSC.

Also featured will be OSU’s Bill Chadwick, who will present a summary of a research expedition searching for new hydrothermal vents, and a time-lapse video of the R/V Thompson going through the locks into Lake Union in Seattle.

The university’s latest marine-themed commercial will also be shown.

“These films exemplify the Marine Studies Initiative recently launched by OSU, said Bob Cowen, director of the OSU center. “We are excited about the opportunity to share our cutting-edge research with a wide audience through these dynamic and impactful films.”

More information is available at the center’s event website, http://hmsc.oregonstate.edu/events. Visitors traveling from the Willamette Valley should check on road closure information for U.S. Highway 20 at http://us20pme.org

 

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Maryann Bozza, 541-867-0234, maryann.bozza@oregonstate.edu

Findings about protein could open door to new class of antibiotics

CORVALLIS, Ore. – Researchers have made the first-ever detailed, atomic-level images of a peroxiredoxin, which has revealed a peculiar characteristic of this protein and might form the foundation for a new approach to antibiotics.

Scientists at Oregon State University have used X-ray crystallography, a powerful technique that can reveal structures down to their individual atoms, to study the fundamental nature and behavior of this peroxiredoxin. Their findings were announced today in the journal Structure.

Peroxiredoxin is needed by all cells to help eliminate hydrogen peroxide, a toxin, and in normal cells this process is healthy and valuable. But peroxiredoxins inside bacteria also help provide protection from our immune cells and increase the virulence of bacterial cells that cause infections.

The researchers were able to visualize peroxiredoxin chemistry in action. They found that when it’s restrained and loses its mobility, it also loses its function. And if the normal function is lost, it can lead to cell death.

If a molecule can be found that selectively blocks the motions of peroxiredoxin only in bacterial cells – which the researchers believe may be possible – it could function as an entirely new way to kill those cells. This would leave normal cells undamaged and set the stage for new types of antibiotics.

With the increasing problem of antibiotic resistance to many existing drugs, this approach could have significant value, researchers said. It might also work in synergy with existing antibiotics to improve their efficacy, they said.

“Peroxiredoxins are found in animals, plants, and bacteria, and are proteins that are crucial for cell survival,” said Arden Perkins, the lead author on this study which was done at OSU, in collaboration with Andrew Karplus, a distinguished professor of biochemistry in the OSU College of Science.

“The main function of peroxiredoxins is to eliminate hydrogen peroxide in cells by converting it to water,” Perkins said. “This toxin is a byproduct of normal cell metabolism, and hydrogen peroxide has to be removed so it doesn’t damage the cell. If peroxiredoxin doesn’t do its job, cells will die.”

With the extraordinary images provided by X-ray crystallography, the research also discovered that there are special regions on bacterial peroxiredoxins, different from those found in humans, that could be specifically targeted. If compounds could aim at those targets and selectively shut down the protective function of peroxiredoxin just in bacteria, it would weaken or kill those cells.

“There’s a lot of potential for this to be foundational work, something we can build on to create a new class of antibiotics,” Perkins said. “The key concept is selectively restraining the motions of peroxiredoxins in some cells, inactivating its function and leading to the death of the cells you want to kill.”

In related approaches, Perkins said, the concept may also hold some value against certain non-bacterial pathogens, like those that cause malaria or African sleeping sickness, which increasingly are difficult to treat.

This work, titled Peroxiredoxin Catalysis at Atomic Resolution, was supported by the National Science Foundation, the National Institutes of Health, and the U.S. Department of Energy. It was done in collaboration with the OSU Department of Chemistry and the Wake Forest School of Medicine.

Perkins is now a postdoctoral scholar at the University of Oregon. Karplus is a fellow of the American Association for the Advancement of Science, the world’s largest scientific society, in recognition of his contributions to protein structure determination and for improving the analysis of crystallographic data.

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Andrew Karplus, 541-737-3196

karplusp@science.oregonstate.edu

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Peroxiredoxin
Peroxiredoxin chemistry

System may help treat rare genetic disorder, reduce severe side effects

PORTLAND, Ore. – Researchers at Oregon State University and other institutions have discovered a type of drug delivery system that may offer new hope for patients with a rare, ultimately fatal genetic disorder – and make what might become a terrible choice a little easier.

No treatment currently exists for this disease, known as Niemann Pick Type C1 disease, or NPC1, that affects about one in every 120,000 children globally, and results in abnormal cholesterol accumulation, progressive neurodegeneration and eventual death.

However, a compound that shows promise is now undergoing clinical trials, but it has major drawbacks – the high doses necessary also cause significant hearing loss, requires direct brain injection and causes lung damage.

New findings, published today in Scientific Reports, outline the potential for a nanotech-based delivery system to carry the new drug into cells far more effectively, improve its efficacy by about five times, and allow use of much lower doses that may still help treat this condition without causing such severe hearing loss.

The same system, they say, may ultimately show similar benefits for 50 or more other genetic disorders, especially those that require “brain targeting” of treatments.

“Right now there’s nothing that can be done for patients with this disease, and the median survival time is 20 years,” said Gaurav Sahay, an assistant professor in the Oregon State University/Oregon Health & Science University College of Pharmacy, and corresponding author on the new study.

“The new cholesterol-scavenging drug proposed to treat this disorder, called cyclodextrin or HPβCD, may for the first time offer a real treatment. But it can cause significant hearing loss and requires multiple injections directly into the brain, which can be very traumatic. I’m very excited about the potential of our new drug delivery system to address these problems.”

In this approach, the HPβCD drug is attached to an extraordinarily small, nanotech-sized lipid particle that can carry it into cells, where it helps to flush out cholesterol. Researchers were surprised to discover, however, that the carrier itself also helped address the problem, while working in synergy with the drug it carries to greatly increase its effectiveness.

This should allow use of much lower dosages, Sahay said, and possibly an easier delivery through intravenous injection, instead of brain injection. In the form currently used, only 0.2 percent of the drug is able to cross the blood brain barrier.

In previous research with the HPβCD drug in animal models, the treatment did slow the progression of this disease, but did not reverse it. The disease focuses its damage on liver and brain cells.

In their report, researchers noted that this type of drug delivery system has several advantages, including prolonged circulation times, the ability to incorporate multiple drugs with different mechanisms of action, and a variety of “targeting ligands” that can help cross the blood brain barrier.

The researchers have also partnered with Dr. Edward Neuwelt at the OHSU Blood Brain Barrier Program, who has pioneered temporary opening of the blood brain barrier in humans to access drugs to the brain. They are also working leaders in the NPC disease field to translate these findings in-vivo.

“Taken together, nanocarriers can serve as a platform that can effectively deliver small molecules, genes and perhaps imaging agents for treatment and diagnosis of a wide variety of other rare lysosomal storage disorders,” the researchers wrote in their conclusion.

This research was supported by the OSU College of Pharmacy, OSU Venture Development Funds, AACP New Investigator Award, Birmingham Fellowship and Wellcome Trust Seed Award. Collaborating researchers were from the University of Birmingham, Oregon Health & Science University, and Newcastle University.

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Gaurav Sahay, 503-346-4698

sahay@ohsu.edu

Research outlines cellular communication processes that make life possible

CORVALLIS, Ore. – Researchers have discovered a mechanism of intercellular communication that helps explain how biological systems and actions – ranging from a beating heart to the ability to hit a home run – function properly most of the time, and in some scenarios quite remarkably.

The findings are an important basic advance in how cell sensory systems function. They shed light on the poorly-understood interaction between cells - and they also suggest that some of the damage done by cancer cells can be seen as a “failure to communicate.”

The work was reported today in Proceedings of the National Academy of Sciences by physicists from Oregon State University and Purdue University, done with support from the National Science Foundation and the Simons Foundation.

Scientists have long known that cells have various types of sensory abilities that are key to their function, such as sensing light, heat, nerve signals, damage, chemicals or other inputs.

In this process, a chemical stimulus called ATP functions as a signaling molecule, which, in turn, causes calcium levels in a cell to rise and decline, and tells a cell it’s time to do its job – whether that be sending a nerve impulse, seeing a bird in flight or repairing a wound. These sensing processes are fundamental to the function of life.

“We’ve understood for some time the basics of cellular sensory function and how it helps a cell respond to its environment,” said Bo Sun, an assistant professor of physics in the College of Science at Oregon State University, and a corresponding author on this study.

“The thing is, individual cells don’t always get the message right, their sensory process can be noisy, confusing, and they make mistakes,” Sun said. “But there’s strength in numbers, and the collective sensory ability of many cells working together usually comes up with the right answer. This collective communication is essential to life.”

In this study, researchers helped explain just how that works for animal cells.

When cells meet, a small channel usually forms between them that’s called a gap junction. On an individual level, a cell in response to ATP begins to oscillate, part of its call to action. But with gap junction-mediated communications, despite significant variability in sensing from one cell to another, the sensitivity to ATP is increased. Oscillation is picked up and becomes more uniform.

This interactive chatter continues, and a preponderance of cells receiving one sensation persuade a lesser number of cells reporting a different sensation that they must be wrong. By working in communication and collaboration, most of the cells eventually decide what the correct sensory input is, and the signal that gets passed along is pretty accurate.

With this accuracy of communication, cells in a heart chamber collectively decide to contract at the appropriate time, and blood gets pumped, dozens of times a minute, for a lifetime. Neuron cells send accurate signals. Photoreceptor cells see clearly.

This research was done with fibroblast cells, which are used in wound healing, but the results should apply to many cellular sensing mechanisms, researchers said.

Cancer cells, by contrast, are poor communicators. This study showed that they resist this process of collective communication, and when enough of them are present, the communicative process begins to lessen and break down. This may be at least one of the ways in which cancer does its biologic damage.

“These processes of collective sensory communication are usually accurate, but sometimes work better than others. Mistakes are made,” Sun said. “Even so, this process makes life possible. And when everything goes just right, the results can be remarkable.”

Consider a baseball player trying to get a hit, which Ted Williams once called “the hardest single thing to do in sport.” A major league pitcher hurls a 93 mile-per-hour fastball, low but possibly a strike. 

The photoreceptor cells in the batter’s eyes see the pitch coming. Some cells see it as a curve in the dirt, and some mistake it for a changeup, a slower pitch. But the majority of the cells come to the correct conclusion, it’s a fastball at the knees, and they spread the word. After extensive communication between all these cells, a conclusion is reached and the correct message is sent to neurons in the brain.

The brain cells, in turn, send a strong signal through nerves to muscles all over the batter’s body, the shoulders, legs, and especially arms. The signals arrive and once again a collaborative process takes place, deciding what the message is and how to react. Calcium ions in muscle cells are triggered and a brutally fast-but-accurate response is triggered, swinging the bat. This entire process, from the ball leaving the pitcher’s hand to contact with the bat, takes less than half a second.

On a perfect day – the cellular debate over what pitch was coming was sufficiently short-lived, the timing exact, the muscle contractions just right – the ball explodes off the bat and sails over the center field fence.

On a more realistic day – since the best hitters in the world only succeed 3 times out of 10 – the ball bounces weakly to the second baseman for an easy out. This in turn triggers the collective groans of 30,000 disappointed fans. But the heart has cellular communication that continues to guarantee its normal beating, and the player lives to bat another day.

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Bo Sun, 541-737-8203

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ATP model
ATP signaling molecule

Important advance made with new approach to “control” cancer, not eliminate it

PORTLAND, Ore. – Researchers have created a new drug delivery system that could improve the effectiveness of an emerging concept in cancer treatment – to dramatically slow and control tumors on a long-term, sustained basis, not necessarily aiming for their complete elimination.

The approach, called a “metronomic dosage regimen,” uses significantly lower doses of chemotherapeutic drugs but at more frequent time intervals. This would have multiple goals of killing cancer cells, creating a hostile biological environment for their growth, reducing toxicity from the drug regimen and avoiding the development of resistance to the cancer drugs being used.

A system just published in Chemistry of Materials by a group of researchers from Oregon and the United Kingdom offers an even more effective way to deliver such drugs and may be able to greatly improve this approach, scientists say. Further testing is needed in both animals and humans for safety and efficacy.

“This new system takes some existing cancer therapy drugs for ovarian cancer, delivers both of them at the same time and allows them to work synergistically,” said Adam Alani, an associate professor in the Oregon State University/Oregon Health & Science University College of Pharmacy, and lead author on the new study.

“Imagine if we could manage cancer on a long-term basis as a chronic condition, like we now do high blood pressure or diabetes. This could be a huge leap forward.”

This approach is still in trial stages, Alani said, but shows promise. In some prior work with related systems in animal tests, OSU and collaborating researchers have been able to completely eradicate tumors.

Total remission, Alani said, may be possible with metronomic dosage, but the initial goal is not only to kill cancer cells but to create an environment in which it’s very difficult for them to grow, largely by cutting off the large blood supply these types of cells often need.

Most conventional cancer chemotherapy is based on the use of “maximum tolerable doses” of a drug, in an attempt to completely eliminate cancer or tumors. In some cases such as ovarian cancer, however, drug-free intervals are needed to allow patient recovery from side effects, during which tumors can sometimes begin to grow again or develop resistance to the drugs being used.

The types of cancers this approach may best lend itself to are those that are quite complex and difficult to treat with conventional regimens based on “maximum tolerable dose.” This includes ovarian, sarcoma, breast, prostate, and lung cancers.

One example of the new metronomic regimen, in this instance, is use of two drugs already common in ovarian cancer treatment – paclitaxel and rapamycin – but at levels a tenth to a third of the maximum tolerable dose. One drug attacks cancer cells; the other inhibits cancer cell formation and the growth of blood vessels at tumor sites.

The new system developed in this research takes the process a step further. It attaches these drugs to polymer nanoparticles that migrate specifically into cancer cells and are designed to release the drugs at a particular level of acidity that is common to those cells. The low doses, careful targeting of the drugs and their ability to work in synergy at the same time appeared to greatly increase their effectiveness, while almost completely eliminating toxicity.
“Our goal is to significantly reduce tumors, slow or stop their regrowth, and allow a person’s body and immune system time to recover its health and natural abilities to fight cancer,” Alani said. “I’m very optimistic this is possible, and that it could provide an entirely new approach to cancer treatment.”

This research was supported by OSU, the Medical Research Foundation of Oregon, and the AACP New Pharmacy Faculty Research Award Program. It was done in collaboration with researchers from the Oregon Health & Science University, Pacific University, and Kingston University in the United Kingdom.

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Adam Alani, 503-346-4702

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Cancer therapy
Cancer therapy

OSU research funds reach second consecutive record of $336 million

CORVALLIS, Ore. – Oregon State University research funding reached $336 million in the fiscal year that ended June 30 – a second consecutive year of record-breaking growth and an increase of more than 60 percent over the past decade.

In 2006, the university garnered $209 million from state, federal and private-sector sources. Since then, OSU has received research revenues totaling more than $3 billion. In the last year, Oregon State researchers brought in $27 million more from all sources than they did in 2015, a 15 percent increase in competitive federal grants and an overall 9 percent increase.

OSU accounts for more research funding than nearly all of the state’s comprehensive public universities combined.

“Our researchers deserve all the credit for this amazing accomplishment,” said Cynthia Sagers, Oregon State vice president for research. “They have stepped up to the challenge of securing research funds that support our programs and our students, and create an impact on Oregon, the nation and the world.”

Through salaries, student stipends and expenditures, Oregon State research generates an annual societal and economic impact of about $762 million in the state and globally, based on an assessment conducted in 2015 by ECONorthwest.

Ongoing projects funded last year include:

  • Shannon Lipscomb at OSU-Cascades in Bend, an associate professor in the College of Public Health and Human Sciences, is leading a four-year, $1.5 million project funded by the U.S. Department of Education to train teachers to work with children exposed to trauma such as abuse, neglect, parental mental illness or parental substance abuse.
  • With grants totaling $227,000 from the Simons Foundation, Angelicque White and Laurie Juranek in the College of Earth, Ocean, and Atmospheric Sciences, are collaborating with scientists from the University of Washington, MIT, the University of Hawaii and the University of Southern California on a research project in the remote North Pacific Ocean. Preliminary results suggest that changes in the ratios of nitrogen, carbon and other nutrients lead to distinct shifts in microorganisms, affecting climate and the growth of plants and animals that live in the sea.
  • With a $2 million grant from the U.S. Army, Joseph Beckman, distinguished professor in the Linus Pauling Institute and the College of Science, is developing a potential ALS treatment cased on copper ASTM. He has demonstrated that this compound in mice can halt the progression of what is also known as Lou Gehrig’s disease.
  • With a $1.4 million grant from the Walmart U.S. Manufacturing Innovation Fund, the College of Engineering has been developing improvements to plastic injection molding processes and investigating the use of biopigments for digital printing on fabric. The aim in both initiatives is to increase manufacturing competitiveness by reducing waste and boosting energy efficiency.

 OSU researchers undertook projects to study and manage forests, coastal waters and other natural resources; to protect human health by identifying new treatments for infectious diseases; and to support communities and businesses by solving problems in food, energy and water systems.

Scientists are developing new ways to deliver education in the STEM fields — science, technology, engineering and math — and tracking the performance of students learning English as a second language.

Success, Sagers added, is due in part to collaborations among researchers across disciplines in areas such as robotics, marine sciences and information technologies.

“Working with people outside one’s own field can lead to real advances in knowledge and innovation,” Sagers said. “We’re seeing progress in unmanned aerial systems for agriculture, forestry and infrastructure inspections, in genetic testing to understand disease and improve food security, and in software for environmental monitoring and crop improvements.”

Research results are finding their way into businesses, fueling economic growth. For example, two newly formed companies — Agility Robotics and e-MSion, Inc. — have grown out of OSU labs with help from the Oregon State University Advantage program and RAIN, the Regional Accelerator and Innovation Network.

Agility Robotics is developing the second generation of a bi-pedal robot with funding from the federal Defense Advanced Research Projects Agency, or DARPA. E-MSion is driven by an advance in mass spectrometry, a workhorse technology in research labs worldwide. The company aims to transform this high-end research tool into an easy-to-use appliance and hire 20 to 30 employees within five years.

Among funds received in 2016 were the following:

  • $5.3 million from the Agricultural Research Foundation for projects to enhance the productivity and sustainability of food and ornamental crops across the state
  • $2.8 million from the National Oceanic and Atmospheric Administration for the Cooperative Institute for Marine Resources Studies, focusing on undersea eruptions, fisheries and acoustic techniques for monitoring marine mammals and other animals
  • $1.2 million for the Long Term Ecological Research program at the H.J. Andrews Experimental Forest, emphasizing environmental responses to climate change
  • $3 million for design and bid preparation for two to three new regional class coastal research vessels
  • $1 million from Oregon BEST for 17 sustainability projects in wood science, engineering and agriculture
  • 11 NSF CAREER Awards to jumpstart research programs by young researchers in engineering, computer science, physics, chemistry and statistics
  • 35 grants over $1 million, for projects ranging from biomass fuels for the Northwest and plant genetics to changing Arctic and North Atlantic Ocean conditions, aquaculture, nutrition, pharmaceuticals, STEM education and health risks of air pollution

Funds provided by federal agencies increased over what was received in 2015 from the Department of Commerce, up 72 percent; Department of Energy, up 69 percent; Department of Defense, up 39 percent; and Department of Health and Human Services, up 30 percent. Total federal funding grew from $185 million last year to more than $212 million in 2016.

State appropriations for land grant funding — money that supports work in agriculture, wood products, engineering and other fields —increased by $7 million, from $61 million in 2015 to $68 million in 2016. Funds are being used to hire experts to work with farmers, ranchers and others on issues from water quality and disease control to food safety and value-added manufacturing.

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Cynthia Sagers, 541-737-0664

cynthia.sagers@oregonstate.edu

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New research vessel

 

Robert Tanguay

Zebrafish research


ATRIAS, a two-legged robot created at Oregon State University, ambles down the sideline at Reser Stadium, home of Beaver football. (Photo courtesy of Oregon State University)
Bipedal robot

 

YouTube video

https://youtu.be/q8TCAClYais 

 

High resolution downloadable video:

http://bit.ly/2c4Ta7b