OREGON STATE UNIVERSITY

college of veterinary medicine

Biomarker could provide early warning of kidney disease in cats

CORVALLIS, Ore. – Researchers from Oregon State University and other institutions have developed a new biomarker called “SDMA” that can provide earlier identification of chronic kidney disease in cats, which is one of the leading causes of their death.

A new test based on this biomarker, when commercialized, should help pet owners and their veterinarians watch for this problem through periodic checkups, and treat it with diet or other therapies to help add months or years to their pet’s life.

Special diets have been shown to slow the progression of this disease once it’s identified.

The findings were made in a controlled study of 32 healthy, but older cats, and have been published in The Veterinary Journal by researchers from OSU and IDEXX Laboratories. They demonstrated the efficacy of a biomarker that could form the basis for a new diagnostic test.

“Chronic kidney disease is common in geriatric cats and often causes their death,” said Jean Hall, a small animal medical expert and professor in the OSU College of Veterinary Medicine. “Damage from it is irreversible, but this is an important advance, in that we should be able to identify the problem earlier and use special diets to slow the disease.”

Many of these same health issues also relate to older dogs, and in continued research scientists believe they may make similar findings.

Renal decline is normal in most cats, experts say, as they reach 12-18 years of age, and along with issues such as cancer and gastrointestinal disease is one of the more common causes of death. But studies have shown that the problem can also be managed with special foods that reduce protein and phosphorus, while adding fish oil, antioxidants, L-carnitine and medium-chain triglycerides.

This biomarker was able to identify the onset of kidney disease in cats on average 17 months earlier than any existing approach, and in at least one case four years earlier. With special diets and care, some cats have lived several years after the disease was diagnosed.

The only existing test for the disease, which has been used for decades, is a blood test that checks creatinine levels, a marker of the breakdown of muscle protein. However, cats lose lean body mass as they age, so creatinine levels may be normal.  SDMA is not influenced by lean body mass and thus more accurately diagnoses the loss of kidney function, even if lean body mass has decreased.

The early symptoms of this disease are fairly non-specific, such as loss of appetite, weight loss, or vomiting.

The cats in this research were housed at the Science and Technology Center of Hill’s Pet Nutrition Inc.  The company provided data and samples for analysis in order to better understand the dietary needs of cats with early renal disease, and initiated the study to investigate how best to lengthen and enrich the lives of cats with the condition.

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Jean Hall, 541-737-6537

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Aging cat
Aging cat

Virulent bacteria affecting oysters found to be a case of mistaken identity

CORVALLIS, Ore. -  The bacteria that helped cause the near-ruin of two large oyster hatcheries in the Pacific Northwest have been mistakenly identified for years, researchers say in a recent report.

In addition, the study shows that the bacteria now believed to have participated in that problem are even more widespread and deadly than the previous suspect.

Although the hatchery industry has largely recovered, primarily by better control of ocean water acidity that was also part of the problem, the bacterial pathogens remain a significant concern for wild oysters along the coast, researchers said.

For many years, it had been believed that the primary bacteria causing oyster larval death in the Pacific Northwest was Vibrio tubiashii. Now, scientists say that most, or possibly all of the bacterial problem was caused by a different pathogen, Vibrio coralliilyticus, a close cousin that’s now known to be even more virulent to Pacific oysters.

The findings were published in Applied and Environmental Microbiology, by researchers from the College of Veterinary Medicine at Oregon State University, the U.S. Department of Agriculture, and Rutgers University. The research was supported by the USDA.

“These bacteria are very similar, they’re close cousins,” said Claudia Häse, an OSU associate professor and expert in microbial pathogenesis. “V. coralliilyticus was believed to primarily infect warm water corals and contributes to coral bleaching around the world. It shares some gene sequences with V. tubiashii, but when we finally were able to compare the entire genomes, it became apparent that most of what we’re dealing with in the Pacific Northwest is V. coralliilyticus.”

Scientists now say that V. coralliilyticus is not only far more widespread than previously believed, but that it can infect a variety of fish, shellfish and oysters, including rainbow trout and larval brine shrimp. And it appears to be the primary offender in bacterial attacks on Pacific Northwest oyster larvae.

OSU experts have developed a rapid diagnostic assay for this bacteria that is nearing commercialization, and it may help assess problems both in oyster and coral health, Häse said.

“Although we’ve largely addressed the problems the hatcheries face, these bacteria continue to pose threats to wild oysters,” Häse said. “And corals are still declining in many places, the Great Barrier Reef in Australia is dying at an alarming rate. Better diagnostics might help in all of these situations.”

In what’s now understood to be a problem with multiple causes, these pathogenic bacteria were involved in major crashes of oyster hatcheries, causing shortages in seed oysters for commercial producers. Dramatic losses were suffered in a Netarts Bay, Oregon, hatchery in 2005, and Washington hatcheries were also hard hit. Bacterial infection, water acidity, oxygen depletion and rising seawater temperatures are all believed to have been part of the problem.

By better monitoring and control of water acidity, which was one serious concern, hatcheries have been able to regain most of their productive capabilities. Wild oysters, however, continue to face the multiple pressures from rising acidity, pathogenic bacteria and other forces that have led to serious hatchery mortality.

Those problems have not been made any easier by the lack of funding for identification and studies of the bacteria that researchers now know to be causing infection.

In laboratory tests, strains of V. tubiashii did not show significant pathogenicity to Pacific oysters. V. coralliilyticus, by contrast, is highly infectious to both Pacific and Eastern oyster larvae, and perhaps other shellfish species.

“The Vibrio genus and many bacteria associated with it are a huge problem in fish and shellfish aquaculture, and we should be studying them more aggressively,” Häse said. “V. coralliilyticus, in particular, has a very powerful toxin delivery system, and vibrios are some of the smartest of all bacteria. They can smell, sense things and swim toward a host.”

It’s believed that increasing environmental stresses may make oysters and other marine life more vulnerable to these types of bacterial infection, researchers say.

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Claudia Häse, 541-737-7001

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Oyster larvae
Oyster larvae

Hygienic funerals, better protection for health workers offer best chance to stop Ebola

CORVALLIS, Ore. – Hygienic funeral practices, case isolation, contact tracing with quarantines, and better protection for health care workers are the keys to stopping the Ebola epidemic that continues to expand in West Africa, researchers said today in a new report in the journal Science.

Continuing the status quo of intervention efforts that were in place as of Sept. 19 would allow continued expansion of the epidemic by about 224 new cases daily in Liberia by Dec. 1, and 348 new daily cases by Dec. 30, the scientists reported in their analysis.

However, they said broad implementation “with utmost urgency” of more aggressive approaches they recommended, used at a reasonably high level of efficiency, could by mid-March lead to its control in Liberia, the focal point of the epidemic.

Researchers from Yale University, Oregon State University, and the Ministry of Health and Social Welfare in Liberia concluded that funerals, as they have been customarily practiced in this region, were what they called “super-spreader events” that have had a disproportionate impact on the early transmission of the virus.

Changes in those practices are the single most important, practical step that could help place the number of new Ebola infections on a downward path. But a whole suite of actions are needed, they cautioned, and reducing transmission in hospitals and the community will not by itself bring the epidemic under control.

“The cultural body preparation and funeral practices that are common in West Africa have driven the initial spread of this disease,” said Jan Medlock, an assistant professor in the OSU Department of Biomedical Sciences and an expert in mathematical epidemiology and evolution of infectious disease.

“These funeral practices often included washing, touching and kissing of bodies that were still capable of spreading the Ebola virus,” Medlock said. “It is imperative that funeral transmission be stopped, and also that we take other aggressive steps to isolate cases and better protect health care workers.”

The findings were made with complex mathematical models that consider many variables in how the disease is spreading, what steps are being taken to slow its progression and how effective those steps are. The research sought to identify not only what would theoretically work, but what was most practical and achievable.

The goal, the researchers said, should be to shift the current Ebola epidemic from one that is expanding to one that is slowly declining – to change what scientists call the “basic reproductive number” to less than 1, so the epidemic is on the road to ultimate extinction. They estimated that in Liberia the Ebola reproductive number is currently 1.63, meaning that two infected people would infect, on average, about three more people, and the epidemic continues to expand.

Getting that reproductive number below 1 will require adequate and proper use of personal protective equipment, more complete case isolations, contact precautions, quarantines, and particularly improved funeral practices. Achieving these goals at a success rate of about 60 percent could ultimately curtail the epidemic, the researchers said.

To arrive at their conclusions, the scientists used mathematical analysis to consider such factors as the density of infected and uninfected people in an area, numbers attending a funeral, those hospitalized, their relatives, health care workers in the hospital, and the general community.

Instead of traditional burial preparations, the researchers endorsed a very hygienic approach that includes disinfecting the cadaver before placing it in a plastic body bag and doing further disinfecting. Human-to-human transmission of Ebola occurs mostly through direct or indirect contact with body fluids, the researchers noted in their report, and deceased victims still carry a high viral load in their blood and excretions.

Another significant concern, the researchers said, is under-reporting of cases, both in hospitals and the general community. This could slow the stoppage of the epidemic and increase the level of intervention needed to stop it.

Other things could also change as the epidemic evolves. Funeral attendance and traditional burial practices may decline as awareness builds about the disease, but contacting people who may have been exposed could become even more difficult as people move from urban to rural areas.

This study was supported by the National Institutes of Health and the Notsew Orm Sands Foundation. It was a collaboration of researchers from the OSU College of Veterinary Medicine, the Yale School of Public Health and the Ministry of Health and Social Welfare in Liberia. The corresponding author was Alison Galvani at the Yale School of Public Health. It is being published in the journal Science at its online Science Express web site.

The findings of this study were specific to Liberia but should have some relevance to other places with similar cultural practices or approaches to disease management, Medlock said. They are less relevant in situations where the disease has spread beyond Africa into the United States, Europe and other parts of the developed world, he said, where aggressive isolation and containment of infected people or quarantine of those exposed is more practical.

Given the magnitude of this health crisis, it’s already apparent that Ebola poses an international threat that requires an international response and aid, the scientists said in their conclusion.

“Ebola poses an urgent threat not only to West Africa but also to the international community,” they wrote.

“The implementation of effective interventions needed to reverse the growth of the Ebola outbreak in impoverished West African countries will be logistically challenging even with substantial international aid, but impossible without it.”

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Jan Medlock, 541-737-6874

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Ebola protection
Protective equipment


Jan Medlock
Jan Medlock

Compound from hops aids cognitive function in young animals

CORVALLIS, Ore. – Xanthohumol, a type of flavonoid found in hops and beer, has been shown in a new study to improve cognitive function in young mice, but not in older animals.

The research was just published in Behavioral Brain Research by scientists from the Linus Pauling Institute and College of Veterinary Medicine at Oregon State University. It’s another step toward understanding, and ultimately reducing the degradation of memory that happens with age in many mammalian species, including humans.

Flavonoids are compounds found in plants that often give them their color. The study of them – whether in blueberries, dark chocolate or red wine - has increased in recent years due to their apparent nutritional benefits, on issues ranging from cancer to inflammation or cardiovascular disease. Several have also been shown to be important in cognition.

Xanthohumol has been of particular interest because of possible value in treating metabolic syndrome, a condition associated with obesity, high blood pressure and other concerns, including age-related deficits in memory. The compound has been used successfully to lower body weight and blood sugar in a rat model of obesity.

The new research studied use of xanthohumol in high dosages, far beyond what could be obtained just by diet. At least in young animals, it appeared to enhance their ability to adapt to changes in the environment. This cognitive flexibility was tested with a special type of maze designed for that purpose.

“Our goal was to determine whether xanthohumol could affect a process we call palmitoylation, which is a normal biological process but in older animals may become harmful,” said Daniel Zamzow, a former OSU doctoral student and now a lecturer at the University of Wisconsin/Rock County.

“Xanthohumol can speed the metabolism, reduce fatty acids in the liver and, at least with young mice, appeared to improve their cognitive flexibility, or higher level thinking,” Zamzow said. “Unfortunately it did not reduce palmitoylation in older mice, or improve their learning or cognitive performance, at least in the amounts of the compound we gave them.”

Kathy Magnusson, a professor in the OSU Department of Biomedical Sciences, principal investigator with the Linus Pauling Institute and corresponding author on this study, said that xanthohumol continues to be of significant interest for its biological properties, as are many other flavonoids.

“This flavonoid and others may have a function in the optimal ability to form memories,” Magnusson said. “Part of what this study seems to be suggesting is that it’s important to begin early in life to gain the full benefits of healthy nutrition.”

It’s also important to note, Magnusson said, that the levels of xanthohumol used in this study were only possible with supplements. As a fairly rare micronutrient, the only normal dietary source of it would be through the hops used in making beer, and “a human would have to drink 2000 liters of beer a day to reach the xanthohumol levels we used in this research.”

In this and other research, Magnusson’s research has primarily focused on two subunits of the NMDA receptor, called GluN1 and GluN2B. Their decline with age appears to be related to the decreased ability to form and quickly recall memories.

In humans, many adults start to experience deficits in memory around the age of 50, and some aspects of cognition begin to decline around age 40, the researchers noted in their report.

This research was supported by the National Institutes of Health.

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Kathy Magnusson, 541-737-6923

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Hops

Hops

Use of dengue vaccine may cause short-term spikes in its prevalence

CORVALLIS, Ore. – As researchers continue to work toward vaccines for serious tropical diseases such as dengue fever, experts caution in a new report that such vaccines will probably cause temporary but significant spikes in the disease in the years after they are first used.

This counter-intuitive and unwanted result could lead to frustrated policy makers, a skeptical public and concerns that the vaccine is making things worse instead of better, researchers say.

In fact, it will just be the natural result of complex interactions between less-than-perfect vaccine protection and routine fluctuations in the populations of insects who carry the diseases.

“Our analysis suggests that if we develop and widely use a vaccine for dengue fever, there may later be spikes in the incidence of the disease that are two to three times higher than its normal level,” said Jan Medlock, an assistant professor in the Department of Biomedical Sciences at Oregon State University, and expert on the evolution and epidemiology of infectious disease.

“We can explain why this will happen and show how, in the long run, vaccine use will clearly result in fewer cases of disease,” Medlock said. “Our concern is to warn people in advance about this issue, so that policy makers and the public don’t freak out and lose faith in the vaccination programs.”

This research, published in Epidemiology and Infection, was done by experts at the OSU College of Veterinary Medicine and Clemson University, both of which supported the studies. Scientists used mathematical modeling to examine the quirks of infectious disease transmission that may lead to this quandary. The work was specific to dengue fever, but may also be relevant to other diseases for which vaccines are being sought, such as malaria, and in which the level of protection is less than total.

Dengue fever is a serious illness that affects about 50 million people a year, and for which researchers are hoping to develop effective vaccines in the near future. It’s not usually fatal but is extremely common in the tropics and subtropics, and has re-emerged in recent decades as the use of insecticides such as DDT has been stopped.

There are several serotypes, or strains of the dengue virus, that are spread by mosquitoes. One infection provides some protection, and two infections usually make a person resistant for the rest of their life. In Thailand, where the disease is prevalent, about 80 percent of children have two infections by the age of 11 and develop resistance. Dengue fever is found in 100 countries around the world and 2.5 billion people are at risk of infection.

“The problem, if and when we develop and use a vaccine, is that it will provide some, but not complete protection, and it will interrupt the natural, fairly steady rate of infections among children,” Medlock said.

In this scenario, the beginning of a vaccination program will slow the numbers of children getting the disease – for a while. But it’s expected that a dengue vaccine will not provide total protection against infection. Then, during a period when naturally fluctuating mosquito populations reach an unusually high level, a disproportionate number of children – who are still vulnerable to infection and have never had the disease – will become infected in a short period.

This could cause loss of faith in the vaccination program among the public or policy makers who have never seen such high levels of the disease, stretch the capabilities of health care facilities and workers to care for the sick, and in a worst-case scenario lead people to avoid the vaccine, researchers said. Some short-term spikes could even be as high as seven times the average rate, they said.

“In fact, we conclude in this analysis that over a 15-year period, a vaccination program will clearly reduce the number of overall infections,” Medlock said. “These significant spikes will mostly occur as the program is beginning. What we need to do is help people understand these forces so they anticipate them.”

A possible way to deal with this phenomenon, researchers said, is literally to vaccinate fewer people. This would cause higher numbers of people to get the disease in the long run but reduce the intensity of the spikes and the associated demands on a health care system.

The levels of disease will fluctuate based on such variables as location, climate, the efficacy of a vaccine, the numbers of people vaccinated, surges in insect populations, and other factors. This phenomenon may have occurred, or may occur in the future, with almost any vaccine that provides partial, but not total protection against infection.

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Dengue mosquito

Dengue transmission

Research could lead to new cancer assay, aid both dogs and humans

CORVALLIS, Ore. – Veterinary researchers at Oregon State University have identified a unique group of proteins that indicate the presence of transitional cell carcinoma – the most common cause of bladder cancer – and may lead to a new assay which could better diagnose this disease in both dogs and humans.

Bladder cancer is particularly common in some dog breeds, such as collies, sheepdogs and terriers, but is rarely diagnosed in animals before it has spread significantly. Some assays exist to detect it in humans, but they often have a high-number of false-positive identifications.

An improved assay to detect this serious disease much earlier in both animals and humans should be possible, scientists said, and may even become affordable enough that it could be used as an over-the-counter product to test urine, much like a human pregnancy test. Some of the work may also contribute to new therapies, they said.

“Research of this type should first help us develop a reliable assay for this cancer in dogs, and improve the chance the disease can be caught early enough that treatments are effective,” said Shay Bracha, an assistant professor in the OSU College of Veterinary Medicine.

“However, this type of cancer is essentially the same in dogs and humans,” Bracha said. “Dogs are an excellent model for human cancer research, and an assay that works with dogs should be directly relevant to creation of a similar assay for humans. We hope to make it inexpensive and convenient, something that people could use routinely to protect either the health of their pets or themselves.”

The findings were published recently in Analytical Chemistry, a professional journal.

In this research, scientists used mass spectrometry and the evolving science of proteomics to identify 96 proteins that appear related to transitional cell carcinoma. This is a fairly common cancer in dogs, often as a result of exposure to pesticides, herbicides, and poor quality foods; and in humans is closely related to smoking.

Advanced-stage disease in both dogs and humans has a poor prognosis, as chemotherapy and radiation treatments are often ineffective. Average survival time is less than one year. Some assays exist to help identify the disease in humans but can produce false positive results, often as a result of urinary tract infections. And the biopsies used to make a definitive diagnosis require general anesthesia and also run the risk of actually spreading the disease.

The group of proteins identified in this research already have a 90 percent accuracy, and researchers say they hope to improve upon that with continued research.

However, researchers say that some of these proteins are more than just biomarkers of the disease – they are part of the disease process. Identifying proteins that are integral to the spread of the cancer may allow new targets for intervention and cancer therapies, they said.

Collaborators on this research included the OSU Department of Chemistry. A mathematical model that was integral to the study was created by Jan Medlock, an OSU assistant professor of veterinary medicine, and veterinary researchers Michael McNamara and Ian Hilgart helped initiate the project. The work was supported in part by the National Institutes of Health.

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Shay Bracha, 541-737-4844

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Border collie

Border collie

OSU assisting in alpaca rescue operation

CORVALLIS, Ore. - The last of about 175 imperiled alpacas that are being removed from a farm near Falls City, Ore., will arrive today or early this week at Oregon State University as part of a continuing rescue operation to help care for and save the lives of these animals.

Transport began late last week but only 54 got through, and operations had to be suspended due to the heavy winter storm, a traffic accident and difficult travel conditions. A team of doctors and veterinary students at OSU will now work with the incoming animals to assess their health, do necessary procedures, improve their nutritional status and aid their recovery.

Owners of the ranch that had housed the alpacas are facing legal charges in Polk County. Meanwhile, the College of Veterinary Medicine has volunteered its facilities to help continue the rescue operation that was begun by the Polk County Sheriff’s Department and Cross Creek Alpaca Rescue volunteers.

Ultimately, all of the animals will be made available for adoption, officials said.

“The OSU College of Veterinary Medicine is one of the few agencies in Oregon that has the ability and expertise to manage an operation of this size,” said Helen Diggs, a professor of veterinary medicine and director of the OSU Laboratory Animal Resources Center. “The Research Office at OSU has also made it clear that we will do what we can to help with this difficult situation.”

Although travel is still difficult, officials hope that most of the remaining alpacas will arrive today or early this week at the Research Animal Isolation Laboratory, one of the campus facilities large enough to handle so many animals at once. Some with special needs are also being treated in the large animal hospital in Magruder Hall on the OSU campus.

“Many of these animals are very thin and we’ve been told that a substantial number have already died,” said Chris Cebra, a professor of large animal internal medicine in the College of Veterinary Medicine, and an expert in the treatment of camelids such as llamas and alpacas.

“From what we’ve seen, we’ll be dealing with malnutrition, heavy parasite loads, some pregnant animals, newborns, and various health conditions,” Cebra said. “We’ll continue to feed the animals, assess and treat medical conditions, check vaccination status, and generally improve their quality of life and suitability for a new home.”

Given the unusually large influx of animals at one time, a number of supervised veterinary students will also work in the rescue operation, allowing them a substantial amount of hands-on training while helping veterinary doctors more quickly and effectively give the entire herd the treatment it needs.

Once the alpacas recover their health, adoption will be possible from the Polk County Sheriff’s Office, which is working with Cross Creek Alpaca Rescue to identify suitable placements. Initial inquiries for adopting one or more of the animals may be directed to Cross Creek Alpaca Rescue, at http://www.crosscreekalpacarescue.org/.

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Helen Diggs, 541-737-6213

 

Chris Cebra, 541-737-4456

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Alpaca

Alpaca needs care


Alpacas being fed

Alpacas being fed

Amber fossil reveals ancient reproduction in flowering plants

CORVALLIS, Ore. – A 100-million-year old piece of amber has been discovered which reveals the oldest evidence of sexual reproduction in a flowering plant – a cluster of 18 tiny flowers from the Cretaceous Period – with one of them in the process of making some new seeds for the next generation.

The perfectly-preserved scene, in a plant now extinct, is part of a portrait created in the mid-Cretaceous when flowering plants were changing the face of the Earth forever, adding beauty, biodiversity and food. It appears identical to the reproduction process that “angiosperms,” or flowering plants still use today.

Researchers from Oregon State University and Germany published their findings on the fossils in the Journal of the Botanical Institute of Texas.

The flowers themselves are in remarkable condition, as are many such plants and insects preserved for all time in amber. The flowing tree sap covered the specimens and then began the long process of turning into a fossilized, semi-precious gem. The flower cluster is one of the most complete ever found in amber and appeared at a time when many of the flowering plants were still quite small.

Even more remarkable is the microscopic image of pollen tubes growing out of two grains of pollen and penetrating the flower’s stigma, the receptive part of the female reproductive system. This sets the stage for fertilization of the egg and would begin the process of seed formation – had the reproductive act been completed.

“In Cretaceous flowers we’ve never before seen a fossil that shows the pollen tube actually entering the stigma,” said George Poinar, Jr., a professor emeritus in the Department of Integrative Biology at the OSU College of Science. “This is the beauty of amber fossils. They are preserved so rapidly after entering the resin that structures such as pollen grains and tubes can be detected with a microscope.”

The pollen of these flowers appeared to be sticky, Poinar said, suggesting it was carried by a pollinating insect, and adding further insights into the biodiversity and biology of life in this distant era. At that time much of the plant life was composed of conifers, ferns, mosses, and cycads.  During the Cretaceous, new lineages of mammals and birds were beginning to appear, along with the flowering plants. But dinosaurs still dominated the Earth.

“The evolution of flowering plants caused an enormous change in the biodiversity of life on Earth, especially in the tropics and subtropics,” Poinar said.

“New associations between these small flowering plants and various types of insects and other animal life resulted in the successful distribution and evolution of these plants through most of the world today,” he said. “It’s interesting that the mechanisms for reproduction that are still with us today had already been established some 100 million years ago.”

The fossils were discovered from amber mines in the Hukawng Valley of Myanmar, previously known as Burma. The newly-described genus and species of flower was named Micropetasos burmensis.

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Ancient flowers

Ancient flower


Pollen tubes

Pollen tubes

Innovative approach could ultimately end deadly disease of sleeping sickness

CORVALLIS, Ore. – A tag team of two bacteria, one of them genetically modified, has a good chance to reduce or even eliminate the deadly disease African trypanosomiasis, or sleeping sickness, researchers at Oregon State University conclude in a recent mathematical modeling study.

African trypanosomiasis, caused by a parasite carried by the tsetse fly, infects 30,000 people in sub-Saharan Africa each year and is almost always fatal without treatment. In a 2008 epidemic, 48,000 people died.

In this research, scientists evaluated the potential for success of a new approach to combat the disease – creating a genetically modified version of the Sodalis bacteria commonly found in the gut of the flies that carry the disease, and using different bacteria called Wolbachia to drive the GMO version of Sodalis into fly populations.

When that’s done, the GMO version of Sodalis would kill the disease-causing trypanosome parasite. According to the analysis published in PLOS Neglected Tropical Diseases, researchers say this should work – and could offer a model system for other tropical, insect-carried diseases of even greater importance, including dengue fever and malaria.

“There are a few ‘ifs’ necessary for this to succeed, but none of them look like an obstacle that could not be overcome,” said Jan Medlock, an assistant professor in the OSU Department of Biomedical Sciences, and lead author on the new report.

“If everything goes right, and we are optimistic that it will, this could be enormously important,” Medlock said. “There’s a potential here to completely solve this disease that has killed many thousands of people, and open new approaches to dealing with even more serious diseases such as malaria.”

Some of the “ifs” include: the transgenic Sodalis has to be reasonably effective at blocking the parasite, at or above a level of about 85 percent; the Wolbachia bacteria, which has some effect on the health of flies affected with it, must not kill too many of them; and the target species of fly has to be a majority of the tsetse flies in the areas being treated.

The research shows that dealing with all of those obstacles should be possible. If so, this might spell the end of a tropical disease that has plagued humans for hundreds, possibly thousands of years. African trypanosomiasis causes serious mental and physical deterioration – including the altered sleep patterns that give the disease its name – and is fatal without treatment. It’s still difficult to treat, and neurologic damage is permanent.

Past efforts to control the disease, including insect traps, insecticide spraying, and use of sterile insects have been of some value, but only in limited areas and the effects were not permanent.

The strength of the new approach, researchers say, is that once the process begins it should spread and be self-sustaining - it should not be necessary to repeatedly take action in the huge geographic areas of Africa. Due to some genetic manipulation, the flies carrying the Wolbachia bacteria should naturally increase their populations and have an inherent survival advantage over conventional tsetse flies.

As the flies carrying transgenic bacteria continue to dominate and their populations spread, trypanosomiasis should fairly rapidly disappear. Whether the mechanism of control could wane in effectiveness over time is an issue that requires further study, scientists said.

Work has begun on the GMO version of Sodalis that has the capability to resist trypanosomes . It’s not yet finalized, Medlock said, but it should be possible, and when complete, the bacteria will be very specific to tsetse flies.

Medlock, an expert in modeling the transmission of various diseases – including human influenza – says the analysis is clear that this approach has significant promise of success. Because of the relatively low infectiousness of the parasite and the ability of Wolbachia to drive the resistance genes, no part of the system has to be 100 percent perfect in order to ultimately achieve near eradication of this disease, he said.

Accomplishing a similar goal with diseases such as malaria may be more difficult, he said, because that disease historically has shown a remarkable ability to mutate and overcome many of the approaches used to attack it. However, at least some near-term gains may be possible, he said.

Collaborators on this study included scientists from the OSU College of Veterinary Medicine and the Yale School of Public Health. It was supported by the National Institutes of Health and the Miriam Weston Trust.

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Tsetse fly

Tsetse fly

Gut microbes closely linked to range of health issues

CORVALLIS, Ore. –A new understanding of the essential role of gut microbes in the immune system may hold the key to dealing with some of the more significant health problems facing people in the world today, Oregon State University researchers say in a new analysis.

Problems ranging from autoimmune disease to clinical depression and simple obesity may in fact be linked to immune dysfunction that begins with a “failure to communicate” in the human gut, the scientists say. Health care of the future may include personalized diagnosis of an individual’s “microbiome” to determine what prebiotics or probiotics are needed to provide balance.

Appropriate sanitation such as clean water and sewers are good. But some erroneous lessons in health care may need to be unlearned – leaving behind the fear of dirt, the love of antimicrobial cleansers, and the outdated notion that an antibiotic is always a good idea. We live in a world of “germs” and many of them are good for us.

“Asked about their immune system, most people might think of white blood cells, lymph glands or vaccines,” said Dr. Natalia Shulzhenko, author of a new report in Clinical Reviews in Allergy and Immunology, and assistant professor and physician in the OSU Department of Biomedical Sciences. “They would be surprised that’s not where most of the action is. Our intestines contain more immune cells than the entire rest of our body.

“The human gut plays a huge role in immune function,” Shulzhenko said. “This is little appreciated by people who think its only role is digestion. The combined number of genes in the microbiota genome is 150 times larger than the person in which they reside. They do help us digest food, but they do a lot more than that.”

An emerging theory of disease, Shulzhenko said, is a disruption in the “crosstalk” between the microbes in the human gut and other cells involved in the immune system and metabolic processes.

“In a healthy person, these microbes in the gut stimulate the immune system as needed, and it in turn talks back,” Shulzhenko said. “There’s an increasing disruption of these microbes from modern lifestyle, diet, overuse of antibiotics and other issues. With that disruption, the conversation is breaking down.”

An explosion of research in the field of genomic sequencing is for the first time allowing researchers to understand some of this conversation and appreciate its significance, Shulzhenko said. The results are surprising, with links that lead to a range of diseases, including celiac disease and inflammatory bowel disease. Obesity may be related. And some studies have found relevance to depression, late-onset autism, allergies, asthma and cancer.

In the new review, researchers analyzed how microbe dysfunction can sometimes result in malabsorption and diarrhea, which affects tens of millions of children worldwide and is often not cured merely by better nutrition. In contrast, a high-fat diet may cause the gut microbes to quickly adapt to and prefer these foods, leading to increased lipid absorption and weight gain.

The chronic inflammation linked to most of the diseases that kill people in the developed world today – heart disease, cancer, diabetes – may begin with dysfunctional gut microbiota.

Understanding these processes is a first step to addressing them, Shulzhenko said. Once researchers have a better idea of what constitutes healthy microbiota in the gut, they may be able to personalize therapies to restore that balance. It should also be possible to identify and use new types of probiotics to mitigate the impact of antibiotics, when such drugs are necessary and must be used.

Such approaches are “an exciting target for therapeutic interventions” to treat health problems in the future, the researchers concluded.

The study, supported by OSU, included researchers from both the College of Veterinary Medicine and the College of Pharmacy.

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Dr. Natalia Shulzhenko, 541-737-1051