How Ducks Host Influenza Unharmed: Could Findings Shield Humans from Bird Flu Viruses?

A University of Alberta-led research team has discovered an influenza detector gene that could potentially prevent the transmission of the virus to humans.

Mallard duck with fifteen ducklings. Researchers have identified the genetic detector that allows ducks to live, unharmed, as the host of influenza. 

Katharine Magor, a U of A associate professor of biology, has identified the genetic detector that allows ducks to live, unharmed, as the host of influenza. The duck's virus detector gene, called retinoic acid inducible gene -- I, or RIG-I, enables a duck's immune system to contain the virus, which typically spreads from ducks to chickens, where it mutates and can evolve to be a human threat like the H5N1 influenza virus. The first human H5N1 cases were in Hong Kong in 1997. Eighteen people with close contact to chickens became infected and six died.
Magor's research shows chickens do not have a RIG-I gene. A healthy chicken can die within 18 hours after infection, but researchers have successfully transferred the RIG-I gene from ducks to chicken cells. The chicken's defenses against influenza were augmented and RIG-I reduced viral replication by half.
One potential application of this research could affect the worldwide poultry industry by production of an influenza-resistant chicken created by transgenesis.
The work of Katharine Magor, her U of A PhD candidate Megan Barber, and researchers from the United States (Jerry Aldridge and Robert Webster) was published March 22, in the online, early edition of Proceedings from the National Academy of Sciences.

Life on Saturn's Moon Titan: Stand Well Back and Hold Your Nose!

Research by astrobiologist William Bains suggests that if life has evolved on the frozen surface of Saturn's moon, Titan, it would be strange, smelly and explosive compared to life on Earth.

Dr Bains will present his work at the National Astronomy Meeting in Glasgow on April 13.
"Hollywood would have problems with these aliens" says Dr. Bains. "Beam one onto the Starship Enterprise and it would boil and then burst into flames, and the fumes would kill everyone in range. Even a tiny whiff of its breath would smell unbelievably horrible. But I think it is all the more interesting for that reason. Wouldn't it be sad if the most alien things we found in the galaxy were just like us, but blue and with tails?"
Dr Bains, whose research is carried out through Rufus Scientific in Cambridge, UK, and MIT in the USA, is seeking to work out just how extreme the chemistry of life can be. Life on Titan, Saturn's largest moon, represents one of the more bizarre scenarios being studied. Titan is twice as large as our Moon and has a thick atmosphere of frozen, orange smog. At ten times our distance from the Sun, it is a frigid place, with a surface temperature of -180 degrees Celsius. Water is permanently frozen into ice and the only liquid available is liquid methane and ethane, which the Cassini/Huygens mission has shown is present in ponds and lakes on the surface of the moon.
"Life needs a liquid; even the driest desert plant on Earth needs water for its metabolism to work. So, if life were to exist on Titan, it must have blood based on liquid methane, not water. That means its whole chemistry is radically different. The molecules must be made of a wider variety of elements than we use, but put together in smaller molecules. It would also be much more chemically reactive," said Dr Bains.
The solubility of chemicals in liquid methane is very limited, and strongly dependent on molecular weight. With a few exceptions, molecules with more than 6 heavy (non-hydrogen) atoms are essentially insoluble. So a metabolism running in liquid methane will have to be built of smaller molecules than terrestrial biochemistry, which is typically built of modules of around 10 heavy atoms. However you can only build around 3400 molecules from such a small number of atoms if you are limited to the chemistry that terrestrial life uses i.e. carbon, nitrogen, oxygen, and sulphur and phosphorus in very limited chemical contexts.
Dr Bains explained, "Terrestrial life uses about 700 molecules, but to find the right 700 there is reason to suppose that you need to be able to make 10 million or more. The issue is not how many molecules you can make, but whether you can make the collection you need to assemble a metabolism. It is like trying to find bits of wood in a lumber-yard to make a table. In theory you only need 5. But you may have a lumber-yard full of offcuts and still not find exactly the right five that fit together. So you need the potential to make many more molecules than you actually need. Thus the 6-atom chemicals on Titan would have to include much more diverse bond types and probably more diverse elements, including sulphur and phosphorus in much more diverse and (to us) unstable forms, and other elements such as silicon."
Energy is another factor that would affect the type of life that could evolve on Titan. With Sunlight a tenth of a percent as intense on Titan's surface as on the surface of Earth, energy is likely to be in short supply.
"Rapid movement or growth needs a lot of energy, so slow-growing, lichen-like organisms are possible in theory, but velociraptors are pretty much ruled out," said Bains.

Tainted Produce More Likely for Shoppers in Low-Income Neighborhoods, Study Suggests

No one wants a mixed salad tossed with extra bacteria, mold and yeast, but those are just what you might find when you try to eat a healthier diet in poorer neighborhoods. A new study shows that the level of bacteria found on the fresh produce can vary according to the income level of the neighborhoods where it is for sale.
Researchers compared levels of bacteria, yeast and mold on identical products sold in six Philadelphia-area neighborhoods. They selected three of the neighborhoods because they had the city’s highest poverty levels. In these, consumer options tended to be small markets that offered less variety in fruits and vegetables.
The result: ready-to-eat salads and strawberries sold in stores in the poorer neighborhoods had significantly higher counts of microorganisms, yeasts and molds than the same products purchased elsewhere, while cucumbers had a higher yeast count and mold and watermelon contained more bacteria.
“Food deteriorates when there is microbial growth,” said study co-author Jennifer Quinlan, a professor of nutrition and biology at Drexel University. “The bacterial count is used to determine the quality of the produce and it was poorer quality, closer to being spoiled. Three of the things that had a higher bacteria count — strawberries, ready-to-go salad and fresh-cut watermelon — have been associated with food-borne illnesses.”
The study appears online and in the May issue of the American Journal of Preventive Medicine.
When your access to produce is of inferior quality, it discourages you from adding more fruits and vegetables to your diet. Part of the problem, Quinlan said, is that much of the food available in poorer neighborhoods is for sale in smaller stores that might not have the infrastructure to handle produce in the safest way.
“The food may be of poorer quality to begin with; then it may be transported to the stores and not be refrigerated properly,” she said. “Large supermarkets have entire units focused on food safety, refrigeration, sanitation. While a small facility with only one or two people may not have the resources.”
Although the bacteria that can cause spoilage are not the same bacteria that are dangerous from a standpoint of food-borne illness, consumers can take some important steps to ensure they get the freshest produce.
“One thing consumers can look for is that fresh-cut produce be refrigerated at the point of sale,” said Shelley Feist, executive director of Partnership for Food Safety Education. “When they get fresh produce home, it’s important to clean it thoroughly. Whole fresh produce should be rinsed under running tap water just before eating and produce should be kept separate from meat, poultry, raw eggs and fish to avoid cross-contamination.”

'Microtentacles' on Tumor Cells Appear to Play Role in How Breast Cancer Spreads

Two breast tumor cells attaching to each other. The red color shows the surface of both tumor cells, while the green color shows how the microtentacles from one cell encircle the neighboring cell

Researchers at the University of Maryland Marlene and Stewart Greenebaum Cancer Center have discovered that "microtentacles," or extensions of the plasma membrane of breast cancer cells, appear to play a key role in how cancers spread to distant locations in the body. Targeting these microtentacles might prove to be a new way to prevent or slow the growth of these secondary cancers, the scientists say.
They report in an article to be published online March 15, 2010, in the journal Oncogene that a protein called "tau" promotes the formation of these microtentacles on breast tumor cells which break away from primary cancers and circulate in the bloodstream. While twisted remnants of tau protein have been seen in the brain tissue of patients with Alzheimer's disease, this is the first report that tau could play a role in tumor metastasis by changing the shape of cancer cells. These tau-induced microtentacles can help the cells reattach to the walls of small blood vessels to create new pockets of cancer.
"Our study demonstrates that tau promotes the creation of microtentacles in breast tumor cells. These microtentacles increase the ability of circulating breast tumor cells to reattach in the small capillaries of the lung, where they can survive until they can seed new cancers," says the senior author, Stuart S. Martin, Ph.D., a researcher at the University of Maryland Greenebaum Cancer Center and associate professor of physiology at the University of Maryland School of Medicine. Michael A. Matrone, Ph.D., is the study's lead author.
Healthy cells are programmed to die -- a process called apoptosis -- after they break off of epithelial layers that cover internal organs in the body. They also can be crushed if they are forced through small capillaries. However, cancer cells are able to survive for weeks, months and even years in the body. Once they are trapped in small blood vessels, the cells can squeeze through microscopic gaps in the vessels' lining and spread to organs such as the brain, lung and liver.
"We hope that through our research, we will be able to identify drugs that will target the growth of these microtentacles and help to stop the spread of the original cancer. Drugs that reduce tau expression may hold potential to inhibit tumor metastasis," Dr. Martin says.
He notes that metastatic cancers are the leading cause of death in people with cancer, but methods used to treat primary tumors have limited success in treating metastatic cancer. In breast cancer, metastases can develop years after primary tumors are first discovered.
Tau is present in a subset of chemotherapy-resistant breast cancers and is also associated with poor prognosis, but Dr. Martin adds, "While tau expression has been studied in breast cancers for contributing to chemotherapy resistance, the protein's role in tumor cells circulating in the bloodstream hasn't been investigated. And that's the focus of our research."
In this recent study, the University of Maryland researchers analyzed breast tumor cells from 102 patients and found that 52 percent had tau in their metastatic tumors and 26 percent (27 patients) showed a significant increase in tau as their cancer progressed. Twenty-two of these patients even had tau in metastatic tumors despite having none in their primary tumors.
Dr. Martin says more studies are needed to determine if tau is a clear predictor of metastasis. Given the complex nature of tumors, there most likely are other factors involved in causing cancers to spread, he says.
"Metastasis is a very major concern for people diagnosed with cancer, and the discovery of these microtentacles and the role that tau plays in their formation is a very exciting development that holds great promise for developing new drugs," says E. Albert Reece, M.D., Ph.D., M.B.A., acting president of the University of Maryland, Baltimore, and dean of the University of Maryland School of Medicine.
The University of Maryland, Baltimore, has filed patents on the microtentacle discoveries of Dr. Martin's lab group and is looking to partner with biopharmaceutical companies on new drug development. The researchers identified these cell extensions while they were studying the effects of two drugs that prevent cell division, or mitosis. Most chemotherapy drugs target cell division, aiming to slow or stop tumor growth.
Dr. Martin says his team found that a popular chemotherapy drug, taxol, actually causes cancer cell microtentacles to grow longer and allows tumor cells to reattach faster, which may have important treatment implications for breast cancer patients. Their studies are continuing.
"We think more research is needed into how chemotherapies that slow down cell division affect metastasis. The timing of giving these drugs can be particularly important. If you treat people with taxol before surgery to shrink the primary tumor, levels of circulating tumor cells go up 1,000 to 10,000 fold, potentially increasing metastasis," he adds.
The study being published in Oncogene was funded by grants from the National Cancer Institute, the USA Medical Research and Materiel Command, and the Flight Attendants Medical Research Institute.

Chemotherapy Plus Synthetic Compound Provides Potent Anti-Tumor Effect in Pancreatic Cancers

Human pancreatic cancer cells dramatically regress when treated with chemotherapy in combination with a synthetic compound that mimics the action of a naturally occurring "death-promoting" protein found in cells, researchers at UT Southwestern Medical Center have found.

Researchers led by Dr. Rolf Brekken have shown in mice that pancreatic cancer cells dramatically regress when treated with chemotherapy in combination with a synthetic "death-promoting" compound. 

The research, conducted in mice, appears in the March 23 issue of Cancer Research and could lead to more effective therapies for pancreatic and possibly other cancers, the researchers said.
"This compound enhanced the efficacy of chemotherapy and improved survival in multiple animal models of pancreatic cancer," said Dr. Rolf Brekken, associate professor of surgery and pharmacology and the study's senior author. "We now have multiple lines of evidence in animals showing that this combination is having a potent effect on pancreatic cancer, which is a devastating disease."
In this study, Dr. Brekken and his team transplanted human pancreatic tumors into mice, then allowed the tumors to grow to a significant size. They then administered a synthetic compound called JP1201 in combination with gemcitabine, a chemotherapeutic drug that is considered the standard of care for patients with pancreatic cancer. They found that the drug combination caused regression of the tumors.
"There was a 50 percent regression in tumor size during a two-week treatment of the mice," Dr. Brekken said. "We also looked at survival groups of the animals, which is often depressing in human therapeutic studies for pancreatic cancer because virtually nothing works. We found not only significant decrease in tumor size, but meaningful prolongation of life with the drug combination."
The drug combination was also effective in an aggressive model of spontaneous pancreatic cancer in mice.
The compound JP1201 was created in 2004 by UT Southwestern researchers to mimic the action of a protein called Smac. The researchers discovered Smac in 2000 and found that this protein plays a key role in the normal self-destruction process present in every cell.
Cell death, or apoptosis, is activated when a cell needs to be terminated, such as when a cell is defective or is no longer needed for normal growth and development. In cancer cells, this self-destruct mechanism is faulty and lead to breaks in the cell-death cascade of events. The synthetic Smac, or Smac mimetic, developed at UT Southwestern inhibits these breaks, allowing the cell to die.
"In essence, we're inhibiting an inhibitor," Dr. Brekken said. "And we're allowing the apoptotic cascade to kick off, resulting in the death of cancer cells."
UT Southwestern researchers are using Smac mimetics in breast and lung cancer research, as well. Dr. Brekken said the next step is to develop a compound based on JP1201 that can be tested in humans in clinical trials.
Other UT Southwestern researchers involved in the study included lead author Dr. Sean Dineen, surgery resident; Dr. Christina Roland, surgery resident; Rachel Greer, student research assistant in the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology Research; Juliet Carbon, senior research associate in surgery and in the Hamon Center; Jason Toombs, research assistant in surgery and in the Hamon Center; Dr. Puja Gupta, a pediatric hematology/oncology fellow; Dr. Noelle Williams, associate professor of biochemistry; and Dr. John Minna, director of the W.A. "Tex" and Deborah Moncrief Jr. Center for Cancer Genetics and of the Hamon Center.
The research was supported by Susan G. Komen for the Cure and Joyant Pharmaceuticals, a Dallas-based company and UT Southwestern spinoff that is developing medical applications of Smac-mimetic compounds.