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Archive - Feb 17, 2015

Major Advance May Enable Safe Islet Transplants to Cure Type 1 Diabetes; CXCL12-Encapsulated Islets Protect Insulin-Producing Cells from Recipient's Immune Response

An approach developed by Massachusetts General Hospital (MGH) investigators may provide a solution to the limitations that have kept pancreatic islet transplantation from meeting its promise as a cure for type 1 diabetes. In the March 2015 issue of the American Journal of Transplantation, the research team reports that encapsulating insulin-producing islets in gel capsules, infused with a protein that repels key immune cells, protected islets from attack by the recipient's immune system, without the need for immunosuppressive drugs, restoring long-term blood sugar control in mouse models. The technique was effective both for islets from unrelated mice and for islets harvested from pigs. "Protecting donor islets from the recipient's immune system is the next big hurdle toward making islet transplantation a true cure for type 1 diabetes," says Mark Poznansky, M.D., Ph.D., Director of the MGH Vaccine and Immunotherapy Center, who led the study. "The first was generating enough insulin-producing islets, which has been addressed by several groups using pig islets, or, as announced last fall by Doug Melton's team at the Harvard Stem Cell Institute, with islet cells derived from human stem cells. Now our technology provides a way to protect islets or other stem-cell-derived insulin-producing cells from being destroyed as soon as they are implanted into a diabetic individual, without the need for high-intensity immunosuppression, which has its own serious side effects." While transplantation of pancreatic islets has been investigated for several decades, as a treatment and potential cure for type 1 diabetes, its success has been limited.

Secondary Metabolites in Floral Nectar May Play Vital Role in Reducing Bee-Parasite Interactions

Nicotine isn't healthy for people, but such naturally occurring chemicals found in flowers of tobacco and other plants could be just the right prescription for ailing bees, according to a Dartmouth College-led study. The researchers found that chemicals in floral nectar, including the alkaloids anabasine and nicotine, the iridoid glycoside catalpol, and the terpenoid thymol, significantly reduce parasite infection in bees. The results suggest that growing plants high in these compounds around farm fields could create a natural "medicine cabinet" that improves survival of diseased bees and pollination of crops. The researchers studied parasite infections in bumble bees, which like honey bees are important pollinators that are in decline around the world, a trend that threatens fruits, vegetables, and other crops that make up much of the food supply for people. The findings appear in the journal Proceedings of the Royal Society B. The study included researchers from Dartmouth and the University of Massachusetts-Amherst. Plants produce chemicals called secondary metabolites to defend leaves against herbivores. These chemicals are also found in nectar for pollinators, but little is known about the impacts of nectar chemistry on pollinators, including bees. The researchers hypothesized that some nectar compounds could reduce parasite infections in bees, so they inoculated individual bumble bees with an intestinal parasite and tested the effects of eight naturally occurring nectar chemicals on parasite population growth. The results showed that consumption of these chemicals lessened the intensity of infection by up to 81 percent, which could significantly reduce the spread of parasites within and between bee colonies.

Genetic Editing for Immediate Adaptation: The “Astonishing” Squid Edits Up to 60% of Its Nervous System RNA Transcripts On-the-Fly; Drosophila Just 3%

The principle of adaptation--the gradual modification of a species' structures and features--is one of the pillars of evolution. While there exists ample evidence to support the slow, ongoing process that alters the genetic makeup of a species, scientists could only suspect that there were also organisms capable of transforming themselves ad hoc to adjust to changing conditions. Now, a new study published online on January 8, 2015 in eLife by Dr. Eli Eisenberg of Tel Aviv University's (TAU’s) Department of Physics and Sagol School of Neuroscience, in collaboration with Dr. Joshua J. Rosenthal of the University of Puerto Rico, showcases the first example of an animal editing its own genetic makeup on-the-fly to modify most of its proteins, enabling adjustments to its immediate surroundings. The article is titled “The Majority of Transcripts in the Squid Nervous System Are Extensively Recoded by A-to-I RNA Editing.” The research, conducted in part by TAU graduate student Shahar Alon, explored RNA editing in the Doryteuthis pealieii squid. "We have demonstrated that RNA editing is a major player in genetic information processing, rather than an exception to the rule," said Dr. Eisenberg. "By showing that the squid's RNA editing dramatically reshaped its entire proteome — the entire set of proteins expressed by a genome, cell, tissue, or organism at a certain time — we proved that an organism’s self-editing of mRNA is a critical evolutionary and adaptive force." This demonstration, he said, may have implications for human diseases as well. RNA is a copy of the genetic code that is translated into protein. But the RNA "transcript" can be edited before being translated into protein, paving the way for different versions of proteins. Abnormal RNA editing in humans has been observed in patients with neurological diseases.

New Results Suggest That Altered Electrical Activity of Selective Dopamine Midbrain Neurons Is Crucial for Schizophrenia

Schizophrenia is not only associated with positive symptoms such as hallucinations and delusions, but also with negative symptoms e.g., cognitive deficits and impairments of the emotional drive. Until now, the underlying mechanisms for these negative symptoms have not been well characterized. In an article published online on February 9, 2015 in PNAS, a German-American team of researchers, with the cooperation of the Goethe University, reports that a selective dopamine midbrain neuron population that is crucial for emotional and cognitive processing shows reduced electrical in vivo activity in a disease mouse model. The title of the PNAS article is “Increased Dopamine D2 Receptor Activity in the Striatum Alters the Firing Pattern of Dopamine Neurons in the Ventral Tegmental Area.” ”Schizophrenia is a severe and incurable psychiatric illness, which affects approximately one percent of the world population. While acute psychotic states of the disease have been successfully treated with psycho-pharmaceutical drugs (anti-psychotic agents) for many decades, cognitive deficits and impairments of motivation do not respond well to standard drug therapy. This is a crucial problem, as the long-term prognosis of a patient is determined above all by the severity of these negative symptoms. Therefore, the shortened average life-span of about 25 years for schizophrenia patients remained largely unaltered in recent decades. "In order to develop new therapy strategies, we need an improved neurobiological understanding of the negative symptoms of schizophrenia" explains Professor Jochen Roeper of the Institute for Neurophysiology of the Goethe University.

Can Dingoes Help Halt Australia’s Biodiversity Collapse? Will They Suppress Red Foxes, Feral Cats, and Introduced Species; Will They Assist Re-Introduction of Greater Bilby and Burrowing Bettong?

Allowing dingoes to return to Sturt National Park in New South Wales, Australia and researching the results may be the key to managing the future of dingoes and many threatened native mammals, University of Sydney researchers believe. "Our approach is purposefully bold because only an experiment on this scale can resolve the long-running debate over whether the dingo can help halt Australia's biodiversity collapse and restore degraded rangeland environments," said Dr. Thomas Newsome from the School of Biological Sciences at the University of Sydney and lead author of an article published February 16, 2015 in Restoration Ecology. Written with Dr. Newsome's colleagues from the University of Sydney and other universities in Australia, and in America, where Dr. Newsome completed a Fulbright Scholarship, the article outlines how the experiment could be undertaken. "Half the world's mammal extinctions over the last two hundred years have occurred in Australia and we are on track for an acceleration of that loss. This experiment would provide robust data to address an issue of national and international significance," said Dr. Newsome. "Our approach is based on dingoes' ability to suppress populations of invasive predators such as red foxes and feral cats that prey on threatened native species. Dingoes can also control numbers of introduced species such as European wild rabbits, feral pigs, and goats or native herbivores such as kangaroos, that in high numbers can contribute to rangeland degradation. "There are major challenges, including convincing livestock producers and local communities to support the experiment, but we currently have almost no understanding of the impact of increased dingo populations over large areas.

Single Nucleotide Mutation Found to Alter Staph aureus ST21 Tropism from Humans to Rabbits; Surprising Result Dictates Paradigm Shift in Thinking about Transmission of Bacterial Diseases between Humans and Animals

A new study suggests that bacteria may be able to jump between host species far more easily than was previously thought. Researchers have discovered that a single genetic mutation in a strain of bacteria infectious to humans enables it to jump species to also become infectious to rabbits. The discovery has major implications for how we assess the risk of bacterial diseases that can pass between humans and animals. It is well known that relatively few mutations are required to support the transmission of viruses, such as influenza, from one species to another. Until now, it was thought that the process was likely to be far more complicated for bacteria. The new study was published online on February 16, 2015 in Nature Genetics. The title of the article was “A Single Natural Nucleotide Mutation Alters Bacterial Pathogen Host Tropism.” Scientists at the Universities of CEU Cardenal Herrera (Spain), and of Glasgow (UK), and of Edinburgh (UK) studied a strain of bacteria called Staphylococcus aureus ST121, which is responsible for widespread epidemics of disease in the global rabbit farming industry. The team looked at the genetic make-up of S. aureus ST121 to work out where the strain originated and the changes that occurred that enabled it to infect rabbits. The scientists found that S. aureus ST121 most likely evolved through a host jump from humans to rabbits approximately 40 years ago, with a genetic mutation at a single site in the bacterial DNA code being the cause for this.

New Results Underscore Importance of Non-Coding Super-Enhancers (SEs)—Especially Powerful Switches--in Autoimmune Diseases; SEs Mark Disease-Associated Regulatory Nodules in T-Cells

Investigators with the National Institutes of Health (NIH) have discovered the genomic switches of a blood cell that is key to regulating the human immune system. The findings, published online in Nature on February 16, 2015, open the door to new research and development in drugs and personalized medicine to help those with autoimmune disorders such as inflammatory bowel disease or rheumatoid arthritis. The Nature paper was titled, “Super-Enhancers Delineate Disease-Associated Regulatory Nodes in T Cells.” The senior author of the Nature paper, John J. O'Shea, M.D., is the Scientific Director at NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The lead author, Golnaz Vahedi, Ph.D., is a post-doctoral fellow in Dr. O'Shea's lab in the Molecular Immunology and Inflammation Branch of the NIAMS. The study was performed in collaboration with investigators led by NIH Director Francis S. Collins, M.D., Ph.D., in the Medical Genomics and Metabolic Genetics Branch at the National Human Genome Research Institute (NHGRI). Autoimmune diseases occur when the immune system mistakenly attacks its own cells, causing inflammation. Different tissues are affected in different diseases. For example, the joints become swollen and inflamed in rheumatoid arthritis, and the brain and spinal cord are damaged in multiple sclerosis. The causes of these diseases are not well understood, but scientists believe that they have a genetic component because they often run in families. "We now know more about the genetics of autoimmune diseases," said NIAMS Director Stephen I. Katz, M.D., Ph.D. "Knowledge of the genetic risk factors helps us assess a person's susceptibility to disease. With further research on the associated biological mechanisms, it could eventually enable physicians to tailor treatments to each individual."

Next-Generation Taxane (Cabazitaxel) May Be More Effective Earlier Than Standard Taxane (Docataxel) for Certain Prostate Cancer Patients; Those with Inactive RB Gene More Likely to Become Hormone-Resistant, But Also More Likely to Respond to Cabazitaxel

Prostate cancer is the second leading cause of cancer for men in the United States. Only one class of chemotherapy, called taxanes, is effective against the disease. A study published online on February 15, 2015 in Clinical Cancer Research, researchers have found that a newer member of the taxane family, called cabazitaxel, an FDA-approved drug, has properties that could make it more effective for some patients, a hypothesis currently being tested in clinical trials. Researchers also found a genomic marker that could help physicians identify which patients might benefit most from cabazitaxel. The article was titled, “Novel Actions of Next-Generation Taxanes Benefit Advanced Stages of Prostate Cancer.” "It was surprising to find that cabazitaxel functions differently than docetaxel in killing cancer cells, even though they're both taxanes," says senior author Karen Knudsen, Ph.D., Interim Director of the Sidney Kimmel Cancer Center and a Professor of Cancer Biology at the Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia. It shows that we may not be taking full advantage of this next-generation taxane in the clinic." For years, docetaxel has been the only effective chemotherapy for men whose cancer was no longer responding to hormone treatments. The next-generation drug in the taxane family, cabazitaxel, was approved in 2010, but only for patients whose cancer no longer responded to hormone therapy or docetaxel treatment. Dr. Knudsen and colleagues explored how cabazitaxel worked, and demonstrated that it might be more effective sooner in treatment than docetaxel.