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Archive - Jan 2014

January 13th

Two Sources of Reactive Oxygen Appear Required in Diabetic Retinopathy

The retina can be bombarded by reactive oxygen species in diabetes, prompting events that destroy healthy blood vessels, form leaky new ones, and ruin vision. Now researchers have learned that those chemically reactive molecules must come from both the bone marrow as well as the retinal cells themselves to cause such serious consequences. "It's a cascade that requires two players to signal the next event that causes the damage," said Dr. Ruth Caldwell, cell biologist at the Vascular Biology Center at the Medical College of Georgia (MCG) at Georgia Regents University. The good news is the finding also provides two new points for intervention, said Dr. Modesto Rojas, MCG postdoctoral fellow and first author of the study published online on December 17, 2013 in the open-access journal PLOS ONE. Excessive glucose in the blood prompts excessive production of reactive oxygen species, or ROS, and the light-sensitive retina is particularly vulnerable. Dr. Caldwell's research team had previously documented that ROS from white blood cells produced by the bone marrow as well as from retinal cells were the major instigators in diabetic retinopathy, a leading cause of blindness worldwide. But they weren't sure which mattered most. So they looked as several different scenarios, including mice lacking the ability to produce ROS by either the retinal or white blood cells, and found that if either were lacking, future damage was essentially eliminated. "One alone can't do it," said Dr. Caldwell, the study's corresponding author. "They did not develop the early signs of diabetic retinopathy that we were measuring." While blocking ROS production by retinal cells could be difficult, drugs already exist that reduce activation of white blood cells.

January 12th

Unique Molecular Tool Developed to Isolate mRNA from Single Live Cells

A multi-disciplinary team from the University of Pennsylvania (Penn) has published online on January 12, 2014 in Nature Methods a first-of-its-kind technique to isolate mRNA from live cells in their natural tissue microenvironment without damaging nearby cells. This allows the researchers to analyze how cell-to-cell chemical connections influence individual cell function and overall protein production. Tissues, of course, are complex structures composed of various cell types. The identity and function of individual cells within each tissue type – heart, skin, brain, for example -- are closely linked by which genes are transcribed into mRNA, and ultimately proteins. To study gene expression in single cells in their natural tissue setting, researchers must be able to look at a cell's inner workings, much as an ecologist does when studying how an individual species interacts with its habitat. Even cells of seemingly the same type are not identical at the molecular level. Most knowledge about variability in gene expression has been from studies using heterogeneous groups of cells grown in culture. Researchers doubt the ability to extrapolate "real biology" from these unnatural conditions. Tools for investigating what type and how much RNA is present in single cells in intact tissue provide a unique opportunity to assess how mammalian cells really work and how that function may go awry in various diseases, and eventually in testing new drugs. James Eberwine, Ph.D., professor of Pharmacology, Perelman School of Medicine, and co-director of the Penn Genome Frontiers Institute (PGFI), and Ivan Dmochowski, Ph.D., associate professor of Chemistry, School of Arts and Sciences, co-directed this study. Other Penn co-authors include Jai-Yoon Sul, Ph.D., assistant professor of Pharmacology,and M.

Non-Coding DNA Implicated in Type 2 Diabetes

Variations in non-coding sections of the genome might be important contributors to type 2 diabetes risk, according to a new study. DNA sequences that do not encode proteins were once dismissed as "junk DNA," but scientists are increasingly discovering that some such regions are important for controlling which genes are switched on. The new study, published online on January 12, 2014 in Nature Genetics, is one of the first to show how such regions, called regulatory elements, can influence people's risk of disease. Type 2 diabetes affects over 300 million people worldwide. Genetic factors have long been known to have an important role in determining a person's risk of type 2 diabetes, alongside other factors such as body weight, diet, and age. Many studies have identified regions of the genome where variations are linked to diabetes risk, but the function of many of these regions is unknown, making it difficult for scientists to glean insights into how and why the disease develops. Only approximately two per cent of the genome is made up of genes: the sequences that contain code for making proteins. Most of the remainder is shrouded in mystery. "Non-coding DNA, or junk DNA as it is sometimes known, is the dark matter of the genome. We're only just beginning to unravel what it does," said leading author Professor Jorge Ferrer, a Wellcome Trust Senior Investigator from the Department of Medicine at Imperial College London. In the new study, scientists mapped the regulatory elements that orchestrate gene activity in the cells of the pancreas that produce insulin. In type 2 diabetes, the tissues become less responsive to insulin, resulting in blood sugar levels being too high.

Targetable BRAF Mutation Found to Drive Rare Brain Tumor

Scientists have identified a mutated gene that causes a type of tenacious, benign brain tumor that can have devastating lifelong effects. Currently, the tumor can only be treated with challenging repeated surgeries and radiation. The discovery, reported online on January 12, 2014 in Nature Genetics, is encouraging, because it may be possible to attack the tumors with targeted drugs already in use for other kinds of tumors, said the investigators from Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Massachusetts General Hospital (MGH), and the Broad Institute of MIT and Harvard. The mutated gene, known as BRAF, was found in almost all samples of tumors called papillary craniopharyngiomas. This is one of two types of craniopharyngiomas—the other being adamantinomatous—that develop in the base of the brain near the pituitary gland, hypothalamus, and optic nerves. The papillary craniopharyngiomas occur mainly in adults; adamantinomatous tumors generally affect children. The researchers identified a different mutant gene that drives the tumors in children. Drugs that target these adamantinomatous tumors are not yet clinically available, but may be in the future, said the researchers. "From a clinical perspective, identifying the BRAF mutation in the papillary tumors is really wonderful, because we have drugs that get into the brain and inhibit this pathway," said Sandro Santagata, M.D., Ph.D., a co-senior author of the paper. "Previously, there were no medical treatments—only surgery and radiation—and now we may be able to go from this discovery right to a well-established drug therapy." BRAF inhibitors are currently used in treating malignant melanoma when that BRAF mutation is present. Priscilla Brastianos, M.D., co-first author of the study, and Dr.

January 11th

Team Seeks Source of Body Louse Pathology for Humans

A new study seeks to determine how one parasitic species can give rise to two drastically different outcomes in its host: The human body louse (Pediculus humanus) can transmit dangerous bacterial infections to humans, while the human head louse (also Pediculus humanus) does not. A report of the new study as published online on January 9, 2014 in the journal Insect Molecular Biology. "Body louse-transmitted diseases include trench fever, relapsing fever, and epidemic typhus," said University of Illinois entomology professor Dr. Barry Pittendrigh, who led the research. In a previous study, Dr. Pittendrigh and his colleagues compared the sequences of all protein-coding genes in head and body lice and determined that the two belonged to the same species – despite the fact that body lice are bigger than head lice, cling to clothing instead of hair, and can transmit disease. Since the early 2000s, Dr. Pittendrigh has worked with Dr. John M. Clark, a professor of environmental toxicology and chemistry at the University of Massachusetts, on the molecular biology and genomics of lice. Dr. Clark was a collaborator on the 2012 study, and the two have had "a long-term goal of trying to solve this question of why body lice transmit bacterial diseases and head lice don't," Dr. Pittendrigh said. In the new study, Dr. Clark's group infected head and body lice with Bartonella quintana, the bacterium that causes trench fever. Dr. Pittendrigh's laboratory then looked at gene expression in each to see how the insects responded to the infection. "Our experiments suggest that the head louse immune system is fairly effective in fighting off the bacteria that cause trench fever," Dr. Pittendrigh said.

MIT Study Discovers Extracellular Vesicles Produced by Ocean Microbes

Marine cyanobacteria — tiny ocean plants that produce oxygen and make organic carbon using sunlight and carbon dioxide — are primary engines of the Earth’s biogeochemical and nutrient cycles. They nourish other organisms through the provision of oxygen and with their own body mass, which forms the base of the ocean food chain. Now scientists at MIT have discovered another dimension of the outsized role played by these tiny cells: The cyanobacteria continually produce and release vesicles, spherical packages containing carbon and other nutrients that can serve as food parcels for marine organisms. The vesicles also contain DNA, likely providing a means of gene transfer within and among communities of similar bacteria, and they may even act as decoys for deflecting viruses. In a paper published in the January 10, 2014 issue of Science, postdoc Dr. Steven Biller, Professor Sallie (Penny) Chisholm, and co-authors report the discovery of large numbers of extracellular vesicles associated with the two most abundant types of cyanobacteria, Prochlorococcus and Synechoccocus. The scientists found the vesicles (each about 100 nanometers in diameter) suspended in cultures of the cyanobacteria as well as in seawater samples taken from both the nutrient-rich coastal waters of New England and the nutrient-sparse waters of the Sargasso Sea. Although extracellular vesicles were discovered in 1967 and have been studied in human-related bacteria, this is the first evidence of their existence in the ocean. “The finding that vesicles are so abundant in the oceans really expands the context in which we need to understand these structures,” says Dr. Biller, first author on the Science paper.

Bacteriophage phiM12 Analyzed

Innovative work by two Florida State University (FSU) scientists and colleagues shows the structural and DNA breakdown of a bacteria-invading virus and is being featured on the cover of the February 2014 issue of the journal Virology. Dr. Kathryn Jones and Dr. Elizabeth Stroupe, both assistant professors in the FSU Department of Biological Science, have deconstructed a type of virus called a bacteriophage, which infects bacteria. Their work will help researchers gain a better understanding of how this type of virus invades and impacts bacteria, and could be particularly useful for the agriculture industry. "It turns out there are a lot of novel things about it," Dr. Jones said. Until now, there was little known about this particular bacteriophage, called phiM12, which infects a nitrogen-fixing bacterium called Sinorhizobium meliloti. Dr. Jones focused on sequencing the DNA of phiM12 and analyzing its evolutionary context, while Dr. Stroupe examined its overall physical structure. "The bacteriophage is really just a tool for studying the bacterium," Dr. Stroupe said. "No one thought to sequence it before." That tool, Dr. Stroupe said, will give scientists more insight into the basic functions of the phiM12 bacteriophage. phiM12 is the first reported bacteriophage to have its particular combination of DNA sequences and the particular shape of its protein shell determined. Understanding both the DNA and structure may provide an understanding of the proteins a bacteriophage produces and how it chooses the bacteria it invades. In the case of phiM12, this could be particularly useful in the future for the agriculture community and seed companies. Important crop plants depend on biological nitrogen fixation by the bacteria that is preyed upon by this phage.

January 10th

Cilia in Same Organism Found to Use Different Molecular Motors

Cilia are one of nature’s great multipurpose tools. The tiny, hair-like fibers protrude from cell membranes and perform all kinds of tasks in all kinds of creatures, from helping clear debris from human lungs to enabling single-celled organisms to swim. Now, physicists from Brown University have discovered something that could help scientists understand how cilia have been adapted for so many varied tasks. The study, led by graduate student Ilyong Jung, looked at the cilia of the single-celled, water-dwelling paramecium. Paramecia are covered with cilia that beat like thousands of tiny oars, propelling the creatures through the water. At the same time, cilia around the paramecium’s “oral groove” sweep nutrients inward, providing all-important nourishment. Through a series of experiments, the researchers showed that oral groove cilia appear to have different molecular motors than the rest of a paramecium’s cilia. This is the first time anyone has shown two motor behaviors by cilia in a single cell, says Dr. James Valles, chair of the Department of Physics at Brown and one of the paper’s senior authors. With a bit more study, Dr. Valles hopes this finding could shed light on the molecular mechanisms responsible for these two motor behaviors. “These motors are behaving differently in these two places in the same cell,” Dr. Valles said. “We’re hoping now that we can start pulling the two apart, maybe we can figure out what gives rise to these differences in behaviors. That could help us see why cilia can be so ubiquitous.” The findings were published in the January 7, 2014 issue of the Biophysical Journal. The researchers probed the behavior of the cilia by manipulating the viscosity of the liquid in which the paramecia swam.

Targeting Leishmaniasis “Superspreader” Dogs May Reduce Unnecessary Killing and Help Curb Deadly Disease

A new way to test for the parasite which causes the potentially fatal disease leishmaniasis could help control its spread to humans and stop dogs being needlessly killed in parts of South America. Zoonotic visceral leishmaniasis is a vector-transmitted parasitic infection which can be fatal if left untreated. It generally affects the poorest of the poor, particularly malnourished children in developing countries, with an estimated 200,000 to 400,000 new cases in humans occurring annually, according to World Health Organization (WHO) figures. Dogs have been shown to be the ‘reservoir’ for the parasite, which is transmitted to humans via bites from female sandflies that have fed on blood from infected dogs. In Brazil, tens of thousands of dogs that test positive for anti-Leishmania antibodies are killed every year in an effort to control the disease. However the presence of antibodies does not necessarily mean that the dog is symptomatic or is infectious to sandflies so that it can pass the parasite onto humans. This means that it is likely many dogs are killed unnecessarily, which usually results in dog owners acquiring a new dog, often a puppy that has not encountered the parasite before and that is then likely to become infected, thus helping to drive transmission. Previous studies have questioned the effectiveness of these measures in controlling leishmaniasis in dogs and humans and the policy is also undermined by significant levels of non-compliance among dog owners. An alternative approach is outlined in a new study by scientists at the University of Warwick in the UK who have shown that parasite load – a count of the number of parasites present in a dog’s skin tissue – is related to its infectiousness to sandflies.

January 9th

Young Girl’s Service Dog Senses Onset of Potentially Fatal Allergy Reactions

For the first time ever, physicians at Duke University Medical Center have allowed the service dog of a young female patient into the sterile operating room. According to an article by CBS News, the young girl, seven-year-old Kaelyn “KK” Krawczyk, suffers from a rare disease called mastocytosis or mast cell activation disorder. This causes her to have an abnormally high number of mast cells, which contain many inflammatory compounds that respond to allergens. For patients with mastocytosis, certain allergy triggers cause the body to release large amounts of these inflammatory compounds from the mast cells, resulting in facial flushing, significant drops in blood pressure, serious allergy symptoms, or life-threatening anaphylaxis. If untreated, death can occur. In the CBS News article, Dr. Brad Taicher, a Duke anesthesiologist who has worked with Kaelyn, said that “for KK, any countless number of things can trigger her mast cells to degranulate and release these mediators.” But Kaelyn has a service dog, JJ, that has been trained to somehow sense when Kaelyn is in danger from an allergy trigger. According to the CBS News story, the former shelter dog started his service dog career as a canine that could detect high and low blood sugars in patients with diabetes. Kaelyn’s mother, Michelle Krawczyk, approached JJ’s trainer and asked if the dog could be taught how to monitor Kaelyn’s condition. And, perhaps amazingly, it turned out that he could. According to the article, if JJ senses a threatening situation for Kaelyn, he will first start running in circles, possibly before Kaelyn herself realizes she is going to be sick. As the trigger gets worse and Kaelyn is in greater danger, JJ will start barking, and finally, start tugging on an adult to let him or her know that something is seriously wrong.