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Archive - 2014

January 11th

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.

January 8th

Scientists Identify Possible Key to Drug Resistance in Crohn’s Disease

Two-thirds to three-quarters of the estimated 700,000 Americans living with Crohn’s disease, an autoimmune condition that can disrupt the entire gastrointestinal tract, will require surgery at some point during their lives. Patients and physicians often turn to this surgical intervention after a patient develops resistance to current treatments, such as steroids. Now scientists from the Florida campus of The Scripps Research Institute (TSRI) have identified a normally small subset of immune cells that may play a major role in the development of Crohn’s disease generally and in disease-associated steroid resistance specifically. The study, published online January 6, 2014 in the Journal of Experimental Medicine, focused on Th17 cells, part of a family of white blood cells that have been implicated in numerous autoimmune diseases, including Crohn’s disease. In the new study, the researchers found that a subset of TH17 cells in humans expresses the multidrug transporter MDR1 and that these cells are linked to inflammation in Crohn’s patients. MDR1—a protein famous for promoting drug-resistance in tumors—may also act as a survival and steroid resistance factor in T cells, particularly in harsh environments such as the inflamed gut mucosa of Crohn’s disease patients. “Our study is the first to identify and characterize this uniquely pro-inflammatory T-cell subset,” said biologist Dr. Mark Sundrud, a TSRI assistant professor who led the study. “We were able to sort these cells directly out of damaged tissue resected from Crohn’s patients and found that these pro-inflammatory cells are over-expressing genes that contribute to disease.” Within healthy individuals, only approximately 5 to 10 percent of CD4+ T cells are MDR1-expressing TH17 cells.

Zone in with Zon—Nucleic Acid Chemist Tackles Direct-to-Consumer Genetic Testing

Dr. Gerald Zon’s latest blog post, dated January 6, 2014, and published by TriLink BioTechnologies of San Diego, focuses on the controversial subject of direct-to-consumer (DTC) genetic testing. Dr. Zon shares some personal history, beginning in 2009, of dealing with Navigenics, the first provider of direct-to-consumer (DTC) SNP-based genetic testing and medical counseling. He then discusses 23andMe, a company that has been a lightning rod of controversy in the area of DTC genetic testing and received a “bombshell” November 2013 letter from the FDA calling on the company to stop marketing its testing kit until it received proper authorization. D. Zon also noted the FDA’s November issuance of marketing authorization for the first high-throughput (next-generation) genomic sequencer (Illumina’s MiSeqDx), which will allow development and use of innumerable new genome-based tests, as described in a December 19, 2013 New England Journal of Medicine Perspective piece by Francis Collins, M.D., Ph.D., and Margaret Hamburg, M.D. Dr. Zon further mentioned the “upbeat “Consumer Genetics Conference,” held in September 2013 to emphasize the swirl of developments and debate in this key arena. According to Dr. Zon, Navigenics began selling its genetic testing services in 2008 based on SNP analysis to assess risk for a variety of common health conditions. In July 2008, California health regulators sent cease-and-desist letters to Navigenics and 12 other genetic testing firms, including 23andMe. The state regulators asked the companies to prove a physician was involved in the ordering of each test and that state clinical laboratory licensing requirements were being fulfilled. Two months later, Navigenics and 23andMe received state licenses allowing the companies to continue to do business in California. Dr.

January 7th

Sage Grouse Threatened by Pole-Perching Ravens

A new study by the Wildlife Conservation Society (WCS), Idaho State University, and the U.S. Geological Survey suggests that habitat fragmentation and the addition of makeshift perches such as transmission polls in sagebrush ecosystems are creating preferred habitat for common ravens that threaten sensitive native bird species, including greater sage grouse (image). The study appears in the January issue of the journal The Condor: Ornithological Applications. Authors include Dr. Kristy Howe of the Wildlife Conservation Society and Idaho State University, Dr. Peter Coates of the U.S. Geological Survey, and Dr. David Delehanty of Idaho State University. The authors looked at 82 raven nests on the U.S. Department of Energy's Idaho National Laboratory land in southeastern Idaho, a sagebrush steppe ecosystem where ravens increased in numbers eleven-fold between 1985 and 2009. The study area has been subject to various alterations such as the addition of transmission lines, roads, and other human construction. Results showed that 58 percent of raven nests were located on transmission poles, 19 percent were in trees, and 14 percent were on other human-made towers. A 31 percent decrease in the likelihood of nesting by ravens was observed for every one kilometer increase in distance away from a transmission line when compared to unaltered areas. The authors noted that the transmission poles are taller than any other object in the study area and that nesting in or near them may afford the raven myriad advantages including a wider range of vision, greater attack speed, and easier take-off. Nesting on the poles may also gain them greater security from predators, range fires, and heat stress.

TGen and Collaborators Receive $4 Million Grant to Focus on RNA Biomarkers of Brain Injuries

In an effort to lower medical costs, identify patients at risk for injury, and speed patient recovery, scientists will attempt to identify a molecular signal that indicates severity of brain injury during a $4 million, five-year federal grant to Barrow Neurological Institute at St. Joseph's Hospital and Medical Center, Phoenix Children's Hospital, and the Translational Genomics Research Institute (TGen) (image). TGen made this announcement in a press release dated December 4, 2013. Additional partners in the study include the University of California, San Francisco and Stanford University. The molecular profile - comprised of extracellular RNAs- could help identify which patients are most at risk for vasospasm after hemorrhagic stroke. Hemorrhagic stroke can occur as: subarachnoid hemorrhage, or the bleeding into the area between the brain and a thin membrane that covers it; ruptured brain aneurysm, which is an abnormal bulge or ballooning in the wall of an artery within the brain. By identifying RNA molecular markers, a new standard of individualized care could be established, enabling medical teams to respond more rapidly to quickly changing health conditions, and allowing earlier intervention to prevent a secondary injury from occurring. "We hope this study will lead to less injury, less testing and cost, and shorter stays in the hospital," said Dr. Yashar Kalani, M.D., Ph.D., a resident physician in Neurological Surgery and assistant professor at the Barrow Neurological Institute and one of the study's principal investigators. Additional investigators at Barrow include Drs. Robert Spetzler, Peter Nakaji, Felipe Albuquerque, and Cameron McDougall. Vasospasms are characterized by bleeding in the brain that causes irritation and nearby blood vessels to spasm and narrow.

January 6th

Mystery m6A Modification of mRNA Governs Half-Life of Molecule

Researchers had known for several decades that a certain chemical modification exists on messenger ribonucleic acid (mRNA), which is essential to the flow of genetic information. But only recently did experiments at the University of Chicago show that one major function of this modification governs the longevity and decay of RNA, a process critical to the development of healthy cells. The chemical modification on mRNA in question is called N6-methyladenosine (m6A). A recent study by U. Chicago scientists and collaborators reveals how the m6A modification on mRNA could affect the half-life of mRNA that in turn regulates cellular protein quantities. That discovery could provide fundamental insights into healthy functioning and disorders such as obesity, diabetes, and infertility. The m6A modification "affects a huge number of messenger RNAs in human cells, and yet we did not know its exact function," said Dr. Chuan He, professor in chemistry at U. Chicago and a recently selected investigator of the Howard Hughes Medical Institute. He, Xiao Wang and 11 co-authors from U. Chicago, University of California, San Diego, and Peking University reported their findings on m6A in the January 2, 2014 issue of Nature. RNA in human cells becomes constantly depleted as it produces proteins, an instability that is essential to biology. "Whenever a cells starts to differentiate, transform into a different type of cell, it needs to express a different set of proteins using a different set of messenger RNA," Dr. He said. "It can't be the original set." The disposal of old RNA allows for the addition of new RNA and the production of different proteins. The Nature study documents that this process is regulated by the insertion or removal of a methyl group, a chemical group commonly found in organic compounds.