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Archive - Feb 2015

February 19th

Eylea Outperforms Avastin and Lucentis in Treatment of Diabetic Macular Edema (DME) When Vision Loss Is Moderate to Severe

Neil Bressler, M.D., a researcher from Johns Hopkins Medicine helped lead colleagues from across the country in a government-sponsored study by the Diabetic Retinopathy Clinical Research Network to discover that three drugs--Eylea, Avastin, and Lucentis, used to treat diabetic macular edema (DME) are all effective. They also discovered that Eylea outperformed the other two drugs when vision loss was moderate to severe. Prior to this study, which will be published in the Feb. 18 issue of the New England Journal of Medicine, it was not known how the efficacy or safety of the three drugs compared. The title of the article is “Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema.” "These findings will equip patients with the information they need to discuss with their doctors which drug to choose and will help guide protocols for clinicians using these drugs to treat patients with diabetic macular edema," says Dr. Bressler, past chair of the Diabetic Retinopathy Clinical Research Network and Director of the Retina Division at Johns Hopkins Medicine. There are nearly 750,000 people in the U.S. affected by diabetic macular edema, a diabetes-related eye disease that causes vision loss. About one-quarter of those people may have moderate to severe vision loss from diabetic macular edema when they see an ophthalmologist. In fact, it is a leading cause of vision loss in working-age Americans and is becoming a major global public health issue. Diabetic macular edema affects the area of the eye that is used for reading, driving, and watching television, all common functions of daily living.

In Largest ALS Exome Sequencing Study Ever, International ALS Consortium Identifies Gene (TBK1) Newly Associated with Sporadic ALS; Shines Spotlight on Inflammation and Autophagy Pathways

Using advanced DNA sequencing methods, researchers have identified a new gene that is associated with sporadic, as opposed to familial, amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease. ALS is a devastating neurodegenerative disorder that results in the loss of all voluntary movement and is fatal in the majority of cases. The next-generation genetic sequencing of the exomes (protein-coding portions) of 2,874 ALS patients and 6,405 controls represents the largest number of ALS patients to have been sequenced in a single study to date. Though much is known about the genetic underpinnings of familial ALS, only a handful of genes have been definitively linked to sporadic ALS, which accounts for approximately 90 percent of all ALS cases. The newly associated gene, called TBK1, plays a key role at the intersection of two essential cellular pathways: inflammation (a reaction to injury or infection) and autophagy (a cellular process involved in the removal of damaged cellular components). The new study, conducted by an international ALS consortium that includes scientists and clinicians from Columbia University Medical Center (CUMC), Biogen Idec, and the HudsonAlpha Institute for Biotechnology, was published online on February 19, 2015 in Science.

[BioQuick Editor’s Note: It is perhaps fitting that this major advance in the understanding of Lou Gehrig’s disease (ALS) was achieved, in part, by scientists and clinicians from Columbia, as the great Gehrig himself, a New York City native, attended and played baseball at Columbia before leaving as a junior and heading on to baseball immortality with the New York Yankees. See “Lou Gehrig: Columbia Legend and American Hero” on the web (http://www.columbia.edu/cu/alumni/Magazine/Fall2001/Gehrig.html).]

Luna Moth Uses Long Wing Tails to Undermine Sonar Locator of Attacking Bats

Rachel Nuwer, a freelancer writing for the Smithsonian web site recently, described some fascinating work that scientists had done to establish exactly how the large luna moth is able to fend off the attacks of sonar- directed bats. BioQuick was most impressed and provides much of Ms. Nuwer’s story here. “Animals have evolved countless ways to avoid being eaten, ranging from impeccable camouflage, to deadly venom, to fortress-like shells. Some even adopt a seemingly desperate, last-ditch method: distract predators into attacking a non-essential part of the body. Gaudy eyespots on butterflies and fish encourage predators to strike at the periphery of wings or fins, while some lizards’ bright tails can break off in a confused bird’s mouth. These tricks buy precious time for potential prey to escape their attackers. All of these tactics, however, rely on visual deception, so it would seem that predators using other sensory information would be immune to such strategies. Insect-eating bats, for one, rely on echolocation—sonar cries that bounce off objects—to locate and capture flying prey. Now, however, scientists have found that even echolocation can be fooled by expendable frills. Luna moths, the grandiose fairy queens of the North American Lepidoptera ball, can use their tails to divert bats’ attention away from their juicy, delicate bodies. When luna moths fly, two long frills on the ends of their chartreuse wings spin. According to an article published online on February xx, 2015 in PNAS, that elegant display can muddle bats' sonar and thwart a deadly attack."

In Bowel Cancer Study, ICR Scientists Use New Technique (Capture Hi-C) to Demonstrate Long-Range Cancer Risk Effects of DNA Looping and Single Nucleotide Variants in Gene Deserts

Single-letter genetic variations within parts of the genome once dismissed as “junk DNA” can increase cancer risk through wormhole-like effects on far-off genes, new research shows. Researchers have found that DNA sequences within “gene deserts,” so called because they are completely devoid of genes, can regulate gene activity elsewhere by forming DNA loops across relatively large distances. The study, led by scientists at The Institute of Cancer Research (ICR) (http://www.icr.ac.uk), London, helps solve a mystery about how genetic variations in parts of the genome that don't appear to be doing very much can increase cancer risk. Researchers developed a new technique to study the looping interactions and discovered that single-letter DNA variations linked to the development of bowel cancer were found in regions of the genome involved in DNA looping. Their study, published online on February 19, 2015, in Nature Communications, is the first to look comprehensively at these DNA interactions specifically in bowel cancer cells, and has implications for the study of other complex genetic diseases. The effort was funded by the EU, Cancer Research UK, Leukaemia & Lymphoma Research, and the ICR. The researchers developed a technique called Capture Hi-C to investigate long-range physical interactions between stretches of DNA. This allowed them to look at how specific areas of chromosomes interact physically in more detail than ever before. Previous techniques used to investigate long-range DNA interactions were not sensitive enough to produce definitive results. The researchers assessed 14 regions of DNA that contain single-letter variations previously linked to bowel cancer risk. They detected significant long-range interactions for all 14 regions, confirming their role in gene regulation.

Universtity of Geneva Results Dictate Diffferent View of Endocytosis Process

Cellular biology still harbors mysteries. Notably, there is no unequivocal explanation behind endocytosis, the biological process that allows exchanges between a cell and its environment. Two hypotheses prevail for explaining how the membrane caves in and forms transport vesicles: either the initial impetus is due to a scaffold-like structure which the soccer ball-shaped clathrin proteins build between themselves, or clathrin's role is minor, and it is other, “adaptor” proteins that exert pressure on the cell membrane until endocytosis begins. One recently completed study by the Faculty of Science at the University of Geneva (UNIGE) reconciles the two theories, suggesting that a balance between forces is present: clathrin proteins are only slightly more influential than the others, and it is a clever combination of physical mechanisms that contributes to creating favorable conditions for the deformation of the membrane. The findings and conclusions were published in Nature Communications In vitro procedures by researchers in UNIGE's Department of Biochemistry shed new light on the phenomenon of endocytosis, the biological cycle that takes place at the membrane level, and ends with the formation of the transport compartments necessary for external exchanges. During endocytosis, the cell membrane of eukaryotic organisms becomes deformed, puckering and caving in, creating vesicles for transporting elements such as ions, nutrients, and signals that are necessary for life. This compartment is deployed from the membrane towards the inside of the cell; its creation implies the use of much energy, and a significant physical force. Two hypotheses provide different explanations for the origins of this process.

Sleep Loss May Disrupt Fat Metabolism and Be Associated with Insulin Resistance and Increased Type 2 Diabetes Risk; Simply Getting Enough Sleep May Help Counter the Current Epidemics of Diabetes and Obesity

Lack of sleep can elevate levels of free fatty acids in the blood, accompanied by temporary pre-diabetic conditions in healthy young men, according to new research published online February 19, 2015, in Diabetologia, the journal of the European Association for the Study of Diabetes. The study, which is the first ever to examine the impact of sleep loss on 24-hour fatty acid levels in the blood, adds to emerging evidence that insufficient sleep, a highly prevalent condition in modern society--may disrupt fat metabolism and reduce the ability of insulin to regulate blood sugars. It suggests that something as simple as getting enough sleep could help counteract the current epidemics of diabetes and obesity. "At the population level, multiple studies have reported connections between restricted sleep, weight gain, and type 2 diabetes," said Esra Tasali (photo), M.D., Assistant Professor of Medicine at the University of Chicago and senior author of the study. "Experimental laboratory studies, like ours, help us unravel the mechanisms that may be responsible." The researchers found that after three nights of getting only four hours of sleep, blood levels of fatty acids, which usually peak and then recede overnight, remained elevated from about 4 a.m. to 9 a.m. As long as fatty acid levels remained high, the ability of insulin to regulate blood sugars was reduced. The results provide new insights into the connections, first described by University of Chicago researchers 15 years ago, between sleep loss, insulin resistance, and heightened risk of type 2 diabetes.

Plants Survive Mass Extinction Events Better Than Animals

At least five mass extinction events have profoundly changed the history of life on Earth. But a new study led by researchers at the University of Gothenburg in Sweden shows that plants have been very resilient to these catastrophic events. For over 400 million years, plants have played an essential role in almost all terrestrial environments and covered most of the world's surface. During this long history, many smaller and a few major periods of extinction severely affected Earth's ecosystems and its biodiversity. In the upcoming issue of the journal New Phytologist, the Gothenburg team reports its results based on analysis of more than 20,000 plant fossils with the aim to understand the effects of such dramatic events on plant diversity. The article is entitled “Revisiting the Origin and Diversification of Vascular Plants through a Comprehensive Bayesian Analysis of the Fossil Record.” The team’s findings show that mass extinction events had very different impacts among plant groups. Negative rates of diversification in plants (meaning that more species died out than new species were formed) were never sustained through long time periods. This indicates that, in general, plants have been particularly good at surviving and recovering through tough periods.
"In the plant kingdom, mass extinction events can be seen as opportunities for turnover leading to renewed biodiversity," says lead author Dr. Daniele Silvestro. Most striking were the results for the Cretaceous-Paleogene mass extinction, caused by the impact of an asteroid off the Mexican coast some 66 million years ago. This event had a great impact on the configuration of terrestrial habitats and led to the extinction of all dinosaurs except birds, but surprisingly, it had only limited effects on plant diversity.

February 18th

Duke Results Suggest CRISPR/Cas9-Enabled Gene Editing Might Be Used to Effectively Treat Over Half of Patients with Duchenne Muscular Dystrophy (DMD)

Duke researchers have demonstrated a genetic therapeutic technique that has the potential to treat more than half of the patients suffering from Duchenne muscular dystrophy (DMD). One of the challenges of treating DMD is that the disease can be caused by mutations in a number of different DNA sequences, and few of these mutations occur with any substantial frequency. The new technique, however, gets around this sticking point by targeting a large region of the (DMD) gene that contains many different mutations. The new study was published online on February 18, 2015 in Nature Communications. The article was entitled, “"Multiplex CRISPR/Cas9-Based Genome Editing for Correction of Dystrophin Mutations That Cause Duchenne Muscular Dystrophy." "There are no effective therapies currently available for people with DMD," said Dr. Charles Gersbach, Assistant Professor of Biomedical Engineering at Duke University. "DMD patients are in a wheelchair by age 10 and typically die in their 20s. They have nothing to stop this right now, and we're trying to work on that." DMD is caused by problems with the body's ability to produce dystrophin, a long-chain protein that binds the interior of a muscle fiber to its surrounding support structure. Dystrophin is coded by a gene with 79 genetic "chunks" called exons. If any one exon incurs a debilitating mutation, the dystrophin chain does not get built. Without dystrophin providing support, muscle tends to shred and slowly deteriorate. The disease affects one in 3,500 newborn males. The mutation is on the X chromosome so female children with two copies of X should have at least one functioning copy of the gene.

Doncaster Ichthyosaur Fossil Identified As New Species; Swam the Seas for Millions of Years During the Triassic, Jurassic, and Cretaceous Periods

The fossil had been in the collections of Doncaster Museum and Art Gallery for more than 30 years until Dr. Dean Lomax, a yong paleontologist and Honorary Scientist at The University of Manchester, UK, uncovered its hidden secrets. Dr. Dean first examined the fossil in 2008 when he noticed several abnormalities in the bone structure which made him think he had something previously unidentified. Working with Professor Judy Massare of Brockport College, New York, he spent over five years travelling the world to check his findings and a paper explaining the discovery was published online recently in the Journal of Vertebrate Paleontology. Dr. Dean said: "After examining the specimen extensively, both Professor Massare and I identified several unusual features of the limb bones (humerus and femur) that were completely different [from] any other ichthyosaur known. That became very exciting. After examining perhaps over a thousand specimens, we found four others with the same features as the Doncaster fossil." Similarly shaped to dolphins and sharks, ichthyosaurs, which are often misidentified as “swimming dinosaurs,” swam the seas of the earth for millions of years during the Triassic, Jurassic, and Cretaceous periods, before being wiped out. The Doncaster fossil is between 189 million and 182 million years old, from a time in the early Jurassic period called the Pliensbachian. It is the world's most complete ichthyosaur of this age. "The recognition of this new species is very important for our understanding of ichthyosaur species diversity during the early Jurassic, especially from this time interval,” Dr. Dean added.

Mucus Retained in Goblet Cells of Cystic Fibrosis Patients Leads to Potentially Deadly Infections; New Finding Could Lead to Improved Treatments

Cystic fibrosis (CF) is a genetic disorder that affects one out of every 3,000 children in populations of Northern European descent. One of the key signs of CF is that mucus lining the lungs, pancreas, and other organs is too sticky, which makes it difficult for the organs to work properly, and the CF mucus in the lungs attracts bacteria and viruses resulting in chronic infections. Researchers at the University of Missouri-Columbia (MU-Columbia) recently found that CF mucus actually gets stuck inside some of the cells (goblet cells) that create it, rather than simply becoming stuck on the outside linings of organs. Dr. Lane Clarke, a Professor of Biomedical Sciences in the MU College of Veterinary Medicine, says that now that it is better understood how mucus becomes trapped in the body, scientists can begin working on potential treatments for patients with CF that help cells remove the sticky mucus more quickly. "Normally, special cells (goblet cells) create mucus and easily push it out to the linings of the organs where it belongs," said Dr. Clarke, who also is a Dalton Investigator in the MU Dalton Cardiovascular Research Center. "However, in CF patients, some cells that create the mucus fail to completely release the mucus, so the mucus becomes stuck halfway in and halfway out. This makes mucus clearance more difficult and potentially would allow bacteria to have an easy pathway to infecting cells to cause diseases like pneumonia." Dr. Clarke also examined the characteristics of mucus stored within the cells and found that it is not as acidic as in normal cells. "Previously, CF researchers disagreed as to whether CF cells also have a defect in properly acidifying areas inside cells," Dr. Clarke said.