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Archive - Feb 2016

February 29th

Discovering Epigenetic DNA Modifications Systematically

DNA is made from four nucleosides, each known by its own letter -- A, G, C, and T. However, since the structure of DNA was deciphered in 1953, scientists have discovered several other variants that are often added to the DNA sequences to replace one of the usual four letters. These variants, which may be modified versions of the traditional nucleosides, often help cells to control which genes are turned on and off, and are referred to as "epigenetic marks" in the DNA. In bacteria, they can also protect DNA from invasion by other organisms such as viruses. Until now, these DNA modifications have been discovered by chance, as scientists uncovered unexpected signals in chemical analyses of DNA. However, a new approach from MIT, the University of Florida, and other institutions offers a systematic approach to discovering unknown epigenetic marks and modifications. "It's a way to discover nucleic acid modifications that you didn't know existed," says Peter Dedon, Ph.D., the Underwood-Prescott Professor of Biological Engineering at MIT. "We've developed a technology platform for the discovery and characterization of these new modifications." Dr. Dedon and his colleagues suspect that bacteria and viruses, in particular, have many DNA modifications that have not been discovered yet, which could offer new antibiotic targets and new tools for biotechnology. Using their approach, which combines bioanalytical chemistry, comparative genomics, and a special type of DNA sequencing, the team has discovered a DNA modification that helps bacteria to protect their genomes from viral infection. They report their findings online on February 29, 2016 in PNAS.

International Society for Extracellular Vesicles (ISEV), Including Exosomes, Will Hold Annual 2016 Meeting in Rotterdam, May 4-7; Invitation; BioQuick News Is a Media Partner of Event

It is with great pleasure that the International Organizing Committee invites you to be part of the 5th Annual Meeting of the International Society for Extracellular Vesicles (ISEV) in Rotterdam, the Netherlands, from May 4-7, 2016. It is our honor to organize this meeting where scientists from around the globe gather to share the latest information on extracellular vesicles, including exosomes. The ISEV was funded in 2011 as the authoritative international community for extracellular vesicle (EV) research. It focuses on all aspects of extracellular vesicle investigations, including exosome investigations. Over the past few years, ISEV meetings have received an increasing number of abstracts due to the outstanding quality of these events. The scientific program (http://isev.org/isev2016/agenda/2016program-2/) of ISEV2016 includes a broad range of educational and scientific sessions covering the entire spectrum of topics relevant to EV research. For the first time, we have expanded our Pre-Meeting Education day program (http://isev.org/isev2016/agenda/2016pre-meeting-education-day/) to parallel sessions on two different topics (“New Developments of EV Isolation and Analysis” and “EV Therapeutics”). The ISEV is proud to announce prominent plenary speakers (http://isev.org/isev2016/agenda/2016program-2/plenary-speakers-isev2016/) highlighting important aspects of EVs and cancer (Klaus Pantel and David C. Lyden), EVs and viruses (Leonid Margolis and Robert C. Gallo) and EVs in cell biology (Francisco Sanchez-Madrid). Parallel symposium sessions, posters, and short oral poster presentations will provide platforms to present the newest developments in the field. Between oral and poster presentations, there will be sufficient time for networking and exhibition visits.

February 28th

Gum Disease Bacteria May Be Risk Factor for Esophageal Cancer

University of Louisville (U of L) School of Dentistry researchers have found that a bacterial species, Porphyromonas gingivalis, responsible for gum disease, is present in 61 percent of patients with esophageal squamous cell carcinoma (ESCC). The findings, published online on January 19, 2016 in Infectious Agents and Cancer, only detected P. gingivalis in 12 percent of tissues adjacent to the cancerous cells, while this organism was undetected in normal esophageal tissue. The open-access article is titled “Presence of Porphyromonas gingivalis in esophagus and its association with the clinicopathological characteristics and survival in patients with esophageal cancer.” "These findings provide the first direct evidence that P. gingivalis infection could be a novel risk factor for ESCC, and may also serve as a prognostic biomarker for this type of cancer," said Huizhi Wang, M.D., Ph.D., Assistant Professor of Oral Immunology and Infectious Diseases at the U of L School of Dentistry. "These data, if confirmed, indicate that eradication of a common oral pathogen may contribute to a reduction in the significant number of people suffering with ESCC." The esophagus, a muscular tube critical to the movement of food from the mouth to the stomach, is lined with two main kinds of cells, thus there are two main types of esophageal cancer: adenocarcinoma and squamous cell carcinoma. The latter is more common in developing countries. In collaboration with the College of Clinical Medicine of Henan University of Science and Technology in Luoyang, China, Dr. Wang and his U of L colleagues Richard J. Lamont, Ph.D., Jan Potempa, Ph.D., D.Sc., and David A. Scott, Ph.D., tested tissue samples from 100 patients with ESCC and 30 normal controls.

Eylea, Avastin, & Lucentis Yield Largely Similar Results in Two-Year Clinical Trial for Treatment of Diabetic Macular Edema; Eylea Outperforms Avastin in Those with 20/50 or Worse Vision

A two-year clinical trial that compared three drugs for diabetic macular edema (DME) found that gains in vision were greater for participants receiving the drug Eylea (aflibercept) than for those receiving Avastin (bevacizumab), but only among participants starting treatment with 20/50 or worse vision. Gains after two years were about the same for Eylea and Lucentis (ranibizumab), contrary to year-one results from the study, which showed Eylea with a clear advantage. The three drugs yielded similar gains in vision for patients with 20/32 or 20/40 vision at the start of treatment. The clinical trial was conducted by the Diabetic Retinopathy Clinical Research Network (DRCR.net), which is funded by the National Eye Institute, part of the National Institutes of Health. Results of the study were published online on February 27, 2016 in Ophthalmology, the journal of the American Academy of Ophthalmology. The article is titled “"Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-year Results from a Comparative Effectiveness Randomized Clinical Trial.” “This rigorous trial confirms that Eylea, Avastin, and Lucentis are all effective treatments for diabetic macular edema," said NEI Director Paul A. Sieving, M.D., Ph.D. "Eye care providers and patients can have confidence in all three drugs." Eylea, Avastin, and Lucentis are all widely used to treat DME, a consequence of diabetes that can cause blurring of central vision due to the leakage of fluid from abnormal blood vessels in the retina. The macula is the area of the retina used when looking straight ahead. The drugs are injected into the eye and work by inhibiting vascular endothelial growth factor (VEGF), a substance that can promote abnormal blood vessel growth and leakage. Although the drugs have a similar mode of action, they differ significantly in cost.

February 27th

New Cell-Sorting Technology Could Improve Development of Cell Therapies

Researchers at UCLA have developed a new way to separate and organize cells suspended in fluid samples by their subtle biochemical differences. The system sorts cells more quickly and accurately than current methods, and could lead to a simple, rapid automation of cell analysis, as well as an easier way to separate therapeutic cells from non-therapeutic, or “contaminating,” cells. Cell sorting is widely used in life sciences research and in diagnostic and industrial processing. For example, it is used to isolate progenitor or stem cells from tissues or in vitro cultures; these cells can then be delivered back to a patient to heal injuries or attack tumor cells. The magnetic ratcheting system developed at UCLA can distinguish between subtly different cells so that only the correct, therapeutic cells are used for treatments. “What we think is only one cell type is often a heterogeneous mixture, and without technologies to separate quantitatively, these nuanced differences get lost,” said Dino Di Carlo, Ph.D., the principal investigator on the research and a Professor of Bioengineering at the UCLA Henry Samueli School of Engineering and Applied Science. “For example, therapeutically active progenitor cells may look very similar to the other contaminating cells that provide no therapeutic benefit.” Currently, there are two common cell-sorting techniques. One technique is to use fluorescence to find target cells; this requires a large number of cells to complete an analysis because many are damaged or lost during the process. It’s also relatively slow. The other approach uses magnetic tagging and isolation; this method is faster, but typically can provide only a binary “yes” or “no” analysis, identifying only two types of cells.

New Findings Suggest Leptin and Amylin Work Together to Control Food Intake & Body Weight

The molecular intricacies of hunger and satiety, pivotal for understanding metabolic disorders and the problem of obesity, are not yet fully understood by scientists. However, new research from The Rockefeller University reveals an important new component of the system responsible for regulating food intake: a hormone called amylin, which acts in the brain to help control consumption. “How much a person eats is regulated by a complex circuit, and in order to understand it, we need to identify all the molecules involved,” says Jeffrey Friedman, Ph.D., Marilyn M. Simpson Professor and Head of the Laboratory of Molecular Genetics at Rockefeller. “Amylin caught our attention when we were profiling a set of neurons in the hypothalamus, a part of the brain known to be involved in feeding behavior. Because it plays a role in sugar metabolism elsewhere in the body, we were interested in exploring its function in the brain.” Dr. Friedman is well-known for his 1994 discovery of the hormone leptin, one regulator in this process. Defects in leptin production are associated with obesity. However, treating obesity with leptin alone has not proven effective, except in cases of severe leptin deficiency, suggesting that additional components are involved in this system. The new findings, published in the December 1, 2015 issue of Cell Metabolism, suggest that leptin and amylin work in concert to control food intake and body weight. The article is titled “Hypothalamic Amylin Acts in Concert with Leptin to Regulate Food Intake.” Dr. Friedman and colleagues first identified the precursor to amylin (called islet amyloid polypeptide or Iapp) in the brain by using a technology known as “translating ribosome affinity purification,” previously developed by fellow Rockefeller scientists.

Antibody from Ebola Survivor Protects Macaques and Can Advance to Clinical Trials

Scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and colleagues have discovered that a monoclonal antibody isolated from a human Ebola virus disease survivor protected non-human primates when given as late as five days after lethal Ebola infection. The antibody can now advance to testing in humans as a potential treatment for Ebola virus disease. There are currently no licensed treatments for Ebola infection, which caused more than 11,000 deaths in the 2014-2015 outbreak in West Africa. The findings are described in two articles published in the February 26, 2016 issue of Science. The open-access articles are titled “Protective Monotherapy Against Lethal Ebola Virus Infection by a Potent Neutralizing Antibody” and “Structural and Molecular Basis for Ebola Virus Neutralization by Protective Human Antibodies.” NIAID researchers obtained and tested blood samples from a survivor of the 1995 Ebola outbreak in Kikwit, Democratic Republic of the Congo, and discovered the survivor retained antibodies against Ebola. Investigators from the Institute for Research in Biomedicine in Switzerland then isolated specific antibodies for potential use as a therapeutic for Ebola infection. Investigators from the United States Army Medical Research Institute of Infectious Diseases administered a lethal dose of Zaire ebolavirus to four rhesus macaques, waited five days, and then treated three of the macaques with daily intravenous injections of the isolated monoclonal antibody, known as mAb114, for three consecutive days. The untreated control macaque showed indicators of Ebola virus disease and died on day nine, but the treatment group survived and remained free of Ebola symptoms.

Ultra-Thin Patterned Graphene Sheets, Inspired by Moths’ Eyes, May Help Power Future Smart Technologies, Nanotextured Sheets Absorb 95% of Incident Light

New research published online on February 26, 2016 in Science Advances has shown how graphene can be manipulated to create the most light-absorbent material for its weight, to date. This nanometer-thin material will enable future applications such as “smart wallpaper”that could generate electricity from waste light or heat, and power a host of applications within the growing “internet of things.” Using a technique known as nanotexturing, which involves growing graphene around a textured metallic surface, researchers from the University of Surrey's Advanced Technology Institute took inspiration from nature to create ultra-thin graphene sheets designed to more effectively capture light. Just one atom thick, graphene is very strong, but traditionally inefficient at light absorption. To combat this, the team used the nano-patterning to localize light into the narrow spaces between the textured surface, enhancing the amount of light absorbed by the material by approximately 90%. The open-access Science Advances article is titled “Ultra-Broadband Light Trapping Using Nanotextured Decoupled Graphene Multilayers.” "Nature has evolved simple, yet powerful,adaptations, from which we have taken inspiration in order to answer challenges of future technologies," explained Professor Ravi Silva, Head of the Advanced Technology Institute. "Moths' eyes have microscopic patterning that allows them to see in the dimmest conditions. These work by channelling light towards the middle of the eye, with the added benefit of eliminating reflections, which would otherwise alert predators of their location. We have used the same technique to make an amazingly thin, efficient, light-absorbent material by patterning graphene in a similar fashion."

Cryo-Electron Microscopy Analysis of Coronavirus Spike Protein May Point Way to Effective Vaccine Strategies

High-resolution cryo-electron microscopy and supercomputing have now made it possible to analyze, in detail, the infection mechanisms of coronaviruses. These viruses are notorious for attacking the respiratory tract of humans and animals. A research team that included scientists from the University of Washington (UW), the Pasteur Institute, and the University of Utrecht has obtained an atomic model of a coronavirus spike protein that promotes entry into cells. Analysis of the model is providing ideas for specific vaccine strategies. The study results are outlined in a study published online in Nature on February 8, 2016. David Veesler, UW Assistant Professor of Biochemistry, headed the project. The article is titled “Cryo-Electron Microscopy Structure of a Coronavirus Spike Glycoprotein Trimer.” Coronaviruses, with their crowns of spikes, are responsible for almost a third of mild, cold-like symptoms and atypical pneumonia worldwide, Dr. Veesler explained. But deadly forms of coronaviruses emerged in the form of SARS-CoV (severe acute respiratory syndrome coronavirus) in 2002 and of MERS-CoV (Middle East respiratory syndrome coronavirus) in 2012 with fatality rates between 10 percent and 37 percent. These outbreaks of deadly pneumonia showed that coronaviruses can be transmitted from various animals to people. Currently, only six coronaviruses are known to infect people, but many coronaviruses naturally infect animals. The recent deadly outbreaks resulted from coronaviruses overcoming the species barrier. This suggests that other new, emerging coronavirus with pandemic potential are likely to emerge. There are presently no approved vaccines or antiviral treatments against SARS-CoV or MERS-CoV.

February 26th

Elevated Levels of Certain GEF Proteins Associated with Shorter Progression-Free Survival in Metastatic Colorectal Cancer

Researchers at University of California (UC), San Diego School of Medicine and Moores Cancer Center, together with colleagues in Spain and Germany, have unraveled how elevated levels of particular proteins in cancer cells trigger hyperactivity in other proteins, fueling the growth and spread of a variety of cancers. The findings are published in the February 26, 2016 online publication of Scientific Reports. The open-access article is titled “Prognostic Impact of Modulators of G proteins in Circulating Tumor Cells from Patients with Metastatic Colorectal Cancer.” Specifically, the international team, led by senior author Pradipta Ghosh, MD, Associate Professor at UC San Diego School of Medicine, found that increased levels of expression of some members of a protein family called guanine nucleotide exchange factors (GEFs) triggered unsuspected hyperactivation of G proteins and subsequent progression or metastasis of cancer. The discovery suggests GEFs offer a new and more precise indicator of disease state and prognosis. "We found that elevated expression of each GEF is associated with a shorter progression-free survival in patients with metastatic colorectal cancer," said Dr. Ghosh. "The GEFs fared better as prognostic markers than two well-known markers of cancer progression and the clustering of all GEFs together improved the predictive accuracy of each individual family member." In recent years, circulating tumor cells (CTCs), which are shed from primary tumors into the bloodstream and act as seeds for new tumors taking root in other parts of the body, have become a prognostic and predictive biomarker. The presence of CTCs is used to monitor the efficacy of therapies and to detect early signs of metastasis. But counting CTCs in the bloodstream has limited utility, said Dr. Ghosh.