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Archive - Aug 2017

August 21st

Mutational Signature Points to Ways, in Addition to BRCA1 and BRCA2 Mutations, That DNA Repair Mechanism Can Be Shut Off in Breast Cancer

A mutation pattern or “signature” linked to defects in two genes points to other ways an important DNA repair mechanism can be shut off in breast cancer. Breast cancer cells with defects in the DNA damage repair-genes BRCA1 and BRCA2 have a mutational signature (a pattern of base exchanges -- e.g., T's for G's, C's for A's -- throughout a genome) known in cancer genomics as "Signature 3." But not all breast tumor cells exhibiting Signature 3 have BRCA1 or BRCA2 mutations. Therefore, some consider Signature 3 a biomarker for "BRCAness," a sign of a breakdown in BRCA-related DNA repair (a process called homologous recombination, or HR) in general and not BRCA damage in particular. The question is, what else might deactivate HR and give rise to Signature 3? And beyond that, might Signature 3 have a role in the clinic? To find out, an international team led by Drs. Paz Polak, Jaegil Kim, Lior Braunstein, and Gad Getz of the Broad Institute's Cancer Program, and Dr. William Foulkes of McGill University reanalyzed data from nearly 1,000 breast cancer tumors collected by The Cancer Genome Atlas (TCGA). Their findings, reported online on August 21, 2017 in Nature Genetics, hint that mutational signatures like Signature 3 might fuel a precision medicine approach that uses a tumor's full scope of mutations to guide risk and treatment decisions, instead of focusing on individual genes. The article is titled “A Mutational Signature Reveals Alterations Underlying Deficient Homologous Recombination Repair in Breast Cancer.” Among the breast tumors exhibiting Signature 3, the researchers found that: (1) Tumors with germline (inherited) or somatic (acquired) BRCA1 or BRCA2 mutations were overwhelmingly positive for Signature 3.

People Who Hear Voices Can Detect Disguised Speech in Unusual Sounds

People who hear voices that other people can't hear may use unusual skills when their brains process new sounds, according to research led by Durham University and University College London (UCL). The study, published online on August 20, 2017 in the academic journal Brain, found that voice-hearers could detect disguised speech-like sounds more quickly and easily than people who had never had a voice-hearing experience. The open-access article is titled “Distinct processing of ambiguous speech in people with non-clinical auditory verbal hallucinations.” The findings suggest that voice-hearers have an enhanced tendency to detect meaningful speech patterns in ambiguous sounds. The researchers say this insight into the brain mechanisms of voice-hearers tells us more about how these experiences occur in voice-hearers without a mental health problem, and could ultimately help scientists and clinicians find more effective ways to help people who find their voices disturbing. The study involved people who regularly hear voices, also known as auditory verbal hallucinations, but do not have a mental health problem. Participants listened to a set of disguised speech sounds known as sine-wave speech while they were having an MRI brain scan. Usually these sounds can only be understood once people are either told to listen out for speech, or have been trained to decode the disguised sounds. Sine-wave speech is often described as sounding a bit like birdsong or alien-like noises. However, after training, people can understand the simple sentences hidden underneath (such as "The boy ran down the path" or "The clown had a funny face"). In the experiment, many of the voice-hearers recognized the hidden speech before being told it was there, and on average they tended to notice it earlier than other participants who had no history of hearing voices.

Carbohydrates in Mother’s Milk Show Antimicrobial Activity

Mother's milk, which consists of a complex and continually changing blend of proteins, fats, and sugars, helps protect babies against bacterial infections. In the past, scientists have concentrated their search for the source of its antibacterial properties on the proteins it contains. However, an interdisciplinary team of chemists and doctors at Vanderbilt University has discovered that some of the carbohydrates in human milk not only possess antibacterial properties of their own, but also enhance the effectiveness of the antibacterial proteins also present. "This is the first example of generalized, antimicrobial activity on the part of the carbohydrates in human milk," said Assistant Professor of Chemistry Steven Townsend, who directed the study. "One of the remarkable properties of these compounds is that they are clearly non-toxic, unlike most antibiotics." The results were presented on August 20, 2017 at the annual meeting of the American Chemical Society (ACS) in Washington, DC by doctoral student Dorothy Ackerman and published in the ACS Infectious Diseases journal on June 1, 2017 in a paper titled "Human Milk Oligosaccharides Exhibit Antimicrobial and Anti-Biofilm Properties Against Group B. Streptococcus." The basic motivation for the research was the growing problem of bacterial resistance to antibiotics, which the Center for Disease Control and Prevention (CDC) estimates causes 23,000 deaths annually."We started to look for different methods to defeat infectious bacteria. For inspiration, we turned to one particular bacteria, Group B Strep. We wondered whether its common host, pregnant women, produces compounds that can either weaken or kill strep, which is a leading cause of infections in newborns worldwide," Dr. Townsend said.

Researchers Discover lincRNA That May Hold Key to Triggering Regeneration & Repair of Damaged Heart Cells

New research has discovered a potential means to trigger damaged heart cells to self-heal. The discovery could lead to ground-breaking forms of treatment for heart diseases. For the first time, researchers have identified a long intergenic non-coding ribonucleic acid (lincRNA) that regulates genes controlling the ability of heart cells to undergo repair or regeneration. This novel RNA, which researchers have named "Singheart,” may be targeted for treating heart failure in the future. The discovery was made jointly by A*STAR's Genome Institute of Singapore (GIS) and the National University Health System (NUHS), and was published online on August 9, 2017 in Nature Communications. The open-access article is titled “Single Cardiomyocyte Nuclear Transcriptomes Reveal a lincRNA-Regulated De-Differentiation and Cell Cycle Stress-Response In Vivo.” Unlike most other cells in the human body, heart cells do not have the ability to self-repair or regenerate effectively, making heart attack and heart failure severe and debilitating. Cardiovascular disease (CVD) is the leading cause of death worldwide, with an estimated 17.7 million people dying from CVD in 2015. CVD also accounted for close to 30% of all deaths in Singapore in 2015. In this project, the researchers used single cell technology to explore gene expression patterns in healthy and diseased hearts. The team discovered that a unique subpopulation of heart cells in diseased hearts activates gene programs related to heart cell division, uncovering the gene expression heterogeneity of diseased heart cells for the first time. In addition, the scientists also found the "brakes" that prevent heart cells from dividing and thus from self-healing. Targeting these "brakes" could help trigger the repair and regeneration of heart cells.

Portable DNA Sequencer (MinION) Used in Field to Rapidly Identify Closely-Related Plants

In a paper published online on August 21, 2017 in Scientific Reports (Nature Publishing Group), researchers at the Royal Botanic Gardens, Kew, detail for the first time the opportunities for plant sciences that are now available with portable, real-time DNA sequencing. The open-access article is titled “"Field-Based Species Identification of Closely-Related Plants Using Real-Time Nanopore Sequencing.” Kew scientist and co-author of the paper Joe Parker says, "This research proves that we can now rapidly read the DNA sequence of an organism to identify it with minimum equipment. Rapidly reading DNA anywhere, at will, should become a routine step in many research fields. Despite hundreds of years of taxonomic research, it is still not always easy to work out which species a plant belongs to just by looking at it. Few people could correctly identify all the species in their own gardens." Over the last forty years, DNA sequencing has revolutionized the scientific world, but has remained laboratory-bound. Using current methods, a complete experiment to identify a species, from fieldwork to result, could easily take a scientist months to complete. Species identification is, by nature, largely a field-based area of pursuit, thereby limiting the pace of discovery and decision-making that can depend upon it. Using new technology to identify species quickly and on-site is critical for scientific research, the conservation of biodiversity, and in the fight against species crime. In this new study, Kew scientists used a portable DNA sequencer, the MinION from Oxford Nanopore Technologies, to analyze plant species in Snowdonia National Park. This was the first time genomic sequencing of plants has been performed in the field.

August 20th

Exosome Diagnostics Launches MedOncAlyzer™ Pan-Cancer Panel That Simultaneously Interrogates Exosomal RNA and ctDNA in Single Assay of Liquid Biopsy

On August 9, 2017, Exosome Diagnostics, a leader in the liquid biopsy market, announced the launch of the MedOncAlyzer 170, the first liquid biopsy pan-cancer panel that simultaneously interrogates exosomal RNA (exoRNA) and circulating tumor DNA (ctDNA) in a single assay. The MedOncAlyzer 170 is a targeted panel for tumor profiling that identifies clinically actionable and functionally important mutations across multiple cancer types starting from a small volume (≥ 0.5ml) of patient blood or plasma. “The MedOncAlyzer is the only cancer panel on the market that interrogates information on both RNA and DNA, giving it a higher sensitivity compared to ctDNA assays when profiling early-stage and late-stage cancers in plasma,” said Johan Skog, PhD, Chief Science Officer of Exosome Diagnostics. “ctDNA-only solutions are seeing their most accurate measurements in late-stage cancers. The primary drivers of ctDNA release into the bloodstream are apoptosis and necrosis of tumor cells. Existing solutions that rely on ctDNA alone are building a profile of the tumor that is biased towards consequences of cell death. Exosomes, in contrast, are actively released by living cells including viable tumor cells.

No Guts, No Glory—Scientists Probe Microbiomes of Elite Athletes

Elite athletes work hard to excel in sports, but they may also get a natural edge from the bacteria that inhabit their digestive tracts. Scientists have now tapped into the microbiomes of exceptional runners and rowers, and have identified particular bacteria that may aid athletic performance. The goal is to develop probiotic supplements that may help athletes -- and even amateur fitness enthusiasts -- recover from a tough workout or more efficiently convert nutrients to energy. The researchers presented their work on Sunday August 20, 2017 at the 254th National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world's largest scientific society, is holding the meeting in Washington, DC, through Thursday. It features nearly 9,400 presentations on a wide range of science topics. The microbiome presentation was titled “FitBiomics: Understanding Elite Microbiomes for Performance and Recovery Applications.” "When we first started thinking about this, I was asked whether we could use genomics to predict the next Michael Jordan," Jonathan Scheiman, Ph.D., says. "But my response was that a better question is: Can you extract Jordan's biology and give it to others to help make the next Michael Jordan?" To answer that question, microbes seemed like a good place to start. "We are more bacteria than we are human," says Dr. Scheiman, who is a postdoctoral fellow in the laboratory of George Church, PhD, at Harvard Medical School. "The bugs in our gut affect our energy metabolism, making it easier to break down carbohydrates, protein, and fiber. They are also involved in inflammation and neurological function.

August 19th

New Findings Challenge Dogma of How Dopamine-Releasing Neurons Communicate

Researchers at the University of Pittsburgh (Pitt) have uncovered the mechanism by which neurons keep up with the demands of repeatedly sending signals to other neurons. The new findings, made in fruit flies and mice, challenge the existing dogma about how neurons that release the chemical signal dopamine communicate, and may have important implications for many dopamine-related diseases, including schizophrenia, Parkinson's disease, and addiction. The research conducted at Pitt and Columbia University was published online on August 17, 2017 in Neuron. The article is titled “Neuronal Depolarization Drives Increased Dopamine Synaptic Vesicle Loading via VGLUT.” Neurons communicate with one another by releasing chemicals called neurotransmitters, such as dopamine and glutamate, into the small space between two neurons that is known as a synapse. Inside neurons, neurotransmitters awaiting release are housed in small sacs called synaptic vesicles. "Our findings demonstrate, for the first time, that neurons can change how much dopamine they release as a function of their overall activity. When this mechanism doesn't work properly, it could lead to profound effects on health," explained the study's senior author Zachary Freyberg, MD, PhD, who recently joined Pitt as an Assistant Professor of Psychiatry and Cell Biology. Dr. Freyberg initiated the research while at Columbia University. When the researchers triggered the dopamine neurons to fire, the neurons' vesicles began to release dopamine as expected. But then the team noticed something surprising: additional content was loaded into the vesicles before they had the opportunity to empty. Subsequent experiments showed that this activity-induced vesicle loading was due to an increase in acidity levels inside the vesicles.

New Bio-Optical Imaging Technique Is Fast and Economical

A new approach to optical imaging makes it possible to quickly and economically monitor multiple molecular interactions in a large area of living tissue -- such as an organ or a small animal; technology that could have applications in medical diagnosis, guided surgery, or pre-clinical drug testing. The method, which was published online on June 5, 2017 in Nature Photonics, is capable of simultaneously tracking 16 colors of spatially linked information over an area spanning several centimeters, and can capture interactions that occur in mere billionths of a second. The article is titled “Compressive Hyperspectral Time-Resolved Wide-Field Fluorescence Lifetime Imaging.” "We have developed a smart way to acquire a massive amount of information in a short period of time," said Dr. Xavier Intes, a Professor of Biomedical Engineering at Rensselaer Polytechnic Institute. "Our approach is faster and less expensive than existing technology without any compromise in the precision of the data we acquire." As its name implies, optical imaging uses light to investigate a target. In biomedical applications, optical imaging has many advantages over techniques such as MRI and PET, which use magnetism and positron emissions to acquire images inside of living tissue. The method the Intes lab developed makes use of advanced optical imaging techniques -- fluorescence lifetime imaging, paired with foster resonance energy transfer -- to reveal the molecular state of tissues. In fluorescence lifetime imaging (FLIM), molecules of interest are tagged with fluorescent "reporter" molecules which, when excited by a beam of light, emit a light signal with a certain color over time that is indicative of their immediate environment. Reporter molecules can be tuned to offer information on environmental factors such as viscosity, pH, or the presence of oxygen.

Invitation to ASEMV 2017 Annual Meeting (Exosomes & Microvesicles) in Asilomar, California (October 8-12)

The American Society for Exosomes and Microvesicles (ASEMV) is inviting interested scientists to the ASEMV 2017 meeting, to be held October 8-12, 2017 at the Asilomar Conference Center in California. This center is located on the Monterrey peninsula, just south of San Francisco (www.visitasilomar.com). The meeting will cover the full breadth of the exosome field, from basic cell biology to clinical applications, and follow the ASEMV tradition of inclusion and diversity as participants learn about the latest advances in the field. ASEMV 2017 is a forum for learning the latest discoveries in the field of exosomes, microvesicles, and extracellular RNAs. Over the course of four days at the Asilomar Conference Center, ASEMV 2017 will offer presentations from leading scientists and young researchers. Topics will span the breadth of the extracellular vesicle/RNA field, including the basic sciences, disease research, translation efforts, and clinical applications. Talks will be presented in multiple sessions, beginning at 7 pm on Sunday, October 8, 2017, and concluding at 4 pm on Thursday, October 12, 2017. Poster sessions will run throughout the meeting, with ample time to get to know your colleagues in the field and explore the many opportunities in this rapidly expanding field. Please see the links below.