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Archive - Aug 21, 2017

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Linus Pauling Lives--Scientists Discover Vitamin C Regulates Stem Cell Function and Suppresses Leukemia Development

Not much is known about stem cell metabolism, but a new study from the Children’s Medical Center Research Institute at the University of Texas (UT) Southwestern (CRI) has found that stem cells take up unusually high levels of vitamin C, which then regulates their function and suppresses the development of leukemia. “We have known for a while that people with lower levels of ascorbate (vitamin C) are at increased cancer risk, but we haven’t fully understood why. Our research provides part of the explanation, at least for the blood-forming system,” said Dr. Sean Morrison, the Director of the CRI. The metabolism of stem cells has historically been difficult to study because a large number of cells are required for metabolic analysis, while stem cells in each tissue of the body are rare. Techniques developed during the study, which was published online on August 21, 2017 in Nature, have allowed researchers to routinely measure metabolite levels in rare cell populations such as stem cells. The techniques led researchers to discover that every type of blood-forming cell in the bone marrow had distinct metabolic signatures – taking up and using nutrients in their own individual way. One of the main metabolic features of stem cells is that they soak up unusually high levels of ascorbate. To determine if ascorbate is important for stem cell function, researchers used mice that lacked gulonolactone oxidase (Gulo) – a key enzyme that most mammals, including mice but not humans, use to synthesize their own ascorbate. Loss of the enzyme requires Gulo-deficient mice to obtain ascorbate exclusively through their diet as humans do. This gave CRI scientists strict control over ascorbate intake by the mice and allowed them to mimic ascorbate levels seen in approximately 5 percent of healthy humans.

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.