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Archive - Mar 2016

Date

March 22nd

DNA Molecules Directly Interact with Each Other Based on Sequence, Study Finds

Proteins play a large role in DNA regulation, but a new study finds that DNA molecules directly interact with one another in a way that's dependent on the sequence of the DNA and epigenetic factors. This could have implications for how DNA is organized in the cell and even how genes are regulated in different cell types, the researchers say. Led by Aleksei Aksimentiev, Ph.D., a professor of physics at the University of Illinois, and Taekjip Ha, Ph.D., a professor of biophysics and biophysical chemistry at Johns Hopkins University and an adjunct at the University of Illinois Center for the Physics of Living Cells along with Dr. Aksimentiev, the researchers published their work online on March 22, 2016 in the journal Nature Communications. The open-access article is titled “Direct Evidence for Sequence-Dependent Attraction Between Double-Stranded DNA Controlled by Methylation.” "We are still only starting to explore the physical properties of DNA. It's not just a string of letters," Dr. Aksimentiev said. "It's a complex molecule with unique characteristics. The prevailing hypothesis is that everything that happens inside the nucleus, the way the DNA is organized, is all the work of proteins. What we show is that direct DNA-DNA interactions may play a role in large-scale chromosome organization as well." Using the Blue Waters supercomputer at the National Center for Supercomputing Applications on the Illinois campus, Dr. Aksimentiev and postdoctoral researcher Dr. Jejoong Yoo performed detailed simulations of two DNA molecules interacting in a charged solution such as is found in the cell. The supercomputer allowed them to map each individual atom and its behavior, and to measure the forces between the molecules.

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First Evidence Found That “Cryptic Female Choice” Is Adaptive

Researchers from New Zealand's University of Otago studying chinook salmon have provided the first evidence that "cryptic female choice" (CFC) enhances fertilization success and embryo survival. CFC involves females using physical or chemical mechanisms to control which male fertilizes their eggs after mating, and is known to occur in a number of species. In 2008, Department of Anatomy researchers Dr. Patrice Rosengrave and Professor Neil Gemmell were the first to show that CFC occurred in salmon. When these fish spawn, eggs and sperm are shed simultaneously into the surrounding water with ovarian fluid being secreted with the eggs. The scientists demonstrated that ovarian fluid helped or hindered sperm swiftness depending on the male it came from. Now, after conducting a series of competitive and non-competitive fertilization experiments, the pair and colleagues have provided the first evidence that CFC contributes to reproductive success. Dr. Rosengrave says they found that not only does a particular female's ovarian fluid give a bigger boost to some male's sperm and not others, these speedier sperm have a significantly higher chance of winning the race to fertilize eggs and the resulting offspring have a better survival rate as embryos. "Additionally, after assessing the genetic quality of the males we found embryo survival was linked to being sired by higher-quality fathers," she says. The findings may have wider implications for our understanding of animal, or even human, reproduction, she adds. "There could well be equivalent mechanisms at play in environments such as mucus on vaginal or uterine walls." The research was published online on March 23, 2016 in the UK journal Proceedings of the Royal Society B.

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March 16th

Vaccine Against Dengue 2 Virus Protected Against Infection in 100 Percent of People Who Received It, in Small Trial

In a small clinical trial led by the Johns Hopkins Bloomberg School of Public Health, researchers say that a promising single-dose dengue vaccine, developed by scientists at the NIH, was 100 percent effective in preventing human volunteers from contracting the virus, the most prevalent mosquito-borne virus in the world. The findings, published on March 16, 2016 in Science Translational Medicine, could be the final puzzle piece in developing a vaccine that is effective against dengue, which infects nearly 400 million people across more than 120 countries each year. While most of those who are infected with dengue survive with few or no symptoms, more than two million people annually develop what can be a dangerous dengue hemorrhagic fever, which kills more than 25,000 people each year. The new open-access article is titled “The Live Attenuated Dengue Vaccine TV003 Elicits Complete Protection Against Dengue in a Human Challenge Model.” Preventing dengue has been a particular challenge. A three-dose vaccine called Dengvaxia received limited licensure in 2016 in Mexico, the Philippines, and Brazil. That vaccine produced antibodies against dengue in a clinical trial and protected against dengue during the first year after vaccination. But two years after vaccination, children who were under the age of nine when they received the vaccine were hospitalized for dengue at a significantly higher rate than those who received the placebo. For this reason, the researchers, led by Anna P. Durbin, M.D., an Associate Professor in International Health at the Bloomberg School, were concerned that measuring antibodies alone may not truly indicate the ability of the vaccine to protect against dengue.

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March 16th

Exosome Diagnostics Market Expected to Grow from $10 Million in 2016 to $100 Million in 2021

In the last decade, scientific research showed exponential growth in scientific publications on exosomes. According to a March 16, 2016 press release, BCC Research reveals in its new report that these tiny sub-cellular vesicles may offer unlimited potential in diagnostics and therapeutics, especially in oncology treatments. The new report is titled Exosome Diagnostics and Therapeutics: Global Markets (BIO149A) analyzes the technologies for exosome diagnostics and therapeutics with breakdowns of new and existing diagnostic methods. Analyses of global market drivers and trends, with data from 2015, estimates for 2016, and projections of CAGRs through 2021 also are provided. Exosomes are small membrane-bounded sacs/vesicles (approximately 30-100 nm in diameter), that are released by both healthy and cancerous cells. Substances from cell cytoplasm, such as genomic DNA, various RNA species, proteins, and lipids are encapsulated into exosomes and are shed into the extracellular environment. Research has showed that all fluids in the human body contain exosomes, which can transfer cytoplasmic ingredients to other cells either locally or at distant sites. Once reaching the recipient cells, cytoplasmic ingredients can alter cell biology. The market for the exosome approach can be divided into three main categories: diagnostics, therapeutics, and research tools sectors. The global market should reach about $16.1 million and more than $111 million in 2016 and 2021, respectively, reflecting a five-year compound annual growth rate (CAGR) of 47.3%. Diagnostics as a segment should remain the largest and fastest-growing sector, growing from $10 million in 2016 to $100 million in 2021, demonstrating a five-year CAGR of 58.5%.

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March 10th

Important Biological Differences Between Male & Female Breast Cancer

Male breast cancer (Male BC) has important biological differences that distinguish it from female breast cancer, but to date these have been little studied and Male BC patients have been excluded from many clinical trials in breast cancer. Male patients are also usually diagnosed later when their cancers are more advanced, leading to a worse outcome. New research has now uncovered some of the differences between the two types of breast cancer, and the researchers hope that this will help doctors to make better treatment choices for Male BC patients. Speaking at the 10th European Breast Cancer Conference (EBCC-10) today (Thursday, March 10, 2016), Dr Carolien van Deurzen, MD, a pathologist specializing in breast cancer at the Erasmus Medical Centre, Rotterdam, The Netherlands, reported results from a study of the relationship between the pathology of different types of Male BC and their prognosis. (Abstract no. 7, "Pathologic prognostic factors of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABG International Male Breast Cancer Program", Thursday 11.00 hrs). The study forms part of the International Male Breast Cancer Program, led by the European Organisation for Research and Treatment of Cancer (EORTC) in Europe and the Translational Breast Cancer Research Consortium (TBCRC) in the USA. The team of researchers examined 1203 tumor samples from Male BC patients who made up part of the largest series of this disease ever collected linked to outcome data -- 1483 patients from 23 centres in nine countries.

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Researchers Build Molecule That Could Significantly Reduce Brain Damage in Stroke Victims

Research teams separated by 9,000 miles have collaborated to advance prospective treatment for stroke, the world's second-leading cause of death. University of Nebraska-Lincoln (UNL) chemists partnered with medical researchers from the National University of Singapore to develop a molecule that can inhibit an enzyme linked with the onset of stroke. Most strokes occur when a disruption of blood flow prevents oxygen and glucose from reaching brain tissue, ultimately killing neurons and other cells. The team found that its molecule, known as 6S, reduced the death of brain tissue by as much as 66 percent when administered to the cerebrum of a rat that had recently suffered a stroke. It also appeared to reduce the inflammation that typically accompanies stroke, which the World Health Organization has estimated kills more than 6 million people annually. "The fact that this inhibitor remained effective when given as post-stroke treatment ... is encouraging, as this is the norm in the treatment of acute stroke," the researchers reported in a study published on March 9, 2016 in the journal ACS Central Science. The open-access article is titled “’Zipped Synthesis’ by Cross-Metathesis Provides a Cystathionine β-Synthase Inhibitor that Attenuates Cellular H2S Levels and Reduces Neuronal Infarction in a Rat Ischemic Stroke Model.” The inhibitor works by binding to cystathionine beta-synthase, (CBS) - an enzyme that normally helps regulate cellular function but can also trigger production of toxic levels of hydrogen sulfide in the brain. Though hydrogen sulfide is an important signaling molecule at normal concentrations, stroke patients exhibit elevated concentrations believed to initiate the brain damage they often suffer.

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Cancer Cells Can Consume Exosomes from Microenvironment for Nourishment

Cancer cells are well-known as voracious energy consumers, but even veteran cancer-metabolism researcher Dr. Deepak Nagrath was surprised by their latest exploit: Experiments in his lab at Rice University show that some cancer cells get 30-60 percent of their fuel from consuming their neighbors' exosomes. "Our original hypothesis was that cancer cells were modifying their metabolism based on communications they were receiving from cells in the microenvironment near the tumor," said Dr. Nagrath, Assistant Professor of Chemical and Biomolecular Engineering at Rice and co-author of a new study describing the research published online on February 27, 2016 in the open-access journal eLife. "None of us expected to find that they were converting the signals directly into energy." The article is titled “Tumor Microenvironment Derived Exosomes Pleiotropically Modulate Cancer Cell Metabolism.” The results were part of a four-year study by Dr. Nagrath, his students and collaborators at the University of Texas MD Anderson Cancer Center and other institutions about the role of exosomes in cancer metabolism. Exosomes are tiny packets of proteins, microRNA and nucleic acids that cells emit into their environment to both communicate with neighboring cells and influence their behavior. Dr. Nagrath, who directs Rice's Laboratory for Systems Biology of Human Diseases, found that some cancer cells are capable of using these information packets as a source of energy to fuel tumor growth. Dr. Nagrath's team specializes in analyzing the unique metabolic profiles of various types of cancer. His work is the latest in a series of discoveries about cancer metabolism that date to German chemist Otto Warburg's 1924 discovery that cancer cells produce far more energy from the metabolic process known as glycolysis than do normal cells.

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March 9th

Scientists Produce Purple Lime with Potential for Ornamental, Fresh Fruit Markets

Anthocyanins, pigments that give plants their red, blue, or purple hues, are not typically produced in citrus fruits grown under tropical or subtropical conditions. Now, scientists have genetically engineered a lime that contains anthocyanins, which they say has several potential benefits. Manjul Dutt, Daniel Stanton, and Jude Grosser, from the Citrus Research and Education Center at the University of Florida, say that the discovery will allow the cultivation of new citrus fruits in the major subtropical citrus belt and/or the production of ornamental plants, depending on the cultivar. The process also creates opportunities for novel fruit, leaf, and flower colors to be produced by regulating anthocyanin biosynthesis. In the study in the Journal of the American Society for Horticultural Science, Dutt, Stanton, and Grosser reported on experiments in which they achieved production of anthocyanins in “Mexican” lime, a citrus cultivar that does not produce anthocyanin naturally. The scientists produced transgenic “Mexican” lime (Citrus aurantifolia Swingle) plants expressing either a myb-related anthocyanin biosynthesis regulatory gene cloned from the red grape “Ruby Seedless” or from the “Moro” blood orange. The experiments resulted in anthocyanin pigmentation in the leaves, stems, flowers, and fruit. The researchers observed an increased pigmentation of the outer layer(s) of stem tissue in “Mexican” lime overexpressing the VvmybA1 (from red grape), whereas lower anthocyanin levels were observed in plants overexpressing Ruby (from blood orange). Enhanced pigmentation was also observed in the young leaves; however, pigment intensity levels decreased as the leaves matured. Flower color ranged from light pink to fuchsia. The fruit pulp of several of the lime lines was maroon, similar to a blood orange.

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March 7th

Mice Older Than Four Months Do Not Appear to Need the Huntingtin Gene

Adult mice don't need the gene that, when mutated in humans, causes the inherited neurodegenerative disorder Huntington's disease. The finding suggests that treatment strategies for Huntington's that aim to shut off the huntingtin gene in adults -- now in early clinical stages -- could be safe. The results were published online on Monday, March 7, 2016 in PNAS. The article is titled “Ablation of Huntingtin in Adult Neurons Is Nondeleterious But Its Depletion in Young Mice Causes Acute Pancreatitis.” Huntington's disease is caused by a gene encoding a toxic protein (mutant huntingtin) that causes brain cells to die. Symptoms commonly appear in mid-life and include uncontrolled movements, balance problems, mood swings and cognitive decline. A juvenile form of Huntington's disease also can appear during the teenage years. Researchers led by Xiao-Jiang Li, M.D., Ph.D., and Shihua Li, M.D., at Emory University School of Medicine, used genetically engineered mice in which the huntingtin gene can be deleted, triggered only when the mice are given the drug tamoxifen. When the huntingtin gene is deleted at an age older than four months, these mice appeared to stay healthy, despite having lost their huntingtin genes in cells all over their bodies. They maintained their body weight and could complete tests of movement and grip strength as well as control mice. In contrast with adults, engineered mice younger than four months old whose huntingtin gene was deleted developed lethal pancreatitis. The huntingtin gene encodes a large scaffold protein, with many interaction partners, which is thought to be involved in intracellular trafficking. The huntingtin gene is essential for embryonic development, and scientists have already shown that if mouse embryos don't have it at conception, they die in utero.

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New Drug Class Shows Promise Against Legionnaire’s Disease

A new class of drugs has shown promise for treating the bacteria that cause legionnaires' disease, a potentially fatal lung infection. The discovery that “BH3-mimetic” drugs obliterate cells infected with Legionella bacteria could lead to new treatments for a variety of bacterial infections, even those that are resistant to antibiotics. A research team including Dr. James Vince of the Walter and Eliza Hall Institute in Australia, and Dr. Thomas Naderer and Ph.D. student Ms Mary Spier from the Monash University Biomedicine Discovery Institute, also in Australia, showed for the first time that a protein called BCL-XL is an Achilles' heel of Legionella-infected cells. Turning off BCL-XL with BH3-mimetic drugs killed the infected cells, allowing the infection to be cleared from the body. The research was published in the March 2016 edition of Nature Microbiology. The article is titled “Eliminating Legionella by Inhibiting BCL-XL to Induce Macrophage Apoptosis.” People become infected with Legionella bacteria by inhaling contaminated water droplets, often from cooling towers or spas, or contaminated soil such as potting mix. The bacteria hide within human cells called macrophages, escaping the body's own immune defenses and being shielded from many types of antibiotics. People with a weakened immune system, including the elderly, are at particular risk of the serious lung Legionella infection called legionnaires' disease. Dr. Vince said that soon after infecting a macrophage, Legionella bacteria alter the composition of proteins within their host cell to prevent the host from detecting the infection. "We were particularly interested that this drained the macrophage of a protein called MCL-1, that helps to keep cells alive," he said.

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