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Archive - Nov 2015

November 11th

Exosome-Based Approach to Diagnose Lupus in Patients with Renal Impairment; High Levels of miRNA-146a in Urine-Derived Exosomes from Patients May Be Diagnostic for This Pathology

Researchers at the INCLIVA Biomedical Research Institute in Valencia, Spain, together with collaborators, have demonstrated the presence of extracellular vesicles (EVs) in the urine of patients diagnosed with lupus and renal impairment (lupus nephritis) and shown that exosomes (a subset of EVs) in this urine contain unusually high levels of microRNA-146a (miR-146a) that may be diagnostic for this pathology. The work was originally published online on September 21, 2015 in the open-access journal PLOS ONE. This article was titled “Increased Urinary Exosomal MicroRNAs in Patients with Systemic Lupus Erythematosus." A related review article titled “Extracellular Vesicles as Biomarkers of Systemic Lupus Erythematosus,” was published online at about the same time in the open-access journal Disease Markers. Lupus (systemic lupus erythematosus or SLE) is a chronic autoimmune disease that can affect almost every organ of the body, joints, kidneys, heart, skin, blood vessels, lungs, etc., whose cause is unknown. It is a very heterogeneous disease, with symptoms that come and go in outbreaks, hence the complexity of diagnosis. To date, lupus has no single diagnostic technique that has become final. The diagnosis is mainly based on symptoms, clinical findings, and complementary laboratory tests. It is a disease that most often affects women, at a time of life in which they are fertile, between 20 and 40 years. According to the Spanish Society of Rheumatology, lupus currently affects about 40,000 people in Spain. Coordinated by the Scientific Director of the INCLIVA Research Institute, Josep Redon, M.D., Ph.D., the project has focused on lupus patients with renal impairment (lupus nephritis), as, in the kidney, microRNAs play an indispensable role in regulating the mechanisms of development and maintenance renal function.

Chimpanzees Separated from Mothers in First Two Years of Life Show Impaired Social Behavior As Adults; Separated Chimps Who Have Since Lived in Social Groups for 40 Years Still Show Impaired Behavior

Wild-caught chimpanzees, who were orphaned and imported from Africa in their early infancy, exhibit impaired social behavior, even as adults, and even when living in social groups for many years. So far, long-term effects of early traumatic experiences on social behavior were known only for humans and socially isolated chimpanzees. An Austrian-Dutch research team, led by Elfriede Kalcher-Sommersguter, Ph.D., of the University of Graz and Jorg Massen. Ph.D., of both the University of Vienna and Utrecht University, published these results online on November 10, 2015 in Scientific Reports. The article is titled “Early Maternal Loss Affects Social Integration of Chimpanzees Throughout Their Lifetime.” Between 1950 and 1980, thousands of chimpanzee infants were wild-caught in West Africa and exported to Europe, Japan, and the USA, where these chimpanzees have been used in biomedical research. But also many zoos have wild-caught chimpanzees: the so-called founder populations. The new study shows that chimpanzees, who were maternally deprived within their first two years of life, were restricted in their social grooming behavior, even decades later. Social grooming is highly important for the establishment and maintenance of social relationships within groups of chimpanzees. "The orphaned chimpanzees had a lower number of partners they groomed and were less active than were chimpanzees reared by their mothers," says Dr. Kalcher-Sommersguter. These deficits in social grooming are found, not only in chimpanzees that were kept singly caged for decades in a biomedical laboratory, before being re-socialized, but also in individuals, who, after being orphaned, grew up in social groups in a zoo.

November 11th

Are You Listening, Vincent? DNA-Based Living Replica of van Gogh’s Ear on Exhibit in New York

Vincent van Gogh's ear is nearly as famous as his jaw-dropping painting Starry Night. Though its final resting place may never be found (as the legend goes, van Gogh severed off part of his ear and then gave it to a prostitute), museum-goers in New York can now get a look at the next best thing. ArtNet's Sarah Cascone reports that a living replica of van Gogh's ear, created using the artist's DNA, is now on display at Ronald Feldman Fine Arts in New York City. The ear is the gruesome brainchild of Diemut Strebe, a conceptual artist who partnered with scientists from MIT and other universities to create a copy of van Gogh's ear. Using DNA extracted from a stamp licked by the artist, as well as cell samples collected from van Gogh's great-great-grandnephew, Strebe and team created "Sugababe," an artificially grown ear suspended in a clear gel. Visitors don't have to merely look at the ear—they can talk into it, too. On her website, Strebe writes that "the input sound is connected to a computer processor, using a software program to generate simulated nerve impulses from the sound signal in real time. They mimic sounds recorded from an electrode inserted into the auditory nerve, when firing." Noam Chomsky was the first person to speak into the ear after it debuted in Germany last year. In a 2014 story about the bizarre art project, Cascone wrote that the ear is "just one of a limited edition." Neither van Gogh's relatives nor the Dutch museum that bears his name want copies of their own. If "Sugababe" is a slightly macabre commentary on fame and art, it is also a tribute to a world-famous artistic body part.

Sangamo BioSciences & USC Collaborate to Improve Zinc Finger Nuclease-Based Gene Editing for Hematopoietic Stem and Progenitor Cells (HPSCs)

Genome editing techniques for blood stem cells just got better, thanks to a collaborating team of researchers at the University of Southern California and Sangamo BioSciences. In a study published online on November 9, 2015 in Nature Biotechnology, co-first authors Colin M. Exline, Ph.D., from USC, and Jianbin Wang, Ph.D., from Sangamo BioSciences, describe a new, more efficient way to edit genes in blood-forming or "hematopoietic" stem and progenitor cells (HSPCs). The article is titled “Homology-Driven Genome Editing in Hematopoietic Stem and Progenitor Cells Using ZFN mRNA and AAV6 Donors.” "Gene therapy using HSPCs has enormous potential for treating HIV and other diseases of the blood and immune systems," said co-corresponding author Paula Cannon, Ph.D., Professor of Molecular Microbiology and Immunology, Pediatrics, Biochemistry and Molecular Biology, and Stem Cell Biology and Regenerative Medicine at USC. "And using genome editing techniques now allows us to make very precise changes that could repair genetic mutations -- the gene typos -- that can cause disease." Despite the enormous potential of such targeted gene medicine to cure patients, getting genome editing to work has proven challenging in human HSPCs -- especially in the most primitive, least differentiated cells with the greatest ability to become any blood cell type. Dr. Cannon's group, working with a team at Sangamo, has been using "genetic scissors" called zinc finger nucleases (ZFNs) to cut a cell's DNA at a precise location or sequence. The cell normally uses a copy of the cut DNA sequence as a template to repair the DNA break. During this process, there is the opportunity to introduce new DNA sequences or to repair mutations, effectively fooling the cell into making a genetic edit.

Unprecedented Diversity of Extracellular Vesicles (EVs) & Extracellular Compartments Seen in Human Ejaculates; New Cryo-EM & Tomography Study Published in Journal of Extracellular Vesicles

A new article, published online today (November 11, 2015) in an open-access article in the Journal of Extracellular Vesicles (JEV), reports that studies employing cryo-electron microsopy and tomography show what the authors describe as “an unprecedented diversity of extracellular structures in a single body fluid.” The extracellular environment of human ejaculate was revealed to be quite diverse and multi-faceted, with five major sub-categories of extracellular vesicles (EVs) and six sub-categories of extracellular membrane compartments, including lamellar bodies. Furthermore, three morphological features, including electron density, double-membrane bilayers, and coated surface, were described in all subcategories. The authors identified several novel morphological EV subcategories and suggested that clues to their cellular origin might be found in their morphology. This structural inventory, they added, will be important for developing future experimental approaches, and to interpret previously published data to understand the role of EVs in human male fertility. The new JEV article is titled “Diversity of Extracellular Vesicles in Human Ejaculates Revealed by Cryo-Electron Microscopy,” and was authored by Johanna L. Höög, Ph.D., and Jan Lötvall (photo), M.D., Ph.D., both of the University of Gothenburg in Sweden. Senior author Dr. Lotvall is a Swedish clinical allergist and scientist working on translational research primarily in the field of asthma. He is the Director of the Krefting Research Centre at the University of Gothenburg, and Professor of Allergology at this same institution. Dr.

CHOP-Led Study Suggests Safe Viruses Containing DNA Code for TPP1 Gene Can Be Injected into Brain Ventricles to Slow Childhood Batten Disease, a Rare and Currently Fatal Inherited Lysosomal Storage Disease

In a study of dogs, scientists showed that a new way to deliver replacement genes may be effective at slowing the development of childhood Batten disease, a rare and fatal neurological disease. The key may be to inject viruses that carry the codes for the gene products into the ventricles, which are fluid-filled compartments in the center of the brain that serve as a plumbing system. The study, published online on November 11, 2015 in Science Translational Medicine, was partially funded by the NIH. The article is titled “AAV Gene Transfer Delays Disease Onset in a TPP1-Deficient Canine Model of the Late Infantile Form of Batten Disease.” Batten disease is an inherited, autosomal recessive lysosomal storage disorder, one of a group of diseases that causes problems with a cell's ability to break down specific molecules. Early symptoms may include vision loss, subtle changes in personality and behavior, slow learning, clumsiness, or stumbling. Eventually, the children become blind, bedridden, and demented, and typically die within the first decade of their lives. Currently there are no effective treatments. "Our study opens up the possibility of a one-and-done treatment for this form of Batten disease," said Beverly Davidson (photo), Ph.D., Director of the Raymond G. Perelman Center for Cellular and Molecular Therapeutics at Children's Hospital of Philadelphia (CHOP) and the senior author of the study. Working with scientists at the University of Missouri-Columbia, Dr. Davidson's CHOP team focused on the late infantile form of the disease that starts in children 2 to 4 years of age and is most often caused by mutations in the gene for the soluble lysosomal enzyme tripeptidyl peptidase 1 (TPP1), an enzyme that degrades proteins.

Targeting Systolic Blood Pressure to Under 120 Reduces Rate of CVS Events Such As Heart Attack and Heart Failure, As Well As Stroke, by 25% in Those Over 50 with High BP; Rate of Death Reduced 27% by Lowering from 140 to Under 120

NIH-supported researchers are reporting more details on a landmark study that announced preliminary findings (see link below) in September, showing a lower-than-current-standard blood pressure target can save lives and reduce the risk of cardiovascular disease in a group of non-diabetic adults 50 years and older with high blood pressure. Results of the Systolic Blood Pressure Intervention Trial (SPRINT) appear in an open-access article published on November 9, 2015 in the New England Journal of Medicine and were discussed on at the American Heart Association 2015 Scientific Sessions in Orlando, Florida (November 7-11). The NEJM article is titled “A Randomized Trial of Intensive versus Standard Blood-Pressure Control.” Note that the NEJM article includes a video describing the new results—see link below. The study confirms that, in adults 50 years and older with high blood pressure, targeting a systolic blood pressure of less than 120 millimeters of mercury (mm Hg) reduced rates of cardiovascular events, such as heart attack and heart failure, as well as stroke, by 25 percent. Additionally, this target reduced the risk of death by 27 percent—as compared to a target systolic pressure of 140 mm Hg. The NEJM article is accompanied by an editorial titled “Redefining Blood-Pressure Targets — SPRINT Starts the Marathon” (see link below). “SPRINT is part of a proud legacy of NIH-funded clinical trials that will change clinical practice and save lives for decades to come. These results reinforce the compelling public health importance of enhancing the awareness, treatment, and control of hypertension in this country and around the world,” said Gary H. Gibbons, M.D., Director of the National Heart, Lung, and Blood Institute (NHLBI), the primary sponsor of SPRINT.

“World’s First End-to-End NGS Workflow" for Potential Use in Clinical Testing; QIAGEN Announces GeneReader NGS System; First Application Targets 12 Clinically Actionable Genes in Most Prevalent Types of Cancer; Broad Institute Presents Supportive Data

In a November 4, 2015 news release, QIAGEN N.V. (NASDAQ: QGEN) (Frankfurt Prime Standard: QIA) announced the start of commercialization activities for its GeneReader NGS System, the first complete Sample-to-Insight next-generation sequencing (NGS) solution designed for any laboratory to deliver actionable results. With the introduction of the GeneReader NGS System, QIAGEN is offering the world's first truly end-to-end NGS workflow from primary sample to a final report that provides a simpler, more cost-effective way for clinical testing to take advantage of NGS technology and improve outcomes. The first application for the GeneReader NGS System involves QIAGEN's new Actionable Insights Tumor Panel, the first member of the family of GeneRead QIAact Panels powered by QCI®. This novel gene panel targets 12 clinically actionable genes that are often analyzed in most prevalent types of cancer, including breast, ovarian, colorectal, lung, and melanoma. The panel can detect up to 1,250 different genetic mutations in a tumor sample. The most relevant variants - including those that are part of approved drug labels, reimbursement schemes, professional guidelines, and active phase III clinical trials - have been identified and selected using the QIAGEN Knowledge Base, the industry's largest collection of human-curated genomic findings and scientific literature. QIAGEN demonstrated demonstrate this integrated Sample-to-Insight™ workflow at the Association for Molecular Pathology (AMP) 2015 Annual Meeting from November 4-7 in Austin, Texas (http://www.amp.org/meetings/2015/), where commercialization of the GeneReader NGS System will be initiated.

November 10th

Liquid Biopsy of CSF for Circulating Brain-Tumor-Derived DNA Allows Less Invasive, More Effective Policing of Brain Tumors; CSF Is Far Better Source of Brain Tumor DNA Than Plasma; “Potential Game-Changer in Brain Cancer”

Vall d’Hebron Institute of Oncology (VHIO) in Barcelona, Spain is an institutional leader in research proposing cerebrospinal fluid (CSF) as liquid biopsy for the early diagnosis, prognosis, therapeutic management, and tracking of brain cancer. The exploitation of CSF-derived circulating DNA as liquid biopsy promises a more accurate, more effective, and less invasive approach to unmasking the molecular characteristics of brain tumors, the VHIO scientist believe. As reported in an open-access article published on November 10, 2015 in Nature Communications, the VHIO Gene Expression and Cancer Group, led by Joan Seoane, Ph.D., has pioneered research evidencing demonstrating the utility of cerebrospinal fluid (CSF) as liquid biopsy for the potential prognosis, treatment, identification, and tracking of brain tumor genomic alterations, not only in real time, but over time. Concentrations of circulating CNS-tumor-derived DNA are very low in plasma, but very high in CSF. The new article in Nature Communications is titled “Cerebrospinal Fluid-Derived Circulating Tumor DNA Better Represents the Genomic Alterations of Brain Tumors Than Plasma.” Dr. Seoane, the senior author of this article, is Director of Translational Research, VHIO; Head of the Gene Expression and Cancer Laboratory, VHIO, ICREA Professor, and Professor at the Universitat Autònoma de Barcelona (UAB), and he led the current study. The first author of the new article is Leticia De Mattos-Arruda (photo), M.D., a medical oncologist in Dr. Soane’s group. In addition to her affiliation with VHIO, Dr. Mattoa-Aruda is also affiliated with the Memorial Sloan Kettering Cancer Center (MSCC) in New York, and with the UAB in Barcelona.

Why Humans Like to Look at Attractive Faces--University of Oslo PhD Thesis

Few visual impressions can be compared to humans’ interest for faces. New research suggests that our brain rewards us for looking at pretty faces. A quick glimpse of a face provides us with rich information about the person in front of us. Are we acquainted? Man or woman? Happy or angry? Attractive? In her Ph.D. thesis, conducted at the Department of Psychology, University of Oslo in Norway, Olga Chelnokova (photo) has explored how our visual system is able to direct attention to the most important information in a face. Her study suggest that evolution has made us experts on faces. “We are very curious about others’ faces, we read stories in them and evaluate their aestetic value,” says Ms. Chelnokova. Together with colleagues from the research group Hedonic Pharmacology lab, she revealed that the brain reward system – a cluster of regions deep in our brain – is involved in our evaluation of other people’s attractiveness. “The reward system is involved in generating the experience of pleasure when, for instance, we enjoy tasty food or happen to win a lottery. It turns out that the same system is also engaged in creating the feelings of pleasure when we look at a pretty face,” Ms. Chelnokova says. Previous research has shown a high level of agreement between/among people when it comes to evaluating facial attractiveness. In the current study, the scientists let participants view images of faces pre-rated as most, intermediate, or less attractive. This was done after participants received a small dose of morphin, a drug that stimulates the reward system. “Participants rated the most attractive faces as even more attractive, and were willing to do more presses on the button that let them look at the picture for a longer time. They also spent more time looking at the eyes of the people in the pictures.”