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Archive - Aug 2015

August 14th

Octopus Genome Sequenced; Dramatic Expansion Seen in Family of Genes Involved in Neuronal Development; Scientists Wrap Arms Around Stunning Data; Nobelist Sydney Brenner Is Co-Author

The first whole genome analysis of an octopus reveals unique genomic features that likely played a role in the evolution of traits such as large complex nervous systems and adaptive camouflage. An international team of scientists sequenced the genome of the California two-spot octopus, the first cephalopod ever to be fully sequenced, and mapped gene expression profiles in 12 different tissues. The findings were published as the cover story (open-access) of the August 12, 2015 issue of Nature. The article is titled “The Octopus Genome and the Evolution of Cephalopod Neural and Morphological Novelties.” Renowned Nobelist Dr. Sydney Brenner is an author on this landmark paper. The researchers discovered striking differences from other invertebrates, including widespread genomic rearrangements and a dramatic expansion of a family of genes involved in neuronal development that was once thought to be unique to vertebrates. Hundreds of octopus-specific genes were identified, with many highly expressed in structures such as the brain, skin, and suckers. The results serve as an important foundation for evolutionary studies and deeper investigations into the genetic and molecular mechanisms that underlie cephalopod-specific traits. The work was conducted by teams from the University of Chicago; University of California, Berkeley; and Okinawa Institute of Science and Technology, as part of the Cephalopod Sequencing Consortium. "The octopus appears to be utterly different from all other animals, even other molluscs, with its eight prehensile arms, its large brain, and its clever problem-solving capabilities," said co-senior author Clifton Ragsdale, Ph.D., Associate Professor in the Departments of Neurobiology and Organismal Biology and Anatomy at the University of Chicago.

Landmark Transcriptome Analysis Reveals Unexpected Metabolic Capabilities for Carbohydrate and Natural Product Biochemistry in “Simple” Pond-Dwelling Euglena; Many New Euglena-Derived Products Envisioned

Scientists at the John Innes Centre (JIC) in the Norwich, UK have discovered that Euglena gracilis, the single-cell algae that inhabits most garden ponds, has a whole host of newly identified, unclassified genes that can make new forms of carbohydrates and natural products. Even with the latest technologies, sequencing all the DNA in Euglena remains a complex and laborious undertaking. Dr. Ellis O’Neill and Professor Rob Field from the JIC in Norwich, UK, together with colleagues, have therefore sequenced the transcriptome of Euglena gracilis, which provides information about all of the genes that the organism is actively using to make proteins. From this analysis of its protein-coding mRNA molecules, Professor Field and his team projected that Euglena has at least 32,000 active, protein-coding genes, significantly more than humans, who have approximately 21,000 such genes. The researchers discovered that Euglena has the genetic information to make many different natural compounds; we simply don’t yet know what they are or what they can do. Nearly 60% of the active genes don’t match those found in any other organism studied to date, suggesting that there is much to learn about the biology of Euglena. The new research was published online on August 13, 2015 in Molecular BioSystems. The article is titled “The Transcriptome of Euglena gracilis Reveals Unexpected Metabolic Capabilities for Carbohydrate and Natural Product Biochemistry.” The team also found that different sets of genes become active when Euglena is grown in the dark as opposed to when it is grown in the light. This indicates that Euglena can dramatically shift its metabolism depending on its environment, which reflects its ability to live successfully in many highly varied environments.

August 13th

Toward Permanent Engineered Solutions to Genetic Diseases; New Advance Enables Evolution of More Targeted Gene Editing Tools; Continuous Directed Evolution of DNA-Binding Proteins Improves TALEN Specificity 100-Fold

In his mind, Dr. Basil Hubbard can already picture a new world of therapeutic treatments for millions of patients just over the horizon. It's a future in which diseases like muscular dystrophy, cystic fibrosis, polycystic kidney disease (PKD), and many others may be treated permanently through the science of genome engineering. Thanks to his latest work, Dr. Hubbard is bringing that future closer to reality. His latest research, published online on August 10, 2015 in Nature Methods, demonstrates a new technology advancing the field of genome engineering. The method significantly improves the ability of scientists to target specific faulty genes, and then "edit" them, replacing the damaged genetic code with healthy DNA. "There is a trend in the scientific community to develop therapeutics in a more rational fashion, rather than just relying on traditional chemical screens," says Dr. Hubbard, now an Assistant Professor of Pharmacology in the University of Alberta's Faculty of Medicine & Dentistry. "We're moving towards a very logical type of treatment for genetic diseases, where we can actually say, 'Your disease is caused by a mutation in gene X, and we're going to correct this mutation to treat it'. In theory, genome engineering will eventually allow us to permanently cure genetic diseases by editing the specific faulty gene(s)." The Nature Methods article is titled “The article is titled “Continuous Directed Evolution of DNA-binding Proteins to Improve TALEN Specificity.” Genome engineering involves the targeted, specific modification of an organism's genetic information. Much as a computer programmer edits computer code, scientists could one day replace a person's broken or unhealthy genes with healthy ones through the use of sequence-specific DNA-binding proteins attached to DNA-editing tools.

Exosome Diagnostics Launches CLIA-Certified Laboratory in Cambridge, MA; Company Uses Exosome-Based Platform for Detection of Exosomal RNA and Cell-Free DNA; Cancer Liquid Biopsy Test to Launch Later in 2015

Exosome Diagnostics, Inc., a developer of revolutionary, biofluid-based molecular diagnostics, today announced, August 12, 2015, that it has opened a Clinical Laboratory Improvement Amendments (CLIA)-Certified laboratory in Cambridge, Massacusetts (near Boston). The state-of-the-art clinical services laboratory will manage analysis and reporting for several liquid biopsy tests that the company plans to launch this year for prostate, lung, and other solid tumor cancers. These novel diagnostics will help clinicians detect disease sooner and obtain access to real-time molecular insights that can help better inform treatment decisions for patients with cancer and other serious diseases. “Exosome Diagnostics is dedicated to effectively solving challenges in health care and overcoming barriers to disease detection, monitoring, and treatment,” said Thomas McLain, CEO of Exosome Diagnostics. “We are taking this important step to centralize our operations at our U.S. corporate headquarters in Cambridge, as we work to seamlessly launch new molecular diagnostics, while also accelerating the application of our technology platform to other important disease areas.” Exosome Diagnostics is currently developing a suite of innovative plasma- and urine-based liquid biopsies that analyze exosomal RNA (exoRNA) for biomarkers. The company’s technology platform is uniquely versatile, offering the additional capability to simultaneously isolate and analyze exoRNA and cell-free DNA (cfDNA) to enhance detection of rare mutations. Exosomes are messenger-containing or bearing vesicles released by all living cells into biofluids, such as plasma/serum, urine, cerebrospinal fluid, and saliva. Exosomes can, and often do, contain RNA, DNA and proteins from their cell of origin.

Clinical Next-Gen Sequencing Reveals Ancient Origins and Evolution of Deadly Lassa Virus

Working as part of an international team in the United States and West Africa, a researcher at The Scripps Research Institute (TSRI) has published new findings showing the ancient roots of the deadly Lassa virus, a relative of Ebola virus, and how Lassa virus has changed over time. “This gives us a clear view of how the virus is evolving, which is important to know as we develop vaccines and therapies,” said TSRI biologist Dr. Kristian G. Andersen, a lead author of the new study. At least 5,000 people die each year from Lassa fever. The virus is spread through contact with urine and droppings from infected Mastomys natalensis rodents (sometimes called “multimammate rats” or “multimammate mice” because of the female’s multiple and prominent mammary glands), which are a natural “reservoir” of the virus, and the disease can spread from human to human. In the new study, published as the cover story of the August 13, 2013 issue of the prestigious journal Cell, the international research team used a technique called next-generation sequencing to analyze genomes of Lassa virus samples taken from wild Mastomys natalensis and human patients in Nigeria and Sierra Leone. —whose senior members included Dr. Pardis Sabeti and Dr. Joshua Levin of Harvard University and the Broad Institute, Dr. Robert F. Garry of Tulane University and Dr. Christian Happi of Nigeria’s Irrua Specialist Teaching Hospital and Sierra Leone’s Kenema Government Hospita. The article is titled “Clinical Sequencing Uncovers Origins and Evolution of Lassa Virus.” The genomic data showed that far-flung strains of Lassa virus share a common ancestor that can be traced back more than 1,000 years to an area today known as Nigeria. This surprised the researchers, as Lassa fever was first described in Nigeria only in 1969. “The virus has very ancient roots,” said Dr. Andersen.

August 12th

Mysterious Altitude Changes in Nighttime Flight Paths of Migrating Songbirds

A new mystery has been discovered in the migratory behavior of birds! Many songbirds travel long distances during their annual migrations, and it makes sense for them to do everything they can to conserve their energy during these journeys. Researchers have guessed that, for this reason, they might pick an altitude with favorable winds and stick with it rather than climbing and descending repeatedly, but there has been little data to back this up. In a study published online on August 12, 2015 in an open-access article in The Auk: Ornithological Advances, presenting the first full-altitude flight data for migrating songbirds, Dr. Melissa Bowlin of the University of Michigan-Dearborn and colleagues used radio transmitters to track the altitudes of migrating Swainson's thrushes (Catharus ustulatus)(image) and were surprised to find that the thrushes actually made repeated altitude adjustments of more than 100 meters over the course of their nighttime migratory flights. The reasons for these altitude changes are not clear, but the researchers have a few theories. The new article is titled “"Unexplained Altitude Changes in a Migrating Thrush: Long-Flight Altitude Data from Radiotelemetry.” Funded in part by the National Geographic Society, Dr. Bowlin and her colleagues captured 9 Swainson's thrushes in a small forest fragment in Illinois during spring migration season in 2011-13, outfitted them with transmitters, and followed them with a radio-tracking vehicle to gather altitude data once they took off on a migratory flight. "I really thought that the birds would mostly behave like commercial aircraft, ascending to a particular altitude, leveling off and cruising near that altitude, and then coming down just before they landed," explains Dr. Bowlin.

Hopkins Scientists Identify Nerve-Guiding Protein (Semaphorin 3D) That Aids Pancreatic Cancer Metastasis; Exosome Involvement a Possibility

Scientists at the Johns Hopkins Kimmel Cancer Center have identified a molecular partnership in pancreatic cancer cells that might help to explain how the disease spreads (metastasizes) in some cases. Their findings reveal urgently needed new targets to treat pancreatic cancer, which strikes nearly 50,000 people in the U.S. each year and has only a 5 percent survival rate five years after diagnosis. One of the molecular partners is annexin A2, a protein that scientists say was already linked to poor survival rates in these cancers. In a report published in the August 4, 2015 issue of Science Signaling, Lei Zheng, M.D., Ph.D., and his colleagues show that annexin A2 helps usher a protein called semaphorin 3D (Sema3D) out of pancreatic cancer cells. Once outside the cells, Sema3D joins with another molecule (plexin D1) to fuel the cancer's spread. The new article is titled “Semaphorin 3D Autocrine Signaling Mediates the Metastatic role of *Annexin A2 in Pancreatic Cancer.: Sema3D is a protein that guides the projecting arms of nerve cells, called axons, as the nerve cells grow and develop. In experiments with mice, the researchers calculated a seventy-fold drop in the amount of Sema3D secreted from mouse pancreatic cancer cells in animals that lacked annexin A2. In an experiment involving 23 mice, none of the annexin-free animals developed visible metastatic tumors. By contrast, 16 out of 17 mice that produced annexin A2 in their cells developed metastatic tumors in the liver, lungs or abdominal cavity. In a second group of experiments using human tissue from patients with pancreatic ductal adenocarcinoma, which accounts for more than 90 percent of pancreatic cancers, Dr.

Unique Scent Profile Is Crucial to Mother Antarctic Fur Seal Re-Locating Her Pup on Beach After Return from Food-Gathering Trips into Ocean

Researchers studying Antarctic fur seals have discovered the seals’ scent has a unique “profile” which enables them to recognize their offspring and family members. Until now, researchers had thought voice recognition was the most important means for finding their young, but now it is proven that scent also plays a crucial role. The results were published online on August 10, 201510 in PNAS. The article is titled “Chemical Fingerprints Encode Mother-Offspring Similarity, Colony Membership, Relatedness and Genetic Quality in Fur Seals.” The sense of smell and an animal’s scent is an important means of communication in the animal kingdom. This applies not only to social interactions, but also to territorial behavior, recognizing kin, and selecting a mate. However, understanding communication by smell is very challenging because of the mixture of chemicals on an animal’s skin. The odor emitted may be affected by hormones, the microbial flora, body condition and health, and environmental factors. A team of scientists from the Bielefeld University and the British Antarctic Survey sampled the skin and fur from dozens of mothers and their pups from two different fur seal colonies on the breeding beaches at Bird Island Research Station near the sub Antarctic Island of South Georgia. They found the scent of mothers and pups had similar characteristics. Dr. Martin Stoffel, lead author from Bielefeld University says: “Our results are surprising for a marine animal that spends more than 80% of its time at sea. They show that fur seal pups smell similar to their mothers, as many of the chemicals on their skin are shared and genetically encoded.

August 11th

Loss of mGluR5 Receptors from Key Inhibitory Brain Neurons (Parvalbumin-Positive Interneurons) May Be at Root of Many Neurodevelopmental Disorders, Including Autism and Schizophrenia; Receptor Loss May Be Reversible

The loss of a critical receptor in a special class of inhibitory neurons in the brain may be responsible for neurodevelopmental disorders including autism and schizophrenia, according to new research by researchers from the Salk Institute for Biological Sciences and the University of California, San Diego (UCSD). The importance of the receptor, called mGluR5, in other areas of the brain had been previously established. Until now, however, no one had studied the receptor’s specific role in a cell type known as parvalbumin-positive interneurons, thought to be important in general cognition and generating certain types of oscillatory wave patterns in the brain. "We found that without this receptor in the parvalbumin cells, mice have many serious behavioral deficits," says Dr. Terrence Sejnowski, head of Salk's Computational Neurobiology Laboratory, which led the research published online in Molecular Psychiatry on August 11, 2015. "And a lot of them really mimic closely what we see in schizophrenia." The article is titled “Disruption of mGluR5 in Parvalbumin-Positive Interneurons Induces Core Features of Neurodevelopmental Disorders.” Scientists had previously discovered that when molecular signaling was disrupted in these cells during development, the brain's networks did not form correctly. Separate studies have revealed that mGluR5 receptors, which transmit glutamate signaling in the brain, are linked to addiction disorders, anxiety, and fragile X syndrome. But, in those cases, mGluR5 is affected in excitatory cells, not inhibitory cells like the parvalbumin-positive interneurons. The Salk team wondered what the role of mGluR5 was in the parvalbumin cells because these cells are deemed so important in brain development. The scientists partnered with Dr.

Polyglutamine Repeats Play Key Role in Normal Functional Development; Often Found in Proteins With Regulatory Functions; Act As Tuning Dial; Repeat Number Modulates Transcriptional Responses of Genes; Too Many Repeats Can Cause Diseases Like Huntington’s

Scientists at VIB (Flanders Interuniversity Institute for Biotechnology) and KU Leuven (Katholieke Universiteit Leuven) in Belgium have discovered that variable repeats in the triplet nucleotide code (CAG) for the amino acid glutamine tune the function of the protein in which the resulting polyglutamine residues (e.g., the huntingtin protein of Huntington’s disease). To date, these repeats were known only to cause severe neurodegenerative diseases such as Huntington’s. The new findings from Belgium show that polyglutamine repeats may be more than just harmful elements. The study was published online on August 6, 2015 in an open-access article in Molecular Cell and opens the door to further studies exploring new therapies for human polyglutamine repeat diseases. Moreover, this study lays the foundation for future research into the role of repeats in the emergence and evolution of novel functions and life forms. The Molecular Cell article is titled “Variable Glutamine-Rich Repeats Modulate Transcription Factor Activity.” Excessive numbers of glutamine-rich repeats in various human proteins are known to result in severe neurodegenerative disorders such as Huntington’s disease. Little is known, however, about the physiological role of these repeats and the consequences of more moderate repeat expansions. Dr. Rita Gemayel (VIB/KU Leuven) said, “We found that the polyglutamine repeats act like the dial on a tuner. The length of the repeat modulates the transcriptional response of genes in the cell. More specifically, using a polyglutamine-containing protein called Ssn6 as a model, we showed that the repeat length modulates the solubility of Ssn6 and its interaction with other proteins.