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Archive - Sep 2015

September 22nd

Particular Genotype for Serotonin Transporter Gene Magnifies Psychological Impact of Life Events, for Better and Worse, New Study Shows

People with a certain geneotype for a particular serotonin transporter gene are more deeply affected by their life experiences, a new study has revealed. The findings challenge traditional thinking about depression, showing that what might be considered a risk gene for depression in one context, may actually be beneficial in another. Researchers at the University of Melbourne in Australia were interested in why some, but not all, adults who have experienced sexual or physical abuse as children go on to develop long-term depression. The research, published in an open-access article in the September 2015 issue of the British Journal of Psychiatry Open focused on a particular gene, known as the sodium-dependent serotonin transporter (SLC6A4) gene, that codes for a protein that transports the mood-regulating chemical serotonin. Due to length polymorphisms (short and long) in the 5′-flanking promoter region (5-HTT gene-linked polymorphic region, 5HTTLPR) of the SLC6A4 gene, every person has one of three possible SLC6A4 genotypes for his or her two alleles for the SLC6A4 gene: either the long-long (l/l) genotype, the short-long (s/l) genotype, or the short-short (s/s) genotype. The new research article is titled “Serotonin Transporter Polymorphism (5HTTLPR), Severe Childhood Abuse and Depressive Symptom Trajectories in Adulthood.” The team tested the DNA of 333 middle-aged Victorians of Northern and Western European ancestry. [It is important to note that the participants in this study were of Northern and Western European descent, as there are substantial differences in prevalence of the s/s genotype in different populations.] The scientists also recorded these subjects’ depressive symptoms each year over a five-year period.

September 22nd

Advance of Destructive Moth Threatens $2 Billion US Tomato Industry

The rapid spread of a highly destructive invasive moth species that threatens tomato crops has prompted a Virginia Tech scientist to lead the charge in issuing a set of recommendations, including quarantine measures, designed to thwart the advance of the pest around the globe, according to a September 22, 2015 press release from Virginia Tech. The insect – established in Panama and Costa Rica – is moving northward, but has not yet arrived in the United States. Its potential arrival is a big concern among U.S. government agricultural officials. "Our domestic tomato industry could be severely affected," said Dr. Devaiah Muruvanda, Senior Risk Manager for the U.S. Department of Agriculture, says. "The United States is taking it so seriously, we haven’t even given permits to do research, in order to prevent any possibility of the insect's escape." The pest in question is the South American tomato leafminer, Tuta absoluta. No larger than an eyelash, the tiny moth spread from its native Latin America to Europe in 2006 and later crossed the Mediterranean to Africa. Now threatening Asia, the moth strikes at the world’s most commercially important horticulture crop – the tomato, valuable to farmers around the world. The pest’s path is destructive and its advance is rapid, as it has moved from Spain in 2006 through Europe, the Middle East, Africa, and India. "When the tomato leafminer strikes, it can cause between 80 and 100 percent crop loss unless proper management technologies are adopted," says Dr. Muni Muniappan, entomologist and Director of the Virginia Tech-led Integrated Pest Management Innovation Lab. "The moth can’t be completely eradicated. The best you can do is control it." Dr. Muniappan convened a group of plant protection scientists at the 18th International Plant Protection Congress in Berlin in August.

Dr. Albert La Spada Receives $900,000 Gund-Harrington Scholar Award to Advance His Work on Spinocerebellar Ataxia Type 7 (SCA7), a Genetic Triplet-Repeat Expansion Disorder Like Huntington’s Disease

Albert La Spada, M.D., Ph.D., Professor of Pediatrics, Cellular and Molecular Medicine, and Neurosciences at the University of California, San Diego (UCSD) School of Medicine, has received a 2015 Harrington Scholar award to advance his work on a therapy for spinocerebellar ataxia type 7 (SCA7), a rare but devastating neurological disorder that can lead to blindness and progressive loss of physical coordination. Dr. La Spada, Chief of the Division of Genetics in the Department of Pediatrics at the UCSD School of Medicine, received a $900,000 award toward further development of a treatment which blocks the gene mutation underlying SCA7. The research may also have implications for Huntington's disease and amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, which are neurodegenerative disorders with similar types of genetic mutations. The scholar award is given by the Harrington Discovery Institute at University Hospitals in Cleveland, which collaborates with various organizations to accelerate the development of promising research by physician-scientists. In particular, the funding helps researchers to bridge the gap from basic research to clinical application, known as the "Valley of Death," which can keep innovative discoveries from advancing far enough to attract pharmaceutical drug development. Dr. La Spada, who is also at Rady Children's Hospital-San Diego, was one of three inaugural Gund-Harrington Scholars, named after Gordon Gund, founder of the Foundation Fighting Blindness, a consortium of groups funding research in the area of degenerative retinal diseases. "People with this disorder (SCA7) have trouble walking, talking, seeing - anything that requires coordinated movement," said Dr. La Spada.

Aspirin-Related Arthritis Drug Targets Tau Acetylation and Reverses All Aspects of Tau Toxicity in Animal Model of Dementia; May Prove Effective Prevention/Treatment Option for Alzheimer’s; Immediate Clinical Implications Possible

Scientists from the Gladstone Institutes in San Francisco, California, together with collaborators from Stanford, UCSF, Buck Institute for Research on Aging, and UCSD, have discovered that salsalate, a drug used to treat rheumatoid arthritis and a chemical relative of aspirin, effectively reversed tau-related dysfunction in an animal model of frontotemporal dementia (FTD). Salsalate prevented the accumulation of tau in the brain and protected against cognitive impairments resembling impairments seen in Alzheimer's disease and FTD. Salsalate inhibits tau acetylation, a chemical process that can change the function and properties of a protein. In results published online on September 21, 2015 in Nature Medicine, the researchers revealed that acetylated tau is a particularly toxic form of the protein, driving neurodegeneration and cognitive deficits. Salsalate successfully reversed these toxic effects in a mouse model of FTD, lowering tau levels in the brain, rescuing memory impairments, and protecting against atrophy of the hippocampus--a brain region essential for memory formation that is impacted by dementia. The Nature Medicine article is titled “Critical Role of Acetylation in Tau-Mediated Neurodegeneration and Cognitive Deficits.” "We identified, for the first time, a pharmacological approach that reverses all aspects of tau toxicity," says co-senior author Li Gan, Ph.D., an Associate Investigator at the Gladstone Institutes. "Remarkably, the profound protective effects of salsalate were achieved even though it was administered after disease onset, indicating that it may be an effective treatment option." Although tau has been a target in dementia research for some time, there are no tau-targeted drugs available for patients.

Exosomal RNA-Based Urine Liquid Biopsy Test Detects High-Grade Prostate Cancer With 97.5% Accuracy Prior to Initial Biopsy; Initial Positive Clinical Study Results Published; Novel Test Has Potential to Stem Tide of Unnecessary Initial Prostate Biopsies

On Monday, September 21, 2015, Exosome Diagnostics, Inc., a Cambridge, Massachusetts-based developer of revolutionary, biofluid-based molecular diagnostics, announced the publication of positive data from its initial clinical study of ExoIntelliScore™ Prostate (previously referred to as EXO 106), the first-catch-urine-based, three-gene-signature liquid biopsy test that does not require a digital rectal exam (DRE) or prostate massage before sample collection showing that the test results can predict high-grade prostate cancer (Gleason score ≥ 7) with 97.5 percent accuracy prior to initial biopsy. The paper in which the results are published is titled “A Molecular Signature of PCA3 and ERG Exosomal RNA from Non-DRE Urine Is Predictive of Initial Prostate Biopsy Result.” It was published online on September 8, 2015 in Prostate Cancer and Prostatic Diseases, a peer-reviewed journal of the Nature Publishing Group. Distinct from all other predictive tests on the market or in clinical development for prostate cancer, ExoIntelliScore Prostate is the first assay to give urologists and their patients molecular insights about prostate cancer using exosomal RNA (exoRNA). The test involves patients giving a simple, first-catch urine sample without having to first undergo a digital rectal exam (DRE). ExoIntelliScore™ Prostate is poised to drive a new prognostic paradigm in which the aggressiveness of prostate cancer can be predicted completely non-invasively from genetic-based information ahead of initial prostate biopsy. For men demonstrating a low-risk for aggressive disease using the assay, urologists may determine that an initial prostate biopsy is not warranted.

September 21st

Genes from Parasitic Wasps Are Present in Many Butterflies Following Integration of Wasp-Associated Bracoviruses into Butterfly Genomes During Parasitization Process

Research teams from the University of Valencia in Spain and the University of Tours in France have discovered that genes originating from parasitic wasps are present in the genomes of many butterflies. These genes were acquired through a wasp-associated virus that integrates into DNA. Wasp genes have now been domesticated and likely play a role in in protecting butterflies against other pathogenic viruses. These results, published online in the open-access journal PLOS Genetics on September 17, 2015, reveal that butterflies, including the Monarch, an iconic species for naturalists and well-known for its spectacular migrations, constitute naturally produced genetically modified organisms (GMOs) during the course of evolution. This finding “relativizes” the novelty of producing GM insects, because such insects already exist in nature, but also highlights that genes introduced in GM insects can be transferred between distant species. The PLOS Genetics article is titled “Recurrent Domestication by Lepidoptera of Genes from Their Parasites Mediated by Bracoviruses.” To reproduce, braconid wasps lay their eggs inside caterpillars and inject a “giant virus” named bracovirus to circumvent the caterpillars' immune response. Bracoviruses can integrate into the DNA of parasitized caterpillars and control caterpillar development, enabling wasp larvae to colonize their host. Bracovirus genes can be detected in the genomes of several species of butterfly and moth, including the famous Monarch (Danaus plexippus), the silkworm (Bombyx mori), and insect pests such as the Fall Armyworm (Spodoptera frugiperda) and the Beet Armyworm (Spodoptera exigua).

Modular System of Zinc Finger Proteins, Inteins, and Exteins Can Detect Any Particular DNA Sequence in Cells and Trigger a Specific Response Such As Cell Death

MIT biological engineers have developed a modular system of proteins that can detect a particular DNA sequence in a cell and then trigger a specific response, such as cell death. This system can be customized to detect any DNA sequence in a mammalian cell and then trigger a desired response, including killing cancer cells or cells infected with a virus, the researchers say. “There is a range of applications for which this could be important,” says Dr. James Collins, the Termeer Professor of Medical Engineering and Science in MIT’s Department of Biological Engineering and Institute of Medical Engineering and Science (IMES). “This allows you to readily design constructs that enable a programmed cell to both detect DNA and act on that detection, with a report system and/or a respond system.” Dr. Collins is the senior author of an article published online on September 21, 2015 in Nature Methods paper describing the technology, which is based on a type of DNA-binding proteins known as zinc fingers. The article is titled “DNA Sense-and-Respond Protein Modules for Mammalian Cells.” These zinc finger proteins can be designed to recognize any DNA sequence. “The technologies are out there to engineer proteins to bind to virtually any DNA sequence that you want,” says Dr. Shimyn Slomovic, an IMES postdoc and the paper’s lead author. “This is used in many ways, but not so much for detection. We felt that there was a lot of potential in harnessing this designable DNA-binding technology for detection.” To create their new system, the researchers needed to link zinc fingers’ DNA-binding capability with a consequence — either turning on a fluorescent protein to reveal that the target DNA is present or generating another type of action inside the cell.

Epicardial Protein FSTL1 Stimulates Heart Muscle Regeneration and Scarring Reduction Following Heart Attack; FSTL1 Patch Implanted in Heart Improves Cardiac Function and Survival Rates in Animal Models; Team Working Toward 2017 Human Clinical Trials

An international team of researchers has identified a protein that helps heart muscle cells regenerate after a heart attack. Researchers also showed that a patch loaded with the protein and placed inside the heart improved cardiac function and survival rates after a heart attack in mice and pigs. Animal hearts regained close to normal function within four to eight weeks after treatment with the protein patch. It might be possible to test the patch in human clinical trials as early as 2017. The team, led by Professor Pilar Ruiz-Lozano at Stanford University and including researchers from the University of California, San Diego (UC San Diego) and Sanford Burnham Prebys Medical Discovery Institute (SBP), published its findings online on September 16, 2015 in Nature. The article is titled “Epicardial FSTL1 Reconstitution Regenerates the Adult Mammalian Heart.” "We are really excited about the prospect of bringing this technology to the clinic," said Dr. Mark Mercola, Professor of Bioengineering at UC San Diego and Professor in the Development, Aging, and Regeneration Program at SBP. "It's commercially viable, clinically attractive, and you don't need immunosuppressive drugs." High-throughput technology in Dr. Mercola's lab was critical in identifying a natural human protein, called follistatin-like 1 (FSTL1), and showing that it can stimulate cultured heart muscle cells to divide. Researchers, led by Dr. Ruiz-Lozano, at Stanford embedded the protein in a patch and applied it to the surface of mouse and pig hearts that had undergone an experimental form of myocardial infarction or "heart attack." Remarkably, FSTL1 caused heart muscle cells already present within the heart to multiply and re-build the damaged heart and reduce scarring.

September 19th

Serum Exosomal MicroRNAs May Be Novel Biomarkers for Hepatocellular Carcinoma (HCC)

In an open-access article published online on September 18, 2015 in Experimental & Molecular Medicine, scientists from Sungkyunkwan University School of Medicine in Seoul, Korea, show that levels of the serum exosomal microRNAs miR-18a, miR-221, miR-222, and miR-224 were significantly higher in patients with hepatocellular carcinoma (HCC) than in patients with either chronic hepatitis B (CHB) or liver cirrhosis (LC). Meanwhile, the scientists also showed that that the serum exosomal levels of miR-101, miR-106b, miR-122, and miR-195 were lower in those with HCC than in those with CHB. The scientists conclude that their data suggests that serum exosomal microRNA may be used as novel biomarkers for HCC. The EMM article is titled “Serum Exosomal MicroRNAs As Novel Biomarkers for Hepatocellular Carcinoma.”

[Experimental & Molecular Medicine article]

3.5-Billion-Year-Old Tree of Life Contains 2.3 Million Named Species; First Attempt at Comprehensive Tree Ever Released; First Draft Is Compiled from Digitally Available Smaller Trees; Tens of Millions of Species Estimated to Have Lived on Earth

A first draft of the "tree of life" for the roughly 2.3 million named species of animals, plants, fungi, and microbes has been released. A collaborative effort among eleven institutions, the tree depicts the relationships among living things as they diverged from one another over time, tracing back to the beginning of life on Earth more than 3.5 billion years ago. Tens of thousands of smaller trees have been published over the years for select branches of the tree of life -- some containing upwards of 100,000 species -- but this is the first time those results have been combined into a single tree that encompasses all of life. The end result is a digital resource that is available free online for anyone to use or edit, much like a "Wikipedia" for evolutionary trees. "This is the first real attempt to connect the dots and put it all together," said principal investigator Dr. Karen Cranston of Duke University. "Think of it as Version 1.0." The current version of the tree -- along with the underlying data and source code -- is available to browse and download at https://tree.opentreeoflife.org. It is also described in an open-access article appearing online on September 18, 2015 in PNAS. The article is titled “Synthesis of Phylogeny and Taxonomy Into a Comprehensive Tree of Life.” Evolutionary trees, branching diagrams that often look like a cross between a candelabra and a subway map, aren't just for figuring out whether aardvarks are more closely related to moles or manatees, or pinpointing a slime mold's closest cousins. Understanding how the millions of species on Earth are related to one another helps scientists discover new drugs, increase crop and livestock yields, and trace the origins and spread of infectious diseases such as HIV, Ebola, and influenza.