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Archive - Apr 6, 2017

Discovery of Congenital Blindness Gene in Zebrafish Could Provide Useful Model for Better Understanding of Inherited Blindness Disease (LCA) in Human Children

Newborns can be at risk of congenital blindness, presenting sight defects due to lesions or to genetic mutations in their genome. Among the latter, Leber congenital amaurosis -- or LCA -- is one of the most widespread causes of child blindness and accounts for nearly 5% of vision impairments overall. The syndrome can be genetically transmitted to a child when both parents possess at least one dysfunctional copy of a gene involved in eye development. However, the molecular mechanism behind the disease remains unclear. Now OIST researchers in the Developmental Neurobiology Unit at the Okinawa Institute and Technology (OIST) have exposed a similar syndrome in zebrafish, which are an excellent model for studying human diseases. From this research, published online on April 5, 2017 in Scientific Reports, scientists aim to unravel the causes behind the disease in zebrafish and therefore provide new leads for a treatment for human LCA. The open-access article is titled “Aipl1 Is Required for Cone Photoreceptor Function and Survival Through the Stability of Pde6c and Gc3 in Zebrafish.” LCA affect the retina, the thin layer of tissue at the back of the eye that detects light as well as differentiates colors and communicates the information to the brain via the optic nerve. A healthy retina usually features light-sensitive cells -- photoreceptors -- called cones and rods. Cones are specialized in bright environment and detect colors while rods are used in dim light but are monochrome, which is why we see in black and white at night. A person with LCA will display deformed or absent cones and rods, thus preventing the detection of light.

Squid Trade Genome Evolution for Prolific RNA Editing: Over 60% of RNA Transcripts in Squid Brain Are Recoded by Editing Versus <1% in Humans

Octopus, squid, and cuttlefish are famous for engaging in complex behavior, from unlocking an aquarium tank and escaping, to instantaneous skin camouflage to hide from predators. A new study suggests their evolutionary path to neural sophistication includes a novel mechanism: prolific RNA editing at the expense of evolution in their genomic DNA. The study, led by Joshua J.C. Rosenthal, Ph.D., of the Marine Biological Laboratory (MBL), Woods Hole; and Eli Eisenberg, Ph.D., and Noa Liscovitch-Brauer, Ph.D., of Tel Aviv University, was published on April 6, 2017 in Cell. The open-access featured article is titled “Trade-Off Between Transcriptome Plasticity and Genome Evolution in Cephalopods.” The research builds on the scientists' prior discovery that squid display an extraordinarily high rate of editing in coding regions of their RNA -- particularly in nervous system cells -- which has the effect of diversifying the proteins that the cells can produce. (More than 60 percent of RNA transcripts in the squid brain are recoded by editing, while in humans or fruit flies, only a fraction of 1 percent of their RNAs have a recoding event.) In the present study, the scientists found similarly high levels of RNA editing in three other "smart" cephalopod species (two octopus and one cuttlefish) and identified tens of thousands of evolutionarily conserved RNA recoding sites in this class of cephalopods, called coleoid. Editing is especially enriched in the coleoid nervous system, they found, affecting proteins that are the key players in neural excitability and neuronal morphology. In contrast, RNA editing in the more primitive cephalopod Nautilus and in the mollusk Aplysia occurs at orders of magnitude lower levels than in the coleoids, they found.

FDA Approves AUSTEDO™ Tablets for Treatment of Chorea Associated with Huntington’s Disease

On April 3, 2017, Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) in Israel announced that the U.S. Food and Drug Administration (FDA) has approved AUSTEDO™ (deutetrabenazine) tablets for the treatment of chorea associated with Huntington’s disease (HD). Teva is the world’s largest generic medicines producer. Previously referred to by the developmental name SD-809, AUSTEDOTM is the first deuterated product approved by the FDA and only the second product approved in HD. The product was previously granted Orphan Drug Designation by the FDA. A rare and fatal neurodegenerative disorder, HD affects more than 35,000 people in the United States. Chorea – involuntary, random, and sudden, twisting and/or writhing movements – is one of the most striking physical manifestations of this disease and occurs in approximately 90% of patients. “Chorea is a major symptom for many living with Huntington disease. It impacts patients’ functionality and activities of daily living, and there have been limited treatment options for these patients,” said Michael Hayden, M.D., Ph.D., President of Global R&D and Chief Scientific Officer at Teva. “Based on the results demonstrated in the clinical development program which supported the approval of AUSTEDO™ and our ongoing commitment to patients, we feel uniquely positioned to bring this treatment option forward.” The FDA approval was based on results from a Phase III randomized, placebo-controlled study to assess the safety and efficacy of AUSTEDO™ in reducing chorea in patients with HD (First-HD). “At Teva, we have a long history of establishing comprehensive disease management programs in chronic disease areas.

New Tool Illuminates Cell Signaling Pathways Key to Disease, Likely to Advance Study of Cellular Processes in Major Psychiatric Disorders, Opioid Addiction, and Host Of Other Diseases

In a major advance for fundamental biological research, University of California (UC) San Francisco (UCSF) scientists have developed a tool capable of illuminating previously inscrutable cellular signaling networks that play a wide variety of roles in human biology and disease. In particular, the technique opens up exciting new avenues for understanding and treating psychiatric disease, the researchers say. The new technology, described in a paper published on April 6, 2016 in Cell, makes it vastly easier for scientists to study the complex workings of a large family of sensor proteins called G-protein-coupled receptors (GPCRs), which sit in cell membranes and enable cells to respond to chemical signals from other parts of the body or the outside world. In a first proof-of-principle study, the UCSF team used their new approach to identify new biochemical players involved in the development of tolerance to opioid painkillers -- which target a particular type of GPCR -- findings they anticipate will enable researchers to develop safer and more effective pain control. The new Cell article is titled “An Approach to Spatiotemporally Resolve Protein Interaction Networks in Living Cells.” "This technology will let us understand how these critical signaling molecules work in a way we've never been able to before," said Nevan Krogan, Ph.D., a Professor of Cellular and Molecular Pharmacology and Director of the Quantitative Biosciences Institute (QBI) at UCSF and a Senior Investigator at the Gladstone Institutes, who was one of the new paper's senior authors.

Improving Restorative Sleep in Aging Adults May Help Ward Off Mental and Physical Ailments, Extend Health Span

As we grow old, our nights are frequently plagued by bouts of wakefulness, bathroom trips, and other nuisances as we lose our ability to generate the deep, restorative slumber we enjoyed in youth. But does that mean older people just need less sleep? Not according to University of California (UC) Berkeley researchers, who argue, in a review article published online on April 5, 2017 in Neuron, that the unmet sleep needs of the elderly elevate their risk of memory loss and a wide range of mental and physical disorders. The open-access review is titled “Sleep and Human Aging.” "Nearly every disease killing us in later life has a causal link to lack of sleep," said the article's senior author, Matthew Walker, Ph.D., a UC Berkeley Professor of Psychology and Neuroscience. "We've done a good job of extending life span, but a poor job of extending our health span. We now see sleep, and improving sleep, as a new pathway for helping remedy that." Unlike more cosmetic markers of aging, such as wrinkles and gray hair, sleep deterioration has been linked to such conditions as Alzheimer's disease, heart disease, obesity, diabetes, and stroke, he said. Though older people are less likely than younger cohorts to notice and/or report mental fogginess and other symptoms of sleep deprivation, numerous brain studies reveal how poor sleep leave the older people cognitively worse off. Moreover, the shift from deep, consolidated sleep in youth to fitful, dissatisfying sleep can start as early as one's 30s, paving the way for sleep-related cognitive and physical ailments in middle age. And, while the pharmaceutical industry is raking in billions by catering to insomniacs, Dr.