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Archive - Apr 2017

April 8th

Salk Institute & Peking University Scientists Develop Stable Stem Cell Line with Totipotent-Like Features; Single Derived “Extended” Stem Cell Could Give Rise to Whole Mouse; Advance “Will Have Broad and Resounding Impact on Stem Cell Field”

When scientists talk about laboratory stem cells being totipotent or pluripotent, they mean that the cells have the potential, like an embryo, to develop into any type of tissue in the body. What totipotent stem cells can do that pluripotent ones can't do, however, is develop into tissues that support the embryo, like the placenta. These are called extra-embryonic tissues, and are vital in development and healthy growth. Now, scientists at the Salk Institute, in collaboration with researchers from Peking University, in China, are reporting their discovery of a chemical cocktail that enables cultured mouse and human stem cells to do just that: generate both embryonic and extra-embryonic tissues. Their technique, described in the April 6, 2017 issue of Cell, could yield new insights into mammalian development that lead to better disease modeling, drug discovery and even tissue regeneration. This new technique is expected to be particularly useful for modeling early developmental processes and diseases affecting embryo implantation and placental function, possibly paving the way for improved in vitro fertilization techniques. The Cell article is titled” Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency.” "During embryonic development, both the fertilized egg and its initial cells are considered totipotent, as they can give rise to all embryonic and extra-embryonic lineages. However, the capture of stem cells with such developmental potential in vitro has been a major challenge in stem cell biology," says Salk Professor Juan Carlos Izpisua Bemonte, Ph.D., co-senior author of the paper and holder of Salk's Roger Guillemin Chair.

Neighboring Biofilms Practice Time-Sharing When Nutrients Are Scarce

While the idea of splitting getaway condos in exotic destinations among various owners has been popular in real estate for decades, biologists at the University of California San Diego have discovered that communities of bacteria have been employing a similar strategy for millions of years. Researchers in molecular biologist Dr. Gürol Süel's laboratory in UC San Diego's Division of Biological Sciences, along with colleagues at the Universitat Pompeu Fabra in Spain, asked what competing communities of bacteria might do when food becomes scarce. The team found that bacteria faced with limited nutrients will enter an elegant time-sharing strategy in which communities alternate feeding periods to maximize efficiency in consumption. The study was published online on April 6, 2017 in Science. The article is titled “Coupling Between Distant Biofilms and Emergence of Nutrient Time-Sharing.” "What's interesting here is that you have these simple, single-celled bacteria that are tiny and seem to be lonely creatures, but in a community, they start to exhibit very dynamic and complex behaviors you would attribute to more sophisticated organisms or a social network," said Dr. Süel, Associate Director of the San Diego Center for Systems Biology and a Howard Hughes Medical Institute - Simons Faculty Scholar at UC San Diego. "It's the same time-sharing concept used in computer science, vacation homes, and a lot of social applications. "In January, Dr. Süel and his colleagues discovered that structured communities of bacteria, or "biofilms," use electrical signals to communicate with, and recruit, neighboring bacterial species. The new study investigates how two biofilm communities interact.

ESCRT-III Acts Downstream of MLKL to Regulate Necroptotic Cell Death

A research team led by St. Jude Children's Research Hospital immunologists has discovered how a set of proteins delays the "executioner" machinery that kills damaged or infected cells in a process called necroptosis. The scientists believe the finding may have wide clinical implications if researchers can develop drugs to control the cellular rescue machinery. Rescue treatments that prevent necroptosis in transplanted organs could reduce injury to the transplant caused by lack of oxygen, researchers said. Drugs to rescue cells from necroptosis could also help prevent injuries to tissue deprived of blood by heart attack and stroke. In such cases, restoring blood flow and oxygenation triggers inflammation that kills tissue. The researchers said cell-rescuing drugs could also thwart cancer spread by protecting blood vessel cells from being killed by tumor cells. Tumor cells escape the bloodstream to spread in the body by killing blood vessels. Blocking the rescue machinery might also prove useful in treating cancers, by enhancing death of cancer cells by necroptosis. In treating neurodegenerative disorders such as ALS--also known as Lou Gehrig's Disease--activating the rescue machinery could help prevent death of brain cells. And in treating viral infections such as influenza, rescue treatment could extend the life of cells infected by the virus, so that the body's immune system would be more strongly alerted to fight the infection. The researchers were led by Douglas Green, Ph.D., Chair of the St. Jude Department of Immunology. The first author was Yi-Nan Gong, Ph.D., a scientist in Dr. Green's laboratory. The research appears in the the April 6, 2017 issue of the prestigious journal Cell.

Involuntary Movement (Tardive Dyskinesia) Side-Effects of Anti-Psychotic Drugs Are Reduced by Treatment with Valbenzanine, an Anti-VMAT2 Inhibitor

Involuntary Movement (Tardive Dyskinesia) Side-Effects of Anti-Psychotic Drugs Are Reduced by Treatment with Valbenzanine,an Anti-VMAT2 Inhibitor. Anti-psychotic medications can cause involuntary movements such as lip smacking, tongue protrusions and excessive eye blinking. These movements typically occur after more than three months of treatment and are called tardive dyskinesia. Robert A. Hauser, M.D., M.B.A., Professor of Neurology at the University of South Florida (USF) in Tampa, is the lead author of a study published recently in the American Journal of Psychiatry that concludes that valbenazine administered once daily can significantly reduce tardive dyskinesia in patients with schizophrenia, schizoaffective disorder, and mood disorder. The article is titled “KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia.”"One approach to managing tardive dyskinesia is to discontinue anti-psychotic treatment or reduce the dosage, but these options are not always feasible, because withdrawal can exacerbate tardive dyskinesia symptoms or have a negative impact on psychiatric status. Moreover, tardive dyskinesia symptoms often persist even after discontinuation or dosage reduction," wrote Dr. Hauser, who directs the Parkinson's Disease and Movement Disorders Center at USF. Valbenazine is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor. VMAT2 is an integral membrane protein that transports monoamines—particularly neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine—from the cellular cytosol into synaptic vesicles. In nigrostriatal pathway and mesolimbic pathway dopamine-releasing neurons, VMAT2 function is also necessary for the vesicular release of the neurotransmitter GABA.

April 6th

Major Discovery in Division Process of Animal Cells

An international group of scientists, led by the University of Granada (UGR) in Spain, has made an unexpected finding about animal cytokinesis, the cellular process that causes the segmentation or division of the cytoplasm to give rise to two daughter cells. This work, which has counted the participation of Canadian researchers and was published on January 6, 2017 in Scientific Reports belonging to Nature Publishing Group, has identified the neuronal apoptosis inhibitory protein (NAIP) throughout cytokinesis. The article is titled “Neuronal Apoptosis Inhibitory Protein (NAIP) Localizes to the Cytokinetic Machinery During Cell Division.” The study basically used microscopic techniques (confocal microscopy and super-resolution microscopy) to show the dynamic of NAIP during the final stages of cell division. The scientists responsible for this study hope that this finding, whose first signs were observed during research that did not address issues about cell division, may lead to other studies that allow a better analysis of the molecular mechanisms that control the final stages of cellular division. As explained by the main author, Francisco Abadía-Molina, Ph.D., from the department of Cellular Biology at the UGR, “Knowing the basic mechanisms that control cell division is fundamental to understand(ing) processes such as development, growth, tissue maintenance, and regeneration, or what are the causes that lead to proliferative pathologies such as cancer, which would allow us to identify new therapeutic targets and strategies."

April 6th

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.