Neural Cell News 10.46 November 23, 2016 | |
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TOP STORYSite-Specific Phosphorylation of Tau Inhibits Amyloid-β Toxicity in Alzheimer’s Mice Amyloid-β (Aβ) toxicity in Alzheimer’s disease is considered to be mediated by phosphorylated tau protein. In contrast, the authors found that, at least in early disease, site-specific phosphorylation of tau inhibited Aβ toxicity. This specific tau phosphorylation was mediated by the neuronal p38 mitogen-activated protein kinase p38γ and interfered with postsynaptic excitotoxic signaling complexes engaged by Aβ. [Science] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)Epigenetic Activation of WNT5A Drives Glioblastoma Stem Cell Differentiation and Invasive Growth Glioblastoma stem cells (GSCs) are implicated in tumor neovascularization, invasiveness, and therapeutic resistance. To illuminate mechanisms governing these hallmark features, scientists developed a de novo glioblastoma multiforme model derived from immortalized human neural stem/progenitor cells (NSCs) to enable precise system-level comparisons of pre-malignant and oncogene-induced malignant states of NSCs. Integrated transcriptomic and epigenomic analyses uncovered a PAX6/DLX5 transcriptional program driving WNT5A-mediated GSC differentiation into endothelial-like cells. [Cell] Abstract | Press Release | Graphical Abstract Investigators have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract A Rapidly Acting Glutamatergic ARC→PVH Satiety Circuit Postsynaptically Regulated by α-MSH Researchers showed that glutamate-releasing arcuate nucleus (ARC) neurons expressing oxytocin receptor, unlike pro-opiomelanocortin ARCPOMC neurons, rapidly cause satiety when chemo- or optogenetically manipulated. These glutamatergic ARC projections synaptically converge with GABAergic agouti-related protein ARCAgRP projections on melanocortin-4 receptor-expressing satiety neurons in the paraventricular hypothalamus (PVHMC4R neurons). [Nat Neurosci] Abstract | Press Release Long-Distance Descending Spinal Neurons Ensure Quadrupedal Locomotor Stability Investigators employed mouse genetic and viral approaches to reveal organizational principles of long-projecting spinal circuits and their role in quadrupedal locomotion. They demonstrated that selective ablation of descending spinal neurons linking cervical to lumbar segments impairs coherent locomotion, by reducing postural stability and speed during exploratory locomotion, as well as perturbing interlimb coordination during reinforced high-speed stepping. [Neuron] Abstract | Press Release VCAM1 Acts in Parallel with CD69 and Is Required for the Initiation of Oligodendrocyte Myelination The authors demonstrated that VCAM1, which plays a key role throughout the immune system, is also expressed in oligodendrocytes, where it regulates the initiation of myelination. VCAM1 contributes not only to the initiation of myelination but also to its regulation through controlling the abundance of CD69, demonstrating that an intercellular molecule whose primary role is in the immune system can also play an unexpected role in the CNS. [Nat Commun] Full Article Lack of Diaph3 Relaxes the Spindle Checkpoint Causing the Loss of Neural Progenitors Scientists reported that Diaph3 is required before cell fission, to ensure the accurate segregation of chromosomes. Inactivation of the Diaph3 gene causes a massive loss of cortical progenitor cells, with subsequent depletion of intermediate progenitors and neurons, and results in microcephaly. [Nat Commun] Full Article Investigators showed here that nucleosome depletion regions form in both proximal promoters and distal enhancers during neural stem cells differentiating into neurons in the early Drosophila embryonic development. [Cell Death Differ] Full Article The authors showed that Tet3, a DNA dioxygenase, can rapidly and efficiently convert fibroblasts directly into functional neurons. The induced neurons (iNs) express pan and mature neuronal markers such as Tuj1, Synapsin, and neuronal nuclei. Gene expression profiles demonstrated distinct neuron-specific gene clusters in iNs compared with primary neurons. Induced neurons displayed maturing firing patterns and form functional synapses. [Cell Rep] Full Article | Graphical Abstract To gain an insight on brain apolipoprotein E (apoE) regulation, scientists performed an unbiased high-throughput screening of known drugs and bioactive compounds in cultured human primary astrocytes, the major apoE-producing cell type in the brain. [Chem Biol] Abstract Investigators demonstrated that poly-L-ornithine (PO) could promote migration of neural stem/progenitor cells (NSPCs) in vitro, and the underlying mechanism is PO activates α-Actinins 4, which is firstly certified to be expressed in NSPCs, to promote filopodia formation and therefore enhances NSPCs migration. [Sci Rep] Full Article Researchers described a new platform which enables, rapid and efficient CRISPR/Cas9-mediated genome targeting simultaneously with three different paradigms for in vitro generation of neurons. This system was employed to inactivate two genes associated with neurological disorder (TSC2 and KCNQ2) and achieved up to 85% efficiency of gene targeting in the differentiated cells. [Sci Rep] Full Article | |
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REVIEWSSonic Hedgehog Signaling and Hippocampal Neuroplasticity Sonic hedgehog (Shh) is a secreted protein that controls the patterning of neural progenitor cells, and their neuronal and glial progeny, during development. The authors discuss emerging findings which suggest that Shh also has important roles in the formation and plasticity of neuronal circuits in the hippocampus, a brain region of fundamental importance in learning and memory. [Trends Neurosci] Abstract Visit our reviews page to see a complete list of reviews in the neural cell research field. | |
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SCIENCE NEWSAlzheon, Inc. announced that the company will be making two presentations of a new Alzheimer’s disease analysis. After the recent publication of clinical analyses from Phase III tramiprosate studies showing promising efficacy in Alzheimer’s disease patients homozygous for the epsilon 4 allele of apolipoprotein E, the new analyses to be presented will build further on this data and help refine the target population for future confirmatory studies. [Press release from Alzheon, Inc. discussing research to be presented at the 9th Annual Clinical Trials on Alzheimer’s Disease (CTAD) congress, San Diego] Press Release | |
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INDUSTRY NEWSLilly Announces Top-Line Results of Solanezumab Phase III Clinical Trial Eli Lilly and Company announced that solanezumab did not meet the primary endpoint in the EXPEDITION3 clinical trial, a Phase III study of solanezumab in people with mild dementia due to Alzheimer’s disease. [Eli Lilly and Company] Press Release Allergan plc. announced that it has completed the acquisition of Chase Pharmaceuticals Corporation, a clinical-stage biopharmaceutical company focused on the development of improved treatments for neurodegenerative disorders including Alzheimer’s disease. [Allergan plc.] Press Release Novocure announced that a long-term analysis of the full trial cohort from its Phase III pivotal EF-14 trial of Optune® in combination with temozolomide for the treatment of newly diagnosed glioblastoma confirmed the superior survival results seen at interim analysis. The long-term analysis demonstrated superior two-, three- and four-year survival of patients treated with Optune together with temozolomide compared to temozolomide alone. [Novocure] Press Release CPRIT Advances Cancer Research at UT Southwestern with New Awards UT Southwestern Medical Center researchers recently received $5.8 million in support from the Cancer Prevention and Research Institute of Texas (CPRIT). [Ut Southwestern Medical Center] Press Release $25 Million Awarded to Center for Study of Regulatory Science The FDA is funding a collaboration between Stanford and UCSF to improve the regulatory infrastructure that helps to shape modern biomedical research. [Stanford Medicine] Press Release Center for Regenerative Medicine Receives Three Prestigious NIH Awards To Further Stem Cell Research The Center for Regenerative Medicine at Boston Medical Center and Boston University School of Medicine has received three prestigious awards from the National Institutes of Health (NIH) to further its commitment to induced pluripotent stem cell research and education. [Boston University School of Medicine] Press Release | |
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POLICY NEWSNgAgo Gene-Editing Controversy Escalates in Peer-Reviewed Papers A heated dispute over gene-editing that began online is now playing out in the scientific literature. Six months ago, Chinese researchers reported that an enzyme called NgAgo could be used to edit mammalian genes – and that it might be more accurate and more versatile than the popular CRISPR-Cas9 gene-editing technique. [Nature News] Editorial Immigrant and Minority Scientists Shaken by Trump Win Scientists are reconsidering whether to work or study in the United States. Worries include job prospects, discrimination — and safety. [Nature News] Editorial Peer-Review ‘Heroes’ Do Lion’s Share of the Work In 2015, the number of scientists in the life sciences far exceeded the demand on them for peer review, according to Michail Kovanis, a computational physicist at the French National Institute of Health and Medical Research in Paris, and his colleagues. Yet their study also suggests – based on data obtained from a rapidly-growing website of peer-review activity – that 20% of the scientists undertook between 69% and 94% of reviews last year, lending credence to some researchers’ complaints that they are overburdened. “These ‘peer-review heroes’ may be overworked, with risk of downgraded peer-review standards,” Kovanis and colleagues write in a paper published in PLOS One. [Nature News] Editorial Cautious Welcome for UK’s Vague £2 Billion Research Pledge UK scientists have welcomed a surprise government promise to invest an extra £2 billion (US$2.5 billion) per year into research and development by 2020 – although details of the pledge will not be made clear for at least another two days. [Nature News] Editorial Conservatives, Liberals Team Up against Animal Research “Painful, bizarre, and wasteful experiments.” Buying dogs “just to cut them apart … and kill them.” These statements might sound like the rhetoric used by extreme animal rights groups, but they come from White Coat Waste—a new, unlikely coalition of fiscal conservatives and liberal activists that aims to end federal funding for research involving dogs and other animals by targeting people’s pocketbooks in addition to their heartstrings. [ScienceInsider] Editorial
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EVENTSNEW 19th International Conference on Clinical Application of Adult Stem Cells Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNeuroscience Postdoctoral Fellow (Harvard University) Research Associate Position in Neural Rehabilitation Experiments (Nanyang Technological University) Postdoctoral Researcher – Alzheimer’s Disease (University of Arkansas) Computational Biologist – Aging Brain (Columbia University) Postdoctoral Fellow – Parkinson’s Disease Research (Van Andel Research Institute) NYSCF Investigator – Stem Cell And Neuroscience (New York Stem Cell Foundation) Cancer Research – PhD Studentships (University of Cambridge) Postdoctoral Fellow – Neural Stem/Progenitor Cells (University of California – San Francisco) Assistant Professor – Neural Mechanisms of Motor Control (University of California – Davis) Postdoctoral Researcher – iPS & ESC Parkinson’s Disease (VIB) Postdoctoral Researcher – Neural Basis of Brain States (Ecole Polytechnique Fédérale de Lausanne) Systems Neuroscientist (University of Rochester) PhD – Neural Circuits (The International Max Planck Research School for Neural Circuits) Assistant Professor (Tenure) – Developmental Biology) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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Home Neural Cell News Volume 10.46 | Nov 23 2016