Neural Cell News Volume 12.09 | Mar 7 2018

TOP STORY

Nociceptor Sensory Neurons Suppress Neutrophil and γδ T Cell Responses in Bacterial Lung Infections and Lethal Pneumonia

Scientists found that TRPV1⁺ nociceptors suppressed protective immunity against lethal Staphylococcus aureus pneumonia. Targeted TRPV1⁺-neuron ablation increased survival, cytokine induction, and lung bacterial clearance. [Nat Med] Abstract | Press Release

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CRISPR-Cas9 Screens in Human Cells and Primary Neurons Identify Modifiers of C9ORF72 Dipeptide-Repeat-Protein Toxicity

Investigators used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 dipeptide-repeat toxicity in human cells. They validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. [Nat Genet] Abstract | Press Release

B-1a Lymphocytes Promote Oligodendrogenesis during Brain Development

Researchers identified the subtypes of lymphocytes that are present in neonatal mouse brains and investigated their functions. They found that B-1a cells, a subtype of B cells, were abundant in the neonatal mouse brain and infiltrated into the brain in a CXCL13–CXCR5-dependent manner. [Nat Neurosci] Abstract

Fast Direct Neuronal Signaling via the IL-4 Receptor as Therapeutic Target in Neuroinflammation

Investigators demonstrated that intrathecal IL-4 treatment during the chronic phase of several experimental autoimmune encephalomyelitis models reversed disease progression without affecting inflammation. Amelioration of disability was abrogated upon neuronal deletion of IL-4R. They discovered direct neuronal signaling via the IRS1-PI3K-PKC pathway underlying cytoskeletal remodeling and axonal repair. [Sci Transl Med] Abstract

Insm1 Induces Neural Progenitor Delamination in Developing Neocortex via Downregulation of the Adherens Junction Belt-Specific Protein Plekha7

Scientists dissected the molecular mechanism by which the transcription factor Insm1 promotes the generation of basal progenitors (BPs). Insm1 protein was most highly expressed in newborn BPs in mouse and human developing neocortex. [Neuron] Abstract | Graphical Abstract

Elongator and Codon Bias Regulate Protein Levels in Mammalian Peripheral Neurons

Familial dysautonomia (FD) results from mutation in IKBKAP/ELP1, a gene encoding the scaffolding protein for the Elongator complex. This highly conserved complex is required for the translation of codon-biased genes in lower organisms. The authors investigated whether Elongator serves a similar function in mammalian peripheral neurons, the population devastated in FD. [Nat Commun] Full Article

Itch/β-Arrestin2-Dependent Non-Proteolytic Ubiquitylation of SuFu Controls Hedgehog Signaling and Medulloblastoma Tumorigenesis

The authors showed that the Itch/β-arrestin2 complex binds suppressor of fused (SuFu) and induces its Lys63-linked polyubiquitylation without affecting its stability. [Nat Commun] Full Article

Single-Cell RNA-Seq of Mouse Dopaminergic Neurons Informs Candidate Gene Selection for Sporadic Parkinson Disease

Investigators used single-cell RNA-seq to characterize dopaminergic (DA) neuron populations in the mouse brain at embryonic and early postnatal time points. These data facilitated unbiased identification of DA neuron subpopulations through their unique transcriptional profiles, including a postnatal neuroblast population and substantia nigra DA neurons. [Am J Hum Genet] Abstract

Retinal Cell Type DNA Methylation and Histone Modifications Predict Reprogramming Efficiency and Retinogenesis in 3D Organoid Cultures

The authors compared reprogramming efficiency of five different retinal cell types at two different stages of development. Retinal differentiation from each induced pluripotent stem cell (iPSC) line was measured using a quantitative standardized scoring system called STEM-RET and compared to the epigenetic memory. Neurons with the lowest reprogramming efficiency produced iPSC lines with the best retinal differentiation and were more likely to retain epigenetic memory of their cellular origins. [Cell Rep] Full Article | Graphical Abstract

Distinct Requirements for Extracellular and Intracellular MMP12 in the Development of the Adult V-SVZ Neural Stem Cell Niche

Researchers examined matrix metalloproteinases for potential roles in ventricular-subventricular zone stem cell niche development. MMP12 was found to promote appropriate niche cellular arrangements, the formation of specialized niche extracellular matrix, and the translational planar cell polarity of ependymal cells that surround and support niche neural stem cells. [Stem Cell Reports] Full Article | Graphical Abstract

Stabilizing the Retromer Complex in a Human Stem Cell Model of Alzheimer’s Disease Reduces TAU Phosphorylation Independently of Amyloid Precursor Protein

Scientists used hiPSC-derived neurons to test a compound that stabilizes the retromer, a highly conserved multiprotein assembly that plays a pivotal role in trafficking molecules through the endosomal network. [Stem Cell Reports] Full Article | Graphical Abstract

Methylphenidate Enhances Neuronal Differentiation and Reduces Proliferation Concomitant to Activation of Wnt Signal Transduction Pathways

The termination of cell proliferation concomitant to neuronal maturation following methylphenidate treatment was observed in all of the cell-models tested: murine neural stem-, rat PC12- and the human SH-SY5Y-cells. [Transl Psychiatry] Full Article

Epigenetic Modifiers Promote Mitochondrial Biogenesis and Oxidative Metabolism Leading to Enhanced Differentiation of Neuroprogenitor Cells

Investigators showed that the HDAC inhibitor, sodium butyrate, promotes mitochondrial biogenesis via the NRF-1/Tfam axis in embryonic hippocampal progenitor cells and neuroprogenitor-like PC12-NeuroD6 cells, thereby enhancing their neuronal differentiation competency. [Cell Death Dis] Full Article

Redox Metals Homeostasis in Multiple Sclerosis and Amyotrophic Lateral Sclerosis: A Review

Scientists describes the physiology of redox metals that produce oxidative stress, which in turn leads to cascades of immunomodulatory alteration of neurons in multiple sclerosis and amyotrophic lateral sclerosis. [Cell Death Dis] Full Article

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IONIS-HTT Rx (RG6042) Top-Line Data Demonstrate Significant Reductions of Disease-Causing Mutant Huntingtin Protein in People with Huntington’s Disease

Ionis Pharmaceuticals Inc. announced the presentation of positive top-line data from a completed Phase I/II study of IONIS-HTTRx in people with early stage Huntington’s disease. [Press release from Ionis Pharmaceuticals, Inc. discussing research presented at the 13^th Annual CHDI Huntington’s Disease Conference, Palm Springs] Press Release

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Asterias Provides Update for Its AST-OPC1 Phase I/IIa Clinical Trial in Severe Spinal Cord Injury

Asterias Biotherapeutics, Inc. provided additional data from the company’s ongoing Phase I/IIa SCiStar study designed to evaluate the safety and potential efficacy of AST-OPC1 in the treatment of severe cervical spinal cord injury. [Asterias Biotherapeutics Inc.] Press Release

Tocagen Receives European Medicines Agency Orphan Medicinal Product Designation for Toca 511 & Toca FC for the Treatment of Glioma

Tocagen Inc. announced the European Medicines Agency has granted orphan medicinal product designation to Toca 511 (vocimagene amiretrorepvec) & Toca FC (flucytosine) for the treatment of patients with glioma. [Tocagen Inc.] Press Release

Constant Pharmaceuticals, LLC Announces Japanese Patent Issuance for TXA302 in Treatment of Stroke

Constant Pharmaceuticals LLC announced that the Japanese Patent Office has issued a patent covering the use of TXA302 in the treatment of stroke. [Constant Pharmaceuticals LLC] Press Release

Apexigen and the Pediatric Brain Tumor Consortium Announce a Clinical Collaboration to Evaluate APX005M in Children with Brain Tumors

Apexigen, Inc. and the Pediatric Brain Tumor Consortium, announced a clinical trial collaboration to evaluate Apexigen’s APX005M, an investigational immune activating compound that targets CD40, in pediatric patients with recurrent or refractory brain tumors. [Apexigen, Inc.] Press Release

Chi-Med Initiates a Phase Ib/II Proof-of-Concept Trial of Epitinib in Glioblastoma in China

Hutchison China MediTech Limited has initiated a Phase Ib/II proof-of-concept study of epitinib in glioblastoma patients with epidermal growth factor receptor gene amplification in China. [Hutchison China MediTech Limited] Press Release

Rise of Nationalist and Populist Parties Has Italian Scientists Worried

The outcome of parliamentary elections in Italy was a stunning victory for populist and nationalist parties, and a clear warning to Italy’s political establishment and the European Union. But some in Italy worry that the results may also have a negative impact on science. [ScienceInsider] Editorial

What Researchers Can Expect from China’s Top-Level Political Meetings

As Chinese leaders gather for the government’s most significant meetings of the year, researchers are anticipating major policy announcements for science and innovation that could shape the country’s research agenda for years. [Nature News] Editorial

New NSF Rules on Sexual Harassment Leave Many Questions Unanswered

The National Science Foundation (NSF) in Alexandria, Virginia, hopes that its new policy on sexual harassment will spur universities to deal more aggressively with the pervasive problem. But the additional reporting requirements, which will be officially published in the Federal Register, are far from a definitive statement about how NSF plans to deal with this complex and sensitive subject. [ScienceInsider] Editorial

NEW MDI Biological Laboratory: Applications of Organoid Technology
May 27-June 2, 2018
Bar Harbor, Maine, United States

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NEW Research Associate – Cell Biology (Cambridge Institute for Medical Research)

Research Technologist – Neural (STEMCELL Technologies Inc.)

Scientist – Molecular Neuroscience (Loyola University Chicago)

Postdoctoral Associate – hiPSC-Based Brain Organoids (Rutgers University)

Postdoctoral Position – Neuroscience and Mitochondrial Physiology (University of Moncton)

Postdoctoral Position – Pain in Mouse Models of Spinal Cord Injury (Indiana University)

Postdoctoral Position – Spinal Cord Injury (Nanyang Technological University)

PhD/Postdoctoral Research Position – Neuroscience (Max Planck Society)

Postdoctoral Fellowship – Neurodegeneration (Lund University)

Postdoctoral Associate – Cerebral Organoids (Weill Cornell Medicine)

Multiple Faculty Positions – Neuroscience and Neuroengineering (Tsinghua University)

Postdoctoral Position – Brain Injury and Repair (University of Pennsylvania)

Faculty Members – Neuroscience (Mercer University)

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