Volume 7.41 | Oct 16

Neural Cell News 7.41 October 16, 2013
Neural Cell News
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SHANK3 and IGF1 Restore Synaptic Deficits in Neurons from 22q13 Deletion Syndrome Patients
Investigators generated induced pluripotent stem cells from individuals with Phelan-McDermid syndrome (PMDS) and autism and used them to produce functional neurons. They showed that PMDS neurons have reduced SHANK3 expression and major defects in excitatory, but not inhibitory, synaptic transmission. [Nature] Abstract
Take the "if" out of "diff": Reduce variability when differentiating to neural progenitors
PUBLICATIONS (Ranked by impact factor of the journal)
Asymmetric Inheritance of Centrosome-Associated Primary Cilium Membrane Directs Ciliogenesis after Cell Division
Researchers followed the ciliary membrane in dividing embryonic neocortical stem cells and cultured cells. Ciliary membrane attached to the mother centriole was endocytosed at mitosis onset, persisted through mitosis at one spindle pole, and was asymmetrically inherited by one daughter cell, which retained stem cell character. [Cell] Abstract | Full Article | Graphical Abstract

EGFR Phosphorylates Tumor-Derived EGFRvIII Driving STAT3/5 and Progression in Glioblastoma
Scientists document coexpression of EGFR and EGFRvIII in primary human glioblastoma that drives transformation and tumorigenesis in a cell-intrinsic manner. They demonstrated enhancement of downstream STAT signaling triggered by EGFR-catalyzed phosphorylation of EGFRvIII, implicating EGFRvIII as a substrate for EGFR. [Cancer Cell] Abstract | Full Article

Exercise Induces Hippocampal BDNF through a PGC-1α/FNDC5 Pathway
Researchers showed that FNDC5, a previously identified muscle protein that is induced in exercise and is cleaved and secreted as irisin, is also elevated by endurance exercise in the hippocampus of mice. Forced expression of FNDC5 in primary cortical neurons increases brain-derived neurotrophic factor (Bdnf) expression, whereas RNAi-mediated knockdown of FNDC5 reduces Bdnf. [Cell Metab]
Abstract | Press Release

Structural and Functional Characterization of Two Alpha-Synuclein Strains
Scientists structurally and functionally characterized two polymorphs of α-synuclein. They presented evidence that the two forms indeed fulfill the molecular criteria to be identified as two strains of α-synuclein. Specifically, they showed that the two strains have different structures, levels of toxicity, and in vitro and in vivo seeding and propagation properties. [Nat Commun] Full Article

Septins Promote Dendrite and Axon Development by Negatively Regulating Microtubule Stability via HDAC6-Mediated Deacetylation
Scientists showed that the acute knockdown or knockout of the pivotal septin subunit SEPT7 from cerebrocortical neurons impairs their interhemispheric and cerebrospinal axon projections and dendritogenesis in perinatal mice, when the microtubules are severely hyperacetylated. The resulting hyperstabilization and growth retardation of microtubules were demonstrated in vitro. [Nat Commun]
Full Article

Endonuclease G Mediates α-Synuclein Cytotoxicity during Parkinson’s Disease
Researchers showed that endonuclease G (EndoG) displays cytotoxic nuclear localization in dopaminergic neurons of human Parkinson-diseased patients, while EndoG depletion largely reduces α-synuclein-induced cell death in human neuroblastoma cells. [EMBO J] Full Article

Therapeutic Targeting of Constitutive Poly-ADP-Ribose Polymerase Activation Compromises Stem Cell Phenotype and Survival of Glioblastoma-Initiating Cells
Scientists report that glioblastoma-initiating cells (GICs) are primed to handle additional stress due to basal activation of single-strand break repair, the main DNA damage response pathway activated by reactive oxygen species (ROS), compared with non-GICs. ROS levels were higher in GICs and likely contributed to the oxidative base damage and single-strand DNA breaks found elevated in GICs. [Cell Death Differ] Abstract

Chlorhexidine Inhibits L1 Cell Adhesion Molecule Mediated Neurite Outgrowth In Vitro
Researchers assessed the potential neurotoxicity of chlorhexidine on the developing central nervous system using a well-established in vitro model of neurite outgrowth that includes laminin and L1 cell adhesion molecule (L1) as neurite outgrowth promoting substrates. [Pediatr Res] Abstract

Recombinant Human Prion Protein Inhibits Prion Propagation In Vitro
Researchers report that the recombinant full-length human prion protein (rHuPrP23-231) is a strong inhibitor of human prion propagation. Furthermore, rHuPrP23-231 also inhibited mouse prion propagation in a scrapie-infected mouse cell line. [Sci Rep] Full Article

Efficient and Rapid Derivation of Primitive Neural Stem Cells and Generation of Brain Subtype Neurons From Human Pluripotent Stem Cells
Researchers report a highly efficient serum-free pluripotent stem cell neural induction medium that can induce human pluripotent stem cells into primitive neural stem cells in seven days, obviating the need for time-consuming, laborious embryoid body generation or rosette picking. [Stem Cells Transl Med] Abstract

Brain Food: NeuroCult SM1 for Long-Term Primary Neuronal Culture. View Data!
NURR1 in Parkinson Disease – From Pathogenesis to Therapeutic Potential
Orphan nuclear receptor NURR1 is involved in the differentiation of midbrain dopamine (DA) neurons, but also has an important role in the adult brain. Emerging evidence indicates that impaired NURR1 function might contribute to the pathogenesis of Parkinson disease: NURR1 and its transcriptional targets are downregulated in midbrain DA neurons that express high levels of the disease-causing protein α-synuclein. [Nat Rev Neurol] Abstract

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Lundbeck and Otsuka Initiate Phase III Clinical Trials on Lu AE58054 as a New Add-On Treatment for Alzheimer’s Disease
H. Lundbeck A/S and Otsuka Pharmaceutical Co. Ltd. announced the continuation of the development program of Lu AE58054 for the treatment of Alzheimer’s disease, initiating the first out of four currently planned Phase III clinical trials with the compound in Alzheimer’s disease. [H. Lundbeck A/S] Press Release

Bexion Pharmaceuticals Awarded $2.9 Million SBIR Bridge Award by National Cancer Institute to Support Phase I First-in-Human Clinical Trial in Cancer
Bexion Pharmaceuticals announced that it has been awarded a Small Business Innovation Research “Bridge Award” by the National Cancer Institute. The award of $2.9 million over three years will help Bexion further its clinical development of BXQ-350. [Bexion Pharmaceuticals] Press Release

The Michael J. Fox Foundation to Host Clinical Trials Fair in New York City
The Michael J. Fox Foundation for Parkinson’s Research will host a Clinical Trials Fair in New York City to raise awareness and understanding of local Parkinson’s research opportunities among patients, their families and friends, and other interested volunteers. [PR Newswire Association LLC] Press Release

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NEW Postdoctoral Fellow – Neuroscience (Harvard Medical School)

Postdoctoral Fellow Position – Neuroscience (Johns Hopkins University)

Postdoctoral Fellowship – Reprogramming, Stem Cells, and Neuroscience (University of Southern California)

Manufacturing Manager (StemCells Inc.)

Postdoctoral Fellow – Brain Cancer (Vanderbilt University Medical Center)

PhD Studentship – Neuroscience (Tübingen University)

Postdoctoral Fellowship – Neural Stem Cells (University of Wisconsin – Madison)

Postdoctoral Position – Glia and Neural Stem/Progenitor Cell Interactions (University of Kentucky College)

Tenure-Track Faculty Position – Neuroscience (University of Utah)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Technologist – Cell Culture Media & Matrices (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)

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