Neural Cell News Volume 11.21 | May 31 2017

TOP STORY

Llgl1 Connects Cell Polarity with Cell-Cell Adhesion in Embryonic Neural Stem Cells

Scientists report that mice with embryonic neural stem-cell-specific deletion of Llgl1, a mammalian ortholog of the Drosophila cell polarity gene lgl, exhibited malformations of the cerebral cortex resembling severe periventricular heterotopia. [Dev Cell] Abstract

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Ligand Mediated and Enzyme-Directed Precise Targeting and Retention for Enhanced Treatment of Glioblastoma

Researchers used dual-functional gold nanoparticles (AuNPs) to figure out the biological barrier and improve their accumulation in glioblastoma (GBM). In vivo optical imaging demonstrated that AuNPs-A&C-R were efficiently delivered to the GBM site and were retained with high selectivity. They confirmed that AuNPs-A&C-R acquired a higher accumulation at GBM site compared with AuNPs-A&C and AuNPs-R due to the synergistic effect. [ACS Appl Mater Interfaces] Abstract

Chemical Modulation of Protein O-GlcNAcylation via OGT Inhibition Promotes Human Neural Cell Differentiation

The authors studied the effects of perturbing O-GlcNAcylation during neural induction of human embryonic stem cells (hESCs) using the metabolic inhibitor of O-GlcNAc transferase (OGT), peracetylated 5-thio-N-acetylglucosamine (Ac4-5SGlcNAc). Treatment of hESCs with Ac4-5SGlcNAc during induction limited protein O-GlcNAcylation had caused a dramatic decrease in global levels of UDP-GlcNAc. [ACS Chem Biol] Abstract

ORF7 of Varicella-Zoster Virus Is Required for Viral Cytoplasmic Envelopment in Differentiated Neuronal Cells

Scientists investigated the effect of open reading frame 7 (ORF7) deletion on varicella-zoster virus (VZV) replication cycle at virus entry, genome replication, gene expression, capsid assembly and cytoplasmic envelopment, and transcellular transmission in differentiated neural progenitor cells and neuroblastoma SH-SY5Y cells. Their results demonstrated that the ORF7 protein is a component of the tegument layer of VZV virions. [J Virol] Abstract

Alpha-7 Nicotinic Receptor Signaling Pathway Participates in the Neurogenesis Induced by ChAT-Positive Neurons in the Subventricular Zone

Researchers investigated the neurogenic role of the alpha-7 nicotinic acetylcholine receptor (α7 nAChR) in a mouse model of middle cerebral artery occlusion (MCAO) by using α7 nAChR inhibitor methyllycaconitine. Mice subjected to MCAO exhibited elevated expression of cytomembrane and nuclear fibroblast growth factor receptor 1, as well as increased expression of PI3K, pAkt, doublecortin, polysialylated-neuronal cell adhesion molecule, and mammalian achaete-scute homolog 1. [Transl Stroke Res] Abstract

A Comparison of the Sexually Dimorphic Dexamethasone Transcriptome in Mouse Cerebral Cortical and Hypothalamic Embryonic Neural Stem Cells

Investigators characterized the transcriptome of primary, embryonic mouse cerebral cortical and hypothalamic neural progenitor/stem cells derived from individual male and female embryos exposed to the synthetic glucocorticoid, dexamethasone. Gene expression profiling by RNA-Seq identified differential expression of common and unique genes based upon brain region, sex, and/or dexamethasone exposure. [Mol Cell Endocrinol] Abstract

Geminin Participates in Differentiation Decisions of Adult Neural Stem Cells Transplanted in the Hemiparkinsonian Mouse Brain

Researchers examined whether alterations in geminin’s expression, a protein that coordinates the balance between self-renewal and differentiation, could improve the properties of stem cells transplanted in a 6 OHDA hemiparkinsonian mouse model. Their results indicated that in the absence of geminin grafted cells differentiating into dopaminergic neurons were decreased, while an increased number of oligodendrocytes were detected. [Stem Cells Dev] Abstract

Factors Released from Endothelial Cells Exposed to Flow Impact Adhesion, Proliferation, and Fate Choice in the Adult Neural Stem Cell Lineage

Scientists evaluated adult mouse neural progenitor cell response to soluble factors isolated from static or dynamic (flow) endothelial cells cultures. Endothelial factors generated under dynamic conditions significantly increased neuronal differentiation, while those released under static conditions stimulated oligodendrocyte differentiation. [Stem Cells Dev] Abstract

Different Molecular Mechanisms Mediate Direct or Glia-Dependent Prion Protein Fragment 90–231 Neurotoxic Effects in Cerebellar Granule Neurons

Investigators analyzed the molecular mechanisms mediating microglia-dependent neurotoxicity induced by prion protein fragment 90–231, an amyloidogenic polypeptide corresponding to the protease-resistant portion of the pathological prion protein scrapie. [Neurotox Res] Abstract

Quantitative Proteomic Analysis Revealed Changes in Protein Synthesis and Mitochondrial Functions after Acute DNA Damage in Mouse Neural Stem Cells

The authors utilized hydroxyurea (HU) treatment to cultured mouse neural stem cells (NSCs) to induce acute DNA damages. After HU treatment, mouse NSCs displayed elevated reactive oxygen species level and compromised DNA repair in HR and NHEJ pathways. [Neurosci Lett] Abstract

Translation of WNT Developmental Programs into Stem Cell Replacement Strategies for the Treatment of Parkinson’s Disease

Researchers review novel pharmacological tools to activate Wnt signaling and how single-cell RNA-sequencing is contributing to unravel the complexity of this pathway in the developing human ventral midbrain, generating novel hypotheses and identifying new players and opportunities to further improve cell replacement therapy for Parkinson’s disease. [Br J Pharmacol] Abstract

Microglia-Glioblastoma Interactions: New Role for Wnt Signaling

The authors discuss recent findings that support a role for Wnt signaling pathways in the microglia-glioblastoma crosstalk. [Biochim Biophys Acta] Abstract

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Lysogene Completes Enrollment in First International Pivotal Observational Study in MPS IIIA

Lysogene announced the completion of enrollment in its Sanfilippo A Multinational Observational Study (SAMOS). SAMOS has been designed to evaluate clinical change in untreated MPS IIIA patients. [Lysogene] Press Release

Lysogene Selects Brammer Bio to Produce GM1 Gangliosidosis Gene Therapy Product

Lysogene announced that it has entered into a strategic manufacturing agreement with Brammer Bio. Brammer Bio will produce LYS-GM101, an AAVrh10-based gene therapy, for clinical testing of the therapeutic candidate in patients with GM1 gangliosidosis, a rare neuronopathic lysosomal storage disorder. [Lysogene] Press Release

ProMIS Neurosciences Identifies Novel Therapeutic Epitope Target for ALS and Dementia

ProMIS Neurosciences, Inc. announced the identification of a novel therapeutic epitope target on misfolded forms of TDP43, implicated in the development and progression of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. [ProMIS Neurosciences] Press Release

New Research into Delaying the Onset of Motor Neurone Disease Shows Positive Results

New research into a drug candidate which could help to delay the onset of motor neurone disease has shown encouraging early results. The study found significant and reproducible indications that the drug prevents the death of motor neurones in patient cell models and delayed the onset of the disease in the gold standard of models. [The University of Sheffield Western Bank] Press Release

Athenex and Its Partner, Guangzhou Xiangxue Pharmaceutical, Announced Chinese FDA IND Approval to Begin Clinical Trials of KX-02 Tablet for Glioblastoma

Athenex, Inc. announced that its partner, Guangzhou Xiangxue Pharmaceutical Co. Ltd. has received the Chinese FDA Investigational New Drug (IND) approval to begin clinical trials for KX-02 tablet for glioblastoma in May 2017 under the Class 1 New Drug Regulation in China. [Athenex, Inc.] Press Release

UK Election: Science Spending Pledges Overshadowed by Brexit

Ahead of a UK election that will decide who leads the country’s exit negotiations with the European Union, a remarkable consensus has emerged among the main national parties. All three have pledged in their manifestos to spend more money on science. Each is “putting science at the heart of their program for the future of Britain”, says Sarah Main, director of the London-based Campaign for Science and Engineering. Yet as the uncertainty of Brexit hangs over the future of British science, for many researchers the promises may seem more like consolation prizes. [Nature News] Editorial

NIH Scales Back Plan to Curb Support for Big Labs after Hearing Concerns

Faced with a barrage of criticism, the National Institutes of Health (NIH) has scaled back a plan to cap its support for individual labs in order to free up funds for more scientists. The changes did not appease scientists who gave NIH a tongue-lashing at a meeting of NIH’s Council of Councils. [ScienceInsider] Editorial

House Science Panel Joins Trump in Questioning Research Overhead Payments

A hearing on how the U.S. government defrays the cost of doing federally funded research on college campuses might put most people to sleep. But when budgets are tight, the billions of dollars being spent each year on so-called overhead become an irresistible target for lawmakers. [ScienceInsider] Editorial

Trials of Embryonic Stem Cells to Launch in China

In the next few months, surgeons in the Chinese city of Zhengzhou will carefully drill through the skulls of people with Parkinson’s disease and inject four million immature neurons derived from human embryonic stem (ES) cells into their brains. Then they will patch the patients up, send them home and wait. This will mark the start of the first clinical trial in China using human ES cells, and the first one worldwide aimed at treating Parkinson’s disease using ES cells from fertilized embryos. [Nature News] Editorial

NEW Worldwide Innovative Networking in Personalized Cancer Medicine (WIN) 2017
June 26-27, 2017
Paris, France

NEW Gordon Research Conferences: Cell Growth & Proliferation
July 9-14, 2017
Mount Snow, United States

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NEW Postdoctoral Fellow – Applied Neural Interfaces (Florida International University)

NEW Postdoctoral Position – Neuroscience-Neural Engineering (University of California, Los Angeles)

Postdoctoral Scientist – Neural Stem Cell Biology (Institute for Neuroscience of Montpellier)

Postdoctoral Research Fellow – Brain Neural Networks (Melbourne University)

Faculty Position(s) – Pain Medicine (Southern University of Science and Technology)

Senior/Principle Research Associate – Cell and Molecular Biology (Editas Medicine)

Postdoctoral Fellow – Neuroendocrine Biology of Metabolism (The Scripps Research Institute)

Research Fellow – Neuroscience and Behavioral Disorders (Duke-NUS Medical School)

Postdoctoral Position – Molecular Biology (KU Leuven)

Postdoctoral Researcher – Neuroscience and Imaging (Howard Hughes Medical Institute)

Director – BrainHub (Carnegie Mellon University)

Postdoctoral Position(s) – Visual Neuroscience (Yale University)

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

Postdoctoral Positions – Stem Cell Technology/Neuroscience/Drug Discovery (University of California Davis)

Neuroscientist – Precision Neurotherapeutics (University of California Davis)

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