Neural Cell News Volume 12.48 | Dec 05 2018

TOP STORY

Single-Cell Sequencing of iPSC-Dopamine Neurons Reconstructs Disease Progression and Identifies HDAC4 as a Regulator of Parkinson Cell Phenotypes

Using high-resolution, single-cell transcriptomic analyses of induced pluripotent stem cell-derived dopamine neurons carrying the GBA-N370S PD risk variant, scientists identified a progressive axis of gene expression variation leading to endoplasmic reticulum stress. [Cell Stem Cell] Full Article | Graphical Abstract

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Probing the Mechanism of Inhibition of Amyloid-β(1–42)–induced Neurotoxicity by the Chaperonin GroEL

To understand the mechanism of GroEL-mediated abrogation of neurotoxicity, authors studied the interaction of amyloid-β(1–42) (Aβ42) with GroEL using a variety of biophysical techniques. The authors showed that the bacterial homolog GroEL reduced the neurotoxic effects of amyloid-β(1-42) on human neural stem cell-derived neuronal cultures. [Proc Natl Acad Sci USA] Abstract

A Primate-Specific Isoform of PLEKHG6 Regulates Neurogenesis and Neuronal Migration

Scientists analyzed the exomes of 65 patients with the structural brain malformation periventricular nodular heterotopia. De novo coding variants were observed in excess in genes defining a transcriptomic signature of basal radial glia, a cell type linked to brain evolution. [Cell Rep] Full Article | Graphical Abstract

CSAP Acts as a Regulator of TTll-Mediated Microtubule Glutamylation

Investigators found that CSAP forms a complex with TTLL5, they demonstrated that the two proteins regulate their reciprocal abundance. They showed that CSAP increases TTLL5-mediated glutamylation and identified the TTLL5-interacting domain. Deletion of this domain lead to complete loss of CSAP activating function without impacting its MT binding. [Cell Rep] Full Article | Graphical Abstract

Nutritional Stress Reprograms Dedifferention in Glioblastoma Multiforme Driven by PTEN/Wnt/Hedgehog Axis: A Stochastic Model of Cancer Stem Cells

Nutritional deprivation induced enhanced expression of glioblastoma stem-like cells specific biomarkers with higher invasive and angiogenic properties. This nutritional stress-induced cells showed higher xenobiotic efflux ability, and hence exhibit resistance to multiple anticancer drugs. [Cell Death Dis] Full Article

Pituitary Adenylate Cyclase Activating Polypeptide Elicits Neuroprotection against Acute Ischemic Neuronal Cell Death Associated with NMDA Receptors

Primary rat neural cells were exposed to peptides pituitary adenylate cyclase-activating polypeptides-27 or PACAP-38 before induction of experimental acute ischemic stroke via oxygen-glucose deprivation-reperfusion (OGD/R) injury. [Cell Physiol Biochem] Full Article

Simvastatin Protects Dopaminergic Neurons against MPP⁺-Induced Oxidative Stress and Regulates the Endogenous Anti-Oxidant System through ERK

Simvastatin enhanced the viability of SH-SY5Y cells and primary neurons treated with l-methyl-4-phenylpyridine ion (MPP⁺), and significantly alleviated the oxidative stress induced by MPP⁺ in SH-SY5Y cells by regulating the production of superoxide dismutase, analytical grade micro-reduced glutathione, and reactive oxygen species, which may be associated with the activation of the Nrf2 anti-oxidant system. [Cell Physiol Biochem] Full Article

Kinesin Family of Proteins Kif11 and Kif21B Act as Inhibitory Constraints of Excitatory Synaptic Transmission through Distinct Mechanisms

Researchers assessed the necessity of 18 kinesin family of motor proteins (Kifs) in excitatory synaptic transmission in mouse primary hippocampal neurons prepared from both sexes. Measurements of excitatory post-synaptic currents (EPSCs) have identified 7 Kifs that were found to be not critical and 11 Kifs that are essential for synaptic transmission by impacting either frequency or amplitude or both components of EPSCs. [Sci Rep] Full Article

Glutamatergic and Dopaminergic Modulation of Cortico-Striatal Circuits Probed by Dynamic Calcium Imaging of Networks Reconstructed in Microfluidic Chips

Researchers developed a microfluidic device where cortical neurons projected onto striatal neurons in a separate compartment. They exploited real-time (low-resolution/high-output) calcium imaging to register network dynamics and characterize the response to glutamatergic and dopaminergic agents. [Sci Rep] Full Article

Replication Stress: An Achilles’ Heel of Glioma Cancer Stem-Like Cells

The authors explore the efficacy of combined ataxia telangiectasia and Rad3-related kinase and PARP inhibitors as a strategy to leverage these mechanisms and overcome radiation resistance. [Cancer Res] Abstract

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Domain Therapeutics Signs a Multi-Target Research Collaboration and License Agreement with Boehringer Ingelheim

Domain Therapeutics announced a multi-target drug discovery collaboration and licensing agreement with Boehringer Ingelheim on orphan G Protein-Coupled Receptors in the Central Nervous System disease area. [Domain Therapeutics SA] Press Release

Local Titans of Healthcare and Medical Research-Barrow and TGen-Receive $3 Million from Piper Trust to Advance Transformative, Lifesaving Work

Two world-class healthcare and research institutions received a total of $3 million from Virginia G. Piper Charitable Trust in support of their quests to advance scientific and medical discovery. [Barrow Neurological Foundation (Business Wire, Inc.)] Press Release

The Women’s Alzheimer’s Movement Awards Seven Grants to Accelerate Gender-Based Research in Alzheimer’s Disease

The Women’s Alzheimer’s Movement^™ (WAM) announced that it has awarded seven research grants to leading scientific institutions actively seeking to understand why Alzheimer’s disease disproportionately affects more women than men. This year’s grants bring WAM’s research funding total to $1.5 million in just three years since the program began. [The Women’s Alzheimer’s Movement] Press Release

VHLA Announces 2018 Research Grant Recipients

Von Hippel-Lindau Alliance announced it awarded three research grants totaling nearly $300,000 as part of the 2018 VHLA Research Grant Program. [The VHL Alliance (PR Newswire Association LLC)] Press Release

Tocagen and NRG Oncology to Collaborate on a Phase II/III Trial of Toca 511 & Toca FC in Newly Diagnosed Glioblastoma

Tocagen Inc. announced that the Cancer Therapy and Evaluation Program Brain Malignancies Steering Committee has approved a concept to develop a clinical trial utilizing the investigational therapeutic regimen Toca 511 & Toca FC for the treatment of patients with newly diagnosed glioblastoma. [Tocagen Inc] Press Release

Government Loyalist Appointed New UK Science Minister as Brexit Woes Continue

Amid the carnage of Brexit, the UK government has gained a new science minister. Chris Skidmore was appointed on 5 December, succeeding Sam Gyimah, who resigned last week over the direction of Brexit negotiations. [Nature News] Editorial

Researchers Sign Petition Backing Plans to End Paywalls

More than 1,400 researchers have signed an online letter backing the principles of Plan S, the bold open-access initiative led by research agencies who say that, by 2020, papers resulting from their funding should be immediately free to read on publication. [Nature News] Editorial

NEW Lorne Cancer Conference 2019
February 14-16, 2019
Lorne, Australia

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NEW Assistant/Associate Professor – Neurodevelopmental Disease (Children’s National Health System)

NEW Research Associate – Neuroscience (Cardiff University)

Assistant Professor – Neuroscience (Dalhousie University)

Senior Scientist – Neuroscience Drug Discovery (Ionis Pharmaceuticals)

PhD – Neuroscience (Institute for Neuroscience)

Postdoctoral Associate – Cancer & Stem Cell (Weill Cornell Medicine)

Director – Tanz Centre for Research in Neurodegenerative Diseases (University of Toronto)

Postdoctoral Position – Neuroscience (Boston Children’s Hospital)

Faculty Positions – Translational Neurosciences (Wayne State University)

Postdoctoral Scholar – Medulloblastoma (University of California, San Francisco)

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