Neural Cell News Volume 13.35 | Sep 11 2019

TOP STORY

Reconstruction of 1,000 Projection Neurons Reveals New Cell Types and Organization of Long-Range Connectivity in the Mouse Brain

Scientists present a robust and efficient platform for imaging and reconstructing complete neuronal morphologies, including axonal arbors that span substantial portions of the brain. They used this platform to reconstruct more than 1,000 projection neurons in the motor cortex, thalamus, subiculum, and hypothalamus. [Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Self-Organizing Neuruloids Model Developmental Aspects of Huntington’s Disease in the Ectodermal Compartment

Using isogenic Huntington’s disease human embryonic stem cells and deep neural network analysis, researchers showed how specific phenotypic signatures arose in their model of early human development as a consequence of mutant huntingtin protein, outlining an approach for phenotypic drug screening. [Nat Biotechnol] Abstract

Simultaneous Profiling of 3D Genome Structure and DNA Methylation in Single Human Cells

The authors developed single-nucleus methyl-3C sequencing to capture chromatin organization and DNA methylation information and robustly separate heterogeneous cell types. Applying this method to >4,200 single human brain prefrontal cortex cells, they reconstructed cell-type specific chromatin conformation maps from 14 cortical cell types. [Nat Methods] Full Article

SETD5 Regulates Chromatin Methylation State and Preserves Global Transcriptional Fidelity during Brain Development and Neuronal Wiring

Scientists found that Setd5 haploinsufficiency impaired the proliferative dynamics of neural progenitors and synaptic wiring of neurons, ultimately resulting in behavioral deficits in mice. [Neuron] Abstract | Graphical Abstract

Nuclear Factor I-A Regulates Diverse Reactive Astrocyte Responses after CNS Injury

Investigators showed that nuclear factor I-A was highly expressed in reactive astrocytes in human neurological injury and identified unique roles across distinct injury states and regions of the CNS. [J Clin Invest] Full Article

Synaptotagmin 1 Clamps Synaptic Vesicle Fusion in Mammalian Neurons Independent of Complexin

Researchers showed that the C2B domain of synaptotagmin, independent of complexin, was the molecular clamp that arrested synaptic vesicles prior to Ca²⁺-triggered fusion. [Nat Commun] Full Article

Oligodendrocytes Express Synaptic Proteins that Modulate Myelin Sheath Formation

Scientists used fusion proteins to track synaptic vesicle localization and membrane fusion in zebrafish during developmental myelination and investigated expression and localization of PSD95, a dendritic post-synaptic protein, within oligodendrocytes. [Nat Commun] Full Article

Discovery of a New Pyrimidine Synthesis Inhibitor Eradicating Glioblastoma-Initiating Cells

Among the effective compounds, scientists identified 10580, which induced cell cycle arrest, decreased the expression of stem cell factors in glioblastoma-initiating cells and prevented tumorigenesis upon oral administration without any visible side effects. [Neuro Oncol] Abstract

PHF2 Histone Demethylase Prevents DNA Damage and Genome Instability by Controlling Cell Cycle Progression of Neural Progenitors

Scientists demonstrated that the histone H3 lysine 9 methylation demethylase PHF2 was essential for neural progenitor proliferation in vitro and for early neurogenesis in the chicken spinal cord. [Proc Natl Acad Sci USA] Abstract

A NeuroD1 AAV-Based Gene Therapy for Functional Brain Repair after Ischemic Injury through In Vivo Astrocyte-to-Neuron Conversion

The authors demonstrated that NeuroD1-mediated in situ astrocyte-to-neuron conversion could regenerate a large number of functional new neurons after ischemic injury. [Mol Ther] Abstract | Full Article | Graphical Abstract

Drug Repurposing for Alzheimer’s Disease Based on Transcriptional Profiling of Human iPSC-Derived Cortical Neurons

Scientists developed a methodology harnessing the transcriptional changes associated with Alzheimer’s disease to develop a high content quantitative disease phenotype that can be used to repurpose existing drugs. [Transl Psychiatry] Full Article

RIP1/RIP3/MLKL Mediates Dopaminergic Neuron Necroptosis in a Mouse Model of Parkinson Disease

Upregulation of inflammatory cytokines in methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride-treated mice was partially inhibited by deletion of receptor interacting protein kinase-3 (RIP3) or mixed lineage kinase domain-like (MLKL) gene, indicating that a positive feedback loop exists between these genes and inflammatory cytokines. [Lab Invest] Abstract

Atomoxetine Produces Oxidative Stress and Alters Mitochondrial Function in Human Neuron-Like Cells

Investigators found that the highest concentrations of atomoxetine in neuron-like cells, caused cell death and an increase in cytosolic and mitochondrial reactive oxygen species, and alterations in mitochondrial mass, membrane potential and autophagy. [Sci Rep] Full Article

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Aging as a Risk Factor for Neurodegenerative Disease

Scientists discuss the pathogenesis of Alzheimer’s disease, Parkinson’s disease and other neurodegenerative diseases, and describe their associations with the nine biological hallmarks of aging: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, deregulated nutrient sensing, stem cell exhaustion and altered intercellular communication. [Nat Rev Neurol] Abstract

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New Head-to-Head Phase III Study Data Show Ponesimod Superiority Versus Aubagio^® (Teriflunomide) 14 mg in Adults with Relapsing Multiple Sclerosis (MS)

The Janssen Pharmaceutical Companies of Johnson & Johnson announced the results from the Phase III OPTIMUM study for ponesimod, an investigational selective S1P1 receptor modulator, showing superior efficacy on the primary endpoint and most secondary endpoints compared to Aubagio^® 14 mg in adults with relapsing MS. [Janssen Global Services, LLC.] Press Release

Bristol-Myers Squibb Provides Update on Phase III Opdivo (Nivolumab) CheckMate -548 Trial in Patients with Newly Diagnosed MGMT-Methylated Glioblastoma Multiforme

Bristol-Myers Squibb announced that the Phase III CheckMate -548 trial evaluating the addition of Opdivo to the current standard of care versus the standard of care alone did not meet one of its primary endpoints, progression-free survival, in patients with newly diagnosed glioblastoma multiforme. [Bristol-Myers Squibb] Press Release

Axon Announces Positive Results from Phase II ADAMANT Trial for AADvac1 in Alzheimer’s Disease

AXON Neuroscience SE announced the results of the Phase II trial for AADvac1, its first-in-class vaccine to slow down the progression of Alzheimer’s Disease. [AXON Neuroscience SE] Press Release

VBI Vaccines Announces Phase IIa Clinical Evaluation of VBI-1901 Cancer Vaccine Candidate in Combination with GSK’s AS01B Adjuvant System in Recurrent Glioblastoma Patients

VBI Vaccines Inc. announced a collaboration with GlaxoSmithKline (GSK) to clinically evaluate the combination of VBI-1901, VBI’s cancer vaccine immunotherapeutic, with GSK’s proprietary AS01B adjuvant system. [VBI Vaccines Inc.] Press Release

Alector Initiates Phase II Trial of AL001 in Patients with Frontotemporal Dementia

Alector, Inc. announced the initiation of patient screening and enrollment for the INFRONT Phase II clinical trial for its product candidate AL001. [Alector, Inc.] Press Release

Lineage Cell Therapeutics Announces Issuance of US Patent for Method of Treating Spinal Cord Injury with Stem Cell-Derived Oligodendrocyte Progenitor Cells

Lineage Cell Therapeutics, Inc. announced that the United States Patent and Trademark Office has issued U.S. Patent No. 10,286,009, entitled “Pluripotent stem cell-derived oligodendrocyte progenitor cells for the treatment of spinal cord injury” covering methods for utilizing pluripotent stem cell-derived oligodendrocyte progenitor cells for the treatment of spinal cord injury. [Lineage Cell Therapeutics, Inc.] Press Release

EU Research Commissioner Named, but Lacks ‘Research’ in Her Title

Mariya Gabriel, a conservative politician from Bulgaria, is slated to become the next European research chief- although her job title, unlike that of her predecessors, doesn’t include the words “research” or “science.” [ScienceInsider] Editorial

Frontrunner to Lead FDA, Dogged by Controversies, Has Developed Knack for Confronting Them

Before he interviewed with President Trump to become FDA commissioner, Dr. Stephen Hahn had only been here once in a formal capacity: to apologize to Congress. [STAT News] Editorial

Northwestern University Stem Cell Therapy Clinic Closes Abruptly

A pioneering stem cell clinical trial program in the US is closing up shop, a surprise move for what had appeared to be a successful endeavor at testing hematopoietic stem cell transplantations for autoimmune and other diseases. [STAT News] Editorial

Google Bans Ads for Experimental Medical Treatments

Google announced it would “prohibit advertising for unproven or experimental medical techniques such as most stem cell therapy, cellular (non-stem) therapy, and gene therapy.” [STAT News] Editorial

NEW Cancer Epigenetics: New Mechanisms and Therapeutic Opportunities
January 26-30, 2020
Keystone, Colorado, United States

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NEW Assistant/Associate Professor – Pediatric Brain Tumors (Baylor College of Medicine)

NEW Research Fellow – Neurodegenerative Disease (University College London)

NEW Faculty Positions – Brain Disorders (IDG/McGovern Institute for Brain Research)

NEW Postdoctoral Position – Neural Cell Research (New York Medical College)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Brain Organoids and Neurodegeneration Research (DZNE)

Postdoctoral Researcher – Neural Research (Flanders Institute for Biotechnology)

Assistant Professor – Neurobiology (University of California, Berkeley)

Postdoctoral Research Associate – Neural Stem Cell Research (St. Jude Children’s Research Hospital)

Associate Research Scientist – Brain Research (Mortimer B. Zuckerman Mind Brain Behavior Institute)

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