Neural Cell News Volume 13.39 | Oct 9 2019

TOP STORY

Genomic Decoding of Neuronal Depolarization by Stimulus-Specific NPAS4 Heterodimers

Investigators showed that action potentials and excitatory postsynaptic potentials in mouse hippocampal neurons triggered two spatially segregated and molecularly distinct induction mechanisms that led to the expression of the ITF NPAS4. These two pathways culminated in the formation of stimulus-specific NPAS4 heterodimers that exhibited distinct DNA binding patterns. [Cell] Abstract | Graphical Abstract

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Neuromodulator Signaling Bidirectionally Controls Vesicle Numbers in Human Synapses

Researchers discovered in human neurons an unanticipated presynaptic mechanism that acutely changed synaptic ultrastructure and regulated synaptic communication. Activation of neuromodulator receptors bidirectionally controlled synaptic vesicle numbers within nerve terminals. [Cell] Abstract | Graphical Abstract

Engineering of Human Brain Organoids with a Functional Vascular-Like System

The authors engineered human embryonic stem cells to ectopically expressed human ETS variant 2 (ETV2). ETV2-expressing cells in human cortical organoids (hCOs) contributed to forming a complex vascular-like network in hCOs. Importantly, the presence of vasculature-like structures resulted in enhanced functional maturation of organoids. [Nat Med] Abstract

Metformin Restores CNS Remyelination Capacity by Rejuvenating Aged Stem Cells

Scientists showed that the differentiation potential of adult rodent oligodendrocyte progenitor cells (OPCs) decreased with age. Aged OPCs became unresponsive to pro-differentiation signals, suggesting intrinsic constraints on therapeutic approaches aimed at enhancing OPC differentiation. [Cell Stem Cell] Full Article | Graphical Abstract

Oligodendrocyte Death in Pelizaeus-Merzbacher Disease Is Rescued by Iron Chelation

Using induced pluripotent stem cell and gene-correction, researchers showed that patient-derived oligodendrocytes could develop to the pre-myelinating stage, but subsequently underwent cell death. Mutant oligodendrocytes demonstrated key hallmarks of ferroptosis including lipid peroxidation, abnormal iron metabolism, and hypersensitivity to free iron. [Cell Stem Cell] Abstract | Graphical Abstract

Impaired Adult Neurogenesis Is an Early Event in Alzheimer’s Disease Neurodegeneration, Mediated by Intracellular Aβ Oligomers

Impaired neurogenesis of Tg2576 progenitors was remarkably rescued both in vitro and in vivo by the expression of a conformation-specific anti-AβOs intrabody, which selectively interfered with the intracellular generation of AβOs in the endoplasmic reticulum. [Nat Neurosci] Full Article

FUS-Mediated Regulation of Acetylcholine Receptor Transcription at Neuromuscular Junctions Is Compromised in Amyotrophic Lateral Sclerosis

Mechanistically, FUS collaborated with the ETS transcription factor ERM to stimulate transcription of acetylcholine receptor genes. Co-cultures of induced pluripotent stem cell-derived motor neurons and myotubes from patients with FUS-amyotrophic lateral sclerosis revealed endplate maturation defects due to intrinsic FUS toxicity in both motor neurons and myotubes. [Nat Neurosci] Abstract

CRISPR-Cas9 Screens Identify the RNA Helicase DDX3X as a Repressor of C9ORF72 (GGGGCC)n Repeat-Associated Non-AUG Translation

Investigators performed genome-wide CRISPR-Cas9 screens for modifiers of dipeptide repeat protein production in human cells. They found that DDX3X, an RNA helicase, suppressed the repeat-associated non-AUG translation of GGGGCC repeats. [Neuron] Abstract | Graphical Abstract

3D Extracellular Matrix Microenvironment in Bioengineered Tissue Models of Primary Pediatric and Adult Brain Tumors

Using pediatric ependymoma and adult glioblastoma as examples, the 3D brain extracellular matrix (ECM)-containing micro-environment with a balance of cell-cell and cell-matrix interactions supports distinctive phenotypes associated with tumor type-specific and ECM-dependent patterns in the tumor cells’ transcriptomic and release profiles. [Nat Commun] Full Article

Neuronal O-GlcNAcylation Improves Cognitive Function in the Aged Mouse Brain

Overexpressing O-GlcNAc transferase (OGT) in mature hippocampal neurons using a viral-mediated approach enhanced associative fear memory in young adult mice. Excitingly, in aged mice overexpressing neuronal OGT in the aged hippocampus rescued in part age-related impairments in spatial learning and memory as well as associative fear memory. [Curr Biol] Full Article | Graphical Abstract

The Necroptosis Machinery Mediates Axonal Degeneration in a Model of Parkinson Disease

Researchers demonstrated activation of necroptosis in postmortem brain tissue from Parkinson’s disease patients and in a toxin-based mouse model of the disease. Inhibition of key components of the necroptotic pathway resulted in a significant delay of 6-hydroxydopamine-dependent axonal degeneration of dopaminergic and cortical neurons in vitro. [Cell Death Differ] Abstract

Stem Cell Modeling of Neuroferritinopathy Reveals Iron as a Determinant of Senescence and Ferroptosis during Neuronal Aging

Scientists established lines of induced pluripotent stem cells from fibroblasts from two neuroferritinopathy (NF) patients and one isogenic control obtained by CRISPR/Cas9 technology. NF fibroblasts, neural progenitors, and neurons exhibited the presence of increased cytosolic iron, which was also detectable as: ferritin aggregates, alterations in the iron parameters, oxidative damage, and the onset of a senescence phenotype, particularly severe in the neurons. [Stem Cell Reports] Full Article | Graphical Abstract

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Deciphering Brain Complexity Using Single-Cell Sequencing

Scientists introduce the progresses in both experimental and computational methods of single-cell sequencing technology. Applications of single-cell sequencing-based technologies in brain research, including cell type classification, brain development, and brain disease mechanisms, are then elucidated by representative studies. [Genomics Proteomics Bioinformatics] Full Article

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Amylyx Pharmaceuticals Announces Last Patient Completes Last Study Visit in CENTAUR Phase II Study of AMX0035 in ALS

Amylyx Pharmaceuticals, Inc. announced that the last participant has completed the planned 24 weeks of study treatment in CENTAUR, a clinical trial assessing the safety and efficacy of AMX0035 in people with ALS. [Amylyx Pharmaceuticals, Inc. (Business Wire, Inc.)] Press Release

Yumanity Therapeutics Initiates Phase I Clinical Trial of Lead Candidate YTX-7739 for The Treatment of Parkinson’s Disease

Yumanity Therapeutics announced that the first subject cohort has been dosed in a Phase I clinical trial evaluating the safety and tolerability of YTX-7739 in healthy volunteers. [Yumanity Therapeutics] Press Release

Annexon Biosciences Reports Top-Line Phase Ib Results for Novel C1q Inhibitor ANX007 in Glaucoma

Annexon Biosciences announced encouraging results from a Phase Ib dose-ranging clinical trial to evaluate its anti-C1q antibody, ANX007, in patients with glaucoma. ANX007 is an investigational monoclonal antibody antigen-binding fragment formulated for intravitreal administration. [Annexon Biosciences] Press Release

City of Hope Is Enrolling Patients in First of Its Kind Clinical Trial for Brain Tumor Patients

City of Hope has opened a first-in-human clinical trial for patients with recurrent glioblastoma – the trial is the first to combine City of Hope’s chimeric antigen receptor T cells that target the IL13Rα2 antigen common on brain tumor cells in combination with nivolumab, an anti-PD1 antibody, and ipilimumab, also a checkpoint inhibitor that blocks the CTLA-4 protein. [City of Hope] Press Release

NIH Marquee Awards for ‘High Risk, High Reward’ Projects Skew Male—Again

For three of the four types of “high risk, high reward” awards, women won in numbers that met or exceeded their representation in the applicant pool. However, that representation was meager: 18% percent to 38% of the applicants for these four awards were women, although women have earned more than 50% of US PhDs in biological sciences in every year since 2008. [ScienceMagazine] Editorial

Biologists Who Decoded How Cells Sense Oxygen Win Medicine Nobel

A trio of researchers has won the 2019 Nobel Prize in Physiology or Medicine for describing how cells sense and respond to changing oxygen levels by switching genes on and off – a discovery that has been key in understanding human diseases such as cancer and anemia. [Nature News] Editorial

Split Decisions: How Brexit Has Taken a Toll on Five Researchers

On 23 June 2016, 34 million UK citizens took to the polls to vote on a simple, fateful question: Should the United Kingdom remain a part of the European Union, or should it leave? Nearly 52%—a majority of 1.3 million—wanted out, and conservative politicians vowed to carry out the people’s wishes. [ScienceInsider] Editorial

NEW Tumor Immunology and Immunotherapy
November 17-20, 2019
Boston, Massachusetts, United States

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NEW Assistant Professor – The Neural Basis of Behavior (Mortimer B. Zuckerman Mind Brain Behavior Institute)

Postdoctoral Scholar – Neural Precursor Cells (University of South Florida)

Faculty Positions – Autism and Neurodevelopmental Disorders (University of South Carolina)

Postdoctoral Researcher – Amyloid Filiments in Neurodegenerative Disease (MRC Laboratory of Molecular Biology)

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

Research Fellow – Neurodegenerative Disease (University College London)

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

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

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)

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