Neural Cell News Volume 11.46 | Nov 22 2017

TOP STORY

Vasohibins/SVBP Are Tubulin Carboxypeptidases (TCP) that Regulate Neuron Differentiation

Investigators used chemical proteomics with a potent unique irreversible inhibitor to show that the major brain TCP is a complex of vasohibin-1 with the small vasohibin binding protein (SVBP). Knock down of vasohibins disrupted neuronal migration in developing mouse neocortex. [Science] Abstract

(Ranked by impact factor of the journal)

Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons

Researchers showed that the secreted guidance cue semaphorin 3F (Sema3F) and its neuropilin-2/plexinA3 holoreceptor mediate homeostatic plasticity in cortical neurons. [Neuron] Abstract

Patient-Derived iPSCs Show Premature Neural Differentiation and Neuron Type-Specific Phenotypes Relevant to Neurodevelopment

Scientists studied the role of the mutation BRAF^Q257R, the most common cause of cardiofaciocutaneous syndrome (CFC), in an induced pluripotent stem cell (iPSC)-derived model of human neurodevelopment. In iPSC-derived neuronal cultures from CFC subjects, they observed decreased p-AKT and p-ERK1/2 compared to controls, as well as a depleted neural progenitor pool and rapid neuronal maturation. [Mol Psychiatry] Abstract

Changes in Chromatin State Reveal ARNT2 at a Node of a Tumorigenic Transcription Factor Signature Driving Glioblastoma Cell Aggressiveness

The authors mapped the changes in active (H3K4me3) and repressive (H3K27me3) histone modifications accompanying the repression of glioblastoma stem-like cells tumorigenicity. [Acta Neuropathol] Full Article

TRIM24 Is an Oncogenic Transcriptional Co-Activator of STAT3 in Glioblastoma

In multiple glioma cell lines and patient-derived glioma stem cells, epidermal growth factor receptor (EGFR) signaling promoted H3K23 acetylation and association with tripartite motif-containing 24 (TRIM24). Consequently, TRIM24 functioned as a transcriptional co-activator and recruited STAT3, leading to stabilized STAT3-chromatin interactions and subsequent activation of STAT3 downstream signaling, thereby enhancing EGFR-driven tumorigenesis. [Nat Commun] Full Article

Human Stem Cell–Derived Astrocytes Replicate Human Prions in a PRNP Genotype–Dependent Manner

The authors showed that astrocytes derived from human induced pluripotent stem cells (iPSCs) support the replication of prions from brain samples of Creutzfeldt–Jakob disease (CJD) patients. For experimental exposure of astrocytes to variant CJD (vCJD), the kinetics of prion replication occur in a prion protein codon 129 genotype–dependent manner, reflecting the genotype-dependent susceptibility to clinical vCJD found in patients. [J Exp Med] Abstract | Press Release

S-Nitrosylation of PINK1 Attenuates PINK1/Parkin-Dependent Mitophagy in hiPSC-Based Parkinson’s Disease Models

Researchers describe a molecular mechanism for impairment of mitophagy via formation of S-nitrosylated PINK1 (SNO-PINK1). Mitochondrial insults simulating age- or environmental-related stress lead to increased SNO-PINK1, inhibiting its kinase activity. SNO-PINK1 decreases parkin translocation to mitochondrial membranes, disrupting mitophagy in cell lines and human-iPSC-derived neurons. [Cell Rep] Full Article | Press Release | Graphical Abstract

Cell-Type Dependent Alzheimer’s Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability

Scientists examined neurons derived from iPSCs of patients harboring an amyloid precursor protein mutation to quantify Alzheimer’s disease (AD)-relevant phenotypes following directed differentiation to rostral fates of the brain (vulnerable) and caudal fates (relatively spared) in AD. [Stem Cell Reports] Full Article | Press Release | Graphical Abstract

PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer’s Disease

Researchers describe the generation of functional astrocytes from induced pluripotent stem cells (iPSCs) derived from Alzheimer’s disease (AD) patients with PSEN1 ΔE9 mutation, as well as healthy and gene-corrected isogenic controls. AD astrocytes manifest hallmarks of disease pathology, including increased β-amyloid production, altered cytokine release, and dysregulated Ca²⁺ homeostasis. [Stem Cell Reports] Full Article | Press Release

Parkinson’s Disease-Associated LRRK2 Hyperactive Kinase Mutant Disrupts Synaptic Vesicle Trafficking in Ventral Midbrain Neurons

Investigators showed that the most common Parkinson’s disease mutation LRRK2 G2019S impairs synaptic vesicle endocytosis in ventral midbrain neurons, including dopaminergic neurons, and the slowed endocytosis can be rescued by inhibition of LRRK2 kinase activity. [J Neurosci] Abstract

Neural Differentiation of Spheroids Derived from HiPSC-MSC Co-Culture

The authors investigated the impact of the composition and structure of 3-D hybrid spheroids of human induced pluripotent stem cells (hiPSCs) and human mesenchymal stem cells (hMSCs) on dorsal cortical differentiation and the secretion of extracellular matrices and trophic factors in vitro. The hybrid spheroids were formed at different hiPSC:hMSC ratios using direct mixing or pre-hiPSC aggregation method, which generated dynamic spheroid structure. [Tissue Eng Part A] Abstract

Microglia and Macrophages in Brain Homeostasis and Disease

Investigators review the current knowledge of how and where brain macrophages are generated, with a focus on parenchymal microglia. [Nat Rev Immunol] Abstract

Parkinson’s Disease: Experimental Models and Reality

The authors highlight progress in generating rodent models of Parkinson’s disease (PD) based on impairments of four major cellular functions. They attempt to evaluate how impairment of these major cellular systems contribute to PD and how they can be exploited in rodent models. They review recent cell biological studies suggesting a link between αS aggregation and impairment of nuclear membrane integrity, as observed during cellular models of apoptosis. [Acta Neuropathol] Abstract

3-D Bioprinting of Neural Tissue for Applications in Cell Therapy and Drug Screening

This review details current efforts at bioprinting neural tissue and highlights promising avenues for future work. [Front Bioeng Biotechnol] Full Article

Visit our reviews page to see a complete list of reviews in the neural cell research field.

DSU Neuroscience Center Awarded $10.9M NIH Grant

The National Institutes of Health (NIH) has awarded DSU’s Delaware Center for Neuroscience Research the largest grant in the University’s history, $10.9 million over five years. [Delaware State University] Press Release

Stanford Researchers Get NIH Grant to Study Autism

Researchers at the School of Medicine and at UCLA have received a $9.3 million grant from the National Institutes of Mental Health to study the ways that many genes associated with autism spectrum disorder may converge to affect a smaller number of molecular pathways or cellular processes responsible for the condition. [Stanford Medicine] Press Release

Kessler Foundation Awarded Traumatic Brain Injury Model System Grant

The National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) has awarded Kessler Foundation a $2.23 million, five-year grant to fund the Northern New Jersey Traumatic Brain Injury System (NNJTBIS). The NNJTBIS is a comprehensive system of clinical care, research, information and resource dissemination aimed at improving quality of life for people with traumatic brain injury. [Kessler Foundation] Press Release

ALS Canada Awards $3 Million for 12 New Research Projects to Help Make Amyotrophic Lateral Sclerosis (ALS) a Treatable, Not Terminal Disease

The ALS Society of Canada announced 12 exciting new research projects being funded in 2017 through the ALS Canada Research Program. [ALS Society of Canada] Press Release

Evelo Biosciences and Mayo Clinic Collaborate to Advance Monoclonal Microbials for the Treatment of Inflammatory and Neuroinflammatory Diseases

Evelo Biosciences announced a collaboration with Mayo Clinic to develop and commercialize monoclonal microbials for the treatment of inflammatory and neuroinflammatory diseases. [Evelo Biosciences (PR Newswire Association LLC.)] Press Release

Acorda Discontinues Tozadenant Development Program

Acorda Therapeutics, Inc. announced that it is discontinuing its clinical development program for tozadenant, an investigational treatment for Parkinson’s disease, including immediately discontinuing dosing of all participants currently enrolled in its tozadenant studies. [Acorda Therapeutics, Inc.] Press Release

Still No Science Advisor at the White House

Ten months into his presidency, Donald Trump has yet to name a science advisor. It’s the longest amount of time a modern president has taken to nominate someone to the position since at least 1976, when Congress established the White House’s Office of Science and Technology Policy. [MIT Technology Review] Editorial

Sudden Shift at a Public Health Journal Leaves Scientists Feeling Censored

For much of its 22-year existence, few outside the corner of science devoted to toxic chemicals paid much attention to the International Journal of Occupational and Environmental Health. But now, a feud has erupted over the small academic publication, as its editorial board — the scientists who advise the journal’s direction and handle article submissions — has accused the journal’s new owner of suppressing a paper and promoting “corporate interests over independent science in the public interest.” [Pro Publica Inc.] Editorial

Director of HHS Scientific Fraud Office Is out after Stormy 2-Year Tenure

The controversial director of the office that polices research fraud in U.S.-funded biomedical labs is temporarily moving to another agency. Kathy Partin has been removed after nearly two years as director of the U.S. Office of Research Integrity in Rockville, Maryland, according to Retraction Watch. [ScienceInsider] Editorial

European Medicines Agency Will Move to Amsterdam

The European Medicines Agency, charged with evaluating human and animal medicinal products for the European Union, will relocate to Amsterdam after it was selected in a draw of lots between it and Milan. [ScienceInsider] Editorial

NEW Keystone Symposia: Neuroinflammation: Causes, Concepts and Consequences
December 12, 2017
Online

Visit our events page to see a complete list of events in the community.

NEW Bioengineer – Stem Cell Research (Scaled Biolabs Inc.)

NEW Postdoctoral Position – Brain Injury and Repair (University of Pennsylvania)

Faculty Position – Neurobiology (NYU Shanghai)

Chief Neuroscience Officer (Wyss Center for Bio and NeuroEngineering)

Postdoctoral Fellow/Associate – Developmental Neurobiology (SUNY Upstate Medical College)

Associate Research Scientist – Neurophysiology (Columbia University)

Associate Professor – Neurology (Massachusetts General Hospital & Harvard Medical School)

Postdoctoral Fellow – Stem Cell Biology and Neuroscience (The University of Texas Health Science Center at Houston)

Assistant Professor – Cellular and Molecular Neuroscience (University of British Columbia)

Faculty Position – Spinal Cord and Brain Injury Research (Indiana University)

Faculty Members – Neuroscience (Mercer University)

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

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