Neural Cell News Volume 12.44 | Nov 7 2018

TOP STORY

Shared and Distinct Transcriptomic Cell Types across Neocortical Areas

To investigate the diversity of cell types across the mouse neocortex, researchers analyzed 23,822 cells from two areas at distant poles of the mouse neocortex: the primary visual cortex and the anterior lateral motor cortex. [Nature] Abstract | Press Release | Editorial

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N⁶-Methyladenine DNA Modification in Glioblastoma

Scientists report the identification of novel N⁶-methyladenine DNA modifications in human tissues and implicate this epigenetic mark in human disease, specifically the highly malignant brain cancer glioblastoma. [Cell] Abstract | Press Release | Graphical Abstract

Reversal of Proliferation Deficits Caused by Chromosome 16p13.11 Microduplication through Targeting NFκB Signaling: An Integrated Study of Patient-Derived Neuronal Precursor Cells, Cerebral Organoids and In Vivo Brain Imaging

Researchers have undertaken brain imaging of patients carrying microduplications in chromosome 16p13.11 and unaffected family controls, in parallel with induced-pluripotent stem cell-derived cerebral organoid studies of the same patients. [Mol Psychiatry] Full Article

Dynamic Ubiquitylation of Sox2 Regulates Proteostasis and Governs Neural Progenitor Cell Differentiation

The authors showed that the RING-finger ubiquitin ligase complex CUL4A^DET1-COP1 and the deubiquitylase OTUD7B govern Sox2 protein stability during neural progenitor cells (NPCs) differentiation. Sox2 expression declined concordantly with OTUD7B and reciprocally with CUL4A and COP1 levels upon NPCs differentiation. [Nat Commun] Full Article

Inhibition of HDAC3 Reverses Alzheimer’s Disease-Related Pathologies In Vitro and in the 3xTg-AD Mouse Model

RGFP-966, a brain-penetrant and selective HDAC3 inhibitor, or HDAC3 silencing, increased BDNF expression, increased histone H3 and H4 acetylation, decreased tau phosphorylation and tau acetylation at disease-associated sites, reduced β-secretase cleavage of the amyloid precursor protein (APP), and decreased Aβ1–42 accumulation in HEK-293 cells overexpressing APP with the double Swedish mutation. [Proc Natl Acad Sci USA] Full Article

The Scalloped and Nerfin-1 Transcription Factors Cooperate to Maintain Neuronal Cell Fate

The authors showed that the scalloped and nervous fingers-1 (Nerfin-1) transcription factors physically and functionally interact to maintain medulla neuron fate in the Drosophila melanogaster CNS. [Cell Rep] Full Article | Graphical Abstract

A Pathway for Parkinson’s Disease LRRK2 Kinase to Block Primary Cilia and Sonic Hedgehog Signaling in the Brain

Scientists showed that LRRK2 kinase interferes with primary cilia formation in cultured cells, human LRRK2 G2019S iPS cells and in the cortex of LRRK2 R1441C mice. Rab10 phosphorylation strengthened its intrinsic ability to block ciliogenesis by enhancing binding to RILPL1. [Elife] Full Article

The Cellular NMD Pathway Restricts Zika Virus Infection and Is Targeted by the Viral Capsid Protein

Researchers showed that in vitro Zika virus infection of human cells, including neural progenitor cells, causes disruption of the nonsense-mediated mRNA decay (NMD) pathway. NMD is a cellular mRNA surveillance mechanism that is required for normal brain size in mice. [MBio] Full Article

Calcium Dysregulation Mediates Mitochondrial and Neurite Outgrowth Abnormalities in SOD2 Deficient Embryonic Cerebral Cortical Neurons

Investigators showed that superoxide dismutase 2 (SOD2) plays critical roles in maintaining calcium homeostasis in newly generated embryonic cerebral cortical neurons, which is essential for normal mitochondrial function and subcellular distribution, and neurite outgrowth [Cell Death Differ] Abstract

Conditioned Media from AICAR-Treated Skeletal Muscle Cells Increases Neuronal Differentiation of Adult Neural Progenitor Cells

Researchers used an in vitro cell assay and proteomic analysis to investigate the effects of proteins secreted from skeletal muscle cells on adult hippocampal neural progenitor cell differentiation. [Neuropharmacology] Abstract

Aggregated SOD1 Causes Selective Death of Cultured Human Motor Neurons

Scientists investigated the uptake of pre-formed superoxide dismutase (SOD1) aggregates by cultures containing pluripotent stem cell-derived human motor neurons. They found that all cells take up aggregates by a process resembling fluid-phase endocytosis, just as found in earlier studies. However, motor neurons, despite taking up smaller amounts of SOD1, were much more vulnerable to the accumulating aggregates. [Sci Rep] Full Article

Involvement of Oxidative Stress in Di-2-Ethylhexyl Phthalate (DEHP)-Induced Apoptosis of Mouse NE-4C Neural Stem Cells

Investigators found that DEHP significantly inhibited viability of mouse NE-4C neural stem cells and caused lactate dehydrogenase release from the cells. [Neurotoxicology] Abstract

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Cellular and Molecular Aspects of Parkinson Treatment: Future Therapeutic Perspectives

Variations in treatment response and side effects of current drugs have convinced scientists to think of treating Parkinson’s disease at the cellular and molecular level. Molecular and cellular therapy for Parkinson’s disease include (i) cell transplantation therapy with human embryonic stem cells, human induced pluripotent stem cells and human fetal mesencephalic tissue, (ii) immunological and inflammatory therapy which is done using antibodies, and (iii) gene therapy with AADC-TH-GCH gene therapy, viral vector-mediated gene delivery, RNA interference-based therapy, CRISPR-Cas9 gene editing system, and alternative methods such as optogenetics and chemogenetics. [Mol Neurobiol] Abstract

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Celprogen Introduces 3D Printed Human Brain Organelle Model System for Studying Neurological Disease That Can Be Utilized in Generating Novel Drugs

Celprogen Inc. announced that they have successfully finished printing 3D Brains from brain stem cells for studying neurological disease stages. [Press release from Celprogen Inc. (Business Wire Inc.) discussing research presented at the Annual Neuroscience Meeting, San Diego] Press Release

Concert Pharmaceuticals Presents Preclinical Data on CTP-692, a Novel Drug Candidate for Schizophrenia, Supporting Potential to Improve Safety Profile of D-Serine

Concert Pharmaceuticals, Inc. presented preclinical results that support the potential of CTP-692, the company’s novel drug candidate for schizophrenia, to improve the safety profile of D-serine. [Press release from Concert Pharmaceuticals, Inc. discussing research presented at the American College of Toxicology 2018 Annual Meeting, West Palm Beach] Press Release

Cavion’s T-Type Calcium Channel Modulator CX-8998 Is Superior to Current Standard of Care in Suppressing Absence Seizures in a Genetic Epilepsy Model

Cavion, Inc. announced that their first-in-class T-type calcium channel modulator CX-8998 significantly suppressed seizures in two translational animal models of absence epilepsy. [Press release from Cavion, Inc. (Business Wire Inc.) discussing research presented at the Annual Neuroscience Meeting, San Diego] Press Release

NIH Greatly Expands Investment in BRAIN Initiative

The National Institutes of Health (NIH) announced funding of more than 200 new awards, totaling over $220 million, through the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, an exciting trans-agency effort to arm researchers with revolutionary tools to fundamentally understand the neural circuits that underlie the healthy and diseased brain. [The National Institutes of Health] Press Release

NCAA and Department of Defense Expand Concussion Study with $22.5 Million in New Funding

The world’s most comprehensive concussion study is being dramatically expanded with an infusion of nearly $22.5 million in new funding from the U.S. Department of Defense and the NCAA to examine the impacts of head injuries over several years. [Indiana University] Press Release

SanBio Announces Phase II STEMTRA Trial Using SB623 Cells for Treatment of Patients with Traumatic Brain Injury Met Primary Endpoint

The SanBio Group announced that the Phase II STEMTRA trial using SB623 cells for the treatment of patients with traumatic brain injury, met its primary endpoint. [The SanBio Group (Bussiness Wire Inc.)] Press Release

First Patient Enrolled in Investigator-Initiated Study of Tinostamustine in Glioblastoma

Purdue Pharma L.P. announced that the first patient has been enrolled in a Phase I investigator-initiated clinical trial of tinostamustine, an investigational treatment, in patients with newly-diagnosed unmethylated O⁶-Methylguanine-DNA-methyltransferase glioblastoma multiforme. [Purdue Pharma L.P.] Press Release

Four New BertarelliNeuro Research Projects Announced

The Bertarelli Foundation has awarded collaborative research grants to four teams of scientists representing Harvard Medical School, its affiliated teaching hospitals, and the Institute of Molecular and Clinical Ophthalmology in Basel, Switzerland, all focused on understanding and treating some of the most devastating sensory disorders, including deafness, blindness and pain. [The Bertarelli Foundation] Press Release

Society for Neuroscience Makes Record Number of Trainee Awards

For the second year, the Society for Neuroscience (SfN) awarded a record number of Trainee Professional Development Awards. Funding from the SfN Council and other generous donors allowed 261 young scientists to present their research and collaborate with leading neuroscientists from around the world at Neuroscience 2018. [Society for Neuroscience] Press Release

Some Takeaways for Science from Yesterday’s U.S. Elections

For scientists, the new Democratic majority in the U.S. House of Representatives isn’t the only important result from the midterm election. Four House incumbents active on science issues have been defeated, and a fifth is trailing. [ScienceInsider] Editorial

Wellcome and Gates Join Bold European Open-Access Plan

Two of the world’s largest biomedical research funders have backed a plan to make all papers resulting from work they fund open access on publication by 2020. The London-based Wellcome Trust and the Bill and Melinda Gates Foundation in Seattle, Washington, announced they were both endorsing ‘Plan S’, adding their weight to an initiative already backed by 13 research funders across Europe since its launch in September. [Nature News] Editorial

Europe’s Researchers Benefit From Reduced Bureaucracy

The European Union has made good on its promise to reduce the amount of red tape that scientists must wade through when applying for grants from its flagship funding program, according to a report released by the European Court of Auditors. [Nature News] Editorial

NEW Cancer Stem Cells: Impact on Treatment 2018
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