Neural Cell News Volume 11.30 | Aug 2 2017

TOP STORY

Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration

The authors describe the generation of medial ganglionic eminence (MGE) and cortex-specific organoids from human pluripotent stem cells (hPSCs) that recapitulate the development of MGE and cortex domains, respectively. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Zika Virus Directly Infects Peripheral Neurons and Induces Cell Death

Researchers showed that intraperitoneally or intraventricularly injected Zika virus (ZIKV) in the mouse can infect and impact peripheral neurons in vivo. ZIKV productively infected stem-cell-derived human neural crest cells and peripheral neurons in vitro, leading to increased cell death, transcriptional dysregulation and cell-type-specific molecular pathology. [Nat Neurosci] Full Article

Inhibition of Colony Stimulating Factor-1 Receptor Abrogates Microenvironment-Mediated Therapeutic Resistance in Gliomas

Using a PDGF-B-driven proneural glioma mouse model, the authors assessed a panel of tyrosine kinase inhibitors with different selectivity profiles. They found that PLX3397, an inhibitor of colony stimulating factor-1 receptor, blocks glioma progression, markedly suppresses tumor cell proliferation and reduces tumor grade. [Oncogene] Full Article

Loss of Brap Results in Premature G1/S Phase Transition and Impeded Neural Progenitor Differentiation

Researchers report that proper G1 phase completion in neural progenitor cells requires Brap, a Ras-Erk signaling modulator with ubiquitin E3 ligase activity. They identified Skp2 and Skp2-associated SCF ubiquitin ligase as a key target of Brap-mediated polyubiquitination. [Cell Rep] Full Article | Graphical Abstract

Enhanced Neuronal Regeneration in the CAST/Ei Mouse Strain Is Linked to Expression of Differentiation Markers after Injury

The authors investigated the basis for the enhanced nerve regenerative capacity of the CAST/Ei mouse strain relative to C57BL/6 mice. RNA sequencing of dorsal root ganglia (DRG) showed a CAST/Ei-specific upregulation of Ascl1 after injury. Ascl1 overexpression in DRG neurons of C57BL/6 mice enhanced their neurite outgrowth. [Cell Rep] Full Article | Graphical Abstract

Evaluating Synthetic Activation and Repression of Neuropsychiatric-Related Genes in hiPSC-Derived NPCs, Neurons, and Astrocytes

By applying a CRISPR-mediated gene-activation/repression platform to populations of human-induced pluripotent stem cell (hiPSC)-derived neural progenitor cells (NPCs), neurons, and astrocytes, investigators demonstrated that it is possible to manipulate endogenous expression levels of candidate neuropsychiatric risk genes across these three cell types. [Stem Cell Reports] Full Article

An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells

Scientists describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell intermediate. Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals were highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. [Stem Cell Reports] Full Article

Human Cytomegalovirus IE1 Downregulates Hes1 in Neural Progenitor Cells as a Potential E3 Ubiquitin Ligase

Researchers report that human cytomegalovirus (HCMV) infection downregulates hairy and enhancer of split 1 (Hes1) protein levels in infected neural progenitor cells (NPCs). The HCMV 72-kDa immediate-early 1 protein (IE1) was involved in Hes1 degradation by assembling a ubiquitination complex and promoting Hes1 ubiquitination as a potential E3 ubiquitin ligase, followed by proteasomal degradation of Hes1. [PLoS Pathog] Full Article

Quiescent Oct4⁺ Neural Stem Cells (NSCs) Repopulate Ablated Glial Fibrillary Acidic Protein⁺ NSCs in the Adult Mouse Brain

Scientists hypothesized that while primitive NSCs (pNSCs) are not very proliferative at baseline, they may exist as a reserve pool of NSCs in case of injury. To test this function of pNSCs, they obtained conditional Oct4 knockout mice, Oct4^fl/fl;Sox1^Cre, which do not yield adult pNSC-derived neurospheres. [Stem Cells] Abstract

Pre-Synaptic TrkB in Basolateral Amygdala Neurons Mediates BDNF Signaling Transmission in Memory Extinction

Investigators constructed a fluorescent coiled-coil domain 1 (CC1) and enhanced green fluorescent protein (EGFP) fused protein, CC1-EGFP, and found that CC1-EGFP could specifically interrupt TrkB anterograde axonal transport and its localization at the pre-synaptic site. Consistent with this, TrkB-mediated pre-synaptic vesicle release and retrograde axonal signaling transmission were disrupted by CC1-EGFP. [Cell Death Dis] Full Article

Nuclear Deterrents: Intrinsic Regulators of IL-1β-Induced Effects on Hippocampal Neurogenesis

The authors focus on the signaling mechanisms of specific nuclear receptors involved in regulating neurogenesis. They propose that these nuclear receptors could be targeted to inhibit neuroinflammatory signaling pathways associated with interleukin-1β. [Brain Behav Immun] Abstract

Stem Cells and Other Emerging Agents as Innovative ‘Drugs’ in Neurodegenerative Diseases: Benefits and Limitations

The brain has a limited process of repair/regeneration linked to the restricted and localized activity of neuronal stem cells. Consequently, it shows a reduced capacity to counteract the age-related loss of neural and glial cells and to repair the consequent injuries/lesions of nervous system. [Rejuvenation Res] Abstract

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Flex Pharma Initiates ALS Phase II Trial with FLX-787 in US

Flex Pharma, Inc. announced that, under its open investigational new drug application, the company has initiated a Phase II randomized, controlled, double-blinded, parallel design trial in the US, referred to as the COMMEND trial. [Flex Pharma, Inc.] Press Release

First Human Subject Enrolled in Lumosa Therapeutics’ Phase I Trial for LT3001, a New Drug Molecule for Acute Ischemic Stroke

Lumosa Therapeutics Co., Ltd. announced the enrollment of the first subject for the Phase I clinical trial of its new drug candidate, LT3001, for acute ischemic stroke. [Lumosa Therapeutics Co., Ltd. (PR Newswire Association LLC.)] Press Release

InVivo Therapeutics Announces Updates on the INSPIRE Study

InVivo Therapeutics Holdings Corp. provided an update on the progress of the company’s INSPIRE Study (InVivo Study of Probable Benefit of the Neuro-Spinal Scaffold^™ for Safety and Neurologic Recovery in Subjects with Complete Thoracic AIS A Spinal Cord Injury), which is designed to demonstrate the safety and probable benefit of the Neuro-Spinal Scaffold^™ for the treatment of complete thoracic spinal cord injury. [InVivo Therapeutics Holdings Corp.] Press Release

Oxeia Biopharmaceuticals Announces Clinical Advancement of Concussion Treatment

Oxeia Biopharmaceuticals Inc. announced its acquisition of the license to SUN11031, synthetic human ghrelin, from Kinemed Inc. Oxeia will develop SUN11031 as OXE-103 to treat concussions and other acute neurotrauma. [Oxeia Biopharmaceuticals Inc.] Press Release

UC Davis to Lead $14 Million Alzheimer’s Disease Study in Latinos

The University of California (UC) has been awarded a nearly $14.7 million multi-year grant from the National Institutes of Health to study contributors to dementia in the Latino population in the United States. The multicenter study will examine the biological underpinnings of stroke, mild cognitive impairment and Alzheimer’s disease among Hispanics, and pursue new therapeutic directions to reduce brain health disparities. [University of California, Davis] Press Release

ABTA Awards 18 Research Grants to Support Early Career Investigators and High-Impact, Collaborative Brain Tumor Research

The American Brain Tumor Association (ABTA) announced the recipients of their 2017-2019 Research Collaboration Grants, 2017 Discovery Grants, 2017-2019 Basic Research Fellowships and 2017 Medical Student Summer Fellowships. [The American Brain Tumor Association] Press Release

St. Baldrick’s Awards Eight Faculty with Cancer Research Grants

The St. Baldrick’s Foundation has announced its 2017 summer grant recipients, including eight from Baylor College of Medicine and Texas Children’s Cancer Center. [Baylor College of Medicine] Press Release

After French Drug Trial Tragedy, European Union Issues New Rules to Protect Study Volunteers

The European Medicines Agency has issued new, stricter rules for studies that test drugs in people for the first time. They aim to better protect participants in such first-in-human studies—often healthy volunteers who receive a financial reward. [ScienceInsider] Editorial

University of Tokyo Probe Says Chromosome Team Doctored Images

After a nearly year-long investigation into anonymous allegations of data and image falsification in numerous papers, a University of Tokyo committee announced it had confirmed that one research group falsified images and graphs in five papers. The panel cleared five other research groups of wrongdoing. [ScienceInsider] Editorial

Why Would a University Pay a Scientist Found Guilty of Misconduct to Leave?

In June 2016, investigators at the University of Georgia in Athens concluded that Azza El-Remessy, a faculty member who studied the impact of diabetes on the eye, had committed misconduct and recommended she be terminated. El-Remessy hired a lawyer to dispute the findings, but the following October she gave up her challenge after the university paid her $100,000—essentially to leave. [ScienceInsider] Editorial

NEW Keystone Symposia: Multiple Sclerosis: Conventional and Alternative Therapeutic Approaches
August 15, 2017
Online

NEW Keystone Symposia: State of the Brain: Genetic Dissection of Brain Circuits and Behavior in Health and Disease
January 14-18, 2018
Keystone, Colorado, United States

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NEW Postdoctoral Fellowship Positions and Principal Investigator – Brain Tumors (University of California, San Francisco)

NEW Postdoctoral Researchers – Glial Cells (University of California, Davis)

NEW Faculty Scientists – Neuroscience (Cedars-Sinai Medical Center)

NEW Postdoctoral Fellow – Neural Regeneration (Johns Hopkins University)

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

Postdoctoral Fellow Position – Alzheimer’s and Parkinson’s Diseases (Brigham and Women’s Hospital)

Postdoctoral Scientist – Developmental Neuroscience (University of North Carolina School of Medicine)

Postdoctoral and Scientist Positions – CNS (Shriners Hospitals Pediatric Research Center)

Postdoctoral Research Fellow – Synthetic Biology/Neurobiology (University of Edinburgh)

Biomedical Engineering Faculty Position – Neural Regeneration and Functional Tissue Engineering (Pennsylvania State University)

Postdoctoral Position – Neuroscience (Max Planck Society)

Postdoctoral Fellow – Development and Function of Neural Circuits (Cold Spring Harbor Laboratory)

Postdoctoral Position – Developmental Neurobiology (State University of New York)

Postdoctoral Scientist – Neural Stem Cell Biology (Institute for Neuroscience of Montpellier)

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

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