Neural Cell News Volume 13.16 | May 1 2019

TOP STORY

Childhood Cerebellar Tumors Mirror Conserved Fetal Transcriptional Programs

Researchers used single-cell transcriptomics to study more than 60,000 cells from the developing mouse cerebellum and showed that different molecular subgroups of childhood cerebellar tumors mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Hyperactivity with Disrupted Attention by Activation of an Astrocyte Synaptogenic Cue

Hyperactivity and disturbances of attention are common behavioral disorders whose underlying cellular and neural circuit causes are not understood. Scientists report the discovery that striatal astrocytes drive such phenotypes through a hitherto unknown synaptic mechanism. They found that striatal medium spiny neurons triggered astrocyte signaling via γ-aminobutyric acid B receptors. [Cell] Abstract | Press Release | Graphical Abstract

Neocortical Projection Neurons Instruct Inhibitory Interneuron Circuit Development in a Lineage-Dependent Manner

Loss of intratelencephalic-type projection neurons (PNs) selectively disrupted the lamination and circuit integration of interneurons (INs) derived from the caudal ganglionic eminence (CGE). Strikingly, reprogrammed PNs demonstrated reduced synaptic targeting of CGE-derived INs relative to controls. [Neuron] Abstract

Capicua Regulates Neural Stem Cell Proliferation and Lineage Specification through Control of Ets Factors

Investigators demonstrated that forebrain-specific capicua (Cic) deletion increased proliferation and self-renewal of neural stem cells. Furthermore, Cic loss biased neural stem cells toward glial lineage selection, expanding the pool of oligodendrocyte precursor cells. These proliferation and lineage effects were dependent on de-repression of Ets transcription factors. [Nat Commun] Full Article

Genome-Wide CRISPR Screen for Zika Virus Resistance in Human Neural Cells

The authors identified Zika virus (ZIKV) host genes in human pluripotent stem cell-derived neural progenitors (NPs) using a genome-wide CRISPR-Cas9 knockout screen. Host genes essential for ZIKV replication identified in human NPs also provided a low level of protection against ZIKV in isogenic human astrocytes. [Proc Natl Acad Sci USA] Abstract | Press Release

Partial Inhibition of the Overactivated Ku80-Dependent DNA Repair Pathway Rescues Neurodegeneration in C9ORF72-ALS/FTD

Ku80 expression was greatly elevated in flies expressing poly(GR) and in C9ORF72 induced pluripotent stem cell-derived patient neurons. As a result, the levels of phosphorylated ATM and P53 as well as other downstream proapoptotic proteins such as PUMA, Bax, and cleaved caspase-3 were all significantly increased in C9ORF72 patient neurons. [Proc Natl Acad Sci USA] Abstract

Mutations in ACTL6B Cause Neurodevelopmental Deficits and Epilepsy and Lead to Loss of Dendrites in Human Neurons

Engineered knock-out of ACTL6B in wild-type human neurons resulted in profound deficits in dendrite development, a result recapitulated in two individuals with different bi-allelic mutations, and reversed on clonal genetic repair or exogenous expression of ACTL6B. [Am J Hum Genet] Abstract | Editorial

APP-Mediated Signaling Prevents Memory Decline in Alzheimer’s Disease Mouse Model

Investigators revealed that amyloid precursor protein (APP) possessed autonomous regulatory capacity within its intracellular domain that promoted APP cell surface residence, precluded amyloid-β production, facilitated axodendritic development, and preserved cellular substrates of memory. [Cell Rep] Full Article | Graphical Abstract

Glial Ca²⁺ Signaling Links Endocytosis to K⁺ Buffering around Neuronal Somas to Regulate Excitability

Researchers showed that elevation of glial Ca²⁺ caused hyperactivation of calcineurin-dependent endocytosis and accumulation of early endosomes. Knockdown of sandman, a K_2P channel, recapitulated NCKX^zydeco seizures. Indeed, sandman expression on cortex glial membranes was substantially reduced in NCKX^zydeco mutants, indicating enhanced internalization of sandman predisposed animals to seizures. [eLife] Full Article

Blockade of the Forward Na⁺/Ca²⁺ Exchanger (NCX) Suppresses the Growth of Glioblastoma Cells through Ca²⁺-Mediated Cell Death

NCX blockers with or without mode-specificity were tested on cultured glioblastoma cells. Patch-clamp recording, Ca²⁺ imaging, flow cytometry and western blot were used to study action of NCX blockers. In vivo bioluminescent imaging was used to measure grafted glioblastoma. [Br J Pharmacol] Abstract

RNA Profiling of the Human and Mouse Spinal Cord Stem Cell Niches Reveals an Embryonic-Like Regionalization with MSX1⁺ Roof-Plate-Derived Cells

A cellular and molecular resource is provided for the mouse and human ependymal zone based on RNA profiling, immunostaining, and fluorescent transgenic mice. This uncovered the conserved expression of 1,200 genes including 120 transcription factors. [Stem Cell Reports] Full Article | Graphical Abstract

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Testing Models of Human Declarative Memory at the Single-Neuron Level

The author summarizes the cell types that have been described in the medial temporal lobe and posterior parietal cortex, discusses their properties, and reflects on how these findings inform theoretical work. This body of work exemplifies the scientific power of a synergistic combination of modeling and human single-neuron recordings to advance cognitive neuroscience. [Trends Cogn Sci] Abstract

Iron, Myelin, and the Brain: Neuroimaging Meets Neurobiology

Interdisciplinary collaborations will be key to advance beyond simple correlative analyses in the biological interpretation of MRI data and to gain deeper insights into key factors leading to iron accumulation and/or redistribution associated with neurodegeneration. [Trends Neurosci] Abstract

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

Biogen to Present Data Highlighting Its Innovative Marketed Treatments and Investigational Pipeline Programs for Complex Neurodegenerative Diseases

Biogen Inc. announced it will present new data across its industry-leading neuroscience portfolio and advancing clinical development programs. Of Biogen’s 33 total presentations, key data will focus on spinal muscular atrophy, multiple sclerosis and amyotrophic lateral sclerosis. [Press release from Biogen Inc. discussing research to be presented at the 71^st annual meeting of the American Academy of Neurology (AAN), Philadelphia] Press Release

New Roche Data Showcase Breadth and Promise of Neuroscience Portfolio

Roche announced that new data for its approved and investigational medicines for the treatment of neurological conditions will be presented. Presentations include data from a pivotal study for risdiplam in spinal muscular atrophy, which has the potential to become the first oral treatment for this community. [Press release from F. Hoffmann-La Roche Ltd discussing research to be presented at the 71^st annual meeting of the American Academy of Neurology (AAN), Philadelphia] Press Release

Voyager Therapeutics Announces New Data in Multiple Presentations

New preclinical data relate to Voyager’s vectorized antibody program directed against tau for the potential treatment of Alzheimer’s disease, its new TRACER^™ system to discover adeno-associated virus capsids with blood-brain barrier crossing and cell-specific transduction properties, as well as VY-SOD102 targeting a monogenic form of amyotrophic lateral sclerosis called SOD1. [Press release from Voyager Therapeutics, Inc. discussing research presented at the American Society of Gene and Cell Therapy (ASGCT), Washington, DC] Press Release

StemoniX^® Announces Collaborative Research Agreement with the NIH’s National Center for Advancing Translational Sciences (NCATS)

StemoniX^® Inc. announced that it entered into a Research Collaboration Agreement with the NCATS to screen a library of neuronal signaling and opioid compounds using microBrain 3D as part of the NIH HEAL Initiative, a trans-NIH effort to advance national priorities in addressing the opioid crisis through science. [StemoniX] Press Release

Medicenna Announces Completion of Enrolment in MDNA55 Phase IIb Recurrent Glioblastoma Clinical Study

Medicenna Therapeutics Corp. announced that it has completed enrollment in the Phase IIb clinical study of MDNA55 for the treatment of recurrent glioblastoma, the most common and uniformly fatal form of brain cancer. [Medicenna Therapeutics Corp.] Press Release

Tetra Discovery Partners Initiates Phase II Clinical Trial of BPN14770 in Patients with Early Alzheimer’s Disease

Tetra Discovery Partners announced the initiation of a Phase II clinical trial of BPN14770 in patients diagnosed with early Alzheimer’s disease (AD). BPN14770, a novel agent that selectively inhibits phosphodiesterase-4D, is designed to enhance early and late stages of memory formation and to potentially improve cognition and memory in central nervous system disorders including AD. [Tetra Discovery Partners] Press Release

Xeris Pharmaceuticals Announces Results from a Phase I Study of Its Novel Formulation of Diazepam

Xeris Pharmaceuticals, Inc. announced positive findings from a Phase I study of its novel formulation of diazepam. Diazepam is in a class of medications called benzodiazepines. It works by calming abnormal overactivity in the brain. Diazepam is used in emergency situations to stop cluster seizures in people who are already taking medications to control their seizures. [Xeris Pharmaceuticals, Inc.] Press Release

Aptinyx Reports Positive Data from Phase I Study of Novel NMDA Receptor Modulator, NYX-458, in Healthy Volunteers

Aptinyx Inc. reported positive results from a Phase I study of its novel NMDA receptor modulator, NYX-458, in clinical development for the treatment of cognitive impairment associated with Parkinson’s disease. [Aptinyx Inc.] Press Release

Cerevance Achieves Key Endpoints in Phase I Clinical Trial of Novel Parkinson’s Disease Drug CVN424

Cerevance has successfully completed its Phase I clinical trial of CVN424, the company’s first-in-class, orally-delivered compound in development for the treatment of Parkinson’s disease. The clinical study successfully met its primary endpoint of safety in healthy volunteers. [Cerevance, Inc.] Press Release

International Stem Cell Corporation Completes Enrollment and Dosing in Its Parkinson’s Disease Clinical Trial

International Stem Cell Corporation announced the completion of subject enrollment in its Phase I clinical trial of ISC-hpNSC^® for the treatment of Parkinson’s disease. The fourth subject of the third cohort, who was the twelfth and final subject of the Phase I clinical study, was successfully transplanted with the highest dose of ISC-hpNSC^® cells. [International Stem Cell Corporation] Press Release

Axogen, Inc. Announces Completion of Planned Interim Analysis and One-Time Enrollment Expansion for Recon^® Study

Axogen, Inc. announced completion of the planned blinded interim analysis for its RECON Study. The study will support the submission of a Biologic License Application to the FDA for Avance^® Nerve Graft. [Axogen, Inc.] Press Release

BU Receives Massachusetts Life Sciences Capital Grant

A $4.9 million grant from the Massachusetts Life Sciences Center has been awarded to the Center for Translation Neurotrauma Imaging (CTNI) at the Boston University (BU) School of Medicine. With support from the grant, the CTNI will improve brain imaging techniques and open doors to developing diagnostics and treatments for neurodegenerative diseases. [Boston University School of Medicine] Press Release

BrainStorm’s Cellular Technology Platform Expanded to Include Exosomes for Neurodegenerative Diseases

Brainstorm-Cell Therapeutics Inc. announced that it has expanded its proprietary cellular technology platform to include NurOwn^®-derived exosomes for potential development across a broad range of central nervous system disorders. [Brainstorm-Cell Therapeutics Inc.] Press Release

Thousands of Scientists in Argentina Strike to Protest Budget Cuts

Scientists from labs across Argentina stayed home, joining a nationwide strike against the government’s latest round of austerity measures. One of their key rallying points: a call to restore lost opportunities for young researchers who began their education during a time of high investment in science but now have little hope of continuing their careers in Argentina. [ScienceInsider] Editorial

US Science Academy Leaders Approve Plan to Expel Sexual Harassers

The US National Academy of Sciences (NAS) is moving ahead with a policy that would allow it to expel members found guilty of sexual harassment. The academy’s governing council voted to proceed with the plan at the NAS annual meeting in Washington DC. [Nature News] Editorial

What Study Findings? Most European Universities Fail to Report Clinical Trial Results

Despite European Union rules that require clinical trial reporting, a new survey finds results from more than four of every five studies run by 30 European universities have not been registered, the latest such finding to stir concerns about the impact on health systems and patient care. [STAT News] Editorial

NEW Gordon Research Conference: Parkinson’s Disease
June 23-28, 2019
Newry, Maine, United States

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

NEW Postdoctoral Fellow/Research Assistant Positions – Glioma Research (NIH National Cancer Institute Laboratory of Pathology)

Senior Scientist – Neuroscience (STEMCELL Technologies Inc.)

Postdoctoral Positions – Astrocyte Research (Washington University in St.Louis)

Postdoctoral Research Scientist – Systems Neuroscience (University of Oxford)

Postdoctoral Researcher – Neurobiological Mechanisms (Columbia University)

Senior Scientist – Tau Biology in Neuroscience Discovery (AbbVie Deutschland GmbH)

Postdoctoral Position – Retinal Stem Cell Biology (Johns Hopkins University)

Postdoctoral Fellow – Alcohol & Adult Neurogenesis (The University of Texas at Austin)

Postdoctoral Research Fellow – Neuroscience (The University of Texas at Austin)

Postdoctoral Researcher – Neurobiology (University of Rochester)

Staff Scientist – Molecular & Behavioral Neuroscience (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Associate – Neurological Diseases (University of Utah)

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