Neural Cell News Volume 11.26 | Jul 5 2017

TOP STORY

The Methyltransferase SETDB1 Regulates a Large Neuron-Specific Topological Chromatin Domain

The authors report locus-specific disintegration of megabase-scale chromosomal conformations in the brain after neuronal ablation of Setdb1, including a large topologically associated 1.2-Mb domain conserved in humans and mice that encompasses >70 genes at the clustered protocadherin locus (cPcdh). They showed that the SETDB1 repressor complex, which involves multiple KRAB zinc finger proteins, shields neuronal genomes from excess CTCF binding and is critically required for structural maintenance of cPcdh topologically associated domain. [Nat Genet] Abstract | Press Release

(Ranked by impact factor of the journal)

Asparagine Endopeptidase Cleaves α-Synuclein and Mediates Pathologic Activities in Parkinson’s Disease

Investigators showed that asparagine endopeptidase cleaves human α-synuclein, triggers its aggregation and escalates its neurotoxicity, thus leading to dopaminergic neuronal loss and motor impairments in a mouse model. [Nat Struct Mol Biol] Abstract | Press Release

Electrical Guidance of Human Stem Cells in the Rat Brain

Researchers report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. They developed a safe stimulation paradigm to deliver directional currents in the brain. [Stem Cell Reports] Full Article | Press Release | Graphical Abstract

Autophagy Fails to Prevent Glucose Deprivation/Glucose Reintroduction-Induced Neuronal Death Due to Calpain-Mediated Lysosomal Dysfunction in Cortical Neurons

Scientists analyzed the changes in the content of the autophagy proteins BECN1, LC3-II and p62/SQSTM1 by western blot, and autophagosome formation was followed through time-lapse experiments, during glucose deprivation (GD) and glucose reintroduction in cortical cultures. Autophagosome formation rapidly increased during GD, and was followed by an active autophagic flux early after glucose replenishment. [Cell Death Dis] Full Article

Proneurogenic Effects of Trazodone in Murine and Human Neural Progenitor Cells

The authors evaluated, in vitro, the effects of the antidepressant trazodone (TZD) on adult hippocampal neurogenesis by using primary cultures of murine adult hippocampal neural progenitor cells (NPCs) and human induced pluripotent stem cell-derived NPCs. They demonstrated that TZD enhanced neuronal differentiation of murine as well as human NPCs. [ACS Chem Neurosci] Abstract | Graphical Abstract

Smad4 Is Essential for Directional Progression from Committed Neural Progenitor Cells through Neuronal Differentiation in the Postnatal Mouse Brain

Investigators examined the functional contribution of Smad4, a key integrator of TGFβ/bone morphogenetic protein signaling pathways, to the regulation of neural progenitor cells in the subventricular zone (SVZ). Conditional loss of Smad4 function in neural progenitor cells caused an increase in the number of neural stem like cells in the SVZ. [Mol Cell Neurosci] Abstract

Neural Stem Cells for Disease Modeling of Wolman Disease and Evaluation of Therapeutics

Researchers generated induced pluripotent stem cells from two Wolman disease (WD) patient dermal fibroblast lines and subsequently differentiated them into neural stem cells (NSCs). The results demonstrated that these WD NSCs are valid cell-based disease models with characteristic disease phenotypes that can be used to evaluate drug efficacy and screen compounds. [Orphanet J Rare Dis] Full Article

Nanofibrous Scaffolds for the Guidance of Stem Cell-Derived Neurons for Auditory Nerve Regeneration

The authors present novel nanofibrous scaffolds designed to guide the integration of human stem cell-derived neurons in the internal auditory meatus, the foramen, allowing passage of the spiral ganglion to the auditory brainstem. While neural precursor cell (NPC) survival was found to be poor, both subjects implanted with NPC-seeded and cell-free control scaffolds showed partial recovery of electrically-evoked auditory brainstem thresholds. [PLoS One] Full Article

Subcellular Electrical Stimulation of Neurons Enhances the Myelination of Axons by Oligodendrocytes

Investigators demonstrated a microfluidic compartmentalized culture system with integrated electrical stimulation capabilities that could induce neural activity by whole cell and focal stimulation. They further investigated if oligodendrocytes have to be exposed to the electrical field to induce axon myelination. [PLoS One] Full Article

Antibody–Drug Conjugates in Glioblastoma Therapy: The Right Drugs to the Right Cells

The authors summarize clinical data regarding antibody–drug conjugates (ADCs) against a variety of targets in glioblastoma, and compare the efficacy and toxicity of targeting EGFR with ADCs versus naked antibodies in order to illustrate key aspects of the use of ADCs in this malignancy. [Nat Rev Clin Oncol] Abstract

Efficient Prevention of Neurodegenerative Diseases by Depletion of Starvation Response Factor Ataxin-2

During periods of starvation, Ataxin-2 (ATXN2) is transcriptionally induced and localized to cytosolic stress granules, where nuclear factors dock to compensate RNA pathology. These physiological actions were revealed to be crucial for human neurodegenerative diseases, given that ATXN2 depletion is surprisingly efficient in preventing motor neuron and cerebellar atrophy, as demonstrated in mouse models, flies, and yeast. [Trends Neurosci] Abstract

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ProMIS Neurosciences to Present Preclinical Data from Alzheimer’s Disease Program

ProMIS Neurosciences, Inc. announced the company will present preclinical data for its lead product candidate, PMN310. They will describe the use of ProMIS’ proprietary discovery engine for the identification and generation of monoclonal antibodies against specific targets on toxic forms of amyloid beta, a recognized root cause of Alzheimer’s. [Press release from ProMIS Neurosciences, Inc. discussing research to be presented at the 2017 Alzheimer’s Association International Conference (AAIC), London] Press Release

The Paul G. Allen Frontiers Group Announces Two New Allen Discovery Centers

The Paul G. Allen Frontiers Group announced the creation of two new Allen Discovery Centers, one at University of Washington Medicine and one at Boston Children’s Hospital and Harvard Medical School. Each center is funded at $10 million over four years, with the potential for $30 million over eight years. [Allen Institute] Press Release

Worldwide Clinical Trials Selected by BrainStorm as CRO for Phase III NurOwn Trial in ALS

BrainStorm Cell Therapeutics Inc. announced that it has selected Worldwide Clinical Trials as its Clinical Research Organization (CRO) for its planned Phase III study of NurOwn^® in the treatment of ALS. [BrainStorm Cell Therapeutics Inc.] Press Release

AgeneBio Receives Grant from Alzheimer’s Drug Discovery Foundation for Drug-Discovery Program to Delay the Onset of Alzheimer’s Dementia

AgeneBio announced that the company has received an additional $750,000 grant from the Alzheimer’s Drug Discovery Foundation. The grant will support drug development of AgeneBio’s novel GABA_A discovery program to treat mild cognitive impairment due to Alzheimer’s disease and delay the onset of Alzheimer’s dementia. [AgeneBio, Inc.] Press Release

French Scientist Fined for Failure to Disclose Industry Ties

In an unprecedented court case in Paris, an eminent French lung specialist has been fined €50,000 and given a six-month suspended jail sentence because he didn’t disclose his ties to the oil industry during a Senate air-pollution inquiry. [Nature News] Editorial

House Lawmakers Balk at Most Trump Science Cuts in Early Bills

No. That’s the first official answer from lawmakers in the U.S. House of Representatives to President Donald Trump’s request to make deep budget cuts at several key science funding agencies. [ScienceInsider] Editorial

Europe’s next Big Science-Funding Program Urged to Double Its Budget

Midway through the European Union’s sprawling seven-year, €75-billion research-funding program known as Horizon 2020, scientists are already angling for more money and less red tape in its successor. [Nature News] Editorial

Germany and Poland Launch Research ‘Twinning’ Effort

Germany and Poland are to jointly fund top scientists to start research groups at Polish institutes, in a scheme that could provide a new blueprint for east–west research collaboration in the European Union. [Nature News] Editorial

NEW VII InterAmerican Oncology Conference
October 5-6, 2017
Buenos Aires, Argentina

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

Postdoctoral Fellow – Neuroscience/Neuroplasticity (University of Oslo)

Tenure-Track Positions – Neuroscience Research (The State Key Laboratory of Medicinal Chemical Biology of Nankai University)

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

Assistant Professor – Reparative Medicine (Karolinska Institutet)

Postdoctoral Position – Neurobiology (Cincinnati Children’s Hospital Medical Center)

Postdoctoral Fellow – Neuroscience (State University of New York)

Postdoctoral Fellow – Applied Neural Interfaces (Florida International University)

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

Faculty Position(s) – Pain Medicine (Southern University of Science and Technology)

Senior/Principle Research Associate – Cell and Molecular Biology (Editas Medicine)

Postdoctoral Fellow – Neuroendocrine Biology of Metabolism (The Scripps Research Institute)

Research Fellow – Neuroscience and Behavioral Disorders (Duke-NUS Medical School)

Postdoctoral Researcher – Neuroscience and Imaging (Howard Hughes Medical Institute)

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

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