Neural Cell News Volume 10.49 | Dec 14 2016

TOP STORY

A Multi-Step Transcriptional and Chromatin State Cascade underlies Motor Neuron Programming from Embryonic Stem Cells

The authors found that motor neuron programming is the product of two initially independent transcriptional modules that converge with a feedforward transcriptional logic. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

New Transgenic Mouse Lines for Selectively Targeting Astrocytes and Studying Calcium Signals in Astrocyte Processes In Situ and In Vivo

Studying astrocytes has proven difficult because of the lack of tools permitting astrocyte-selective genetic manipulations. Researchers reported the generation of Aldh1l1-Cre/ERT2 transgenic mice to selectively target astrocytes in vivo. [Neuron] Abstract | Press Release

Patient-Specific Models of Microglia-Mediated Engulfment of Synapses and Neural Progenitors

Engulfment of synapses and neural progenitor cells (NPCs) by microglia is critical for the development and maintenance of proper brain circuitry, and has been implicated in neurodevelopmental as well as neurodegenerative disease etiology. Investigators have developed and validated models of these mechanisms by reprogramming microglia-like cells from peripheral blood mononuclear cells, and combining them with NPCs and neurons derived from induced pluripotent stem cells to create patient-specific cellular models of complement-dependent synaptic pruning and elimination of NPCs. [Mol Psychiatry] Full Article

Complement Peptide C3a Stimulates Neural Plasticity after Experimental Brain Ischaemia

To determine the role of C3a–C3a receptor signaling in ischaemia-induced neural plasticity, researchers subjected C3a receptor-deficient mice, GFAP-C3a transgenic mice expressing biologically active C3a in the central nervous system, and their respective wild-type controls to photothrombotic stroke. They found that C3a overexpression increased, whereas C3a receptor deficiency decreased post-stroke expression of GAP43, a marker of axonal sprouting and plasticity, in the peri-infarct cortex. [Brain] Full Article | Press Release

Gamma Motor Neurons Survive and Exacerbate Alpha Motor Neuron Degeneration in ALS

Scientists established the resistance of γ-motor neurons (MNs) as a general feature of amyotrophic lateral sclerosis (ALS) mouse models and demonstrated that synaptic excitation of MNs within a complex circuit is an important determinant of relative vulnerability in ALS. [Proc Natl Acad Sci USA] Full Article

Loss of O-GlcNAc Glycosylation in Forebrain Excitatory Neurons Induces Neurodegeneration

Investigators report that forebrain-specific loss of O-GlcNAc transferase (OGT) in adult mice leads to progressive neurodegeneration, including widespread neuronal cell death, neuroinflammation, increased production of hyperphosphorylated tau and amyloidogenic Aβ-peptides, and memory deficits. They showed that human cortical brain tissue from Alzheimer’s disease patients has significantly reduced levels of OGT protein expression compared with cortical tissue from control individuals. [Proc Natl Acad Sci USA] Abstract

An Alternative Splicing Switch Shapes Neurexin Repertoires in Principal Neurons Versus Interneurons in the Mouse Hippocampus

Scientists demonstrated that transcripts encoding the synaptic adhesion molecules neurexin-1,2,3 are commonly expressed in principal cells and interneurons of the mouse hippocampus but undergo highly differential, cell type-specific alternative splicing. [eLife] Full Article

Global Ischemia Induces Lysosomal-Mediated Degradation of mTOR and Activation of Autophagy in Hippocampal Neurons Destined to Die

The authors showed that global ischemia triggers a transient increase in mammalian target of rapamycin (mTOR) phosphorylation at S2448, whereas decreasing p-mTOR and functional activity in selectively vulnerable hippocampal CA1 neurons. [Cell Death Differ] Full Article

Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition

Scientists established libraries of glioma-initiating cell clones from patient samples and find extensive molecular and phenotypic variability among clones, including a range of responses to radiation and drugs. This widespread variability was observed as a continuum of multitherapy resistance phenotypes linked to a proneural-mesenchymal shift in the transcriptome. [Cell Rep] Full Article | Press Release | Graphical Abstract

High-Throughput Compound Evaluation on 3D Networks of Neurons and Glia in a Microfluidic Platform

The authors demonstrate a method for culturing three-dimensional networks of spontaneously active neurons and supporting glial cells in a microfluidic platform. [Sci Rep] Full Article

Motor Neurons Derived from ALS-Related Mouse iPS Cells Recapitulate Pathological Features of ALS

To determine the pathological mechanism of amyotrophic lateral sclerosis (ALS), researchers generated mouse induced pluripotent stemcells (miPS) from experimental ALS transgenic mice and control mice and characterized the cells using molecular biological methods. The generated miPS cells expressed many pluripotent genes and differentiated into three germ layers in vitro and in vivo. Motor neurons derived from ALS-related miPS cells recapitulated the pathological features of ALS. [Exp Mol Med] Full Article

A Drop Array Culture for Patterning Adherent Mouse Embryonic Stem Cell-Derived Neurospheres

Scientists describe a simple technique for creating an array of adherent mouse embryonic stem cell-derived neurospheres using a conventional plastic culture dish and a patterning template. [J Tissue Eng Regen Med] Abstract

3D Culture Models of Alzheimer’s Disease: A Road Map to A “Cure-in-A-Dish”

In this review, the authors summarize the current progress in recapitulating Alzheimer’s disease (AD) pathogenic cascades in human neural cell culture models using AD patient-derived induced pluripotent stem cells or genetically modified human stem cell lines. [Mol Neurodegener] Full Article

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

Lilly Announces Detailed Results of Solanezumab Phase III EXPEDITION3 Study

Eli Lilly and Company presented detailed results of its phase III EXPEDITION3 trial. As previously disclosed, solanezumab did not meet the primary endpoint in the EXPEDITION3 clinical trial, a study of solanezumab initiated in people with mild dementia due to Alzheimer’s disease (AD), and Lilly will not pursue regulatory submissions for solanezumab for the treatment of mild dementia due to AD. [Press release from Eli Lilly and Company discussing research presented at the 9^th Clinical Trials on Alzheimer’s Disease (CTAD) meeting, San Diego] Press Release

$1.7 Million Awarded to Dr. Zahra Moussavi for Clinical Trial of rTMS for Treatment of Alzheimer’s Disease

Dr. Zahra Moussavi, the Canada Research Chair in Biomedical Engineering in the Faculty of Engineering at the University of Manitoba, is receiving $1,737,960 from our Clinical Trials program for her project investigating the efficacy of high-frequency rTMS as a treatment for Alzheimer’s disease. [Weston Brain Institute] Press Release

Rush University Medical Center Awarded $11.5 Million for Fragile X Research

Rush University Medical Center was awarded an $11.5 million grant by the National Institutes of Health to conduct a Phase II national clinical trial for children with fragile X syndrome. This randomized, double-blind study will examine if the drug AFQ056 can enhance neural plasticity in the form of language learning in young children with fragile X syndrome. [Rush University Medical Center] Press Release

Penn Medicine Neuroscientist Among First to Receive NIH Funding under Novel, Multi-Year Pilot Program

Greg J. Bashaw, PhD, a professor of Neuroscience at the Perelman School of Medicine at the University of Pennsylvania, has been awarded research funding under a novel, multi-year pilot program from the National Institute of Neurological Disorders and Stroke. The award, one of 31 nationally, will allow outstanding investigators to receive continuous, predictable, and flexible funding for their research on the brain and nervous system. [Penn Medical University] Press Release

Creative Medical Technology Holdings Files Patent on AmnioStem Stroke Therapy

Creative Medical Technology Holdings announced the filing of US patent application entitled “Treatment of Stroke by Amniotic Fluid Derived Stem Cell Conditioned Media and Products Derived Thereof”. The patent application covers the use of the company’s newly licensed AmnioStem stem cell as a production means for generation of nanoparticles termed “exosomes,” which regenerate damaged brain tissue after stroke. [Creative Medical Technology Holdings [PR Newswire Association LLC.]] Press Release

MeiraGTx Expands Neurodegenerative Gene Therapy Pipeline in Alzheimer’s and Parkinson’s Disease in Collaboration with Weill Cornell Medicine

MeiraGTx announced the expansion of its neurodegenerative disease gene therapy pipeline. Research into the causes of neurodegenerative disease has converged upon the central idea that misfolded proteins play a critical role in damaging neuronal function and the ultimate progression to neuronal cell death. The new program, a collaboration with Dr. Greg Petsko of Weill Cornell Medicine, targets neurodegenerative disease by altering neuronal protein processing. [MeiraGTx] Press Release

Biohaven’ BHV-0223 Is Granted Orphan Drug Designation in the Treatment of Amyotrophic Lateral Sclerosis

Biohaven Pharmaceutical Holding Company Ltd. announced that the U.S. Food and Drug Administration has granted the company’s orphan drug designation request covering its drug candidate BHV-0223, an orally dissolving tablet being developed for the treatment of Amyotrophic Lateral Sclerosis, also referred to as Lou Gehrig’s disease. [Biohaven Pharmaceutical Holding Company Ltd. [PR Newswire Association LLC.]] Press Release

Canada’s Government Scientists Get Antimuzzling Clause in Contract

Scientists working for the Canadian government have successfully negotiated a clause in their new contract that guarantees their right to speak to the public and the media about science and their research, without needing approval from their managers. [ScienceInsider] Editorial

In Canada, Case Spurs Concern over Misconduct Secrecy

An investigation by UBC ultimately confirmed their fears: In 2014, investigators identified 29 instances of scholarly misconduct, 16 of them “serious,” including falsification and fabrication of data, according to university correspondence obtained by Retraction Watch. The tainted work had been included in 12 papers published in six journals between 2005 and 2012, investigators found, and had drawn financial support from more than a dozen government and private funders. [ScienceInsider] Editorial

Is Donald Trump Pushing More Scientists towards Political Activism?

Around the world, individual researchers and representatives of scientific societies are signing letters of protest or advice, offering to counsel Trump’s transition team and ramping up efforts to communicate the value of science to the public. [Nature News] Editorial

NEW Stem Cells in Drug Discovery
March 6-7, 2017
Cambridge, United Kingdom

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

NEW Neuroscientist – Precision Neurotherapeutics (University of California, Davis)

Postdoctoral Research Scholar – Neurodegenerative Diseases (Buck Insititute)

Post-Doctoral Research Fellow – Neurobiology (Institut of Molecular Biology)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Postdoctoral Fellow – Neurobiology of Hunger And Other Homestatic Drivers (Beth Israel Deaconess Medical Center/Harvard Medical School)

Neuroscience Postdoctoral Fellow (Harvard University)

Research Associate Position in Neural Rehabilitation Experiments (Nanyang Technological University)

Postdoctoral Researcher – Alzheimer’s Disease (University of Arkansas)

Computational Biologist – Aging Brain (Columbia University)

NYSCF Investigator – Stem Cell And Neuroscience (New York Stem Cell Foundation)

Postdoctoral Fellow – Genetic and Epigenetic Features Parkinson’s and Alzheimer’s Diseases (Van Andel Research Institute)

Assistant Professor (Tenure) – Developmental Biology)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Neural Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.